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National electronic Library for Medicines Medicines Management Overview September 2011 DRUG-RELATED PROBLEMS CAUSING HOSPITALISATION AN UPDATE Contents Summary Key findings Annotated bibliography 1 2 3 Produced for the National electronic Library for Medicines by: Tom Burnham, Information Specialist, London and South East Medicines Information Service, Guy’s Hospital, London SE1 9RT Tel: 020 7188 5026 [email protected] Summary One objective of the QIPP programme is to minimise avoidable admissions to hospital, which are not only responsible for a large cost burden, but also have an impact on patient safety. There is general agreement that drug-related problems are responsible for an appreciable proportion of hospital admissions and that a substantial proportion of these problems are potentially preventable. Drug-related problems include not only adverse drug reactions (ADRs) in the strict sense, but also other types of adverse drug events, such as failure by the patient to adhere to prescribed treatment, various types of medication errors, inappropriate treatment, failure to prescribe indicated treatment, and drug interactions. This report summarises recent publications (mostly in 2010 and 2011) which attempt to quantify the contribution of drug-related problems to the overall level of patient admissions to hospital. It does not consider studies referring only to a specific medication or a specific medical condition. Key Findings A review from the School of Pharmacy and Pharmaceutical Sciences, University of Manchester1 found that the prevalence of ADRs in patients admitted to hospital was a median of 5.3%, with a somewhat lower incidence in children and somewhat higher in elderly patients. However, the range varied widely between individual studies (0.16% to 15.7%). The authors admit that there was considerable variation in the definitions used for ADRs. A larger review2 found a range for prevalence of medication-related hospitalisation from 0.1% to 54% but draws attention to a number of methodological problems which make it difficult to pool data from different sources. An earlier review3 including 25 studies had also encountered problems of definition, but concluded that a median of 5.8% of admissions to medical departments were caused by ADRs. A study using the Hospital Episode Statistics database for all English hospital admissions (1999-2008)4 found that ADR-associated admissions represented 0.9% of all hospital admissions for the period, considerably lower than the findings of the above reviews, or of most individual studies. Similar results were obtained for all acute hospital admissions in Spain in 20012006 (1.69% due to ADRs)5 while in the Netherlands a figure of 0.44% was found for ADR-related admissions in 2000-20056. In this case, there was a small but significant difference in the rates between men (0.41%) and women (0.47%). Higher rates have been found in studies using data for individual hospitals or groups of hospitals. For example, 4% of unplanned admissions to the main wards of the Royal Liverpool Children’s Hospital over a 2-week period were attributed to ADRs7. Two studies in emergency units in Canada8,9 found figures of 2.4% and 4.7% respectively (and the second study investigated whether doctors always recorded presentations due to ADRs as medication related). A study in Germany10 found that 3.25% of a sample of some 57,000 hospitalisations were caused by serious outpatient ADRs, and presented a cost analysis. Similarly, the HARM study in the Netherlands11 found that 5.6% of unplanned admissions to 21 hospitals over 40 days were medication related, and the authors later presented a cost analysis12 showing average costs of Euro 6009 for one, potentially preventable, medication-related hospital admission for all ages. In line with a generally higher incidence of ADRs in older patients, an Italian study found that 5.6% of admissions to a geriatric unit were caused by definite or probable ADRs13. A study in Barcelona, Spain, found that medication-related problems (not just ADRs) were wholly or partially involved in as many as 12% of admissions14. Davies et al.15 found that 20.8% of emergency readmissions within one year were due to ADRs, of which more than half were considered avoidable. This adds interest to the findings of an analysis of integrated medicines management of elderly inpatients in Lund, Sweden, by a multidisciplinary team including a clinical pharmacist16, which was found to reduce the number of drug-related emergency re-admissions. Finally, a study of the causes of preventable drug-related admissions (PDRAs) to a hospital in Nottingham17 found that they were complex and multi-faceted, and concluded that a solution would need to address human factors in addition to technical aspects. Annotated Bibliography 1) Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies C Kongkaew, PR Noyce, DM Ashcroft Annals of Pharmacotherapy, Jul-Aug 2008, vol. 42, no. 7-8, p. 1017-1025 25 studies were identified including 106,586 patients who were hospitalised; 2143 of these patients had experienced ADRs. The prevalence rates of ADRs ranged from 0.16% to 15.7%, with an overall median of 5.3%. Higher rates were found in elderly patients who are likely to be receiving multiple medications for long-term illnesses. The methods used to detect ADRs are also likely to explain much of the variation in the reported ADR prevalence rates between different studies. (54 refs.) http://www.theannals.com/content/42/7/1017.abstract 2) The relationship between study characteristics and the prevalence of medication-related hospitalizations: a literature review and novel analysis AJ Leendertse, D Visser, ACG Egberts, PMLA van den Bemt Drug Safety Mar 2010;33(3):233-244 Background: Studies on medication-related hospitalisations differ in study setting, studied population, outcome, and method of data collection. Thus, extrapolations based on a metaanalysis of unselected studies may be biased. Objective: To explore the influence of study characteristics on the prevalence of medicationrelated hospitalisations. Methods: After a structured literature search, the retrieved studies were categorised based on the following aspects: (i) study setting (e.g. all hospital admissions vs only acute hospital admissions); (ii) study population (e.g. an entire hospital, study ward(s), selected population and/or age group); (iii) outcome of medication-related problem (e.g. adverse drug reaction [ADR] vs adverse drug event [ADE]); (iv) method of data collection (e.g. medical chart review, spontaneous reporting or database research); and (v) continent in which the study took place (only for studies looking at all acute admissions). Authors then examined the relationship between these factors and reported prevalence of medication-related hospital admissions. Results: Ninety-five studies were analysed, with a range of reported prevalence of medication-related hospitalisations from 0.1% to 54%. Higher prevalences were found in the studies examining all hospital admissions than in the studies examining only acute hospital admissions. In addition, higher prevalences were found in the elderly population than in children. As would be expected, higher prevalences were also found in studies examining ADEs than in studies examining only ADRs. With respect to the method of data collection, medical chart screening resulted in higher prevalences of medication-related hospitalizations than database methods or spontaneous reporting. Combined studies in Europe show lower prevalences of medication-related hospital admissions than in other continents included in the study. Discussion: The reported prevalence of medication-related hospital admissions varies as a function of the setting (all admissions or only acute admissions), studied population (entire hospital, specific wards, selected population and age group), outcome (ADR/ADE), the method of data collection and the continent in which the study is performed. Conclusion: Extrapolation using national hospital admission data and the prevalence identified by pooling international studies should be carried out with great caution. (103 refs.) http://adisonline.com/drugsafety/Abstract/2010/33030/The_Relationship_Between_Study_Ch aracteristics_and.5.aspx 3) Adverse drug reaction monitoring - cost and benefit considerations. Part I: Frequency of adverse drug reactions causing hospital admissions N Muehlberger, S Schneeweiss, J Hasford Pharmacoepidemiology and Drug Safety, 1997, vol. 6, no. Suppl.3, p. S71-S77 Paper presented at the European Society of Pharmacovigilance 4th Annual Meeting, Lisbon, Portugal, 1996. The objective of this paper is to summarise all original work on ADR frequencies at hospital admission and to come up with a valid estimate for the actual frequency of ADR-related hospital admissions. Additionally, established concepts of ADR monitoring were compared with respect to their utility for drug safety monitoring and pharmacoepidemiological research. 25 studies from the past 25 years were reviewed. Analysing the effect of methodological characteristics showed that variation of reported ADR frequency mainly depends on differing study bases and the concepts of ADR monitoring. Investigations that thoroughly screened all members of the study population for the presence of adverse drug reactions (comprehensive ADR monitoring) generally yielded highest ADR proportions. Studies that concentrated screening on selected high-risk patients (preselective ADR monitoring) and those applying spontaneous or intensified spontaneous reporting detected lower ADR proportions (2.9% and 2.5%). The ADR proportion among admissions to departments of internal medicine was higher than among mixed hospital populations including surgical patients. In conclusion 4.2-6.0% (lower and upper quartile) and in median 5.8% of all admissions to medical departments are caused by adverse drug reactions. A 2-step preselective ADR monitoring appears to be appropriate and efficient for both signal generation and signal validation as compared to spontaneous reporting and comprehensive monitoring. In conclusion, adverse drug reactions are a common cause of hospital admissions. As hospital care is expensive, attempts to prevent ADR and thus hospital admission need active encouragement. http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1099-1557(199710)6:3%2B%3CS71::AIDPDS282%3E3.0.CO;2-I/abstract 4) Ten-year trends in hospital admissions for adverse drug reactions in England 1999-2009 T-Y Wu, M-H Jen, A Bottle, M Molokhia, et al. Journal of the Royal Society of Medicine Jun 2010;103(6):239-250 Objectives: Adverse drug reactions (ADR) are an important cause of morbidity and mortality. We analysed trends in hospital admissions associated with ADRs in English hospitals between 1999 and 2008. Design: Data from the Hospital Episode Statistics database were examined for all English hospital admissions (1999-2008) with a primary or secondary diagnosis of an ADR recorded. Setting: All NHS (public) hospitals in England. Main outcome measures: The number of admissions and in-hospital mortality rate with a primary (codes including 'adverse drug reaction', 'drug-induced', 'due to drug', 'due to medicament' or 'drug allergy') or secondary diagnosis of ADR (ICD-10 Y40-59) were obtained and analysed. Further analysis for the year 2008-09 was performed with regard to age, gender, proportion older than 65 years and total bed-days. Results: Between 1999 and 2008, there were 557,978 ADR-associated admissions, representing 0.9% of total hospital admissions. Over this period the annual number of ADRs increased by 76.8% (from 42,453 to 75,076), and in-hospital mortality rate increased by 10% (from 4.3% to 4.7%). In 2008, there were 6,830,067 emergency admissions of which 75,076 (1.1%) were drug-related. Systemic agents were most commonly implicated (19.2%), followed by analgesics (13.3%) and cardiovascular drugs (12.9%). There has been a near 2fold increase in nephropathy and cardiovascular consequences secondary to drugs and a 6.8% fall in mental and behavioural disorders due to drugs. Conclusions: ADRs have a major impact on public health. Our data suggest the number of ADR admissions has increased at a greater rate than the increase in total hospital admissions; some of this may be due to improved diagnostic coding. However, in-hospital mortality due to ADR admissions also increased during the period. Our findings should prompt policymakers to implement further measures to reduce ADR incidence and their associated in-hospital mortality, and methods to improve the recording of ADRs. http://jrsm.rsmjournals.com/cgi/reprint/103/6/239 5) Trends of adverse drug reactions related-hospitalizations in Spain (2001-2006) P Carrasco-Garrido, A Lopez de Andres, V Hernandez-Barrera, A Gil de Miguel, R JimenezGarcia BMC Health Services Research 13 Oct 2010;10:287 Background: Adverse drug reactions (ADR) are a substantial cause of hospital admissions. We conducted a nationwide study to estimate the burden of hospital admissions for ADRs in Spain during a 6-year period (2001-06) along with the associated total health cost. Methods: Data were obtained from the national surveillance system for hospital data (Minimum Basic Data Set) maintained by the Ministry of Health and Consumer Affairs, and covering more than 95% of Spanish hospitals. From these admissions we selected all hospitalisations that were coded as drug-related (ICD-9-CM codes E), but intended forms of overdoses, errors in administration and therapeutics failure were excluded. The average number of hospitalisations per year, annual incidence of hospital admissions, average length of stay in the hospital and case-fatality rate, were calculated. Results: During the 2001-06 periods, the total number of hospitalised patients with ADR diagnosis was 350,835 subjects, 1.69% of all acute hospital admissions in Spain. The estimated incidence of admissions due to ADR decreased during the period 2001-06 (p less than 0.05). More than 5% of patients (n=19,734) died during an ADR-related hospitalisation. The drugs most commonly associated with ADR-related hospitalisation were antineoplastic and immunosuppressive drugs (n = 75,760), adrenal cortical steroids (n = 47,539), anticoagulants (n = 26,546) and antibiotics (n = 22,144). The costs generated by patients in our study increased by 19.05% between 2001 and 2006. Conclusions: Approximately 1.69% of all acute hospital admissions were associated with ADRs. The rates were much higher for elderly patients. The total cost of ADR-related hospitalisation to the Spanish health system is high and has increased between 2001 and 2006. ADRs are an important cause of admission, resulting in considerable use of national health system beds and a significant number of deaths. http://www.biomedcentral.com/content/pdf/1472-6963-10-287.pdf 6) Sex-related differences in hospital admissions attributed to adverse drug reactions in the Netherlands EM Rodenburg, BHC Stricker, LE Visser British Journal of Clinical Pharmacology Jan 2011;71(1):95-104 Aim: Adverse drug reactions (ADRs) are a major burden in health care, regularly leading to hospital admission, morbidity or death. Women tend to have a higher risk of adverse drug reactions with a 1.5 to 1.7-fold greater risk than men. Our primary aim was to study differences in ADR-related hospitalisations between the sexes. Methods: We conducted a nationwide study of all ADR-related hospitalisations in the period between 2000 and 2005 in the Netherlands, which were selected from all 9,287,162 hospital admissions in this period. ADR-drug group combinations with at least 50 admissions in one of the sexes were selected. Relative risks and confidence intervals were calculated with respect to total admissions and total prescriptions with men as reference. Results: In total, 0.41% of the 4,236,368 admissions in men (95% CI, 0.40, 0.42%) and 0.47% of the 5,050,794 admissions in women (95% CI, 0.46, 0.48%) were attributed to an ADR by medical specialists (57% of all ADR-related admissions were in women). Differences between the sexes in risk for ADR-related hospitalisation were found for antineoplastic and immunosuppressive drugs, antirheumatics, anticoagulants and salicylates, cardiovascular and neurological drugs, steroids and antibiotics. In certain drug categories, risks for hospitalisation changed after taking into account total drug prescriptions. Conclusions: In all different drug classes, significant differences exist between the sexes in ADR-related hospital admissions. Cardiovascular drugs account for the most pronounced differences between men and women. More research is needed to explain the clear sex differences in ADR-related hospital admissions. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2010.03811.x/pdf 7) Adverse drug reactions causing admission to a paediatric hospital: a pilot study RM Gallagher, KA Bird, JR Mason, M Peak, PR Williamson, AJ Nunn, MA Turner, M Pirmohamed, RL Smyth Journal of Clinical Pharmacy and Therapeutics Apr 2011;36(2):194-199 Objective: It is known that adverse drug reactions (ADRs) cause admission to hospital in adults and children. A recent adult study showed that ADRs are an important and frequent cause of hospital admission. The objective of this study is to develop methodology to ascertain the current burden of ADRs through a prospective analysis of all unplanned admissions to a paediatric hospital. Methods: Prospective observational study over a 2-week period at the Royal Liverpool Children's Hospital. Results and Discussion: There were 19 admissions to the main hospital wards related to an ADR, giving an estimated incidence of 4%, with the ADR directly leading to the admission in 71% of cases. There were no deaths attributable to ADR. 33% of the reactions were possibly avoidable. The drugs most commonly implicated in causing admissions were antineoplastic agents. The most common reactions were neutropenia, vomiting and diarrhoea. The health burden of ADRs in the paediatric population is likely to be significant. This pilot study will be used to inform a much larger prospective study providing more detailed evidence of the burden of ill-health from ADRs in children. This larger study will add to a body of research aiming to identify drug-related problems within children to aid paediatric pharmacovigilance. Conclusions: This study provides knowledge regarding the methodology to be used for a larger study investigating ADRs in children. The study will allow authors who wish to replicate the study in their own populations (internationally) to avoid some of the pitfalls in planning a large epidemiological study of paediatric ADRs. The study also provides an estimate of the incidence and problem of admissions caused by ADRs in a UK paediatric population. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2710.2010.01194.x/abstract 8) Adverse drug events in adult patients leading to emergency department visits KC Sikdar, R Alaghehbandan, D MacDonald, et al. Annals of Pharmacotherapy Apr 2010;44(4):641-649 Background: Adverse drug events (ADEs) occurring in the community and treated in emergency departments (EDs) have not been well studied. Objective: To determine the prevalence, severity, and preventability of ADEs in patients presenting at EDs in 2 university-affiliated tertiary care hospitals in the Canadian province of Newfoundland and Labrador. Methods: A retrospective chart review was conducted on a stratified random sample (n = 1458) of adults (18 years and older) who presented to EDs from 1 Jan to 31 Dec 2005. Prior to the chart review, the sample frame was developed by first eliminating visits that were clearly not the result of an ADE. The ED summary of each patient was initially reviewed by 2 trained reviewers in order to identify probable ADEs. All eligible charts were subsequently reviewed by a clinical team, consisting of 2 pharmacists and 2 ED physicians, to identify ADEs and determine their severity and preventability. Results: Of the 1458 patients presenting to the 2 EDs, 55 were determined to have an ADE or a possible ADE (PADE). After a sample-weight adjustment, the prevalence of ADEs/PADEs was found to be 2.4%. Prevalence increased with age (0.7%, 18–44 yr; 1.9%, 45–64 yr; 7.8%, 65 yr or older) and the mean age for patients with ADEs was higher than for those with no ADEs (69.9 vs 63.8 yr; p < 0.01). A higher number of comorbidities and medications was associated with drug-related visits. Approximately 29% of the ADEs/PADEs identified were considered to be preventable, with 42% requiring hospitalisation. Cardiovascular agents (37.4%) were the most common drug class associated with ADEs/PADEs. Conclusions: Adult ADE-related ED visits are frequent in Newfoundland and Labrador, and in many cases are preventable. Further efforts are needed to reduce the occurrence of preventable ADEs leading to ED visits. http://www.theannals.com/content/44/4/641.abstract 9) Do emergency physicians attribute drug-related emergency department visits to medication-related problems? CM Hohl, PJ Zed, JR Brubacher, RB Abu-Laban, PS Loewen, RA Purssell Annals of Emergency Medicine Jun 2010;55(6):493-502.e4 Study objective: Adverse drug events represent the most common cause of preventable nonsurgical adverse events in medicine but may remain undetected. Our objective is to determine the proportion of drug-related visits emergency physicians attribute to medicationrelated problems. Methods: This prospective observational study enrolled adults presenting to a tertiary care emergency department (ED) in Canada during 12 weeks. Drug-related visits were defined as ED visits caused by adverse drug events. The definition of adverse drug event was varied to examine both narrow and broad adverse drug event classification systems. Clinical pharmacists evaluated all patients for drug-related visits, using standardised assessment algorithms, and then followed patients until hospital discharge. Interrater agreement for the clinical pharmacist diagnosis of drug-related visit was assessed. Emergency physicians, blinded to the clinical pharmacist opinion, were interviewed at the end of each shift to determine whether they attributed the visit to a medication-related problem. An independent committee reviewed and adjudicated all cases in which the emergency physicians' and clinical pharmacists' assessments were discordant, or either the emergency physician or clinical pharmacist was uncertain. The primary outcome was the proportion of drug-related visits attributed to a medication-related problem by emergency physicians. Results: 944 patients were enrolled, of whom 44 patients received a diagnosis of the narrowest definition of an adverse drug event, an adverse drug reaction (4.7%; 95% CI, 3.5% to 6.2%). 27 of these were categorised as medication-related by emergency physicians (61.4%; 95% CI, 46.5% to 74.3%), 10 were categorised as uncertain (22.7%; 95% CI, 12.9% to 37.1%), and 7 categorised as a non-medication-related problem (15.9%; 95% CI, 8.0% to 29.5%). 78 patients (8.3%; 95% CI, 6.7% to 10.2%) received a diagnosis of an adverse drug event caused by an adverse drug reaction, a drug interaction, drug withdrawal, a medication error or noncompliance. Emergency physicians attributed 49 of these to a medication-related problem (62.8%; 95% CI, 51.7% to 72.7%), were uncertain about 15 (19.2%; 95% CI, 12.0% to 29.4%) and attributed 14 to non-medication-related problems (17.9%; 95% CI, 11.0% to 27.9%). 25 of 29 (86.2%; 95% CI, 69.3% to 94.4%) adverse drug events not considered medication related by emergency physicians were rated at least moderate in severity. Conclusions: A significant proportion of drug-related visits are not deemed medication related by emergency physicians. Drug-related visits not attributed to medication-related problems by emergency physicians may be missed in ongoing outpatient adverse drug event surveillance programmes intended to develop strategies to enhance drug safety. Further research is needed to determine what the effect may be of not attributing adverse drug events to medication-related problems. http://www.annemergmed.com/article/S0196-0644(09)01648-5/abstract 10) Adverse drug reactions in Germany: direct costs of internal medicine hospitalizations D Rottenkolber, S Schmiedl, M Rottenkolber, K Farker, et al. Pharmacoepidemiology and Drug Safety Jun 2011;20(6):626-634 Purpose: German hospital reimbursement modalities changed as a result of the introduction of Diagnosis Related Groups (DRG) in 2004. Therefore, no data on the direct costs of adverse drug reactions (ADRs) resulting in admissions to departments of internal medicine are available. The objective was to quantify the ADR-related economic burden (direct costs) of hospitalisations in internal medicine wards in Germany. Methods: Record-based study analysing the patient records of about 57,000 hospitalisations between 2006 and 2007 of the Network of Regional Pharmacovigilance Centers (Germany). All ADRs were evaluated by a team of experts in pharmacovigilance for severity, causality and preventability. The calculation of accurate person-related costs for ADRs relied on the German DRG system (G-DRG 2009). Descriptive and bootstrap statistical methods were applied for data analysis. Results: The incidence of hospitalisation due to at least 'possible' serious outpatient ADRs was estimated to be approximately 3.25%. Mean age of the 1834 patients was 71.0 years (SD 14.7). Most frequent ADRs were gastrointestinal haemorrhage (n = 336) and druginduced hypoglycaemia (n = 270). Average inpatient length-of-stay was 9.3 days (SD 7.1). Average treatment costs of a single ADR were estimated to be approximately Euro 2250. The total costs sum to Euro 434 million per year for Germany. Considering the proportion of preventable cases (20.1%), this equals a saving potential of Euro 87 million per year. Conclusions: Preventing ADRs is advisable in order to realise significant nationwide savings potential. Our cost estimates provide a reliable benchmark as they were calculated based on an intensified ADR surveillance and an accurate person-related cost allocation. http://onlinelibrary.wiley.com/doi/10.1002/pds.2118/abstract 11) Frequency of and risk factors for preventable medication-related hospital admissions in the Netherlands AJ Leendertse, ACG Egberts, LJ Stoker, PMLA van den Bemt (HARM Study Group) Archives of Internal Medicine, 22 Sep 2008, vol. 168, no. 17, p. 1890-1896 A prospective multicentre study was conducted to determine the frequency and patient outcomes of medication-related hospital admissions. A case-control design was used to determine risk factors for potentially preventable admissions. All unplanned admissions in 21 hospitals were assessed over 40 days. Controls were patients admitted for elective surgery. Cases and controls were followed up until hospital discharge. The frequency of medication-related hospital admissions, potential preventability and outcomes were assessed. For potentially preventable medication-related admissions, risk factors were identified in the case-control study. Almost 13,000 unplanned admissions were screened, of which 714 (5.6%) were medication related. Almost half (46.5%) of these admissions were potentially preventable, resulting in 332 case patients matched with 332 controls. Outcomes were favourable in most patients. The main determinants of preventable medication-related hospital admissions were impaired cognition (odds ratio, 11.9; 95% CI, 3.9-36.3), 4 or more comorbidities (8.1; 3.1-21.7), dependent living situation (3.0; 1.4-6.5), impaired renal function (2.6; 1.6-4.2), nonadherence to medication regimen (2.3; 1.4-3.8) and polypharmacy (2.7; 1.6-4.4). Concludes that adverse drug events are an important cause of hospitalisations, and almost half are potentially preventable. The identified risk factors provide a starting point for preventing medication-related hospital admissions. http://archinte.ama-assn.org/cgi/reprint/168/17/1890 12) Preventable hospital admissions related to medication (HARM): cost analysis of the HARM study AJ Leendertse, PMLA Van Den Bemt, JB Poolman, LJ Stoker, ACG Egberts, MJ Postma Value in Health Jan 2011;14(1):34-40 Objective: Adverse drug events (ADEs) can cause serious harm to patients and can lead to hospitalisation or even death. ADEs are a burden not only to patients and their relatives, but also to society and have the potential to involve high costs. To provide more information on the economic burden of preventable adverse drug events of outpatients, we performed a cost study on the data collected in the Hospital Admissions Related to Medication (HARM) study. In this study we examined the frequency, preventability and risk factors for hospital admissions related to medication. Methods: The average costs for a preventable medication-related hospital admission were calculated by summing the direct medical costs and the production losses of all the preventable admissions, taking into account the different types of hospitals (academic and general) and the age of the patients admitted. Results: The average medical costs for one preventable medication-related hospital admission were Euro 5461. The average production loss costs for one admission were Euro 1712 for a person younger than 65 years of age. Combining the medical costs and the costs of production losses resulted in average costs of Euro 6009 for one, potentially preventable, medication-related hospital admission for all ages. Conclusions: The costs of potentially preventable hospital admissions related to medication are considerable. Therefore, patient safety interventions to prevent ADEs and hospital admissions may be cost-effective or even cost saving. http://dx.doi.org/10.1016/j.jval.2010.10.024 13) Prevalence, clinical features and avoidability of adverse drug reactions as cause of admission to a geriatric unit: a prospective study of 1756 patients M Franceschi, C Scarcelli, V Niro, et al. Drug Safety, 2008, vol. 31, no. 6, p. 545-556 Background: Drug use increases with advancing age, and in older patients it is associated with an increase in adverse drug reactions (ADRs). ADRs are a primary cause of morbidity and mortality worldwide. Objectives: To evaluate the prevalence, clinical characteristics and avoidability of ADR-related hospital admissions in elderly patients. Methods: From November 2004 to December 2005, all patients aged greater than or equal to 65 years consecutively admitted to the Geriatric Unit of the Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo in Italy, were evaluated for enrolment in the study. ADRs were defined according to the WHO Adverse Reaction Terminology system. Drugs were classified according to Anatomical Therapeutic Chemical classification system. The Naranjo algorithm was used to evaluate the relationship between drug use and the ADR (definite, probable, possible or doubtful) and Hallas criteria were used to evaluate the avoidability of the ADR (definitely avoidable, possibly avoidable or unavoidable). All cases of a suspected ADR were discussed by a team trained in drug safety, including three geriatricians, one clinical pharmacologist and one pharmacist. Only cases of an ADR with an agreement greater than or equal to 80% were included. Results: Of the 1756 patients observed, 102 (5.8%, 42 males, 60 females, mean age 76.5 +/7.4 years, range 65-93 years) showed certain (6.8%) or probable (91.2%) ADR-related hospitalisation. Gastrointestinal disorders (48 patients, 47.1%); platelet, bleeding and clotting disorders (20 patients, 19.6%); and cardiovascular disorders (13 patients, 12.7%) were the most frequent ADRs. NSAIDs (23.5%), oral anticoagulants (20.6%), low-dose aspirin (acetylsalicylic acid) [13.7%] and digoxin (12.7%) were the drugs most frequently involved in ADRs. Of the ADRs, 45.1% were defined as definitely avoidable, 31.4% as possibly avoidable, 18.6% as unavoidable and 4.9% as unclassifiable. Of 78 patients with definitely or possibly avoidable ADRs, 17 patients (21.8%) had received an inappropriate prescription, 29 patients (37.2%) had not received a prescription for an effective gastroprotective drug concomitantly with NSAID or low-dose aspirin treatment and 32 patients (41%) were not monitored during drug treatment. Conclusions: In the elderly, almost 6% of hospitalizations are ADR related. Most of these ADRs are potentially avoidable. Strategies that reduce inappropriate prescriptions and monitoring errors, as well as improving active prevention of ADRs, are needed in elderly subjects. (49 refs.) http://adisonline.com/drugsafety/Abstract/2008/31060/Prevalence,_Clinical_Features_and_Av oidability_of.9.aspx 14) Medication-related problems which cause admission to hospital Original title: Problemas relacionados con la medicación que causan ingresos hospitalarios JM Sotoca Momblona, S Canivell Fuste, L Alemany Vilches, et al. Atencion Primaria, Mar 2009, vol. 41, no. 3, p. 141-146 Retrospective, observational and descriptive study at Les Corts Health Centre (HC), which is an urban health and teaching centre with a reference population of 32,318 inhabitants, including users of the les Corts HC, Barcelona, Spain, admitted to the Barcelona hospital from Aug 2005 to Jan 2006. A pharmacist and a family doctor analysed the clinical histories and determined whether or not there was a drug-related problem (DRP). A DRP was present in 13.4% of all hospital discharges, and DRPs were implicated (wholly or partially) in 12% of hospital admissions. It was considered that 57.3% of all the discharges with a DRP as the causing factor in the hospital admission were avoidable. Admissions due to DRP were mainly in internal medicine, cardiology and pneumology. The health problems that lead to hospital admission due to DRP are mainly circulatory (38.5%) and respiratory (11.5%). Concludes that the number of hospital admissions due to drug-related problems is avoidably high. http://www.elsevier.es/es/revistas/atencion-primaria-27/problemas-relacionados-medicacionque-causan-ingresos-hospitalarios-13135902-originales-2009 15) Emergency re-admissions to hospital due to adverse drug reactions within 1 year of the index admission EC Davies, CF Green, DR Mottram, PH Rowe, M Pirmohamed British Journal of Clinical Pharmacology Nov 2010;70(5):749-755 Aim: The proportion of re-admissions to hospital caused by ADRs is poorly documented in the UK. The aim of this study was to evaluate the impact of ADRs on re-admission to hospital after a period as an inpatient. Methods: 1000 patients consecutively admitted to 12 wards were included. All subsequent admissions for this cohort within 1 year of discharge from the index admission were retrospectively reviewed. Results: Of the 1000 patients included, 403 (40.3%; 95% CI, 39.1, 45.4%) were re-admitted within 1 year. Complete data were available for 290 (70.2%) re-admitted patients, with an ADR contributing to admission in 60 (20.8%; 95% CI, 16.4, 25.6%) patients. Presence of an ADR in the index admission did not predict for an ADR-related re-admission (10.5% vs 7.2%; P = 0.25) or re-admission overall (47.2% vs 41.2%; P = 0.15). The implicated drug was commenced in the index admission in 33/148 (22.3%) instances, with 37/148 (25%) commenced elsewhere since the index admission. Increasing age and an index admission in a medical ward were associated with a higher incidence of re-admission ADR. The most frequent causative drugs were anti-platelets and loop diuretics, with bleeding and renal impairment the most frequent ADRs. Over half (52/91, 57.1%) of the ADRs were judged to be definitely or possibly avoidable. Conclusions: One-fifth of patients re-admitted to hospital within 1 year of discharge from their index admission are re-admitted due to an ADR. Our data highlight drug and patient groups where interventions are needed to reduce the incidence of ADRs leading to readmission. Note: This paper was originally presented in the pharmacy practice session of the British Pharmaceutical Conference, Manchester, 6-7 Sep 2009. Paper No. 18. See: International Journal of Pharmacy Practice, Sep 2009, vol. 17, no. Suppl.2, p. B17-B18 http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2010.03751.x/abstract 16) Impact of the Lund Integrated Medicines Management (LIMM) model on medication appropriateness and drug-related hospital revisits LM Hellstrom, A Bondesson, P Hoglund, P Midlov, L Holmdahl, E Rickhag, T Eriksson European Journal of Clinical Pharmacology Jul 2011;67(7):741-752 Purpose: To examine the impact of systematic medication reconciliations upon hospital admission and of a medication review while in hospital on the number of inappropriate medications and unscheduled drug-related hospital revisits in elderly patients. Methods: This was a prospective, controlled study in 210 patients, aged 65 years or older, who were admitted to one of three internal medicine wards at a University Hospital in Sweden. Intervention patients received the complete Lund Integrated Medicines Management model (medication reconciliation upon admission and discharge, and medication review and monitoring) provided by a multi-professional team, including a clinical pharmacist. Control patients received standard care and medication reconciliation upon discharge. Blinded reviewers evaluated the appropriateness of the prescribing (using the Medication Appropriateness Index) on admission and discharge, and assessed the probability that a drug-related problem was the reason for any patient readmitted to hospital or visiting the emergency department within 3 months of discharge (using World Health Organisation causality criteria). Results: There was a greater decrease in the number of inappropriate drugs in the intervention group than in the control group for both the intention-to-treat population {51%; 95% CI, 43-58% vs 39%; 95% CI, 30-48%); p = 0.0446} and the per-protocol population (60%; 95% CI, 51-67% vs 44%; 95% CI; 34-52%; p = 0.0106). There were 6 revisits to hospital in the intervention group which were judged as 'possibly, probably or certainly drugrelated', compared with 12 in the control group (p = 0.0469). Conclusions: In this study, medication reconciliation and review provided by a clinical pharmacist in a multi-professional team significantly reduced the number of inappropriate drugs and unscheduled drug-related hospital revisits among elderly patients. http://www.springerlink.com/content/286840426v0pwq37/ 17) Causes of preventable drug-related hospital admissions: a qualitative study R Howard, A Avery, P Bissell Quality and Safety in Health Care, Apr 2008, vol. 17, no. 2, p. 109-116 The causes of preventable drug-related admissions (PDRAs) to hospital in Nottingham were examined in qualitative case studies using semi-structured interviews and medical record review; data were analysed using a framework derived from Reason's model of organisational accidents and cascade analysis. There were 62 participants, including 18 patients, 8 informal carers, 17 general practitioners, 12 community pharmacists, 3 practice nurses and 4 other members of healthcare staff, involved in events leading up to the patients' hospital admissions. PDRAs were found to be associated with problems at multiple stages in the medication use process, including prescribing, dispensing, administration, monitoring and help seeking. The main causes of these problems are communication failures (between patients and healthcare professionals and different groups of healthcare professionals) and knowledge gaps (about drugs and patients' medical and medication histories). The causes of PDRAs are similar irrespective of whether the hospital admission is associated with a prescribing, monitoring or patient adherence problem. Concludes that the causes of PDRAs are multifaceted and complex. Technical solutions to PDRAs will need to take account of this complexity and are unlikely to be sufficient on their own. Interventions targeting the human causes of PDRAs are also necessary - for example, improving methods of communication. http://qualitysafety.bmj.com/content/17/2/109.abstract