THE CASE FOR EXTENDED BRIEF INTERVENTIONS
Nick Heather1
Brief interventions directed against hazardous and harmful drinking have become popular in recent years, both among researchers and, to some extent, among general practitioners and other health professionals. There is a strong evidence-base, at least in primary health care, to justify this popularity (Kaner, Newbury-Birch & Heather, 2009). But there is often confusion about what exactly alcohol brief intervention consists of. In fact, the term ""brief intervention" does not describe a single, well-defined activity but rather a family of interventions that differ in a range of ways (Heather, 1995). Although they all share the characteristics of being briefer than most formal treatment programmes for alcohol problems and of being aimed at drinkers with less severe problems and levels of dependence than those typically attending specialised treatment services, brief interventions differ among themselves in duration over time, number of scheduled sessions, procedures and accompanying materials, styles of interaction, delivery personnel and settings, and the underlying theoretical approach on which they are based.
Two main classes of brief intervention
Despite this diversity, it is possible to discern two broad classes of therapeutic activity that encompass most of the actual forms of brief intervention to be found in the scientific literature and in practice; these are "brief advice" and "extended brief intervention". This distinction was incorporated in a review of the effectiveness of treatment for alcohol problems commissioned by the UK Department of Health (Raistrick, Heather & Godfrey, 2006) and was also included in the recommendations of the National Institute for Health and Clinical Excellence in recently published guidance on the prevention of hazardous and harmful drinking in the UK (National Institute for Health and Clinical Excellence, 2010; see also Kaner, 2010). These two classes of brief intervention will now be described.
Brief advice
This type of brief intervention is also sometimes called "simple advice" or "structured brief advice", in
Guest Editorial
the latter case to make the point that, to be effective, the advice in question should be delivered according to a defined form and structure and not merely as the practitioner sees fit. The main settings in which brief advice has been studied and applied are busy medical services, particularly primary health care or accident and emergency services, in which time is at a premium. Intervention usually proceeds immediately following a positive screen for hazardous or harmful drinking, although occasionally the patient is asked to return to the service to receive a brief intervention. In such time-limited and pressurised situations, the most that can be allowed for intervention is 5-10 minutes or sometimes even less.
Brief advice usually consists of a standard package involving information on drinking risk levels, the patient's own risk status in relation to those levels, encouragement to cut down and to set a date to begin, and perhaps a few simple hints on how cutting down might best be achieved, often accompanied by self-help material giving more tips on cutting down. Practitioners are often urged to adopt a style of interaction with the patient summarised by the well-known FRAMES principles:
Feedback - provide feedback on the patient's risk for alcohol problems
Responsibility—make clear that the individual is responsible for change
Advice—advise reduction or give explicit direction to change
Menu—provide a variety of options for change Empathy—adopt a warm, reflective and understanding approach
Self-efficacy—encourage optimism about changing behaviour
Extended brief intervention
This type of brief intervention is obviously of longer duration than brief advice and is sometimes called ""brief counselling". It usually lasts between 20-40 minutes in a single session and often includes follow-up sessions. Apart from this difference, perhaps the main contrast with brief advice is the theoretical underpinning of the intervention; extended brief intervention nowadays is almost always based on the principles of motivational
1 Department of Psychology, School of Life Sciences, Northumbria University, Newcastle upon Tyne, UK Correspondence to: e-mail: nick.heather@northumbria.ac.uk
interviewing as described by Miller and Rollnick (1991, 2002). A brief form of motivational interviewing was described by Rollnick, Heather and Bell (1992) and its contents and methods have subsequently been influenced by the work of Steven Rollnick and colleagues on applying the principles and techniques of motivational interviewing to changing health-damaging behaviour in healthcare settings (Rollnick, Mason & Butler, 1999; Rollnick, Miller & Butler, 2008). In contrast to brief advice, it can be considered a more refined, flexible and patient-centred approach that explicitly avoids giving advice unless specifically requested by the patient. For obvious reasons, brief motivational interviewing has usually been applied in settings and situations where there is more time for intervention and where staff trained in the approach are available. At its upper limit, brief motivational interviewing merges with Motivational Enhancement Therapy (Miller et al., 1992) and other adaptations of motivational interviewing (Burke, Arkowitz & Dunn, 2003) given in specialist treatment settings. Although almost all examples of extended brief intervention found in the current literature are derived from motivational interviewing, it should be noted that there exists an earlier form of extended brief intervention which might be called "condensed cognitive behaviour therapy' and which involves shorter versions of the methods that make up the cognitive-behavioural approach to treatment: identification of high-risk situations, training in ways of coping with those situations without excessive drinking, skills training in alternative behaviours, cognitive restructuring of attitudes and beliefs about self and drinking, relapse prevention techniques, etc. This kind of brief intervention was studied in the first trials in primary health care in the 1980s (Heather et al., 1987; Wallace, Cutler & Haines, 1988) and was compared with a motivational interviewing approach by Heather and colleagues (1996). Following the enormous popularity of motivational interviewing, it is now virtually restricted to self-help manuals, often distributed without direct therapist contact. It will not be considered further here.
What does the evidence tell us?
So what is the evidence for the effectiveness of these two classes of brief intervention to support their implementation in practice? A recent Cochrane review of research in primary health care by Kaner and colleagues (2009) has confirmed the conclusions of
previous systematic reviews and meta-analyses that brief advice delivered in primary health care is effective compared to control conditions. The success rate of brief advice has been calculated at between 8% and 12% (Moyer et al., 2002). While comparing favourably with the success rate for advice by physicians to quit smoking (20%: Silagy & Stead, 2003), some practitioners might regard this as low in clinical terms; in public health terms, however, if brief advice of this kind were consistently delivered in, for example, the great majority of general medical practices in a country and given to all those screening positive, it would lead to substantial reductions in hazardous and harmful drinking in the population at large and make a very important contribution to public health. Thus, although many individual patients will benefit, brief advice in primary health care may be thought of as a "shotgun" approach to reducing alcohol-related harm with important public health potential. Evidence to support brief advice in other medical setting, such as accident and emergency departments (Crawford et al., 2004) and general hospital wards (Holloway et al., 2007) is promising, although still considered inconclusive (Harvard et al., 2008; McQueen et al., 2009) and research is proceeding in these settings. In addition there are a range of other settings, both medical and non-medical, for which the evidence of effectiveness of brief advice ranges from inconclusive to non-existent but where there are reasons to believe that they have potential to reduce alcohol-related harm (see, eg, Heather & Kaner, 2010).
Given the established effectiveness of brief advice, it is clearly necessary to demonstrate that extended brief intervention offer additional benefits to patients who receive it compared with brief advice. However, the evidence on this issue is best described as mixed. Studies and observations that go against the conclusion that extended brief advice offers anything more than brief advice are as follows:
a)	In the systematic review by Kaner and colleagues (2009) referred to above, there was a tendency for patients given more extended brief intervention to show greater reductions in consumption at one-year follow-up than those given shorter interventions but this difference was not statistically significant;
b)	An earlier systematic review by Ballesteros et al. (2004) found no clear evidence for a "dose-response relationship" between duration of brief intervention and outcome, meaning that there were no firm grounds for concluding that more extended interventions added to the benefits of shorter interventions;
c) Phase II of the WHO Collaborative Study on the Identification and Management of Alcohol-related Problems in Primary Care (Babor, 1996) found that, compared with five minutes simple advice following 15 minutes of assessment, there was no added benefit of an additional 15 minutes brief counselling or of extended counselling over three more sessions.
On the other hand, evidence suggestive of an added
benefit of extended brief interventions is as follows:
a)	The greater reduction in consumption at follow-up among patients who received an extended brief intervention in the Kaner and colleagues meta-analysis (see above) approached statistical significance (p = 0.09) and may reflect a Type 2 error, ie, accepting the hypothesis of no difference between groups when it is in fact false;
b)	In the WHO Collaborative Study (see above), there was an interesting interaction in the data such that simple advice was more beneficial among men who recognised a recent alcohol-related problem and extended brief intervention was more effective among men who did not recognise a recent problem, suggesting that the latter worked better for patients who did not readily accept the need for change;
c)	Some studies and reviews have reported increased benefits of extended brief interventions over brief advice (eg, Richmond et al., 1995; Israel et al., 1996; Poikolainen, 1999);
d)	An analysis by Berglund (2005) of data collected by the Swedish Technology Assessment (Berglund, Thelander & Jonsson, 2003) showed that, compared with a robust and stable effect of singlesession brief interventions, those with repeat sessions demonstrated a larger average effect but one which was not uniform across studies;
e)	Most of the "classic" trials of brief intervention in the older literature (eg, Wallace, Cutler & Haines, Anderson & Scott, 1992; Fleming et al., 1997) studied interventions that could only be described as extended according to the description given above. These all showed a clear benefit of intervention compared with non-intervention controls or treatment as usual but did not include another control group consisting of briefer or simple advice. Thus, although the additional benefits of extended brief interventions cannot be deduced from these studies, they do represent prima facie evidence that brief interventions are effective;
f)	Finally, for brief interventions delivered to heavy drinking students in educational establishments in the USA, there is clear evidence from a
large number of studies of the effectiveness of extended brief interventions based on motivational interviewing principles (Carey et al., 2007).
Implications for practice
Given the evidence reviewed above, one conclusion might be that only brief advice should be implemented in practice at the present time; if and when evidence for the extra benefits of extended brief intervention becomes stronger, this view would say, implementation could be considered at that time. This certainly seems to have been the view of Anderson and Baumberg (2006) in their report to the European Commission on alcohol and alcohol policy in Europe. "Brief physician advice' was included in a recommended package of effective policies and programmes for implementation in the European Union. The recommendation in respect of brief advice was based on World Health Organisation modelling of the impact and cost of providing primary-care based brief advice to 25% of the at-risk population; applying this to the European Union would avoid an estimated 408,000 years of disability and premature death at a cost of 740 million Euros per year. It was noted that brief intervention for hazardous and harmful drinking, in the form of physician brief advice, was one of the most cost-effective of all health service interventions in promoting health gains. However, there was no mention in the report of brief counselling, brief motivational interviewing or any other form of more extended brief intervention beyond brief advice. The argument for widespread implementation of brief advice by physicians made by Anderson and Baumberg is compelling, especially on the grounds of cost-effective harm prevention. But could there yet be a current role for extended brief intervention in a recommended package of measures to prevent alcohol-related harm? Are there circumstances in which it is justifiable to implement extended brief interventions in practice? There are reasons for believing so and this was also the view of the NICE guidance referred to above (National Institute for Health & Clinical Excellence, 2010). These reasons are as follows:
i. First and most obviously, having been given brief advice some patients will request more discussion of their drinking with a health professional. Such a request is best served by brief motivational interviewing to explore what obstacles stand in the way of an attempt by the patient to cut down drinking to less risky levels.
ii.	The clinician may also judge that the seriousness of the patient's alcohol problem requires more than just brief advice. Although practice should be based on evidence, there will always be place for clinical judgement too and it is likely that some health professionals would object to offering nothing more than brief advice to all the problem drinkers presenting to them.
iii.	Some patients, probably the majority, will not respond to brief advice on follow-up and, in some cases, the offer of more extended brief intervention could be judged appropriate. This would be part of a stepped care model in which successively more intensive levels of intervention are tried if previous levels have proved unsuccessful (see Raistrick, Heather & Godfrey, 2006).
iv.	Extended brief interventions might also be given to young people aged 16-17 with alcohol-related difficulties (National Institute for Health & Clinical Excellence, 2010). Many would consider the offer of brief advice here to be inappropriate because young people of that age are not well-known for accepting advice! In addition, the evidence from educational establishments shows that brief motivational interviewing is appropriate and effective in the age -range.
v.	In a manual on the use of brief interventions for hazardous and harmful drinking issued by the World Health Organisation (Babor & Higgins-Biddle, 2001), "brief counselling' based on the stages of change model (Prochaska & DiClemente, 1986) is explicitly recommended for patient who score between 16 and 19 inclusive on the Alcohol Use Disorders Identification Test (AUDIT: Saunders et al., 1993).
vi.	Brief motivational interviewing is ideally suited to individuals who are ambivalent about the need to cut down their drinking - in other words, those who are in the Contemplation stage of the stages of change model (Prochaska & DiClemente, 1986). As noted above, there is some evidence from the Phase II study of the WHO Collaborative Project (Babor, 1996) that brief counselling is especially suited to patients who are not ready to cut down drinking and the effectiveness of brief motivational interviewing among such patients was shown by Heather and colleagues (1996). In addition, there is very good evidence for the effectiveness of motivational interviewing in the treatment of behavioural disorders in general (Lundhal et al., 2010).
None of these reasons should be taken as arguments against the deployment of brief advice in primary health care and other settings. On the contrary, the position here is that brief advice should always be offered as a first step to all patients who screen positive or who are otherwise judged to be hazardous or harmful drinkers. This is because the evidence firmly indicates that this is an effective and cost-effective policy and that, as noted above, it could make a considerable contribution to public health. It is only as an adjunct or addition to brief advice, in the circumstances outlined above, that the implementation of extended brief intervention is argued for here.
Implications for research
It is clear that the case for extended brief interventions that which has been made in this article is not based firmly on evidence of effectiveness, which it has been conceded is mixed, but on pragmatic grounds of everyday practice and patient need. As such, it is vulnerable to counter-arguments and other points of view.
There is one recommendation, however, that seems incontrovertible. This is the need for further research on this issue. Ironically, a comparison of brief advice and more extended brief intervention was included in the first trial of brief intervention in general medical practice which began almost 30 years ago (Heather et al., 1987); unfortunately that trial was under-funded and under-powered to provide a proper test of the relative effectiveness of the two approaches. Since that, time, despite a few relevant findings that have been mentioned earlier in the article, the issue has been largely ignored.
It is now time that this issue was taken very seriously by researchers and investigated in a proper manner. Assuming the additional benefits of extended brief interventions will not apply to all patients on all occasions, we need to know for what kinds of problem excessive drinker and in what kinds of settings and circumstances, if any, those benefits do apply. The findings of the Screening and Intervention Programme for Sensible Drinking (SIPS) in England (Coulton et al., 2009; Kaner et al., 2009; Newbury-Birch et al., 2009), which will be available during 2011, may be able to clarify this issue.
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RAZLOGI ZA UPORABO KRATKIH INTERVENCIJ
Nick Heather1
V zadnjih letih se kratke intervencije zaradi tveganega in škodljivega uživanja alkohola vedno bolj uveljavljajo, tako med raziskovalci, kot delno tudi med splošnimi zdravniki in drugimi zdravstvenimi delavci. To povečano zanimanje za ta ukrep, vsaj na primarni ravni, je močno podprto z dokazi o njegovi učinkovitosti (Kaner, Newbury-Birch&Heather, 2009). Pogosto pa ni povsem jasno, kaj natančno predstavlja kratka intervencija zaradi pitja alkohola. Dejstvo je, da izraz »kratka intervencija« ne opisuje enkratne, natančno določene storitve, temveč se nanaša na skupino posegov, ki se med seboj razlikujejo (Heather,1995). Čeprav je vsem kratkim intervencijam skupno to, da so krajše kot večina uveljavljenih programov zdravljenja težav z alkoholom, in so namenjene obravnavi pivcev, ki imajo manj resne težave in so manj odvisni od alkohola kot posamezniki vključeni v specializirane programe zdravljenja, se kratke intervencije razlikujejo med seboj v trajanju, številu obravnav, v postopkih in uporabljenih materialih, oblikah terapevtske interakcije, izvajalcev in okolja ter v teoretičnem pristopu na katerem temeljijo.
Dve glavni skupini kratkih intervencij
Kljub razlikam, lahko govorimo o dveh večjih skupinah terapevtskih obravnav, kamor sodi večina oblik kratkih intervencij, ki jih srečamo v strokovni literaturi in v praksi. Gre za tako imenovane »kratke nasvete« in »razširjene kratke intervencije«. O tem razlikovanju je govora v pregledu učinkovitosti zdravljenja težav z alkoholom, ki ga je naročil Oddelek za zdravstvo Velike Britanije (UK Department of Health) (Raistric; Heather & Godfrey, 2006) in v priporočilih nacionalnega inštituta za zdravje in klinično odličnost v nedavno objavljenih smernicah za preprečevanje tveganega in škodljivega uživanja alkohola v Veliki Britaniji (National Institute for Health and Clinical Excellence, 2010; glej še Kaner, 2010). V nadaljevanju opisujemo ti dve skupini kratkih intervencij.
Kratki nasvet
To vrsto kratke intervencije včasih imenujemo tudi »enostavni nasvet« ali "strukturirani kratki nasvet«, to
Uvodnik
pa zato, ker ni dovolj, da zdravnik nasvet posreduje kot se mu zdi najbolj primerno, temveč mora - če naj bo učinkovit - upoštevati določeno obliko in strukturo. Kratke nasvete so preučevali in uporabljali v glavnem v zelo dejavnih zdravstvenih okoljih, predvsem v primarnem zdravstvenem varstvu in na urgentnih oddelkih, kjer je čas zelo dragocen. Intervencija običajno neposredno sledi oceni, da gre pri posamezniku za tvegano in škodljivo uživanje alkohola. Včasih pacientu predlagamo, naj se po kratko intervencijo vrne v ustanovo. V teh okoljih, kjer poteka delo pod časovnim pritiskom, lahko intervenciji namenimo le pet do deset minut, včasih celo manj. Kratki nasvet navadno obsega standardni sveženj informacij o stopnjah tveganja pri uživanju alkohola in o statusu bolnika glede na te stopnje tveganja, vsebuje pa tudi spodbudo za zmanjšanje porabe alkohola in časovno opredelitev začetka te spremembe. Sem sodi še nekaj enostavnih napotkov za uspešno zmanjšanje uživanja alkohola in priročniki za samopomoč z dodatnimi nasveti. Zdravniki morajo pogosto uporabiti način interakcije z bolnikom, ki ga na kratko povzemajo znana načela FRAMES (Feedback-Responsibility-Advice-Menu-Empathy).
Povratna informacija - pridobitev povratne informacije o bolnikovem tveganju za težave z alkoholom; Odgovornost - jasna informacija o tem, da je posameznik sam odgovoren za spremembe; Nasvet - nasvet za zmanjšanje uživanja alkohola ali jasno navodilo za spremembo; Izbor - ponudba različnih možnosti za doseganje sprememb vedenja;
Empatija - topel odnos do bolnika in izražanje razumevanja do njegovih težav; Samoučinkovitost - spodbujanje optimističnega pogleda na vedenjske spremembe.
Raz{irjena kratka intervencija
Ta vrsta kratke intervencije je seveda daljša od kratkega nasveta in jo imenujemo tudi »kratko svetovanje«. Običajno traja ena obravnava 20 do 40 minut, večkrat pa ji sledijo še kontrolna srečanja. Od kratkega nasveta se razlikuje predvsem po teoretični osnovi intervencije. Razširjena kratka intervencija, ki jo uporabljamo danes, skoraj vedno temelji na načelih
1 Department of Psychology, School of Life Sciences, Northumbria University, Newcastle upon Tyne, UK Kontaktni naslov: e-pošta\nick.heather@northumbria.ac.uk
motivacijskega pogovora, kot ga opisujeta Miller in Rollinck (1991, 2002). Rollinck, Heather in Bell (1992) so opisali krajšo obliko motivacijskega pogovora, na vsebino in uporabljene metode pa so pozneje vplivale študije Stevena Rollincka in sodelavcev o uporabi načel in tehnik motivacijskega pogovora pri spreminjanju tveganega vedenja v zdravstvenih ustanovah (Rollinck, Mason & Butler, 1999; Rollinck, Miller & Butler, 2008). Za razliko od kratkega nasveta, gre tu za izpopolnjen, prožen in k bolniku usmerjen pristop, pri katerem se dosledno izogibamo dajanju nasvetov, razen v primeru, da zanje zaprosi bolnik sam. Seveda je zato kratki motivacijski pogovor v rabi v tistih okoljih in situacijah, kjer je za intervencijo več časa in so na voljo izvajalci izurjeni v tej tehniki. V svoji skrajni obliki kratki motivacijski pogovor prehaja v terapijo za spodbujanje motivacije (Motivational Enhancement Therapy) (Miller in sod., 1992) in v druge oblike motivacijskega pogovora (Burke, Arkowitz & Dunn, 2003), ki potekajo v specializiranih terapevtskih ustanovah. Čeprav skoraj vsi primeri razširjenih kratkih intervencij, opisani v literaturi, izhajajo iz motivacijskega pogovora, je treba opozoriti na to, da obstaja tudi zgodnejša oblika razširjene kratke intervencije, ki bi jo lahko poimenovali »zgoščena kognitivna behavioristična terapija«. Ta obsega krajše oblike metod, ki sestavljajo kognitivno-behavioristični pristop k zdravljenju: opredelitev situacij z visokim tveganjem, učenje strategij za obvladovanje teh situacij brez pretiranega pitja alkohola, učenje veščin za alternativne oblike vedenja, kognitivno restrukturiranje prepričanja in odnosa do sebe in pitja alkohola; tehnike za preprečevanje relapsov itd. Te vrste kratkih intervencij so preučevali v prvih študijah na primarni zdravstveni ravni v 80-ih letih prejšnjega stoletja (Heather in sod., 1987; Wallace, Cutler & Haines,1988) in jo primerjali z motivacijskim pogovorom (Heather in sod., 1996). Po obdobju izrednega zanimanja za motivacijski pogovor, je njegova uporaba danes omejena le še na priročnike za samopomoč, ki jih večkrat dobijo posamezniki brez neposrednega stika s terapevtom. Tega pristopa v nadaljevanju ne bomo obravnavali.
Kaj nam govore dokazi?
Kakšni so torej dokazi o učinkovitosti teh dveh skupin kratkih intervencij, ki naj bi podprli njihovo uporabo v praksi? Pregledna študija raziskav na primarni ravni, ki jo je nedavno objavil Kaner s sodelavci (2009), je potrdila ugotovitve prejšnjih sistematičnih ocen in meta analiz o uspešnosti kratkih nasvetov na primarni ravni v primerjavi s kontrolnimi primeri, t.j. z uporabo
tega pristopa pri drugih težavah. Ugotovili so, da je uspešnost kratkega nasveta 8 do 12 odstotna (Moyer in sod., 2002). Čeprav je odstotek ugoden v primerjavi z ocenjeno uspešnostjo nasvetov, ki jih dajejo zdravniki za opustitev kajenja (20%; Silagy & Stead, 2003) se nekaterim zdravnikom morda zdi, da je v kliničnem smislu dokaj nizek. S stališča javnega zdravstva pa ugotavljamo, da bi ta pristop lahko v veliki meri zmanjšal tvegano in škodljivo uživanje alkohola med splošnim prebivalstvom in tako bistveno prispevali k boljšemu javnemu zdravju, če bi bili v večini ustanov primarnega zdravstva vsi posamezniki s potrjeno diagnozo tveganega pitja dosledno deležni teh nasvetov. Ob tem, da je kratki nasvet koristen za mnoge posameznike, na primarni zdravstveni ravni nanj lahko gledamo kot na »udarni« ukrep za zmanjševanje škode, ki jo povzroča alkohol, z velikimi obeti za javno zdravstvo.
Dokazi v prid uporabi kratkega nasveta v drugih zdravstvenih ustanovah, kot so oddelki za poškodbe in urgentno medicino (Crawford in sod., 2004) in oddelki splošnih bolnišnic (Hallowey in sod., 2007), so obetavni, čeprav nekateri menijo, da so še nezadostni (Harvard in sod., 2008, McQueen in sod., 2009). Nadaljnje raziskave v teh okoljih so še v teku. Dokazi o učinkovitost kratkega nasveta v drugih zdravstvenih in nezdravstvenih okoljih so pomanjkljivi oziroma jih sploh ni, vendar kljub temu obstajajo razlogi za to, da verjamemo v vlogo teh ukrepov pri zmanjševanju škode, ki jo povzroči uživanje alkohola (Heather & Kaner, 2010).
Glede na ugotovljeno učinkovitost kratkega nasveta, je treba ugotoviti, katere dodatne koristi, prinaša bolniku razširjeni kratki pogovor v primerjavi s kratkim nasvetom.
Dokaze v prid razširjenemu kratkemu pogovoru lahko najbolje opišemo kot neenotne. Spodaj naštete raziskave nasprotujejo mnenju, da lahko razširjeni kratki nasvet ponudi bolniku več kot kratki nasvet.
a)	V sistematični pregledni študiji tega področja, je Kaner s sodelavci (2009) ob enoletnem kontrolnem pregledu ugotovil, da se je uživanje alkohola bolj zmanjšalo pri tistih bolnikih, ki so bili deležni več razširjenih kratkih ukrepov kot pri tistih, ki so dobili le kratke nasvete, vendar razlika med skupinama ni bila statistično pomembna.
b)	V zgodnejši sistematični raziskavi (2004) Ballesteros in sodelavci niso našli trdnih dokazov za »povezavo med odmerkom in odzivom«, med trajanjem kratke intervencije in izidom, kar kaže na to, da ni osnove za trditev, da so daljše intervencije bolj učinkovite kot krajše.
c) V drugi fazi skupne raziskave SZO o prepoznavanju in obravnavi težav povezanih z alkoholom v primarnem zdravstvu (WHO Collaborative Study on the Identification and Management of Alcohol-related Problems in Primary Care ) (Babor, 1996) so ugotovili, da ukrepi , kot je podaljšanje petminutnega enostavnega nasveta, ki je sledil petnajstminutni opredelitvi težave za dodatnih petnajst minut, oziroma razširitev svetovanja na tri obravnave, bolniku niso prinesli nobenih dodatnih koristi.
Po drugi strani pa obstajajo tudi dokazi o tem, da so
razširjene kratke intervencije bolj uspešne.
a)	Rezultati meta analize Kranerja in sodelavcev(glej zgoraj), ki so pokazali, da se je ob enoletnem kontrolnem pregledu uživanje alkohola bolj zmanjšalo pri posameznikih, ki so bili deležni razširjenih kratkih intervencij, so se približali statistični pomembnosti (p=0.09) in lahko odražajo napako tipa 2, kar pomeni, da sprejmemo hipotezo, da med skupinama ni razlike, kadar je ta v resnici lažna.
b)	Zgoraj omenjena skupna raziskava SZO je pokazala, da je bil enostavni nasvet bolj uspešen pri moških, ki so prepoznali svoje nedavne težave povezane s pitjem alkohola, razširjena kratka intervencija pa med tistimi, ki te težave niso priznavali. Te ugotovitve kažejo, da je slednji ukrep bolj učinkovit pri tistih posameznikih, ki težko priznajo potrebo po spremembah vedenja.
c)	Nekatere raziskave in pregledne študije kažejo, da so razširjene kratke intervencije bolj učinkovite kot kratki nasveti (npr. Richmond in sod.,1995; Israel in sod.,1996, Poikolainen, 1999).
d)	Berglund (2005), ki je analiziral podatke švedske tehnološke evalvacije (Swedish Technology Assessment) (Berglund, Thelander & Jonsson, 2003), poroča, da je bil, v primerjavi z močnim stabilnim učinkom kratkih enkratnih obravnav, poprečni učinek večkratnih obravnav večji, vendar ni bil enak v vseh študijah.
e)	Večina »klasičnih« raziskav v starejši literaturi (npr. Wallace, Cutler & Haines, Anderson & Scott, 1992, Fleming in sod., 1997) je preučevala intervencije, ki jih glede na zgornji opis lahko opredelimo kot razširjene. Vse te raziskave so jasno potrdile prednosti, ki jih imajo intervencije v primerjavi s običajnimi obravnavami, vendar pa študije niso vključevale še druge kontrolne skupine, ki bi predstavljala krajše ali enostavne nasvete. Zato na osnovi izsledkov teh študij ne moremo sklepati, da imajo razširjene kratke intervencije dodatne učinke, vendar predstavljajo t.i. dokaz prima facie o uspešnosti kratkih intervencij.
f) Številne študije kratkih intervencij pri študentih na izobraževalnih ustanovah v ZDA, ki so čezmerno uživali alkohol, jasno potrjujejo učinkovitost razširjenih kratkih intervencij, ki temelje na načelih motivacijskega pogovora (Carey in sod., 2007).
Pomen za prakso
Na osnovi pregledanih dokazov lahko zaključimo, da je danes v praksi uporaben le kratki nasvet. Razširjeni kratki pogovor pa naj bi začeli uporabljati takrat, ko bo zbranih več dokazov za to, da ima ta ukrep še dodatne prednosti za bolnika. Takšno je tudi mnenje Andersona in Baumberga (2006), ki sta ga v svojem poročilu predstavila Evropski komisiji za alkohol in alkoholno politiko v Evropi (European Commission on Alcohol and Alcohol policy in Europe) »Kratki nasvet zdravnika« so vključili v priporočeni sveženj učinkovitih ukrepov in programov, ki naj bi jih izvajali v EU. Priporočilo v zvezi s kratkim nasvetom je temeljilo na modeliranju vpliva in stroškov kratkih nasvetov, ki bi jih na primarni ravni nudili 25 odstotkom ogroženih prebivalcev. Po ocenah bi v EU s temi ukrepi prihranili 408,000 let invalidnosti in prezgodnjih smrti za ceno 740 milijonov evrov na leto. Ugotovili so, da je kratka intervencija pri tveganem in škodljivem uživanju alkohola v obliki kratkega nasveta zdravnika eden stroškovno najbolj učinkovitih zdravstvenih ukrepov v skrbi za boljše zdravje. Poročilo pa razen kratkega nasveta ne obravnava drugih ukrepov, kot so to, kratko svetovanje, kratek motivacijski pogovor ali kakšna druga oblika razširjene kratke intervencije. Razlogi za priljubljenost zdravnikovega kratkega nasveta, ki jih predstavljata Anderson in Baumberg, so zelo prepričljivi, še zlasti z vidika stroškovne učinkovitosti ukrepov za preprečevanja škode. Sprašujemo pa se, če je v priporočenem svežnju ukrepov za preprečevanje škode, ki jo povzroča pitje alkoholnih pijač, morda prostor tudi za razširjeno kratko intervencijo? Ali obstajajo okoliščine, v katerih je upravičena uporaba razširjenih kratkih intervencij v praksi? Obstajajo razlogi, ki govorijo temu v prid in o njih je govora tudi v zgoraj omenjenih smernicah NICE (National Institute for Health&Clinical Excellence, 2010). Ti razlogi so naslednji: 1. Prvi in najbolj očiten razlog je v tem, da po kratkem nasvetu nekateri posamezniki zaprosijo še za dodatni pogovor o svojem pitju z zdravstvenim strokovnjakom. Tej želji najlaže ustrežemo s kratkim motivacijskim pogovorom, v katerem raziščemo na kakšne ovire naleti posameznik ko skuša zmanjšati uživanje alkohola na manj tvegano stopnjo.
2.	Zdravnik lahko presodi, da resnost težav, ki jih ima bolnik z alkoholom, zahteva več kot le kratki nasvet. Čeprav mora praksa temeljiti na dokazih, bo vedno pomembna tudi klinična presoja in nekaterim zdravstvenim delavcev se ne zdi prav, da bi vsem problematičnim pivcem, ki pridejo k njim, ponudili zgolj kratki nasvet.
3.	Pri nekaterih bolnikih, verjetno pri večini, ob kontrolnem srečanju ne ugotavljamo nobene reakcije na kratki nasvet in zato se nam zdi v določenih primerih primerno ponuditi tem posameznikom še razširjeni kratki pogovor. Ta pogovor je sestavni del stopnjujočega se modela obravnave, kjer se intenziteta veča z vsakim naslednjim ukrepom, če se izkaže, da prejšnje stopnje obravnave niso bile uspešne (Raistrick, Heather in Godfrey, 2006).
4.	Razširjene kratke intervencije so primerne tudi za mladostnike s težavami povezanimi s pitjem alkohola, stare od 16 do 17 let (National Institute for Health and Clinical Excellence, 2001). Mnogim se ta možnost morda ne zdi primerna, saj mladi pri teh letih niso ravno znani po dojemljivosti za nasvete! Podatki iz izobraževalnih ustanov kažejo , da je kratki motivacijski pogovor primeren in učinkovit za to starostno skupino.
5.	V priročniku o uporabi kratkih intervencij v obravnavi tveganega in škodljivega pitja alkoholnih pijač, ki ga je izdala SZO (Babor & Higgins-Biddle, 2001), «kratko svetovanje«, ki temelji na stopnjah modela sprememb avtorjev Prochaske in DiClementeja (1986) še posebej priporočajo pri bolnikih, ki z vprašalnikom za samooceno o pitju alkoholnih pijač AUDIT zberejo 16 do 19 točk (Alcohol Use Disorders Identification Test; Saunders in sod., 1993).
6.	Kratko motivacijsko svetovanje je idealna oblika obravnave pri posameznikih, ki so razdvojeni glede nujnosti, da omejijo svoje pitje alkohola, z drugimi besedami, pri tistih, ki so na stopnji premisleka na modelu sprememb (Prochaska in DiClemente, 1986). Zgoraj omenjena druga faza skupne raziskave SZO (Babor, 1996) je potrdila, da je kratko svetovanje še zlasti primerno pri tistih posameznikih, ki še niso pripravljeni omejiti pitja. O učinkovitosti kratkega motivacijskega pogovora pri teh bolnikih poroča Heather s sodelavci (1996). Poleg tega, so zbrani zelo trdni dokazi za uspešnost motivacijskega pogovora pri obravnavi vedenjskih motenj na splošno (Lundhal in sod., 2010).
Nobenega od teh razlogov ne moremo obravnavati kot argument proti uporabi kratkega nasveta v primarnem zdravstvenem varstvu in v drugih okoljih. Prav nasprotno, mnenja smo, da moramo kratki nasvet vedno ponuditi
kot prvi ukrep vsem bolnikom s potrjeno anamnezo tveganega pitja, oziroma vsem tistim, za katere sodimo, da uživajo alkohol na tvegan in škodljiv način. Z gotovostjo so dokazali, da je ta oblika obravnave uspešna in stroškovno učinkovita in da lahko z njeno pomočjo, kot smo že omenili, bistveno prispevamo k boljšemu javnemu zdravju. Seveda zagovarjamo razširjeno kratko intervencijo le kot dodatek k kratkemu nasvetu v zgoraj opisanih okoliščinah.
Pomen za raziskave
Jasno je, da podpora razširjeni kratki intervenciji v tem prispevku ne temelji na dokazih o njeni učinkovitosti. Priznati je treba, da ni enotnih rezultatov o uspešnosti tega ukrepa, govorimo lahko le o pragmatičnih ugotovitvah vsakodnevne prakse in o potrebah bolnikov. Ta podpora je zato seveda občutljiva za protidokaze in vsa drugačna stališča. Dejstvo, ki mu ni moč ugovarjati, pa je potreba po nadaljnjih raziskavah na tem področju. Zanimivo je, da je bila primerjava med kratkim nasvetom in razširjeno kratko intervencijo vključena že v prvi preskus kratke intervencije v splošnem zdravstvene varstvu pred skoraj 30 leti (Heather in sod., 1987). Zaradi nezadostnih finančnih in kadrovskih možnosti preskusa učinkovitosti obeh oblik ukrepov na žalost ni bilo mogoče ustrezno izpeljati. Kljub nekaterim pomembnim izsledkom, ki smo jih v prispevku že omenili, pravega zanimanja za to področje vse od takrat ni bilo več.
Čas je, da se začnejo resne in prave raziskave o tem vprašanju. Ker domnevamo, da razširjeni kratki ukrepi nimajo dodatnih koristnih učinkov na vse bolnike in v vseh okoliščinah, moramo vedeti pri katerih problematičnih pivcih, v katerih okoljih in v kakšnih okoliščinah, če sploh, te pozitivne učinke lahko pričakujemo. Izsledki raziskave o presejanju in intervencijah za razumno uživanje alkohola (Screening and Intervention Programme for Sensible Drinking, SIPS, Coulton in sod., 2009; Kaner in sod., 2009; Newbury-Birch in sod., 2009), ki bodo na voljo leta 2011, bodo lahko pojasnili to vprašanje.
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UVAJANJE NOVIH FARMACEVTSKIH STORITEV OB PREHODU NA CENTRALIZIRANO PRIPRAVO PROTITUMORSKIH ZDRAVIL
IMPLEMENTING NEW CLINICAL PHARMACY SERVICES PARALLEL TO THE INTRODUCTION OF CENTRALIZED PREPARATION OF ANTI-CANCER DRUGS
Lea Knez1, Maja Jošf, Janez Toni1, Nadja Triller1, Tanja Čufer1 Prispelo: 6. 1. 2010 - Sprejeto: 20. 3. 2010
Izvirni znanstveni ~lanek UDK 615.2 + 616-006
Izvle~ek
Uvod: Pr^otitumor^skaa zdravila uvr{~amo med zdravila z velik^im tveganjem. Pri zagotavljanju kakovosti, varnosti in u~inkovitosti uporabe protitumors^ih zdravil vloga farmacevta ne sme biti omejena le na njihovo pripravo. S prispevkom želimo predstaviti vpeljavo farmacevtske storitve pregled predpisa keemoterapije v klini~no prakso in z analizo zabeleženih ukrepov prikazati njene koristi.
Metode: Raziskava je potekala v Bolnišnici Golnik KOPA, kjer p^o^itumo^s^a zdravila pripravljajo (centralizirano. Uporabili so metode za vpeljavo storitve pregled predpisa kemoterapije. Po njeni vpeljavi so farmacevti leta 2009 v petmese~nem obdobju beležili ukrepe med njenim izvajanjem in jih analizirali.
Rezultati: Pregled predpisa keemoterapije s strani farmacevta smo vpeljali v rutinsko klini~no prakso in ob tem opredelili njegove naloge in dolžnosti. V opazovanem obdobju je bilo vklju~enih 506 naro~il kemoterapije, pri njihovem pregledu pa je pet farmacevtov zabeležilo 211 ukrepov. Velik delež ukrepov dokazuje, da je vpeljana storitev koristna. Ukrepi so v^lju~e^ali p^otitumo^s^a zdravila (31 %), antiemetike (41 %) in druga zdravila v podpornem zdr^avljenju (12 %). Do neskladij je prišlo pri kategorijah »odmerek in režim odmerjanja« (64 %), »izbija zdravila« (21 %) in »administi-ativna« kategorija (14 %). Najbolj pogoste kategorije in podkategorije z zaznanimi neskladji kažejo, katera podro~ja je potrebno izboljšati. Zdravniki so uresni~ili večiino predlaganih ukrepov (76 %), kar potrjuje potrebo in smiselnost predlaganih intervencij tudi z zdravniškega zornega kota. Zbrani podatki zaenkrat ne vsebujejo informacij o klini~nem pomenu predlaganih uresni~enih in neuresničenih ukrepov za bolnikovo zdravstveno oskrbo.
Zaključek: Velik delež intervencij, opisan v tej študiji, potrjuje, kako pomembno je, da v onkološko dejavnost vklju~imo farmacevtova klinična znanja, da bi zagotavili visoko kakovost njenih storitev.
Ključne besede: klinična farmacija, zdravljenje z zdravili, kemoterapija, onkologija, rak
Original scientific article UDC 615.2 + 616-006
Abstract
Introduction: Anti-cancer drugs belong to a group of high-risk medications. In guaranteeing the quality, safety and efficacy of these drugs, pharmacists' role should not be restricted to overseeing their preparation. This study describes the implementation of a new pharmacy service - chemotherapy prescription screening - and evaluates its benefits by analysing the recorded interventions.
Methods: The study was conducted in a Slovene teaching hospital with centralized chemotherapy pr^eparation, in which methods to implement chemother^apy prescription screening were introduced. After this service had been implemented, the performed interventions were recorded over a five-month period in 2009. Results: Chemotherapy prescription screening by pharmacists was integrated into r-outine clinical practice, and pharmacists' responsibilities and duties were defined. During the study period, 506 cancer prescriptions were reviewed by five pharmacists, who recorded 211 interventions. The high rate of interventions emphasizes the role
1Bolnišnica Golnik KOPA, Golnik 36, 4204 Golnik, Slovenija Kontaktni naslov: e-pošta: lea.knez@klinika-golnik.si
that pharmacists play in oncology services. The interventions involved cancer drugs (31%), antiemetics (41%) and other support care drugs (12%). The identified problems were related to the following categories: "dose, frequency and regimen" (64%), "drug selection" (21%) and "administrative" (14%). Clinicians accepted most pharmacists' recommendations (76%), thereby confirming the need for the proposed interventions also from a medical point of view. However, the study provides no information on the clinical significance of the recorded interventions, whether accepted or not.
Conclusion: The high rate of interventions recorded in this study stresses the importance of integrating pharmacists' clinical roles into oncology services in order to maintain high quality standards of cancer treatment.
Key words: clinical pharmacy, drug therapy, chemotherapy, oncology, cancer
1 Uvod
Ob pove~evanju incidence raka se mora onkolo{ka dejavnost nenehno razvijati in izpopolnjevati. Neizogiben del razvoja je tudi raziskovanje, ki v onkolo{ki dejavnosti ne sme biti usmerjeno le k odkrivanju novih diagnosti~nih metod, zdravil in na~inov zdravljenja, temve~ mora stremeti tudi k optimizaciji in izboljšanju že ute~enih na~inov dela. Če dandanes nova, tar~na zdravila obljubljajo možnost individualne izbire zdravljenja glede na zna~ilnosti posameznega bolnika in biologijo posamezne vrste raka, ohranja kemoterapija osrednjo vlogo pri zdravljenju velikega števila razli~nih vrst raka.
Protitumorska zdravila uvrš~amo med zdravila z visokim tveganjem: napake pri njihovem predpisovanju, pripravi in uporabi pa so povezane z visokim tveganjem za neželene u~inke, ki jih imajo na bolnikovo zdravje in življenje (1, 2). Tveganje za pojav resnih neželenih u~inkov ni omejeno le na napake pri uporabi teh zdravil, ampak je prisotno tudi ob doslednem upoštevanju vseh preverjenih znanj, veljavnih navodil in priporo~il za njihovo uporabo v vsakodnevni klini~ni praksi. Prav zaradi prisotnosti tveganja so postopki predpisovanja, priprave in dajanja protitumorskih zdravil ustrezno predpisani in zahtevajo sodelovanje zdravstvenih delavcev razli~nih strok (3, 4). Farmacevti imajo zelo pomembno vlogo pri upravljanju tveganja, povezanega s protitumorskimi zdravili (3, 4, 5, 6, 7). Priporo~ila o farmacevtski onkološki dejavnosti so si enotna pri opisovanju vloge in dolžnosti farmacevta pri pripravi teh zdravil in poudarjajo nujnost vzpostavitve centralizirane priprave protitumorskih zdravil. Priporo~ila so si enotna tudi glede nujnosti vklju~itve farmacevta v onkološko dejavnost z razli~nimi klini~nimi dejavnostmi, vendar pa je ta vloga opisana ohlapno in vsebuje veliko razlik v obsegu ter vsebino farmacevtovih nalog in dolžnosti opredeljuje zelo razli~no (3, 4, 5, 6, 7). Tako nekatera priporo~ila opisujejo preverjanje izra~una odmerkov predpisanih zdravil glede na bolnikovo telesno
površino zgolj kot zaželeno (3), druga priporo~ila pa ob tem izpostavljajo pomembnost preverjanja odmerka glede na bolnikovo krvno sliko, ledvi~no in jetrno funkcijo, potrditev stabilnosti u~inkovin v izbranem mediju in njegovem volumnu, ugotavljanje ustreznosti predpisa antiemeti~nega in drugega podpornega zdravljenja in še zlasti pregleda morebitnih interakcij med predpisanimi zdravili in bolnikovim kroni~nim zdravljenjem (6). Z razvojem novih protitumorskih u~inkovin se je pove~alo tudi znanje o možnih sou~inkih med samimi protitumorskimi u~inkovinami ter med njimi in ostalim podpornim in drugim farmakološkim zdravljenjem. Osveš~anje o medsebojnem delovanju je tako postalo ena najpomembnejših nalog klini~nega farmacevta na podro~ju onkologije. Korist dodatnega preverjanja predpisovanja kemoterapije s strani farmacevta trdno podpirajo tudi rezultati sicer maloštevilnih študij (8, 9, 10, 11, 12, 13, 14). Prispevek teh dejavnosti k zagotavljanju varnosti bolnikov najbolj nazorno dokazuje poro~ilo britanske Državne agencije za vpogled v bolnikove izide in smrt (angl. National Enquiry into Patient Outcome and Death, v nadaljevanju NCEPOD), v kateri so pregledali zna~ilnosti in zdravljenje bolnikov, ki so umrli v 30 dneh po dajanju kemoterapije (8). Farmacevt predpisa kemoterapije ni pregledal pri polovici teh bolnikov. Na podlagi teh rezultatov je NCEPOD prepoznala sodelovanje farmacevta pri preverjanju predpisovanja kemoterapije kot nujen ukrep za zmanjšanje pojava napak s potencialno smrtnim izidom. Zgornji podatki dokazujejo, da ima farmacevt pomembno vlogo ne le pri pripravi protitumorskih zdravil, temve~ tudi kot varnostni mehanizem pri njihovem predpisovanju. Sodelovanje farmacevta v multidisciplinarnem timu prispeva ekspertizo s podro~ja farmakokinetike in interakcij med zdravili, zato moramo za izboljšanje kakovosti in varnosti zdravljenja s protitumorskimi zdravili stremeti k sodelovanju farmacevtov v vsakem koraku njihove uporabe.
Namen tega dela je opisati vpeljavo novih farmacevtskih klini~nih storitev ob prehodu na centralizirano pripravo
protitumorskih zdravil v Bolnišnici Golnik KOPA ter ovrednotiti dodano vrednost te storitve.
2 Materiali in metode
članek opisuje razvoj nove onkološke dejavnosti -pregled predpisa kemoterapije s strani farmacevta, ter podaja rezultate farmacevtovih ukrepov v petmesečnem obdobju med junijem in novembrom 2009.
2.1	Materiali
Bolnišnica Golnik - Klinični oddelek za pljučne bolezni in alergijo je s svojo terciarno dejavnostjo usmerjena k diagnostiki in zdravljenju bolnikov s pljučnimi in alergijskimi boleznimi, s svojo raziskovalno dejavnostjo pa k razvoju novih storitev in izboljšanju utečenih procesov dela (15). Obseg onkološke dejavnosti se je od pričetka zdravljenja s kemoterapijo leta 1986 razširil: v bolnišnici letno odkrijejo 400 novih primarnih tumorjev pljuč in s sistemskim zdravljenjem zdravijo okoli 150 bolnikov z drobnoceličnim in nedrobnoceličnim pljučnim rakom ter mezoteliomom. V bolnišnici se na enoti za sistemsko zdravljenje zdravijo ambulantni in hospitalizirani bolniki. V času poteka študije so bili citostatiki edina protitumorska zdravila, potrebna rekonstitucije.
Med potekom študije so kemoterapijo predpisovali štirje zdravniki: trije specialisti internisti pulmologi in en specialist internist onkolog. Naročilo za pripravo kemoterapije je podano v obliki obrazca »klinična pot kemoterapije«, ki služi kot receptni obrazec za kemoterapijo, obenem pa tudi za evidenco, vodenje in načrtovanje celotnega bolnikovega zdravljenja s kemoterapijo (Slika 1).
Pripravo kemoterapije, ki je prvotno potekala na oddelku, so marca 2007 prenesli v lekarno. V času poteka študije je predpis kemoterapije pregledovalo pet magistrov farmacije, kemoterapijo pa so pripravljali trije magistri farmacije in dva farmacevtska tehnika.
2.2	Metode pri uvajanju nove storitve pregleda predpisa kemoterapije
Vključevanje farmacevtov v pregled predpisa kemoterapije se je pričelo takoj ob prenosu priprave kemoterapije v lekarno, vendar se je obseg dejavnosti v času spreminjal. Pri oblikovanju dejavnosti je bilo ključno stalno sodelovanje vseh članov zdravstvenega tima: zdravnikov, medicinskih sester in farmacevtov, ki so predloge o procesu izmenjevali v vsakodnevni praksi in na usmerjenih sestankih. Metodološke točke, ki so bile nujne za dosego sedanje ravni dela, so izpostavljene v nadaljevanju.
2.2.1	Pregled literature
Evropske, angleške, ameriške in kanadske standarde in priporočila za farmacevtsko onkološko dejavnost so pregledali, da bi se seznanili z nalogami in dolžnostmi farmacevtov; večjo pozornost pa so tudi namenili opisu farmacevtovega dela pri pregledu predpisa kemoterapije (3, 5, 6, 7). Pregledane študije, ki so poročale o napakah pri predpisovanju in pripravi kemoterapije ali so vrednotile učinek uvedbe novih storitev za njihovo zmanjšanje, so izpostavile tista področja, pri katerih je tveganje za napake večje (8, 9, 10, 11, 12, 13, 14). Dejavnosti so načrtovali tako, da je bilo tveganje na teh mestih čim manjše.
2.2.2	Izdelava informacijskih listov za uporabljene sheme kemoterapije
Za vsako uporabljeno shemo kemoterapije je bil izdelan informacijski list s podatki o odmerjanju in režimu odmerjanja citostatikov, volumnu nosilnih raztopin protitumorskih zdravil, vrstnemu redu in času dajanja zdravil, natančnim predlogom premedikacije z antiemetiki in drugim podpornim zdravljenjem, z opisom potrebe po prilagoditvi odmerkov citostatikov, pričakovanih neželenih učinkih in z navodili o ukrepanju ob njihovem pojavu ter s podatki o součinkovanju zdravil in drugih načinov zdravljenja. Informacijski listi so bili izdelani na podlagi povzetkov glavnih značilnosti zdravil (16, 17), navodil za posamezno shemo kemoterapije svetovnih terciarnih centrov za zdravljenje onkoloških bolnikov in strokovnih združenj (3, 6, 18, 19) ter druge objavljene literature (20, 21, 22). Pregledane podatke so si zdravniki, medicinske sestre in farmacevti interpretirali na podlagi lastnih kliničnih izkušenj in jih v okviru zmožnosti v ustanovi oblikovali v informacijske liste, ki povzemajo usklajene informacije o zdravljenju s posamezno shemo kemoterapije.
2.3 Metode pri pregledu predpisa kemoterapije s strani farmacevta
Obseg storitve pregleda predpisa kemoterapije s strani farmacevta se je od začetka njegove vpeljave spreminjal in se še vedno spreminja. V nadaljevanju opisujemo proces dela, ki je v veljavi od marca 2009 do konca preučevanega obdobja (Slika 2). Vsako naročilo kemoterapije mora pred sprejemom in začetkom priprave pregledati farmacevt. Ta lahko sprejme in začne s pregledom predpisa kemoterapije le, če je predpis pregledal zdravnik specialist, akreditiran za predpisovanje kemoterapije, in je to označeno z njegovim podpisom na obrazcu »klinična pot kemoterapije«. Farmacevt najprej pregleda, če so izpolnjeni vsi potrebni administrativni podatki.
Slika 1. Del obrazca »klinična pot kemoterapije« Figure 1. Part of the »chemotherapy form«.
Nato mora preveriti ustreznost predpisanih odmerkov protitumorskih zdravil glede na bolnikovo telesno površino, upoštevajo~ bolnikovo jetrno in ledvi~no funkcijo ter izbrano shemo zdravljenja. Farmacevt mora pregledati tudi, ali je glede na izvide krvne slike potrebna prilagoditev odmerkov protitumorskih zdravil ali celo preložitev kemoterapije. Ob pregledu predpisa kemoterapije je potrebno preveriti ustreznost predpisanega podpornega zdravljenja, ki poleg zdravljenja z antiemetiki zajema tudi predpisovanje zdravil za prepre~evanje drugih neželenih u~inkov. Farmacevt preveri tudi potrebo po spremembi dogovorjenega na~ina administracije in nosilnega topila za posamezno zdravilo, ~as in vrstni red dajanje protitumorskih zdravil in podpornega zdravljenja. Pri pregledu predpisa kemoterapije farmacevt uporablja posebni obrazec, ki služi za zapis potrebnih podatkov, ozna~evanje opravljenih pregledov in zapis ukrepov s pripadajo~imi izidi. Vprašanja in nejasnosti, ki se pojavijo ob predpisu kemoterapije, se razrešijo skupaj z odgovornim zdravnikom. Ob zaklju~ku pregleda farmacevt s svojim podpisom na obrazec »klini~na pot kemoterapije« sprejme naro~ilo in ga posreduje v pripravo.
2.4 Metode pri analizi farmacevtovih ukrepov ob pregledu predpisa kemoterapije
Farmacevtovi ukrepi so bili zbrani v retrospektivni prese~ni študiji med junijem in novembrom 2009. Pri vsakem ukrepu so zabeležili ugotovljeno neskladje s priporo~ili na informativnih listih, predlagani ukrep in njegovo uresni~enje. Ugotovljena neskladja so kategorizirali glede na klasifikacijo, izdelano na podlagi pregledane literature (9, 10, 12, 13, 14) in lastnih opazovanj. Neskladja so združili v štiri kategorije: »administrativni«, »zdravilo«, »odmerek in režim odmerjanja« ter »dajanje zdravila«. Vsaka kategorija je imela ve~ podskupin. Predlagane ukrepe je zdravnik lahko uresni~il, uresni~il z manjšimi spremembami ali jih ni uresni~il.
Podatki so bili vnešeni v preglednico, izdelano v programu SPSS, verzija 16. Podatki so predstavljeni kot absolutne vrednosti in deleži. Kjer je možno, so podane povpre~ne vrednosti in razpon vrednosti. Za analizo povezav in razlik smo uporabili test hi-kvadrat in t-test. Kot statisti~no zna~ilnost je privzeta vrednost p, manjša od 0,05.
3 Rezultati
V Bolnišnici Golnik KOPA so bile farmacevtske onkološke storitve v smislu centralizirane priprave
protitumorskih zdravil nadgrajene z uvedbo pregleda predpisa kemoterapije s strani farmacevta, ki je danes obvezen korak v procesu zdravljenja bolnikov s kemoterapijo.
V obdobju med 22. junijem in 30. novembrom 2009 je bilo sprejetih 506 naro~il kemoterapije, pri katerih je bilo zabeleženih 211 ukrepov (Tabela 1). Najve~ naro~il, ki je zahtevalo farmacevtovo ukrepanje, se je nanašalo na sheme cisplatin - gemcitabin (69/211; 32,7 %), cisplatin - etopozid (35/211; 16,6 %) in karboplatin - gemcitabin (27/211; 12,8 %), kar sovpada z najbolj pogosto predpisanimi shemami v bolnišnici. Zabeleženi ukrepi so se v 30,8 % nanašali na protitumorska zdravila, v 41,2 % na antiemetike, v 12,3 % pa na drugo podporno zdravljenje. Kortikosteroidi so bili vpleteni v tretjino ukrepov (70/221). Farmacevtovi ukrepi so bili najbolj pogosto potrebni zaradi neskladij, povezanih z odmerkom ali režimom odmerjanja zdravila (64,0 %). Sledila so neskladja zaradi manjkajo~ega predpisa zdravila ali predpisa nepotrebnega zdravila (21,3 %) in neskladja administrativne narave (14,2 %) (Tabela 2). Izmed posameznih podskupin znotraj kategorije »odmerek in režim odmerjanja« so farmacevtovo ukrepanje najpogosteje (79/211, 37,4 %) zahtevala neskladja predpisanega odmerka podpornega zdravljenja z informacijskim listom. V 58 izmed teh primerov je bilo vpleteno zdravilo deksametazon. V ve~ kot 15 % intervencij, še vedno znotraj kategorije »odmerek in režim odmerjanja«, so farmacevti predlagali spremembo odmerka protitumorskega zdravila zaradi prevelikega odstopanja od izra~una (20/211; 9,5 %), prilagoditev odmerka zaradi izvidov krvne slike (8/211; 3,8 %) ali oslabljene ledvi~ne oziroma jetrne funkcije (6/211; 2,8 %). Znotraj kategorije »zdravila« je bilo potrebnih 10,0 % (21/211) ukrepov, ker ustrezni antiemetiki ali druga zdravila podpornega zdravljenja niso bila predpisana, 7,6 % (16/211) ukrepov pa se je nanašalo na nepotrebni predpis istih zdravil. Znotraj »administrativne« kategorije so manjkajo~i podatki, bodisi administrativne narave (9,5 %; 20/211) bodisi glede odmerka zdravil (7,1 %; 15/211) pogosto zahtevali farmacevtovo ukrepanje. V štirih od 211 intervencij (1,9 %) je ukrepanje zahtevala razlika v predpisu odmerka protitumorskega zdravila na obrazcu »klini~na pot kemoterapije« in terapevtski listi. V omenjene intervencije so bila pri štirih razli~nih bolnikih vpletena zdravila pemetreksed, cisplatin in gemcitabin, in sicer so razlike med predpisoma bile v razponu od 13 do 90 %.
Zdravniki so uresni~ili 75,8 % farmacevtovih predlogov, 4,7 % predlogov so uresni~ili v spremenjeni obliki, 16,6 % predlogov pa niso uresni~ili.
Slika 2. Potek sprejema naročila kemoterapije.
Figure 2. Process flowchart for acceptance of a chemotherapy order.
Legenda: kemoterapija (KT) Footnote: chemotherapy (KT)
Tabela 1. Značilnosti zabeleženih intervencij. Table 1. Characteristics of the recorded interventions.
Zna~ilnost Characteristic	n	%
DELEŽ INTERVENCIJ Number of interventions	211/506	41,7
ZDRAVILA, VPLETENA V INTERVENCIJO Drugs involved in the intervention		
protitumorska zdravila Anti-cancer drugs	65/211	30,8
antiemeti~na zdravila Antiemetics	87/211	41,2
drugo podporno zdravljenje Other support therapy drugs	26/211	12,3
nobeno zdravilo No drug	33/211	15,6
URESNIČENI PREDLOGI INTERVENCIJ Intervention implementation		
uresni~en Implemented	160/211	75,8
uresni~en s spremembo Implemented with amendments	10/211	4,7
ni uresni~en Not implemented	35/211	16,6
Tabela 2. Klasifikacije neskladij, zaznanih znotraj intervencij s pripadajočimi primeri intervencij in frekvencami.
Table 2. Classification of intervention problems including examples and frequencies.
Klasifikacija Classification	Primer Example	N%
ADMINISTRATIVNI Administrative		32/211 15,2
ni administrativnega podatka Administrative data missing
naro~ilo ni avtorizirano Unauthorized CT order
napa~en administrativni podatek Wrong administrative data
drugo Other
Ni zapisanega datuma prejema KT. CT date not recorded.
Naro~ilo KT ni podpisano s strani odgovornega zdravnika. CT order not signed by the responsible clinician.
Telesna vi{ina se med posamezni krogi razlikuje za 9 cm. Patient's height between two cycles differs by 9 cm.
Ni izpolnjenega obrazca »izvajanje sistemske terapije«. CT not ordered through the Chemotherapy form.
20/211 9,5
7/211	3,3
3/211	1,4
2/211	0,9
ZDRAVILA Drug
45/211 21,3
manjkajoče zdravilo Needed drug not ordered
nepotrebno zdravilo Drug
not needded
zdravilo kontraindicirano
The prescribed drug is contraindicated
drugo Other
Ob cisplatinu ni predpisana antiemetično zdravljenje. No antiemetics prescribed alongside cisplatin.
Bolnik ima predpisan metilprednizolon v kronični terapiji in deksametazon kot antiemetično zdravljenje ob kemoterapiji.
Duplication of therapy with methylprednisolone (regular therapy) and dexamethasone (antiemetic during CT).
Bolniku, ki ima ocenjeno GFR pod 50 mL/min, je predpisan cisplatin.
Cisplatin prescribed for patient with GFR below 50 mL/min.
Pri bolniku je naročeno tri-dnevno zdravljenje z etopozidom, vendar je na terapevtski listi napisano zdravljenje samo za en dan.
Three doses of etoposide ordered, but only one dose prescribed on drug chart.
21/211 10,0
16/211 7,6
5/211
3/211
2,4
1,4
ODMEREK IN REZIM ODMERJANJA Dose and regimen
133/211 63,0
neskladje odmerka podporne terapije z informacijskimi listi
Prescribed dose of supportive care drugs differs from internal recommendation
odstopanje odmerka protitumorskega zdravila glede na izračun Discrepancy between the prescribed dose and calculated dose
ni podatka o odmerku
Chosen drug dose not written on the CT order
potrebna prilagoditev protitumornega zdravila zaradi krvne slike Need for adjustment of anti-cancer drug dose due to altered blood test results
potrebna prilagoditev protitumorskega zdravila zaradi ledvične ali jetrne funkcije Need for adjustment of anti-cancer drug dose in impaired renal or liver function
drugo Other
Ob shemi na osnovi cisplatina je predpisan deksametazon 12 mg.
Dexamethasone 12mg ordered for patients on cisplatin-based CT.
Predpisani odmerek karboplatina se razlikuje za več kot 10 % od izračuna na podlagi sedanje ocene GFR. A difference of more than 10% between the prescribed carboplatin dose and the dose calculated based on current GFR estimation.
Na obrazcu »izvajanje sistemske terapije« ni zapisana želena koncentracija pod krivuljo za karboplatin. The targeted concentration under the curve for carboplatin is not recorded on the CT form.
Ni prilagoditve odmerka enega ali vseh protitumorskih zdravil glede na krvno sliko .
Dose of one or several anti-cancer drugs is not adjusted according to blood test results.
Ni prilagoditve odmerka glede na oslabljeno ledvično ali jetrno funkcijo.
No dose adjustment in impaired renal or liver function.
Na obrazcu »izvajanje sistemske terapije« je predpisan drugačen odmerek citostatika kot na terapevtski listi. Discrepancy between anti-cancer drug doses prescribed on the chemotherapy form and on the drug chart.
79/211 37,4
20/211 9,5
15/211 7,1
8/211
6/211
5/211
3,8
2,8
2,4
APLIKACIJA Administration
1/211
0,5
drugo Other
Pri bolniku je predpisan antiemetik za intravensko dajanje, čeprav je vsa ostalo zdravljenje z zdravili za peroralno dajanje.
Patient was prescribed intravenous antiemetics whereas other drugs wer^e prescribed for oral administr^ation.
1/211
0,5
Legenda: kemoterapija (KT); glomerulna filtracija (GFR) Footnote: chemotherapy (CT); glomerular filtration rate (GFR)
Določene kategorije neskladij so bile bolj pogosto povezane z določenimi skupinami zdravil (hi-kvadrat, df=6, p<0,001): ukrepi v »administrativni« kategoriji pogosto niso bili vezani na nobeno posamezno zdravilo, temveč na naročilo kot celoto, neskladja iz kategorije »zdravilo« so se bolj pogosto kot na protitumorska zdravila nanašala na antiemetična zdravila in drugo podporno zdravljenje, medtem ko so se neskladja iz kategorije »odmerek in režim odmerjanja« bolj pogosto kot na zdravila drugega podpornega zdravljenja nanašala na protitumorska zdravila in antiemetično zdravljenje. Zdravniki so tudi bolj pogosto sprejeli in uresničili ukrepe različne narave (hi-kvadrat, df=4, p=0,003): ukrepi administrativne narave so bolj pogosto uresničili, in sicer vse predlagane ukrepe (29/29), kot intervencije, vezane na odmerek in režim odmerjanja zdravil, ki so jih zdravniki uresničili v 72,5 % (95/131). Večji delež neuresničenih ukrepov je bil tudi med tistimi, ki so predlagale spremembo odmerka protitumorskega zdravila. Od 34 ukrepov tako ni bilo uresničenih 10 intervencij (29,4 %), dve (5,9 %) pa sta bili delno uresničeni. V štirih izmed teh primerov je bila ugotovljena več kot 10-odstotna razlika med predpisanim in izračunanim odmerkom zdravila (razpon razlik od 11,8 % do 20,5 %). Odmerek zdravila ni bil spremenjen, ker so bolniki isti odmerek prejemali že v preteklosti. V dveh ukrepih so predlagali znižanje odmerka zdravila ob vrednosti nevtrofilcev pod 1,5 x 109/L, vendar so se zdravniki ob njihovi mejni vrednosti (1,4 x 109/L) in dobri telesni zmogljivosti bolnika odločili za polni odmerek. Obratno je bilo zabeleženo v dveh drugih ukrepih, kjer je bil odmerek gemcitabina v krogu B znižan na 50 % kljub vrednosti nevtrofilcev nad 1,0 x 109/L, ki tega niso zahtevale. Preostali štiri ukrepi so predlagali prilagoditev odmerkov zdravil glede na izvide jetrnih testov. Dva izmed teh ukrepov nista bila sprejeta, saj je zdravnik ocenil, da izvidi jetrnih testov odražajo prisotnost zasevkov v jetrih in ne oslabele jetrne funkcije, pri ostalih dveh ukrepih pa sta bila odmerka prilagojena deloma upoštevajoč izvide jetrnih testov, deloma ob upoštevanju ocene bolnikove telesne zmogljivosti.
4 Razpravljanje
Prispevek je prikazal razvoj nove farmacevtske storitve v onkološki dejavnosti in z analiziranjem dosedanjega dela pokazal njen doprinos h kakovosti oskrbe onkoloških bolnikov.
4.1 Razprava rezultatov farmacevtovih ukrepanj ob pregledu predpisa kemoterapije
V	opazovanem obdobju petih mesecev je bilo pri 506 sprejetih naročilih kemoterapije zabeleženih 211 ukrepov. Pri posameznem naročilu je bil lahko zabeležen več kot en ukrep. V študijo so bila vključena vsa naročila v tem obdobju. Ukrepi so bili zabeleženi ob rutinskem izvajanju pregleda predpisa kemoterapije. Delež ukrepov na naročilo kemoterapije je visok, in sicer znaša 41,7 %. Iz zbranih podatkov za obdobje samo petih mesecev ni mogoče analizirati trenda deleža ukrepov, vendar pričakujemo njihovo upadanje. Problemi, prepoznani v posameznem ukrepu, kažejo na področja, kjer so potrebne izboljšave; te pričakujemo že ob stalnem opozarjanju na probleme sorodne vsebine.
Največ ukrepov je bilo zabeleženih pri shemah zdravljenja, ki se najbolj pogosto uporabljajo pri pljučnem raku, in sicer kombinacije gemcitabina oziroma etopozida s spojinami na osnovi platine. Ta rezultat je pričakovan in ne pomeni, da je tveganje za napake večje pri predpisovanju omenjenih shem ali pri posameznem izmed tovrstnih citostatikov.
V	sklopu sprejema naročila kemoterapije je zajet tudi pregled predpisa zdravil v podpornem zdravljenju, tako je lahko tudi predpis teh zdravil zahteval ukrepanje. Različne skupine zdravil: protitumorna, antiemetična in zdravila za podporno zdravljenje so bila pogosto povezana z ukrepi različne narave. V nadaljevanju so za vsako skupino zdravil opisana najbolj pogosta neskladja s priporočili v informacijskih listih.
4.1.1 Intervencije, vezane na predpis zdravil v podpornem zdravljenju
Zdravila v antiemetičnem in podpornem zdravljenju so bila neposredno vpletena v več kot polovico ukrepov. Farmacevti so pogosto (79/211; 37,4 %) opozarjali na neskladja med predpisanim odmerkom zdravila v podpornem zdravljenju, najpogosteje deksametazonom in odmerkom na informacijskemu listu. Razlog za to je lahko v zelo natančnem predpisu vrste in posameznega odmerka antiemetičnih zdravil v priporočilih na informacijskih listih vsake posamezne sheme kemoterapije. Rezultat kaže na to, da je predpisovanje antiemetičnega zdravljenja zelo individualno in je odvisno tako od lastnosti bolnika, spremljajočih bolezni in zdravil, kakor tudi od predhodnih izkušenj vsakega posameznega bolnika glede slabosti in bruhanja. Naše opažanje kaže na potrebo po ponovni uskladitvi priporočil za antiemetično zdravljenje z vsemi odgovornimi
zdravstvenimi delavci in po pripravi bolj ohlapnih priporočil. Znotraj kategorije »zdravila« ustrezni antiemetiki ali druga zdravila za podporno zdravljenje niso bila predpisana in so zahtevala 10,0 % (21/211) ukrepov, do 7,6 % (16/211) ukrepov pa je prišlo zaradi njihovega nepotrebnega predpisa. Ti rezultati zagovarjajo vključitev pregleda podpornega zdravljenja v sklopu sprejema naročila kemoterapije. Podporno zdravljenje je sestavni del zdravljenja s kemoterapijo, saj preprečuje ali omili njene neželene učinke (24). Neželeni učinki zdravljenja s kemoterapijo ne poslabšajo le kakovost življenja bolnika in vodijo tudi do bolnikove zavrnitve nadaljnjega zdravljenja, temveč tudi poslabšajo bolnikovo zdravstveno stanje in ogrozijo njegovo življenje.
4.1.2 Ukrepi, povezani s predpisom protitumorskih zdravil
Protitumorska zdravila so bila neposredno vpletena v 61 ukrepov, v katerih je bila najpogosteje predlagana sprememba odmerka zdravila. Zabeleženih je bilo 34 ukrepov (16,1 %) take narave, kjer je bila predlagana sprememba odmerka zaradi prevelikega odstopanja predpisanega odmerka od izračunanega ali zaradi potrebne prilagoditve odmerka glede na krvne in biokemijske izvide. Čeprav se posamezni izmed teh sklopov ukrepov pojavljajo relativno redko, imajo posledice nenamerno neusklajenega odmerka protitumornega zdravila take razsežnosti, da utemeljujejo potrebo po kontrolnem preračunu odmerka protitumornega zdravila in pregledu odmerka v sklopu krvnih in biokemičnih izvidov tudi s strani farmacevtov. Ker odločitev o odmerku protitumorskega zdravila in njegovem prilagajanju temelji na zdravnikovi individualni oceni bolnika, pričakujemo, da je velik delež zaznanih odstopanj namernih. To potrjuje tudi delež neuresničenih in delno uresničenih ukrepov (35,3 %), ki je opazno višji od celokupnega deleža (21,3 %). Zdravniki se niso odločili za uresničitev ukrepov ob odstopanju med predpisanim in izračunanim odmerkom protitumorskega zdravila, kjer je bolnik že v preteklosti prejemal predpisani odmerek, pri mejno spremenjeni vrednosti krvnih izvidov ali pri povišanih jetrnih testih, ki so bil ocenjeni kot posledica zasevkov v jetrih in ne znak oslabljene jetrne funkcije; slednje je v skladu z veljavnimi priporočili in ga bomo upoštevali pri pripravi novih informacijskih listov. Ti rezultati potrjujejo, da je ob vsakem ukrepanju nujen pogovor z zdravnikom; ta je toliko bolj pomemben, ko gre za spremembo protitumorskega odmerka. Uresničenje predlaganega ukrepa brez ustreznega pogovora z zdravnikom lahko vodi celo do slabše oskrbe bolnika.
4.1.3	Intervencije administrativne narave
V	zabeleženih intervencijah so bila pogosta neskladja administrativne narave (14,2 %). V te ukrepe pogosto niso bila vpletena nobena zdravila. Nekatera izmed teh neskladij, kot so pomanjkanje zapisa datuma prejema kemoterapije na obrazcu »klinična pot kemoterapije«, verjetno nimajo neposrednega vpliva na bolnikovo zdravljenje, so pa ti podatki pomembni pri vodenju bolnikovega zdravljenja in njegovega načrtovanja. Nekateri drugi podatki, kot so telesna teža, pa so nujni za izračun odmerka protitumorskega zdravila. Natančnost in doslednost pri izpolnjevanju obrazca »klinična pot kemoterapije« z razvidnim potekom zdravljenja, izbrano shemo in odmerki ter razlogi za njihovo morebitno prilagoditev omogočata enoznačno razumevanje zdravnikovih preteklih odločitev o bolnikovem zdravljenju. Slednje je še posebno pomembno za zagotavljanje kontinuitete zdravljenja v primerih, ko mora zaradi nadomeščanja ali drugih razlogov predpisati kemoterapijo zdravnik, ki bolnika ni vodil v preteklosti.
4.1.4	Uresni~itev ukrepov
Zdravniki so se strinjali in uresničili veliko večino ukrepov (več kot 75 %), kar nakazuje na pomembnost zaznanih problemov in smiselnost predlaganih ukrepov tudi z medicinskega stališča. Iz zbranih podatkov ne moremo sklepati o razsežnosti neposrednega vpliva ukrepov in njihovega pomena za bolnikovo zdravljenje. Zaznali smo, da so zdravniki manj pogosto uresničili ukrepe, povezane z odmerkom in režimom odmerjanja, najpogosteje protitumorskih zdravil in antiemetičnega zdravljenja. To dokazuje, da je zdravljenje s kemoterapijo individualno za vsakega bolnika in da je ob upoštevanju značilnosti bolnika, bolezni in preteklega zdravljenja včasih potrebno odstopiti od bolnišničnih priporočil za zdravljenje s posamezno shemo kemoterapije. Seveda pa bi za potrditev tega potrebovali klinično vrednotenje izidov zdravljenja pri bolnikih glede na uresničevanje predlaganih ukrepov.
4.2 Primerjava rezultatov farmacevtovih ukrepov ob pregledu predpisa kemoterapije s sorodnimi {tudijami
V	literaturi objavljene študije o ukrepih farmacevta pri pregledu predpisa kemoterapije so potekale v bolnišnicah s širšo onkološko dejavnostjo (9, 13, 14). Objavljene študije so zajele med 130 in več kot 22.000 naročil protitumorskih zdravil, kar uvršča našo študijo med srednje velike. Z izjemo študije Knezove s
sodelavci (9) so bili ukrepi zbrani s samoporočanjem in se v tem smislu metodološko ne razlikujejo od tukaj predstavljene študije.
Vse tri študije so poročale o nižjih deležih ukrepov na naročilo kemoterapije, in sicer v razponu od 16,2 % do 27,6 % (9, 13, 14) v primerjavi z našimi rezultati (41,7 %). Omenjene študije so vključevale tudi ukrepe zaradi fizikalno-kemijskih inkompatibilnosti (13) ali ukrepe zaradi neizpolnjenega bolnikovega soglasja za zdravljenje s kemoterapijo (14), kar je bil vzrok za 73,9 % ukrepov v prvi študiji in 50,9 % ukrepov v drugi študiji. Ker tukaj opisana študija ni zajela ukrepov te narave, moramo to upoštevati pri primerjavi rezultatov. Višji delež ukrepov v tukaj opisani študiji je tudi pričakovan, saj so se dejavnosti za obvladovanje tveganja, povezanega s kemoterapijo, okrepile pred kratkim in se njihovi dolgoročni učinki še niso pokazali. Pri razlagi rezultatov naše študije je potrebno upoštevati tudi to, da je bil predpis podpornega zdravljenja v informacijskih listih zelo natančen in ni omogočal individualne obravnave bolnika, kar je tudi vodilo do velikega deleža neskladij. K nizkemu deležu ukrepov v študiji Markerta in sodelavcev je lahko pripomogla tudi uporaba elektronskega naročanja kemoterapije (14), v študiji Knezove in sodelavcev pa uporaba receptnih obrazcev, ki vsebujejo informacije o predlaganem antiemetičnem in drugem podpornem zdravljenju pri določeni shemi kemoterapije (9). Seveda pa take rešitve ne omogočajo individualizacije podpornega zdravljenja, na pomembnost katerega se je začelo opozarjati šele v zadnjem času (24). Zaradi uporabe različne klasifikacije problemov, ki so zahtevali farmacevtovo ukrepanje, je primerjava njihovih deležev med različnimi študijami zapletena. Študija Slama in sodelavcev ter Markerta in sodelavcev ne poroča o deležu ukrepov, ki so bili uresničeni, v tretji študiji je bil ta delež podoben (86 %) kot tukaj opisani delež.
4.3 Omejitve študije
Podatki o ukrepih pri pregledu predpisa kemoterapije so bile zbrani s samo-poročanjem, in sicer so ukrepe zabeležili farmacevti med svojim rutinskim delom. To sicer omogoča vključitev vseh naročil kemoterapije v analizo, vendar hkrati lahko vodi do nepopolnih podatkov, kar smo zmanjšali z uporabo obrazca za pregled predpisa kemoterapije in beleženje ukrepov (23). Samoporočanje lahko vodi do tega, da ne poročajo o ukrepih, ki so po oceni poročevalcev manj pomembne.
Čeprav študija omogoča zelo dober vpogled v število in naravo ukrepov in najbolj pogoste neskladnosti
v predpisu kemoterapije, pomen teh za bolnikovo oskrbo ni bil neposredno ovrednoten. Neposredni pomen zabeleženih ukrepov za bolnikovo oskrbo bi lahko ocenili z metodo strokovnega panela, v katerem bi morali sodelovati tako zdravniki, kakor tudi farmacevti. Pri ukrepih, ki niso bile uresničeni, bi lahko v ločeni študiji pogledali klinične posledice zaznanega neskladja. Zato bi potrebovali večje število bolnikov oziroma predpisanih kemoterapij, kar bi vodilo do večjega absolutnega števila bolnikov z neuresničenimi ukrepi. Sistematično pa bi morali voditi tudi podatke o neželenih učinkih, uspešnosti zdravljenja in preživetju vseh bolnikov, ki se zdravijo pri nas.
4.4 Implikacija rezultatov študije za klinično prakso
Rezultati ukrepov, zabeleženih ob pregledu predpisa kemoterapije, dokazujejo potrebo po opisani storitvi in njeno vpeljavo v rutinski proces zdravljenja s kemoterapijo, opozarja pa tudi na dejstvo, da je delež ukrepov zelo odvisen od natančnosti informacijskega obrazca. Po pregledu objavljene literature le ta prispevek opisuje vključitev pregleda predpisa kemoterapije s strani farmacevta v rutinsko klinično prakso v slovenskem prostoru in lahko kot tak služi kot zgled za uresničevanje opisane storitve v drugih slovenskih bolnišnicah.
Rezultati študije in njihova primerjava z objavljeno literaturo kažejo na relativno velik delež ukrepov in z njimi povezanih neskladij v sedanjem predpisovanju kemoterapije. Analiza je pokazala, da so najpogostejša neskladja v predpisovanju antiemetičnega zdravljenja, katerega individualizacijo je potrebno do določene mere predvideti že z informacijskimi obrazci. Prepoznati moramo neskladja, ki so najpomembnejša za dobro oskrbo bolnika, in neskladja, ki so povezana z največjim tveganjem za bolnika, analizirati njihov pomen za klinični izid zdravljenja ter nato pripraviti predloge za njihovo zmanjšanje in izboljšanje sedanjega načina dela. Pri oblikovanju predlogov je potrebno sodelovanje vseh profilov zdravstvenih delavcev, vpletenih v zdravljenje s kemoterapijo, z zaključki pa morajo biti seznanjeni vsi zdravstveni delavci, ki predpisujejo, pregledujejo, pripravljajo in dajejo kemoterapijo.
5 Zaključek
Prispevek opisuje izvajanje nove storitve, in sicer pregleda predpisa kemoterapije s strani farmacevta ob prehodu na centralizirano pripravo protitumorskih zdravil. Hkrati podaja tudi dokaze o koristi farmacevtovih
ukrepov pri pregledu predpisa kemoterapije za zmanjšanje nenamernih odstopanj od dogovorjenih priporo~il za posamezno shemo zdravljenja. Rezultati študije kažejo, da je pregled predpisa kemoterapije s strani farmacevta potreben in u~inkovit ukrep za obvladovanje tveganja pri zdravljenju s protitumorskimi zdravili ter da je pregled ukrepov, zabeleženih znotraj te storitve, u~inkovit na~in za prepoznavo šibkih to~k v sedanjem na~inu dela in za njihovo izboljšanje.
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21.	Roila F, Hesketh PJ, Herrstedt J; Antiemetic Subcommitte of the Multinational Association of Supportive Care in Cancer: Prevention of chemotherapy- and radiotherapy-indiced emesis: results of the 2004 Perugia Internetional Antiemetic Consensus Conference. Ann Oncol 2006; 17: 20-28.
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25.	Jaehde U, Liekwig A, Simos S, et al: Minimising treatment-associated risks in systemic cancer therapy. Pharm World Sci 2008; 30: 161-168.
TIME TRENDS IN ABILITY LEVEL AND FUNCTIONAL OUTCOME OF STROKE AND MULTIPLE SCLEROSIS PATIENTS UNDERGOING COMPREHENSIVE REHABILITATION IN
SLOVENIA
ČASOVNE SPREMEMBE NIVOJA ZMOŽNOSTI IN FUNKCIJSKEGA IZIDA BOLNIKOV PO MOŽGANSKI KAPI IN Z MULTIPLO SKLEROZO NA CELOSTNI REHABILITACIJI V
SLOVENIJI
Gaj Vidmar1, Helena Burger1, Črt Marinček1 Prispelo: 1. 2. 2010 - Sprejeto: 4. 7. 2010
Original scientific article UDC 615.851.3:616.8
Abstract
Background: The University Rehabilitation Institute in Ljubljana provides comprehensive rehabilitation for the whole territory of Slovenia. The aim of the study was to verify a clinical observation that the demandingness of rehabilitation has been incr^easing because of a decrease in patients' functional abilitites on admission, with rehabilitation outcomes having remained unchanged or even improved.
Methods: Functional Independence Measure (FIM) scores of 651 cerebrovascular insult (CVI) and 151 multiple sclerosis (MS) patients gathered between September2004 and September2006 (all eligible cases) were compared with those for patients with the same diagnosis (N=144 and 74, respectively) collected during the period from September 1999 to September2000 (a random sample), considering only first-admission cases. The average FIM (motor, cognitive and total) scores and FIM gain after rehabilitation during the two periods were determined for each diagnostic group adjusted for patient age. Rehabilitation efficiency and effectiveness levels were compared in the same way. Effect Size and Standardised Response Mean were also analysed.
Results: There were no differences in gender st^uctu^e of the groups between the periods studied. During the recent period, the a^er^age age was higher by around two years in both groups. The length of stay was marginally shortened for CVI patients and remained unchanged for MS patients. There were no differences between the two periods concerning the time elapsed since stroke. In both groups, admission motor and cognitive FIM scores were on aver^age approximately five points lower in the recent period, while the average rehabilitation gain from admission to discharge incr^eased over time (in total by 1 in CVI patients and by 3 in MS patients). Regarding motor and total FIM scores, the standardised gain, r^ehabilitation efficiency and rehabilitation effectiveness increased as well. Conclusions: The Institute is admitting more severely affected patients than it did five to ten years ago, and parallelly the patient age has increased. Despite that and notwithstanding the tendency towards shorter rehabilitation, expected age-adjusted functional independence gain, rehabilitation efficiency, r^ehabilitation effectiveness, and the standardised functional independence gain have increased.
Key words: stroke, multiple sclerosis, outcome and process assessment (health care), rehabilitation centers
Izvirni znanstveni članek UDK 615.851.3:616.8
Izvle~ek
Izhodišča: Univerzitetni rehabilitacijski inštitut v Ljubljani nudi kompleksno rehabilitacijo za celotno ozemlje
1University Rehabilitation Institute, Republic of Slovenia, Linhartova 51, 1000 Ljubljana, Slovenia Correspondence to: e-mail: gaj.vidmar@ir-rs.si
Slovenije. Želeli smo preveriti klinične izkušnje, da zahtevnost rehabilitacije narašča zaradi vse manjših funkcijskih zmožnosti bolnikov ob sprejemu, hkrati pa se izidi rehabilitacije ne slabšajo ali se celo izboljšujejo. Metode: Dosežke na Lestvici funkcijske neodvisnosti (Functional Independence Measure - FIM) pri 651 bolnikih po možganski kapi (CVI) in 151 bolnikih z multiplo sklerozo (MS), zbrane v obdobju IX/2004-IX/2006 (vsi ustrezni bolniki), smo primerjali z bolniki z istima diagnozama (N=144 in 74) iz obdobja IX/1999-IX/2000 (slučajni vzorec), pri čemer smo upoštevali le prve sprejeme. Povprečni dosežek na FIM (na motorični in kognitivni podlestvici ter skupni lestvici) in porast FIM po rehabilitaciji smo primerjali med obdobjema znotraj vsake diagnostične skupine, pri čemer smo odstranili vpliv starosti bolnikov. Učinkovitost in uspešnost rehabilitacije smo primerjali na enak način. Analizirali smo tudi velikost učinka in standardizirani povprečni odziv.
Rezultati: Struktura spola se med obdobjema ni razlikovala v nobeni skupini. Povprečna starost je bila v obeh skupinah višja za okoli 2 leti v novejšem obdobju. Ležalna doba se je nekoliko skrajšala za bolnike s CVI, za bolnike z MS pa se ni spremenila. Čas od kapi se med obdobjema ni razlikoval. V obeh skupinah so bili dosežki na motorični in kognitivni podlestvici FIM ob sprejemu v povprečju za okoli 5 točk nižji v novejšem obdobju, hkrati pa se je povprečni porast od sprejema do odpusta povečal (skupaj za okoli 1 pri CVI in okoli 3 pri MS). Glede motoričnega in skupnega dosežka na FIM so se s časom povečali tudi standardizirani porast, učinkovitost rehabilitacije in uspešnost rehabilitacije.
Zaključek: Na našem inštitutu sprejemamo zahtevnejše bolnike kot pred 5-10 leti, kar spremlja povečanje njihove starosti. Kljub temu in težnji po skrajševanju ležalne dobe so se pričakovani starostno neodvisni porast funkcijske neodvisnosti, učinkovitost rehabilitacije in uspešnost rehabilitacije povečali, kar velja tudi za standardizirani porast funkcijske neodvisnosti.
Ključne besede: možganska kap, multipla skleroza, ocenjevanje izidov in postopkov v zdravstvu, rehabilitacijski centri
1 Introduction
The Functional Independence Measure (FIM) scale is arguably the main outcome measure in rehabilitation medicine (1) and an important casemix tool (2). It was devised in 1984 at a workshop held by the American Congress for Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabiltiation to be used as a universal assessment tool in the medical rehabilitation Uniform Data System (UDS) (3, 4). Its use in patients with various pathologies and for various purposes has since been reported in over one thousand articles, counting only those abstracted in the PubMed/MEDLINE bibliographic database. The FIM is used for evaluation of disability in stroke (5), traumatic brain injury (6), multiple sclerosis (7), in patients after trauma (8, 9), in patients with Parkinson disease (10) and other pathologies in order to identify rehabilitation needs (11), demonstrate effectiveness of rehabilitation interventions (7, 12), compare rehabilitation programmes in different areas (13), as well as to predict functional independence at discharge
(14)	and in the longer term (9).
The FIM has demonstrated acceptable reliability across a wide variety of settings, assessors and patients
(15).	In neurological patients, it has been found to be more valid than the Barthel Index and equally reliable
in the assessment of disability (4). Stineman (16) demonstrated reliability, item internal consistency and item discriminant validity in 20 impairment categories. Later studies revealed some problems in comparing raw FIM data in different countries (17, 18), yet the validity is unquestionable in comparisons within a country (within the same hospital), as is the case in our study. FIM has two dominant subdomains of difficulty, one for the motor items and the other for the cognitive items. The patterns are consistent although not identical across impairment groups (19, 20) and differences exist in this regards between countries (17, 18), but those concerns do not affect our study, either. The University Rehabilitation Institute in Ljubljana (URI) is the only tertiary health care institution in the field of physical and rehabilitation medicine in Slovenia and the only rehabilitation hospital in the country. As such, it provides comprehensive rehabilitation for the whole territory of Slovenia, admitting about 1300 cases per year. Compulsory FIM assessment at admission and discharge, integrated into the hospital information system, was introduced in 2004. This study used these FIM data and a cross-sectional comparison with the historical data available in order to verify a clinical observation that rehabilitation demandingness has been increasing because of increasing numbers of patients with lower admission functional ability.
Another aim was to determine possible differences in rehabilitation effects, taking into account patient demographics, duration of rehabilitation and potential for measured progress given the FIM score at admission.
2 Materials and Methods
2.1	Research design and subjects
FIM scores of patients with cerebrovascular insult (CVI) and multiple sclerosis (MS) gathered between September 2004 and September 2006 were compared to those of patients with the same diagnosis, collected between September 1999 and September 2000 (N=144 and 74 for CVI and MS, respectively). Data for the earlier period were obtained within the PRO-ESOR international research project (21). Those were all first admission cases, so only first admission cases were selected from the 2004-2006 period (N=651 and 151 for CVI and MS, respectively). The same admission criteria applied for both time periods:
•	For CVI - stable neurological condition; considerable and non-diminishing neurological deficits; at least two areas of impairment among ambulation, daily activities, continence, cognitive abilities, communication, swollowing, and pain syndrome; sufficient cognitive ability for learning; adequate communication ability (preferably ability to follow two- or three-way instructions); physical ability to participate in active programmes for at least three hours daily.
•	For MS - worsened functional status, especially regarding daily activities or ambulation; or need for fitting advanced technical aids; or need for advanced therapeutic interventions for spasticity or pain.
A random sample of eligible cases was selected during the period 1999-2000. The sample size was designed to meet the needs of the research project and was limited by the resources available. For the 2004-2006 period, all eligible cases were retrieved from the hospital information system. The study protocol was approved by the Medical Ethics Committee of the University Rehabilitation Institute, Republic of Slovenia. Because of the retrospective documentation-based nature of the study, no informed patient consent was needed.
2.2	Derived outcome measures
In order to allow a more direct comparison between periods, mean admission-to discharge changes in
FIM scores were standardised using the following two common measures (22):
•	Effect Size (ES, also known as Cohen's d), computed as the mean change divided by the standard deviation at admission;
•	Standardised Response Mean (SRM), computed as the mean change divided by the standard deviation of change.
In addition to FIM scores two outcomes were calculated and analysed in order to take into account the duration of rehabilitation and the reduced potential for observing functional gain in patients with higher admission scores, respectively (23):
•	Rehabilitation efficiency is the amount of change averaged over the duration of rehabilitation, i.e., the increase in functional ability per day of stay;
•	Rehabilitation effectiveness is the proportion of potential improvement obtained during rehabilitation, calculated as the difference between discharge and admission scores, divided by the maximum potential improvement (i.e. difference between maximum possible score and admission score).
2.3 Statistical analysis
Descriptive statistics and graphical displays were produced for all the variables studied. Possible differences between both time periods as concerns gender structures within each diagnostic group were assessed using the Fisher's exact test. The two-sample f-test was employed to compare the average patient age and the average length of stay, and the MannWhitney test was used to compare times elapsed since stroke. Because of differences in the average age between the periods studied (see Results), analysis of covariance (ANCOVA) was used to determine possible differences between the two time periods in average age-adjusted FIM scores (motor, cognitive and total) within each diagnostic group. Since rehabilitation efficiency and effectiveness data clearly violate the assumptions of such parametric analysis, those variables were age-adjusted by first fitting a robust linear regression (iteratively reweighted least squares using Huber M-estimator (24)) model and then testing the differences between periods on the residuals from that model using exact nonparametric Mann-Whitney test. Statistical analyses were conducted using SPSS Statistics 17.0.1 (SPSS Inc., Chicago, IL, USA, 2008), whereby robust regression was performed with the SPSSINC ROBUST REGR extension command that uses the R (25) plugin to execute the rim function from the MASS package (26). P-values <0.05 were considered statistically significant.
3 Results
Men accounted for 62% of the CVI patients in the 19992000 sample (71 men vs. 43 women) and for 61% in the 2004-2006 sample (396 men vs. 255 women; p=0.835 for the difference between periods). Women prevailed among the MS patients - there were 62% of women in the 1999-2000 sample (45 women vs. 29 men) and 70% in the 2004-2006 sample (106 women vs. 45 men; p=0.176 for the difference between periods). A difference in the age of both groups was observed between the two periods: the average age of CVI patients was 57.9 years (SD 11.1) in the period 1999-2000, and 60.4 years (SD 13.0) in the period 2004-2006 (p=0.049 from the two-sample f-test). The average age of MS patients was 48.3 years (SD 14.3) in the period 1999-2000 and 50.9 years (SD 12.6) in the period from 2004 to 2006 (p=0.164). There was no significant difference in the length of stay of CVI patients (Figure 1) between the two periods,
150-
although a trend towards a shorter rehabilitation is observed (1999-2000: mean 50.2 days, SD 21.4 days; 2004-2006: mean 45.6 days, SD 20.5 days; p=0.107). For MS patients, the average length of rehabilitation remained unchanged (1999-2000: mean=25.2 days, SD=10.4 days; 2004-2006: mean=25.3 days, SD=10.7 days; p=0.938). For CVI patients, there was no difference in times since stroke between the two periods (1999-2000: median=6.0 months, 2004-2006: median=5.0 months; p=0.200). Comparisons between the time periods regarding FIM scores are summarised in Table 1 and Figure 2. In both groups, admission motor and cognitive subscale scores were on average 5 points lower in the 2004-2006 period, the average total score being approximately 10 points lower. The average difference between discharge and admission scores had increased over time, in total by about 1 and 3 points in CVI and MS patients, respectively. Lack of a statistically significant interaction effect implies that the observed differences do not vary with patient age.
1999-2000
2004-2006
1 I I I I r
0 20 40 60 80 100 120 0 20 40 60 80
Length of stay (days) / Ležalna doba (dni)
Figure 1. Disfribufion of lengfh of sfay (wifh superimposed fiffed normal disfribufion) of sfroke (CVI) and
mulfiple sclerosis (MS) pafienfs during fhe 1999-2000 and 2004-2006 periods. Slika 1. Porazdelitev ležalne dobe (z dodano najbolje prilegajočo se normalno porazdelifvijo) v obdobju 1999-2000 in 2004-2006 za bolnike po možganski kapi (CVI) in z mulfiplo sklerozo (MS).
The results of rehabilitation efficiency and effectiveness analyses are summarised in Table 2. In CVI patients, we found a marginally significant increase in efficiency
_CVI_
Score at
admission
Dosežek ob
sprejemu
Progress at
discharge
Napredek ob
odpustu
and no noteworthy changes in effectiveness. In MS patients, both efficiency and effectiveness significantly increased over the time period observed.
_MS_
Figure 2. Boxplots depicting distribution of motor and cognitive FIM subscale scores at admission, and of progress level at discharge for stroke (CVI) and multiple sclerosis (MS) patients, for the periods 1999-2000 and2004-2006. Thick line denotes the median; the box denotes the interquartile range (IQR); whiskers indicate the non-outlier range (smallest and lai-gest observed value within 1.5 IQR below and above the 1st and 3rd quartiles, respectively); and the circles indicate the outliers.
Slika 2. [katlasti diagrami za prikaz porazdelitve dosežkov na motorični in kognitivni podlestvici FIM ob spr-ejemu ter napredka ob odpustu v obdobju 1999-2000 in 2004-2006 za bolnike po možganski kapi (CVI) in z multiplo sklerozo (MS). Debela črta označuje mediano; škatla označuje interkvartilni razmik (IKR); ročaji označujejo razpon brez odstopajočih vrednosti (najmanjšo in največjo opaženo vrednost znotraj 1,5 IKR pod oziroma nad 1. oziroma 3. kvartilom); krožci označujejo osamelce.
Table 1. Descriptive sfafisfics and sfafisfical significance of differences befween fhe 1999-2000 and fhe 2004-2006 periods regarding admission FIM scores and progress in FIM scores af discharge, for sfroke (CVI) and mulfiple sclerosis (MS) pafienfs.
Tabela 1. Opisne sfafisfike in sfafisfična značilnosf za primerjavo med obdobjema 1999-2000 in 2004-2006 glede dosežka na FIM ob sprejemu in napredka v dosežku na FIM ob odpusfu za bolnike po možganski kapi (CVI) in z mulfiplo sklerozo (MS).
					p for the effect of	
FIM score		Group	Period	Mean ± SE	p za u~inek	
Dosežek na FIM		Skupina	Obdobje	Povp. ± St.nap.	Period obdobja	Interaction interakcije
	Total	CVI	1999-2000 2004-2006	83.91 ± 2.48 74.90 ± 1.03	0.001	0.685
FIM score on	Skupni	MS	1999-2000 2004-2006	92.09 ± 3.45 83.00 ± 2.56	0.036	0.247
admission	Motor	CVI	1999-2000 2004-2006	54.41 ± 2.06 50.62 ± 0.85	0.089	0.752
Dosežek ob	Motorični	MS	1999-2000 2004-2006	59.64 ± 3.02 54.70 ± 2.24	0.191	0.201
sprejemu	Cognitive	CVI	1999-2000 2004-2006	29.49 ± 0.64 24.28 ± 0.27	<0.001	0.582
	Kognitivni	MS	1999-2000 2004-2006	32.45 ± 0.65 28.30 ± 0.49	<0.001	0.837
	Total	CVI	1999-2000 2004-2006	8.75 ± 1.45 9.56 ± 0.41	0.586	0.347
Progress	Skupni	MS	1999-2000 2004-2006	0.47 ± 0.68 3.77 ± 0.50	<0.001	0.964
at discharge	Motor	CVI	1999-2000 2004-2006	8.41 ± 1.35 8.40 ± 0.38	0.989	0.440
Napredek ob	Motorični	MS	1999-2000 2004-2006	0.52 ± 0.67 3.36 ± 0.49	0.001	0.793
odpustu	Cognitive	CVI	1999-2000 2004-2006	0.34 ± 0.30 1.17 ± 0.09	0.007	0.281
	Kognitivni	MS	1999-2000 2004-2006	-0.05 ± 0.11 0.42 ± 0.08	0.001	0.053
Efficiency and effectiveness analyses necessarily exclude the patients who were admitted with the maximum possible score. Regarding the total score and the motor subscale, there were two such patients during the period 1999-2000, and none in the period 2004-2006, neither in the CVI group nor in the MS group. The figure is considered negligible for the purpose of our study. For the cognitive subscale, the proportion was generally higher and statistically significantly higher for the period 1999-2000 than for the period 2004-2006 (22% vs. 3% in the CVI group,
50% vs. 10% in the MS group, p<0.001 from Fisher's exact test). Hence, the comparisons reported above in relation to Table 2 are only unquestionably valid for - and primarily refer only to - the total score and the motor subscale score.
Standardised FIM change measures are reported in Table 3. For the total score and for both subscale scores, both standardised change measures were larger for the recent period in both groups (with the sole exception of the effect size for motor score in CVI patients).
Table 2. Descriptive statistics and statistical significance of differences between the 1999-2000 and2004-2006 periods regarding the rehabilitation efficiency and effectiveness, calculated from FIM scores, for stroke (CVI) and multiple sclerosis (MS) patients.
Tabela 2. Opisne statistike in statistična značilnost za primerjavo med obdobjema 1999-2000 in 2004-2006 glede učinkovitosti in uspešnosti rehabilitacije, izračunane na podlagi dosežkov na FIM, za bolnike po možganski kapi (CVI) in z multiplo sklerozo (MS).
Me (Q1,Q3)		Efficiency U~inkovitost			Effectiveness Uspe{nost		
FIM		Total Skupni	Motor Motori~ni	Cognitive Kognitivni	Total Skupni	Motor Motorični	Cognitive Kognitivni
CVI	1999-	9.4%	8.3%	0.0%	23.5%	23.2%	0.0%
	2000	(3.4%,21.3%)	(2.2%,19.3%)	(0.0%,1.4%)	(5.7%,42.4%)	(3.9%,43.3%)	(0.0%,33.3%)
	2004-	15.2%	12.0%	0.0%	18.5%	19.0%	0.0%
	2006	(5.1%,28.3%)	(3.1%,25.6%)	(0.0%,4.3%)	(4.3%,33.3%)	(3.0%,38.2%)	(0.0%,25.0%)
p		0.070	0.215	0.021	0.148	0.285	0.947
MS	1999-	0.0%	0.0%	0.0%	0.0%	0.0%	0.0%
	2000	(0.0%,5.8%)	(0.0%,5.8%)	(0.0%,0.0%)	(0.0%,4.2%)	(0.0%,3.7%)	(0.0%,0.0%)
	2004-	8.0%	4.3%	0.0%	6.7%	4.3%	0.0%
	2006	(2.2%,18.4%)	(0.0%,16.7%)	(0.0%,4.2%)	(1.3%,17.2%)	(0.0%,16.7%)	(0.0%,21.7%)
p		<0.001	0.002	<0.001	<0.001	<0.001	0.003
Note: Values are reported as the Opomba: Vrednosti so prikazane
median (1st quartile, 3rd quartile). kot mediana (1. kvartil, 3. kvartil).
Table 3. Standardised FIM change measui-es for the periods 1999-2000 and 2004-2006, for stroke (CVI)
and multiple sclerosis (MS) patients. Tabela 3. Standardizirane mere spremembe dosežka na FIM za obdobji 1999-2000 in 2004-2006 z^a bolnike po možganski kapi (CVI) in z multiplo sklerozo (MS).
Group Skupina	Period Obdobje	Total FIM Skupni FIM		Motor FIM Motorični FIM		Cognit Kognit	ive FIM vni FIM
		ES	SRM	ES	SRM	ES	SRM
CVI	1999-2000	0.348	0.757	0.385	0.729	0.093	0.333
	2004-2006	0.357	0.952	0.373	0.904	0.174	0.546
MS	1999-2000	0.018	0.143	0.021	0.165	-0.008	-0.063
	2004-2006	0.133	0.621	0.134	0.541	0.094	0.538
Legend: ES=effect size; SRM=standardised response mean. Legenda: ES=velikost učinka; SRM=standardizirani povprečni odziv.
4 Discussion
It is evident that today, at least as concerns CVI and MS cases, more severely affected patients are admitted than five to ten years ago. Because of S-shaped nonlinearity of the FIM scale (20), the actual difference in ability may differ somewhat from what the FIM scores show, but a difference certainly exists over and above the increasing patient age. At least in CVI patients, this cannot be attributed to earlier admissions after stroke.
A critical observation that can be made is that the interval level of measurement is questionable for FIM (sub)scores: they are obtained by summation of ordinal-level items (27), so subtracting them or dividing them by a truly numeric quantity - be it for the purpose of calculating a t-test or deriving standardised change measures (28) - is not recommended. However, the approach we adopted is a widespread practice, empirically verified to produce small errors, and the classical test theory is a sufficiently valid framework for the aim of our study, which is a practical decision support cum gr-ano salis comparable to the Shewhart's and Deming's spirit of Statistical Process Control, or better yet, Wheeler's concept of Continual Improvement (29).
It should also be recognised that, in general, FIM scores (particularly the cognitive subscale) are subject to a ceiling effect, and that they exhibit a distinctly bimodal distribution in our patient population (30). This is well-modelled by a mixture of around one third of patients with a mean of aroud 60, SD of around 25 and expected gain of around 10 on admission; and around two thirds of patients with a mean of around 105, SD around 10 and expected gain of approximately 5 on admission (31). Nevertheless, the reported means and standard deviations provide a useful description of the data because of a reasonable symmetry of the observed FIM score distributions in the two groups studied. Similarly, given the relatively large samples, fairly homogeneous FIM score variances across age groups, and bell-shaped age distributions in both groups, the analysis of covariance performed yields sufficiently valid significance tests (32). Furthermore, the presented findings are in agreement with other time-trend analyses, conducted at this Institute for the purpose of quality control, internal auditing and funding issues. Those analyses indicated an increasing ratio of tetraplegia vs. paraplegia among the patients with spinal cord injury (from around 1:5 before 2004 to around 4:3 in 2006; p<0.001 from the Fisher-Freeman-Halton exact test), a decreasing
length of stay on hospital level (median decreasing from 23.2 days in 2000 to 17.6 days in 2007; negative slope from LOESS regression throughout the period), and increasing rates of complications and concomitant diagnoses in all departments (by approx. 20% between 2001 and 2007; p<0.05 for comparisons of Poisson rates).
Despite such trends, the expected age-adjusted functional independence gain during rehabilitation, assessed by by the FIM progress, has not decreased but has even slightly increased. For the motor subscale, the difference in progress between the time periods studied was only statistically significant in the MS group, while for the cognitive FIM subscale it was statistically significant for both groups, an observation that is partly an artefact due to a ceiling effect, but nevertheless constitutes evidence against an undesired trend if not proper evidence for a desired trend. Further light is shed on this issue by assessments of rehabilitation efficiency and effectiveness, which - though limited in validity to total and motor scores - demonstrate a marginally significant progress in efficiency in the CVI group and a clearly significant progress in both measures for the MS group.
Standardised change scores provide the same picture. Again, they are mainly relevant only for the total and the motor scores, and should be interpreted with caution (33, 34), including avoiding categorising the observed SRM values into the Cohen's size-classes. Nevertheless, they offer additional grounds for our overall conclusions to be drawn. On a final note, we cannot ignore the possibility that the observed differences are at least partly attributable to the assessment bias. All assessors had completed the same formal FIM training, but different assessors participated during the two periods studied (except for two phisicians who were among the four assessors during the first period and among the assessors during the second period; and even those two had gained further experience after the first period). The possibility of bias should be addressed because after the initial report on a very high interrater reliability and high test-retest and equivalence reliability of summary FIM scores prepared by four formally trained assessors regarding summary FIM scores (15), a moderate interrater agreement on FIM items (even in its modified version based on Rasch analysis) was emphasised in various settings and contexts (35-39). However, at least for the first time period studied the item-response approach proved that our assessors appropriately used all seven levels of each item in accordance with the patients' functional independence
(21). Furthermore, as admitted in the recent report on considerable discrepancies at the item level (39), it is reasonable to expect the individual item variation can be smoothed by a sufficiently large number of FIM items (especially for the total and motor scores), thus yielding sufficient summary score agreement.
5 Conclusion
Our findings can be related to the global trends in population ageing and to progress of medicine, resulting in older and more severely ill patients being admitted to tertiary hospitals. It is encouraging that despite such trends, the expected functional independence gain, as well as rehabilitation efficiency and effectiveness assessed at this Institute have increased, at least as indicated by total and cognitive FIM scores, and at least in multiple sclerosis patients. From a healthcare quality standpoint, this study (combined with related analyses mentioned in the discussion) provides valuable information needed for monitoring, training and planning purposes. Since FIM is integrated into the hospital information system, we will be able to analyse admission and outcome trends in all patients, applying longitudinal and time-series models to the data in order to gain a more comprehensive insight into the situation and reach more reliable conclusions.
Acknowledgement
The authors are grateful to Robert Cugelj, MSc, Director General of the University Rehabilitation Institute, Republic of Slovenia, for supporting the research.
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ANALIZA NEPRIMERNEGA PREDPISOVANJA ZDRAVIL STAROSTNIKOM V SLOVENIJI NA PODLAGI BEERSOVIH IN
LAROCHEVIH MERIL
ANALYSIS OF INAPPROPRIATE MEDICATION PRESCRIBING IN SLOVENIAN ELDERLY PATIENTS BASED ON THE BEERS AND
LAROCHE CRITERIA
Tomaž Nerat1, Mitja Kos1 Prispelo: 26. 2. 2010 - Sprejeto: 15. 6. 2010
Izvirni znanstveni članek UDK 614.27
Izvleček
Namen: Zaradi velikega števila starostnikov, ki jemljejo zdravila, je bil cilj analize ugotoviti razširjenost neprimernega predpisovanja zdravil v letu 2006 med starostniki v Sloveniji. Za analizo neprimernega predpisovanja smo izbrali merila Beers 2002 in merila Laroche 2007 in Skupna merila neprimernega predpisovanja. Metode: Analiza je bila opravljena na anonimizirani zbirki podatkov Zavoda za zdravstveno zavarovanje Slovenije o izdaji ambulantno predpisanih zdravil v letu 2006. Analizo z merili Beers 2002 smo opravili na vzorcu starostnikov, starih 65 let in ve~, analizo z merili Laroche 2007 in s Skupnimi merili pa na vzorcu starostnikov, starih 75 let in ve~.
Rezultati: Po merilih Beers 2002 je 22,41 % star^ostnikov prejelo vsaj eno neprimerno u~inko^ino, po merilih Laroche 2007 25,72 %o, po Skupnih merilih pa 35,95 °%o. Glede na objavljene raziskave so deleži dokaj visoki. Delež receptov z neprimerno predpisanimi zdravili (glede na vse recepte) je v primeru analize z merili Beers 2002 znašal 3,43 °%o, v primeru z merili Laroche 2007 4,01 °%o in na podlagi Skupnih meril 6,03 °%o. Deleži so višji kot na Hrvaškem, predvsem zaradi ve~jega števila zdravil, ki jih uporabljamo v Sloveniji. Ugotovili smo tudi, da se verjetnost, da bolnik prejme neprimerno zdravilo, pove~uje s številom predpisanih zdravil. Zaključek: Kljub ugotovljenemu dokaj visokemu deležu neprimernega predpisovanja so mnenja v objavljeni literaturi glede vpliva na zdravstveno stanje starostnikov deljena. Pomembno je poudariti, da naj bi merila bila pomo~ zdravnikom pri izbiri zdravljenja in ne kot zapoved. Prav takoo so namenjeni uporabi v farmahoološ^ih in epidemioloških študijah. Predlagani so na~ini, kako zmanjšati delež neprimernega predpisovanja zdravil.
Ključne besede: neprimerno predpisovanje, neprimerna zdravila, starostniki, Beers, Laroche, merila
Original scientific article UDC 614.27
Abstract
Purpose: Given a great number of elderly people using medications, the main objective of the analysis was to determine the prevalence of prescribing inappropriate medications to the elderly in 2006. Potentially inappropriate medications were identified on the basis of the Beers 2002 and the Laroche 2007 criteria and according to the combined criteria of inappropriate prescribing.
Methods: We analysed the anonymous database of dispensed outpatient medications prescribed in 2006provided by The Health Insurance Institute of Slovenia. Beers's 2002 criteria were used for the elderly people aged 65 or more and the Laroche 2007 and the combined criteria for the age group of 75 years and over. Results: According to the Beers 2002 criteria, 22.41 per cent of the elderly patients were prescribed at least one inappropriate medical ingredient; by the Laroche 2007 criteria, the percentage of older people receiving inappropriate drugs was 25.72 and by the combined criteria 35.95. Judging by the published data, these shares
^Univerza v Ljubljani, Fakulteta za farmacijo, Aškerčeva 7, 1000 Ljubljana Kontaktni naslov: e-pošta: tomaz.nerat@gmail.com
are rather high. The prevalence of inappropriately prescribed n^edications (with respect to all prescriptions) was 3.43 per cent by the Beers 2002 criteria, 4.01 per cent, according to the Laroche 2007 criteria and 6.03 per cent according to the combined criteria. These shares are higher than in Croatia mainly because of the greater quantity of inappropriate medications used in Slovenia. Further it was discovered, that the probability of being prescribed an inappropriate medication increases along with the number of prescribed medications. Discussion: Despite the established high prevalence of potentially inappropriate prescriptions, there is no unanimity in the literature concerning the influence of inappropriate prescribing on the health of older people. We would emphasise here that the criteria discussed are intended to help rather than convince physicians to choose the appropriate therapy. They are also meant to be used in pharmacoepidemiological studies. Ways to reduce the rate of inappropriate medication prescribing are put forward.
Key words: inappropriate prescribing, inappropriate medications, elderly, Beers, Laroche, criteria
1 UVOD
1.1	Uporaba zdravil pri starostnikih
Predpisovanje zdravil je temeljna sestavina skrbi za starej{e ljudi. Ti imajo pogosto hkrati ve~ bolezni in zato jemljejo ve~ zdravil (1). V Sloveniji je med starej{im prebivalstvom delež predpisanih zdravil najve~ji. Po podatkih iz literature je bilo 30. 6. 2005 v Sloveniji 2.001.114 prebivalcev, od tega 412.876 prebivalcev, starih 60 let in ve~, kar je 20,63 % vsega prebivalstva (2). Z upo{tevanjem podatkov iz Zdravstvenega statisti~nega letopisa je bilo tako petini prebivalstva v letu 2006 predpisanih 49,24 % vseh receptov (3).
1.2	Neželeni učinki zdravil in starostniki
Po Zakonu o zdravilih Republike Slovenije je neželeni u~inek zdravila {kodljiv in nenameren odziv, do katerega lahko pride pri odmerkih, ki se pri ljudeh ali živalih obi~ajno uporabljajo za prepre~evanje, diagnosticiranje ali zdravljenje bolezni ali za ponovno vzpostavitev, izbolj{anje ali spremembo fiziolo{ke funkcije. Pojavnost neželenih u~inkov je pri starostnikih pove~ana zaradi treh pomembnih dejavnikov:
-	starostnih sprememb, ki vplivajo na farmakokinetiko zdravil (zmanj{ana mi{i~na masa in posledi~no relativno pove~anje telesne ma{~obe, zmanj{ana koncentracija serumskega albumina, upad jetrne funkcije ter upad glomerulne filtracije (4, 5, 6, 7));
-	starostnih sprememb, ki vplivajo na farmakodinamiko zdravil (vpliv na sr~no-žilni sistem, centralni živ~ni sistem in na homeostatske mehanizme; primer so beta
adrenergi~ni receptorji, katerih delovanje s starostjo pojenja (7));
-	polifarmacije, kar je v najožjem pomenu so~asno jemanje ve~ zdravil, po novej{i opredelitvi pa je predpisovanje oziroma uporaba ve~ zdravil, kot je glede na klini~no sliko potrebno (8). Pomembna je ugotovitev,
da obstaja tesna povezava med nastankom neželenih u~inkov in {tevilom predpisanih zdravil (9, 10). Zato pri starostnikih prej pride do neželenih u~inkov, saj jemljejo v povpre~ju najve~ zdravil hkrati. Po nekaterih ocenah se je pri 5 % do 35 % starostnikov, ki so jim bila zdravila predpisana ambulantno, pojavil vsaj en neželen u~inek (11, 12, 13). Raziskava, ki jo je leta 2000 opravil Gurwitz, je ugotovila 546 neželenih u~inkov pri 2916 stanovalcih domov za ostarele, ki so jih opazovali 12 mesecev (14). Študije so tudi pokazale, da so neželeni u~inki pri starostnikih odgovorni za 18 do 24 odstotkov sprejemov v bolni{nico (15, 16). 27,6 odstotka neželenih u~inkov, ki se pojavijo v populaciji ambulantnih starostnikov, pa bi lahko prepre~ili (12). Med oskrbovanci domov za ostarele je ta delež ve~ji, in sicer zna{a 51 odstotkov. Ve~ino tako nastalih neželenih u~inkov bi lahko prepre~ili, ~e bi starostniki dobili primerna zdravila (14).
1.3 Merila za ugotavljanje neprimernega predpisovanja zdravil pri starostnikih
Pri starostnikih je težko dolo~iti primerna zdravila, saj primanjkuje kakovostnih {tudij, ki bi se ukvarjale s predpisovanjem zdravil starej{im osebam. Klini~na testiranja pogosto ne vklju~ujejo starostnikov in obravnavajo tiste, ki so relativno mladi in zdravi (17). Obstaja na~in, kako premostiti to težavo. Zdravniki in raziskovalci lahko presojajo morebitne ugodne u~inke in tveganja uporabe zdravil na {ir{i populaciji bolnikov, nato pa ugotovitve prilagodijo specifi~ni skupini bolnikov, kot so starostniki. Nastala so merila, ki opredeljujejo neprimerno predpisovanje zdravil starostnikom tako, da navajajo seznam u~inkovin, ki so potencialno neprimerne za uporabo pri starostnikih. Merila so slede~a (poimenovanje glede na literaturo v angle{kem jeziku):
-	merila neprimernega predpisovanja Beers 1991,
-	merila neprimernega predpisovanja Stuck 1994,
-	merila neprimernega predpisovanja Beers 1997,
-	merila neprimernega predpisovanja McLeod 1997,
-	merila neprimernega predpisovanja Zhan 2001,
-	merila neprimernega predpisovanja Beers 2002,
-	merila neprimernega predpisovanja Laroche 2007. V nadaljevanju strokovnega ~lanka bomo praviloma uporabljali skraj{ano obliko poimenovanja meril le z imeni in letnico. Opisali bomo le merila Beers 2002 in Laroche 2007, saj smo z njimi opravili analizo neprimernega predpisovanja.
1.3.1	Merila neprimernega predpisovanja Beers 2002
Merila so bili objavljena leta 2003 (18), vendar oblikovana leta 2002, zato jih imenujemo merila Beers 2002. Pri izdelavi so avtorji sledili trem zastavljenim ciljem. Prvi je posodobitev meril iz leta 1997 z novimi u~inkovinami in podatki iz literature, drugi cilj je posodobitev ocene nevarnosti možnih neželenih u~inkov in tretji prepoznanje novih bolezenskih stanj, ki jih niso upo{tevali v merilih iz leta 1997 (ti so nasledniki in nadgradnja meril Beers 1991). Merila sestavljata dva seznama. Prvi seznam vsebuje 48 u~inkovin oziroma skupin zdravil, ki naj jih ne bi izdajali ljudem, starej{im od 65 let, drugi seznam pa vsebuje 20 u~inkovin, ki naj jih starostniki ne bi uporabljali pri dolo~enih bolezenskih stanjih. Z merili Beers 2002 so opravili {tevilne {tudije, s pomo~jo katerih smo lahko primerjali pridobljene rezultate.
1.3.2	Merila neprimernega predpisovanja Laroche 2007
Francoska merila oziroma merila Laroche 2007 so nastala zaradi razlik v razpoložljivosti zdravil, klini~ni praksi, socialni ureditvi, ekonomiji in ureditvi zdravstvenih sistemov med Evropo ter Severno Ameriko (). Avtorji so želeli oblikovati nova merila z uporabo delfske tehnike in vklju~iti predloge za varnej{e alternative. S soglasjem petnajstih strokovnjakov (5 farmakologov, 1 farmakoepidemiolog, 5 geriatrov, 2 farmacevta, 2 splo{na zdravnika) so nastala merila za ljudi, stare 75 let in ve~.
Merila so nastala po vzoru meril Beers. Vsebujejo nekatere u~inkovine z njihovega seznama. Vendar mnogo u~inkovin niso vklju~ili v merila Laroche 2007, ker jih na francoskem trgu ni (pentazocin, trimetobenzamid, flurazepam, meperidin, tioridazin, mesoridazin, etakrinska kislina in barbiturati). S seznama so izklju~ili tudi peroralno uporabo estrogenov, ker jih v Franciji ne predpisujejo brez
progesterona. Fenilbutazon so odstranili s seznama Beers 2002, v merilih Laroche 2007 pa ga ponovno vklju~ili zaradi resnih hematolo{kih neželenih u~inkov, ki jih lahko povzro~a. Fluoksetina in amiodarona ne ozna~ujejo kot neprimerna, saj po mnenju avtorjev nista ni~ manj u~inkovita in ne povzro~ata ni~ ve~ neželenih u~inkov kot kateri koli drugi selektivni inhibitor privzema serotonina ali antiaritmik.
1.4	Izidi predpisovanja neprimernih zdravil starostnikom
Mnenja glede vpliva, ki ga ima lahko neprimerno zdravilo v smislu neželenih u~inkov, so v literaturi deljena. Študija, opravljena na podlagi meril Beers 1991 v domu za ostarele ni odkrila povezave med {tevilom prejetih neprimernih zdravil in umrljivostjo (20). Obstajala pa je povezava med {tevilom neprimernih zdravil in stro{ki zdravljenja. Do tak{nega zaklju~ka so avtorji pri{li pod predpostavko, da neprimerna zdravila vodijo do neželenih u~inkov, za njihovo zdravljenje pa potrebujemo {e ve~ sredstev. V analizi, ki je zajemala bolnike na urgenci v Chicagu (21), so avtorji iskali povezavo med uporabo neprimernih zdravil po merilih Beers 1997 in zdravstvenim stanjem bolnikov. Ugotovili so, da jemanje neprimernih zdravil ne vpliva na {tevilo obiskov urgence, na {tevilo sprejemov v bolni{nico in na smrtnost, poslab{a pa telesno po~utje in bole~ino. Prav tako so analizirali izide starostnikov, ki so bili zavarovani v ameri{kem socialnem zavarovanju Medicare (22). Ugotovili so, da je uporaba neprimernega zdravila (po merilih Beers 1997) zna~ilno vplivala na {tevilo ambulantnih obiskov, obiskov na urgenci in na hospitalizacijo bolnikov. Leta 2005 sta bili opravljeni raziskavi, ki sta ponovno vklju~ili starostnike v domovih za ostarele. Prva (23) je ugotovila, da so možnosti za hospitalizacijo, obisk urgence ali smrt 2,3-krat ve~je pri starostnikih, ki prejemajo vsaj eno neprimerno zdravilo. Druga raziskava (24) je ugotovila zna~ilno povezavo med jemanjem neprimernega zdravila (po merilih Beers 1997) in možnostjo hospitalizacije ali smrti. Tovrstno analizo so opravili tudi v Franciji (25). Ugotovili so, da je od 2018 starostnikov samo 79 starostnikov doživelo neželen u~inek, ki je bil posledica jemanja neprimernega zdravila.
1.5	Namen analize neprimernega predpisovanja
Zaradi velikega {tevila starostnikov, ki jemljejo zdravila, smo z analizo želeli na podlagi meril Beers 2002, Laroche 2007 in Skupnimi merili ugotoviti raz{irjenost neprimernega predpisovanja zdravil v letu 2006 med starostniki v Sloveniji in rezultate primerjati s podatki iz že objavljenih raziskav.
2 METODE
3 REZULTATI
Analizo smo opravili s pomo~jo anonimizirane zbirke Zavoda za zdravstveno zavarovanje Slovenije o izdajah ambulantno predpisanih zdravil v letu 2006. Z merili Beers 2002 smo preu~ili podatke o starostnikih, starih 65 let in ve~. Pri analizi z merili Laroche 2007 in Skupnimi merili pa smo uporabili podatke starostnikov, starih 75 let in ve~. Skupna merila so merila, ki smo jih sestavili na podlagi u~inkovin iz meril Beers 2002 in Laroche 2007, ki so bile prisotne v anonimizirani zbirki. Pri ugotavljanju raz{irjenosti neprimernega predpisovanja smo uporabili samo tiste dele meril, ki se ne nana{ajo na zdravstveno stanje bolnika. V Tabeli 1 so podane u~inkovine, pri katerih smo analizirali neprimerno predpisovanje. Zaradi obsežnosti zbirke smo napisali postopke SPSS (Syntaxe), s katerimi smo v kratkem ~asu pridobili rezultate za vse tri vrste meril. Rezultati analize zajemajo podatke o zna~ilnostih vseh starostnikov v osnovni zbirki in zna~ilnostih starostnikov, ki so prejeli vsaj eno neprimerno u~inkovino. Prav tako smo preu~ili podatke o deležih receptov po u~inkovinah glede na vse recepte s predpisanim vsaj enim neprimernim zdravilom, podatke o deležih starostnikov po {tevilu prejetih neprimernih u~inkovin in opredelili povezavo med {tevilom prejetih neprimernih u~inkovin in povpre~nim {tevilom vseh prejetih u~inkovin. Prav tako smo analizirali podatke o {tevilu zdravnikov, ki so predpisali vsaj eno neprimerno zdravilo in o {tevilu lekarn, ki so izdale vsaj eno neprimerno zdravilo.
3.1	Značilnosti vseh starostnikov v osnovni zbirki
V anonimizirani zbirki podatkov Zavoda za zdravstveno zavarovanje Slovenije o izdaji ambulantno predpisanih zdravil je zna{alo {tevilo starostnikov, starej{ih od 65 let, pri katerih smo analizirali neprimerno predpisovanje po merilih Beers 2002, 298.990. Starostnikov, starej{ih od 75 let, ki smo jih analizirali po merilih Laroche 2007 in Skupnih merilih, pa je bilo 136.076. Starostnikom, vklju~enim v analizo po merilih Beers 2002, je bilo predpisanih 5.818.913 receptov, vklju~enim v analizo po merilih Laroche 2007 in Skupnih merilih pa je bilo predpisanih 2.954.730 receptov. Starostniki, vklju~eni v analizo po merilih Laroche 2007 in Skupnih merilih so v letu 2006 prejemali zna~ilno ve~ razli~nih u~inkovin (8,32 ± 5,02) kot starostniki, vklju~eni v analizo po merilih Beers 2002 (7,65 ± 4,85).
3.2	Zna~ilnosti starostnikov v osnovni zbirki, ki so prejeli vsaj eno neprimerno zdravilo
Ugotovili smo, da je delež neprimernega predpisovanja ({tevilo starostnikov z neprimerno predpisanim zdravilom glede na vse starostnike) po merilih Beers 2002 zna{al 22,41 %, po merilih Laroche pa 25,72 %. Podatki so predstavljeni v Tabeli 2. V analizi z združenimi u~inkovinami (Skupna merila) je zna{al delež neprimernega predpisovanja 35,95 %. Delež receptov z neprimerno predpisanimi zdravili (glede na vse recepte) je v primeru analize z merili Beers 2002 zna{al 3,43 %, 4,01 % z merili Laroche 2007 in 6,03 % glede na Skupna merila.
Tabela 1. Kon~en seznam učinkovin, s katerimi smo opravili analizo neprimernega predpisovanja. Table 1. Final list of aktive ingredients used in the analysis of inappropriate prescribing.
Učinkovina/ Active ingredient	ATC/delovna šifra/ ATC/work code	Merila*/ Criteria*
estradiol (peros)/estradiol (peros)	97381	B
butilskopolamin/butylscopolamine	A0dBB01	L
bisakodil/bisacodyl	A06AB02	B,L
glipizid/glipizide	A10BB07	L
tiklopidin/ticlopidine	B01AC05	B,L
dipiridamol/dipyridamole	B01AC07	B,L
amiodaron/amiodarone	C01BD01	B
moksonidin/moxonidine	C02AC05	L
doksazosin/doxazosin	C02CA00	B
pentoksifilin/pentoxifylline	C00AD0d	L
ergoloidijev mesilat/ergoloid mesylate	C00AE01	B
nicergolin/nicergoline	C00AE02	L
trokserutin/troxerutine	C05CA00	L
tolterodin/tolterodine	G00BD07	L
indometacin/indometacine	M01AB01	B,L
piroksikam/piroxicam	M01AC01	B
naproksen/naproxen	M01AE02	B
baklofen/baclofen	M0dBX01	L
pentazocin/pentazocine	N02AD01	B
levomepromazin/levomepromazine	N05AA02	L
flufenazin/fluphenazine	N05AB02	L
tioridazin/thioridazine	N05AC02	B
diazepam/diazepam	N05BA01	B,L
bromazepam/bromazepam	N05BA08	L
klobazam/clobazam	N05BA09	L
flurazepam/flurazepam	N05CD01	B
nitrazepam/nitrazepam	N05CD02	L
klomipramin/clomipramine	N06AA00	L
amitriptilin/amytriptiline	N06AA09	B,L
doksepin/doxepin	N06AA12	B,L
maprotilin/maprotilin	N06AA21	L
fluoksetin/fluoxetine	N06AB0d	B
piracetam/piracetam	N06BX0d	L
difenhidramin/diphenhydramine	R06AA02	B,L
* B - merila Beers 2002, L - merila Laroche 2007
B- Beers 2002 criteria, L - Laroche 2007 criteria
** V analizi po Skupnih merilih smo uporabili vse učinkovine iz Tabele 1.
In the analysis with the combined criteria we used all active ingredients from Table 1.
Tabela 2. Značilnosti starostnikov v osnovni zbirki, ki so prejeli vsaj eno neprimerno zdravilo. Table 2. Characteristics of the elderly in the database, who received at least one inappropriate medication.
Starostniki, ki so prejeli vsaj eno neprimerno zdravilo/ Elderly prescribed at least one inappropriate medication	Merila neprimernega predpisovanja/Inappropriate prescribing criteria		
	Beers 2002/Beers 2002 (nad 65 let)/ (above 65 years)	Laroche 2007/ Laroche 2007 (nad 75 let)/ (above 75 years)	Skupna/ Combined (nad 75 let)/ (above 75 years)
Število starostnikov/ Number of elderly people	66.994 (22,41 %)	34.999 (25,72 %)	48.917 (35,95 %)
Število predpisanih receptov/Number of prescriptions	199 430 (3,43 %)	118 475 (4,01 %)	178 311 (6,03 %)
3.3 Deleži receptov po učinkovinah glede na vse recepte s predpisanim vsaj enim neprimernim zdravilom
Tabela 3. Deleži receptov po učinkovinah glede na vse recepte s predpisanim vsaj enim neprimernim zdravilom.
Table 3. Shares of prescriptions by active ingredients with regard to all prescriptions with at least one inappropriate medication.
Merila neprimernega predpisovanja/ Inappropriate prescribing criteria
Beers 2002/ Beers 2002
Laroche 2007/ Laroche 2007
Skupna/ Combined
naproksen/naproxen (33,36 %) diazepam/diazepam (24,98 %) doksazosin/ doxazosin (23,66 %) amiodaron/amiodarone (8,91 %)
tiklopidin/ ticlopidine (5,54 %) flurazepam/flurazepam (4,64 %) amitriptilin/amytriptiline (4,26 %)
bromazepam/ bromazepam (40,58 %)
diazepam/ diazepam (23,76 %)
pentoksifilin/ pentoxifylline (11,49
%)
glipizid/glipizide (6,18 %)
tiklopidin/ticlopidine (5,40 %)
moksonidin/ moxonidine (4,03 %) nitrazepam/ nitrazepam (3,79 %)
bromazepam/bromazepam (29,03 %)
naproksen/naproxen (18,86 %) diazepam/diazepam (17,00 %) doksazosin/doxazosin (13,90 %) pentoksifilin/pentoxifylline (8,22 %) amiodaron/amiodarone (6,69 %) tiklopidin/ticlopidine (4,42 %)
Najpogosteje predpisane neprimerne u~inkovine (dvomestna {tevilka deleža receptov) po merilih Beers 2002 so: naproksen, diazepam in doksazosin. Po deležu sledijo amiodaron, tiklopidin, flurazepam in amitriptilin. Rezultati so podani v Tabeli 3. Po merilih Laroche 2007 so bili najpogosteje predpisani bromazepam, diazepam in pentoksifilin. Navedenim u~inkovinam sledijo glede na delež receptov glipizid, tiklopidin, moksonidin in nitrazepam. Po Skupnih merilih (dvomestna {tevilka deleža receptov) so bili najpogosteje predpisani bromazepam, naproksen, diazepam in doksazosin. Po deležu sledijo pentoksifilin, amiodaron in tiklopidin.
3.4 Deleži starostnikov po številu prejetih neprimernih učinkovin
Tabela 4 navaja, kolik{en delež starostnikov je v letu 2006 prejel eno, dve ali ve~ neprimernih u~inkovin. V analizah po vseh merilih so predstavljali starostniki z eno neprimerno u~inkovino najve~ji delež, 10 % starostnikov pa je ve~inoma jemalo po dve neprimerni u~inkovini. Opazili smo, da je delež starostnikov, ki so prejeli samo eno neprimerno u~inkovino, v analizi po Skupnih merilih mnogo manj{i kot pri ostalih analizah.
Podobne rezultate po deležu starostnikov, ki so jemali eno, dve, tri, {tiri, pet ali {est neprimernih u~inkovin, so ugotovili v raziskavi z merili Beers 1997 v Domu za ostarele Šentjur, kjer je 90 % starostnikov imelo predpisano eno neprimerno u~inkovino, 8 % dve in 1 % tri ali {tiri, kar je podobno rezultatom analize po merilih Beers 2002 in merilih Laroche 2007 (26).
3.5	Povezava med številom prejetih neprimernih učinkovin in povprečnim številom vseh prejetih učinkovin
V analizi smo ugotovili, da je osrednji vzrok za zve~ano možnost prejema neprimernega zdravila {tevilo razli~nih u~inkovin, ki jih starostnik prejema. Slednje je razvidno iz Grafa 1, v katerem vidimo skoraj linearno povezanost med povpre~nim {tevilom vseh prejetih u~inkovin in {tevilom prejetih neprimernih u~inkovin. Odstopanje v primeru Skupnih meril je posledica dejstva, da so samo trije starostniki prejeli {est ali ve~ neprimernih u~inkovin, od katerih je eden prejel zna~ilno manj vseh u~inkovin.
3.6	Ugotovitev števila zdravnikov, ki so predpisali vsaj eno neprimerno zdravilo
Analiza zdravnikov je pokazala, da je v primeru meril Beers 2002 predpisalo vsaj eno neprimerno zdravilo 48,15 % zdravnikov (3597 od 7471), v primeru meril Laroche 2007 43,72 % (2734 od 6253), v primeru Skupnih meril pa 51,98 % (3250 od 6253) zdravnikov. Deleži so dokaj visoki, {e posebej ~e upo{tevamo, da je v primeru meril Beers 2002 in Skupnih meril 51 oziroma 53 zdravnikov v letu 2006 predpisalo od 401 do 1000 receptov za neprimerna zdravila.
3.7	Ugotovitev števila lekarn, ki so izdale vsaj eno neprimerno zdravilo
Vse lekarne so izdale najmanj eno neprimerno zdravilo. Najve~je {tevilo lekarn je opravilo od 0 do 750 izdaj neprimernih zdravil oziroma od 0 do 500 izdaj neprimernih zdravil. V analizi po Skupnih merilih moramo izpostaviti, da je od 273 lekarn samo 61 lekarn opravilo polovico vseh neprimernih izdaj zdravil.
Tabela 4. Deleži starostnikov po številu p^eje^ih neprimernih učinkovin. Table 4. Shares of the elderly by the number of r^eceived inappropriate drugs.
Število prejetih neprimernih u~inkovin/ Number of inapropriate active ingredients received	Merila neprimernega predpisovanja/ Inappropriate prescribing criteria		
	Beers 2002/ Beers 2002	Laroche 2007/ Laroche 2007	Skupna/ Combined
1	86,97 %	85,37 %	76,48 %
2	11,70 %	13,04 %	19,30 %
3	1,20 %	1,47 %	3,53 %
4	0,12 %	0,12 %	0,56 %
5	0,01 %	0,01 %	0,11 %
6	0,00 %	/	0,01 %
0 >
< ■

Povprečno število prejetih učinkovin glede na število prejetih neprimernih učinkovin po Skupnih merilih/ Amount of all received active ingredients regarding to the amount of received inappropriate active
ingredients
30,00
25,00
S^ 20,00
o
CS
(T TU i; a)
s: cj 0 o
(A 0) > '-
>
O Q.
15,00
10,00
0,00
■ Merila Beers 2002/ Beers 2002 criteria ---■■-- Merila Laroche 2007/ Laroche 2007 criteria — -A — Skupni kriteriji/
Combined criteria
Število prejetih neprimernih učinkovin/ Number of received inappropriate active ingredients
Slika 1. Povpre~no število vseh prejetih u~inkovin glede na število prejetih neprimernih u~inkovin. Graph 1. Average number of all received active ingredients with regard to the number of received inappropriate active ingredients.
4 RAZPRAVLJANJE
4.1 Komentar rezultatov, pridobljenih z analizo neprimernega predpisovanja zdravil po merilih Beers 2002, merilih Laroche 2007 in po Skupnih merilih
Opravljena analiza je prva raziskava neprimernega predpisovanja zdravil na večjem številu starostnikov v Sloveniji. Nadalje je tudi edina raziskava, ki je v Sloveniji uporabila merila Beers 2002 in merila Laroche 2007 neprimernega predpisovanja ter merila, ki združujejo učinkovine obojih (Skupna merila). Prikazali smo, da je bilo v Sloveniji v letu 2006 prisotno neprimerno predpisovanje. Po merilih Beers 2002 v obsegu 22,01 % (delež starostnikov z vsaj enim neprimernim zdravilom glede na vse starostnike), po merilih Laroche 2007 25,72 % in po Skupnih
merilih d5,95 %. Kot vzrok za razliko v deležih med merili Beers 2002 in Laroche 2007 smo izključili predpostavko, da so starostniki, stari od 65 do 75 let, v manjšem obsegu prejemali neprimerna zdravila in tako nižali povprečje. Razlike po deležih med starostnimi skupinami so bile namreč premajhne. Vzrok za razliko je v tem, da so merila Laroche 2007 novejša in prilagojena evropskemu trgu. Tako so vključevali več učinkovin, dostopnih v Sloveniji. Glede na to, da v bibliografski podatkovni zbirki MEDLINE (27) nismo zasledili študij, opravljenih z merili Laroche 2007, lahko opravimo primerjavo rezultatov samo v primeru meril Beers 2002. Objavljene študije navajajo od 5,8-odstotni do d8,5-odstotni delež oseb z vsaj enim prejetim neprimernim zdravilom. Nižje deleže neprimernega predpisovanja (5,8 % do 22,0 %) od naših so zasledile raziskave v Turčiji, Italiji, na Nizozemskem, Japonskem, v Libanonu, na Danskem, v Angliji, na Islandiji in na Norveškem (28, 29, d0, d1, d2, dd). Vse raziskave, razen Japonske, so zajemale
0
2
3
5
6
1
4
starostnike z ambulantno predpisanimi zdravili in ki živijo doma brez oskrbe na domu. Anonimizirana zbirka o ambulantno izdanih zdravilih je prav tako zajemala predvsem starostnike, ki živijo doma. Pri raziskavah, kjer so bili deleži neprimernega predpisovanja vi{ji, so bile analize opravljene s starostniki, ki so bili negibni in so bili deležni oskrbe na domu ali so živeli v domovih za ostarele ali pa so vsi starostniki v vzorcu jemali 2 zdravili ali ve~ (34, 35, 36, 37, 38). V eni raziskavi so celo upo{tevali samo starostnike, ki so jemali 5 zdravil ali ve~ (39). Po objavljenih pregledanih ~lankih tak{ne zna~ilnosti vzorca pove~ajo delež neprimernega predpisovanja (40). Tako je delež neprimernega predpisovanja, ki smo ga zaznali v osnovni zbirki, ve~inoma ve~ji od deležev, pridobljenih na starostnikih, katerih lastnosti ne vi{ajo deležev neprimernega predpisovanja. Tiste raziskave, v katerih so zaznali ve~ji delež neprimernega predpisovanja, so opravili na starostnikih, katerih lastnosti vi{ajo deleže. Iz tega lahko sklepamo, da je neprimerno predpisovanje v Sloveniji po merilih Beers 2002 dokaj raz{irjeno. Delež receptov z neprimerno predpisano u~inkovino glede na vse recepte je zna{al po merilih Beersovih 2002 3,43 %, po merilih Laroche 2007 4,01 % in po Skupnih merilih 6,03 %. Rezultate lahko primerjamo samo z analizo, opravljeno na Hrva{kem (41). Tam je zna{al delež receptov 2,2 %, kar je sicer manj kot v Sloveniji, toda na Hrva{kem so opravili analizo s samo 8 u~inkovinami, saj jih ve~ ni bilo dostopnih. V celotni populaciji starostnikov (nad 75 let) so bile najpogosteje predpisane (dvomestna {tevilka deleža receptov) u~inkovine bromazepam (anksiolitik), doksazosin (antihipertenziv), diazepam (anksiolitik), naproksen (analgetik) in pentoksifilin (periferni vazodilatator). Med njimi sta tako dva anksiolitika, dolgo delujo~a benzodiazepina. Po merilih Beers 2002 ima skupina dolgo delujo~ih benzodiazepinov oznako nevarnosti neželenih u~inkov ""visoko". Znaten delež starostnikov v Sloveniji je tako leta 2006 prejel u~inkovino, katere neželeni u~inki so zaradi starostnih sprememb v farmakokinetiki podalj{ani in izrazitej{i. Zaradi tega so bili starostniki izpostavljeni pove~anim možnostim za padce. Nevarnost neželenih u~inkov doksazosina je ozna~ena z ""nizko", povzro~i pa lahko ortostatsko hipotenzijo in posledi~no padce ter zlome, vendar ne v tolik{ni meri kot bromazepam in diazepam. Tudi nevarnost neželenih u~inkov pentoksifilina ni ocenjena z "visoko". Med merila Laroche 2007 je namre~ vklju~en predvsem zaradi pomanjkanja delovanja. Neželeni u~inki, ki jih povzro~a naproksen, pa so ocenjeni z ""visoko". Kot neprimerna je ozna~ena njegova dolgotrajna uporaba. Ugotovili smo, da je bil
v povpre~ju predpisan 1,92-krat oziroma 1,99-krat na osebo. V obeh primerih ga je to uvr{~alo glede na ostale rezultate med nižje. Sklepamo, da se ne uporablja dolgotrajno in tako posledi~no ne predstavlja velike nevarnosti, vendar je kljub temu priporo~ljivo, da zdravniki spremljajo zdravstveno stanje starostnikov, ki uporabljajo naproksen. Med prvimi petimi najpogosteje predpisanimi u~inkovina sta torej dve, katerih neželeni u~inki so za starostnike nevarnej{i. U~inkovine, ki sledijo zgoraj na{tetim, imajo oznako nevarnosti neželenih u~inkov "visoko". To so amiodaron (antiaritmik), glipizid (antidiabetik), tiklopidin (antitrombotik), flurazepam (hipnotik in sedativ), moksonidin (antihipertenziv), nitrazepam (hipnotik in sedativ) ter amitriptilin (antidepresiv). Starostniki so bili v letu 2006 tako v ve~ji meri dovzetnej{i za naslednje neželene u~inke: motnje intervala QT, pnevmonitis, hipoglikemija, nevtropenija, agranulocitoza, tromboti~na trombocitopeni~na purpura, aplasti~na anemija, sedacija, hipotenzija, antiholinergi~ni neželeni u~inki in upo~asnitev intraventrikularnega prevajanja.
4.2	Komentar meril neprimernega predpisovanja
Avtorji meril, ki opredeljujejo neprimerno predpisovanje, opozarjajo na omejitve, ki jih je potrebno upo{tevati pri analizah (18, 19). Merila, ki opredeljujejo neprimerno predpisovanje, so namenjena uporabi v splo{ni populaciji starostnikov in ne dolo~ajo za vsakega starostnika absolutno, katera u~inkovina je zanj primerna in katera ne. Pri nekaterih starostnikih je namre~ razmerje med koristjo in tveganjem zaradi posebnih okoli{~in (klini~no stanje, so~asne bolezni, zdravila, ki jih starostnik jemlje, napoved izida bolezni) ve~je kot v splo{ni populaciji starostnikov. Zato avtorji navajajo, da je priporo~ljivo ob terminu "neprimerno predpisovanje" navesti, da gre dejansko za primer potencialnega neprimernega predpisovanja. Tako moramo tudi mi navesti obstoj možnosti, da vsi starostniki, ki smo jih ozna~ili kot prejemnike neprimernega zdravila, to niso bili.
4.3	Kako prepre~iti potencialno neprimerno predpisovanje zdravil
Kljub pomislekom glede izidov zdravljenja obstaja možnost, da neprimerna zdravila povzro~ijo neželene u~inke, ki se z uporabo pravilnega zdravljenja ne bi pojavili. Zato je potrebno razmisliti, kako omejiti predpisovanje potencialno neprimernih zdravil. Eden izmed na~inov pri omejevanju predpisovanja je upo{tevanje meril neprimernega predpisovanja s strani
zdravnikov, kadar predpisujejo zdravila starostnikom, in s strani farmacevtov, kadar zdravila izdajajo. Ker so pri neprimernih zdravilih posebej izpostavljeni dolo~eni neželeni u~inki, je pomembno, da zdravnik in farmacevt ob predpisovanju ali ob izdaji zdravila povpra{ata bolnika o pojavljanju neželenih u~inkov ter se ustrezno odzoveta ob njihovi prisotnosti, to je tako, da zdravnik predpi{e alternativno zdravilo ali pa farmacevt zavrne izdajo zdravila in o tem obvesti zdravnika.
Obseg neprimernega predpisovanja lahko zmanj{a tudi vklju~itev klini~nega farmacevta v proces dolo~anja terapijske strategije. Priporo~ila klini~nega farmacevta, ki temeljijo na pregledu zdravstvene kartoteke bolnika in zdravil, ki jih ta jemlje, znižajo obseg neprimernega predpisovanja, znižajo skupno {tevilo predpisanih zdravil in znižajo pojavnost neželenih u~inkov (42). Dejavnik, ki lahko vpliva na delež neprimernega predpisovanja, je tudi uporaba opozoril med postopkom predpisovanja zdravil. Opozorila, ki vsebujejo podatke o medsebojnem u~inkovanju zdravil, alergijah na zdravila in preob~utljivost na zdravila v povezavi z bolnikovo kartoteko, so zna~ilno znižala pojavnost napak, ki se lahko pojavijo ob njihovem predpisovanju (42).
V	vsaj {tirih {tudijah so dokazali, da obseg polifarmacije in neprimernega predpisovanja znižuje pregled zdravil, ki jih bolnik jemlje. V to so v{teta zdravila na recept, OTC zdravila in prehranska dopolnila (42).
Peti dejavnik, ki lahko vpliva na primernost predpisovanja, je izobraževanje bolnika. V objavljenih {tudijah sta tako kraj{e osebno svetovanje farmacevta kot predavanje ve~ji skupini bolnikom o neželenih u~inkih zdravil znižala obseg polifarmacije in posledi~no obseg neprimernega predpisovanja (42).
5 ZAKLJUČEK
Neprimerno predpisovanje zdravil starostnikom je bilo v Sloveniji v letu 2006 prisotno v dokaj pogosto. Kljub temu da so mnenja glede izidov zdravljenja z neprimernimi zdravili deljena, je zaželeno, da neprimerno predpisovanje zdravil zmanj{amo. Glede na objavljeno literaturo predlagamo na~ine, kako bi s sodelovanjem zdravnikov, farmacevtov in bolnikov lahko delno urediti podro~je neprimernega predpisovanja zdravil starostnikom.
V	prihodnje bi bilo potrebno izdelati analizo neprimernega predpisovanja zdravil z upo{tevanjem odmerkov zdravil in z upo{tevanjem neprimernih kombinacij zdravil. Prav tako bi bilo potrebno izdelati
raziskavo o vplivih uporabe neprimernih zdravil na pojavljanje neželenih u~inkov.
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ADHERENCA PRI ZDRAVLJENJU OSTEOPOROZE Z ENKRAT
MESEČNIM BISFOSFONATOM
ADHERENCE TO OSTEOPOROSIS TREATMENT WITH ONCE-MONTHLY BISPHOSPHONATE
Marija Petek [ter1, Igor [vab1, Davorina Petek1, Gordana Kalan Živčec1 Prispelo: 19. 4. 2010 - Sprejeto: 26. 7. 2010
Izvirni znanstveni članek UDK 615:616.4
Izvle~ek
Izhodišča: A^dherenca pri zdravljenju kroničnih bolezni, zlasti tistih, ki ne povzroča^jo simptomov, predstavlja pr^oblem. Zanimalo nas je, l^a^šna je adhe^enca pri enkrat mesečnem jemanju bisfosfonata za zdravljenje osteopor^oze, kakšen je v^pliv podpornega progra^ma na adherenco ter kakšna so stališča bolnic in njihovih zdravnikov o pomenu zdravljenja osteopor^oze ^er podpornega programa.
Preiskovanci in metode: V raziskavi je sodelovalo 329 bolnic s primarno osteoporozo. 6-mesečno adher^enco pri zdravljenju smo ugotavljali na podlagi števila predpisanih škatlic zdravila. Kot vir podatkov nam je služil zdravstveni karton splošne medicine. Stališča bolnic o osteopor^ozi in podpornem programu za osteoporozo smo ugotavljali s pomočjo strukturiranega intervjuja, stališča zdravnikov pa s pomočjo vprašalnika, izdelanega za namen te raziskave.
Rezultati: Bolnice z osteoporozo so bile v povprečju stare 70,9 let (SD 10,0 let). Na 7-stopenjski Likerto^i skali so ocenile pomembnost zdravljenja osteoporoze z oceno 6,23 (SD 1,28), zdravniki pa z oceno 6,22 (SD 0,83). Ugotovili smo, da je 6-mesečna adherenca pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata 90,6 %. Boljšo adherenco pri zdr^avljenju je napovedovala višja stopnja šolske izobrazbe (razmerje obetov: 2,17, 95-odstotni interval zaupanja 1,33-^3,55) ter pozitivno stališče bolnic do zdr^avljenja osteoporoze (razmerje obetov: 1,74, 95-odstotni interval zaupanja 1,27-^2,38). Sodelovanje v podpornem programu ni vplivalo na boljšo adherenco pri zdravljenju, čeprav so ga bolnice in zdravniki ocenili kot k^oristnega.
Zaklju~ki: /Adherenca pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata je visoka. Pomemben dejavnik, ki je napovedoval adherenco, je prepričanje bolnic, da je zdravljenje osteoproze zelo pomembno.
Ključne besede: osteoporoza, adherenca, podporni program, stališča
Original scientific article UDC 615:616.4
Abstract
Background: Adherence to drug treatment of chronic diseases, especially symptomless conditions, poses a problem. The aim of our study was to determine the level of patient adherence to once-monthly bisphosphonate treatment of osteoporosis, to evaluate the impact of patient support on adherence and to determine attitudes of patients and their general practitioners towards the value of treatment for osteoprosis and patient support. Patients and methods: 329 female patients with primary osteoporosis participated in the study. The patients were followed for six months. The adherence level was measured on the basis of the number of drug packs prescribed. Data were derived from the patients' medical records. The patients' attitudes towards osteoporosis and patient support programme were assesed through a structured interview, and the attitudes of general practitioners were assessed using a questionnaire developed for the purpose of the research.
Results: The mean age of the patients was 70.9 years (SD 10.0 years). The importance of osteoporosis was assessed on a 7-point Likert scale. The mean value was 6.23 (SD 1.28) for the patients and 6.22 (SD 0.83) for the physicians.
1Univerza v Ljubljani, Medicinska fakulteta, Katedra za družinsko medicino, Poljanski nasip 58, 1000 Ljubljana Kontaktni naslov: e-pošta: marija.petek-ster@mf.uni-lj.si
Sixmonth adherence to once-monthly bisphosphonate was 90.6%. Better adherence was predicted for patients with higher levels of education (OR 2.17, 95% CI 1.33-3.55) and more positive attitudes towards treatment (OR 1.74, 95% CI 1.27-2.38). Participation in the patient support programme had no impact on adherence, yet both patients and physicians considered the programme to be useful.
Conclusions: Adherence to once-monthly bisphosphonate was high. The important factor influencing the level of adherence was the patients' positive attitude towards osteoporosis treatment.
Key words: osteoporosis, adherence, patient support, attitudes
1 Uvod
Adherenca je izraz, ki ga najpogosteje sre~amo v anglosa{ki literaturi (angl. adherence) in pomeni sodelovanje, partnerstvo in uravnoteženost odnosa z bolnikom. Obi~ajno izraz uporabljamo v povezavi z jemanjem zdravil ter pomeni pravilno in redno jemanje zdravil v dalj{em obdobju z upo{tevanjem aktivne vloge bolnika (1).
Adherenca je obi~ajno visoka, ko gre za zdravljenje akutnih stanj, velik problem pa predstavlja pri obravnavi kroni~nih bolnikov in je dejavnik tveganja za slab izid zdravljenja (2,3).
Za osteoporozo je zna~ilno zmanj{anje kostne mase in pove~ano tveganje za zlome. Bolezen do zloma ne povzro~a posebnih težav, kar predstavlja dejavnik tveganja za slabo sodelovanje. Ob ugotovljeni prevalenci osteoporoze v Sloveniji, ki je pri ženskah, starih 50 let in ve~, 27,5 %, se zdravi manj kot ~etrtina bolnic z osteoporozo (4).
Zdravljenje osteoporoze je kompleksno in vklju~uje dietne ukrepe ter zdravljenje z zdravili. Da bo zdravljenje uspe{no, mora biti dolgotrajno in redno, zahteva pa tudi poseben na~in jemanja zdravil. Najpogosteje uporabljana zdravila za zdravljenje osteoporoze - bisfosfonati - imajo pogosto stranske u~inke (dražijo prebavila), kar predstavlja enega od pomembnih dejavnikov, ki zmanj{ujejo adherenco pri zdravljenju, ki je za bisfosfonate v povpre~ju 60 % (5). Tedenski ali mese~ni režim jemanja v primerjavi z dnevnim režimom jemanja je po podatkih ve~ raziskav ob primerljivi u~inkovitosti prispeval k bolj{emu sodelovanju pri zdravljenju (6-12). Enkrat mese~ni odmerek ibadronata 150 mg se je izkazal za enako u~inkovitega v primerjavi z enkrat tedenskim odmerkom alendronata 70 mg (12). Na izrecno željo bolnikov po zdravljenju enkrat na mesec in vplivu na adherenco pri zdravljenju pa je enkrat mese~ni odmerek bisfosfonata lahko izbira, ki izbolj{a sodelovanje pri zdravljenju in tudi izid zdravljenja (11).
Čeprav na pojav strankih u~inkov zdravila nimamo vpliva, pa lahko s skrbnim spremljanjem bolnika ter spodbujanjem k rednemu jemanju zdravila prispevamo,
da bolnik pri predpisanem režimu zdravljenja vztraja.
V	sodobnem pristopu k zdravljenju kroni~nih bolezni poudarjamo vlogo bolnika, ki je vse bolj pomemben partner v procesu zdravljenja. Poleg znanja, ki ga bolnik pridobi z informiranjem o bolezni, so potrebni tudi drugi ukrepi. Potrebna je podpora zdravnika oziroma zdravstvenega delavca, spremljanje in spodbujanje bolnika ter pomo~ pri premagovanju ovir, na katere naleti pri zdravljenju. Te dejavnosti lahko združimo v podporni program, da bi izbolj{ali motiviranost in pove~ali vklju~enost bolnika v lastno zdravljenje. Klini~ne raziskave potrjujejo u~inkovitost podpornih programov pri izbolj{evanju adherence, vendar pa tak{nih programov ne uporabljamo rutinsko v vsakdanji praksi, pa tudi udeležba bolnikov v njih je razmeroma nizka (13). Raziskave dokazujejo, da je najpomembnej{a individualna podpora v procesu zdravljenja, ki jo najpogosteje izvaja usposobljena medicinska sestra (14). Raziskava PERSIST je pokazala, da je vztrajanje bolnikov, ki se zdravijo z enkrat mese~nim odmerkom bisfosfonata v kombinaciji s podpornim programom v obliki telefonskega klica usposobljene medicinske sestre za 47 % ve~je kot pri bolnikih, ki prejemajo zdravilo enkrat tedensko (6). Podporni program za bolnike, ki prejemajo ibandronat enkrat mese~no, vodi Zveza dru{tev bolnikov z osteoporozo Slovenije.
V	Sloveniji smo naredili dve raziskavi o adherenci pri zdravljenju osteoporoze. Ena se je usmerila na adherenco pri enkrat tedenskem jemanju bisfosfonatov in je potrdila izsledke tujih raziskav, da se adherenca pri zdravljenju osteoporoze v prvem letu zmanj{a na 63 % (5,15). Druga je ugotavljala adherenco bolnikov z osteoporozo v povezavi s kakovostjo življenja ob vsakodnevnem jemanju stroncijevega ranelata. Ve~ja zavzetost bolnikov za zdravljenje je bila povezana z zmanj{anjem bole~in in vsakodnevnih težav (16).
Z na{o raziskavo smo želeli ugotoviti adherenco pri jemanju bisfosfonata enkrat na mesec. Želeli smo pridobiti stali{~a bolnic in zdravnikov do zdravljenja in podpornega programa za osteoporozo ter prepoznati dejavnike, ki vplivajo na adherenco.
2 Preiskovanci in metode
2.1	Preiskovanci
V raziskavo so bile vključene zaporedne bolnice, ki so jim v obdobju od 1.11.2008 do 30.6.2009 predpisali enkrat mesečni odmerek bisfosfonata. Bolnice v vzorcu smo izbrali s pomočjo seznama šifriranih diagnoz v računalniškem izpisu opredeljenih bolnikov. Vključene so bile bolnice, ki so imele po MKB 10 naslednje šifre bolezni: M 81.0 (postmenopavzalna osteoporoza) ali M 81.5 (primarna osteoporoza) in so v opredeljenem obdobju začele zdravljenje z enkrat mesečnim odmerkom bisfosfonata. Pri postavitvi diagnoze osteoporoza smo upoštevali merila, ki jih priporočajo Slovenske smernice za odkrivanje in zdravljenje osteoporoze (17). Bolnice so bile pisno obveščene o namenu in ciljih raziskave ter so sodelovale na podlagi prostovoljnega pristanka.
Bolnice smo vključilo tako, da smo k sodelovanju v raziskavi povabili 57 zdravnikov družinske medicine, ki smo jih izbrali naključno iz registra zdravnikov, ki ga vodi Združenje zdravnikov družinske medicine. Med 32 sodelujočimi zdravniki (56,1-odstotni odziv) je bilo 20 (62,5 %) zdravnic in 12 (37,5 %) zdravnikov, ki so bili stari od 33 do 62 let, v povprečju 46,6 let (SD 7,0 let). Imeli so od 176 do 2523 opredeljenih bolnikov, v povprečju 1810,8 opredeljenih bolnikov (SD 460,8). Sodelujoči zdravniki se od zdravnikov, ki so zavrnili sodelovanje v raziskavi, niso pomembno razlikovali po nobeni od naštetih značilnosti.
2.2	Metode
Ugotavljanje adherence
Vključene bolnice smo spremljali 6 mesecev po uvedbi enkrat mesečnega odmerka bisfosfonata in ob koncu opazovanega obdobja ugotavljali adherenco posredno, to je na osnovi predpisanega števila škatel bisfosfonata (1). Ustrezno adherenco smo opredelili kot vsaj dva predpisana recepta za enomesečni odmerek bisfosfonata v opazovanem obdobju, ob tem, da je bolnica v opazovanem obdobju šestih mesecev vztrajala pri jemanju zdravila. Kot vir podatkov smo uporabili zdravstveni karton splošne medicine.
Razloge za opustitev sodelovanja smo ugotavljali s pomočjo strukturiranega intervjuja (z vnaprej pripravljenimi vprašanji o razlogih za prenehanje zdravljenja z enkrat mesečnim odmerkom bisfosfonata in dodanim vprašanjem odprtega tipa, kjer so bolnice lahko navedle tudi morebitne druge vzroke za opustitev zdravljenja). Intervju smo izvedli v ambulanti. Če se
bolnica v ambulanti ni oglasila, smo intervju izvedli po telefonu.
Ugotavljanje stali{~a bolnic in zdravnikov do osteoporoze in podpornega programa
Pred začetkom raziskave smo zdravnike v pisni obliki seznanili z namenom, s cilji ter potekom raziskave. Prosili smo jih, da izpolnijo vprašalnik o stališčih zdravnikov glede pomembnosti zdravljenja osteoporoze in podpornega programa. Stališča bolnic do osteoporoze ter podpornega programa smo ugotavljali ob koncu 6-mesečnega spremljanja s pomočjo vnaprej pripravljenega vprašalnika. Vprašalnik je uporabil zdravnik, ki je na podlagi vprašalnika z bolnico izvedel strukturirani intervju.
Pomembnost zdravljenja osteoporoze, pomembnost sodelovanja v podpornem programu za osteoporozo ter pomembnost razlogov za opustitev zdravljenja z enkrat mesečnim odmerkom bisfosfonata smo ocenjevali s pomočjo 7-stopenjske Likertove lestvice, pri čemer pomeni 1 - sploh ni pomembno in 7 zelo pomembno.
V	primeru ocene 6 ali 7 po Likertovi lestvici smo ocenili, da je ocenjena stopnja pomembnosti zelo visoka.
Statisti~na analiza podatkov
Zbrane podatke smo analizirali z računalniškim paketom SPSS Statistics, verzija 17. V univariatni analizi smo prikazali povprečne vrednosti spremenljivk in standardne odklone (SD). V bivariatni analizi smo uporabili: Studentov t-test za primerjavo med neodvisnimi vzorci ter test x2 za ugotavljanje kvalitativnih razlik med vzorcema. V multivariatni analizi smo uporabili logistično regresijo za napovedovanje dobre adherence pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata. Kot mejo statistične značilnosti smo uporabili vrednost p <0,05. Raziskavo je odobrila komisija za medicinsko etiko pri Ministrstvu za zdravje pod številko, 67/04/08 dne 15. aprila 2008.
3 Rezultati
3.1 Opis vzorca bolnic
V	raziskavi je sodelovalo 329 od povabljenih 330 bolnic, ki so bile stare od 40 do 92 let, v povprečju 70,9 let (SD 10,0 let).
117 bolnic (35,7 %) je živelo samih, 211 (64,3 %) bolnic pa skupaj s partnerjem in/ali z družino. 132 (40,1 %) bolnic je imelo osnovnošolsko ali nižjo izobrazbo, ostale bolnice pa so imele poklicno ali višjo izobrazbo. Največjo sposobnost gibanja, ki ga bolnica lahko izvaja vsaj 2 minuti, prikazuje Tabela 1.
Tabela 1. Sposobnost gibanja bolnic z osteoporozo. Table 1. Mobility in patients with osteoporosis.
Sposobnost gibanja ability to move	Število (N=328) Number (N=328)	Delež Percentage
hiter tek fast running	41	12,5 %
počasen tek slow running	68	20,7 %
hitra hoja fast walking	116	35,4 %
zmerna hoja moderate walking	74	22,6 %
počasna hoja ali ni sposoben hoditi slow walking or inability to walk	29	8,8 %
3.2 Stališča do zdravljenja osteoporoze ter podpornega programa za osteoporozo
3.2.1 Stali{~a zdravnikov do zdravljenja
osteoporoze ter podpornega programa za osteoprozo
Sodelujoči zdravniki so na vprašanje, kako pomembno se jim zdi zdravljenje osteoporoze, po 7-stopenjski Likertovi skali odgovorili z oceno od 5 do 7, v povprečju 6,22 (SD 0,83). 24 od 32 (75 %) zdravnikov je menilo, da je zdravljenje osteoporoze zelo pomembno (ocena 6 ali 7 po Likertovi skali).
Zdravniki, ki so zavrnili sodelovanje v raziskavi, so na vprašanje, kako pomembno se jim zdi zdravljenje osteoporoze, v povprečju ocenili s 5,48 (SD 1,20).
Razlika v stališčih do pomembnosti zdravljenja osteoporoze med sodelujočimi in nesodelujočimi zdravniki je bila statistično pomembna (t=2,548, p=0,015).
Prav vsi zdravniki so menili, da za bolnice možnost enkrat mesečnega zdravljenja predstavlja prednost pred tedenskim ali dnevnim zdravljenjem. Na vprašanje, kolikšen delež žensk, ki jim je bil predpisan enkrat mesečni odmerek bisfosfonata, pol leta po predpisu nadaljuje z rednim zdravljenjem, so zdravniki menili, da je takšnih žensk povprečju 82,2 % (od 50 do 100 %; SD 12,4 %). Odgovore zdravnikov na vprašanje, zakaj bolnice najpogosteje prenehajo jemati bisfosfonat, prikazuje Tabela 2.
Tabela 2. Razlogi, zaradi katerih po mnenju zdravnikov bolnice najpogosteje prenehajo jemati bisfosfonat.
Stopnja pomembnosti je bila označena s številko od 1 do 7, kjer pomeni: 1 - ni pomembno, 7 - zelo pomembno.
Table 2. Physicians'attitudes towards the r^easons for discontinuing treatment of bisphosphonate. The level of importance was rated from 1 to 7 ( 1 - not at all, 7 entirely).
Razlog za opustitev jemanja bisfosfonatov Reason for discontinuation of bisphosphonate	Povprečna vrednost (SD) Mean (SD)
ker niso prepričani v učinkovitost zdravljenja they do not believe in the efficacy of treatment	3,8 (2,1)
ker je predpis odmerka (1x mesečno) neprimeren once-monthly regimen of treatment is not acceptable	2,2 (1,9)
ker je režim jemanja zahteven (prazen želodec, pokončen položaj telesa) treatment regime (on an empty stomach,in an upright position) is too demanding	4,5 (1,7)
ker občutijo stranske učinke side effect of treatment	5,4 (1,8)
ker ne marajo dolgotrajnega jemanja zdravil long term treatment is not acceptable	4,2 (1,6)
25 (78,1 %) zdravnikov je vedelo, da obstaja podporni program za osteoprozo. Zdravniki so menili, da podporni program lahko pomaga pri rednem jemanju zdravil (po 7-stopenjski Likertovi lestvici 5,8; SD 1,4), je koristen, ker omogoča pridobivanje dodatnih informacij o osteoporozi (po 7-stopenjski Likertovi lestvici 5,9; SD 1,3) ter omogoča izmenjavo izkušenj med bolnicami z enakimi težavami (po 7-stopenjski Likertovi lestvici 5,3; SD 1,7).
3.2.2 Stališča bolnic do zdravljenja osteoporoze, potrebe po dodatnih informacijah o osteoporozi ter podpornem programu za osteoporozo
Bolnice so na 7-stopenjski Likertovi lestvici ocenile pomembnost zdravljenja osteoporoze z oceno 6,23 (v razponu od 1 do 7; SD 1,28). 260 (79,0 %) bolnic je ocenilo pomen zdravljenja osteoporoze z oceno 6 ali 7 po Likertovi lestvici.
Pred zdravljenjem z enkrat mesečnim odmerkom bisfosfonata je 190 (57,8 %) bolnic prejemalo druga zdravila za zdravljenje osteoporoze. Na vprašanje, ali enkrat mesečno zdravljenje z zdravili za osteoporozo predstavlja prednost pred tedenskim zdravljenjem, je 301 (94,1 %) oseba menila, da je to prednost, 19 (5,9 %) bolnic pa je menilo, da enkrat mesečno jemanje zdravila ne prinaša prednosti. Na vprašanje, ali bi si bolnice želele več informacij o osteporozi in njenem zdravljenju, je 195 (59,3 %) bolnic izjavilo pritrdilno. V Tabeli 3 so navedeni odgovori bolnic na vprašanje, kje bi si želele pridobiti dodatne informacije o osteoporozi in njenem zdravljenju. Podporni program za osteoporozo je bil predstavljen le 88 (26,7 %) bolnicam. Te bolnice so odgovarjale na vprašanje, kaj menijo o podpornem programu za osteoporozo. Njihovi odgovori so predstavljeni v Tabeli 4.
Tabela 3. Viri, ki so jih bolnice, ki želijo več informacij o osteoporozi in njenem zdravljenju, navedle kot tiste,
ki bi jih želele uporabiti pri pridobivanju informacij. Table 3. Source of information in which patients who want to have more information about osteoporosis and treatment would like to find additional information.
Vir informacij Source of information	Število (N=195) Number (N=195)	Delež Percentage
Pri osebnem zdravniku General practitioner	163	83,6 %
Pri specialistu, kjer sem opravila merjenje kostne gostote Specialist who made densitometry	75	38,5 %
V lekarni Pharmacy	64	32,8 %
Pri proizvajalcu zdravil za osteoporozo Pharmaceutical company	13	6,7 %
V poljudnih zdravstvenih revijah Magazins	49	25,1 %
Na internetu The Internet	10	5,1 %
Na radiu in televiziji Radio and television	64	32,8 %
*Bolnice so lahko navedle več virov dodatnih informacij. *Patients were allowed to provide more than one answer.
Tabela 4. Mnenja bolnic z osteopo^ozo o podpornem programu za osteoporozo. Table 4. Patients' attitudes towards patients support programme.
Mnenje o podpornem programu za osteoporozo Attitudes towards patient support programme	Število (N=88) Number (N=88)	Delež Percentage
Je koristen, ker bolnik dobi veliko informacij o osteoporozi It is useful, because the patient receives extensive information about osteoporosis	79	89,8 %
Je koristen, ker pomaga pri rednem jemanju zdravil It is useful, because it helps achieve better medication adherence	64	72,7 %
Je koristen, ker omogoča, da se srečaš z ljudmi s podobnimi težavami It is useful, because it enables you to meet people with similar health problems	30	34,1 %
Namenjen je doseganju boljšega zdravja It helps people achieve better health	54	61,4 %
Namenjen je predvsem povečevanju prodaje zdravila The main purpose of the programme is drug marketing	13	14,8 %
*Bolnice so lahko navedle več možnih odgovorov. *Patients were allowed to provide more than one answer.
48 (54,5 %) bolnic, ki jim je bil predstavljen podporni program, se je prijavilo v podporni program za osteoporozo. Najpogostejši razlog, zaradi katerega se bolnice niso odzvale povabilu, je bilo prepričanje, da lahko zdravilo jemljejo redno tudi brez podpornega programa, in sicer pri 26 (65,0 %) bolnicah.
3.3 Adherenca pri zdravljenju z enkrat mese~nim odmerkom bisfosfonata
V	opazovanem obdobju, ki je bilo v povprečju 195,2 dni (SD 59,7 dni), so bolnice obiskale zdravnika v ambulanti v povprečju 2,7-krat (od 0- do 8-krat; SD 1,5-krat) ter opravile v povprečju 2,2 administrativna obiska (od 1 do 9; SD 1,3).
V	opazovanem obdobju, ki je trajalo v povprečju 195,2 dni (6,5 meseca), smo dobro adherenco ugotavljali pri 298 (90,6 %) bolnicah.
20 (6,1 %) bolnic je v opazovanem obdobju prenehalo z zdravljenjem z enkrat mesečnim odmerkom bisfosfonata. Najpogostejši razlog, ki so ga bolnice, ko so prenehale z jemanjem zdravila, navedle, so bili stranki učinki zdravila pri 12 (60,0 %) bolnicah. Kot razlog za opustitev zdravljenja so navedle še
zahteven režim jemanja zdravila, medtem ko se dvom v koristnost zdravljenja ni pojavil kot razlog za prenehanje zdravljenja.
3.4 Dejavniki, ki napovedujejo adherenco pri zdravljenju z enkrat mese~nim odmerkom bisfosfonata
V	univariatni analizi sta se le spremenljivki izobrazba ( p<0,001) ter pomen zdravljenja osteoporoze (p=0,002) izkazali za statistično pomembno povezani z dobro adherenco pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata, medtem ko spremenljivke starost, sposobnost gibanja, živi sama/z družino, vrednost mineralne kostne gostote v predelu celotnega kolka ter v predelu ledvene hrbtenice (L1 do L4), število obiskov v ambulanti, želja po dodatnih informacijah o osteoporozi in prijava v podporni program za osteoporozo niso bile statistično pomembno povezane z dobro adherenco, a smo jih vseeno vključili v model za napovedovanje dobre adherence pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata.
V	Tabeli 5 je prikazan model logistične regresije, s katero smo napovedovali dobro adherenco
Tabela 5. Logistična regresija za model adherence pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata.
Model X2 = 28,88; 10 stopinj prostosti, p<0,001. Model pojasnjuje 23,2 %o celotne variabilnosti. Table 5. Logistic regression of independant variables for the model adherence to once-monthly bisphosphonate.
Model X2 = 28,88, 10 degrees of freedom, p<0,001. Model explains 23,2% of total variablity.
	B	S.E.	X2	p	Exp (B)	95% meja intervala zaupanja - spodnja 95% CI-lower	95% meja intervala zaupanja - zgornja 95% CI- upper
Konstanta Constant	-6,166		2,810	0.028			
Izobrazba Education level	0,777	0,250	9,674	0,002	2,175	1,333	3,549
Pomen zdravljenja osteoporoze Attitudes towards the importance of osteoporosis treatment	0,553	0,160	11,932	0,001	1,738	1,270	2,378
pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata.
V Tabeli so navedene le spremenljivke, ki neodvisno napovedujejo dobro adherenco pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata. V model so bile vključene še naslednje spremenljivke: starost, sposobnost gibanja, živi sama/z družino, vrednost mineralne kostne gostote v predelu celotnega kolka ter v predelu ledvene hrbtenice (L1 do L4), število obiskov v ambulanti, želja po dodatnih informacijah o osteoporozi in prijava v podporni program za osteoporozo.
Bolj izobražene ženske in tiste, ki so višje ocenile pomen zdravljenja osteoporoze, so z večjo verjetnostjo izkazovale adherenco pri zdravljenju osteoporoze z enkrat mesečnim odmerkom bisfosfonata.
4 Razprava
4.1 Povzetek ključnih ugotovitev raziskave
Adherenca pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata je visoka. Pomemben dejavnik, ki napoveduje adherenco pri zdravljenju z bisfosfonatom, je prepričanje bolnic, da je zdravljenje
osteoporoze zelo pomembno. Izkazalo se je, da so za adherenco pri zdravljenju pomembna stališča, medtem ko znanje o osteoporozi k njej ne prispeva bistveno. Podporni program so tako bolnice kot zdravniki ocenili kot koristnega, vendar pa sodelovanje v podpornem programu ni napovedovalo boljše adherence pri zdravljenju.
4.2 Omejitve raziskave
Raziskava ima tudi nekaj pomanjkljivosti in omejitev. Strukturirani intervju je izvajal osebni zdravnik, kar lahko pomeni pristranost in vpliva na odgovore bolnic, čeprav smo zdravnike prosili, da naj bolnicam ne ponujajo odgovorov.
Stališča bolnic do osteoporoze ter podpornega programa smo ugotavljali ob koncu 6-mesečnega spremljanja s pomočjo sedemstopenjske Likertove lestvice (18). Nekatere bolnice, ki so sicer redno jemale zdravila za osteoporozo, so pomen zdravljenja osteoporoze po Likertovi lestvici ocenile kot nepomembnega ali zelo majhnega, kar pa se verjetno ne ujema z njihovim dejanskim stališčem, ampak je odraz nerazumevanja lestvice. Adherenco smo opredelili kot vsaj dva predpisana recepta za enkrat mesečni odmerek bisfosfonata
v opazovanem obdobju, ob tem, da je bolnica v opazovanem obdobju {estih mesecev vztrajala pri jemanju zdravila. Omenjeni na~in merjenja adherence je bil v na{i raziskavi edini mogo~, se pa zavedamo njegovih omejitev, saj ni nujno, da bolnik na recept predpisano zdravilo v resnici dvigne v lekarni in da zdravilo tudi vzame, ~e ga je dvignil (19). Opazovano obdobje je bilo kratko, saj je trajalo le dobrega pol leta. Iz predhodnih raziskav vemo, da adherenca upada do {tiri leta po za~etku zdravljenja (1,20), kar pomeni, da bi ob nadaljnjem spremljanju adherence verjetno beležili nekoliko manj{o adherenco.
4.3 Stališča zdravnikov in bolnic do pomena zdravljenja osteoporoze ter podpornega programa
Sodelujo~i zdravniki in bolnice so zdravljenje osteoporoze ocenili kot zelo pomembno. V raziskavi so sodelovali zdravniki s pozitivnimi stali{~i do zdravljenja osteoporoze, kar kaže da je stali{~e do pomena obravnave dolo~ene bolezni lahko dejavnik, ki vpliva na odlo~itev zdravnika za sodelovanje v raziskavi.
Možnost zdravljenja z enkrat mese~nim odmerkom bisfosfonata so tako bolnice kot zdravniki ocenili kot prednost. Ve~ kot polovica sodelujo~ih bolnic je že imela predhodno izku{njo z dnevnim ali tedenskim jemanjem zdravil za osteoporozo, kar njihovi oceni daje dodatno težo.
Ve~ina bolnic, ki si je želela dodatnih informacij o osteoprozi, jih pri~akuje od osebnega zdravnika, ~eprav so omenjale tudi druge vire (množi~ne medije, poljudno literaturo) ter farmacevta in zdravnika specialista, ki je opravil merjenje kostne gostote. Zaupanje osebnemu zdravniku, tudi ko gre za pridobivanje podatkov o bolezni in njenem zdravljenju, je bilo med bolnicami veliko, kar podpira tudi ugotovitev javnomnenjske raziskave, v kateri ve~ kot osemdeset odstotkov ljudi zaupa osebnemu zdravniku (21). Izkazano zaupanje razumemo v lu~i individualnega in k bolniku usmerjenega pristopa k obravnavi, saj osebni zdravnik bolnika najbolje pozna, upo{tevajo~ njegove spremljajo~e zdravstvene težave, socialne okoli{~ine ter obravnava bolnika kot celovito osebnost (22).
V podporni program »Danes je moj dan«, ki ga vodi Zveza dru{tev bolnikov z osteoporozo Slovenije, so bile povabljene le bolnice v izbranih lekarnah po Sloveniji, zato je bila le dobra ~etrtina seznanjena s podpornim programom, ostale pa ne.
Le dobra polovica bolnic, ki jim je bil predstavljen podporni program, se je odlo~ila za sodelovanje. Bolnice in zdravniki so podporni program ocenili kot koristnega zaradi možnosti pridobitve dodatnih informacij o osteoporozi in njenem zdravljenju ter kot pomo~ pri rednem jemanju zdravil. Možnost druženja z bolniki s podobnimi težavami se bolnicam ni zdela posebej pomembna, zdravniki pa so to možnost ocenili kot pomemben doprinos podpornega programa.
Med bolnicami, ki so bile povabljene v podporni program, pa se niso odlo~ile za sodelovanje, sta dve tretjini menili, da lahko zdravilo redno jemljejo brez pomo~i. Omenjeno stali{~e smo nato potrdili z analizo dejavnikov, ki vplivajo na adherenco, pri ~emer se sodelovanje v podpornem programu ni izkazalo kot dejavnik bolj{e adherence pri zdravljenju.
4.4 Adherenca pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata in dejavniki, ki vplivajo na adherenco
Ugotovljena adherenca, ki se nana{a le na zdravljenje z enkrat mese~nim odmerkom bisfosfonata, je bila glede na izsledke predhodne raziskave vi{ja (11) kot 6-mese~na adherenca pri zdravljenju z vsakodnevnim jemanjem modulatorja estrogenskih receptorjev raloksifena (82 %) ter enkrat tedenskim jemanjem bisfosfonata alendronata (69 %) (23). Sklepamo lahko, da je klju~ni dejavnik, ki prispeva k visoki adherenci pri zdravljenju z enkrat mese~nim odmerkom bisfosfonata dejstvo, da bolnice, ki imajo po odmerku zdravila stranski u~inek draženja prebavil, to laže sprejmejo enkrat mese~no kot enkrat tedensko.
Zavedati se moramo, da adherenca upada {e po {estih mesecih zdravljenja (1,20), vendar pa je najve~ji upad zdravljenja opaziti v prvih {estih mesecih zdravljenja. V najve~ji meri pa se adherenca zmanj{a že v prvem mesecu po za~etku zdravljenja, ve~inoma zaradi prisotnosti stranskih u~inkov zdravil (5,23).
Delež bolnic, ki so opustile zdravljenje z enkrat mese~nim odmerkom bisfosfonata, je bil približno 6 %. Bolnice so kot poglavitni razlog navedle neželene u~inke zdravila (5,16), omenile so tudi zahteven na~in jemanja, nobena pa ni izrazila dvoma v koristnost jemanja zdravila. Bolnice z negativnimi stali{~i do osteoporoze in njenega zdravljenja verjetno sploh ne opravijo merjenja mineralne kostne gostote, ki je podlaga za postavitev diagnoze, oziroma ob
morebitnem nestrinjanju z zdravljenjem z zdravili niso imele možnosti, da bi se vključile v raziskavo. Ugotovili smo, da demografske značilnosti bolnic (starost) ter podatek o tem, s kom bolnica živi, ne napovedujejo boljšega sodelovanja pri zdravljenju (5), smo pa za razliko od predhodno izvedene raziskave ugotovili, da je boljša izobrazba povezana z boljšim sodelovanjem. Ključna ugotovitev naše analize pa je ugotovitev, da k rednemu jemanju zdravil najbolj prispeva pozitivno stališče do zdravljenja osteoporoze. Pri oblikovanju stališč ima verjetno pomembno vlogo osebni zdravnik, ki je najpomembnejša oseba pri pridobivanju informacij o osteoporozi in njenem zdravljenju.
Sodelovanje v podpornem programu ni statistično pomembno vplivalo na sodelovanje pri zdravljenju z enkrat mesečnim odmerkom bisfosfonata, kar so ugotavljali v raziskavi PERSIST (6). Vzrok za našo ugotovitev je lahko tudi relativno majhno število bolnic, ki so se prijavile v podporni program.
5 Zaklju~ek
Osteoporoza je bolezen, ki bolnikom dolgo časa ne povzroča težav, kar je dejavnik tveganja za slabo adherenco. Možnost enkrat mesečnega jemanja zdravil prispeva k izboljšanju adherence pri zdravljenju. Informiranost o bolezni in njenem zdravljenju še ne napoveduje sodelovanja pri zdravljenju, oblikovanje pozitivnih stališč bolnic do pomena zdravljenja pa prispeva k izboljšanju adherence. Zdravnik družinske medicine, ki mu bolnik zaupa, je navadno ključna oseba, ki bolniku na osnovi njemu prilagojenih informacij o bolezni in zdravljenju pomaga pri oblikovanju stališč. S skrbnim spremljanjem bolnika ter spodbujanjem k rednemu jemanju zdravila prispeva, da pri predpisanem načinu zdravljenja tudi vztraja.
Zahvala
Zahvaljujemo se vsem zdravnikom ter njihovim bolnicam, ki so sodelovali pri izvedbi raziskave, ter gospe Ani Artnak za administrativno pomoč. Zahvaljujemo se farmacevtskima družbama Roche, farmacevtska družba d.o.o. ter GlaxoSmithKline d.o.o., družba za promet s farmacevtskimi izdelki, Ljubljana, ki sta raziskavo finančno podprli.
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PARENTS' OPINIONS ABOUT THEIR OWN AND THEIR
CHILDREN'S LIFESTYLE MNENJA STARŠEV O NJIHOVEM ŽIVLJENJSKEM SLOGU IN ŽIVLJENJSKEM SLOGU NJIHOVIH OTROK
Jera Zajec1, Mateje Videmšek1, Jože Štihec1, Boštjan Šimunič1
Prispelo: 6. 4. 2010 - Sprejeto: 20. 7. 2010
Original scientific article UDC 615:796.053.9
Abstract
Objective: The aim of the study was to investigate dietary habits of pr^eschool children and their pai-ents. Parents' opinions on lifestyles and physical characteristics of their children were analysed with the aim to identify possible relationships between active lifestyles and positive attitudes towar^ds healthy eating habits. Methods: The study included 520 par-ents of 3-to-6-year old children. The data were gathered within the scope of a large-scale research project entitled "Otrok med vplivi sodobnega življensk^ega sloga - gibalne sposobnosti, telesne znač^ilnosti in zdravstveni status slovenskih o^rok" ("The Child in the Midst of Modern Li^est^le Influences - Motor Abilities, Physical Characteristics, and the Health Status of Slovenian Children"), which was conducted by the researchers of the Institute of Kinesiology Research, University of Primorska, led by Dr. Boštjan Šimunič, in collaboration with the Faculty of Sports, Ljubljana and the Faculties of Education of Ljubljana, Koper, and Maribor, between 1 October 2006 and 31 September 2008. Data analysis was done using basic statistical parameters, the CORRELATION (analysis of correlations between variables) and ANOVA (analysis of variance) subprogrammes. The data obtained were processed by the SPSS statistical package for Windows. All statistically significant hypotheses were either accepted or rejected at a statistical significance level of 5% (p=0.05). Results: Most par-ents surveyed (74.2%) were of the opinion that their childr^en predominantly spend their leisur^e time in a motor/athletically active manner. Children have better eating habits than their par-ents. Athletically active parents have a significantly more negative attitude towards alcohol consumption and a more positive attitude towards a healthy diet than less athletically active par-ents.
Conclusion: Children should be introduced to healthy li^est^le by our setting an example of healthy life habits. The responsibility of promoting healthy life is shar^ed by all: par-ents, educators, teachers, and each and everyone helping both childr^en and adults adopt a positive a^itude towar^ds an active lifestyle.
Key words: motor activity, athletic activity, active lifestyle, children, parents.
Izvirni znanstveni članek UDK 615:796.053.9
Izvle~ek
Namen: Osnovni namen raziskave je ugotoviti preh^anske navade predšolskih otrok in njihovih staršev. Avtorji so analizirali mnenja staršev o življenjskem slogu in telesnih značilnostih njihovih predšolskih otrok, da bi ugotovili povezavo med aktivnim načinom življenja in odnosom do zdravega prehranjevanja otrok ter njihovih staršev. Metode: V raziskavo smo zajeli 520 staršev in njihovih otrok, starih od 3 do 6 let. Podatke smo zbrali v okviru širšega raziskovalnega projekta »Otrok med vplivi sodobnega življenjskega sloga - gibalne sposobnosti, telesne značilnosti in zdravstveni status slovenskih otrok«, ki je potekal na Univerzi na Primorskem, na Inštitutu za Kineziološke raziskave pod vodstvom doc. dr. Boštjana Šimuniča ter v sodelovanju s Fakulteto za šport in s Pedagoškimi fakultetami v Ljubljani, Kopru in Mariboru, in sicer od 1.10.2006 do 31.09.2008. Z^a analizo
^University of Ljubljana, Faculty of Education, Kardeljeva ploščad 16, 1000 Ljubljana, Slovenia Correspondence to: e-mail: jera.zajec@pef.uni-lj.si
podatkov smo uporabili osnovne statistične parametre ter podprograma correlation in anova (enosmerna analiza variance). Podatke smo obdelali s pomo~jo statisti~nega programa SPSS za okolje Windows. Vse statisti~no zna~ilne zaklju~ke smo sprejemali pri 5-odstotnem tveganju.
Rezultati: Največ staršev meni (74,2 %), da njihovi otroci prosti čas preživljajo pretežno gibalno/športno aktivno. Otroci imajo bolj{e prehranjevalne navade kot njihovi star{i. Tisti star{i, ki se ve~ ukvarjajo s {portom, pa imajo tudi statisti~no zna~ilno bolj odklonilen odnos do alkohola in bolj naklonjen odnos do zdrave prehrane kot star{i, ki so manj {portno dejavni.
Zaključek: Dejavnike zdravega načina življenja moramo otrokom predstaviti z ustreznim lastnim zgledom. Zanj smo odgovorni tako star{i, vzgojitelji in učitelji kot tudi vsi, ki pomagamo tako otrokom ter odraslim pri oblikovanju mnenja o aktivnem življenjskem slogu.
Ključne besede: gibalna/športna dejavnost, aktivni življenjski slog, otroci, starši
1 Introduction
Obesity is a complex and the most common contemporary mass illness. In the 1980s, obesity was recorded for only 5% of the adult population worldwide. Until today, this figure has been subject to a six-fold increase, rising to approximately 30% on a global scale (1). Obesity has been spreading in adults and children alike. According to the World Health Organisation (WHO), as much as 25% of all the children in developed countries are categorized as overweight. Researchers from the Institute of Public Health of the Republic of Slovenia (Inštitut za varovanje zdravja Republike Slovenije) found that the level of obesity in Slovenian children has increased during the past 22 years from 15% in 1987 to 28.9% in 2008 (3). The increase in the prevalence of obesity among children and adults is not exclusive to the economically developed world but is encountered also in developing countries. Obesity is one of the key factors causing chronic non-contagious diseases, including all illesses associated with unhealthy lifestyles and risk factors, such as motor/athletic inactivity, smoking, excessive alcohol consumption, unhealthy diet and others. The most frequent consequences of the aforementioned health risks are hypertension (high blood pressure), hyperglycemia (high blood sugar), and hypercholesterolemia (high blood cholesterol) (4), which constitute a challenge to both physicians and kinesiologists. Motor/athletic inactivity alone does not cause obesity, yet there is a clear relationship between a sedentary lifestyle and excessive body weight. Studies have shown that childhood obesity increases the risk for the development of a wide range of diseases in adulthood, such as cardiovascular diseases, diabetes mellitus type 2, osteoarthritis, and colorectal cancer (5).
According to contemporary research (5, 6, 7, 8), a motor/athletically active lifestyle has direct health benefits, especially in terms of:
-	preventing excessive body weight and obesity;
-	creating an environment that benefits the development of denser bones, healthy joints, and an efficient cardiovascular system,
-	improving and maintaining good mental health, and a positive self-image, and
-	laying solid foundations for a healthy lifestyle which can be maintained during adulthood.
Children are mostly healthy and their attitude towards health is different from that of adults; but nowadays morbidity rates among children and the youth tend to increase, too. In recent years obesity has become one of the most common illnesses affecting children and youth (9). Although the beginnings of overfeeding and the subsequent weight gain can be attributed to inappropriate dietary habits in the within-family environment, obesity is also related to psychosocial and psychological factors, which may persist well into adulthood (10).
The majority of studies focusing on preschool children obesity (4, 9, 11, 12) emphasise that regular motor/ athletic activity combined with changes in dietary habits represents the most efficient approach to obesity control and maintenance of normal body weight.
During the development of concepts of their lifestyle, children are influenced by the environment, heredity, and their own level of activity. In order to be able to teach children how to live healthily, it is crucial that parents are aware of the importance and benefits of healthy lifestyles, and that they have already embraced the principles of healthy living as beneficial and vitally important. Understanding long-term effects of the collective and individual environment is the only suitable basis for developing guidelines on how to
raise a child properly (13). The previously mentioned risk factors may lead to a wide range of chronic noncontagious diseases, which may permanently affect a child's health and turn into hereditary ailments in later life (14).
Adverse consequences of motor/athletic inactivity and unhealthy dietary habits are inevitable. When combined with other risk factors, such as excessive alcohol consumption or smoking, unhealthy eating patterns may become the primary cause of numerous chronic, non-contagious diseases. An article in the WHO The World Health Report 2002 (15) states that risk factors that often lead to hypertension (high blood pressure), hypercholesterolemia (high blood cholesterol), and excessive body weight, are frequently linked to the following potentially fatal ailments: cerebral apoplexy, cardiac ischaemia, diabetes, osteoarthritis, endometrial cancer, and breast cancer (16).
The purpose of the present study was to investigate dietary habits of preschool children and their parents, to analyse the relationships between them, and to explore the parents' opinions on their lifestyles and on physical characteristics of their children. The aim of this study was to determine the association between healthy lifestyles and healthy dietary habits of preschool children and their parents.
2 Research methods
2.1 Survey sample
The survey sample was purposefully assembled from three broader Slovenian regions, i.e. the eastern, the central, and the western, taking into consideration the percentage of kindergartens in each of the regions. The kindergartens located in each region were chosen randomly. The sample included 520 parents of children aged between three and six years; 128 parents came from the western part of Slovenia, 219 from central Slovenia, and 173 from eastern Slovenia. Among the parents surveyed 282 were parents of boys (54.2%) and 233 were parents of girls (44.8%). The average age of the children studied was 5.4 years, with a standard deviation of 0.7. The average age of the parents was 35.3 years, with a standard deviation of 4.8.
The study was part of a large-scale research project entitled "Otrok med vplivi sodobnega življenskega sloga - gibalne sposobnosti, telesne značilnosti in
zdravstveni status slovenskih otrok" (The Child in the Midst of Modern Lifestyle Influences - Motor Abilities, Physical Characteristics, and the Health Status of Slovenian Children), which was conducted by the investigators of the Institute of Kinesiology Research at the University of Primorska led by Dr. Boštjan Šimunic, in cooperation with the Faculty of Sports in Ljubljana and the Faculties of Education in Ljubljana, Koper and Maribor. During the preliminary meetings with the kindergartens included in the study, the principals and the parents were informed about the purpose of the study. They were given informed consent forms for participation in the research study and relevant questionnaires. We answered all their questions regarding the questionnaire, and agreed upon the manner of returning the surveys. Prior to any study-related procedures a written informed consent was obtained from all the participants willing to take part in the survey. All personal data remained undisclosed. The formal data collection was carried out according to the Personal Data Protection Act of the Republic of Slovenia (Official Gazette of the Republic of Slovenia, No. 59/99).
2.2 Sample of variables
The sample of variables was encompassed by the parental questionnaire, which comprised 29 multiple-choice and open-ended questions, and a combination of both. The questionnaire was divided into two parts. The first part included questions asking the parents about their living environment, their motor/athletic activity, presence of smoking and alcohol in their lives, and their dietary habits. The second part inquired about their children, particularly about their motor/ athletic activity, the quality of their leisure activities, and their dietary habits.
All questions were answered exclusively by the parents.
The questionnaire was designed by Šimunic, Videmšek, Pišot, Štihec, Štemberger, Završnik and Zajec (2008) who also tested the measurement characteristics as part of a large-scale research project entitled "Otrok med vplivi sodobnega življenskega sloga - gibalne sposobnosti, telesne značilnosti in zdravstveni status slovenskih otrok" (The Child in the Midst of Modern Lifestyle Influences - Motor Abilities, Physical Characteristics, and the Health Status of Slovenian Children).
2.3 Methods of data processing
The SPSS 15.0 statistical package for Windows, issued by SPSS Inc., based in Chicago, IL, USA was used for data processing and the subprogram FREQUENCIES was employed to calculate the frequencies of individual answers provided in the questionnaires. The subprograms DESCRIPTIVES (descriptive statistics), ANOVA (analysis of variance), and CORRELATION (analysis of correlations between variables) were applied to numeric and other appropriately transformed variables. The statistical significance was tested at a level of 5% (p = 0.05).
3 Results
Leisure activities
Leisure activities of children were determined separately for weekends and holidays. Table 1 shows that 74.2% of the parents surveyed are of opinion that their children spend their leisure time in a motor/ athletically active manner; 18.3% percent answered that their children spend their leisure time in a motor/ athletically inactive manner, and 7.5% offered no opinion on their children's leisure activities.
Table 1. Leisure activities during weekends
and holidays. Tabela 1. Na~in preživljanja prostega ~asa otroka med vikendi in v ~asu po~itnic.
Leisure activities Načini preživljanja prostega časa	N	%
Motor/athletically inactive (watching TV, playing computer games, going out to the cinema ) / Gibalno/{portno nedejavno (gledanje TV, igranje igric na računalniku, obiski kina ^)	95	18.3
Motor/athletically active (swimming, skiing, cycling, hiking ^) / Gibalno/ {portno dejavno (plavanje, smučanje, kolesarjenje, pohodi, sprehodi ^)	386	74.2
No answer / Ni odgovora	39	7.5
Total / Skupaj	520	100.0
Table 2 shows the parents' opinions about their children's motor/athletic activity and about its influence on their children's integral development. The parents surveyed gave their opinions based on a 5-point Likert scale; from 1 (strongly disagree) to 5 (strongly agree). Data were analysed using applied conditional descriptive statistics; the parents' opinions were expressed as mean values. We found that the respondents though of motor/athletic activity as having a very positive influence on their children's integral development, awarding this particular issue 4.7 out of 5 points. They were of the opinion, however, that their children could be more motor/athletically active.
Table 2. Parents' opinions about their children's motor/athletic activity.
Tabela 2. Mnenje staršev o otrokovi gibalni/ športni dejavnosti.
Parents' opinions / Mnenja star{ev	Mean value / Srednja vrednost	Standard deviation / Standardni odklon
Sufficiently motor/ athletically active / Dovolj gibalno/{portno dejaven	3,75	0,874
Influence of motor/ athletic activity on integral development / Vpliv gibalne/{portne dejavnosti na razvoj	4,70	0,586
Physical fitness / Telesna pripravljenost	3,95	0,811
Legend: N = Tally of responses; % = Percentage. Legenda: N = {tevilo odgovorov; % = odstotek.
Legend: Mean value and standard deviation are based on a 5-point Likert item.
Legenda: Srednja vrednost in standardni odklon na podlagi iz 5-stopenjske lestvice.
Dietary habits of children and their parents
The study has shown that the majority of the parents surveyed (90.4%) are of the opinion that their children have an appropriate body weight. In view of the fact that body weight mostly depends on the level of
motor/athletic activity and the quantity and quality of daily meals, the study undertook to investigate both motor/ athletic activity and dietary schemes of children and parents. The findings showed that 90% of the children and only 65% of the parents surveyed eat breakfast regularly. Slightly less than 1% of the children and as much as one-third of the parents surveyed were found to abstain from breakfast. A vast majority of the children (98.5%) have lunch on a daily basis, while the share of the parents eating lunch is by nearly 10% lower. Quite a large proportion of the children (89.6%) eat dinner regularly as compared to two-thirds of the parents having regular dinners. Since children in kindergarten spend most of their time awake, it seems sensible to presume that they consume there all their important daily meals except dinner and snacks. We found that over half of the children (51.7%) eat breakfast in kindergarten. The study focused not only on the amount and frequency but also on the quality of the meals taken. Data analysis showed that fruit, the most frequently offered snack, is regularly taken by 27.2% of the children, and very frequently by 51.7%. Slightly less than 2% of the children do not eat fruit at all. Another frequently offered snack is chocolate; it is very frequently consumed by 25.2% of the children. We also studied the children's diet outside the kindergarten; 38.2% of them eat vegetables on a daily basis, 35.4% eat vegetables every day, and the rest of them eat vegetables less than once a week or do not eat vegetables at all. As regards fruit in the diet, 60.3% of the children eat fruit on a daily basis, and 27.2% almost every day. The majority of the children consume potato, rice, and pasta nearly every day. A vast majority of the children eat white bread on a daily basis. Most children eat meat between once and a few times weekly. Milk and dairy products are consumed daily by 57.6% of the children and nearly every day by 25.4%; 31.4% of the children are served fried foods once a week and 40% once a month. Sweets and desserts are part of the menu several times per week for 35% of the children. Nearly 65.5% of the children
do not eat fast food and 27.4% consume it once a month. In slightly less than 1% of the children, fast food features in a daily menu several times a week. Since parents only occasionally dine with their children, their dietary scheme differs from that of their children: they eat fruit, vegetables, potatoes, white bread, dairy products, and meat daily or almost every day, and consume pasta, whole wheat bread, fish and other seafood, eggs, and fried foods a few times or once a week. The majority of parents eat fried foods and fast food only rarely, never, or once per month In addition to dietary habits, types of ingested beverages and frequency of beverage consumption were determined. Most children were found to drink water (66.7%) and non-carbonated non-alcoholic beverages (39.4%) several times per day, only a slightly lesser percent consume various natural fruit juices equally frequently; 1.2% drink carbonated non-alcoholic beverages several times per day, 3.7% of the children never drink any kind of natural fruit juice, and 57.1% never drink carbonated beverages. Most parents drink water several times per day as well. Non-carbonated and carbonated non-alcoholic beverages are ranked second and third, respectively. Alcoholic beverages occupy the last place in this particular category, being consumed once or a few times per week by 78% of the parents surveyed, i.e. by 15% of all the parents included in the study.
Parents who are more athletically active drink less alcohol
We compared the frequency of parental alcohol consumption and the level of their athletic activity using the Pearson's correlation coefficient with the aim to establish a possible relationship between alcohol consumption and athletic activity during weekends and holidays. Parents who are more athletically active consume alcoholic beverages significantly less frequently than those who are less active in athletic pursuits (p < 0.05).
Table 3. Relationship between the amount of time the parents devote to athletic activity and the frequency of alcohol consumption.
Tabela 3. Izra~un povezanosti med ~asom, ki ga starši namenijo športni dejavnosti, in pitjem alkohola.
Time devoted to athletic activity vs. alcohol consumption / Čas, namenjen {portni dejavnosti glede na pitje alkohola
Correlation Statistical ratio /	significance
Povezanost / Statistična značilnost
Unorganized		
athletic activity		
during weekends		
and holidays vs.		
frequency of alcohol		
consumption /	8,831	0,003*
Neorganizirana		
{portna dejavnost		
med počitnicami in		
vikendi glede na pitje		
alkohola		
Legend: * = statistical significance level of 5% (p 0.05); vs. = against.
Legenda: Z * je označena statistična značilnost pri 5-odstotnem tveganju (p <0,05).
Parents who are athletically active have a positive attitude towards a healthy diet
Parental attitudes towards healthy eating and their level of athletic activity were studied using the Pearson's correlation coefficient with the aim to establish a possible relationship between a composite variable labeled ""healthy diet" (zdrava prehrana - ZP) (12) and the amount of time the parents devote to athletic activity (Table 4). The parents who lead an athletically active life, partaking in either organized or non-organized activities during the week and during weekends and holidays have a significantly more positive attitude towards healthy eating than the parents who are less athletically active. The association between a healthy diet and the consumption of healthy beverages is also statistically significant.
Table 4. The relationship between the amount of time the parents devote to athletic activity and their attitude towards a healthy diet.
Tabela 4. Povezanost med odnosom do športa in zdravo prehrano.
Pearson's correlation coefficient / Pearsonov koeficient korelacije
Correlation ratio /
Povezanost
Statistical significance / Statistična značilnost
Healthy diet vs. athletic activity during the week (PARENTS) / Zdrava prehrana in športna dejavnost med tednom (STARŠI)	0,118	0,007 (**)
Healthy diet vs. non-organized athletic activity during weekends and holidays (PARENTS) / Zdrava prehrana in neorganizirana {portna dejavnost med vikendi in počitnicami (STARŠI)	0,139	0,004 (**)
Healthy diet vs. consumption of healthy beverages / zdrava prehrana in zdrava pijača	0,232	0,000 (**)
Legend: * = statistical significance level of 5% (p 0.05); vs. = against.
Legenda: Z * je označena statistična značilnost pri 5-odstotnem tveganju (p <0,05), vs - versus (proti).
Children of parents who lead a motor/ athletically active life are more motor/athletically active
The levels of motor/athletic activity in parents and their children were compared using the Pearson's correlation coefficient.
Table 5 shows the relationship between the amount of time devoted by the children and their parents to nonorganized motor/athletic activity during the week. The relationship was tested using the Pearson's correlation coefficient. The levels of children's and parental motor/ athletic activities during the week were positively associated. Children of parents who spend more time engaging in either organized or non-organized motor/ athletic activities are more motor/athletically active
as well. The same holds true for the amount of time devoted by children and their parents to motor/athletic activity during weekends and holidays.
Table 5. The amount of time devoted to motor/ athletic activities by children and their parents.
Tabela 5. Povezanost med gibalno/{portno dejavnostjo otrok in njihovih star{ev.
Pearson's correlation coefficient / Pearsonov koeficient korelacije
Correlation ratio /
povezanost
Statistical significance / statistična pomembnost
Motor/Athletic activity during the week (CHILDREN vs. PARENTS) / Gibalna/ športna dejavnost med tednom OTROCI vs STARŠI	0,194	0,001(**)
Non-organized motor/athletic activity during weekends and holidays (CHILDREN vs. PARENTS) / Neorganizirana gibalna/športna dejavnost med vikendi in počitnicami OTROCI vs STARŠI	0,377	0,000 (**)
Legend: * = statistical significance level of 5% (p 0.05); vs. = against.
Legenda: Z * je označena statistična značilnost pri 5-odstotnem tveganju (p <0,05), vs - versus (proti).
4 Discussion and conclusion
The aim of the study was to investigate lifestyles of preschool children and their parents, and to explore some facts about obesity, a complex and the most common mass illness of the present, which may be a consequence of unhealthy dietary habits and lack of motor/athletic activity. Children were found to spend on average less than 90 minutes per day on non-organized motor/athletic activities: 46% of the children whose parents took part in the study engage in less than 30 minutes of non-organized
motor/athletic activity per day. Similar results were obtained by Zurc, Pišot, and Žerjal (17), who reported that 55.2% of the children included in their study were engaged in motor/athletic activities two to three times weekly, and that nearly 20% of the children studied were completely motor/athletically inactive. Šentič et al. (18) emphasized a decrease in the level of motor/athletic activity during the period of transition from childhood to adulthood, when a lesser amount of time is devoted to motor/athletic activities. Kropej and Videmšek (19) found that preschool children mostly engage in non-organized motor/athletic activities. Similar conclusions have been drawn by other researchers, including Štihec and Strel (20), Štihec, Karpljuk, Videmšek and Kondrič (21), and Ritgers et al. (22). Motor/athletic activities have been found to affect favourably a string of health indicators and to directly contribute to lower morbidity and mortality rates (23), lesser body weight, higher HDL-C ("good cholesterol") levels (24), increased bone density, and less insulin resistance. All activities that consitute an integral part of a healthy lifestyle should therefore be more vigorously promoted.
It is difficult to determine accurately the quality of the motor/athletic activity of the population studied, i.e. of children three to six years of age. Nonetheless the results indicate convincingly that nearly half of the children included in the study are motor/athletically active less than 60 minutes per day, i.e. less than the amount of time recommended by experts as crucial for health maintenance (26) and normal development.
The ways children spend their leisure time are often intertwined with spare time activities and habits of their parents. Studies have proven that lifestyles of parents and their children are often intertwined. Analysis of behaviours of children and youth showed that they both share an extraordinarily similar tendency to be influenced by modern lifestyles. Different studies show that the foundations of what is perceived as "lifestyle" begin to develop within a close-knit, family environment (20, 21). The results of our study showed that 35.4% of the parents surveyed devote less than two hours a week to non-organized athletic activities. Considering that experts recommend that this "input" should be at least doubled to maintain one's health, this is a worrisome situation. Our results are compatible with those of some other Slovenian studies (26, 27, 28, 29), reporting that on average people engage in athletic activities infrequently and for too short periods of time. Recent research has shown that people are aware of the
importance of sport and athletic activity, and that they tend to increase the time devoted to athletic activity. A gap between athletically inactive individuals and those who devote most of their leisure time to athletic activity, however, has been increasing. In addition to a motor/athletically active life, many authors (30) regard healthy eating, abstaining from tobacco, alcohol and drugs, and keeping the level of stress as low as possible as important health preserving measures. Our study has shown that children are awake for the majority of time spent in kindergarten, therefore the amount and the quality of main daily meals they take during the week are the responsibility of day care institutions. We have found that the majority of the children studied eat their breakfast, mid-noon snack, lunch, and afternoon snack in kindergarten, while dinner is prepared by their parents at home. Parents have substantially less meals, they often skip breakfast, and consume unhealthy food more often than their children. Children eat most daily meals while in kindergarten. Parents should therefore take special care to offer their children proper evening meals, and to meet their dietary requirements during weekends and holidays. The results of the study show that parental dietary habits are inferior to those of their children. The study has confirmed the importance of regular athletic activity, showing that athletically active parents hold a more negative attitude to alcohol consumption and a more positive attitude towards healthy eating than their peers who are less inclined to engage in athletic activitities. Parents should introduce children to healthy lifestyle by setting a good example for them. Parents, educators, teachers, and all those who support children and adults during the process of their forming a personal attitude towards an active lifestyle, are responsible to act accordingly.
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PROSTORSKA ANALIZA NENUJNIH REŠEVALNIH PREVOZOV: MOŽNOST UVEDBE NOČITEV ZA BOLNIKE, KI SE VOZIJO NA OBSEVANJE NA ONKOLOŠKI INŠTITUT
SPATIAL ANALYSIS OF NON-URGENT AMBULANCE TRANSPORT: A POSSIBILITY OF OVERNIGHT STAY FOR RADIOTHERAPY PATIENTS AT THE INSTITUTE OF ONCOLOGY
Valentina Prevolnik RupelMarko Ogorevc1 Prispelo: 14. 1. 2010 - Sprejeto: 3. 5. 2010
Pregledni znanstveni članek UDK 614.2
Izvleček
Uvod: Onkološkim bolnikom, ki se vozijo na obsevanje, v Sloveniji ni ponujena možnost nočitve v kraju, kjer poteka obsevanje. V analizi smo proučili želje bolnikov glede nočitev in stroškovno ovrednotili različne koombinacije prevoza in nočitev.
Metode. Podatke o željah bolnikov smo dobili z anketiranjem bolnikov, ki so prišli na obsevanje na Onkološki inštitut v Ljubljani na določen dan. T^a oceno preferenc smo uporabili regresijsko drevo CART, različne možnosti plačevanja prevozov in nočitev pa smo stroškovno ovrednotili z izračunom točke preloma ter na podlagi uradnih dokumentov, l^i urejajo financiranje nenujnih reševalnih prevozov.
Rezultati: Analiza podatkov je pokazala, da je nočitev bolnikov ekonomsko smotrna, če je razdalja večja od 38 km in ob predpostavki, da je cena nočitve 40 evrov. 55 % vseh anketirancev se na obsevanje raje vozi, 20 % bi raje prenočevalo v Ljubljani, ostali pa se niso mogli odločiti zaradi pomanjkanja informacij. Pri bolnikih, ki ne uporabljajo reševalnega vozila, je analiza z odločitvenim drevesom pokazala, da bi raje prenočevali predvsem tisti bolniki, ki so oddaljeni več kot 24 k^m in mlajši od 37 let. Celotni stroški sedanjega načina prevozov znašajo 3,31 milijonov evrov letno.
Zaključki: Finančno najbolj smotrna rešitev je sprememba načina financiranja prevozov ter hkratna uvedba pravice do nočitev za oddaljene bolnike, s čimer bi stroške zmanjšali za 57 %. V primeru, da sprememba načina financiranja prevozov ni mogoča, je vsebinsko najbolj primerna rešitev uvedba pravice do nočitve v Ljubljani za oddaljene bolnice, saj prihranek stroškov znaša 17 % glede na trenutno stanje.
Ključne besede: prostorska analiza, nenujni reševalni prevozi, onkologija, nočitve, radioterapija, CART, preference bolnikov
Review article UDC 614.2
Abstract
Introduction: Cancer patients from different regions of Slovenia who come to the Institute of Oncology to attend radiotherapy are not offered the option of paid overnight stay in Ljubljana. The patients' preferences regarding overnight stay were analysed and costs of different transport/overnight stay combinations were calculated. Methods: Data on patient preferences were acquired through questionnaires completed by patients receiving radiotherapy at the Institute of Oncology in Ljubljana at a specified date. The preferences were estimated using CART methods (classification and regression trees). The costs of different combinations of financing overnight stay/transport were estimated using breakeven point analysis based on official documents dealing with payment of non-urgent ambulance transport.
Results: Data analysis showed that overnight stays are cost effective for transports of patients who live more than 38 km away from the Institute, assuming that the cost of overnight stay is 40 EUR. Transport was preferred
^Zavod za zdravstveno zavarovanje Slovenije, Miklošičeva 24, 1000 Ljubljana 2Inštitut za ekonomska raziskovanja, Kardeljeva ploščad 17, 1000 Ljubljana Kontaktni naslov: e-pošta: rupelv@ier.si
by 55% of the patients, and overnight stay in Ljubljana by 20%. The rest of them could not decide because of the lack of information. CART analysis showed that among the nonusers of ambulance transport overnight stays were preferred by patients younger than 37 years, living at a distance of more than 24 km from Ljubljana. Total annual costs of non-urgent tr^ansports were found to amount to 3.31 million EUR.
Conclusions: The best solution would be to change the policy of financing non-urgent transports, and at the same ^ime, to give patients from distant locations the right to stay in Ljubljana overnight; as estimated, the costs would thereby be reduced by 57%. If this change in financing transports is not possible, the best solution would be to enable patients from distant locations to stay in Ljubljana overnight, a measure that would result in 17% savings of current costs.
Key words: spatial analysis, non-urgent ambulance transportation, oncology, overnight stay, radiotherapy, CART, patients' preferences
1 Uvod
V	tujini se v zadnjih letih uveljavlja možnost, da bolniki, ki se vozijo na obsevanje do onkoloških centrov, lahko prenočujejo v neposredni bližini onkološkega centra.
V	Sloveniji bolnikom, ki se vsakodnevno vozijo na Onkološki inštitut (OI) v Ljubljano, te možnosti do zdaj nismo ponudili, pač pa imajo zagotovljen reševalni prevoz, če to terja njihovo zdravstveno stanje, oz. so jim povrnjeni potni stroški, če se na OI vozijo s svojim lastnim vozilom ali z javnim prevozom. Da bi zagotovili večje zadovoljstvo bolnikov, smo se v Sloveniji odločili, da preučimo tudi možnost nočitev v bližini OI, ki bi jo ponudili bolnikom, ki prebivajo daleč in jih vsakodnevna vožnja obremenjuje. Ob tem smo upoštevali stroške obeh možnosti, njihove kombinacije in možne nove predloge. Da bi preference bolnikov bolje razumeli, smo med bolniki, ki se vsakodnevno vozijo na OI, opravili tudi anketo, na podlagi katere smo skušali oceniti zadovoljstvo bolnikov ob potencialnih scenarijih.
podlagi odgovorov nanje pa se vzorec deli na vedno manjše dele. CART lahko operira tako z numeričnimi kot tudi s kategoričnimi (opisnimi) spremenljivkami.
2.2 Regresijsko drevo
Pri uporabi metode CART moramo nujno poznati (določiti) razrede. To pri regresijskih drevesih ne drži popolnoma, saj je vektor Y (odvisna spremenljivka) zvezna spremenljivka in tako predstavlja vrednosti »odgovorov« za vsako izmed opazovanj matrike X (neodvisne spremenljivke) (3). Ker regresijska drevesa nimajo vnaprej opredeljenih razredov, ne moremo uporabiti običajnih tehnik razvrščanja (npr. Ginijeva tehnika pri klasifikacijskih drevesih). Zato cepljenje (angl. splitting) napravimo z algoritmom za minimizacijo kvadratov ostankov. To pomeni, da algoritem minimizira pričakovano vsoto varianc dveh vozlišč (angl. node):
Tii\nV\Var (l^;) + P^Var (YJ\
(1)
2 Metode
2.1 Klasifikacijska in regresijska drevesa (CART)
CART je metoda, pri kateri uporabljamo zgodovinske (pretekle) podatke za izdelavo t.i. odločitvenih dreves, odločitvena drevesa pa nato uporabimo za klasificiranje (razvrščanje v razrede) novih podatkov. Da lahko uporabimo CART, moramo vnaprej poznati razrede. Metodologijo CART so prvi objavili Breiman, Friedman, Olshen in Stone (1984) v članku z naslovom »Classification and Regression Trees« (3). Odločitvena drevesa so predstavljena kot niz vprašanj (da/ne), na
kjer je Y vektor odgovorov, črki l in d označujeta levo in desno nasledstveno vozlišče, P pa so pripadajoče verjetnosti. Na ta način izdelamo maksimalno drevo, ki pa ga moramo nato porezati (angl. pruning) z ustreznimi tehnikami. Če dodelimo vrednost 1 objektom, ki so v razredu k, vsem ostalim pa vrednost 0, dobimo varianco vozlišča t:
pUlOx (1 -p(fci£)>ai£)x (1
(2)
Če seštejemo varianco po vseh razredih K, dobimo mero nečistosti (angl. impurity measure):
Kö = 1 -(fcio^tö = 1 -(MO (3)
Mera nečistosti nam pove, kolikšen delež enot je nepravilno razporejenih v razrede K. Tako je vrednost i(t) pri maksimalnem drevesu minimalna in enaka 0, število končnih vozlišč pa maksimalno. Zato moramo za določanje optimalne velikosti drevesa najti ustrezno razmerje med kompleksnostjo drevesa (številom končnih vozlišč) in mero nečistosti. V ta namen lahko uporabimo navzkrižno preverjanje (angl. cross-validation). Pri tem učeči del podatkov (angl. learning sample) uporabimo za izdelavo drevesa, testni del (angl. testing sample) pa za preverjanje ustreznosti dobljenega rezultata. Proces nekajkrat ponovimo, pri čemer naključno izbiramo testni vzorec. Tako se lahko drevesa, čeprav so zgrajena iz istih podatkov, v času razlikujejo.
3 Anketa
Na anketo je odgovarjalo 241 od 248 onkoloških bolnikov, ki so dne 5. februarja 2009 prišli na obsevanje na OI na Zaloški cesti 2, v Ljubljani (1). Vzorec vprašanih je velik, saj zajema skoraj vse bolnike, ki so na izbrani dan prišli na obsevanje na OI, tako da predstavlja 97 % populacije tistega dne. Bolniki so odgovarjali na dve vprašanji, in sicer: »S kakšnim prevoznim sredstvom prihajate na zdravljenje?« (možni odgovori so: prevoz z reševalnim vozilom + število bolnikov, lastni prevoz, javni prevoz) in »Katera možnost vam bolj ustreza? (odgovori: prevoz z reševalnim vozilom, hostel, vseeno). Na obe vprašanji je nedvoumno odgovorilo 213 bolnikov, vendar so pri statistični analizi posameznega vprašanja oz. odgovora upoštevani vsi bolniki, ki so na obravnavano vprašanje odgovorili nedvoumno. Med anketiranimi je bilo 51,5 %o moških in 48,5 %o žensk. Povprečna (aritmetična sredina) starost anketiranih je bila 60,4 let, mediana 62 let. Povprečna oddaljenost od doma do OI je znašala 70 km, mediana 64 km. Nekatere druge podatke za izračun stroškov prevoza smo pridobili iz uradnih dokumentov in pravnih podlag. Pravica do nenujnih reševalnih prevozov bolnikov je določena v Zakonu o zdravstvenem varstvu in zdravstvenem zavarovanju (4) ter Pravilih obveznega zdravstvenega zavarovanja (5). Splošni dogovor za leto 2009 določa ceno kilometra. Tako je trenutna veljavna cena 0,51 € na bolnika (6). Poleg tega za vsak prevoz osebe izvajalec Zavodu za zdravstveno zavarovanje (v nadaljevanju ZZZS) obračuna tudi startnino, ki znaša 8 km za razdalje do vključno 10 km in 16 km za razdalje nad 10 kilometrov. Bolniki, ki za prevoz na onkološka obsevanja uporabljajo lastni oz. javni prevoz, dobijo povrnjene
stroške v višini cene javnega prevoza (avtobusne vozovnice, vozovnice za vlak). Cenik avtobusnih prevozov do vseh krajev smo pridobili na avtobusni postaji v Ljubljani (7).
Razdalje in čas med posameznim poštnim okolišem in OI smo pridobili na podlagi viaMichellin (15). V analizi sta kot strošek nočitve onkološkega bolnika (t.i.»hostel«) privzeti dve vrednosti, in sicer 40 in 50 evrov. Glede na podatke o številu postelj ter povprečni zasedenosti postelj je mogoče predpostaviti, da je število prostih zmogljivosti za nočitev onkoloških bolnikov v KC zadostno (10,11). Na podlagi podatkov o razdaljah, stroških prevoza in ceni nočitev onkoloških bolnikov v KC smo določili stroškovno upravičenost glede na občino prebivališča oziroma razdaljo do OI. Čeprav se strošek prevoza razdeli med ZZZS in zavarovalnice, ki ponujajo prostovoljno zdravstveno zavarovanje, in sicer v razmerju 30:70, smo v analizi upoštevali polno ceno (100 %) in tako upoštevali družbeni vidik. Za obe predpostavljeni ceni nočitve bolnikov ter ob upoštevanju stroškov prevoza z reševalnimi vozili, ki so navedeni v pravnih podlagah, smo izračunali točko preloma, ki predstavlja število kilometrov, do katere nočitev še ni upravičena.
4 Rezultati
Na podlagi zbranih podatkov o cenah nočitev in cenah prevoza sva avtorja v izhodišču izračunala točko preloma oz. tisto razdaljo, pri kateri nočitev postane ekonomsko smiselna. Z naraščanjem razdalje od Onkološkega inštituta se stroški prevoza povečujejo in na določeni razdalji se stroški prevoza izenačijo s stroški nočitev - nočitev postane ekonomsko smiselna. Rezultati so predstavljeni na Sliki 1, na kateri je označena ekonomska upravičenost vsakodnevnega prevoza v primerjavi z nočitvijo na KC. Temnejša barva označuje območja upravičenosti vsakodnevnega prevoza, če je cena nočitve 40 evrov (razdalja do 38 km), svetlejša in temnejša skupaj pa označujeta območja upravičenosti, če je cena nočitve 50 evrov (razdalja do 52 km). Za vsa območja, ki so bele barve, ob določenih predpostavkah o cenah vsakodnevni prevoz ekonomsko ni upravičen. Sprememb v pravicah zavarovanih oseb iz zdravstvenega zavarovanja pa ne moremo uvajati le na podlagi preprostih ekonomsko-finančnih izračunov, pač pa je potrebno upoštevati želje oz. preference zavarovancev. Preference zavarovancev smo skušali opredeliti s pomočjo ankete.
Slika 1. Stroškovna upravičenost prevoza pri različnih nočitvenih cenah (40 in 50 EUR). Figure 1. Cost efficiency of transport, considering different prices of overnight stay.
Vir: viaMichelin, lastni izračuni, 2009 Source: viaMichelin, own calculations, 2009
Od 241 bolnikov, ki so izpolnili anketo, jih 5 ni odgovorilo na vprašanje, na kakšen način so prišli do OI. Od 236, ki so odgovorili, se jih 57,3 % na zdravljenje vozi z reševalnim vozilom, 35,7 % jih uporablja osebni prevoz, 7 % pa javni prevoz. Geografsko (po poštnih okoliših) so prikazani na Sliki 2. S Slike 2 je razvidno, da se skoraj vsi bolniki iz vzhodnega dela Slovenije (Prekmurje, Štajerska, Koroška) na OI vozijo z reševalnim vozilom, medtem ko reševalno vozilo bolniki iz zahodnega dela Slovenije (Gorenjska) uporabljajo bistveno manj. Večina bolnikov iz zahodnega dela Slovenije uporablja osebni (v manjši meri tudi javni) prevoz. Tako se kar 95 % vseh bolnikov iz območij s poštnimi številkami v območju 2000 in 9000 (Maribor in Murska Sobota) na OI pripelje z reševalnim vozilom (59 od 62 bolnikov). Po drugi strani se iz zahodne Slovenije (območja s poštnimi številkami 4000 (Kranj), 5000 (Nova Gorica) in 6000 (Koper) kar 50 % bolnikov vozi na OI z osebnim prevozom (28 od 56 bolnikov).
4.1 Upoštevanje želja bolnikov
Namen izvedene ankete je bil preveriti želje bolnikov, da bi oblikovali končno rešitev, ki bi bila v njihovo čim večje zadovoljstvo. Rezultati so pokazali, da 55 % vseh anketirancev preferira vsakodnevno vožnjo z reševalnim vozilom, 20 % jih želi, da bi imeli možnost nočitve (»hostel«), ostalih 25 % se ni moglo odločiti zaradi pomanjkanja informacij. Ker smo predvidevali, da si bodo nočitev v bližini Onkološkega inštituta želeli predvsem starejši in tisti, ki se vozijo od daleč (nad 70 km), smo posebej preverili še delež starejših in oddaljenih bolnikov, ki bi si želeli prenočevati v Ljubljani. Med starejšimi nad 60 let se je za nočitve opredelilo 19 % (58 % se jih rajši vozi), med bolniki, ki so oddaljeni več kot 70 km, pa se jih je za nočitve opredelilo 16 % (64 % se jih rajši vozi).
Slika 2. Način prevoza. Figure 2. Mode of transport. Vir: Lastni izračuni, 2009 Source: Own calculations, 2009
Tabela 1. Število in delež bolnikov, razdeljen glede na svoje preference, po starosti, razdalji od doma do
Onkološkega inštituta in spolu. Table 1. Number and share of patients, preferences by age, sex and distance from home to the Institute.
Preferenca Preference	Skupaj (Total)	Starost nad 60 let Age over 60 years	Razdalja nad 70 km Distance over 70 km	Št. moških No. of men
P-Prevoz (Transport)	117	66	61	57
P-Nočitev (Overnight)	43	22	15	27
P-Vseeno (No preference)	53	25	19	23
Skupaj (Total)	213	113	95	107
Preferenca Preference	Skupaj (Total)	Starost nad 60 let Age over 60 years	Razdalja nad 70km Distance over 70 km	Delež moških Share of men
P-Prevoz (Transport)	55 %	58 %	64 %	53 %
P-Nočitev (Overnight)	20 %	19 %	16 %	25 %
P-Vseeno (No preference)	25 %	22 %	20 %	21 %
Skupaj (Total)	100 %	100 %	100 %	100 %
Vir: Anketa, lastni izračuni, 2009
Source: Questionnaire, Own calculations, 2009
V Tabeli 2 so preference bolnikov do nočitve/prevozov prikazane glede na sedanji način prevoza. Od bolnikov, ki se vozijo z reševalnim vozilom (teh je 57,3 %), bi si jih 18 % želelo, da bi lahko čez teden prenočili v Ljubljani, 77 % bi jih nadaljevalo z vsakodnevnimi prevozi, 5 % pa je vseeno.
Bolnike, ki uporabljajo lastni ali javni prevoz, smo združili, saj je tistih, ki uporabljajo javni prevoz, zelo malo. Od bolnikov, ki uporabljajo bodisi javni ali lastni prevoz, si jih 21 % želi, da bi lahko uporabljali vsakodnevni reševalni prevoz, 19 % pa bi si želelo čez teden prenočiti v Ljubljani. Med bolniki, ki ne uporabljajo reševalnega vozila, je kar 60 % takšnih, ki jim je vseeno in svojih želja niso izrazili.
Tabela 2. Preference bolnikov, ki se vsakodnevno vozijo na obsevanje na OI, v deležih. Table 2. Preferences of patients who use daily transport to the Institute (shares).
Način Mode	Preferenca Preference	Starost nad 60 let Age over 60 years	Razdalja nad 70 km Distance over 70 km	Št. moških No. of men	Skupaj Total	
NRP Ambulance	P-prevoz (Transport)	54,3 %	57,4 %	50,0 %	77,0 %	
	P-nočitev (Overnight)	68,2 %	50,0 %	77,3 %	18,0 %	
	P-vseeno (No preference)	66,7 %	83,3 %	33,3 %	4,9 %	57,3 %
Lastni in javni Private and public	P-prevoz (Transport)	65,2 %	30,4 %	43,5 %	30,3 %	
	P-nočitev (Overnight)	33,3 %	19,0 %	47,6 %	27,6 %	
	P-vseeno (No preference)	44,7 %	29,8 %	44,7 %	61,8 %	42,7 %
		53,1 %	44,6 %	50,2 %	100,0 %	
Vir: Anketa, lastni izračuni, 2009
Source: Questionnaire, own calculations, 2009
Izbiro prevoza sva preverila tudi v odvisnosti od oddaljenosti kraja prebivališča do OI. S Slike 3 je razvidno, da večina ljudi, ki bi radi prenočili v Ljubljani, ni zelo oddaljena od Ljubljane. Pri bolnikih, ki se vozijo iz najbolj oddaljenih delov Slovenije (vzhodna Slovenija), želje po nočitvah v bližini Onkološkega inštituta tako rekoč ni. Če združimo Sliko 1, v kateri so prikazana območja, iz katerih bi bila vožnja ekonomsko smotrna (bela območja na Sliki 1), si le 18 % bolnikov želi prenočiti v bližini Onkološkega inštituta in predstavljajo 42 % vseh, ki preferirajo nočitev. To pomeni, da pri 58 % bolnikov, ki si želijo nočitev, ta ni ekonomsko upravičena oz. živijo preblizu Ljubljane, da bi nočitev bila cenejša od stroška vsakodnevne vožnje.
4.2 Podrobnejši pregled preferenc bolnikov
Podrobnejši pogled na odločitve bolnikov pa lahko razkrijemo s podatkovnim rudarjenjem - z odločitvenim drevesom. Z njim lahko pojasnimo, na kakšen način so se anketiranci odločali za posamezno možnost ter katere značilnosti vplivajo na njihovo izbiro. V nadaljevanju je prikazano odločitveno drevo, ki smo ga ustvarili s pomočjo programske opreme Orange. Vozlišča predstavljajo vprašanja, na vejah so odgovori, pod listi pa so podane verjetnosti oziroma predstavljajo čistost (npr. med bolniki, ki za prevoz uporabljajo reševalno vozilo, drevo predvideva, da imajo preference do reševalnega vozila kljub ponujeni možnosti nočitev. To velja za 74,9 % bolnikov). Označeni del drevesa smo uporabili za napoved preferenc bodočih bolnikov v nadaljevanju.
Slika 3. Izbira prevoza/nočitve glede na poštni okoliš stalnega prebivališča. Figure 3. Choice of transport and overnight stay by postal a^eas.
Vir: Anketa, lastni izračuni, 2009
Source: Questionnaire, Own calculations, 2009
Slika 4. Odločitveno drevo. Figure 4. Decision tree. Vir: Anketa, Register raka, lastni izračuni, 2009 Source: Questionnaire, Cancer registry, own calculations, 2009
Iz odločitvenega drevesa je razvidno, da na izbiro glede možnosti najbolj vpliva trenutno stanje oziroma sedanji način prevoza, s katerim prihajajo na zdravljenje. Tako je večina tistih, ki se vozijo z reševalnim vozilom, izbrala možnost (1) reševalno vozilo (75 %), 18,7 % nočitve, 6,4 % pa je vseeno.
Pri ostalih, ki se vozijo bodisi z lastnim bodisi z javnim prevozom, je odločitev glede nočitev najprej odvisna od povprečne hitrosti vožnje z osebnim avtomobilom. Bolniki, ki se lahko vozijo z osebnim vozilom (glede na omejitve na cestah, ki jih uporabljajo za prevoz do OI LJ) s povprečno hitrostjo več kot 83 km/h in so stari manj kot 38 let, so izbrali možnost nočitev, medtem ko je večini (81 %) starejših od 38 let vseeno. Odločitev bolnikov, ki se ne vozijo z reševalnim vozilom in pri katerih je povprečna hitrost prevoza manjša od 83 km/h, lahko najbolje pojasnimo z oddaljenostjo od OI. Bolniki, ki so oddaljeni manj kot 17 km in so mlajši od 47 let, so izbrali možnost vsakodnevnega prevoza. Bolnikom, ki imajo poleg omenjenih značilnosti stalno prebivališče, oddaljeno med 17 in 26 km, in pa večini (54 %) starejših od 47 let, je vseeno. V zadnji skupini bolnikov (to so bolniki, ki se ne vozijo z reševalnim vozilom, s povprečno hitrostjo prevoza manjšo od 83 km/h ter z razdaljo do OI, večjo od 26 km), pa razlike v odločitvah najbolje pojasnimo s starostjo. V omenjeni skupini bi nočitve izbrali mlajši od 63 let, ki živijo v krajih, ki so od OI oddaljeni od 26
Tabela 3. Matrika r^azvrstitev.
Table 3. Confusion matrix.
do 63 km (61 %), medtem ko bi vsakodnevni prevoz z reševalnim vozilom ustrezal tistim, ki so starejši od 63 let (58,6 %).
Iz drevesa je torej jasno razvidno, da na preference bolnikov najbolj vpliva sedanje stanje, da število potnikov v reševalnem vozilu bistveno ne vpliva na odločitev glede nočitev ter da je druga najbolj pomembna kategorija pri pojasnjevanju bolnikovih preferenc povprečna hitrost prevoza. Natančnost omenjene metode lahko preverimo z matriko (pravilnih in napačnih) razvrstitev, v kateri so najprej navedene prave oziroma opazovane vrednosti, nato pa še predvidena vrednost. Iz tabele je razvidno, da je model (odločitveno drevo) sposoben predvideti preference glede reševalnega vozila/nočitev (117/141; 117 jih je izbralo možnost, 141 pa je predvideno število iz odločitvenega drevesa) in tiste, ki jim je vseeno (55/60), zelo pa podceni tiste, ki bi izbrali možnost nočitve (45/14).
4.3 Napovedi želje bodočih bolnikov
Z zgrajenim odločitvenim drevesom lahko napovemo želje bodočih bolnikov. Glede na to, da za bodoče bolnike sedanji način prevoza ni bistven, smo želje ocenili na podlagi glavne leve veje odločitvenega drevesa. Podatki, ki smo jih uporabili za napoved preferenc novih bolnikov, izhajajo iz Registra raka RS za leto 2006, rezultati pa so prikazani v Tabeli 4.
	Prevoz Transport	Nočitev Overnight	Vseeno No preference	
Prevoz/Transport	94 / 76	6 / 7,55	17 / 33,43	117
Nočitev/Overnight	26 / 29	2 / 2,90	17 / 12,86	45
Vseeno/No preference	21 / 36	6 / 3,55	28 / 15,71	55
	141	14	60	217
Vir: Lastni izračuni, 2009 Source: Own calculations, 2009
Tabela 4. Napoved preferenc za bolnike, pri katerih je bila bolezen odkrita leta 2006, na podlagi
klasifikacijskega (odlo~itvenega) drevesa. Table 4. Preference prediction for patients diagnosed with cancer in 2006.
	Število Number	Delež Share	Delež (2) Share (2)
Prevoz (Transport)	2161	42,22 %	66,25 %
Nočitev (Overnight)	1101	21,51 %	33,75 %
Vseeno (No preference)	1857	36,28 %	
Vir: Register raka, lastni izračuni, 2009 Source: Cancer Registry, Own calculations, 2009
Iz Tabele 4 je razvidno, da bi si največ »novih« bolnikov (42 %) želelo vsakodnevnega prevoza z reševalnim vozilom, 22 % bi si izbralo možnost nočitev, 36 % pa se ne bi opredelilo oziroma bi jim bilo vseeno. Če pa primerjamo le tiste bolnike, ki imajo izražene preference (prevoz ali nočitev), pa opazimo, da je število bolnikov, ki bi izbrali možnost »prevoz«, enkrat večje (66,3 % proti 33,7 %). Hkrati pa je potrebno dodati, da uvedbi nočitev ne bi nasprotovalo 57,8 % (nočitev + vseeno) bolnikov. Poleg tega bi bila nočitev ekonomsko upravičena (pri tistih, ki si nočitve želijo) pri 38 % bolnikov ob ceni 50 evrov in le pri 18 % bolnikov pri nočitveni ceni 40 evrov.
4.4 Ovrednotenje posameznih različic - izračun stroškov različnih možnosti
Celotni stroški sedanjega načina prevoza znašajo 3,31 milijonov evrov na leto1. Te stroške smo primerjali z naslednjima možnostima:
1. Bolniki, ki se vozijo na obsevanje z reševalnim vozilom in za katere je nočitev ekonomsko smotrna, izberejo, ali želijo prespati v Ljubljani ali pa se voziti (pri izračunu smo upoštevali preference bolnikov glede na rezultate analize). Predpostavili smo, da upoštevamo njihove preference. Cena nočitve je 40 evrov, bolniki, ki prespijo, pa imajo plačan prevoz z reševalnim vozilom od doma v Ljubljano v ponedeljek in iz Ljubljane do doma v petek. Bolniki, ki danes uporabljajo javni ali zasebni prevoz, ga uporabljajo tudi v tej možnosti.
2. Možnost 1 smo nadgradili z možnostjo, da prevozniki niso plačani na kilometer na bolnika, pač pa na prevoženi kilometer. Pri tej možnosti predpostavljamo, da je sprejet predpis, ki bolnikom zagotavlja kakovost prevoza in vzpostavlja omejitve glede najmanjšega in največjega števila potnikov v avtomobilu.
Obe opisani možnosti smo ovrednotili, pri čemer smo pri vseh izračunih uporabili iste vire in podatke, tako da do morebitnih napak ali odstopanj v nobenem primeru ne more priti zaradi različnih ali neprimerljivih podatkovnih baz ali metodologije. Stroške smo ocenili na podlagi posredovanih podatkov o številu frakcij glede na občino prebivališča za leto 2008. Vseh frakcij je bilo 48.720, vendar pri 14.986 primerih ni bila navedena prostorska referenca (občina ali poštni okoliš), zato je bilo število frakcij (pri katerih je bila navedena občina) večje za delež med neznanimi in znanimi prostorskimi referencami. Pri vseh izračunih smo upoštevali iste podatke o cenah avtobusnih vozovnic, in sicer 10 centov na prevoženi kilometer ter 0,51 evra na prevoženi kilometer na bolnika z reševalnim vozilom. Delež bolnikov, ki se vozijo z reševalnim vozilom ali javnim (in osebnim) prevozom, smo ocenili na podlagi števila frakcij po občinah s pomočjo klasifikacijskega (odločitvenega) drevesa z upoštevanjem samo razdalje in časa. Ocenjeni deleži so prikazane v Tabeli 5.
Tabela 5. Primerjava deležev izbranih načinov prevoza. Table 5. Comparison of transport preferences (in %).
SEDANJI NAČIN PREFERENCE Now Preferences		RAZLIČICI 1 in 2 Possibilities 1 and 2
NRP LASTNI Ambulance Own 51,1% 48,9%	NRP HOSTEL LASTNI Ambulance Hostel Own 51,2% 38,2% 10,6%	NRP HOSTEL LASTNI Ambulance Hostel Own 72,5% 16,8% 10,6%
Vir: Frakcije, anketa, lastni izračuni, 2009
Source: Fractions, Questionnaire, own calculations, 2009
Iz Tabele 5 je razvidno, da se za nočitve odločajo le bolniki, ki ne uporabljajo reševalnega prevoza. Na podlagi ocen za sedanji način smo ocenili tudi stroške prevoza bolnikov za leto 2008. Pri različicah 1 in 2 pa smo deleže spremenili glede na
ekonomsko upravičenost. Tako bi imeli prosto izbiro o nočitvi oziroma prevozu le tisti bolniki, pri katerih je bila nočitev ekonomsko smotrna. Ocene stroškov sedanjega načina financiranja prevoza bolnikov in ocene različic 1 in 2 so prikazane v Tabeli 6.
1 Izračun stroškov temelji na podatkih o številu frakcij ter na pravilih o obračunavanju prevozov in na podlagi ankete ocenjenega deleža uporabe javnega in zasebnega prevoza. Povprečno število bolnikom v reševalnem vozilu smo ocenili z anketo in znaša 2,59.
Tabela 6. Primerjava ocen stroškov prevoza bolnikov. Table 6. Comparison of estimated transport costs.
	SEDANJI NAČIN Now	RAZLIČICA 1 RAZLIČICA 2 Option 1 Option 2	
EUR (EUR) Delež (share)	3.309.128	2.758.008	1.417.497
	100%	83%	43%
Vir: Frakcije, Register raka, Lastni izračuni, 2009 Source: Fractions, Cancer Registry, Own calculations, 2009
Glede na to, da predlagana sprememba z uvedbo nočitev za zavarovance, ki živijo daleč od OI, ni naletela na pretirano dober odziv med anketiranimi, eden izmed ciljev analize pa je bil poiskati možne prihranke, smo iskali še druge kombinacije in možnosti rešitev, ki bi ohranile in upoštevale želje bolnikov ter hkrati znižale stroške. Glede na to, da prevoznikom ob sedanjem načinu financiranja na kilometer na bolnika število bolnikov v reševalnem vozilu ne povzroča pomembnih dodatnih stroškov, temveč le dodatne prihodke, bi bilo smiselno razmisliti o spremembi načina financiranja nenujnih reševalnih prevozov in bi prevoznike plačevali glede na število prevoženih kilometrov prevoznega sredstva in ne glede na bolnika. S tem bi obdržali pravico bolnika do nenujnega reševalnega prevoza, hkrati pa upoštevali želje bolnikov. Iz ankete je razvidno, da si 55 % vseh bolnikov (tudi tistih, ki do prevoza z reševalnim avtom niso upravičeni) in 77 % tistih, ki se že zdaj vozijo z reševalnim vozilom, želi vsakodnevnega prevoza z reševalnim vozilom. Način povrnitve stroškov za ostale bolnike, ki se do OI vozijo z lastnim ali javnim prevozom, bi ostal nespremenjen. Glede na to, da predlagani način plačevanja prevoznikov spodbuja prevoznike, da vozijo le enega bolnika, bi morala tak način plačevanja spremljati tudi ustrezna pravna podlaga, ki bi zagotavljala, da prevoznik hkrati v avtomobilu ne pelje manj kot 2 bolnikov in praviloma ne več kot treh. Ob upoštevanju dejstva, da je sedanje povprečno število bolnikov v reševalnem vozilu 2,59, tak način ureditve najbrž ne bi predstavljal problema pri organiziranju prevozov.
5 Zaključek
Ugotovitve analize kažejo na to, da bi bila uvedba nočitev v nasprotju z željami velikega števila bolnikov. Večina bolnikov, ki uporablja nenujne reševalne
prevoze, si jih želi tudi v prihodnosti, zato so možni kandidati za nočitve tisti, ki uporabljajo lastni ali javni prevoz. Analiza tudi kaže, da je z ekonomskega vidika nesmotrno uvesti nočitve za vse bolnike, pač pa samo za oddaljene bolnike. Ekonomsko najbolj smotrna rešitev je sprememba načina financiranja prevozov ter hkrati uvedba pravice do nočitev za oddaljene bolnike, s katero stroške zmanjšamo za 57 %. V primeru, da sprememba načina financiranja prevozov ni mogoča, je vsebinsko najbolj primerna rešitev tista, ki uvaja pravico nočitve v Ljubljani za oddaljene bolnike, pri kateri je prihranek 17 % glede na trenutno stanje.
Literatura
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3.	Timofeev R. Classification and regression trees (CART): theory and applications, a master thesis. Berlin: Humboldt Universitat, 2004.
4.	Zakon o zdravstvenem varstvu in zdravstvenem zavarovanju. UL RS 9/92
5.	Pravila obveznega zdravstvenega zavarovanja. UL RS 64/07, 33/08 in 7/09, člen 54 - 56. Pridobljeno 15.3.2009 s spletne strani: www.zzzs.si.
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12.	Onkološki inštitut. Podatki o številu frakcij po občinah za leto 2008, 2008.
13. Register raka: Incidenca raka 2006, podatki po 5-letnih 14. GURS, Geodetska uprava RS.
starostnih skupinah in spolu in poštnih okoliših.	15. ViaMichelin, http://www.viamichelin.com/.
UNSATISFACTORY CARDIOVASCULAR RISK CONTROL -
OPPORTUNITIES FOR FAMILY MEDICINE NEZADOSTNO OBVLADOVANJE DEJAVNIKOV TVEGANJA ZA SRČNO- ŽILNE BOLEZNI - PRILOŽNOST ZA DRUŽINSKO
MEDICINO
Mirjana Rumboldt1, Marion Kuzmanič1, Dragomir Petric1, Zvonko Rumboldt1
Prispelo: 4. 3. 2010 - Sprejeto: 4. 7. 2010
Abstract
Review article UDC 616.084, 616.1
Although theoretically very effective and appar^ently quite str^aightforward, car^diovascular prevention leaves much to be desired in practice. Several reasons, including ethical, conceptual, psychological, and operative pitfalls (lifestyle changes are mostly ignored; drug therapy is too often prescribed with no good reason, and performed in an episodic or on/off way) are presented in this essay. Discussed are the grounds of these aberrations and suggested a^re some intuitive solutions, best achievable in family practice.
Key words: cardiovascular diseases, prevention, family medicine
Izvleček
Pregledni znanstveni članek UDK 616.084, 616.1
Preprečevanje srčno-žilnih bolezni je teoretično zelo učinkovito in na videz precej enostavno, vendar pa je treba v praksi na tem področju še marsikaj storiti. Prispevek opisuje razloge takšnega stanja, tj. etične, konceptualne in psihološke dejavnike ter težave pri izvajanju. Zdravljenje z zdravili prevečkrat predpišemo brez pravega razloga, potega pa občasno in neredno. Prispevek obravnava vzroke teh slabosti in predlaga nekaj rešitev, ki jih najlaže ponudi družinska medicina.
Ključne besede: srčno-žilne bolezni, preprečevanje, družinska medicina
Medical research has markedly improved the knowledge of etiology and prevention of cardiovascular conditions, particularly coronary heart disease (CHD), so that these disorders could virtually be eliminated. Indeed, several years ago, the global community was seemingly approaching the eradication of atherosclerosis, the leading cause of cardiovascular morbidity and mortality. Unfortunately, in reality the expectations had not been met: nowadays the decrease in CHD in economically developed countries is stagnant (1), the prevalence of CDH is probably increasing (2), while in developing and transitional countries it is escalating (3). This gloom picture is often attributed to unavailability of or to a delay in using modern invasive procedures and new medications, particularly in patients with heart attack or stroke.
Although this segment of management should not be neglected (e.g. prompt and accurate diagnosis, early initiation of treatment in family practice, faster transportation, better organization and distribution of adequately staffed and well equipped interventional units), the bulk of the problem lies at the other end of the clinical spectrum - in unsatisfactory prevention. The EURASPIRE III results (4) show that during the past decade the prevalence of obesity among coronary patients in Europe has increased from 25% to 38%, and that of diabetes from 17.4% to 28%, while smoking and hypertension rates remained unchanged, i.e. approx. 20 % and 60%, respectively. Which are the obstacles on the path to effective primary prevention of CHD, i.e. to adequate protection of apparently healthy, younger people against adverse
^University of Split, School of Medicine, Department of Family Medicine, Soltanska 2, 21000 Split, Croatia Correspondence to: e-mail: mirjana.rumboldt@mefst.hr
cardiovascular events? In this paper some of the most important issues are presented from the family physician's standpoint, partly skewed by the Croatian experience in the field.
1)	Low perception of deferred risk. Any patient will seek urgent medical attention for acute, painful events, such as fibrinous pericarditis or coronary spasm. On the other hand, chronic conditions, such as arterial hypertension, hyperlipoproteinemia or glucose intolerance, are much less alarming and often painless. The management, especially primary prevention, consisting of adequate nutrition, avoidance of weight gain, exercise and/ or smoking cessation, is mostly neglected or at best performed in an episodic way. The reasons are probably psychological (5): in spite of good theoretical knowledge of the problem, practical execution leaves much to be desired because human perception of deferred risk is considerably inferior to the appreciation of imminent danger. For this reason people unwillingly fasten seatbelts, and put them on more for the fear of being fined than for the statistically tiny, but individually immense risk of getting injured in the case of a car crash. More than twenty years ago our study showed that declaratively appropriate and cost-effective measures for managing arterial hypertension are seldom implemented in daily practice (6). There is a wide gap between words and deeds, which needs to be bridged both by physicians, patients and the population at large.
2)	Ethical issues. From the middle of the past century the human rights movement has been rapidly expanding, this development being expected and understandable after incredible crimes against human dignity committed not only during World War II but also previously and subsequently alike (7). Patient autonomy is respected whenever possible, and the traditional, paternalistic doctor-patient relationship is replaced by a kind of negotiating, mutually agreeable partnership, with informed consent as one of its cornerstones. It seems, however, that modern society is moving towards the other extreme: while striving for human rights, the dues tend to be neglected. Although these components of moral judgment should stay in balance - more rights beget more obligations - the ethics of rights is overwhelming the ethics of responsibilities (8). It is increasingly overlooked that individual rights are limited by the rights of the neighbours and the community at large, so that current moral judgment is focusing more closely on individual than on collective interest. Personal
responsibility for careless and hazardous life-style is left out in the cold, but in the case of misfortune instead of silent suffering the health problem is suddenly and vociferously socialized, requesting costly treatment at the expense of solidarity. These inconsistencies in ethics should be corrected if adequate and coherent attitudes towards health care in the community are to be contemplated.
3)	Decisive role of risk factors. A number of large-scale investigations, from the Framingham cohort to the recent INTERHEART case-control study (9, 10), have clearly demonstrated that CHD is uncommon without a concurrent or antecedent exposure to one or several major risk factors. With the clustering of these factors the probability of CHD complications increases exponentially (Table 1). Comparable data have been obtained in Croatia as well (11,12). Unfortunately, these clear and simple facts, explaining over 90% of the global coronary risk (9), often go unknown or ignored. A straightforward evaluation of cumulative individual risk, emanating from these studies, is widely disseminated (charts, calculators etc.) and easily accessible to family practitioners. Although it is scientifically sound to investigate additional, novel risk factors, improvement in population levels of several "conventional" risk factors remains the main goal of scientific elucidation and practical enforcement.
4)	Desirable risk factor levels are uncommon indeed. Alas, this is true for all the populations evaluated, either rich or poor, developed, transitional or developing (12,13). In an analysis of the NHANES-3 data, Vasan et al. (10) have shown that less than 1 % of men aged 35-74 years were non smokers, having systolic blood pressure <120 mm Hg, diastolic blood pressure <80 mm Hg, LDL cholesterol <2.6 mmol/l, HDL cholesterol >1.5 mmol/l, and fasting glucose level <6 mmol/l or 2-h postprandial glucose level <7.8 mmol/l. The same was true for women aged 55 to 74 years (10). Stamler et al. (13) have demonstrated years ago that age-adjusted risk of CHD mortality was 77-92% lower for women and men with no major risk factors in relation to the rest of the cohort. Even all-cause mortality rates were 40-58% less for those with no major risk factors compared with the rest of the series, and the estimated life expectancy gain ranged from 5.8 to 9.5 years (13). In a Croatian sample including 5,840 persons aged 18-65 years, 31.1% of the male examinees had BMI >30, 31.9% had blood pressure >140/90 mm Hg, and the 75th percentiles of serum cholesterol and triglycerides were 6.6 and 2.6 mmol/l, respectively (11)!
Table 1. Exponential increase in the probability of acute myocardial infarction with the aggregation of risk
factors [according to (9)]. Tabela 1. Eksponentni porast verjetnosti miokardnega infarkta pri agregiranih dejavnikih tveganja.
Risk factor Dejavnik tveganja		Odds ratio Razmerje obetov
1	Smoking kajenje	2.9
2	Diabetes mellitus diabetes mellitus	2.4
3	Arterial hypertension arterijska hipertenzija	1.9
4	Apo B/A 3rd vs. 1st tertile koncentracije ApoB/A tretji vs. prvi tercil	3.3
	1+2+3	13.0
CO cc	1+2+3+4	42.3
ta cg k tv	The former + obesity prejšnji + debelost	68.5
> o d) -C ^	The former + psychosocial factors prejšnji + psihosocialni dejavniki	182.9
ng de inrje ^ "t^ m	Combination of the former six factors + lack of physical activity + inadequate alcohol intake (more than moderate or total abstinence) kombinacija prejšnjih šestih dejavnikov + pomanjkanje telesne dejavnosti + neustrezno pitje alkohola (več kot zmerno ali popolna abstinenca)	333.7
Table 2. A comparison of control and high risk 14-year-old pupils in Split, Croatia [according to (14)]. Tabela 2. Primerjava kontrolne skupine in skupine 14-letnih učencev z visokim tveganjem, Split, Hrvaška, glede na (14).
Parameter Parameter	Control children Kontrolna skupina otrok (n=139)	Children of parents having AMI <45 years Otroci staršev z AMI<45 let	
		History only samo anamneza (n= 97)	Additional risk factors Dodatni dejavniki tveganja (n= 50)
Relative weight (%)* Relativna telesna teža	99.5±11.2	103.8±15.2+	110.1±16.7*
Plasma cholesterol (mmol/l) Plazemski holesterol	4.4±0.6	5.2±1.1t	5.4±1.2*
Systolic blood pressure (mm Hg) Sistolični krvni tlak	114.3±8.5	116.6±15.3t	122.9±17.0*
Diastolic blod pressure (mm Hg) Diastolični krvni tlak	73.6±7.3	74.3±12.7t	79.7±13.3*
*Body mass in kg as % of ideal weight for age/gender; +p<0.05; *p<0.001 vs. control group.
5)	Early detection of persons at higher risk for CHD is of paramount importance. The child is recycling the genetic (inner) and micro-social (outer) characteristics of man. Because of risk factors clustering among the offspring of people suffering from premature atherosclerotic events, these ""stigmatized" individuals should be identified, screened, and evaluated early in childhood or at school age. The yield is high and the number of persons to be assessed is low; the cost of intervention is almost negligible, and lifestyle interventions (e.g. dietary habits, exercise and/or antismoking programs) may have a durable and decisive impact on prognosis. Marked differences were demonstrated between school-age children of parents with premature CHD (offspring aged 14.2±4.8, parents 39.9±4.2 years) and their control school-age peers (aged 14.2±0.6 years) (14) (Table 2).
The probability of adverse prognosis was even higher in the presence of additional risk factors; e.g. the prevalence of arterial hypertension among these high-risk children was 46.4%, and that of smoking was even higher, i.e. 51.3% (14). These data send us the following vivid message:
a) The incidence of early atherosclerotic complications at young age is low (<5% of the CHD patients), an the prevalence in those patients' offspring among their peers is even lower (<1%); b) Some conventional risk factors (e.g. smoking, obesity) are detectable at a glance, while others, such as hyperlipoproteinemia and hypertension, are confidently and cheaply identified in those selected individuals;
c) Simple measures, such as dietary advice or smoking cessation programs, and rare, specific interventions (e.g. statins in heterozygous familial hypercholesterolemia) substantially improve the cardiovascular prognosis in these individuals.
6)	General measures are underestimated and largely ignored. The effectiveness of well structured counseling on lifestyle modifications has been ascertained beyond any reasonable doubt (15). However, just a minor portion of persons at increased risk quit smoking, decrease body mass and salt intake, adopt a "Mediterranean" diet or engage in adequate exercise for any longer period of time (16, 17). There are several formal reasons for this situation; some pertain to fluid diagnostic criteria (e.g. for the metabolic syndrome) or overlapping guidelines (e.g. misunderstandings
about global cardiovascular risk assessment by the Framingham and SCORE tables, although the former is obviously related to morbidity, and the latter to mortality) (18). However, fundamental are socio-economic and cultural barriers517 which may be overcome by early gentle and persistent education about healthy lifestyles, extending from family to school and involving the whole community. Additional effects may be obtained through legislation and law enforcement (e.g. higher smoking taxation and/or banning).
7) Drug therapy is hastily prescribed in primary prevention. Potent drugs are too often prescribed on the ground of a single laboratory result or blood pressure reading. Such interventions are frequently superfluous because of false positive findings (e.g. white coat hypertension, biological variation, laboratory flaw) or could be postponed while waiting for the results of effective lifestyle modifications. Moreover, wide implementation of pharmacotherapy in primary prevention bears several burdens:
a)	Individual prognosis in a low-risk population is only marginally, although statistically significantly, improved by the use of highly effective modern drugs (e.g. statins, ACE inhibitors): the medication must be taken by several hundreds of low-risk individuals for years to benefit just a few;
b)	The expected side-effects (e.g. angioedema with ACE inhibitors, myopathy with statins), although rare, (incidence rate well below 0.1% ) become alarming when legions of apparently healthy individuals are exposed to the intervention;
c)	The probability of adequate intake of this medication
is inversely proportional to subjective ailments, motivation, and the number of people exposed. Noncompliance becomes the rule rather than an exception, particularly if the subjects are inadequately informed and motivated;
d)	This approach is extremely expensive, and could absorb up to 25-50% of all the funds available to health service (19). Pharmacoeconomic analyses are invaluable in addressing these issues, but other variables, such as political feasibility and social acceptability, must be kept in mind as well (20). For instance, what about the proposed wide prescribing of statins to children over eight years of age if their LDL cholesterol is above 4.9 mmol/l (or just > 4.1 mmol/l in the case of positive family history or two additional risk factors) (21)?
8)	Only well tolerated, highly effective medications should be prescribed in primary prevention. Which kind of evidence is good enough in this respect? Because of extremely high cost of large randomized clinical trials, conducted under time constraint and based upon logically plausible presumptions, "soft" goals, i.e.„ surrogate endpoints", such as amelioration of a clinical sign or a laboratory result, are investigated instead of "hard" endpoints (e.g. death, stroke, acute myocardial infarction). Although attractive, such trials are often misleading, as shown by a large, randomized and controlled clinical study on antiarrhythmic agents following myocardial infarction (22) carried out several years ago; and recently by the attempts to control the atherosclerotic process by elevating HDL cholesterol levels (23). It is self-evident that results of unconvincing clinical trials should not be implemented in practice. However, even the messages given by large, well-designed, randomized clinical trials with hard end-points (mostly hospital-based and including very sick inpatients) must not be literally extrapolated to family practice i.e. to mostly ambulatory and less sick, outpatients, since two opposite extremes of the same nosologic spectrum are at stake. Then, again, the treatment may have worse effects than the disease itself, as argued in paragraph 7.
9)	Pharmacotherapy is underused in secondary CHD prevention. In contrast to primary prevention which shows a tendency to overprescribe pharmacotherapy, in secondary prevention, protective drugs are quantitatively and qualitatively underprescribed for
individuals at substantially higher risk. Again, the reasons are manifold, from differences in opinions and attitudes encountered in various countries and even regions, to the neglect of convincing scientific evidence. This is sometimes due to fear of possible adverse effects, which, considering a favorable risk/benefit ratio in this case, are quite acceptable (24,25). However, there are differences in the level of therapeutic gain between the available interventions because of unequal intrinsic efficacy and dissimilar patient characteristics. This concept is best illustrated with the number of patients who require treatment to prevent one event (NNT). The relative cost/effectiveness reasoning is clearly illustrated in the following example. Suppose that a country may afford about eight million € to give simvastatin, one of the best known statins, in a daily dose of 20 mg to 25,000 people with increased CHD risk. If such treatment is given to high-risk individuals (4S study criteria) it can save some 190 lives per year; if the treatment is offered to medium-risk individuals (HPS study criteria), it can save about 90 persons, and if the treatment is offered to lower- risk individuals (WOSCOPS or ASCOT-LLA criteria) some 69 deaths can be prevented with the same investment (19). Many coronary patients may need a complicated drug regimen of variable therapeutic gain (Table 3), consisting possibly of aspirin (acetysalicylic acid), a ß-adrenergic blocker, a statin, an ACE inhibitor, a diuretic, an aldosterone antagonist (e.g. eplerenone), a nitrate, some digoxin, a fish-oil formulation, and other ingredients (26).
Table 3. Reduced number of events among 1,000 coronary patients treated for one year [according to (26)]. Tabela 3. Zmanjšano število zapletov pri 1000 koronarnih bolnikih po enem letu zdravljenja (26).
Intervention Ukrep	Fatal and non-fatal complications prevented Preprečene smrtno nevarni ali manj nevarni zapleti	Mortality decrease	
		Deaths prevented Preprečeni smrtni izidi	NNT/ 1 year* NNT/ 1 leto
Beta-blockers Blokatorji beta	42	21	48
Smoking cessation Prenehanje kajenja	61	15	67
Statins Statini	37	7	143
Acetylsalicylic acid Acetilsalicilna kislina	19	7	143
m-3 fatty acids Omega-3 maščobne kisline	<6	<3	>330
*NNT: number needing treatment (i.e. how many people should receive treatment to benefit one)
Hence, individual selection of the most appropriate regimen in terms of efficacy, tolerability and cost is compelling. One should keep in mind that overtreatment usually leads not only to noncompliance but also to omission of vital interventions in favour of marginal ones.
10) The pivotal role of family medicine. In this review, organizational, financial and political pitfalls have been intentionally skipped for the sake of brevity. In order to lower the prevalence of coronary risk factors in the population, instead of sophisticated technology, invasive procedures and expensive medications, many education efforts coupled with human understanding, persuasion, and common sense are desperately needed. These issues can best be addressed in a personalized, family practice. Hypertension, smoking or weight gain embody many behavioural components that are not easily addressed by formal medical therapy alone. Family medicine has a unique opportunity for behavioral modification at the individual and public health levels, based on empathy, role modeling, and personal skills in communication and education. It should be remembered that specialist training in family medicine was introduced in Croatia half a century ago (27) and that at the time, Croatian family practice professionals were among the world's leading experts in the field. Instead of treating diseases, family medicine helps sick individuals by enhancing the quality of their life; instead of depersonalized, industrialized services, it offers human understanding, instead of high technology that benefits a few, it delivers efficient care to many, and instead of fee for service, it ensures comprehensive care. After identifying the level of coronary risk, family physician must give pertinent, evidence-based information to a patient (or a small group of patients). He/she must answer the patients' questions, allow time for data interpretation, and, after a while, schedule a discussion about their views, problems, and steps to be taken. Such a task takes a lot of time, dedication and commitment to be effective. Family physicians must be adequately remunerated for their services and unburdened of huge capitation rates (presumably not more than 1,500 under care in Croatia) and cumbersome administration, setting aside two hours per day for preventive and educational purposes. That such amendments are feasible was recently shown in the field of minor surgery (28). Intrinsic to family medicine are certain attitudes that are not readily taught at medical schools: the need to compromise, humility, tolerance and acceptance of different values (29). The most important teaching
method is acting as a role model, in other words being an exemplar of decorum (i.e. a propriety of appearance and behaviour) that manifest one's inner virtues, e.g. in order for a physician in the field of preventive cardiology to be persuasive, he/she must not be an authoritative, obese smoker.
Preventive programs should be cost-effective. However, humanism is about quality and not quantity. It is hardly defined and measured in a quantitative manner. Fine qualitative research, followed by quantitative studies, should be done to convince the politicians of the benefits and advantages of investing in family practice (29). In this perspective, we foresee the solution for the stagnant or worsening circumstances in preventive cardiology.
Finally, we would mention some additional relevant problems emerging in everyday practice, which a competent family physician must be able to solve individually, on the spot:
•	At which level a risk factor becomes a disease (e.g. millimeters of mercury for blood pressure or millimoles per liter for cholesterol, glucose or uric acid)?
•	Which are the pros and cons of labeling a newly discovered, at-risk but apparently healthy, symptomless person as sick (e.g. hypertension, hyperlipidemia)?
•	Should the patient be scared, encouraged or something else?
•	When it is appropriate to refer a patient for a specialist consultation?
•	How to overcome the apparent conflict between general measures - which as a rule are ignored -, and drug therapy which is accepted and even requested, mostly for episodic, on/off and ineffective treatment? In other words: how to bridge the gap between scientific evidence and crude reality?
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