Background

Influenza is an acute respiratory illness caused by influenza viruses, which occurs in epidemics worldwide every year. Children are an important target for prevention methods, including vaccination. While evidence about the decision on whether to vaccinate healthy children is robust, evidence supporting the decision of which of available vaccines to use remains unclear.

This review will summarize the evidence about the efficacy and safety of the available vaccines for seasonal influenza licensed in the United States for use in healthy children.

Methods/design

An umbrella systematic review (SR) and network meta-analysis will be conducted of randomized controlled trials (RCTs). We will search for SRs to identify parallel RCTs evaluating inactive and/or live attenuated influenza vaccines licensed in the United States for use in healthy children to prevent influenza. Subsequently, we will update the literature search of the selected SRs to the present time to capture recent controlled studies. To complement the work focused on harms, we will also select observational studies focusing on post marketing retrospective studies. Inclusion will not be limited by language, publication date or publication status. To identify additional candidate studies, we will review the reference lists of the eligible primary studies and narrative reviews; we will query the expert members of the Advisory Committee on Immunization Practices and review references from their previous statement. Additionally, we will review the reports from the Institute of Medicine on the adverse effects of vaccines. Two reviewers will independently determine study eligibility and will extract descriptive, methodological (using the Cochrane risk of bias tool for RCTs and the Newcastle–Ottawa scale for observational studies) and efficacy data. When possible, we will conduct meta-analyses and network meta-analyses by combining indirect and direct comparisons.

We will evaluate heterogeneity using the I2 statistic and the agreement of indirect comparisons and direct evidence. We will report the Cochrane Q test to determine the statistical significance of heterogeneity.

The overall quality of evidence will be assessed following the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach.

Discussion

Our systematic review will allow patients, clinicians, guideline developers and policy makers to make evidence-based choices between the two available vaccine options, by providing information regarding benefits and harms of these types of vaccines.

Background

Many drugs and treatments given to patients for various reasons affect their weight. This side effect is of great importance to patients and is also a concern for the treating physician because weight change may lead to the emergence or worsening of other health conditions.

Objective

The aim of this study is to summarize the evidence about commonly prescribed drugs and their association with weight change.

Methods/Design

Umbrella systematic review and meta-analysis of randomized controlled trials.

We will use an umbrella approach to identify eligible randomized controlled trials (RCTs). We will search for systematic reviews of RCTs that compare any of the drugs that have been associated with weight gain (obesogenic) or weight loss (leptogenic); these have been summarized by our experts’ panel in a predefined list. Two reviewers will independently determine RCT eligibility. Disagreement will be solved by consensus and arbitrated by a third reviewer. We will extract descriptive, methodological, and efficacy data in duplicate. Our primary continuous outcomes will be weight loss or gain expressed as a mean difference (MD) for weight (kg) or BMI (kg/m2). We will calculate the MD considering the mean difference in weight or BMI between baseline and the last available follow-up in both study arms (drugs and placebo). Our primary dichotomous outcome, presented as a relative risk, will compare the ratio of the incidence of weight change in each trial arm. When possible, results will be pooled using classic random-effects meta-analyses and a summary estimate with 95% confidence interval will provided. We will use the I2 statistic and Cochran’s Q test to assess heterogeneity. The risk of bias will be assessed using the Cochrane risk of bias tool. Publication bias, if appropriate, will be evaluated, as well as overall strength of the evidence.

Discussion

This systematic review will offer the opportunity to generate a ranking of commonly prescribed drugs in terms of their effect on weight, allowing guideline developers and patient-physician dyad to choose between available therapies.

Background

Hyperprolactinemia is a common endocrine disorder that can be associated with significant morbidity. We conducted a systematic review and meta-analyses of outcomes of hyperprolactinemic patients, including microadenomas and macroadenomas, to provide evidence-based recommendations for practitioners. Through this review, we aimed to compare efficacy and adverse effects of medications, surgery and radiotherapy in the treatment of hyperprolactinemia.

Methods

We searched electronic databases, reviewed bibliographies of included articles, and contacted experts in the field. Eligible studies provided longitudinal follow-up of patients with hyperprolactinemia and evaluated outcomes of interest. We collected descriptive, quality and outcome data (tumor growth, visual field defects, infertility, sexual dysfunction, amenorrhea/oligomenorrhea and prolactin levels).

Results

After review, 8 randomized and 178 nonrandomized studies (over 3,000 patients) met inclusion criteria. Compared to no treatment, dopamine agonists significantly reduced prolactin level (weighted mean difference, -45; 95% confidence interval, -77 to −11) and the likelihood of persistent hyperprolactinemia (relative risk, 0.90; 95% confidence interval, 0.81 to 0.99). Cabergoline was more effective than bromocriptine in reducing persistent hyperprolactinemia, amenorrhea/oligomenorrhea, and galactorrhea. A large body of noncomparative literature showed dopamine agonists improved other patient-important outcomes. Low-to-moderate quality evidence supports improved outcomes with surgery and radiotherapy compared to no treatment in patients who were resistant to or intolerant of dopamine agonists.

Conclusion

Our results provide evidence to support the use of dopamine agonists in reducing prolactin levels and persistent hyperprolactinemia, with cabergoline proving more efficacious than bromocriptine. Radiotherapy and surgery are useful in patients with resistance or intolerance to dopamine agonists.

Background

Hypertriglyceridemia may be associated with important complications. The aim of this study is to estimate the magnitude of association and quality of supporting evidence linking hypertriglyceridemia to cardiovascular events and pancreatitis.

Methods

We conducted a systematic review of multiple electronic bibliographic databases and subsequent meta-analysis using a random effects model. Studies eligible for this review followed patients longitudinally and evaluated quantitatively the association of fasting hypertriglyceridemia with the outcomes of interest. Reviewers working independently and in duplicate reviewed studies and extracted data.

Results

35 studies provided data sufficient for meta-analysis. The quality of these observational studies was moderate to low with fair level of multivariable adjustments and adequate exposure and outcome ascertainment. Fasting hypertriglyceridemia was significantly associated with cardiovascular death (odds ratios (OR) 1.80; 95% confidence interval (CI) 1.31-2.49), cardiovascular events (OR, 1.37; 95% CI, 1.23-1.53), myocardial infarction (OR, 1.31; 95% CI, 1.15-1.49), and pancreatitis (OR, 3.96; 95% CI, 1.27-12.34, in one study only). The association with all-cause mortality was not statistically significant.

Conclusions

The current evidence suggests that fasting hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis.

Précis: hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis