Background: Patients' non-adherence to medical treatment remains a persistent problem. Many interventions to improve patient adherence are unsuccessful and sound theoretical foundations are lacking. Innovations in theory and practice are badly needed. A new and promising way could be to review the existing reviews of adherence to interventions and identify the underlying theories for effective interventions. That is the aim of our study.Methods: The study is a review of 38 systematic reviews of the effectiveness of adherence interventions published between 1990 and 2005. Electronic literature searches were conducted in Medline, Psychinfo, Embase and the Cochrane Library. Explicit inclusion and exclusion criteria were applied. The scope of the study is patient adherence to medical treatment in the cure and care sector.Results: Significant differences in the effectiveness of adherence interventions were found in 23 of the 38 systematic reviews. Effective interventions were found in each of four theoretical approaches to adherence interventions: technical, behavioural, educational and multi-faceted or complex interventions. Technical solutions, such as a simplification of the regimen, were often found to be effective, although that does not count for every therapeutic regimen.Overall, our results show that, firstly, there are effective adherence interventions without an explicit theoretical explanation of the operating mechanisms, for example technical solutions. Secondly, there are effective adherence interventions, which clearly stem from the behavioural theories, for example incentives and reminders. Thirdly, there are other theoretical models that seem plausible for explaining non-adherence, but not very effective in improving adherence behaviour. Fourthly, effective components within promising theories could not be identified because of the complexity of many adherence interventions and the lack of studies that explicitly compare theoretical components.Conclusion: There is a scarcity of comparative studies explicitly contrasting theoretical models or their components. The relative weight of these theories and the effective components in the interventions designed to improve adherence, need to be assessed in future studies.

THERE HAS been evidence of possible risks of concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics.^1-3 The kidney is an important target site for untoward drug reactions associated with the use of NSAIDs, and concomitant use of diuretics may increase the risk of NSAID-associated renal adverse effects.^4-8 The interaction between diuretics and NSAIDs is well known.^8-10 Nonsteroidal anti-inflammatory drugs inhibit the synthesis of renal prostaglandins, which can have serious effects on renal function. Prostaglandins predominantly generated in the kidney are I₂ and E₂, of which prostaglandin E₂ influences sodium resorption in the nephron by causing vasodilation and by directly inhibiting sodium resorption in the thick ascending loop of Henle and in the collecting tubule.⁹ Prostaglandin E₂ also antagonizes the antidiuretic effect of vasopressin in the collecting tubule.^8,9 Therefore, by inhibiting prostaglandin synthesis, NSAIDs can cause sodium and water retention and blunt the response to diuretics. In most users of NSAIDs the inhibition of renal prostaglandins will have no clinical effect, but there have been case reports of patients with a predisposition to sodium retention, in particular because of congestive heart failure (CHF), in which the use of NSAIDs had marked clinical implications.^8,10-13 Existing CHF may worsen after use of NSAIDs by inhibition of diuretic therapy and by adverse renal effects, especially in elderly patients with renal impairment and cardiovascular comorbidity.¹³ These elderly patients at risk are at the same time the most frequent users of NSAIDs and diuretics, with an estimated 10% of all elderly people having a period of concomitant use of diuretics and NSAIDs in a year.^14,15

Case reports and observational studies have both shown an association between use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and abnormal bleeding. Case reports have described patients with various bleeding disorders (eg, ecchymoses, purpura, epistaxis, and vaginal bleeding^1-7), while observational studies have focused on upper gastrointestinal bleeding, intracranial bleeding, and bleeding during surgery.^8-13

HEART FAILURE is a syndrome that results from complex circulatory and neurohormonal responses to cardiac dysfunction.^1,2 The main causes of heart failure are ischemic heart disease and arterial hypertension.^3,4 According to recent guidelines of the European Society of Cardiology, objective evidence of cardiac dysfunction has to be present in addition to symptoms, such as shortness of breath or fatigue at rest or during exercise and ankle swelling, to establish the presence of heart failure.⁵

To assess the proportion of patients starting with antihypertensive drug treatment who continued treatment for at least 10 years. A retrospective cohort study. The PHARMO record linkage system containing drug dispensing records from community pharmacies and linked hospital discharge records of approximately 950 000 subjects. Patients who started using antihypertensive drugs (two or more prescriptions) in 1992 and did not receive a prescription for any antihypertensive drug in the 365 days preceding the first prescription. Persistence with antihypertensive drugs until 10 years. Among a total of 2325 patients who started using antihypertensive drugs, 39% used continuously during the 10 years of follow-up. Approximately 22% temporarily discontinued and restarted treatment, whereas 39% of patients discontinued permanently. Older patients were more persistent than younger patients [20–39 years: odds ratio (OR) 2.08; 95% confidence interval (CI) 1.52–2.84; 40–59 years: (reference), ≥ 60 years: OR 0.69; 95% CI 0.54–0.89]. More patients who started with diuretics (reference) and beta blockers (OR 1.15; 95% CI 0.87–1.52) discontinued compared with those who started with dihydropyridine calcium antagonists (OR 0.54; 95% CI 0.34–0.84), and angiotensin-converting enzyme (ACE) inhibitors (OR 0.38; 95% CI 0.27–0.55). Patients who started with combination therapy (OR 0.29; 95% CI 0.14–0.54 compared with diuretics) or patients who were initially treated by a cardiologist (OR 0.82; 95% CI 0.61–0.97) or internist (OR 0.80; 95% CI 0.62–0.98 compared with general practitioners) also showed higher persistence. Long-term persistence in daily practice is low compared with persistence observed in randomized clinical trials and should be considered in the choice of a first-line antihypertensive agent.