Are concomitant treatments confounding factors in randomized controlled trials on intensive blood-glucose control in type 2 diabetes? a systematic review

International audienceBackgroundOpen-label, randomized controlled trials (RCTs) are subject to observer bias. If patient management is conducted without blinding, a difference between groups may be explained by other factors than study treatment. One factor may come from taking concomitant treatments with an efficacy on the studied outcomes. In type 2 diabetes, some antihypertensive or lipid-lowering drugs are effective against diabetic complications. We wanted to determine if these concomitant treatments were correctly reported in articles of RCTs on type 2 diabetes and if they might have influenced the outcome.MethodsWe performed a systematic review using Medline, Embase, and the Cochrane Library (from January 1950 to July 2010). Open-label RCTs assessing the effectiveness of intensive blood-glucose control in type 2 diabetes were included. We chose five therapeutic classes with proven efficacy against diabetes complications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists (AIIRAs), fibrates, statins, and aspirin. Differences between concomitant treatments were considered statistically significant when p ResultsA total of eight open-label RCTs were included, but only three (37.5%) of them published concomitant treatments. In two studies (ACCORD and ADVANCE), a statistically significant difference was observed between the two groups for aspirin (p = 0.02) and ACEIs (p = 0.02).ConclusionsFew concomitant treatments were published in this sample of open-label RCTs. We cannot completely eliminate an observer bias for these studies. This bias probably influenced the results to an extent that has yet to be determined

Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials

Objective To determine all cause mortality and deaths from cardiovascular events related to intensive glucose lowering treatment in people with type 2 diabetes

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects. METHODS: We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia). RESULTS: Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67-0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74-0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70-0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66-0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76-0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74-0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71-0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77-0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74-0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased. CONCLUSION: Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI

Can we identify response markers to antihypertensive drugs? First results from the Ideal Trial

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.Journal of Human Hypertension advance online publication, 17 April 2014; doi:10.1038/jhh.2014.29

The Global Risk Approach Should Be Better Applied in French Hypertensive Patients: A Comparison between Simulation and Observation Studies

The prediction of the public health impact of a preventive strategy provides valuable support for decision-making. International guidelines for hypertension management have introduced the level of absolute cardiovascular risk in the definition of the treatment target population. The public health impact of implementing such a recommendation has not been measured.We assessed the efficiency of three treatment scenarios according to historical and current versions of practice guidelines on a Realistic Virtual Population representative of the French population aged from 35 to 64 years: 1) BP≥160/95 mm Hg; 2) BP≥140/90 mm Hg and 3) BP≥140/90 mm Hg plus increased CVD risk. We compared the eligibility following the ESC guidelines with the recently observed proportion of treated amongst hypertensive individuals reported by the Etude Nationale Nutrition Santé survey. Lowering the threshold to define hypertension multiplied by 2.5 the number of eligible individuals. Applying the cardiovascular risk rule reduced this number significantly: less than 1/4 of hypertensive women under 55 years and less than 1/3 of hypertensive men below 45 years of age. This was the most efficient strategy. Compared to the simulated guidelines application, men of all ages were undertreated (between 32 and 60%), as were women over 55 years (70%). By contrast, younger women were over-treated (over 200%).The global CVD risk approach to decide for treatment is more efficient than the simple blood pressure level. However, lack of screening rather than guideline application seems to explain the low prescription rates among hypertensive individuals in France. Multidimensional analyses required to obtain these results are possible only through databases at the individual level: realistic virtual populations should become the gold standard for assessing the impact of public health policies at the national level

Temporal trends in the proportion of "cure" in children, adolescents, and young adults diagnosed with chronic myeloid leukemia in England: A population-based study.

BACKGROUND: Survival probability in children, adolescents, and young adults with chronic myeloid leukemia (CML) has dramatically improved during recent years. Tyrosine kinase inhibitors (TKI), targeted drugs developed for patients with CML, were introduced in 2001 in England. We here quantify the trends in the "cure" proportion according to the year of diagnosis. METHODS: We included all children, adolescents, and young patients with CML (0 to 24 years) diagnosed in England during 1980 to 2005. We fitted mixture cure models to estimate the "cure" proportion and the median survival time among the "uncured" patients according to the year of diagnosis, adjusted for age at diagnosis. RESULTS: The "cure" proportion increased dramatically between 1980 and 2005, from under 10% to over 80%, while conversely, the median survival time of "uncured" patients decreased slightly between 1980 and 1999, with the trend from 2000 being uncertain. CONCLUSIONS: The striking improvement of the "cure" fraction in young patients with CML since the early 1980s is concomitant with improvement of treatment, especially the allogeneic hematopoietic stem-cell transplant and, later, the introduction of TKI. The trends over the last years (2000-2005) remain, however, uncertain and would benefit from further studies with more recent data and updated follow-up

Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials

Catherine Cornu and colleagues performed a meta-analysis of randomised controlled trials of metformin efficacy on cardiovascular morbidity or mortality in patients with type 2 diabetes and showed that although metformin is considered the gold standard, its benefit/risk ratio remains uncertain

EurOP2E – the European Open Platform for Prescribing Education, a consensus study among clinical pharmacology and therapeutics teachers

Purpose Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. Methods CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. Results Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. Conclusion Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system