The economic consequences of non‐adherence to lipid‐lowering therapy: results from the Anglo‐Scandinavian‐Cardiac Outcomes Trial

Background: Adherence to lipid‐lowering therapy in clinical practice is less than ideal. Analysis of registry data has indicated that this is associated with poor outcomes. The objective of the present analysis was to assess the impact of high adherence to drug (defined as > 80% of days covered), compared with low adherence to drug (< 50% of days covered) in terms of risk of events and long‐term economic consequences. Design: Open‐label follow up of a randomised placebo‐controlled trial in hypertensive patients. Methods: Cox proportional hazards and Poisson regression models were used to assess the hazard ratio of patients with high adherence compared with low adherence while controlling for cardiovascular risk. A Markov model was used to predict the long‐term costs and health outcomes associated with poor adherence during the follow‐up period. Results: Both statistical models indicated that high adherence is associated with improved prognosis [Cox model: 0.75; 95% confidence interval (CI): 0.56–0.98, Poisson model hazard ratio: 0.73; 95% CI: 0.58–0.98]. Discounted at 3.5% per year, the Markov model predicts that as a consequence of higher adherence during the follow‐up period, costs would be higher (£1689 per patient compared with £1323 per patient) because of higher drug costs, but the projected survival and quality‐adjusted survival (QALY) would also be longer (10.83 compared with 10.81 life years and 8.13 compared with 8.11 QALYs). Conclusion: Given the higher risk of cardiovascular events associated with low adherence shown here, measures to improve adherence are an important part of the prevention of cardiovascular disease.     

Pharmacological and non‐pharmacological treatment of non‐alcoholic fatty liver disease

Non‐alcoholic fatty liver disease (NAFLD) comprises a disease spectrum ranging from simple steatosis and steatohepatitis to cirrhosis. Based on its strongest risk factors namely visceral obesity and insulin resistance, NAFLD is thought to be the hepatic manifestation of the metabolic syndrome and is considered to be the most common liver disorder in Western countries. Pathophysiological mechanisms include an enlarged pool of fatty acids, subclinical inflammation, oxidative stress and imbalances of various adipocytokines such as adiponectin. Accordingly, targets for therapeutic interventions are miscellaneous: amelioration of obesity by pharmacological, surgical or lifestyle intervention has been evaluated with success in numerous, but not all studies. Some efficacy was reported for metformin and short‐term glitazone treatment. In a large recently reported trial, vitamin E supplementation improved biochemical and histological markers in subjects with non‐alcoholic steatohepatitis. Blockade of the endocannabinoid system has been proposed to be a promising target in NAFLD; however, very recently the cannabinoid receptor blocker rimonabant has been withdrawn because of central nervous system toxicity. Cytoprotective therapies and statins have been mainly ineffective in NAFLD. New but so far insufficiently studied therapeutic approaches include inhibitors of the renin‐angiotensin system as well as incretin mimetics respectively.     

Focusing the focus group: impact of the awareness of major factors contributing to non‐adherence to acute paediatric asthma guidelines

Rationale The administration of oral corticosteroids within the first hour in the emergency department is associated with reduced hospitalization rates in children with moderate and severe asthma, yet less than half of patients benefit from this recommendation. To ensure patients receive recommended treatment, a clear understanding of what is causing suboptimal care management is needed. The assessment of barriers and solutions to optimal care is often done without a thorough examination of the factors associated with non‐adherence. Objective To evaluate whether knowledge of factors associated with delayed administration of systemic corticosteroids modifies the focus and prioritization of barriers and solutions identified by focus groups. Methods We conducted two parallel focus groups of emergency health care professionals – one group informed and the other non‐informed of key factors. Both groups received a presentation on the acute asthma guidelines, the evidence supporting its recommendations, and current practice. In addition, the informed group was provided with the factors associated and not associated with delayed administration. The groups were given 20 minutes to discuss barriers and solutions, with 5 minutes each for voting for the main barriers and solutions. Group difference in the misdirection of discussion was measured as time spent discussing barriers that were shown not to be associated with systemic corticosteroids. Prioritization of barriers and solutions was based on group endorsement. Results The non‐informed group spent more time discussing barriers not associated with delayed administration (15 vs. 2 minutes, P = 0.05). Although the non‐informed group proposed more solutions, most were to overcome barriers not associated with delayed administration. Of the main barriers and solutions identified by each group, only one barrier and solution were similar between the two groups: emergency department overcrowding and administrating corticosteroids at triage. Conclusion The awareness of objective factors of non‐adherence enabled a more directed discussion on relevant barriers and solutions, affecting prioritization of each. The administration of oral corticosteroids at triage appears to be the best solution to overcome delayed administration.     

Heparin‐induced non‐necrotizing skin lesions: rarely associated with heparin‐induced thrombocytopenia

See also Warkentin TE, Linkins L‐A. Non‐necrotizing heparin‐induced skin lesions and the 4T’s score. This issue, pp 1483–. Summary. Background: Recently, there has been an increasing number of reports regarding adverse skin reactions to subcutaneous heparin administration. Case series have implied that heparin‐induced skin lesions are predominantly associated with life‐threatening heparin‐induced thrombocytopenia (HIT) in at least 22% of patients. Skin lesions, therefore, have been included in clinical scores for HIT. Objectives: To determine the association of heparin‐induced skin lesions with HIT. This would have a pivotal impact on further anticoagulatory management in patients with heparin‐induced skin lesions. Patients/Methods: In our observational cohort study, 87 consecutive patients with heparin‐induced skin lesions (85 occurring during low‐molecular‐weight heparin administration) were evaluated using a standardized internal protocol, including HIT diagnostics (heparin‐platelet factor 4‐ELISA, heparin‐induced platelet activation assay), platelet count monitoring, clinical/sonographical screening for thrombosis, skin allergy testing and, if necessary, histology. Results: None of the observed heparin‐induced skin lesions was due to HIT; all lesions were caused by delayed‐type IV‐hypersensitivity reactions (DTH) instead. Even the cutaneous reaction in one patient with concomitant HIT could be classified histologically as DTH reaction, amounting to an association of heparin‐induced skin lesions and HIT in 1.2% (1/87; 95% confidence interval, 0.00–0.06). Conclusion: Heparin‐induced skin lesions associated with use of low‐molecular‐weight heparins do not seem to be strongly associated with a systemic immunologic reaction in terms of HIT and might rather be due to DTH reactions than due to microvascular thrombosis. Hence, we propose refining existing pretest probability scores for HIT, unless underlying causes have been clarified.