Background
People who are prescribed self-administered medications typically take less than half the prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications, but also might increase their adverse effects.

Objectives
To update a review summarizing the results of randomized controlled trials (RCTs) of interventions to help patients follow prescriptions for medications for medical problems, including mental disorders but not addictions.

Search methods
We updated searches of The Cochrane Library, MEDLINE, CINAHL, EMBASE, International Pharmaceutical Abstracts (IPA), PsycINFO (all via OVID) and Sociological Abstracts (via CSA) in January 2007 with no language restriction. We also reviewed bibliographies in articles on patient adherence and articles in our personal collections, and contacted authors of relevant original and review articles.

Selection criteria
Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive initial findings.

Data collection and analysis
Study design features, interventions and controls, and results were extracted by one review author and confirmed by at least one other review author. We extracted adherence rates and their measures of variance for all methods of measuring adherence in each study, and all outcome rates and their measures of variance for each study group, as well as levels of statistical significance for differences between study groups, consulting authors and verifying or correcting analyses as needed. The studies differed widely according to medical condition, patient population, intervention, measures of adherence, and clinical outcomes. Therefore, we did not feel that quantitative analysis was scientifically justified; rather, we conducted a qualitative analysis.

Main results
For short-term treatments, four of ten interventions reported in nine RCTs showed an effect on both adherence and at least one clinical outcome, while one intervention reported in one RCT significantly improved patient adherence, but did not enhance the clinical outcome. For long-term treatments, 36 of 83 interventions reported in 70 RCTs were associated with improvements in adherence, but only 25 interventions led to improvement in at least one treatment outcome. Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, reminders, self-monitoring, reinforcement, counseling, family therapy, psychological therapy, crisis intervention, manual telephone follow-up, and supportive care. Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes.

Authors' conclusions
For short-term treatments several quite simple interventions increased adherence and improved patient outcomes, but the effects were inconsistent from study to study with less than half of studies showing benefits. Current methods of improving adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. High priority should be given to fundamental and applied research concerning innovations to assist patients to follow medication prescriptions for long-term medical disorders.

Interventions for enhancing medication adherence.

The purpose of this book is to provide nurses with the best available research, thereby enabling better decisions that result in improved health care and safety practices and lead to better outcomes. Nurses often are the ones who find errors and prevent pa tient harm. In their focus on patient safety, nurses identify critical issues and research for evidence-based practice. This book is a great resource for practicing nurses, nurse educators, re searchers, leaders, and students. The Agency for Healthcare Research and Quality strongly promotes that safety and quality of health care is dependent on the availability of the best research possible and the ability to deliver results of research into the hands of practitioners, policy makers, and consumers. This text is a culmination of subject expert knowledge, practice, and research from 89 contributors who represent a broad range of nurses and senior researchers across the nation. The topics covered in this text provide excellent background for any clinician, nurse educator, or nurse leader. The topics include • evidence-based practice, • patient-centered care, • working environment for nurses, • care models, and • patient acuity. The chapters provide an easy-tounderstand guide and include a background section and analysis of the literature based on the topic presented. Practice implications are identified at the end of each chapter and guide efforts for improving quality and patient care. Research implications for each topic outline target areas for improvement and can be used by clinicians to inform and guide practice. There are also questions and issues to develop or expand thesis topics and research papers, which faculty members may find useful. A section on critical opportunities contains current topics, including wrong site surgery, communication hand offs by nurses, medication administration safety, medication reconciliation, and personal safety for nurses. These topics are very well presented with numerous research citations and examples from all areas of nursing— from patient entry to the facility to discharge and home care. The authors use exhibits, tables, guides, templates, models, and representations within each chapter and conclude with a list of references including web sites for further independent review and citation. The volumes are written in a manner that allows for quick access, and they are

Patient Safety and Quality: An Evidence-Based Handbook for Nurses

Developing and implementing successful interventions often depend upon effectively addressing ethnicity and social class factors, as these influence sexual behavior and its risks. Sexual attitudes differ across cultures. In most cultures, there are strong standards regarding sexual behavior which differ for men and women. Cultural differences also affect the extent to which early sexual behavior is considered acceptable.

Guidelines for Prevention, I

Background Approximately 20% to 50% of patients are not adherent to medical therapy. This review was performed to summarize, categorize, and estimate the effect size (ES) of interventions to improve medication adherence in chronic medical conditions. Methods Randomized controlled trials published from January 1967 to September 2004 were eligible if they described 1 or more unconfounded interventions intended to enhance adherence with self-administered medications in the treatment of chronic medical conditions. Trials that reported at least 1 measure of medication adherence and 1 clinical outcome, with at least 80% follow-up during 6 months, were included. Study characteristics and results for adherence and clinical outcomes were extracted. In addition, ES was calculated for each outcome. Results Among 37 eligible trials (including 12 informational, 10 behavioral, and 15 combined informational, behavioral, and/or social investigations), 20 studies reported a significant improvement in at least 1 adherence measure. Adherence increased most consistently with behavioral interventions that reduced dosing demands (3 of 3 studies, large ES [0.89-1.20]) and those involving monitoring and feedback (3 of 4 studies, small to large ES [0.27-0.81]). Adherence also improved in 6 multisession informational trials (small to large ES [0.35-1.13]) and 8 combined interventions (small to large ES [absolute value, 0.43-1.20]). Eleven studies (4 informational, 3 behavioral, and 4 combined) demonstrated improvement in at least 1 clinical outcome, but effects were variable (very small to large ES [0.17-3.41]) and not consistently related to changes in adherence. Conclusion Several types of interventions are effective in improving medication adherence in chronic medical conditions, but few significantly affected clinical outcomes.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/412057/ira60021_540_550.pdf

Interventions to Enhance Medication Adherence in Chronic Medical Conditions: A Systematic Review

Background Suboptimum medication adherence is common in the United States and leads to serious negative health consequences but may respond to intervention. Purpose To assess the comparative effectiveness of patient, provider, systems, and policy interventions that aim to improve medication adherence for chronic health conditions in the United States. Data sources Eligible peer-reviewed publications from MEDLINE and the Cochrane Library indexed through 4 June 2012 and additional studies from reference lists and technical experts. Study selection Randomized, controlled trials of patient, provider, or systems interventions to improve adherence to long-term medications and nonrandomized studies of policy interventions to improve medication adherence. Data extraction Two investigators independently selected, extracted data from, and rated the risk of bias of relevant studies. Data synthesis The evidence was synthesized separately for each clinical condition; within each condition, the type of intervention was synthesized. Two reviewers graded the strength of evidence by using established criteria. From 4124 eligible abstracts, 62 trials of patient-, provider-, or systems-level interventions evaluated 18 types of interventions; another 4 observational studies and 1 trial of policy interventions evaluated the effect of reduced medication copayments or improved prescription drug coverage. Clinical conditions amenable to multiple approaches to improving adherence include hypertension, heart failure, depression, and asthma. Interventions that improve adherence across multiple clinical conditions include policy interventions to reduce copayments or improve prescription drug coverage, systems interventions to offer case management, and patient-level educational interventions with behavioral support. Limitations Studies were limited to adults with chronic conditions (excluding HIV, AIDS, severe mental illness, and substance abuse) in the United States. Clinical and methodological heterogeneity hindered quantitative data pooling. Conclusion Reduced out-of-pocket expenses, case management, and patient education with behavioral support all improved medication adherence for more than 1 condition. Evidence is limited on whether these approaches are broadly applicable or affect longterm medication adherence and health outcomes. Primary funding source Agency for Healthcare Research and Quality.

Interventions to improve adherence to self-administered medications for chronic diseases in the United States: a systematic review

Lenalidomide and dexamethasone for multiple myeloma

Background: There have been concerns raised about the potential adverse effects of proton pump inhibitors, especially with long-term use. In particular, their potent action can suppress the features and delay the diagnosis of gastric cancer, while prolonged exposure may hasten the development of gastric carcinoids.

Aim: To examine the use of proton pump inhibitors in patients at the major teaching hospital in Tasmania, Australia, principally to determine the appropriateness of the therapy according to published guidelines.

Methods: A retrospective review of the medical records of all patients prescribed any of the proton pump inhibitors at the hospital over a 7-month period, was performed. An extensive range of demographic and clinical variables was recorded for each patient. The patients were also asked a series of questions during their hospitalization to extract some of the relevant information – in particular, if and when they had undergone endoscopy.

Results: The 200 patients (52% males) had a mean age of 69 ± 16·4 years. The most common indications for using proton pump inhibitors were acute gastrointestinal bleeding (20·9%), severe refractory ulcerating oesophagitis (17·3%), mild/moderate oesophageal reflux (17·3%) and refractory peptic ulcer (11·7%). A large number of patients were using a proton pump inhibitor for ‘other’ indications (39·6%). The prescribing of proton pump inhibitors satisfied the approved indications, as outlined in the Australian Schedule of Pharmaceutical Benefits, in only 37·1% of cases. Endoscopy had been performed in 54·1% of patients prior to commencing therapy with a proton pump inhibitor and within the next 7 days in another 12·8% of patients. Only 59% of patients had previously been treated with an H2-receptor antagonist before commencing therapy with a proton pump inhibitor. Even worse, only 58·5% of patients had used an H2-receptor antagonist before a proton pump inhibitor for mild/moderate oesophagitis. The median duration of proton pump inhibitor therapy for patients admitted to the hospital and already receiving one of the drugs was 450 days. Over half of the patients were being concurrently treated with other drugs which are known to cause or exacerbate gastro-oesophageal disease, and 18% were smokers.

Conclusions: Whereas the proton pump inhibitors are undoubtedly effective agents, studies of their prescribing in practice consistently suggest over-use prior to endoscopy, use in patients who do not fit the approved criteria, and prescribing for indications in which ‘less powerful’ agents should have been sufficiently effective for the patient’s symptoms. This poses economic and safety concerns, particularly in light of the suggestion that these drugs could delay the diagnosis of gastric cancer.

Overuse of proton pump inhibitors.

The debate exists amongst clinical pharmacologists as to unlimited supplies of which drug would be most useful when stranded on a deserted island. The tricyclic antidepressants have always rated highly because of their variety of useful therapeutic effects, but valproate also deserves to be high on the list. Of course, it will protect against seizures, if they arise, but it could also be useful for analgesia, preventing migraine and stabilizing the mood particularly if one becomes mentally unbalanced on the island. It might even help to prevent the development of cancer. It would not be an overstatement to suggest that valproate is truly a remarkable drug – a multitude of therapeutic effects from such a simple chemical structure (2-propylpentanoic acid; Fig. 1) – with a remarkable story; it was discovered by chance and is now well-established in the management of a number of neurological conditions and psychiatric disorders. An American chemist (Burton) first synthesized valproate as an organic solvent in 1882 (1). It is a clear, colourless to pale yellow liquid at room and body temperature, and only slightly soluble in water, but highly soluble in organic solvents. The current generic name (valproic acid) was derived from the more descriptive name 2-propylvaleric acid (2). Valproate had been used infrequently as a solvent until its therapeutic properties were serendipitously discovered in 1962 by French researchers, when it was being used as a solvent for other compounds (khelline derivatives) that were being tested for potential anticonvulsant activity (2–4). Eynard and colleagues had encountered difficulty in dissolving some of the derivatives in water or common organic solvents. Valproate was then used to solubilize these compounds and anticonvulsant activity was subsequently observed for the entire test compounds at all doses. Laboratory studies demonstrated anti-seizure activity with valproate (5) and the first clinical trial in epilepsy using the sodium salt of valproic acid was reported in 1964 (6, 7). It was released in France in 1967 (as ‘Depakine’), in Great Britain in 1973 and was approved by the US Food and Drug Administration (FDA) in 1978. It was the only new anticonvulsant drug marketed for many years, beforehand and afterwards. Valproate is currently marketed in over 100 countries and is well established as a first-line and widely used antiepileptic agent, with a very broad spectrum of activity against both generalized and partial seizures in adults and children (4, 8, 9). It is effective against absences and myoclonic, and generalized tonic-clonic seizures. In addition, the drug is useful in the treatment of partial seizures, with or without secondary generalization (2–4, 8, 9). Intravenous valproate has also been shown to be effective against status epilepticus (10). Results from numerous clinical trials suggest that valproate probably has the widest spectrum of anticonvulsant activity of all current antiepileptic drugs in adults and children with epilepsy (4, 8, 9). Received 9 May 2005, Accepted 19 May 2005 Correspondence: Gregory Peterson, Unit for Medication Outcomes Research and Education, School of Pharmacy, University of Tasmania, Locked Bag 26, Hobart TAS 7001, Australia. Tel.: 61 3 62262197; fax: 61 3 62267627; e-mail: g.peterson@utas.edu.au OH H3C H3C

Valproate: a simple chemical with so much to offer.

Objective: To evaluate pharmacist-conducted follow-up at home of high-risk elderly patients discharged from hospital. Method: A randomised controlled study, in which medical patients admitted to hospital and fulfilling high-risk criteria (including age 60 years or older and prescribed four or more regular medications) were randomly assigned to an intervention or control group. Patients in the intervention group were visited at home by a pharmacist five days after discharge. The pharmacist educated patients on their medications, encouraged compliance, assessed for drug-related problems, intervened when appropriate and communicated all relevant findings to community health professionals. The intervention group patients were revisited at home 90 days after discharge to evaluate the outcomes of interventions made on day 5. Patients in the control group were visited at home by a pharmacist 90 days after discharge and provided with an identical comprehensive medication review. Results: One hundred and twenty-one patients completed the study. There were no significant differences between the two groups in key clinical and demographic parameters at baseline. A median of three drug-related problems were identified in each intervention group patient at the five day home visit. Ninety days after discharge this had declined to one, compared to two for the control group patients (p Conclusion: A pharmacist-conducted follow-up at home of high-risk elderly patients discharged from hospital is valuable in identifying and addressing drug-related problems and reducing the risk of readmission to hospital.

Evaluation of home-based follow-up of high-risk elderly patients discharged from hospital

Background: There have been concerns raised about the potential adverse effects of proton pump inhibitors, especially with long‐term use. In particular, their potent action can suppress the features and delay the diagnosis of gastric cancer, while prolonged exposure may hasten the development of gastric carcinoids.

Mark Naunton

Papers

Lenalidomide and dexamethasone for multiple myeloma

Overuse of proton pump inhibitors.

Valproate: a simple chemical with so much to offer.

Evaluation of home-based follow-up of high-risk elderly patients discharged from hospital

Overuse of proton pump inhibitors: Overuse of proton pump inhibitors