Juan P. Brito

GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation's direction and strength.

In the GRADE approach, the strength of a recommendation reflects the extent to which we can be confident that the composite desirable effects of a management strategy outweigh the composite undesirable effects. This article addresses GRADEs approach to determining the direction and strength of a recommendation. The GRADE describes the balance of desirable and undesirable outcomes of interest among alternative management strategies depending on four domains, namely estimates of effect for desirable and undesirable outcomes of interest, confidence in the estimates of effect, estimates of values and preferences, and resource use. Ultimately, guideline panels must use judgment in integrating these factors to make a strong or weak recommendation for or against an intervention.

Patient engagement in research: a systematic review

BackgroundA compelling ethical rationale supports patient engagement in healthcare research. It is also assumed that patient engagement will lead to research findings that are more pertinent to patients’ concerns and dilemmas. However; it is unclear how to best conduct this process. In this systematic review we aimed to answer 4 key questions: what are the best ways to identify patient representatives? How to engage them in designing and conducting research? What are the observed benefits of patient engagement? What are the harms and barriers of patient engagement?MethodsWe searched MEDLINE, EMBASE, PsycInfo, Cochrane, EBSCO, CINAHL, SCOPUS, Web of Science, Business Search Premier, Academic Search Premier and Google Scholar. Included studies were published in English, of any size or design that described engaging patients or their surrogates in research design. We conducted an environmental scan of the grey literature and consulted with experts and patients. Data were analyzed using a non-quantitative, meta-narrative approach.ResultsWe included 142 studies that described a spectrum of engagement. In general, engagement was feasible in most settings and most commonly done in the beginning of research (agenda setting and protocol development) and less commonly during the execution and translation of research. We found no comparative analytic studies to recommend a particular method. Patient engagement increased study enrollment rates and aided researchers in securing funding, designing study protocols and choosing relevant outcomes. The most commonly cited challenges were related to logistics (extra time and funding needed for engagement) and to an overarching worry of a tokenistic engagement.ConclusionsPatient engagement in healthcare research is likely feasible in many settings. However, this engagement comes at a cost and can become tokenistic. Research dedicated to identifying the best methods to achieve engagement is lacking and clearly needed.

Patient and service user engagement in research: a systematic review and synthesized framework

There is growing attention towards increasing patient and service user engagement (PSUE) in biomedical and health services research. Existing variations in language and design inhibit reporting and indexing, which are crucial to comparative effectiveness in determining best practices.

The Optimal Practice of Evidence-Based Medicine: Incorporating Patient Preferences in Practice Guidelines

Research evidence is necessary but insufficient for making patient care decisions. An effective but toxic chemotherapeutic regimen is the treatment one patient with cancer can and will take, another patient can take but will not, and yet another patient could not take even if wanted. Careful attention to the biopsychosocial context of patients and to their informed preferences when crafting treatments requires expertise and practical wisdom. This represents the optimal practice of evidence-based medicine. Patient preferences refer to patient perspectives, beliefs, expectations, and goals for health and life, and to the processes that individuals use in considering the potential benefits, harms, costs, and inconveniences of the management options in relation to one another.1 Patients may have preferences when it comes to defining the problem, identifying the range of management options, selecting the outcomes used to compare these options, and ranking these outcomes by importance. Informed patients may choose not to follow a guideline that does not incorporate their preferences. The ATP III guideline (Adult Treatment Panel III), for example, recommended statins for all patients with diabetes. Patients with diabetes at low cardiovascular risk were 70% less likely to opt for a statin after

Thyroid cancer: zealous imaging has increased detection and treatment of low risk tumours

#### Summary box Thyroid cancer is the most common endocrine malignancy.1 Worldwide, its incidence has increased substantially over the past 50 years. The Cancer Incidence in Five Continents report showed …

Drugs Commonly Associated With Weight Change: A Systematic Review and Meta-analysis

CONTEXT Various drugs affect body weight as a side effect. OBJECTIVE We conducted this systematic review and meta-analysis to summarize the evidence about commonly prescribed drugs and their association with weight change. DATA SOURCES MEDLINE, DARE, and the Cochrane Database of Systematic Reviews were searched to identify published systematic reviews as a source for trials. STUDY SELECTION We included randomized trials that compared an a priori selected list of drugs to placebo and measured weight change. DATA EXTRACTION We extracted data in duplicate and assessed the methodological quality using the Cochrane risk of bias tool. RESULTS We included 257 randomized trials (54 different drugs; 84 696 patients enrolled). Weight gain was associated with the use of amitriptyline (1.8 kg), mirtazapine (1.5 kg), olanzapine (2.4 kg), quetiapine (1.1 kg), risperidone (0.8 kg), gabapentin (2.2 kg), tolbutamide (2.8 kg), pioglitazone (2.6 kg), glimepiride (2.1 kg), gliclazide (1.8 kg), glyburide (2.6 kg), glipizide (2.2 kg), sitagliptin (0.55 kg), and nateglinide (0.3 kg). Weight loss was associated with the use of metformin (1.1 kg), acarbose (0.4 kg), miglitol (0.7 kg), pramlintide (2.3 kg), liraglutide (1.7 kg), exenatide (1.2 kg), zonisamide (7.7 kg), topiramate (3.8 kg), bupropion (1.3 kg), and fluoxetine (1.3 kg). For many other remaining drugs (including antihypertensives and antihistamines), the weight change was either statistically nonsignificant or supported by very low-quality evidence. CONCLUSIONS Several drugs are associated with weight change of varying magnitude. Data are provided to guide the choice of drug when several options exist and institute preemptive weight loss strategies when obesogenic drugs are prescribed.

The efficacy of resiliency training programs: a systematic review and meta-analysis of randomized trials.

Importance Poor mental health places a burden on individuals and populations. Resilient persons are able to adapt to life’s challenges and maintain high quality of life and function. Finding effective strategies to bolster resilience in individuals and populations is of interest to many stakeholders. Objectives To synthesize the evidence for resiliency training programs in improving mental health and capacity in 1) diverse adult populations and 2) persons with chronic diseases. Data Sources Electronic databases, clinical trial registries, and bibliographies. We also contacted study authors and field experts. Study Selection Randomized trials assessing the efficacy of any program intended to enhance resilience in adults and published after 1990. No restrictions were made based on outcome measured or comparator used. Data Extraction and Synthesis Reviewers worked independently and in duplicate to extract study characteristics and data. These were confirmed with authors. We conducted a random effects meta-analysis on available data and tested for interaction in planned subgroups. Main Outcomes The standardized mean difference (SMD) effect of resiliency training programs on 1) resilience/hardiness, 2) quality of life/well-being, 3) self-efficacy/activation, 4) depression, 5) stress, and 6) anxiety. Results We found 25 small trials at moderate to high risk of bias. Interventions varied in format and theoretical approach. Random effects meta-analysis showed a moderate effect of generalized stress-directed programs on enhancing resilience [pooled SMD 0.37 (95% CI 0.18, 0.57) p = .0002; I2 = 41%] within 3 months of follow up. Improvement in other outcomes was favorable to the interventions and reached statistical significance after removing two studies at high risk of bias. Trauma-induced stress-directed programs significantly improved stress [−0.53 (−1.04, −0.03) p = .03; I2 = 73%] and depression [−0.51 (−0.92, −0.10) p = .04; I2 = 61%]. Conclusions We found evidence warranting low confidence that resiliency training programs have a small to moderate effect at improving resilience and other mental health outcomes. Further study is needed to better define the resilience construct and to design interventions specific to it. Registration Number PROSPERO #CRD42014007185

Prevalence of Thyroid Cancer in Multinodular Goiter Versus Single Nodule: A Systematic Review and Meta-Analysis

BACKGROUND Whether the prevalence of thyroid cancer is different in thyroid glands with a single nodule (SN) versus multinodular goiter (MNG) remains uncertain. Therefore, a meta-analysis was performed to evaluate the extant literature on the comparative prevalence of thyroid cancer in SN compared with MNG. METHODS We searched MEDLINE, EMBASE, Scopus, Cochrane Central, and reference list for selected observational, cross-sectional, and longitudinal studies evaluating thyroid cancer in SN and MNG. Toxic nodules were not included in the analysis. Two reviewers working independently extracted descriptive, methodological and outcome data from each study with consensus resolution of discrepancies. Meta-analytic estimates of treatment effects were generated using a random-effect model. RESULTS Fourteen studies encompassing 23565 patients with MNG and 20723 patients with SN were eligible for inclusion. Most eligible studies were at a moderate risk of bias. MNGs were associated with a lower risk of thyroid cancer than SN (pooled odds ratio 0.8 [95% confidence interval 0.67-0.96]; I(2)=35%). Subgroup analysis suggested that this difference depends on the inclusion of studies conducted outside the United States (odds ratio 0.71 [95% confidence interval 0.60-0.83]; I(2)=11%). CONCLUSIONS Thyroid cancer may be less frequent in MNG compared to SN, particularly outside the United States and perhaps in iodine-deficient areas.

Pharmacologic Interventions for Painful Diabetic Neuropathy: An Umbrella Systematic Review and Comparative Effectiveness Network Meta-analysis

BACKGROUND Multiple treatments for painful diabetic peripheral neuropathy are available. PURPOSE To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy. DATA SOURCES Multiple electronic databases between January 2007 and April 2014, without language restriction. STUDY SELECTION Parallel or crossover randomized, controlled trials that evaluated pharmacologic treatments for adults with painful diabetic peripheral neuropathy. DATA EXTRACTION Duplicate extraction of study data and assessment of risk of bias. DATA SYNTHESIS 65 randomized, controlled trials involving 12 632 patients evaluated 27 pharmacologic interventions. Approximately one half of these studies had high or unclear risk of bias. Nine head-to-head trials showed greater pain reduction associated with serotonin-norepinephrine reuptake inhibitors (SNRIs) than anticonvulsants (standardized mean difference [SMD], -0.34 [95% credible interval {CrI}, -0.63 to -0.05]) and with tricyclic antidepressants (TCAs) than topical capsaicin 0.075%. Network meta-analysis showed that SNRIs (SMD, -1.36 [CrI, -1.77 to -0.95]), topical capsaicin (SMD, -0.91 [CrI, -1.18 to -0.08]), TCAs (SMD, -0.78 [CrI, -1.24 to -0.33]), and anticonvulsants (SMD, -0.67 [CrI, -0.97 to -0.37]) were better than placebo for short-term pain control. Specifically, carbamazepine (SMD, -1.57 [CrI, -2.83 to -0.31]), venlafaxine (SMD, -1.53 [CrI, -2.41 to -0.65]), duloxetine (SMD, -1.33 [CrI, -1.82 to -0.86]), and amitriptyline (SMD, -0.72 [CrI, -1.35 to -0.08]) were more effective than placebo. Adverse effects included somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs; and peripheral edema and burning sensation with pregabalin and capsaicin. LIMITATION Confidence in findings was limited because most evidence came from indirect comparisons of trials with short (≤3 months) follow-up and unclear or high risk of bias. CONCLUSION Several medications may be effective for short-term management of painful diabetic neuropathy, although their comparative effectiveness is unclear. PRIMARY FUNDING SOURCE Mayo Foundation for Medical Education and Research.

Patient-centered and practical application of new high cholesterol guidelines to prevent cardiovascular disease

Video.Online Aid to Assist Patient Decisions About Use of Statins This video illustrates use of an online decision aid to help patients understand the benefits and harms of using statins to reduce their 10-year cardiovascular risk. In 2013, the American College of Cardiology and the American Heart Association (ACC/AHA) published new guidelines for assessing cardiovascular disease (CVD) risk1 and for treatment of blood cholesterol to reduce CVD.2 These new guidelines replaced the Adult Treatment Panel III (ATP III) guidelines for the detection, evaluation, and treatment of high blood cholesterol3 that guided clinical practice for more than a decade. The new guidelines divert focus from lowering low-density lipoprotein (LDL) cholesterol levels to treating CVD risk and therefore are no longer pure cholesterol guidelines like the ATP III predecessor. The new guidelines also discourage the prescription of lipid-lowering medications, such as ezetimibe or niacin, that do not have proven effect on reducing CVD risk. These changes represent a major shift in preventive cardiology.