No differences in the incidence of CAP were observed between the use of OAD in monotherapy vs. metformin. Thiazolidinedione use in combination was associated with an increase in the risk of CAP when compared to metformin + sulfonylureas. The use of DPP-4 inhibitors was not associated with an increased risk of CAP.

We found no di erences in total numbers of deaths, heart or vascular deaths, total heart problems, or vascular problems, nor in total serious harms, between lower and standard blood pressure goal approaches. Based on very little information, we found more dropouts resulting from drug-related harms in the lower blood pressure target group and no overall health benefit among people in the lower target group. Quality of the evidence The best available evidence does not support lower blood pressure goals over standard goals in people with elevated blood pressure and heart or vascular problems. More new trials are needed to examine this question. Overall, the quality of evidence was assessed as low to moderate according to the GRADE assessment. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease (Review)

Blood pressure targets for the treatment of people with hypertension and cardiovascular disease (Review)

A Cochrane systematic review on immediate-release methylphenidate for adults with attention deficit hyperactivity disorder (ADHD) was withdrawn from the Cochrane Library on 26 May 2016 after substantial criticism of its methods and flawed conclusions. Retraction of scientific papers on this basis is unusual but can be necessary. We provide a summary of the criticism that led to the withdrawal. We detail the methodological flaws of the withdrawn Cochrane systematic review and general issues of bias and shortcomings of the included ADHD trials: cross-over designs compared with parallelgroup designs, exclusion of participants with psychiatric comorbidity, absence of 'functional outcomes' and use

Background Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown. Objectives To determine if 'lower' blood pressure targets (≤ 135/85 mmHg) are associated with reduction in mortality and morbidity as compared with 'standard' blood pressure targets (≤ 140 to 160/ 90 to 100 mmHg) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease). Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to February 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the Latin American and Caribbean Health Science Literature Database (from 1982) and contacted authors of relevant papers regarding further published and unpublished work. There were no language restrictions. Selection criteria We included randomized controlled trials (RCTs) with more than 50 participants per group and at least six months follow-up. Trial reports needed to present data for at least one primary outcome (total mortality, serious adverse events, total cardiovascular events, cardiovascular mortality). Eligible interventions were lower target for systolic/diastolic blood pressure (≤ 135/85 mmHg) compared with standard target for blood pressure (≤ 140 to 160/90 to 100 mmHg). Participants were adults with documented hypertension or who were receiving treatment for hypertension and cardiovascular history for myocardial infarction, stroke, chronic peripheral vascular occlusive disease or angina pectoris. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease (Review)

Analysis 2.1. Comparison 2: Combination therapy versus monotherapy (men versus women), Outcome

Chronotherapy versus conventional statins therapy for the treatment of hyperlipidaemia.

BackgroundStarting with one drug and starting with a combination of two drugs are strategies suggested in clinical guidelines as initial treatment of hypertension. The recommendations are not based on evidence about clinically relevant outcomes. Some antihypertensive combinations have been shown to be harmful. The actual harm-to-benefit balance of each strategy is unknown. ObjectivesTo determine if there are differences in clinical outcomes between monotherapy and combination therapy as initial treatment for primary hypertension. Search methodsWe searched the Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 2), Ovid MEDLINE, Ovid Embase, LILACS, ClinicalTrials.gov, Current Controlled Trials, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to February 2016. We searched in clinical studies repositories of pharmaceutical companies, reviews of combination drugs in Food and Drug Administration and European Medicines Agency, and lists of references in reviews and clinical practice guidelines. Selection criteriaRandomized, double-blind trials with at least 12 months' follow-up in adults with primary hypertension (systolic blood pressure/diastolic blood pressure 140/90 mmHg or higher, or 130/80 mmHg or higher if participants had diabetes), which compared combination of two first-line antihypertensive drug with monotherapy as initial treatment. Trials had to include at least 50 participants per group and report mortality, cardiovascular mortality, cardiovascular events or serious adverse events. Data collection and analysisTwo authors independently selected trials for inclusion, evaluated the risk of bias and entered the data. Primary outcomes were mortality, serious adverse events, cardiovascular events and cardiovascular mortality. Secondary outcomes were withdrawals due to drug-related adverse effects, reaching blood pressure control (as defined in each trial) and blood pressure change from baseline. Analyses were based on the intention-to-treat principle. We summarized data on dichotomous outcomes as risk ratios with 95% confidence intervals.