Thomas Semlitsch

Benefit assessment of salt reduction in patients with hypertension: systematic overview.

Objective We assessed the benefits and harm of reduced salt intake in patients with essential hypertension focusing on patient-relevant outcomes and blood pressure. Methods A systematic search of five electronic databases was performed to identify high-quality secondary literature based on randomized controlled trials (RCTs). An update primary literature search (RCTs) was performed for the time period up to 2010 that was not covered by secondary literature. Major outcomes were death, cardiovascular morbidity/mortality, hospital stays, terminal renal failure, quality of life, and adverse events. Change in blood pressure was defined as surrogate parameter. Results Four different systematic reviews and two RCTs met the inclusion criteria. Only one review reported limited data on patient-relevant outcomes. Over an intervention period of up to 12 months, mean SBP was reduced by 3.6–8.0 mmHg in all reviews. For the same intervention period, a statistically significant advantage with regard to mean DBP reduction ranging from 1.9 to 2.8 mmHg was found in three reviews. The fourth publication reported a nonsignificant reduction (DBP reduction of 4.7 mmHg). None of the RCTs identified in the primary literature search update reported data on patient-relevant outcomes. However, both RCTs found blood pressure improvements with salt reduction. Conclusion A benefit from a salt-reduced diet in patients with high blood pressure is not proven with regard to patient-relevant outcomes based on systematic reviews and RCTs published up to 2010. The results indicate a blood pressure-lowering effect through reduced salt intake in hypertensive patients.

A systematic review and meta-analysis of the efficacy of lixisenatide in the treatment of patients with type 2 diabetes

The aim of this study is to assess the efficacy and safety of lixisenatide for treating type 2 diabetes. A systematic search in electronic databases (up to October 2012) was conducted and the manufacturer was contacted regarding unpublished data. Randomized controlled trials (RCTs) were included if they provided information on at least one of the following outcomes: mortality, health‐related quality of life, hypoglycaemic events, adverse events, change in HbA1c, body weight, blood pressure, gastric emptying, fasting plasma glucose or 2 h postprandial glucose (PPG). Twenty‐six publications and 10 unpublished study reports, relating to 14 RCTs (6156 patients) were included. Eleven studies related to placebo comparisons; active comparators were in three studies. Compared to placebo, lixisenatide significantly reduced HbA1c (−0.52%; 95% CI: −0.64 to −0.39), bodyweight (−0.65 kg; 95% CI: −0.94 to −0.37) and 2‐h PPG level (−4.58 mmol/l; 95% CI: −5.88 to −3.28). There were significantly more symptomatic hypoglycaemic events among lixisenatide compared to placebo‐treated patients (log OR: 0.54; 95% CI: 0.32–0.75), but significantly fewer compared to other incretin mimetics. In comparison to exenatide and liraglutide, lixisenatide was more effective in reducing 2 h‐PPG with a better adverse events profile, but it showed a lower reduction in HbA1c and body weight. Lixisenatide improves HbA1c levels and moderately reduces body weight compared to placebo and showed less frequent symptomatic hypoglycaemic and gastrointestinal events and an improvement in PPG control compared to other GLP‐1 agonists. Firm conclusions regarding the performance of lixisenatide compared to other incretin mimetics, however, can not yet be drawn, due to limited data.

Clinical effectiveness of stress-reduction techniques in patients with hypertension: systematic review and meta-analysis.

Objective: A systematic review and meta-analysis focusing on patient-relevant outcomes and blood pressure was conducted to assess the clinical effectiveness of stress-reduction techniques in adults with essential hypertension. Methods: Systematic reviews and randomized controlled trials (RCTs) were identified as part of a systematic search in six electronic databases ending September 2012. RCTs comparing stress-reduction techniques versus no such techniques with a follow-up of at least 24 weeks and published in English or German were included. Outcomes of interest were death, cardiovascular morbidity/mortality, end-stage renal disease, health-related quality of life, adverse events, changes in blood pressure, and changes in antihypertensive medication. When appropriate, meta-analyses were used to combine data. Results: Seventeen RCTs analyzing different stress-reduction techniques such as biofeedback, relaxation or combined interventions were identified. Data were not reported for most of the patient-relevant outcomes, and meta-analyses could only be used to evaluate effects on blood pressure. The data indicated a blood pressure-lowering effect, but the studies had methodological shortcomings and heterogeneity between them was high. Mean group differences for DBP ranged from −10 to 1 mmHg and for SBP from −12 to 10 mmHg. In terms of antihypertensive medication, no favorable effects of stress-reduction techniques could be identified. Conclusions: The available RCTs on stress-reduction techniques used for at least 24 weeks appeared to indicate a blood pressure-lowering effect in patients with essential hypertension, but this should be interpreted with caution because of major methodological limitations. A benefit of specific stress-reduction techniques in hypertensive patients remains unproven.

Choosing Wisely: assessment of current US top five list recommendations’ trustworthiness using a pragmatic approach

Objectives Identification of sufficiently trustworthy top 5 list recommendations from the US Choosing Wisely campaign. Setting Not applicable. Participants All top 5 list recommendations available from the American Board of Internal Medicine Foundation website. Main outcome measures/interventions Compilation of US top 5 lists and search for current German highly trustworthy (S3) guidelines. Extraction of guideline recommendations, including grade of recommendation (GoR), for suggestions comparable to top 5 list recommendations. For recommendations without guideline equivalents, the methodological quality of the top 5 list development process was assessed using criteria similar to that used to judge guidelines, and relevant meta-literature was identified in cited references. Judgement of sufficient trustworthiness of top 5 list recommendations was based either on an ‘A’ GoR of guideline equivalents or on high methodological quality and citation of relevant meta-literature. Results 412 top 5 list recommendations were identified. For 75 (18%), equivalents were found in current German S3 guidelines. 44 of these recommendations were associated with an ‘A’ GoR, or a strong recommendation based on strong evidence, and 26 had a ‘B’ or a ‘C’ GoR. No GoR was provided for 5 recommendations. 337 recommendations had no equivalent in the German S3 guidelines. The methodological quality of the development process was high and relevant meta-literature was cited for 87 top 5 list recommendations. For a further 36, either the methodological quality was high without any meta-literature citations or meta-literature citations existed but the methodological quality was lacking. For the remaining 214 recommendations, either the methodological quality was lacking and no literature was cited or the methodological quality was generally unsatisfactory. Conclusions 131 of current US top 5 list recommendations were found to be sufficiently trustworthy. For a substantial number of current US top 5 list recommendations, their trustworthiness remains unclear. Methodological requirements for developing top 5 lists are recommended.

Evaluating Guidelines: A Review of Key Quality Criteria.

BACKGROUND Guidelines of high methodological quality make an essential contribution to the quality assurance of medical knowledge. The detailed evaluation of guideline quality is a complex and time-consuming task. The answers to a few key questions generally suffice for an initial, rapid assessment of the quality and utility of a guideline. METHOD We selectively searched the pertinent literature for guideline-assessing instruments and analyzed selected ones with respect to their target group, purpose, orientation, and comprehensiveness. We identified key questions from brief instruments that can be used to assess guideline quality rapidly. RESULTS A comparison of ten instruments revealed that most were designed to provide a highly detailed assessment of guideline quality. Four recently developed instruments enable a rough and rapid assessment. They focus, in essence, on four key questions: Was the evidence analyzed systematically? Does the evidence support the recommendations? Is the goal of the guideline formulated, and are the authors named? Is the organization of the guideline easy to follow, and are the recommendations clearly signposted? CONCLUSION Alongside the comprehensive instruments for assessing guidelines, such as DELBI and AGREE II, rapid-assessment instruments are a convenient tool for gaining a quick impression of the value of a guideline.

Self-management of Oral Anticoagulation

BACKGROUND Properly dosed oral anticoagulation effectively prevents thromboembolic events. It is unclear whether adult patients with an indication for long-term oral anticoagulation can benefit from self-management in terms of patient-oriented endpoints and improved coagulation values. METHOD We selectively searched the Medline database for high-quality systematic reviews based on randomized controlled trials of self-measurement or self-management of oral anticoagulation, compared to standard treatment. RESULTS We identified eight review articles based on overlapping sets of ran - domized clinical trials. In all of these systematic reviews, patients who performed self-measurement or self-management had a 40% to 50% lower rate of thromboembolic events; in six of them, the mortality was also significantly lower, by 30% to 50%. Subgroup analysis revealed that these effects were present exclusively in patients who performed self-management, and not in those who only performed self-measurement. None of the review articles revealed any difference in the frequency of severe hemorrhagic events. Quality of life and patient satisfaction were rated in five reviews, which, however, used different instruments, with the result that no clear conclusions could be drawn. All of the review articles documented an improvement in coagulation values, but information on statistical significance was mostly lacking. CONCLUSION Adults with an indication for long-term oral anticoagulation benefit from self-management, as compared to standard treatment with management of dosing by a physician. A limitation of this study is that the multiple review articles on which it is based were largely analyses of the same group of clinical trials.