Rachel Elliott

The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review

Abstract Objectives To assess the effectiveness of five gastroprotective strategies for people taking non-steroidal anti-inflammatory drugs (NSAIDs)—H2 receptor antagonists plus non-selective (or cyclo-oxygenase-1) NSAIDs; proton pump inhibitors plus non-selective NSAIDs; misoprostol plus non-selective NSAIDs; COX-2 selective NSAIDs; or COX-2 specific NSAIDs—in reducing serious gastrointestinal complications, symptomatic ulcers, serious cardiovascular or renal disease, and deaths, and improving quality of life. Data sources The Cochrane Library, Medline, Embase, Current Controlled Trials, and System for Information on Grey Literature in Europe (SIGLE) were searched to May 2002. Bibliographies and author contacts were used to identify further studies; non-English articles were included. Review methods Trial selection, data extraction, and quality assessment were performed independently, in duplicate. Articles were rejected only if the study was not a randomised controlled trial; did not assess a gastroprotective strategy versus placebo; included exclusively children or healthy volunteers; lasted less than 21 days; or no review outcomes were measured. Quality assessment included allocation concealment and baseline similarity. Random effects meta-analysis, meta-regression and subgrouping were used to pool effects and analyse associations with length of follow up, mean age, and baseline gastrointestinal status. Heterogeneity was examined and sensitivity analyses performed. Results Of 112 included randomised controlled trials (74 666 participants), five were judged to be at low risk of bias, and 138 deaths and 248 serious gastrointestinal events were reported overall. On comparing gastroprotective strategies versus placebo we found no evidence of effectiveness of H2 receptor antagonists for any primary outcomes (few events reported); proton pump inhibitors may reduce the risk of symptomatic ulcers (relative risk 0.09, 95% confidence interval 0.02 to 0.47); misoprostol reduces the risk of serious gastrointestinal complications (0.57, 0.36 to 0.91) and symptomatic ulcers (0.36, 0.20 to 0.67); COX-2 selectives reduce the risk of symptomatic ulcers (0.41, 0.26 to 0.65) and COX-2 specifics reduce the risk of symptomatic ulcers (0.49, 0.38 to 0.62) and possibly serious gastrointestinal complications (0.55, 0.38 to 0.80). All strategies except COX-2 selectives reduce the risk of endoscopic ulcers (at least 3 mm in diameter). Conclusions Misoprostol, COX-2 specific and selective NSAIDs, and probably proton pump inhibitors significantly reduce the risk of symptomatic ulcers, and misoprostol and probably COX-2 specifics significantly reduce the risk of serious gastrointestinal complications, but data quality is low. More data on H2 receptor antagonists and proton pump inhibitors are needed, as is better reporting of rare but important outcomes.

Effect of pay for performance on the management and outcomes of hypertension in the United Kingdom: interrupted time series study

Objective To assess the impact of a pay for performance incentive on quality of care and outcomes among UK patients with hypertension in primary care. Design Interrupted time series. Setting The Health Improvement Network (THIN) database, United Kingdom. Participants 470 725 patients with hypertension diagnosed between January 2000 and August 2007. Intervention The UK pay for performance incentive (the Quality and Outcomes Framework), which was implemented in April 2004 and included specific targets for general practitioners to show high quality care for patients with hypertension (and other diseases). Main outcome measures Centiles of systolic and diastolic blood pressures over time, rates of blood pressure monitoring, blood pressure control, and treatment intensity at monthly intervals for baseline (48 months) and 36 months after the implementation of pay for performance. Cumulative incidence of major hypertension related outcomes and all cause mortality for subgroups of newly treated (treatment started six months before pay for performance) and treatment experienced (started treatment in year before January 2001) patients to examine different stages of illness. Results After accounting for secular trends, no changes in blood pressure monitoring (level change 0.85, 95% confidence interval −3.04 to 4.74, P=0.669 and trend change −0.01, −0.24 to 0.21, P=0.615), control (−1.19, −2.06 to 1.09, P=0.109 and −0.01, −0.06 to 0.03, P=0.569), or treatment intensity (0.67, −1.27 to 2.81, P=0.412 and 0.02, −0.23 to 0.19, P=0.706) were attributable to pay for performance. Pay for performance had no effect on the cumulative incidence of stroke, myocardial infarction, renal failure, heart failure, or all cause mortality in both treatment experienced and newly treated subgroups. Conclusions Good quality of care for hypertension was stable or improving before pay for performance was introduced. Pay for performance had no discernible effects on processes of care or on hypertension related clinical outcomes. Generous financial incentives, as designed in the UK pay for performance policy, may not be sufficient to improve quality of care and outcomes for hypertension and other common chronic conditions.

Current use of pharmacogenetic testing : a national survey of thiopurine methyltransferase testing prior to azathioprine prescription

Background:  Azathioprine is an immunosuppressant prescribed for the treatment of inflammatory conditions and after organ transplantation. Risk of neutropaenia has limited the effective use of azathioprine (AZA) and driven requirements for careful monitoring and blood tests. Thiopurine methyltransferase (TPMT) is a genetically moderated key enzyme involved in the metabolism of AZA that can be used to stratify individuals into different levels of risk of developing neutropaenia. Two techniques can be used to measure TPMT status: enzyme‐level testing (phenotype testing) and DNA based testing (genotype testing).

Health status of UK care home residents: a cohort study

Background: UK care home residents are often poorly served by existing healthcare arrangements. Published descriptions of residents’ health status have been limited by lack of detail and use of data derived from surveys drawn from social, rather than health, care records. Aim: to describe in detail the health status and healthcare resource use of UK care home residents Design and setting: a 180-day longitudinal cohort study of 227 residents across 11 UK care homes, 5 nursing and 6 residential, selected to be representative for nursing/residential status and dementia registration. Method: Barthel index (BI), Mini-mental state examination (MMSE), Neuropsychiatric index (NPI), Mini-nutritional index (MNA), EuroQoL-5D (EQ-5D), 12-item General Health Questionnaire (GHQ-12), diagnoses and medications were recorded at baseline and BI, NPI, GHQ-12 and EQ-5D at follow-up after 180 days. National Health Service (NHS) resource use data were collected from databases of local healthcare providers. Results: out of a total of 323, 227 residents were recruited. The median BI was 9 (IQR: 2.5–15.5), MMSE 13 (4–22) and number of medications 8 (5.5–10.5). The mean number of diagnoses per resident was 6.2 (SD: 4). Thirty per cent were malnourished, 66% had evidence of behavioural disturbance. Residents had contact with the NHS on average once per month. Conclusion: residents from both residential and nursing settings are dependent, cognitively impaired, have mild frequent behavioural symptoms, multimorbidity, polypharmacy and frequently use NHS resources. Effective care for such a cohort requires broad expertise from multiple disciplines delivered in a co-ordinated and managed way.

Strategies for coping in a complex world: adherence behavior among older adults with chronic illness.

BackgroundIncreasing numbers of medicines increase nonadherence. Little is known about how older adults manage multiple medicines for multiple illnesses.ObjectivesTo explore how older adults with multiple illnesses make choices about medicines.DesignSemistructured interviews with older adults taking several medications. Accounts of respondents’ medicine-taking behavior were collected.ParticipantsTwenty community-dwelling seniors with health insurance, in Eastern Massachusetts, aged 67–90, (4–12 medicines, 3–9 comorbidities).ApproachQualitative analysis using constant comparison to explain real choices made about medicines in the past (“historical”) and hypothetical (“future”) choices.ResultsRespondents reported both past (“historical”) choices and hypothetical (“future”) choices between medicines. Although people discussed effectiveness and future risk of the disease when prompted to prioritize their medicines (future choices), key factors leading to nonadherence (historical choices) were costs and side effects. Specific choices were generally dominated by 1 factor, and respondents rarely reported making explicit trade-offs between different factors. Factors affecting 1 choice were not necessarily the same as those affecting another choice in the same person. There was no evidence of “adherent” personalities.ConclusionPrescribing a new medicine, a change in provider or copayment can provoke new choices about both new and existing medications in older adults with multiple morbidities.

Cost-Effectiveness of Adherence-Enhancing Interventions: A Quality Assessment of the Evidence

OBJECTIVE: To determine whether the current cost-effectiveness evidence on adherence-enhancing interventions (AEIs) was of sufficient quality to aid in decision-making regarding medication adherence policies. DATA SOURCES: A computerized search of Embase, MEDLINE, Cinahl, Econlit, NHSEED, Psychlit, EPIC, and Cochrane databases (1980–April 2004) was performed. English-language human subject articles were identified using the key words compliance, adherence, concordance, patient assistance, therapeutic alliance, costs, economics, efficiency, resource use/utilization, cost-of illness, cost-effectiveness, cost-minimization, cost-utility, and cost-benefit. STUDY SELECTION AND DATA EXTRACTION: Studies that appeared to assess the cost-effectiveness of medication AEIs were included. Methodologic rigor was assessed using 15 minimum quality criteria. DATA SYNTHESIS: We found 45 comparative studies in 43 publications. Asthma (14 studies) and psychiatric illness (12 studies) were most commonly investigated. In 33 studies, interventions were educational, 18 had multiple components, and 23 did not appear to be linked to proven reasons for nonadherence. Reporting of adherence and outcome results was often unclear. Cost data were poorer quality than outcome data, using average or estimated costs and omitting some cost elements. Nine studies carried out incremental economic analysis. No study met all quality criteria. CONCLUSIONS: We were not able to make definitive conclusions about the cost-effectiveness of AEIs due to the heterogeneity of the studies found and incomplete reporting of results. Important policy decisions need to be made about nonadherence; however, they are currently being made in a vacuum of adequate information. AEIs must be based on reasons for nonadherence and be evaluated using accepted clinical and economic quality criteria.

Systematic review of the analgesic efficacy and tolerability of COX-2 inhibitors in post-operative pain control

Objective:  To evaluate the relative analgesic efficacy and tolerability of single‐dose COX‐2 inhibitors in post‐operative pain management.

A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study.

AIM To conduct a pragmatic, randomized controlled trial to assess whether thiopurine methyltransferase (TPMT) genotyping prior to azathioprine reduces adverse drug reactions (ADRs). METHODS A total of 333 participants were randomized 1:1 to undergo TPMT genotyping prior to azathioprine or to commence treatment without genotyping. RESULTS There was no difference in the primary outcome of stopping azathioprine due to an adverse reaction (ADR, p = 0.59) between the two study arms. ADRs were more common in older patients (p = 0.01). There was no increase in stopping azathioprine due to ADRs in TPMT heterozygotes compared with wild-type individuals. The single individual with TPMT variant homozygosity experienced severe neutropenia. CONCLUSION Our work supports the strong evidence that individuals with TPMT variant homozygosity are at high risk of severe neutropenia, whereas TPMT heterozygotes are not at increased risk of ADRs at standard doses of azathioprine.

Non-adherence to medicines: not solved but solvable

Non-adherence to medicines is common, with convincing evidence for adverse effects on patient health and costs to health systems. At least half of reported non-adherence is intentional. An extensive body of research suggests that, while patient characteristics may contribute to this behaviour, key influences are linked to beliefs and experiences of an illness and its medicines. Characteristics of the health system such as patient-practitioner relationships and access are also significant drivers. Inadvertent effects of some policies, such as co-payments, reduce adherence. Interventions to improve adherence have not utilized available research evidence fully and are not integrated into service delivery, so have been disappointing in producing sustained behaviour change. Policies relying on patients’ adherence to medicines will not be as effective as hoped if adherence is assumed rather than supported. Substantial gains could be made by patients and health systems if patients, practitioners, researchers and policy-makers worked together to improve this crucial area of health behaviour.

Poor adherence to medication in adults with rheumatoid arthritis: Reasons and solutions

This review examines evidence on the prevalence of non-adherence to medication in adults with rheumatoid arthritis, the reasons for non-adherence, and the effectiveness of interventions to improve adherence. Medications for rheumatoid arthritis (NSAIDs, corticosteroids, disease-modifiers, and biologic agents) are not curative, but can reduce symptoms and slow progression of the disease. Evidence consistently suggests that adherence to medications for rheumatoid arthritis is low in adults, and is often <50%. These drugs can be associated with serious adverse effects. Evidence suggests that non-adherence in rheumatoid arthritis cannot be explained by gender or age. Other patient characteristics, such as educational level and socioeconomic status, may create literacy and financial barriers to adherence. The strongest associations are reported between adherence and views about rheumatoid arthritis as a disease; beliefs that disease-modifying antirheumatic drugs do not work and have too many adverse effects; unrealistic or uninformed patient expectations of risk; lack of self-efficacy; lack of social support; cost of prescription medications, and poor patient-provider relationships.There have been few interventions designed specifically to improve medication adherence in patients with rheumatoid arthritis. Most interventions have been based on patient education and the teaching of self-management techniques. Educational interventions have had limited effectiveness in changing behavior because of the limited ability of changes in knowledge to produce lasting behavioral change. The effect of group therapy and cognitive-behavioral therapy on medicine adherence is not clear. Those interventions that are effective tend to emphasize developing a daily routine of self-management activities, coping strategies, self-efficacy, and problem-solving.Future work is required to develop evidence-based, pragmatic, patient-centered interventions to improve medication adherence in patients with rheumatoid arthritis. Practitioners require support and training in the communication of risk and incorporation of patients’ beliefs into the consultation process. Policy makers need to reduce barriers to access, such as the costs of drugs.