Direct comparative effectiveness and safety between non-vitamin K antagonist oral anticoagulants for stroke prevention in nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies.

The non-vitamin K antagonist oral anticoagulants (NOACs) have been increasingly prescribed in clinical practice for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Direct comparisons between NOACs in trials are lacking, leaving an important clinical decision-making gap. We aimed to perform a systematic review and meta-analysis to summarize the evidence of observational studies for direct comparative effectiveness and safety amongst NOACs in patients with AF. Conference proceedings and electronic databases including MEDLINE, CINAHL, EMBASE and PUBMED were systematically searched. We included observational studies directly comparing individual NOACs in patients with nonvalvular AF who were aged ≥ 18 years for stroke prevention. Primary outcome included effectiveness outcome (stroke or systemic embolism) and safety outcome (major bleeding). Data were extracted in duplicated by two reviewers independently. A random-effects meta-analysis was conducted to synthesize the data from included observational studies. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to rate the overall quality of evidence for each outcome. Fifteen studies were included for qualitative synthesis, twelve studies for meta-analyses. It was found that rivaroxaban and dabigatran were similar with regard to risk of stroke or systemic embolism (Hazard ratio [HR] = 1.00, 95% CI 0.91-1.10; evidence quality: low), but rivaroxaban was associated with higher risk of major bleeding (HR = 1.39, 95% CI 1.28-1.50; evidence quality: moderate). Compared with apixaban, a significantly higher risk of major bleeding was observed with rivaroxaban (HR = 1.71, 95% CI 1.51-1.94; evidence quality: low). Apixaban was associated with lower risk of major bleeding, in comparison with dabigatran (HR = 0.80, 95% CI 0.68-0.95; evidence quality: low). No differences in risk of stroke or systemic embolism was observed between rivaroxaban versus apixaban, and apixaban versus dabigatran. In this study, apixaban was found to have the most favorable safety profile amongst the three NOACs. No significant difference was observed in risk of stroke or systemic embolism between the NOACs. Such findings may provide some decision-making support for physicians regarding their choices amongst NOACs in patients with AF.Registration PROSPERO (identifier: CRD42016052908).

Relationship between hyperbaric oxygen therapy and quality of life in participants with chronic diabetic foot ulcers: data from a randomized controlled trial.

AIMS: To investigate the effect of hyperbaric oxygen therapy on health-related quality of life (HRQoL) in participants with diabetes and chronic foot ulcers. METHODS: Using data from a randomized controlled trial, we included 103 participants (49 in hyperbaric oxygen therapy group and 54 in sham group) for analyses. The primary outcome was HRQoL as measured by the EQ-5D-3L instrument, while secondary outcomes included quality of life evaluated by the Short Form 36 (SF-36) and Diabetic Foot Ulcers Scale-Short Form (DFS-SF). We used the analysis of covariance to assess whether the EQ-5D index values in hyperbaric oxygen therapy group differed from the sham group. Logistic regression was used to assess the relationship between hyperbaric oxygen therapy and the responses of 'problems' for the EQ-5D health states. RESULTS: No significant differences in EQ-5D index values were found between the hyperbaric oxygen therapy and sham groups: 0.01 (95% CI -0.25, 0.28; p = 0.93) at week 12; 0.07 (95% CI -0.21, 0.34; p = 0.64) at week 6. Hyperbaric oxygen therapy was found to be associated with fewer participants reporting 'problems' in mobility (OR 0.24, 95% CI 0.07, 0.85 at week 12) and pain or discomfort (OR 0.20, 95% CI 0.07, 0.61 at week 6; OR 0.32, 95% CI 0.11, 0.97 at week 12), compared with the sham group. No significant differences in SF-36 or DFS-SF were observed. CONCLUSIONS: No significant effect of hyperbaric oxygen therapy on HRQoL measured by EQ-5D index value was found in this study. Due to the potential insufficient power to assess statistical difference, more large-scale research is needed to further evaluate the effect of hyperbaric oxygen therapy on HRQoL in participants with chronic diabetic foot ulcers.

Effect of green tea supplementation on blood pressure among overweight and obese adults: a systematic review and meta-analysis.

BACKGROUND: Emerging randomized controlled trials (RCTs) investigating the effect of green tea or green tea extract (GTE) supplementation on blood pressure (BP) among overweight and obese adults reported inconsistent findings. OBJECTIVE: To conduct a systematic review and meta-analysis to clarify the efficacy of green tea or GTE on BP among overweight and obese adults. METHODS: Electronic databases, conference proceedings and gray literature were searched systematically to include parallel and cross-over RCTs examining the efficacy of green tea or GTE on BP compared with placebo. Data were meta-analyzed using a random-effects model, to compare the mean difference of the change in BP from baseline in the intervention and the placebo groups. RESULTS: Fourteen RCTs with 971 participants (47% women) were pooled for analysis. Green tea or GTE produced a significant effect on both SBP (mean difference -1.42 mmHg, 95% confidence interval -2.47 to -0.36, P = 0.008; I = 52%, P = 0.01 for heterogeneity) and DBP (mean difference -1.25 mmHg, 95% confidence interval -2.32 to -0.19, P = 0.02; I = 74%, P < 0.001 for heterogeneity), compared with placebo. The quality of evidence across studies was low. Similar results were found in subgroup and sensitivity analyses. CONCLUSION: Among overweight and obese adults, green tea or GTE supplementation is found to cause a small but significant reduction in BP. More high-quality RCTs with large sample sizes are needed to further confirm the efficacy on BP and make strong recommendations for green tea or GTE supplementation among the overweight and obese adults.

Effect of green tea supplementation on blood pressure among overweight and obese adults: a protocol for a systematic review.

INTRODUCTION: Emerging randomised controlled trials (RCTs) exploring the effect of green tea (GT) supplementation or GT extract (GTE) on blood pressure (BP) among overweight and obese adults yielded inconclusive results. We aim to conduct a systematic review to summarise the evidence of RCTs until now, to clarify the efficacy of GT supplementation or GTE in BP in overweight and obese populations. METHODS AND ANALYSIS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and ClinicalTrials.gov will be searched to retrieve potential RCTs. Unpublished studies will be identified by searching the abstract books or websites of the three major conference proceedings: the International Society of Hypertension, the Nutrition & Health Conference and the World Congress of Nutrition and Health. A random-effects meta-analysis will be performed to pool the mean difference for the change in BP from baseline (ie, postintervention BP minus baseline BP) between intervention groups and placebo groups of the included studies, presenting the pooled results with 95% CIs. Subgroups analyses will be conducted according to different doses of GT or GTE, trial duration, geographic regions, overweight versus obese participants, and participants with versus without change in body weight after intervention. Sensitivity analysis will be performed by excluding studies classified as having a high risk of bias, applying a fixed-effects model, using the postintervention BP for analyses and excluding trials with non-study cointerventions. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal. It will be disseminated electronically and in print. Summarising the RCT evidence to clarify the efficacy in BP among overweight and obese adults will aid in making the dietary recommendation of GT and improving the clinical management of hypertension. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014007273.

Canadian cost- utility analysis of intravenous immunoglobulin for acute childhood idiopathic thrombocytopenic purpura.

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is a hematological disorder and can be classified as acute or chronic. The main goal of treatment for acute childhood ITP is the prevention of potentially fatal bleeding complications, the most serious of which is intracranial hemorrhage (ICH). Treatment options for acute childhood ITP include splenectomy, corticosteroids, and blood products such as intravenous immunoglobulin. OBJECTIVES: The objective was to evaluate, from a Canadian perspective, the cost-effectiveness of intravenous immunoglobulin (IVIG) compared to alternative inpatient treatments for acute childhood idiopathic thrombocytopenic purpura (ITP). METHODS: A Markov model with a lifelong time horizon was used to evaluate the costs and quality-adjusted life years (QALYs) for 5 treatments for children hospitalized for ITP: 1) no treatment; 2) IVIG; 3) Anti-D; 4) prednisone; and 5) methylprednisolone. The model predicted the probability of intracranial hemorrhage for each treatment strategy based on the time children spent with platelet counts <20,000µL. The time patients spent with platelet counts <20,000µL with each treatment was estimated by pooling data from published randomized clinical trials. In the basecase analysis, the cohort was assumed to weigh 20kg. Cost and utility model variables were based upon various literature sources. Parameter uncertainty was assessed using probabilistic sensitivity analysis. RESULTS: The treatment strategies that comprised the efficiency frontier were prednisone, Anti-D and IVIG. The incremental cost per QALY was $53,333 moving from prednisone to Anti-D and $53,846 moving from Anti-D to IVIG. Results were sensitive to patient weight. If patient weight is 10kg, IVIG dominates all other strategies and if weight is increased to 30kg, the cost per QALY of IVIG is $163,708. CONCLUSION: Based on common willingness to pay thresholds, IVIG might be considered a cost effective treatment for acute childhood ITP. Cost effectiveness is highly dependent on patient weight.

Self-reported use of natural health products: a cross-sectional telephone survey in older Ontarians.

BACKGROUND: The self-reported use of natural health products (NHPs) (herbal products and vitamin and mineral supplements) has increased over the past decade in Canada. Because the elderly population might have comorbidities and concurrently administered medications, there is a need to explore the perceptions and behaviors associated with NHPs in this age group. OBJECTIVE: The goal of this study was to assess the use of NHPs in a cohort of older Canadian residents and the characteristics, perceptions, and behaviors associated with NHP use. METHODS: Survey participants aged > or = 60 years were randomly selected from telephone listings in the area of greater Hamilton, Ontario, Canada. Data were collected using a standardized computer-assisted telephone interview system. Self-reported data covering 7 domains were collected: (1) demographics; (2) self-reported 12-month NHP use; (3) reasons for NHP use; (4) self-reported 12-month prescription medication use; (5) expenditures on NHPs; (6) patient-reported adverse events and drug-NHP interactions; and (7) perceptions of physicians' attitudes regarding NHPs. Descriptive statistics were used to compare the characteristics of NHP users with those of nonusers and to assess the characteristics of NHP users across these 7 domains. Multivariate regression analysis was conducted to determine the demographic variables that might be associated with NHP user status. RESULTS: Of 2528 persons identified as age > or = 60 years, 1206 (48%) completed the telephone interview. Six hundred sixteen of these respondents (51%) reported the use of > or = 1 NHP during the previous 12 months. On the initial univariate analysis, younger age and higher income were significantly associated with reporting NHP use (mean age, users vs nonusers, 71.1 vs 72.7 years, respectively; 95% CI, 1.02-1.06; P < 0.001; income more than Can $26,000 was 28% and 22% in users and nonusers, respectively; P = 0.028). One hundred seventy of 616 users (28%) used an NHP to treat the same condition for which they were concurrently receiving a prescription medication, and 43 (25%) had not informed their physicians about their NHP use. Patients' characteristics such as sex, education, smoking status, and self-reported health status did not differ significantly between users and nonusers. In individuals who regularly spent money to purchase NHPs (n = 394), the mean cost was $20.38/mo. NHP expenditure was not significantly associated with age, sex, or income. CONCLUSION: Based on these findings, a substantial proportion of those Ontarians aged > or = 60 years reported NHP use, and there is a need for greater communication with physicians to avoid potential drug-NHP interactions.

Drug-herb interaction among commonly used conventional medicines: a compendium for health care professionals.

The objective of the review was to consolidate the clinical and pharmacologic aspects of drug-herb interactions to develop a compendium of information to provide prescribers with a measure of the risk of interactions, a description of the clinical consequences, and an assessment of the quality (ie, validity) of evidence. A variety of electronic databases and hand-searched references were used to identify documentation of interactions between herbal products and drugs from the most commonly used therapeutic classes. MEDLINE, Allied and Complementary Medicine Database, CINHAL, HealthSTAR, and EMBASE were searched from 1966 to the present. One hundred sixty-two citations were identified. Only 22 citations met the inclusion criteria. Using a matrix of 165 possible drug-herb interaction pairs (15 therapeutic drug classes by 11 herbal products), we identified 51 (31%) interactions discussed in the literature. Twenty-two of these 51 drug-herb pairs (43%) were supported by randomized clinical trials, case-control studies, cohort studies, case series, or case studies. The remaining interaction pairs reflected theoretic reasoning in the absence of clinical data. Most interactions were pharmacokinetic, with most actually or theoretically affecting the metabolism of the affected product by way of the cytochrome p450 enzymes. In this review, warfarin was the most common drug and St. John's wort was the most common herbal product reported in drug-herb interactions. To create a comprehensive and valid list of herb-drug interactions would require a substantial increase in research activities in this area. Improvements in the quality of methodology used are also necessary.