Application of the STOPP/START criteria: a systematic review of the prevalence of potentially inappropriate prescribing in older adults, and evidence of clinical, humanistic and economic impact
2013; Wiley; Volume: 38; Issue: 5 Linguagem: Inglês
10.1111/jcpt.12059
ISSN1365-2710
AutoresBarbara Hill-Taylor, Ingrid Sketris, Jill A. Hayden, Stephen Byrne, David O’Sullivan, Ronald J. Christie,
Tópico(s)Healthcare cost, quality, practices
ResumoJournal of Clinical Pharmacy and TherapeuticsVolume 38, Issue 5 p. 360-372 Review ArticleFree Access Application of the STOPP/START criteria: a systematic review of the prevalence of potentially inappropriate prescribing in older adults, and evidence of clinical, humanistic and economic impact B. Hill-Taylor BSP MLIS, Corresponding Author B. Hill-Taylor BSP MLIS College of Pharmacy, Dalhousie University, Halifax, NS, CanadaCorrespondence: B. Hill-Taylor, College of Pharmacy, Dalhousie University, 5968 College Street, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2. Tel.: +1 902 494 2378; fax: +1 902 494 1396; e-mail: murpp@eastlink.caSearch for more papers by this authorI. Sketris Pharm D MPA(HAS), I. Sketris Pharm D MPA(HAS) College of Pharmacy, Dalhousie University, Halifax, NS, Canada Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, CanadaSearch for more papers by this authorJ. Hayden PhD, J. Hayden PhD Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada Nova Scotia Cochrane Resource Centre, Dalhousie University, Halifax, NS, CanadaSearch for more papers by this authorS. Byrne PhD MPSI, S. Byrne PhD MPSI Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, Cork, IrelandSearch for more papers by this authorD. O'Sullivan MPharm MPSI, D. O'Sullivan MPharm MPSI Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, Cork, IrelandSearch for more papers by this authorR. Christie BSc(Pharm), R. Christie BSc(Pharm) Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, CanadaSearch for more papers by this author B. Hill-Taylor BSP MLIS, Corresponding Author B. Hill-Taylor BSP MLIS College of Pharmacy, Dalhousie University, Halifax, NS, CanadaCorrespondence: B. Hill-Taylor, College of Pharmacy, Dalhousie University, 5968 College Street, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2. Tel.: +1 902 494 2378; fax: +1 902 494 1396; e-mail: murpp@eastlink.caSearch for more papers by this authorI. Sketris Pharm D MPA(HAS), I. Sketris Pharm D MPA(HAS) College of Pharmacy, Dalhousie University, Halifax, NS, Canada Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, CanadaSearch for more papers by this authorJ. Hayden PhD, J. Hayden PhD Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada Nova Scotia Cochrane Resource Centre, Dalhousie University, Halifax, NS, CanadaSearch for more papers by this authorS. Byrne PhD MPSI, S. Byrne PhD MPSI Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, Cork, IrelandSearch for more papers by this authorD. O'Sullivan MPharm MPSI, D. O'Sullivan MPharm MPSI Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, Cork, IrelandSearch for more papers by this authorR. Christie BSc(Pharm), R. Christie BSc(Pharm) Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, CanadaSearch for more papers by this author First published: 02 April 2013 https://doi.org/10.1111/jcpt.12059Citations: 231AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Summary What is known and Objective Potentially inappropriate prescribing (PIP) has significant clinical, humanistic and economic impacts. Identifying PIP in older adults may reduce their burden of adverse drug events. Tools with explicit criteria are being developed to screen for PIP in this population. These tools vary in their ability to identify PIP in specific care settings and jurisdictions due to such factors as local prescribing practices and formularies. One promising set of screening tools are the STOPP (Screening Tool of Older Person's potentially inappropriate Prescriptions) and START (Screening Tool of Alert doctors to the Right Treatment) criteria. We conducted a systematic review of research studies that describe the application of the STOPP/START criteria and examined the evidence of the impact of STOPP/START on clinical, humanistic and economic outcomes in older adults. Methods We performed a systematic review of studies from relevant biomedical databases and grey literature sources published from January 2007 to January 2012. We searched citation and reference lists and contacted content experts to identify additional studies. Two authors independently selected studies using a predefined protocol. We did not restrict selection to particular study designs; however, non-English studies were excluded during the selection process. Independent extraction of articles by two authors used predefined data fields. For randomized controlled trials and observational studies comparing STOPP/START to other explicit criteria, we assessed risk of bias using an adapted tool. Results and Discussion We included 13 studies: a single randomized controlled trial and 12 observational studies. We performed a descriptive analysis as heterogeneity of study populations, interventions and study design precluded meta-analysis. All observational studies reported the prevalence of PIP; however, the application of the criteria was not consistent across all studies. Seven of the observational studies compared STOPP/START with other explicit criteria. The STOPP/START criteria were reported to be more sensitive than the more-frequently-cited Beers criteria in six studies, but less sensitive than a set of criteria developed in Australia. The STOPP criteria identified more medications associated with adverse drug events than the 2002 version of the Beers criteria. Patients with PIP, as identified by STOPP, had an 85% increased risk of adverse drug events in one study (OR = 1·85, 95% CI: 1·51–2·26; P < 0·001). There was limited evidence that the application of STOPP/START criteria optimized prescribing. Research involving the application of STOPP/START on the impact on the quality of life was not found. The direct costs of PIP were documented in three studies from Ireland, but more extensive analyses on the economic impact or studies from other jurisdictions were not found. What is new and Conclusion The STOPP/START criteria have been used to review the medication profiles of community-dwelling, acute care and long-term care older patients in Europe, Asia and North America. Observational studies have reported the prevalence and predictors of PIP. The STOPP/START criteria appear to be more sensitive than the 2002 version of the Beers criteria. Limited evidence was found related to the clinical and economic impact of the STOPP/START criteria. What is Known and Objective The health care of older adults presents significant challenges to patients, caregivers, healthcare providers and healthcare systems. Many factors contribute to this challenge, including (i) the increasing size of the demographic1, 2; (ii) the biological process of ageing, which may lead to increased sensitivity to drug effects due to changes in body composition (e.g. altered distribution volumes and altered permeability of the blood–brain barrier), reduced ability to eliminate drugs (e.g. changes in liver metabolism and renal capacity), malnutrition and cachexia3, 4; (iii) the increased potential for and impact of comorbidities, multiple conditions and polypharmacy5; and (iv) limited availability and access to appropriate evidence regarding drug effectiveness and safety in older and frail patients (i.e. studies have not been carried out, not synthesized or not in the public domain).6-8 Older adults exert a significant demand, due to disease burden on healthcare resources.9-11 Potentially inappropriate prescribing (PIP) is reported to be highly prevalent in this age group and has been associated with adverse drug events (ADEs) leading to hospitalization and death.12 In the United States, from 2007 to 2009, ADEs were responsible for approximately 100 000 emergency hospitalizations of adults 65 years and older.13 In Canada, the cost of ADE-related emergency department visits and subsequent hospitalizations for adults aged 66 and older was estimated to be $35·7 million per year in 2007.14 Inappropriate prescribing occurs when the risks associated with prescribing a medication outweigh the potential benefit of the medication in a particular patient. Various measures of PIP have been developed. For example, PIP may occur when medications are prescribed: (i) with no clear evidence-based indication; (ii) in higher doses or for a longer period than necessary; (iii) in combination with other drugs from the same drug class; (iv) in combination with other drugs that may lead to drug–drug or drug–illness interactions; (v) for patients who are susceptible to certain ADEs, for example, benzodiazepines in patients with a history of falls; and (vi) instead of a more cost-effective medication that is equally or more therapeutically effective.15 Potentially inappropriate prescribing may also occur when a patient does not receive a medication indicated for the treatment or prevention of a disease or condition.16 This may occur due to ageism, economic concerns, fear of adverse events or lack of prescribing knowledge.4, 17, 18 Early detection of PIP may prevent ADEs and improve geriatric care.6, 19 PIP prevalence can often prove to be a useful indicator of prescribing quality.7 In addition, evidence indicates that discontinuing inappropriate medications may improve subjective quality of life in older adults.20 In 1991, Mark Beers and colleagues created a list of drugs that were considered to be inappropriate for use in older adults in long-term care facilities.21 The Beers criteria have been revised and updated on a number of occasions since their development, with the most recent iteration being published in 2012.22-24 Although considered a cornerstone to the optimization of pharmaceutical care in older adults in the United States,25 older versions have been criticized for their (i) limited transferability/applicability outside of the United States; (ii) failure to address a number of common PIPs (e.g. drug–drug and drug–disease interactions); (iii) failure to include criteria relating to potential underprescribing; and (iv) lack of user-friendly organization (e.g. by physiological systems).15, 26, 27 As a result, at least 13 other explicit screening tools have been developed, many of which are specific to the country for which they were developed.28-37 Many different clinicians including pharmacists, geriatricians, nurse practitioners, internists and researchers have used these different sets of explicit criteria to assess PIP across different healthcare settings and jurisdictions.19, 27-41 The 2012 iteration of the Beers criteria has addressed some, but not all of the criticisms listed above.24 STOPP (Screening Tool of Older Person's potentially inappropriate Prescriptions) and START (Screening Tool to Alert doctors to the Right Treatment) are evidence-based sets of criteria, which were developed in Ireland using a modified Delphi process that involved 18 experts in geriatric pharmacotherapy from across the United Kingdom and Ireland.42, 43 STOPP consists of 65 criteria that help researchers and healthcare personnel systematically identify potentially inappropriate medications (PIMs). START, consisting of 22 criteria, identifies potential prescribing omissions (PPOs). The STOPP and START criteria may offer advantages over the Beers criteria and other screening tools. The criteria are organized according to the physiological systems to which each relate, thereby enhancing their useability.42, 43 In addition, rather than listing specific medications, which make transferability to different countries with different formularies more difficult, STOPP and START criteria refer to classes of medications. To date, the STOPP/START criteria have been used by a variety of researchers across a number of healthcare settings in a number of different jurisdictions in Europe,44-46 Taiwan47 and the United States.48 There is a demonstrated research momentum towards the STOPP/START criteria, especially in the European Union. Our initial search on this subject found 17 records published in 2007–2009, 16 published in 2010, and 44 in 2011. In 2010, Levy and colleagues indicated that the STOPP/START criteria may be a good choice as an universal explicit criteria.41 In 2012, a group of researchers and clinicians chose the STOPP/START criteria as the ‘most appropriate’ choice for evaluating the prescribing of patients with multiple chronic conditions in Spain.49 These tools have been proposed as the most appropriate for assessing PIP in the Netherlands.50 The European Union Geriatric Medicine Society (EUGMS) have also recently announced their support for the STOPP/START criteria.51 To our knowledge, no systematic review of the application and impact of STOPP/START has been undertaken. Although there is research establishing a relationship between PIP identified by STOPP/START criteria and other screening tools and adverse drug reactions, hospitalization rates and increased health services costs, this research is still in its infancy, and further study is needed to establish the full extent and true impact of this relationship.37, 52 This review informs researchers, clinicians and policy makers about the quality and extent of evidence relating to the STOPP/START criteria. Specifically, it provides an overview of studies documenting STOPP- and START-identified PIP prevalence and outcomes in different healthcare settings and jurisdictions. In addition, with the development of electronic health records, administrative databases and computer-assisted order entry, integration of a reliable and validated set of criteria into these systems offers the potential for optimization of care with reasonable and sustainable expense and effort. Therefore, a systematic review of this nature is of particular value at this time. Our objective was to conduct a systematic review of research studies to describe the application of STOPP/START criteria and to examine the evidence of the impact of STOPP/START on clinical, humanistic and economic outcomes in older adults. Methods Identification of studies Methods of the search strategy and inclusion criteria were specified in advance and documented in a protocol, which is available upon request. The methods of analyses were not predetermined due to the anticipated heterogeneity of the results. Randomized trials and non-randomized study designs investigating the impact and application of the STOPP/START criteria in adults aged 65 years and older were included. No language or publication restrictions were used in the original search; however, non-English studies and unpublished data were not included in the synthesis. Studies were eligible if published or accepted for publication between January 2007 and January 2012; studies only published as abstracts were excluded. The eligibility criteria allowed access to all studies dated from the development of the criteria through to January 2012. Studies that used modified or a truncated list of STOPP/START criteria were considered for inclusion. Data from studies that involved the application of STOPP/START to measure the prevalence of intervene in, or report predictors of, PIP were included. Indicators of the clinical and humanistic impact of the use of STOPP/START criteria on the patient and healthcare system (ADEs, physician visits, emergency department visits, hospitalization and quality of life) were developed by consensus and included in the protocol. Data demonstrating the economic impact of STOPP/START on PIP in older patients were also included. Biomedical databases and grey literature sources were systematically searched for published studies, prepublication presentations and abstracts. Keywords ‘STOPP and START’, ‘STOPP Criteria’ and ‘START Criteria’ with the limit ‘Aged 65+ years’ (January 2007 to January 2012) were applied to Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE), PubMed, EMBASE, CINAHL, ISI Web of Science, International Pharmaceutical Abstracts, Google Scholar, TRIP Database, ClinicalTrials.gov, metaRegister of Controlled Trials (mRCT), ProQuest Dissertation and Theses Database, and Index to Theses in Great Britain and Ireland. References from all included studies and systematic reviews of explicit criteria, which included STOPP/START, were searched. Citing articles, as identified by ISI Web of Science and Google Scholar, were examined. Experts in the field and authors of prepublication presentations, abstracts and registered clinical trials were contacted to identify studies that were in the process of publication. Authors of articles not available in English were contacted to see whether English translations were available. The search was conducted in December 2011 and was followed with RSS feeds from MEDLINE (PubMed) and EMBASE until January 2012 by one author (BHT). A title and abstract review of studies was performed independently in an unblinded standardized manner by two authors (DOS & BHT). Letters to the editor, commentaries and review articles were excluded. The full text of potentially relevant studies not eliminated by title and abstract was reviewed independently by both reviewers. Consensus was easily reached in the selection of included studies, and the two authors independently agreed to choose 13 of 77 citations. Data extraction A data extraction form was designed using Google Docs software (form available on request). The form was pilot-tested on two included studies and revised. Two authors independently performed the data extraction (DOS & BHT). One author checked extracted data for agreement (BHT). There were no disagreements in data extraction, beyond clarification of definitions and criteria. Information extracted included the following: (i) study design including methods and units of randomization, prospective vs. retrospective, characteristics of control group, data sources and time period; (ii) intervention details such as the professional designation of the health professional involved, criteria applied and a brief description; (iii) description of the location and setting, numbers and characteristics of participants including age, sex and numbers of medications prescribed; (iv) type of outcome measures reported; (v) results and key conclusions by the authors; and (vi) sources of funding. Risk of bias assessment Two authors (DOS, RC) independently assessed the risk of bias in eight of the included articles – the randomized controlled trial (RCT) and observational studies that involved a comparison with another criteria.17, 46, 52-57 The assessment was made using a modified quality assessment scale initially designed for studies of prognostic factors (QUIPS)58 and was based on six domains: study participation, data collection, application of the STOPP/START criteria, outcome measurement, study confounding, and statistical analysis and presentation. Each domain contained a checklist of three to nine components, which were used to render a score of low, moderate or high risk of bias for the entire domain. After independent review, both authors met to reconcile discrepancies in scoring each domain. Prior to discussion, reviewers initially agreed on 23 of 49 domain ratings (48%); 94% of domains were rated no more than one category apart with discrepancies commonly due to differing opinions on the potential severity of the possible bias. Consensus was easily reached in all assessments. We did not assess the risk of bias of cross-sectional studies that described the prevalence of PIPs using the STOPP/START criteria. Heterogeneity of study populations, interventions and study design precluded meta-analysis. Descriptive analysis was performed. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) has been used in reporting this review.59 Results and Discussion Search results A search of relevant biomedical databases provided a total of 133 records: other sources including Google Scholar identified 31 records. Duplicates and records that did not meet the inclusion criteria were removed, leaving a total of 13 records: 12 observational studies17, 42, 44, 46, 52, 54, 55, 57 and a RCT.55 (Fig. 1) Figure 1Open in figure viewerPowerPoint Flow diagram. Study characteristics Clinicians and researchers from the Republic of Ireland and Northern Ireland, including members of the original development team of the criteria, published eight of the included studies.17, 42-44, 52, 54, 55, 57 Gallagher was the lead author in both the only international comparative study examining PIP across six European jurisdictions46 and the only RCT55 that examined the effect that the application of the STOPP/START criteria could have on prescribing appropriateness and patient-related outcomes. Five other studies used the STOPP and/or the START criteria to evaluate PIP in older adults in Spain53, 56, the United States48 and Taiwan.47 Retrospective data were used in five of the observational studies.44, 47, 48, 53, 60 This review includes the application of STOPP/START to the health records of approximately 344 957 adults, all aged 65 years and older. (Table 1) The exact number of patients included is impossible to determine due to potential for crossover between the older patients included in the Cork-based hospital or long-term care studies and the database study.17, 42, 44, 46, 52, 54, 55, 57 The majority of participants were from the Northern Ireland and the Republic of Ireland (99·5%), reflecting both the large size of the study performed on the pharmacy database44 and the smaller sizes of the other studies with non-Irish participants.46-48, 53, 56, 60 The mean age of participants ranged from 74·957 to 86·9 years60; however, some studies did not report mean age.44, 46, 54, 55 The majority of participants were female (from 53%55 to 80%56, 60), except in two studies performed in veterans’ hospitals in Taiwan and the United States where 26%47 and 1%48 of the study population were female, respectively. The mean number of medications prescribed per participant ranged from 557 to 12·948 in ten studies.17, 42, 47, 48, 52, 54-56, 60 Table 1. Characteristics of studies included in systematic review of STOPP/START criteria Source Study design Criteria applied Criteria applied by Compared criteria Population Country Data source # Age Sex Mean no. Rx/Patient Barry et al. (2007)42 Observational – prospective Full START Physician None Community-dwelling patients being admitted to acute care Ireland Electronic database and paper-based medical records 600 Mean (range): 77·9 ± 6·8 56% Female Mean: 5·4 Gallagher & O'Mahony (2008)54 Observational – prospective Full STOPP Physician Beers (2002)23 Community-dwelling patients being admitted to acute care Ireland Medical records from community healthcare and acute care facility 715 Median (range): 77 (65–94) 54% Female Mean (range): 6·2 (0–21) Ryan et al. (2009)57 Observational – cross-sectional Full STOPP and full START Research pharmacist Beers (2002)23 Community-dwelling patients Ireland Electronic and paper-based medical records 1329 Mean: 74·9 ± 6·4 (65–97) 61% Female Mean (range): 5·0 (1–19) Pyszka et al. (2010)48 Observational – cohort Modified STOPP Full START Clinical Pharmacist None Community-dwelling patients being admitted to acute care and discharged back to community care United States Electronic medical records 111 Mean: 78·4 ± 5·4 (70+) 1% Female Mean: 12·9 (on Admission); 14·2 (discharge); 14·1 (Follow-up) Conejos et al. (2010)53 Observational – prospective (hospital geriatric clinic) and cross-sectional (community-dwelling and long-term care) Modified STOPP Modified START Independent observer Beers (2002)23 Community-dwelling, hospital geriatric clinic, and long-term care patients Spain Electronic medical records and pharmacy claims database 150 Mean: 81·6 ± 6·3 (69+) 62% Female Not reported Cahir et al. (2010)44 Observational – cross-sectional Partial STOPP Database None Community-dwelling patients Ireland Electronic pharmacy claims database 338801 Not reported (70+) 57% Female Not reported Liu et al. (2011)47 Observational – cross-sectional Full STOPP and full START Physician None Acute care patients at discharge Taiwan Medical records from an acute care facility 520 Mean: 79·2 ± 6·7 (65+) 26% Female 6·6 ± 3·2 Gallagher et al. (2011)55 RCT Full STOPP and full START Physician Medication Appropriateness Index and Assessment of Underutilization index Community-dwelling patients being admitted to acute care and discharged Ireland Patient or caregiver, community care and hospital medical records 382 Median (range), control 77 (65+); intervention 74·5 (65+) 53% Female Control: 8·0, intervention: 7·4 Gallagher et al. (2011)46 Observational – prospective Full STOPP and full START Consultants and senor residents in the field of geriatric medicine Beers (2002)23 Community-dwelling patients admitted to multiple acute care facilities in 6 different countries Switzerland, Ireland, Spain, Belgium, Italy, Czech Republic Patient or caregiver, community care and hospital medical records 900 Median (range): 82 (65+) 61% Female Not reported Byrne et al. (2011)17 Observational – cross-sectional Full STOPP Research pharmacist Beers (2002)23 Long-term-care-dwelling patients in multiple facilities Ireland Electronic database and paper-based medical records 630 Mean (range): 83·4 ± 7·1 (65–99) 75% Female 7·8 García-Gollarte et al. (2011)56 Observational – cross-sectional Full STOPP and full START Physician with experience in the care of older persons Australian (Basger et al.)28 Community-dwelling, hospital or long-term care patients being admitted to multiple long-term care facilities Spain Electronic medical records 100 Mean (range): 84·7 ± 7·5 (65+) 80% Female 6·5 ± 2·9 Hamilton et al. (2011)52 Observational – prospective Full STOPP Not specified Beers (2002)23 Community-dwelling, hospital or long-term care patients being admitted to acute care facility Ireland Patient or caregiver, community care and hospital medical records 600 Range: 65+ 60% Female 7·5 Parsons et al. (2012)60 Observational – cross-sectional Partial STOPP Database None Long-term-care patients living with dementia in multiple facilities Britain Medication Administration Records 119 Mean (range): 86·9 ± 6·7 (69–106) 80% Female 8 ± 3·4 STOPP, screening tool of older person's prescriptions; START, screening tool to alert doctors to right treatment. Rx prescriptions. The majority of participants in the included studies were community dwelling (99·5%), who were assessed in either the primary care setting (community dwelling)44, 53, 57 or while transitioning to a secondary care setting42, 46, 48, 52, 54, 55, 57; 0·5% of participants were divided between secondary care47, 53 and long-term care17, 53, 56, 60 (570 and 799 patients, respectively). Five of the studies, including the RCT, applied the full STOPP and START criteria to participant's medication profiles,46, 47, 55-57 three studies applied the STOPP criteria,17, 52, 54 and one study applied the START criteria.42 Four research teams used modified versions of the criteria.44, 48, 53, 60 Pyszka and colleagues noted that ‘Medications without an appropriate diagnosis were the most common type of STOPP criteria that was identified’,48 although this is not one of the original STOPP criteria.43 Conejos and colleagues53 used the Spanish version of the criteria in their study.61 Two of the studies applied a shortened/condensed version of the STOPP criteria to electronic databases without diagnoses or laboratory data being available.44, 60 The criteria selected for use in these studies were chosen ‘on a consensus basis by an expert panel of five members in geriatric pharmacotherapy, clinical pharmacology, pharmacoepidemiology and academic general practice’.44 Cahir states that their research team applied 30 of the STOPP criteria.44 Parsons states that their team used 31 STOPP criteria based on the list developed by Cahir and colleagues.60 Prevalence of potentially inappropriate prescribing The observational studies reported the prevalence of PIP.17, 42, 44, 46-48, 52-54, 56, 57, 60 The prevalence of patients with at least one instance of PIP identified by the STOPP criteria ranged from 21·4%57 to 79%56; however, interpretation of this range should be made with caution due to the heterogeneity in both sample population and study design between the different studies. The observational studies also outlined the most commonly encountered instances of prescribing potentially inappropriate medications17, 42, 44, 46-48, 52-54, 56, 57, 60: (i) PPI for peptic ulcer disease at full therapeutic dosage for > 8 weeks17, 44, 46, 52, 56, 57, 60; (ii) long-term (i.e. >1 month), long-acting benzodiazepines and benzodiazepines with long-acting metabolites17, 44, 46, 47, 52-54, 56, 57; and (iii) long-term (i.e. >1 month) neuroleptics as long-term hypnotics.46, 47, 56, 60 The START criteria identified at least one instance of PPO in 22·7%57 to 74%56 of patients. Seven studies outlined frequently encountered PPO instances42, 46-48, 53, 56, 57: (i) calcium an
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