A systematic review and meta-analysis of beta-blockers and renin-angiotensin system inhibitors for preventing left ventricular dysfunction due to anthracyclines or trastuzumab in patients with breast cancer.

AIMS: Trastuzumab and anthracyclines, often used in the treatment of breast cancer, may impair myocardial function, and reduce left ventricular ejection fraction (LVEF), potentially causing heart failure. Randomized controlled trials (RCTs) have evaluated the effects of beta-blockers (BBs), angiotensin receptor blockers (ARBs), and angiotensin-converting enzyme inhibitors (ACEI) on trastuzumab- and anthracycline-associated cardiotoxicity. We report a meta-analysis of these RCTs in patients with breast cancer. METHODS AND RESULTS: The primary analysis was on the effect of BBs and ACEI/ARBs on LVEF in patients treated with either trastuzumab or anthracyclines. A secondary analysis was done investigating the effect of BBs or ACEI/ARBs on LVEF in trastuzumab and anthracycline treatments. Only RCTs were included using the search term 'ARBs, ACEIs, BBs, anthracyclines, trastuzumab, and breast cancer' in PubMed, Embase, and CENTRAL up to 31 March 2021. A meta-analysis was conducted to estimate the mean difference (MD) in LVEF between intervention and placebo groups at follow-up. A total of nine RCTs (n = 1362) were included in the analysis. All patients were women. BBs and ACEI/ARBs were shown to attenuate the decline in LVEF during trastuzumab and anthracycline treatments [MD: 2.4; 95% confidence interval (CI): 0.3-4.2 and MD: 1.5; 95% CI: -0.6 to 3.7]. Compared with placebo, LVEF was significantly higher in patients assigned to BB or ACEI/ARB on trastuzumab (MD: 2.3; 95% CI: 0.0-4.6) but not on anthracyclines (MD: 1.9; 95% CI: -0.5 to 4.2). CONCLUSION: Both BB and ACEI/ARB therapies were associated with the preservation of LVEF during trastuzumab and anthracycline-containing regimens as compared with placebo, suggesting both to be beneficial.

The effectiveness of payment for performance in health care: A meta-analysis and exploration of variation in outcomes.

BACKGROUND: Pay for performance (P4P) incentive schemes are increasingly used world-wide to improve health system performance but results of evaluations vary considerably. A systematic analysis of this variation in the effects of P4P schemes is needed. METHODS: Evaluations of P4P schemes from any country were identified by searching for and updating systematic reviews of P4P schemes in health care in four bibliographic databases. Outcomes using different measures of effect were converted into standardized effect sizes (standardized mean difference, SMD) and each study was categorized as to whether or not it found a positive effect. Subgroup analysis, meta-regression and multilevel logistic regression were used to investigate factors explaining heterogeneity. Random-effects models were used because they take into account heterogeneity likely to be due to differences between studies rather than just chance. Sensitivity analysis was used to test the effect of different assumptions. FINDINGS: 96 primary studies were identified; 37 were included in the meta-analysis and meta-regression and all 96 in the logistic regression. The proportion of observed variation in study results that can be explained by true heterogeneity (I2) was 99.9%. Estimates of effect of P4P schemes were lower in evaluations using randomized controlled trials (SMD=0.08; 95% CI: 0.01-0.15) compared to no controls (0.15; 95% CI: 0.09-0.21), and lower for those measuring outcomes (e.g., smoking cessation) (SMD=0.0; 95% CI: -0.01 to 0.01) compared to process measures (e.g., giving cessation advice) (0.18; 95% CI: 0.06-0.31). Adjusting for other design features and the evaluation method, the odds of showing a positive effect was three times higher for schemes with larger incentives (>5% of salary/usual budget) (OR=3.38; 95% CI: 1.07-10.64). There were non-statistically significant increases in the odds of success if the incentive is paid to individuals (as opposed to groups) (OR=2.0; 95% CI: 0.62-6.56) and if there is a lower perceived risk of not earning the incentive (OR=2.9; 95% CI: 0.78-10.83). Schemes evaluated using less rigorous designs were 24 times more likely to have positive estimates of effect than those using randomized controlled trials (OR=24; 95% CI: 6.3-92.8). INTERPRETATION: Estimates of the effectiveness of incentive schemes on health outcomes are probably inflated due to poorly designed evaluations and a focus on process measures rather than health outcomes. Larger incentives and reducing the perceived risk of non-payment may increase the effect of these schemes on provider behavior.

A systematic review on drugs absorption modifications after eradication in Helicobacter pylori positive patients undergoing replacement therapy.

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) infection has been suggested as a cause of impaired drug absorption. This infection leads to alteration of the gastric acid secretion that may change the conformational characteristics of drugs and their intestinal absorption leading to uncertainties about the dose to administer and the therapeutic results. A systematic review was undertaken to clarify the implications of drug absorption during the administration of replacement therapies. METHODS: Electronic databases such as MEDLINE/Pubmed, EMBASE and The Cochrane Library [which includes Cochrane Database of Systematic Review (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstract of Reviews of Effect (DARE)] were searched. Grey literature databases (e.g. the International clinical trials registry platform, Trials Register, Clinical Trials.gov, Controlled Trials and TrialsCentral), Theses database, Government publication and LILACS database were also searched. No language restriction was applied. RESULTS: Infection and altered drug absorption were evaluated in patients under replacement therapies with iron, thyroxin and L-dopa. In all, seven studies included an improvement in drug absorption after eradication and an existing inverse correlation between the grade of gastric inflammation and indices of drug absorption were noticed. CONCLUSION: This systematic review confirmed the presence of an interaction between infection and drug absorption of orally administered replacement therapies. Gastric acid reduction and subsequent alteration of drug composition seem to lead this mechanism. Clinicians should be aware of this possible interaction when starting a replacement therapy in patients and when evaluating poor clinical response.

Lessons from aprotinin: is the routine use and inconsistent dosing of tranexamic acid prudent? Meta-analysis of randomised and large matched observational studies.

In view of the safety concerns that led to the withdrawal of aprotinin, should antifibrinolytics be used indiscriminately in cardiac surgery? This meta-analysis examines the efficacy and safety profile of tranexamic acid, and in comparison to aprotinin. We identified randomised trials and large observational studies investigating the use tranexamic acid from January 1995 to January 2009 using Pubmed/Cochrane search engine and included them in a two-tier meta-analysis. There were 25 randomised trials and four matched studies with a total of 5411 and 5977 patients, respectively, reporting tranexamic acid use in varying dosages. Tranexamic acid is administered intravenously either as single dose, infusion or both, sometimes added to pump prime or applied topically. Total intravenous dose of tranexamic acid varies from 1g to 20 g, administered over a period of 20 min to 12h. Compared with placebo, tranexamic acid is associated with a lower mean difference in blood loss (random effect -298 ml, 95% confidence [CI] -367 to -229, p<0.001) and decease in rates of re-operation for bleeding by 48%, transfusion of packed red cell by 47% and use of haemostatic blood products by 67%. A non-significant tendency for postoperative neurological events but a decrease in operative mortality was observed in patients treated with tranexamic acid compared with non-treatment group. Compared to aprotinin, tranexamic acid has less effective blood-conserving effect and mortality risk. Given the potential to increase neurological complications, the current trend towards indiscriminate use of tranexamic acid for all cardiac patients needs to be re-evaluated. Further studies are needed to clarify the neurological risk, appropriate indications and dosing of tranexamic acid.

A distinctly bimodal distribution pattern in the RR interval histogram predicts early recurrence of atrial fibrillation after electrical cardioversion.

Abnormal AV nodal behaviour could contribute to recurrence of Atrial Fibrillation (AF) after electrical cardioversion (ECV). We constructed RR interval histograms from 24-hour ECGs recorded before ECV in 98 patients with persistent AF. RR histograms were classified as unimodal or bimodal, and bimodal histograms classified into distinctly or indistinctly bimodal. At 1 week after ECV, 52 patients (53%) were in AF and at one-month 66 (67%) were in AF. A bimodal RR interval distribution during AF was found in 17 patients (18%), a distinctly bimodal RR histogram in 8 of these (47%). Compared to those with indistinct bimodality, patients with a distinctly bimodal RR histogram were more likely to have AF at one-week and one-month (88 vs. 33%, 100 vs. 33%, p=0.01, p=0.009, respectively).