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The Patient-Centered Outcomes Research Institute (PCORI) is a nonprofit, nongovernmental organization established by the U.S. Congress to fund comparative clinical effectiveness research focusing on patient-centered outcomes through the engagement of stakeholders. Evaluation of emerging healthcare innovations is one of PCORI’s five National Priorities for Health. One such initiative is PCORI’s Emerging Technologies and Therapeutics Reports program, established to provide timely overviews of evidence on new drugs and other healthcare technologies. This article provides an overview of completed and ongoing Emerging Technologies and Therapeutics Reports including lessons learned to date. In addition to systematic searches, systematic selection of studies, and transparent reporting of the available evidence, informed by a select number of stakeholders (i.e., key informants), these reports focus on contextual factors shaping the diffusion of emerging technologies that are often not reported in the medical literature. This article also compares processes and methodologies of health technology assessments (HTAs) from a selected number of national and international publicly funded agencies with a goal toward potential future enhancement of PCORI’s Emerging Technologies and Therapeutics Reports program. HTAs vary considerably in terms of funding, types of assessments, the role of manufacturers, stakeholder engagement, timeline to complete from the start to the finish of a draft report publication, and communication of uncertainty for informed decision making. Future Emerging Technologies and Therapeutics Reports may focus on rapid reports to support a more expedient development of evidence. Future research could explore the role of contextual factors identified in these reports on targeted evidence generation. [ABSTRACT FROM AUTHOR]

We conducted a systematic review to evaluate the association between folate, vitamin B-6, vitamin B-12, and cognitive function in the elderly. Our search was conducted in Medline for English-language publications of human subjects from 1966 through November 2006; we supplemented these results with information from article reviews and domain experts. We included longitudinal cohort and case-control studies of B vitamins and analyses of cognitive tests or Alzheimer's disease. We evaluated the quality and heterogeneity of study outcomes and assessed 30 different cognitive function tests. Of 24 studies that met eligibility criteria, 16 were determined to be of fair quality. A majority of the studies reviewed 2 or more B vitamins. Considerable heterogeneity was found among B-vitamin-level thresholds, comparisons, and data analyses. Six of 10 folate studies reported a significant association between low baseline blood folate concentrations and subsequent poor test performance in the global cognitive domain, and 4 of 9 folate studies found associations between low blood folate concentrations and increased prevalence of Alzheimer's disease. Studies did not reveal an association of vitamin B-6 and vitamin B-12 blood concentrations with cognitive-test performance or Alzheimer's disease, nor was B-vitamin dietary intake associated with cognitive function. Higher plasma homocysteine concentrations were associated with poorer cognitive function. Although the majority of studies indicated that low blood folate concentrations predicted poorer cognitive function, data supporting this association were limited because of the heterogeneity in cognition-assessment methodology, and scarcity of good quality studies and standardized threshold levels for categorizing low B-vitamin status.

Objective: Strenuous muscular workouts can increase markers of inflammation that can potentially damage components of skeletal muscles. Blueberries contain a variety of nutrients and phytochemicals that have individually been related to reduction in oxidative stress and inflammation. The objective was to conduct a systematic overview using evidence mapping to identify research-dense and evidence gap areas that examine the impact of blueberry consumption on exercise performance and inflammatory markers in adults. Design: The authors searched Medline, Cochrane Central, and Commonwealth Agricultural Bureau for literature published between 1946 and September 2019. Abstracts and full-text publications were screened in duplicate for studies that evaluated outcomes related to metabolism, lipoprotein, muscle damage, markers of oxidative stress, inflammatory markers, or gait after participants consumed blueberries and were subjected to some form of exercise. Results: The authors found nine randomized controlled trials, one single-arm study, and one observational study that met the eligibility criteria. Inflammatory markers, F2-isoprostanes, and gait speed were the most frequently reported outcomes, with each one reported by at least three studies. Outcomes related to metabolism, lipoproteins, muscle damage, and most markers of oxidative stress and most gait-related outcomes were each reported by one study. Intervention trials were generally conducted with a small number of participants and the majority included mostly younger individuals. Using multivariate analysis, the sole observational study examined physical ability among participants who consumed higher doses of blueberries compared with participants who consumed a half cup of blueberries less than once a month. Conclusions: Evidence mapping found that further research in both randomized controlled trials and cohort studies examining the impact of blueberry consumption on exercise performance and inflammatory markers is needed to establish an association. [ABSTRACT FROM AUTHOR]

The PATH (Predictive Approaches to Treatment effect Heterogeneity) Statement was developed to promote the conduct of, and provide guidance for, predictive analyses of heterogeneity of treatment effects (HTE) in clinical trials. The goal of predictive HTE analysis is to provide patient-centered estimates of outcome risk with versus without the intervention, taking into account all relevant patient attributes simultaneously, to support more personalized clinical decision making than can be made on the basis of only an overall average treatment effect. The authors distinguished 2 categories of predictive HTE approaches (a "risk-modeling" and an "effect-modeling" approach) and developed 4 sets of guidance statements: criteria to determine when risk-modeling approaches are likely to identify clinically meaningful HTE, methodological aspects of risk-modeling methods, considerations for translation to clinical practice, and considerations and caveats in the use of effect-modeling approaches. They discuss limitations of these methods and enumerate research priorities for advancing methods designed to generate more personalized evidence. This explanation and elaboration document describes the intent and rationale of each recommendation and discusses related analytic considerations, caveats, and reservations. [ABSTRACT FROM AUTHOR]

Background Although available data suggest that some dietary flavan-3-ol sources reduce cardiometabolic risk, to our knowledge no review has systematically synthesized their specific contribution. Objective We aimed to examine, for the first time, if there is consistent evidence that higher flavan-3-ol intake, irrespective of dietary source, reduces cardiometabolic risk. Methods MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau abstracts were searched for prospective cohorts and randomized controlled trials (RCTs) published from 1946 to March 2019 on flavan-3-ol intake and cardiovascular disease (CVD) risk. Random-effects models meta-analysis was used. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach assessed the strength of evidence. Results Of 15 prospective cohorts (23 publications), 4 found highest compared with lowest habitual intakes of flavan-3-ols were associated with a 13% reduction in risk of CVD mortality and 2 found a 19% reduction in risk of chronic heart disease (CHD) incidence. Highest compared with lowest habitual intakes of monomers were associated with a reduction in risk of type 2 diabetes mellitus (T2DM) (n  = 5) and stroke (n  = 4) (10% and 18%, respectively). No association was found for hypertension. Of 156 RCTs, flavan-3-ol intervention resulted in significant improvements in acute/chronic flow-mediated dilation (FMD), systolic (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), LDL and HDL cholesterol, triglycerides (TGs), hemoglobin A1c (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR). All analyses, except HbA1c, were associated with moderate/high heterogeneity. When analyses were limited to good methodological quality studies, improvements in TC, HDL cholesterol, SBP, DBP, HOMA-IR, and acute/chronic FMD remained significant. In GRADE evaluations, there was moderate evidence in cohort studies that flavan-3-ol and monomer intakes were associated with reduced risk of CVD mortality, CHD, stroke, and T2DM, whereas RCTs reported improved TC, HDL cholesterol, SBP, and HOMA-IR. Conclusions Available evidence supports a beneficial effect of flavan-3-ol intake on cardiometabolic outcomes, but there was considerable heterogeneity in the meta-analysis. Future research should focus on an integrated intake/biomarker approach in cohorts and high-quality dose–response RCTs. This review was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42018035782. [ABSTRACT FROM AUTHOR]

Purpose: Scientific evidence suggests a role for lutein and zeaxanthin, in visual function. The purpose of this research was to summarize the data related to lutein/zeaxanthin intake and visual outcomes in adults with healthy eyes using evidence mapping methods and to describe the research to date that would be useful in guiding future research priorities, systematic reviews, and meta-analyses. Design: A search of Medline®, Cochrane Central, and CAB databases was performed for studies of all designs published from 1946 to October 2016. Our search strategy included lutein, zeaxanthin, meso-zeaxanthin, xanthophylls and carotenoids as well as visual outcomes to include macular pigment density (MPD). Results: Forty-seven studies published in English language were identified and mapped. Most research was conducted in controlled parallel trials (77%) using lutein/zeaxanthin supplements. Studies evaluated effects of lutein/zeaxanthin supplementation (66%) or lutein/zeaxanthin in combination with other nutrients (17%); or evaluated foods rich in lutein/zeaxanthin (17%). MPD (89%) was the most common outcome measure studied. Additional outcome measures included in 47 studies were visual acuity (23%), contrast sensitivity (17%), glare sensitivity (13%), and photostress recovery (11%). Conclusions: This study using evidence mapping found that studies evaluating lutein/zeaxanthin supplementation or intake and visual outcomes had MPD as the most common outcome. We conclude that there is sufficient research to warrant a future systematic review/meta-analysis evaluating the role of lutein/zeaxanthin and visual outcomes in participants with healthy eyes. Of interest would be a systematic review of the studies that evaluated both MPD and visual function to determine the strength of the relationship between these two outcomes in healthy adults. [ABSTRACT FROM AUTHOR]

Background: Nutrients in avocados are associated with cardiovascular benefits. Objective: The aim of this study was to determine the effect of avocado intake on cardiovascular disease (CVD) risk with the use of a systematic review and meta-analysis. Design: MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau abstracts were searched from 1946 through September 2017 for publications on avocado intake and CVD risk. All designs except for cross-sectional studies that evaluated avocado intake were included. Two investigators independently screened citations and extracted data. Random-effects models meta-analysis was used when ≥3 studies reported the same outcome. Results: Of 18 eligible studies (481 subjects), 7 studies compared avocado intake with no intake, 3 studies compared avocado plus monounsaturated fat intake with a control, and 8 studies reported data for qualitative synthesis. In 7 studies, avocado intake significantly increased HDL cholesterol (summary net change: 2.84 mg/dL; 95% CI: 0.18, 5.49 mg/dL), with significant heterogeneity. This remained consistent in sensitivity and subgroup analyses. There was no significant difference between avocado intake and the control for the outcomes of serum total cholesterol (TC), LDL cholesterol, triglycerides (TGs), ratios of TC to HDL cholesterol and LDL cholesterol to HDL cholesterol, and body weight. In qualitative synthesis, there was no significant difference between groups for blood glucose (2 studies), homeostasis model assessment (1 of 2 studies), oxidized LDL (2 studies), high-sensitivity C-reactive protein (2 studies), or apolipoprotein B (2 studies) or, in 1 study each, for body mass index, systolic and diastolic blood pressure, arterial compliance, fibrinogen, interleukin 6, tumor necrosis factor a, and serum nitric oxide. No studies reported incident clinical outcomes of CVD, including myocardial infarction, stroke, and other clinical endpoints. Conclusions: Avocado intake resulted in no difference in serum TC, LDL-cholesterol, and TG concentrations, but it did increase serum HDL-cholesterol concentrations, with significant heterogeneity. The association between avocado intake and CVD risk should be confirmed by well-conducted prospective observational studies or long-term trials. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic renal artery stenosis (ARAS) is associated with high blood pressure (BP), decreased kidney function, renal replacement therapy (RRT), and death.Purpose: To compare benefits and harms of percutaneous transluminal renal angioplasty with stent placement (PTRAS) versus medical therapy alone in adults with ARAS.Data Sources: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from 1993 to 16 March 2016; gray literature; and prior systematic reviews.Study Selection: Randomized, controlled trials (RCTs); nonrandomized, comparative studies (NRCSs); single-group studies; and selected case reports that reported all-cause and cardiovascular mortality, RRT, kidney function, BP, and adverse events.Data Extraction: Six researchers extracted data on design, interventions, outcomes, and study quality into a Web-based database.Data Synthesis: Eighty-three studies met eligibility criteria. In 5 of 7 RCTs, PTRAS and medical therapy led to similar BP control in patients with ARAS, and no RCTs showed statistically significant differences in kidney function, mortality, RRT, cardiovascular events, or pulmonary edema. Eight NRCSs had more variable results, finding mostly no significant differences in mortality, RRT, or cardiovascular events but heterogeneous effects on kidney function and BP. Procedure-related adverse events were rare, and medication-related adverse events were not reported. Two RCTs found no patient characteristics that were associated with outcomes with either PTRAS or medical therapy. Single-group studies found various but inconsistent factors that predict outcomes. Case reports provided examples of clinical improvement after PTRAS in patients with acute decompensation.Limitation: Limited clinical applicability and power in RCTs, and possible publication bias and lack of adjusted analyses in NRCSs.Conclusion: The strength of evidence regarding the relative benefits and harms of PTRAS versus medical therapy alone for patients with ARAS is low. Studies have generally focused on patients with less severe ARAS.Primary Funding Source: Agency for Healthcare Research and Quality. [ABSTRACT FROM AUTHOR]

Background: Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney transplant recipients. We conducted a meta-analysis of trials examining the bioavailability of generic (test) immunosuppressive drugs relative to their brand (reference) counterparts in healthy volunteers, based on the US Food and Drug Administration requirements for approval of generics, and their efficacy and safety in kidney transplant recipients.Methods: Eligible studies were identified in PubMed, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov, and conference abstracts.Results: Twenty crossover trials of healthy volunteers (n = 641) and 6 parallel-arm randomized controlled trials of kidney transplant recipients (n = 594) were identified. The 90% CI of the pooled test-to-reference drug ratio for maximum or peak plasma concentration (Cmax) and area under the plasma concentration time-curve from time 0 to time of last determinable concentration (AUC(0-t)) fell within the required range (0.80-1.25) for cyclosporine (Cmax 0.91; 90% CI 0.86-0.95; and AUC(0-t) 0.97; 90% CI 0.94-1.00), tacrolimus (Cmax 1.17; 90% CI 1.09-1.24; and AUC(0-t) 1.00; 90% CI 0.97-1.03) and mycophenolate mofetil (Cmax 0.98; 90% CI 0.96-1.01; and AUC(0-t) 1.00; 90% CI 0.99-1.01). In subgroup analyses, some generic cyclosporine formulations did not meet criteria for bioequivalence. No significant differences were observed in the time to maximum plasma concentration and terminal plasma half-life between generic and brand drugs. In parallel-arm trials, generic cyclosporine was non-inferior to brand counterpart in terms of acute allograft rejection, infections, and death.Conclusions: Not all generic immunosuppressive drugs have similar relative bioavailability to their brand name counterparts. Evidence on their efficacy and safety is inconclusive. Tighter regulatory requirement for approval of generic drugs with narrow therapeutic index is needed. [ABSTRACT FROM AUTHOR]

Background--Several widely used risk scores for cardiovascular disease (CVD) incorporate sex effects, yet there has been no systematic summary of the role of sex in clinical prediction models (CPMs). To better understand the potential of these models to support sex-specific care, we conducted a field synopsis of sex effects in CPMs for CVD. Methods and Results--We identified CPMs in the Tufts Predictive Analytics and Comparative Effectiveness CPM Registry, a comprehensive database of CVD CPMs published from January 1990 to May 2012. We report the proportion of models including sex effects on CVD incidence or prognosis, summarize the directionality of the predictive effects of sex, and explore factors influencing the inclusion of sex. Of 592 CVD-related CPMs, 193 (33%) included sex as a predictor or presented sex-stratified models. Sex effects were included in 78% (53/68) of models predicting incidence of CVD in a general population, versus only 35% (59/171), 21% (12/58), and 17% (12/72) of models predicting outcomes in patients with coronary artery disease, stroke, and heart failure, respectively. Among sex-including CPMs, women with heart failure were at lower mortality risk in 8 of 8 models; women undergoing revascularization for coronary artery disease were at higher mortality risk in 10 of 12 models. Factors associated with the inclusion of sex effects included the number of outcome events and using cohorts at-risk for CVD (rather than with established CVD). Conclusions--Although CPMs hold promise for supporting sex-specific decision making in CVD clinical care, sex effects are included in only one third of published CPMs. [ABSTRACT FROM AUTHOR]