A Systematic Review for Variables to Be Collected in a Transplant Database for Improving Risk Prediction.

BACKGROUND: This systematic review was commissioned to identify new variables associated with transplant outcomes that are not currently collected by the Organ Procurement and Transplantation Network (OPTN). METHODS: We identified 81 unique studies including 1 193 410 patients with median follow-up of 36 months posttransplant, reporting 108 unique risk factors. RESULTS: Most risk factors (104) were recipient related; few (4) were donor related. Most risk factors were judged to be practical and feasible to routinely collect. Relative association measures were small to moderate for most risk factors (ranging between 1.0 and 2.0). The strongest relative association measure for a heart transplant outcome with a risk factor was 8.6 (recipient with the previous Fontan operation), for a kidney transplant 2.8 (sickle cell nephropathy as primary cause of end-stage renal disease), for a liver transplant 14.3 (recipient serum ferritin >500 µg/L), and for a lung transplant 6.3 (Burkholderia cepacia complex infection for 1 y or less). OPTN may consider some of these 108 variables for future collection to enhance transplant research and clinical care. CONCLUSIONS: Evidence-based approaches can be used to determine variables collected in databases and registries. Several candidate variables have been identified for OPTN.

Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Testosterone prescribing for men has dramatically increased, and there have been concerns about inappropriate use and adverse events. While regulatory bodies have warned about increased risk of venous thromboembolism (VTE), published clinical data supporting an increased risk for VTE are limited. OBJECTIVE: To conduct a systematic review of studies examining the association between testosterone therapy in men and VTE. METHODS: Comprehensive searches of multiple databases were performed from inception through October 3rd, 2018. Randomized control trials (RCTs) and observational studies examining the association between exogenous testosterone (any route) and VTE. Study selection and data extraction were performed by two independent investigators. Random-effect model meta-analyses were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CIs). Heterogeneity among studies was evaluated using the I2 statistic. Risk of bias was assessed using the Cochrane and Newcastle-Ottawa tools. RESULTS: Six RCTs (n = 2236) and 5 observational studies (n = 1,249,640) were included. Five RCTs were performed in men with documented hypogonadism. The observational studies included: 2 case-control studies, 2 retrospective cohorts, and 1 retrospective cohort with a nested case-control study. There was no evidence of a statistically significant association between VTE and testosterone (OR 1.41, 95%CI 0.96-2.07). Heterogeneity was high (I-squared = 84.4%). The association remained nonsignificant when the analysis was stratified by study design: RCTs (2.05, 95% CI 0.78-5.39); cohort (1.06, 95% CI 0.85-1.33); and case-control (1.34, 95% CI 0.78-2.28). The overall risk of bias was moderate. CONCLUSIONS: The current evidence is of low certainty but does not support an association between testosterone use and VTE in men.

A systematic review of surveillance after endovascular aortic repair.

OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the optimal modality and frequency of surveillance after endovascular aortic repair (EVAR) in adult patients with abdominal aortic aneurysms. METHODS: We searched for studies of post-EVAR surveillance in MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Scopus through May 10, 2016. The outcomes of interest were endoleaks, mortality, limb ischemia, renal complications, late rupture, and aneurysm-related mortality. Outcomes were pooled using a random-effects model and were reported as incidence rate and 95% confidence interval. RESULTS: Of 1099 candidate references, we included 6 meta-analyses and 52 observational studies. Complication rates were common after EVAR, particularly in the first year. Magnetic resonance imaging had a higher detection rate of endoleaks than computed tomography angiography. Doppler ultrasound had lower diagnostic accuracy, whereas contrast-enhanced ultrasound was likely to be as sensitive as computed tomography angiography. The highest endoleak detection rates were in surveillance approaches that used combined tests. There were no studies that compared different surveillance intervals to determine optimal intervals; however, most studies reported detection rates of patient-important outcomes at 1, 6, 12, 24, 36, 48, and 60 months. Data were insufficient to provide comparative inferences about the best strategy to reduce the risk of patient-important outcomes, such as mortality, limb ischemia, rupture, and renal complications. CONCLUSIONS: Several tests with reasonable diagnostic accuracy are available for surveillance after EVAR. The available evidence suggests a high complication rate, particularly in the first year, and provides a rationale for surveillance.

Comparative Effectiveness and Safety of Cognitive Behavioral Therapy and Pharmacotherapy for Childhood Anxiety Disorders: A Systematic Review and Meta-analysis.

Importance: Childhood anxiety is common. Multiple treatment options are available, but existing guidelines provide inconsistent advice on which treatment to use. Objectives: To evaluate the comparative effectiveness and adverse events of cognitive behavioral therapy (CBT) and pharmacotherapy for childhood anxiety disorders. Data Sources: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus from database inception through February 1, 2017. Study Selection: Randomized and nonrandomized comparative studies that enrolled children and adolescents with confirmed diagnoses of panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, or separation anxiety and who received CBT, pharmacotherapy, or the combination. Data Extraction and Synthesis: Independent reviewers selected studies and extracted data. Random-effects meta-analysis was used to pool data. Main Outcomes and Measures: Primary anxiety symptoms (measured by child, parent, or clinician), remission, response, and adverse events. Results: A total of 7719 patients were included from 115 studies. Of these, 4290 (55.6%) were female, and the mean (range) age was 9.2 (5.4-16.1) years. Compared with pill placebo, selective serotonin reuptake inhibitors (SSRIs) significantly reduced primary anxiety symptoms and increased remission (relative risk, 2.04; 95% CI, 1.37-3.04) and response (relative risk, 1.96; 95% CI, 1.60-2.40). Serotonin-norepinephrine reuptake inhibitors (SNRIs) significantly reduced clinician-reported primary anxiety symptoms. Benzodiazepines and tricyclics were not found to significantly reduce anxiety symptoms. When CBT was compared with wait-listing/no treatment, CBT significantly improved primary anxiety symptoms, remission, and response. Cognitive behavioral therapy reduced primary anxiety symptoms more than fluoxetine and improved remission more than sertraline. The combination of sertraline and CBT significantly reduced clinician-reported primary anxiety symptoms and response more than either treatment alone. Head-to-head comparisons were sparse, and network meta-analysis estimates were imprecise. Adverse events were common with medications but not with CBT and were not severe. Studies were too small or too short to assess suicidality with SSRIs or SNRIs. One trial showed a statistically nonsignificant increase in suicidal ideation with venlafaxine. Cognitive behavioral therapy was associated with fewer dropouts than pill placebo or medications. Conclusions and Relevance: Evidence supports the effectiveness of CBT and SSRIs for reducing childhood anxiety symptoms. Serotonin-norepinephrine reuptake inhibitors also appear to be effective based on less consistent evidence. Head-to-head comparisons between various medications and comparisons with CBT represent a need for research in the field.

Do not throw the baby out with the bath water: a guide for using non-significant results in practice.

Acting on results that are not statistically significant is challenging for clinicians. Such results are often interpreted as evidence of lack of association or as useless evidence. We provide a framework for interpreting and applying non-significant results at the point of care using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.