Fatemeh Yazdi

Efficacy of food fortification on serum 25-hydroxyvitamin D concentrations: systematic review

BACKGROUND Many residents of the United States and Canada depend on dietary sources of vitamin D to help maintain vitamin D status. Because few natural food sources contain vitamin D, fortified foods may be required. OBJECTIVE We aimed to determine the effects of vitamin D-fortified foods on serum 25-hydroxyvitamin D [25(OH)D] concentrations. DESIGN We searched MEDLINE (1966 to June Week 3 2006), Embase, CINAHL, AMED, Biological Abstracts, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) comparing vitamin D-fortified foods with a control and reporting serum 25(OH)D concentrations. Two reviewers independently determined study eligibility, assessed trial quality, and extracted relevant data. Disagreements were resolved by consensus. Meta-analyses of absolute mean change in 25(OH)D were conducted by using a random-effects model, with evaluation of heterogeneity. RESULTS Nine RCTs (n = 889 subjects) were included, of which 8 consistently showed a significant beneficial effect of food fortification on 25(OH)D concentrations. Although 7 RCTs (n = 585 subjects) potentially were meta-analyzable, we were unable to combine the overall results because of significant heterogeneity. The individual treatment effects ranged from 14.5 (95% CIs: 10.6, 18.4) nmol/L to 34.5 (17.64, 51.36) nmol/L (3.4-25 microg vitamin D/d). Subgroup analyses showed a reduction in heterogeneity and significant treatment effect when 4 trials that used milk as the fortified food source were combined. CONCLUSION Most trials were small in size and inadequately reported allocation concealment, but results showed that vitamin D-fortified foods improved vitamin D status in adults.

Perioperative use of pregabalin for acute pain-a systematic review and meta-analysis.

Abstract Evidence supporting postoperative pain management using pregabalin as an adjunct intervention across various surgical pain models is lacking. The objective of this systematic review was to evaluate “model-specific” comparative effectiveness and harms of pregabalin following a previously published systematic review protocol. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through August 2013. Data were screened and single extraction with independent verification and dual risk of bias assessment was performed. Quality of evidence (QoE) was rated using the GRADE approach. Primary outcomes were pain relief at rest and on movement and reduction in postoperative analgesic consumption. A total of 1423 records were screened, and 43 studies were included. Perioperative pregabalin resulted in: 16% (95% confidence interval [CI], 9%-21%) reduction in analgesic consumption (moderate QoE, 24 trials) and a small reduction in the magnitude of pain in surgeries associated with pronociceptive pain. Per 1000 patients, 10 more will experience blurred vision (95% CI, 5-20 more; moderate QoE, 17 trials) and 41 more sedation (95% CI, 13-77 more, 17 trials). To prevent 1 case of perioperative nausea and vomiting, the number needed to treat is 11 (95% CI: 7-28, 25 trials). Inadequate evidence addressed outcomes of enhanced recovery and serious harms. Pregabalin analgesic effectiveness is largely restricted to surgical procedures associated with pronociceptive mechanisms. The clinical significance of observed pregabalin benefits must be weighed against the uncertainties about serious harms and enhanced recovery to inform the careful selection of surgical patients. Recommendations for future research are proposed.

Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms.

OBJECTIVES To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. METHODS Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. RESULTS A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. CONCLUSIONS There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.

Comparative safety and effectiveness of long-acting inhaled agents for treating chronic obstructive pulmonary disease: a systematic review and network meta-analysis

Objective To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD). Setting Systematic review and network meta-analysis (NMA). Participants 208 randomised clinical trials (RCTs) including 134 692 adults with COPD. Interventions LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo. Primary and secondary outcomes The proportion of patients with moderate-to-severe exacerbations. The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes. Results NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26 141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol. Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve). NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%). NMA was conducted on CVM (37 RCTs, 55 156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR). Triamcinolone acetonide was the most harmful (SUCRA=81%). NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone/salmeterol. The most harmful agent was fluticasone/salmeterol (SUCRA=89%). NMA was conducted for arrhythmia; no statistically significant differences between agents were identified. Conclusions Many inhaled agents are available for COPD, some are safer and more effective than others. Our results can be used by patients and physicians to tailor administration of these agents. Protocol registration number PROSPERO # CRD42013006725.

An evaluation of epidemiological and reporting characteristics of complementary and alternative medicine (CAM) systematic reviews (SRs).

Background Systematic reviews (SRs) are abundant. The optimal reporting of SRs is critical to enable clinicians to use their findings to make informed treatment decisions. Complementary and alternative medicine (CAM) therapies are widely used therefore it is critical that conduct and reporting of systematic research in this field be of high quality. Here, methodological and reporting characteristics of a sample of CAM-related SRs and a sample of control SRs are evaluated and compared. Methods MEDLINE® was searched to identify non-Cochrane SRs indexed from January 2010 to May 2011. Control SRs were retrieved and a search filter was used to identify CAM SRs. Citations were screened and publications that met a pre-specified definition of a SR were included. Pre-designed, standardized data extraction forms were developed to capture reporting and methodological characteristics of the included reviews. Where appropriate, samples were compared descriptively. Results A total of 349 SRs were identified, of which 174 were CAM-related SRs and 175 were conventional SRs. We compared 131 CAM-related non-Cochrane SRs to the 175 conventional non-Cochrane reviews. Fifty-seven percent (75/131) of CAM SRs specified a primary outcome compared to 21% (37/175) of conventional sample reviews. Reporting of publication bias occurred in less than 5% (6/131) of the CAM sample versus 46% (80/175) of the conventional sample of SRs. Source of funding was frequently and consistently under-reported. Less than 5% (11/306) of all SRs reported public availability of a review protocol. Conclusion The two samples of reviews exhibited different strengths and weaknesses. In some cases there were consistencies across items which indicate the need for continued improvements in reporting for all SR reports. We advise authors to utilise the PRISMA Statement or other SR guidance when reporting SRs.

Stop this waste of people, animals and money

Our evidence disputes this view. We spent 12 months rigorously characterizing nearly 2,000 biomedical articles from more than 200 journals thought likely to be predatory. More than half of the corresponding authors hailed from highand upper-middle-income countries as defined by the World Bank. Of the 17% of sampled articles that reported a funding source, the most frequently named funder was the US National Institutes of Health (NIH). The United States produced more articles in our sample than all other countries save India. Harvard University (with 9 articles) in Cambridge, Massachusetts, and the University of Texas (with Predatory journals are easy to please. They seem to accept papers with little regard for quality, at a fraction of the cost charged by mainstream openaccess journals. These supposedly scholarly publishing entities are murky operations, making money by collecting fees while failing to deliver on their claims of being open access and failing to provide services such as peer review and archiving. Despite abundant evidence that the bar is low, not much is known about who publishes in this shady realm, and what the papers are like. Common wisdom assumes that the hazard of predatory publishing is restricted mainly to the developing world. In one famous sting, a journalist for Science sent a purposely flawed paper to 140 presumed predatory titles (and to a roughly equal number of other open-access titles), pretending to be a biologist based in African capital cities. At least two earlier, smaller surveys found that most authors were in India or elsewhere in Asia. A campaign to warn scholars about predatory journals has concentrated its efforts in Africa, China, India, the Middle East and Russia. Frequent, aggressive solicitations from predatory publishers are generally considered merely a nuisance for scientists from rich countries, not a threat to scholarly integrity. Stop this waste of people, animals and money

Comparative effectiveness of monotherapies and combination therapies for patients with hypertension: protocol for a systematic review with network meta-analyses

BackgroundHypertension has been cited as the most common attributable risk factor for death worldwide, and in Canada more than one of every five adults had this diagnosis in 2007. In addition to different lifestyle modifications, such as diet and exercise, there exist many pharmaco-therapies from different drug classes which can be used to lower blood pressure, thereby reducing the risk of serious clinical outcomes. In moderate and severe cases, more than one agent may be used. The optimal mono- and combination therapies for mild hypertension and moderate/severe hypertension are unclear, and clinical guidelines provide different recommendations for first line therapy. The objective of this review is to explore the relative benefits and safety of different pharmacotherapies for management of non-diabetic patients with hypertension, whether of a mild or moderate to severe nature.Methods/DesignSearches involving MEDLINE and the Cochrane Database of Systematic Reviews will be used to identify related systematic reviews and relevant randomized trials. The outcomes of interest include myocardial infarction, stroke, incident diabetes, heart failure, overall and cardiovascular related death, and important side effects (cancers, depression, syncopal episodes/falls and sexual dysfunction). Randomized controlled trials will be sought. Two reviewers will independently screen relevant reviews, titles and abstracts resulting from the literature search, and also potentially relevant full-text articles in duplicate. Data will be abstracted and quality will be appraised by two team members independently. Conflicts at all levels of screening and abstraction will be resolved through team discussion. Random effect pairwise meta-analyses and network meta-analyses will be conducted where deemed appropriate. Analyses will be geared toward studying treatment of mild hypertension and moderate/severe hypertension separately.DiscussionOur systematic review results will assess the extent of currently available evidence for single agent and multi-agent pharmacotherapies in patients with mild, moderate and severe hypertension, and will provide a rigorous and updated synthesis of a range of important clinical outcomes for clinicians, decision makers and patients.Systematic review registrationPROSPERO Registration Number: CRD42013004459

Interactions of commonly used dietary supplements with cardiovascular drugs: a systematic review

BackgroundThe objective of this systematic review was to examine the benefits, harms and pharmacokinetic interactions arising from the co-administration of commonly used dietary supplements with cardiovascular drugs. Many patients on cardiovascular drugs take dietary supplements for presumed benefits and may be at risk for adverse supplement-drug interactions.MethodsThe Allied and Complementary Medicine Database, the Cochrane Library, EMBASE, International Bibliographic Information on Dietary Supplements and MEDLINE were searched from the inception of the review to October 2011. Grey literature was also reviewed.Two reviewers independently screened records to identify studies comparing a supplement plus cardiovascular drug(s) with the drug(s) alone. Reviewers extracted data using standardized forms, assessed the study risk of bias, graded the strength of evidence and reported applicability.ResultsEvidence was obtained from 65 randomized clinical trials, 2 controlled clinical trials and 1 observational study. With only a few small studies available per supplement, evidence was insufficient for all predefined gradable clinical efficacy and harms outcomes, such as mortality and serious adverse events. One long-term pragmatic trial showed no benefit from co-administering vitamin E with aspirin on a composite cardiovascular outcome. Evidence for most intermediate outcomes was insufficient or of low strength, suggesting no effect. Incremental benefits were noted for triglyceridemia with omega-3 fatty acid added to statins; and there was an improvement in levels of high-density lipoprotein cholesterol with garlic supplementation when people also consumed nitratesConclusionsEvidence of low-strength indicates benefits of omega-3 fatty acids (plus statin, or calcium channel blockers and antiplatelets) and garlic (plus nitrates or warfarin) on triglycerides and HDL-C, respectively. Safety concerns, however, persist.

A protocol for a systematic review for perioperative pregabalin use

BackgroundPerioperative pain management has recently been revolutionized with the recognition of novel mechanisms and introduction of newer drugs. Many randomized trials have studied the use of the gabapentinoid anti-epileptic, pregabalin, in acute pain. Published systematic reviews suggest that using pregabalin for perioperative pain management may decrease analgesic requirements and pain scores, at the expense of troublesome side effects. A major limitation of the extant reviews is the lack of rigorous investigation of clinical characteristics that would maximize the benefit harms ratio in favor of surgical patients. We posit that effects of pregabalin for perioperative pain management vary by the type of surgical pain model and propose this systematic review protocol to update previous systematic reviews and investigate the heterogeneity in findings across subgroups of surgical pain models.Methods/DesignUsing a peer-reviewed search strategy, we will search key databases for clinical trials on perioperative pregabalin use in adults. The electronic searches will be supplemented by scanning the reference lists of included studies. No limits of language, country or year will be imposed. Outcomes will include pain; use of co-analgesia, particularly opioids; enhanced recovery; and drug-related harms. We will focus on the identification of surgical models and patient characteristics that have shown benefit and adverse effects from pregabalin.Two clinical experts will independently screen the studies for inclusion using eligibility criteria established a priori. Data extracted by the reviewers will then be verified. Publication bias will be assessed, as will risk of bias using the Cochrane Risk of Bias tool. Meta-analysis and meta-regression are planned if the studies are deemed statistically, methodologically and clinically homogenous. Evidence will be graded for its strength for a select number of outcomes.DiscussionWe will explore the findings of perioperative clinical trials studying the use of pregabalin for acute pain. We will comment on the implications of the findings and provide further direction for the appropriate use of pregabalin in acute pain. This protocol will attempt to bridge the growing gap between clinical experience and emerging evidence, and has the potential to aid future guideline development in the perioperative use of pregabalin.Systematic review registrationPROSPERO registration number CRD42012002078

Comparison of physical interventions, behavioral interventions, natural health products, and pharmacologics to manage hot flashes in patients with breast or prostate cancer: protocol for a systematic review incorporating network meta-analyses

BackgroundBreast and prostate cancers are the most commonly diagnosed non-dermatologic malignancies in Canada. Agents including endocrine therapies (e.g., aromatase inhibitors, gonadotrophin-releasing hormone analogs, anti-androgens, tamoxifen) and chemotherapy have improved survival for both conditions. As endocrine manipulation is a mainstay of treatment, it is not surprising that hot flashes are a common and troublesome adverse effect. Hot flashes can cause chills, night sweats, anxiety, and insomnia, lessening patients’ quality of life. These symptoms impact treatment adherence, worsening prognosis. While short-term estrogen replacement therapy is frequently used to manage hot flashes in healthy menopausal women, its use is contraindicated in breast cancer. Similarly, testosterone replacement therapy is contraindicated in prostate cancer. It is therefore not surprising that non-hormonal pharmacological treatments (anti-depressants, anti-epilectics, anti-hypertensives), physical/behavioral treatments (e.g., acupuncture, yoga/exercise, relaxation techniques, cognitive behavioral therapy), and natural health products (e.g., black cohosh, flax, vitamin E, ginseng) have been studied for control of hot flashes. There is a need to identify which interventions minimize the frequency and severity of hot flashes and their impact on quality of life. This systematic review and network meta-analysis of randomized studies will synthesize available evidence addressing this knowledge gap.Methods/designAn electronic search of Medline, Embase, AMED, PsycINFO, and the Cochrane Register of Controlled Trials has been designed by an information specialist and peer reviewed by a second information specialist. Study selection and data collection will be performed by two reviewers independently. Risk of bias assessments will be completed using the Cochrane Risk of Bias Scale. Outcomes of interest will include validated measures of hot flash severity, hot flash frequency, quality of life, and harms. Bayesian network meta-analyses will be performed where judged appropriate based on review of clinical and methodologic features of included studies.DiscussionOur review will include a broad range of interventions that patients with breast and prostate cancer have attempted to use to manage hot flashes. Our work will establish the extent of evidence underlying these interventions and will employ an inclusive approach to analysis to inform comparisons between them. Our findings will be shared with Cancer Care Ontario for consideration in the development of guidance related to supportive care in these patients.Systematic review registrationPROSPERO: CRD42015024286