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ObjectivesTo describe the characteristics of clinical study report (CSR) documents published by the European Medicines Agency (EMA), and for included pivotal trials, to quantify the timeliness of access to trial results from CSRs compared with conventional published sources.DesignCross-sectional analysis of CSR documents published by the EMA from 2016 to 2018.MethodsCSR files and medication summary information were downloaded from the EMA. Individual trials in each submission were identified using document filenames. Number and length of documents and trials were determined. For pivotal trials, trial phase, dates of EMA document publication and matched journal and registry publications were obtained.ResultsThe EMA published documents on 142 medications that were submitted for regulatory drug approval. Submissions were for initial marketing authorisations in 64.1%. There was a median of 15 (IQR 5–46) documents, 5 (IQR 2–14) trials and 9629 (IQR 2711–26,673) pages per submission, and a median of 1 (IQR 1–4) document and 336 (IQR 21–1192) pages per trial. Of all identified pivotal trials, 60.9% were phase 3 and 18.5% were phase 1. Of 119 unique submissions to the EMA, 46.2% were supported by a single pivotal trial, with 13.4% based on a single pivotal phase 1 trial. No trial registry results were identified for 26.1% trials, no journal publications for 16.7% and 13.5% of trials had neither. EMA publication was the earliest information source for 5.8% of pivotal trials, available a median 523 days (IQR 363–882 days) before the earliest publication.ConclusionsThe EMA Clinical Data website contains lengthy clinical trial documents. Almost half of submissions to the EMA were based on single pivotal trials, many of which were phase 1 trials. CSRs were the only source and a timelier source of information for many trials. Access to unpublished trial information should be open and timely to support decision-making for patients.

ObjectivesInfectious mononucleosis (IM) is a clinical syndrome that is characterised by lymphadenopathy, fever and sore throat. Although generally not considered a serious illness, IM can lead to significant loss of time from school or work due to profound fatigue, or the development of chronic illness. This study aimed to derive and externally validate clinical prediction rules (CPRs) for IM caused by Epstein-Barr virus (EBV).DesignProspective cohort study.Setting and participants328 participants were recruited prospectively for the derivation cohort, from seven university-affiliated student health centres in Ireland. Participants were young adults (17–39 years old, mean age 20.6 years) with sore throat and one other additional symptom suggestive of IM. The validation cohort was a retrospective cohort of 1498 participants from a student health centre at the University of Georgia, USA.Main outcome measuresRegression analyses were used to develop four CPR models, internally validated in the derivation cohort. External validation was carried out in the geographically separate validation cohort.ResultsIn the derivation cohort, there were 328 participants, of whom 42 (12.8%) had a positive EBV serology test result. Of 1498 participants in the validation cohort, 243 (16.2%) had positive heterophile antibody tests for IM. Four alternative CPR models were developed and compared. There was moderate discrimination and good calibration for all models. The sparsest CPR included presence of enlarged/tender posterior cervical lymph nodes and presence of exudate on the pharynx. This model had moderate discrimination (area under the receiver operating characteristic curve (AUC): 0.70; 95% CI: 0.62–0.79) and good calibration. On external validation, this model demonstrated reasonable discrimination (AUC: 0.69; 95% CI: 0.67–0.72) and good calibration.ConclusionsThe alternative CPRs proposed can provide quantitative probability estimates of IM. Used in conjunction with serological testing for atypical lymphocytosis and immunoglobulin testing for viral capsid antigen, CPRs can enhance diagnostic decision-making for IM in community settings.

AimTo apply the drug utilisation 90% (DU90%) indicator (the number of unique drugs which makes up 90% of a doctor’s prescribing) to general practitioner (GP) practices prescribing in England to examine time trends, practice-level variation, and relationships with practice characteristics, prescribing costs and low-value prescribing.Study designRetrospective cohort study.SettingPrimary care in England, using publicly available prescribing data available from the National Health Service (NHS) digital platform for 2013–2017.ParticipantsAll general practices in England (n=7620).Primary and secondary outcome measuresThe DU90% was calculated on an annual basis for each practice based on medication British National Formulary codes. Low-value prescribing was defined using NHS 2017 guidance (including lidocaine plasters, liothyronine, omega-3 supplements). Descriptive statistics were generated per year on time trends and practice-level variation in the DU90%. Multilevel linear regression was used to examine the practice characteristics (relating to staff, patients and deprivation of the practice area).ResultsAmong 7620 practices, mean DU90% ranged from 130.0 to 131.0 across study years, and regarding variation between practices, there was a 1.4-fold difference between the lowest and highest 5% of practices. A range of medications were included in the DU90% of virtually all practices, including atorvastatin, levothyroxine, omeprazole, ramipril, amlodipine, simvastatin and aspirin. A higher volume of prescribing was associated with a lower DU90%, while having more patients, higher proportions of patients who are women or aged ≥45 years, higher number of GPs working in the practice and being in a more deprived area were associated with a higher DU90%. Practices in higher quintiles of DU90% had higher levels of low-priority prescribing and prescribing costs.ConclusionGP practices typically use 130 different medications in the bulk of their prescribing. Higher DU90% was associated with higher levels of low-priority prescribing and prescribing costs. Increasing use of personal formularies may enhance prescribing quality and reduce costs.

Bridget Concepta “Connie” Fahey (nee MacDonagh) was part of the Irish medical generation who migrated to the UK in the 1950s. She initially trained in anaesthesia in the north of England but after meeting and marrying her husband, Sean, she joined him in general practice in 1960, initially in Wolverhampton and then in Oldbury. Together they ran a busy general practice in a deprived area of Birmingham, during a period with significant …

Objectives Decision analysis study that incorporates patient preferences and probability estimates to investigate the impact of women’s preferences for referral or an alternative strategy of watchful waiting if faced with symptoms that could be due to breast cancer. Setting Community-based study. Participants Asymptomatic women aged 30–60 years. Interventions Participants were presented with 11 health scenarios that represent the possible consequences of symptomatic breast problems. Participants were asked the risk of death that they were willing to take in order to avoid the health scenario using the standard gamble utility method. This process was repeated for all 11 health scenarios. Formal decision analysis for the preferred individual decision was then estimated for each participant. Primary outcome measure The preferred diagnostic strategy was either watchful waiting or referral to a breast clinic. Sensitivity analysis was used to examine how each varied according to changes in the probabilities of the health scenarios. Results A total of 35 participants completed the interviews, with a median age 41 years (IQR 35–47 years). The majority of the study sample was employed (n=32, 91.4%), with a third-level (university) education (n=32, 91.4%) and with knowledge of someone with breast cancer (n=30, 85.7%). When individual preferences were accounted for, 25 (71.4%) patients preferred watchful waiting to referral for triple assessment as their preferred initial diagnostic strategy. Sensitivity analysis shows that referral for triple assessment becomes the dominant strategy at the upper probability estimate (18%) of breast cancer in the community. Conclusions Watchful waiting is an acceptable strategy for most women who present to their general practitioner (GP) with breast symptoms. These findings suggest that current referral guidelines should take more explicit account of women’s preferences in relation to their GPs initial management strategy.

Objective To determine whether hospital admission is associated with potentially inappropriate prescribing among older primary care patients (aged ≥65 years) and whether such prescribing was more likely after hospital admission than before. Design Longitudinal study of retrospectively extracted data from general practice records. Setting 44 general practices in Ireland in 2012-15. Participants Adults aged 65 years or over attending participating practices. Exposure Admission to hospital (any hospital admission versus none, and post-admission versus pre-admission). Main outcome measures Prevalence of potentially inappropriate prescribing assessed using 45 criteria from the Screening Tool for Older Persons’ Prescription (STOPP) version 2, analysed both as rate of distinct potentially inappropriate prescribing criteria met (stratified Cox regression) and binary presence of potentially inappropriate prescribing (logistic regression) and adjusted for patients’ characteristics. A sensitivity analysis used matching with propensity scores based on patients’ characteristics and diagnoses. Results Overall 38 229 patients were included, and during 2012 the mean age was 76.8 (SD 8.2) years and 43% (13 212) were male. Each year, 10.4-15.0% (3015/29 077 in 2015 to 4537/30 231 in 2014) of patients had at least one hospital admission. The overall prevalence of potentially inappropriate prescribing ranged from 45.3% (13 940/30 789) of patients in 2012 to 51.0% (14 823/29 077) in 2015. Independently of age, sex, number of prescription items, comorbidity, and health cover, hospital admission was associated with a higher rate of distinct potentially inappropriate prescribing criteria met; the adjusted hazard ratio for hospital admission was 1.24 (95% confidence interval 1.20 to 1.28). Among participants who were admitted to hospital, the likelihood of potentially inappropriate prescribing after admission was higher than before admission, independent of patients’ characteristics; the adjusted odds ratio for after hospital admission was 1.72 (1.63 to 1.84). Analysis of propensity score matched pairs showed a slight reduction in the hazard ratio for hospital admission to 1.22 (1.18 to 1.25). Conclusion Hospital admission was independently associated with potentially inappropriate prescribing. It is important to determine how hospital admission may affect appropriateness of prescribing for older people and how potential adverse consequences of admission can be minimised.

Objective To examine the impact of the Preferred Drugs Initiative (PDI), an Irish health policy aimed at enhancing evidence-based cost-effective prescribing, on prescribing trends and the cost of prescription medicines across seven medication classes. Design Retrospective repeated cross-sectional study spanning the years 2011–2016. Setting Health Service Executive Primary Care Reimbursement Service pharmacy claims data for General Medical Services (GMS) patients, approximately 40% of the Irish population. Participants Adults aged ≥18 years between 2011 and 2016 are eligible for the GMS scheme. Primary and secondary outcomes The percentage of PDI medications within each drug class per calendar quarter. Linear regression was used to model prescribing of the preferred drug within each medication group and to assess the impact of PDI guidelines and other relevant changes in prescribing practice. Savings in drug expenditure were estimated. Results Between 2011 and 2016, around a quarter (23.59%) of all medications were for single-agent drugs licensed in the seven drug classes. There was a small increase in the percentage of PDI drugs, increasing from 4.64% of all medications in 2011 to 4.76% in 2016 (P Conclusion There has been a small increase in prescribing of PDI drugs in response to prescribing guidelines, with inconsistent changes observed across therapeutic classes. These findings are relevant where health services are seeking to develop more active prescribing interventions aimed at changing prescribing practice.

Summarising the complex data generated by multiple cross sectional quality indicators in a way that patients, clinicians, managers and policymakers find useful is challenging. A common approach is aggregation to create summary measures such as star ratings and balanced score cards, but these may conceal the detail needed to focus quality improvement. We propose an alternative way of summarising and presenting multiple quality indicators, suitable for use for quality improvement and governance. This paper discusses (1) control charts for repeated measurements of single processes as used in industrial statistical process control (SPC); (2) control charts for cross sectional comparison of many institutions for a single quality indicator (rarely used in industry but commonly proposed for health care); and (3) small multiple graphics which combine control chart signal extraction with efficient graphical presentations for multiple indicators.

ObjectivesOlder adults are particularly vulnerable to adverse effects from concurrent alcohol and medication use. However, there is limited evidence regarding the prevalence of these adverse outcomes among older adults, and there is a lack of consensus regarding what constitutes an alcohol-interactive medicine. The objective of this study was to develop an explicit list of potentially serious alcohol–medication interactions for use in older adults.DesignFollowing a systematic review, review of drug compendia and clinical guidance documents, a two-round Delphi consensus method was conducted.SettingIreland and the United Kingdom (UK), primary care and hospital setting.ParticipantsThe Project Steering Group developed a list of potentially serious alcohol–medication interactions. The Delphi panel consisted of 19 healthcare professionals (general practitioners, geriatricians, hospital and community pharmacists, clinical pharmacologists and pharmacists, and physicians specialising in substance misuse).ResultsAn inventory of 52 potentially serious alcohol–medication interactions was developed by the Project Steering Group. British National Formulary black dot warnings (n=8) were included in the final criteria as they represent ‘potentially serious’ interactions. The remaining 44 criteria underwent a two-round Delphi process. In the first round, 13 criteria were accepted into the POtentially Serious Alcohol–Medication INteractions in Older adults (POSAMINO) criteria. Consensus was not reached on the remaining 31 criteria; 9 were removed and 8 additional criteria were included following a review of panellist comments. The remaining 30 criteria went to round 2, with 17 criteria reaching consensus, providing a final list of 38 potentially serious alcohol–medication interactions: central nervous system (n=15), cardiovascular system (n=9), endocrine system (n=5), musculoskeletal system (n=3), infections (n=3), malignant disease and immunosuppression (n=2), and respiratory system (n=1).ConclusionsPOSAMINO is the first set of explicit potentially serious alcohol–medication interactions for use in older adults. Following future validation studies, these criteria may allow for the risk stratification of older adults at the point of prescribing.

ObjectivesTo determine the prevalence of potentially inappropriate prescribing (PIP) in a cohort of community-dwelling middle-aged people and assess the relationship between PIP and emergency department (ED) visits, general practitioner (GP) visits and quality of life (QoL).DesignProspective cohort study.SettingThe Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort study of ageing.ParticipantsIndividuals aged 45–64 years recruited to TILDA who were eligible for the means-tested General Medical Services scheme and followed up after 2 years.ExposurePIP was determined in the 12 months preceding baseline and follow-up TILDA data collection by applying the PRescribing Optimally in Middle-aged People’s Treatments (PROMPT) criteria to participants’ medication dispensing data.Outcome measuresAt follow-up, the reported rates of ED and GP visits over 12 months (primary outcome) and the CASP-R12 (Control Autonomy Self-realisation Pleasure) measure of QoL (secondary outcome).AnalysisMultivariate negative binomial (rates) and linear regression (CASP-R12) models controlling for potential confounders.ResultsAt 2-year follow-up (n=808), PIP was detected in 42.9% by the PROMPT criteria. An ED visit was reported by 18.7% and 94.4% visited a GP (median 4 visits, IQR 2–6). Exposure to ≥2 PROMPT criteria was associated with higher rates of healthcare utilisation and lower QoL in unadjusted regression. However, in multivariate analysis, the associations between PIP and rates of ED visits (adjusted incidence rate ratio (IRR) 0.92, 95% CI 0.53 to 1.58), and GP visits (IRR 1.06, 95% CI 0.87 to 1.28), and CASP-R12 score (adjusted β coefficient 0.35, 95% CI −0.93 to 1.64) were not statistically significant. Numbers of medicines and comorbidities were associated with higher healthcare utilisation.ConclusionsAlthough PIP was prevalent in this study population, there was no evidence of a relationship with ED and GP visits and QoL. Further research should evaluate whether the PROMPT criteria are related to these and other adverse outcomes in the general middle-aged population.

Objectives Malignant melanoma has high morbidity and mortality rates. Early diagnosis improves prognosis. Clinical prediction rules (CPRs) can be used to stratify patients with symptoms of suspected malignant melanoma to improve early diagnosis. We conducted a systematic review of CPRs for melanoma diagnosis in ambulatory care. Design Systematic review. Data sources A comprehensive search of PubMed, EMBASE, PROSPERO, CINAHL, the Cochrane Library and SCOPUS was conducted in May 2015, using combinations of keywords and medical subject headings (MeSH) terms. Study selection and data extraction Studies deriving and validating, validating or assessing the impact of a CPR for predicting melanoma diagnosis in ambulatory care were included. Data extraction and methodological quality assessment were guided by the CHARMS checklist. Results From 16 334 studies reviewed, 51 were included, validating the performance of 24 unique CPRs. Three impact analysis studies were identified. Five studies were set in primary care. The most commonly evaluated CPRs were the ABCD, more than one or uneven distribution of Colour, or a large (greater than 6 mm) Diameter (ABCD) dermoscopy rule (at a cut-point of >4.75; 8 studies; pooled sensitivity 0.85, 95% CI 0.73 to 0.93, specificity 0.72, 95% CI 0.65 to 0.78) and the 7-point dermoscopy checklist (at a cut-point of ≥1 recommending ruling in melanoma; 11 studies; pooled sensitivity 0.77, 95% CI 0.61 to 0.88, specificity 0.80, 95% CI 0.59 to 0.92). The methodological quality of studies varied. Conclusions At their recommended cut-points, the ABCD dermoscopy rule is more useful for ruling out melanoma than the 7-point dermoscopy checklist. A focus on impact analysis will help translate melanoma risk prediction rules into useful tools for clinical practice.

Objective: To investigate the impact of patients9 preferences for the treatment of atrial fibrillation, by using individualised decision analysis combining probability and utility assessments into a decision tree. Design: Observational study based on interviews with patients. Setting: Eight general practices in Avon. Participants: 260 randomly selected patients aged 70–85 years with atrial fibrillation. Main outcome measures: Patients9 treatment preferences regarding anticoagulation treatment (warfarin) after individualised decision analysis; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription. Results: Of 195 eligible patients, 97 participated in decision making using decision analysis. Among these 97, the decision analysis indicated that 59 (61%; 95% confidence interval 50% to 71%) would prefer anticoagulation treatment—considerably fewer than those who would be recommended treatment according to guidelines. There was marked disagreement between the decision analysis and guideline recommendations (kappa =0.25 or less). Of 38 patients whose decision analysis indicated a preference for anticoagulation, 17 (45%) were being prescribed warfarin; on the other hand, 28 (47%) of 59 patients were not being prescribed warfarin although the results of their decision analysis suggested they wanted to be. Conclusions: In the context of shared decision making, individualised decision analysis is valuable in a sizeable proportion of elderly patients with atrial fibrillation. Taking account of patients9 preferences would lead to fewer prescriptions for warfarin than under published guideline recommendations. Decision analysis as a shared decision making tool should be evaluated in a randomised controlled trial.

Objectives: To assess whether antibiotic treatment for acute cough is effective and to measure the side effects of such treatment. Design: Quantitative systematic review of randomised placebo controlled trials. Data sources: Nine trials (8 published, 1 unpublished) retrieved from a systematic search (electronic databases, contact with authors, contact with drug manufacturers, reference lists); no restriction on language. Main outcome measures: Proportion of subjects with productive cough at follow up (7›11 days after consultation with general practitioner); proportion of subjects who had not improved clinically at follow up; proportion of subjects who reported side effects from taking antibiotic or placebo. Results: Eight trials contributed to the meta›analysis. Resolution of cough was not affected by antibiotic treatment (relative risk 0.85 (95% confidence interval 0.73 to 1.00)), neither was clinical improvement at re›examination (relative risk 0.62 (0.36 to 1.09)). The side effects of antibiotic were more common in the antibiotic group when compared to placebo (relative risk 1.51 (0.86 to 2.64)). Conclusions: Treatment with antibiotic does not affect the resolution of cough or alter the course of illness. The benefits of antibiotic treatment are marginal for most patients with acute cough and may be outweighed by the side effects of treatment.

Objectives Following appropriate validation, clinical prediction rules (CPRs) should undergo impact analysis to evaluate their effect on patient care. The aim of this systematic review is to narratively review and critically appraise CPR impact analysis studies relevant to primary care. Setting Primary care. Participants Adults and children. Intervention Studies that implemented the CPR compared to usual care were included. Study design Randomised controlled trial (RCT), controlled before–after, and interrupted time series. Primary outcome Physician behaviour and/or patient outcomes. Results A total of 18 studies, incorporating 14 unique CPRs, were included. The main study design was RCT (n=13). Overall, 10 studies reported an improvement in primary outcome with CPR implementation. Of 6 musculoskeletal studies, 5 were effective in altering targeted physician behaviour in ordering imaging for patients presenting with ankle, knee and neck musculoskeletal injuries. Of 6 cardiovascular studies, 4 implemented cardiovascular risk scores, and 3 reported no impact on physician behaviour outcomes, such as prescribing and referral, or patient outcomes, such as reduction in serum lipid levels. 2 studies examined CPRs in decision-making for patients presenting with chest pain and reduced inappropriate admissions. Of 5 respiratory studies, 2 were effective in reducing antibiotic prescribing for sore throat following CPR implementation. Overall, study methodological quality was often unclear due to incomplete reporting. Conclusions Despite increasing interest in developing and validating CPRs relevant to primary care, relatively few have gone through impact analysis. To date, research has focused on a small number of CPRs across few clinical domains only.

Background The numbers of medicines being prescribed has increased in recent years and this presents a challenge to clinicians in balancing the use of indicated medicines against potential overtreatment and its associated risks. This study aims to examine: (i) changes in rates of polypharmacy from 1997 to 2012 and; (ii) changes in potentially inappropriate prescribing (PIP) prevalence and the relationship between PIP and polypharmacy in individuals aged ≥65 years over this 15 year period in Ireland. Methods This repeated cross-sectional study using pharmacy claims data included patients eligible for the means-tested HSE-PCRS General Medical Services scheme in the Eastern Health Board region of Ireland in 1997, 2002, 2007, and 2012 (range 338,025–539,752 individuals). Rates of polypharmacy (prescribed ≥5 regular medicines) and excessive polypharmacy (≥10 medicines) in all individuals and PIP prevalence in the elderly (as determined by 30 Screening Tool for Older Persons’ Prescriptions criteria) were determined for each year. The association of study year with polypharmacy and PIP was analysed using negative binomial regression and logistic regression respectively. Results Between 1997 and 2012 there was a substantial increase in the prescribing of regular medicines, particularly in older adults, with a four-fold increase in polypharmacy (adjusted incident rate ratio (IRR) 4.16) and a ten-fold increase in excessive polypharmacy (adjusted IRR 10.53), independent of age and gender. In those aged ≥65 years, prevalence of PIP rose from 32.6% in 1997 to 37.3% in 2012. However after adjusting for polypharmacy and gender changes, the odds of having any PIP were lower in 2012 compared to 1997, adjusted odds ratio 0.39 (95% CI 0.39–0.4). Although most PIP criteria decreased in prevalence with time, prescription of long-term proton pump inhibitors (PPIs) at maximal dose increased at each time point (from 0.8% to 23.8% over the period). Males, patients with polypharmacy or prescribed aspirin, warfarin, or long-term steroids were more likely to be prescribed a long-term PPI at maximal dose, while older patients and those prescribed an NSAID were less likely. Conclusion Accounting for the marked increase in polypharmacy, prescribing quality appeared to improve with a reduction in the odds of having PIP from 1997 to 2012. The exception to this is long-term use of maximal dose PPIs, and such prescribing was not consistently associated with risk factors of gastrointestinal bleeding (e.g. NSAID use, older age). Although prescribing of most PIP medicines has improved, strategies to address the related challenges of polypharmacy and PIP may further improve quality of care.

Background Potentially inappropriate prescribing (PIP) is the use of medicines that introduce a greater risk of adverse drug-related events where a safer, as effective alternative is available. PIP is common in community dwelling older adults with an estimated prevalence of between 20 and 50% and can contribute to increased morbidity, adverse drug events and hospitalisations. This systematic review aimed to assess the effectiveness of interventions designed to reduce PIP in primary care. Methods Following the PRISMA guidelines, PubMed, Embase, Scopus and the Cochrane library databases were searched (June 2014). Search terms included inappropriate prescribing, inappropriate pharmacotherapy, and primary care. Studies were included where: the population was community dwelling older patients (≥65); the intervention targeted PIP compared to usual care/other intervention; and the outcome was change in PIP measured with explicit (criterion-based, e.g. Beers) or implicit (judgement-based) tools such as the Medicines Appropriateness Index (MAI) which measures appropriateness across ten domains (e.g., nduration, cost). Three reviewers independently assessed studies for eligibility, extracted data, and assessed methodological quality using the Cochrane risk of bias tool. As meta-analysis of results was not possible owing to heterogeneity in interventions, a narrative synthesis was carried out. Results 15 studies were included. Baseline PIP prevalence ranged from 18% to 100%. Five intervention strategies were identified: pharmacist-led advice; multi-disciplinary team (MDT) meetings; multifaceted interventions (combining two or more techniques) computerised clinical decision support systems (CDSSs); and audit and feedback. Pharmacist-led advice in four RCTs was associated with improvement in PIP (mean MAI difference of 3.1). Significant improvement in diminishing PIP was also found in one out of three MDT studies, three out of four multifaceted interventions and the only audit and feedback study. Both CDSSs studies were effective in reducing new PIP, particularly in relation to amitriptyline, but not in the discontinuation of existing PIP. The methodological quality of included studies was often poor, particularly in reporting selection and attrition bias. There were small numbers of studies within each category, considerable heterogeneity in the types of interventions grouped together and PIP assessment used. Conclusion This systematic review found that pharmacist-led interventions appear effective in decreasing PIP in primary care, with other interventions such as MDTs, multifaceted approaches and CDSSs showing promise. However, the heterogeneity of the study interventions and the variable methodological quality mean that results require further confirmation in ongoing RCTs. Furthermore, the clinical significance of reductions in MAI score is difficult to determine. Better quality evidence upon which to base approaches to improving prescribing for these vulnerable patients is needed.

Objective To examine the prevalence and secular trends in benzodiazepine (BZD) prescribing in the Irish paediatric population. In addition, we examine coprescribing of antiepileptic, antipsychotic, antidepressant and psychostimulants in children receiving BZD drugs and compare BZD prescribing in Ireland to that in other European countries. Setting Data were obtained from the Irish General Medical Services (GMS) scheme pharmacy claims database from the Health Service Executive (HSE)—Primary Care Reimbursement Services (PCRS). Participants Children aged 0–15 years, on the HSE-PCRS database between January 2002 and December 2011, were included. Primary and secondary outcome measures Prescribing rates were reported over time (2002–2011) and duration (≤ or >90 days). Age (0–4, 5–11, 12–15) and gender trends were established. Rates of concomitant prescriptions for antiepileptic, antipsychotics, antidepressants and psychostimulants were reported. European prescribing data were retrieved from the literature. Results Rates decreased from 2002 (8.56/1000 GMS population: 95% CI 8.20 to 8.92) to 2011 (5.33/1000 GMS population: 95% CI 5.10 to 5.55). Of those children currently receiving a BZD prescription, 6% were prescribed BZD for >90 days. Rates were higher for boys in the 0–4 and 5–11 age ranges, whereas for girls they were higher in the 12–15 age groups. A substantial proportion of children receiving BZD drugs are also prescribed antiepileptic (27%), antidepressant (11%), antipsychotic (5%) and psychostimulant (2%) medicines. Prescribing rates follow a similar pattern to that in other European countries. Conclusions While BZD prescribing trends have decreased in recent years, this study shows that a significant proportion of the GMS children population are being prescribed BZD in the long term. This study highlights the need for guidelines for BZD prescribing in children in terms of clinical indication and responsibility, coprescribing, dosage and duration of treatment.

Abramson and colleagues highlight uncertainties about adverse effects of statins for the primary prevention of cardiovascular disease in patients at low absolute cardiovascular risk.1 2 There is a substantial discrepancy between observational studies and randomised controlled trials (RCTs) regarding the reporting of adverse effects of statins. This could be the result of under-reporting of “mild” adverse effects in RCTs …

General practitioners who provide effective explanations of treatment achieve better results

Objectives The aim of this systematic review was to examine the epidemiology of malpractice claims in primary care. Design A computerised systematic literature search was conducted. Studies were included if they reported original data (≥10 cases) pertinent to malpractice claims, were based in primary care and were published in the English language. Data were synthesised using a narrative approach. Setting Primary care. Participants Malpractice claimants. Primary outcome Malpractice claim (defined as a written demand for compensation for medical injury). We recorded: medical misadventure cited in claims, missed/delayed diagnoses cited in claims, outcome of claims, prevalence of claims and compensation awarded to claimants. Results Of the 7152 articles retrieved by electronic search, a total of 34 studies met the inclusion criteria and were included in the narrative analysis. Twenty-eight studies presented data from medical indemnity malpractice claims databases and six studies presented survey data. Fifteen studies were based in the USA, nine in the UK, seven in Australia, one in Canada and two in France. The commonest medical misadventure resulting in claims was failure to or delay in diagnosis, which represented 26–63% of all claims across included studies. Common missed or delayed diagnoses included cancer and myocardial infarction in adults and meningitis in children. Medication error represented the second commonest domain representing 5.6–20% of all claims across included studies. The prevalence of malpractice claims in primary care varied across countries. In the USA and Australia when compared with other clinical disciplines, general practice ranked in the top five specialties accounting for the most claims, representing 7.6–20% of all claims. However, the majority of claims were successfully defended. Conclusions This review of malpractice claims in primary care highlights diagnosis and medication error as areas to be prioritised in developing educational strategies and risk management systems.

Background Shoulder complaints are the third most common cause of musculoskeletal problems. Subacromial impingement syndrome (SIS) is the most frequent cause of shoulder pain. SIS is a clinical syndrome that indicates pain and pathology relating to the subacromial bursa and rotator cuff tendons within the subacromial space. Objective The aim of this systematic review and meta-analysis is to examine the diagnostic accuracy of clinical tests for diagnosing SIS. Methods A systematic literature search was conducted to identify all studies that examined the diagnostic accuracy of clinical tests for SIS test with surgery as the reference standard. The methodological quality of selected studies was assessed using the quality assessment of diagnostic accuracy studies (QUADAS) tool. Studies were combined using a bivariate random effects model. Heterogeneity was assessed using the variance of logit transformed sensitivity and specificity. Results Our systematic literature search yielded 16 articles. Ten studies with 1684 patients are included in the meta-analysis. The Hawkins-Kennedy test, Neer9s sign, empty can test are shown to be useful for ruling out rather than ruling in SIS, with greater pooled sensitivity estimates (range 0.69–0.78) than specificity (range 0.57–0.62). A negative Neer9s sign reduces the probability of SIS from 45% to 14%. The drop arm test and lift off test have higher pooled specificities (range 0.92–0.97) than sensitivities (range 0.21–0.42) indicating that they are useful for ruling in SIS if the test is positive. The methodological quality of the studies included ranges from moderate to good. However, the time delay between the clinical test and the reference test is not optimal in some studies and it is unclear if the assessors were blinded to outcome of index and reference tests. Discussion This is the first systematic review to examine the diagnostic accuracy of these common clinical tests, with a surgical diagnosis as the reference standard. However, there is a need for future high quality prospective cohort studies in primary care settings to investigate the diagnostic utility of these clinical tests. Conclusion This systematic review quantifies the diagnostic accuracy of three clinical tests for SIS. Application of these tests as diagnostic tools may serve to improve appropriate diagnosis and management of individuals with shoulder complaints.

Introduction Stroke is a leading cause of death and acquired disability in every society in which it has been studied. Stroke and transient ischaemic attack (TIA) arise from identical aetiologies and a number of studies have demonstrated that TIAs carry a significant risk of stroke. Several independent predictors of stroke have been incorporated into models such as the ABCD 2 clinical prediction rule, which is used to predict risk of stroke following TIA. This systematic review assessed the predictive value of the ABCD 2 rule in relation to 7 and 90 day risk of stroke. Methods A computerised systematic literature search was performed to retrieve articles that validated the ABCD 2 rule. The original derivation study was used as a predictive model and applied to all validation studies, with observed and predicted number of strokes at 7 and 90 days stratified by risk group (0-3 low, 4-5 moderate, 6-7 high). Results from the studies were pooled and risk ratios (RR) with 95% CI produced. Forest plots were used to graphically display the data. A RR score of 1 represents correct prediction by the ABCD 2 rule, 1 over-prediction. Results Nine validation studies (n=5626) predicted 7 day stroke risk. The ABCD 2 rule correctly predicted occurrence of stroke at 7 days across all three risk strata: low risk (n=1933) — RR 1.12, 95% CI (0.61 to 2.05); moderate risk (n=2640)—RR 1.11, 95% CI (0.74 to 1.68); high risk (n=1053)—RR 0.98, 95% CI (0.69 to 1.41). There were 318 strokes predicted and 288 strokes observed at 7 days across all three risk strata. Data on five studies (n=4897) were pooled to predict 90 day stroke risk. The ABCD 2 rule over-predicted the occurrence of stroke across all three risk strata — low risk (n=1660), RR 1.50, 95% CI (0.86 to 2.62); moderate risk (n=2214), RR 2.24, 95% CI (1.29 to 3.91); high risk (n=1033), RR 2.00, 95% CI (0.90 to 4.45). There were 268 strokes observed at 90 days in contrast to 404 predicted strokes. The chi-squared trend for analysis indicated that as the trichotomised ABCD 2 score increased, the rate of stroke increased (p Conclusion The ABCD 2 score correctly predicts 7 day risk of stroke across all risk strata but over-predicts 90 day risk of stroke in all groups. The variation in the study setting and design needs to be considered in the interpretation of these findings. ABCD 2 is a useful CPR, particularly in relation to 7 day risk of stroke.

Objectives Heroin users are at high risk of premature mortality. Despite the evidence supporting methadone maintenance programmes (MMT), methadone itself has been associated with drug-related deaths. This study aims to determine whether people prescribed methadone have an elevated risk of overdose mortality during periods of treatment transition, particularly during treatment initiation. Method Retrospective cohort study of 3162 Scottish people prescribed and dispensed liquid methadone between January 1993 and February 2004. Observation time was defined as a period during methadone treatment or a period of maximum 6 months after leaving treatment. Individual observation time was censored after 6 months off-treatment. A person9s observation time started again if they re-entered treatment after an off-treatment period. The main outcome measure was drug-related mortality by means of Cox-proportional hazards models during the 12 years of follow-up. Drug-related deaths occurring during treatment or within 3 days after last methadone prescription were considered as cases “on treatment”. Fatalities occurring 4 days or more after leaving treatment were considered to be drug-related deaths “off treatment”. Results Overall 130 people died, with 51 deaths identified as drug-related deaths (20 off treatment and 31 in treatment). Risk of drug-related mortality was higher during treatment than off treatment (adjusted hazard ratio 11.17, 95% CI 4.51 to 27.64). Inspection of timing of death showed that the risk of drug-related mortality was higher during the initial two weeks of treatment (adjusted hazard ratio 16.93, 95% CI 5.17 to 55.46) compared to the risk of mortality off treatment. Similarly, retention in treatment for more than 3 weeks was associated with increased mortality relative to being off treatment (adjusted hazard ratio 9.97, 95% CI 4.08 to 24.39). In relation to risk of mortality during treatment, being in treatment for 3–10 weeks (adjusted hazard ratio 0.36, 95% CI 0.15 to 0.85) or greater than 10 weeks (adjusted hazard ratio 0.13, 95% CI 0.04 to 0.39) was associated with a reduced risk of mortality compared to the initial two weeks on treatment. These effects were observed after adjusting for all or some of the following covariates; co-prescribing of benzodiazepines, psychiatric admission, number of methadone treatments, overuse of methadone and urine testing, where appropriate. Conclusion Excess mortality risk in the initial two weeks of methadone treatment indicates the need for more care in prescribing and monitoring of methadone when starting or restarting a patient on methadone maintenance therapy.

Objective High rates of antibiotic prescribing are an increasing worldwide concern, in terms of increased antimicrobial resistance and associated burden to health services. However, there remains a lack of paediatric population-based pharmacoepidemiological research. The aim of the current study is to determine trends in systemic antibiotic prescribing in Irish children. Design Retrospective analysis of routinely collected data. Participants Data were obtained from the General Medical Services (GMS) claims database. This represents patients who are unable to pay for medical services and accounts for about one third of Irish children. Data were obtained from 2004 to 2008, for about 271 000 children per year aged ≤15. Main Outcome Antibiotic prescribing behaviour in a paediatric population. Results Prescribing rates of systemic antibiotics were compared across years, age (0–4, 5–11, 12–15) and gender and are presented with CI and significance values (using negative binomial regression analysis). In 2004, 631/1000 population (95% CI 628 to 634) received at least one antibiotic prescription compared to 578/1000 (95% CI 575 to 581) in 2008. However, the overall trend across the 5-year period did not show a significant change (IRR 0.99, 95% CI 0.96 to 1.0, p=0.23). No significant difference was observed between males (620/1000, 95% CI 618 to 622) and females (631/1000, 95% CI 629 to 633; IRR 1.02, 95% CI 0.97 to 1.06, p=0.46). However, prevalence rates significantly decreased with age. Children in the 0–4 age group were significantly more likely to receive an antibiotic prescription (827/1000, 95% CI 824 to 829), relative to the 5–11-year old (553/1000, 95% CI 552 to 556) and 12–15 years (489/1000, 95% CI 487 to 492), with all p Conclusions Prescribing rates remained stable over the 5-year period. Although the rates observed here are higher than European comparisons, these results should be considered in the context of the GMS population. Nevertheless, the results suggest the possible overuse of antibiotics within the GMS population and the potential benefit from interventions to reduce prescribing.

Objectives To determine the effects of two computer based decision aids on decisional conflict and mode of delivery among pregnant women with a previous caesarean section. Design Randomised trial, conducted from May 2004 to August 2006. Setting Four maternity units in south west England, and Scotland. Participants 742 pregnant women with one previous lower segment caesarean section and delivery expected at ≥37 weeks. Non-English speakers were excluded. Interventions Usual care: standard care given by obstetric and midwifery staff. Information programme: women navigated through descriptions and probabilities of clinical outcomes for mother and baby associated with planned vaginal birth, elective caesarean section, and emergency caesarean section. Decision analysis: mode of delivery was recommended based on utility assessments performed by the woman combined with probabilities of clinical outcomes within a concealed decision tree. Both interventions were delivered via a laptop computer after brief instructions from a researcher. Main outcome measures Total score on decisional conflict scale, and mode of delivery. Results Women in the information programme (adjusted difference −6.2, 95% confidence interval −8.7 to −3.7) and the decision analysis (−4.0, −6.5 to −1.5) groups had reduced decisional conflict compared with women in the usual care group. The rate of vaginal birth was higher for women in the decision analysis group compared with the usual care group (37% v 30%, adjusted odds ratio 1.42, 0.94 to 2.14), but the rates were similar in the information programme and usual care groups. Conclusions Decision aids can help women who have had a previous caesarean section to decide on mode of delivery in a subsequent pregnancy. The decision analysis approach might substantially affect national rates of caesarean section. Trial Registration Current Controlled Trials ISRCTN84367722.

A 9 month old infant presents with his mother with a three month history of dry, red, itchy rash, initially on the face and extensor surfaces of limbs but now affecting flexor surfaces too.

A previously well boy of 24 months is brought in by his mother in February. For 10 days he has had worsening cough, fever, and coryza. Both parents have asthma, and his mother is worried that he too might have asthma.

Editor—The article by Wennberg et al on variation in the use of healthcare resources at the end of life raises several questions.1 It implies that the frequency of use of services is associated with workforce supply, but other studies contradict this. Supplier induced demand does not explain doctor variability in Norway,2 and economists have noted the methodological difficulty of making interpretations about supplier induced demand.3 Variability is still a major phenomenon in countries with centrally planned health systems which have less scope for inducement, such as the NHS in the United Kingdom. There is a fine interpretative line between healthcare activity that is induced by supply and healthcare activity that varies because some patients face inequitable barriers to access. Even if inducement is an issue in the United States, this interpretation may not be generalisable to other countries, given the market orientation of aspects of healthcare there. The claim that greater use is associated with worse outcomes, making variability a direct risk to patient, requires caution. Given the difficulty, and perhaps even the theoretical impossibility,4 of establishing a single “correct” population rate of use for a healthcare intervention, it is difficult to interpret doctor variation as inherently bad. If it is not possible to say what the single, best, population rate of treatment should be, why should we expect clinicians not to vary in their practice when observed across populations? The results presented in this paper are interesting, but their interpretation is very complex and should be treated with caution,5 especially when trying to generalise to settings outside the United States.

Last week (31 January, p 276) we presented the case of Ms Reynolds, a 25 year old woman who presented to her general practitioner when eight weeks pregnant complaining of nausea and vomiting with light headedness. After an unsuccessful trial of prochlorperazine, she asked about alternatives to conventional drugs. We invited responses on which therapeutic options are safe to consider or recommend in pregnancy, what study design might provide evidence for their relative efficacy in an individual patient, and what proportion of patients and pregnant women use complementary therapies. To look at the discussion of the case so far go to bmj.com One of us (NH) is interested in complementary medicine and suggested a trial of vitamin B-6 (pyridoxine) to relieve the patient's symptoms. We searched Medline (1996 onwards, limiting our search to review articles) using the …

EDITOR—Hodson and Marsh say that ultra-sound may be a promising screening or diagnostic test for detecting osteoporosis.1 Clarification is necessary before their findings can be accepted. Their population, selected on the basis of perceived risk, has a higher risk (16%) than would normally be expected in primary care (4%).2 Interpretation of diagnostic data …

Researchers from the United States and Australia have found that deciduous teeth have robust stem cells in their dental pulp. The finding is important, because such teeth may serve as an easily obtainable alternative to embryonic stem cells, the use of which has proved controversial. Moreover, like umbilical cord blood, they may serve as a ready source of autologous and bankable stem cells, the study says (published online before print in the Proceedings of the National Academy of Science of the United States of America , www.pnas.org). Stem cells have …

EDITOR—McManus et al show the difficulties inherent in using currently available risk scoring systems for cardiovascular disease, with only moderate agreement between methods.1 They also show the methods' relatively low accuracy when compared with independently calculated Framingham risk estimates. Much of the inaccuracy was due to a lack of risk factor information in case records and use of risk scoring in people with diagnosed cardiovascular disease, who should be considered at high risk and treated accordingly. As in previous comparison studies, the Framingham …

To investigate the effect of patients' preferences in the treatment of atrial fibrillation by using individualized decision analysis in which probability and utility assessments are combined into a decision tree.Observational study based on interviews with patients.8 general practices in Avon, England.260 randomly selected patients aged 70 to 85 years with atrial fibrillation.Patients' treatment preferences regarding anticoagulation treatment (warfarin sodium) after individualized decision analysis; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription.Of 195 eligible patients, 97 participated in decision making using decision analysis. Among these 97, the decision analysis indicated that 59 (61%; 95% confidence interval, 50%-71%) would prefer anticoagulation treatment, considerably fewer than those who would be recommended treatment according to guidelines. There was marked disagreement between the decision analysis and guideline recommendations (kappaor =0.25). Of 38 patients whose decision analysis indicated a preference for anticoagulation, 17 (45%) were being prescribed warfarin; on the other hand, 28 (47%) of 59 patients were not being prescribed warfarin, although the results of their decision analysis suggested they wanted to be.In the context of shared decision making, individualized decision analysis is valuable in a sizable proportion of elderly patients with atrial fibrillation. Taking account of patients' preferences would lead to fewer prescriptions for warfarin than under published recommendations. Decision analysis as a shared decision-making tool should be evaluated in a randomized controlled trial.

Editor—Wauters et al report on the diagnostic value of rectal bleeding in terms of subsequent development of colorectal cancer.1 We feel that this study requires clarification for several reasons. Firstly, the authors do not report the pre-test probability of colorectal cancer in age specific categories in their population. The diagnostic value of a symptom such as rectal bleeding and the impact on post-test probability and subsequent referral threshold are maximised when the pre-test probability of the disease is known.2 Secondly, they fail to mention that less than half of patients with rectal bleeding have no other symptoms.3 More often it is associated with other bowel symptoms that have higher diagnostic value than rectal bleeding alone.4 Thirdly, the reported positive likelihood ratio of 68.3 “rules in” a diagnosis of colorectal cancer, irrespective of the pre-test probability of the disease.2 The reported specificity of 99.5% has the same effect of ruling in the target disorder of colorectal cancer. These findings imply that any patients attending their general practitioner with rectal bleeding need referral and further evaluation. Our own clinical experience and other community based studies of rectal bleeding indicate that such a high specificity and likelihood ratio is unlikely and may well be misleading.4,5 Finally, the most likely explanation for the results relates to general practitioners underreporting rectal bleeding in the prospective arm of the study. Wauters et al chose “rectal bleeding as the reason for visiting a general practitioner” as the inclusion criterion for their study. They should clarify whether this means that patients in whom rectal bleeding was not the primary reason for consulting their general practitioner were excluded. A prospective study in the Netherlands showed that among patients presenting with rectal bleeding, 51% stated this as the primary reason for consulting their general practitioner; 49% consulted for a different reason, but rectal blood loss was subsequently mentioned during the consultation.4 Another prospective study found that 3% (95% confidence interval 1.4% to 5.8%) of patients with rectal bleeding subsequently developed colorectal cancer, and even in this study patients with “clinically relevant rectal bleeding” were overrepresented.5 In Wauters et al's study, 27 patients with rectal bleeding (7%, 4.6% to 10%) developed colorectal cancer. In summary, there may have been a systematic bias in excluding less severe forms of rectal bleeding which may have not been the primary reason for consulting a general practitioner. This has resulted in inflated values for specificity and positive likelihood ratio. Before their results are incorporated into clinical practice Wauters et al should clarify their inclusion criteria and provide age specific two by two tables so that readers can judge for themselves the diagnostic value of isolated rectal bleeding in general practice.

Ed Leone Ridsdale Harcourt Brace, £17.50, pp 176 ISBN 0 443 05889 X Rating: ![Graphic][1] ![Graphic][2] ![Graphic][3] Using external evidence to inform clinical decision making is now acknowledged as an important and necessary ingredient of good clinical practice. However, using external evidence depends on formulating an answerable question, finding and appraising evidence, and applying the evidence to the individual patient. Leone Ridsdale is to be congratulated on editing a relevant and accessible book that shows how evidence based medicine … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif

EDITOR,—John Shanks and colleagues mention the value of morbidity data collected in general practice.1 Remarkably little is known about the completeness and validity of data on health promotion and chronic diseases. The definition of asthma for the purposes of management of chronic disease has been reported to differ …