Non-tuberculous mycobacterium skin infections after tattooing in healthy individuals: A systematic review of case reports.

In recent years, several case reports and outbreaks reported occurrence of non-tuberculous mycobacteria (NTM) infections within 6 months after receiving a tattoo in healthy individuals. NTM species (e.g., Chelonae, Fortuitum, Hemophillum, and Abscessus) are widespread in the environment and it is often suspected that contamination may occur through unsterile instrumentation or unsterile water used for diluting tattoo ink to dilute color. In reported cases, lesions were mainly restricted to a single color 'gray' part of the tattoo. Mycobacterium Chelonae was the most common cause of tattoo associated NTM infections. Less than 50% of the case reports tested tattoo ink for acid fast bacilli stains and cultures. Subjects required treatment with either clarithromycin alone or in combination with quinolones for 6 to 9 months. An increase in NTM skin infections in healthy individuals after tattooing indicates the need for sterile standards during tattooing and improved local and regional regulatory oversight.

Race, ethnicity, and risk for colonization and infection with key bacterial pathogens: a scoping review.

Background: Racial and ethnic disparities in infectious disease burden have been reported in the USA and globally, most recently for COVID-19. It remains unclear whether such disparities also exist for priority bacterial pathogens that are increasingly antimicrobial-resistant. We conducted a scoping review to summarize published studies that report on colonization or community-acquired infection with pathogens among different races and ethnicities. Methods: We conducted an electronic literature search of MEDLINE®, Daily, Global Health, Embase, Cochrane Central, and Web of Science from inception to January 2022 for eligible observational studies. Abstracts and full-text publications were screened in duplicate for studies that reported data for race or ethnicity for at least one of the pathogens of interest. Results: Fifty-four observational studies in 59 publications met our inclusion criteria. Studies reported results for Staphylococcus aureus (n=56), Escherichia coli (n=8), Pseudomonas aeruginosa (n=2), Enterobacterales (n=1), Enterococcus faecium (n=1), and Klebsiella pneumoniae (n=1), and were conducted in the USA (n=42), Israel (n=5), New Zealand (n=4), Australia (n=2), and Brazil (n=1). USA studies most often examined Black and Hispanic minority groups and regularly reported a higher risk of these pathogens in Black persons and mixed results for Hispanic persons. Ethnic minority groups were often reported to be at a higher risk in other countries. Conclusion: Sufficient evidence was identified to justify systematic reviews and meta-analyses evaluating the relationship between race, ethnicity, and community-acquired S. aureus and E. coli, although data were rare for other pathogens. We recommend that future studies clarify whether race and ethnicity data are self-reported, collect race and ethnicity data in conjunction with the social determinants of health, and make a concerted effort to include non-English speakers and Indigenous populations from the Americas, when possible.

Effectiveness of ezetimibe in human immunodeficiency virus patients treated for hyperlipidaemia: a systematic review and meta-analysis.

OBJECTIVE: Systematic review and meta-analysis of lipid outcomes for human immunodeficiency virus (HIV)-positive or HIV-infected patients treated with ezetimibe. METHODS: We conducted a literature search from 1946 to 2021 for trials studying the effectiveness of ezetimibe in hyperlipidaemic HIV patients. We included trials of all designs in which HIV patients on highly active antiretroviral therapy (HAART)/non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy had hyperlipidaemia, were treated with ezetimibe, and reported lipid outcomes. RESULTS: Of thirteen eligible trials, five were randomized controlled trials (RCTs) and eight were single-arm trials. Two of the eligible RCTs were placebo-controlled; we performed a meta-analysis across those two trials for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG). LDL-C was significantly lower in the ezetimibe arm (net change: -23.56 mg/dL, 95% CI: -40.22, -6.90 mg/dL). We then performed meta-analysis of the single-arm trials examining lipid outcomes after ezetimibe treatment which, like in the RCTs, revealed significant reductions of LDL-C (-23.89 mg/dL, 95% CI -29.94 to -17.83 mg/dL). In addition, significant reductions were seen for total cholesterol (TC) (-26.17 mg/dL, 95% CI -32.81 to -19.54 mg/dL) and TG (-18.57 mg/dL, 95% CI -34.01 to -3.14 mg/dL) but HDL-C did not show a change. CONCLUSIONS: Evidence for LDL-C reduction is limited in RCTs; single-arm trial LDL-C reductions are consistent with the RCTs. In addition, significant reductions in TC and TG were also seen in the meta-analysis of the single arm trials. The single-arm trials' meta-analysis corroborates evidence from RCTs to suggest that ezetimibe can be an option for hyperlipidaemia among HIV patients with mildly elevated TC and LDL-C levels, especially in cases where statins are contra-indicated due to drug-drug interactions with concomitant anti-retroviral therapy.

Blueberry Consumption and Exercise: Gap Analysis Using Evidence Mapping.

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.

The association between macular pigment optical density and visual function outcomes: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis on data related to macular pigment optical density (MPOD) and visual function in adults with healthy eyes. METHODS: MEDLINE®, Cochrane, and Commonwealth of Agriculture Bureau abstracts databases were searched for English-language publications between 1946 and August 2018. Included studies examined correlation of MPOD and visual function in adults with healthy eyes at all timepoints and all designs, except for case-control, case reports, and reviews. Visual function outcomes of interest included photostress recovery, contrast sensitivity, visual acuity, glare sensitivity/disability, and dark adaptation. Random effects model meta-analyses combined study-level correlation (r). RESULTS: Twenty-two publications were included. In meta-analysis MPOD was found to be significantly correlated with contrast sensitivity at 30' (two studies, summary r: 0.37; 95% CI 0.15, 0.56), and at 1° eccentricity with a spatial frequency of 7, 11, and 21 cpd (three studies, summary r: 0.31; 95% CI 0.06, 0.52), with photostress recovery at a 1° eccentricity with a moderate background, 10 cpd, and 16% contrast (two studies, summary r: -0.17; 95% CI -0.31, -0.02), and at 30' (four studies, summary r: -0.57; 95% CI -0.78, -0.24), and with glare disability at 30' eccentricity with a log scale at 460 nm (three studies, summary r = 0.47; 95% CI 0.32; 0.59). There were insufficient data for meta-analysis for other visual functions. CONCLUSIONS: Our review identifies a link between MPOD and visual function with significant correlations with photostress recovery, glare disability, and contrast sensitivity.

Walnut intake, cognitive outcomes and risk factors: a systematic review and meta-analysis.

BACKGROUND: Walnuts contain nutrients that are associated with improved cognitive health. To our knowledge, no review has systematically examined the effects of walnuts on cognitive function and risk for cognitive decline. OBJECTIVE: To conduct a systematic review and meta-analysis evaluating the effects of walnut intake on cognition-related outcomes and risk-factors for cognitive decline in adults. METHODS: Medline®, Commonwealth Agricultural Bureau, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and observational studies published until April 2020 on walnut intake, cognition (e.g. cognitive function, stroke, and mood), and selected risk factors for cognitive decline (e.g. glucose homeostasis and inflammation). Risk-of-bias and strength-of-evidence assessments were conducted using standard validated tools. Random-effects meta-analyses were conducted when ≥3 studies reported quantitative data for each outcome. RESULTS: 32 RCT and 7 observational study publications were included. Meta-analysis of cognition-related outcomes could not be conducted due to heterogeneity of tests. None of the 5 cognition RCTs found significant effects of walnuts on overall cognition, although 3 studies found improvements on subdomains and/or subgroups. All 7 observational studies found significant associations and a dose-response relationship between walnut intake and cognition-related outcomes. Meta-analyses of 27 RCTs reporting glucose homeostasis and inflammation outcomes, selected risk factors for cognitive decline, did not show significant effects of walnut intake. CONCLUSIONS: Due to the non-uniformity of tests for cognition-related outcomes, definitive conclusions regarding the effect of walnut consumption on cognition could not be reached. Additionally, evidence does not show associations between walnut intake and glucose homeostasis or inflammation, cognitive decline risk-factors. High-quality studies with standardized measures are needed to clarify the role of walnuts in cognitive health.KEY MESSAGESThis is a systematic review and meta-analysis of 5 randomized clinical trials and 7 observational study articles of the impact of walnut intake on cognition decline and 27 randomized clinical trials of the effect of walnut intake on risk factors for cognitive decline including glucose homeostasis and inflammation.The non-uniformity of tests performed to measure cognitive function in the various studies did not allow for a meta-analysis of these studies. A definitive conclusion could therefore not be reached regarding the effect of walnut intake on cognitive decline.The evidence available does not show an association between walnut intake and glucose homeostasis or inflammation.

Potato consumption and risk of cardio-metabolic diseases: evidence mapping of observational studies.

BACKGROUND: Recent systematic review of clinical trials concluded that there was no convincing evidence to suggest an association between potatoes and risk of cardio-metabolic diseases. OBJECTIVE: Summarize observational study data related to potato intake and cardio-metabolic health outcomes in adults using evidence mapping to assess the need for a future systematic review. METHODS: We searched MEDLINE®, Commonwealth Agricultural Bureau, and bibliographies for eligible observational studies published between 1946 and July 2020. Included studies evaluated potato intake in any form or as part of a dietary pattern with risk for cardio-metabolic diseases. Outcomes of interest included cardiovascular disease (CVD), cerebrovascular diseases, diabetes, hypertension, blood lipids, and body composition. RESULTS: Of 121 eligible studies, 51 reported two different methods to quantify potato intake (30 studies quantified intake as either grams or serving; 20 studies reported times per week; one reported both methods) and 70 reported potato as part of a dietary pattern and compared higher vs. lower intake, linear change, or difference in potato intake among cases and controls. Studies that quantified potato intake as either grams or serving reported the following outcomes: diabetes (8 studies); cerebrovascular stroke (6 studies); five studies each for CVD, systolic and diastolic blood pressure, and hypertension; three studies each for body mass index, body weight, CVD mortality; two studies for myocardial infarction; and one study each for blood glucose, HOMA-IR, and blood lipids. Higher potato intake was associated with an increased risk for blood pressure and body weight, and the results of all other outcomes observed no association. Potato consumption as part of dietary pattern studies reported a negative association between fried form of potato and all or most cardio-metabolic risk factors and diseases. CONCLUSION: Evidence mapping found sufficient data on the association between potato intake and cardio-metabolic disease risk factors to warrant for a systematic review/meta-analysis of observational studies.

Burden of carbapenem non-susceptible infections in high-risk patients: systematic literature review and meta-analysis.

BACKGROUND: Owing to their resistance to an important class of antibiotics, the prevention and treatment of carbapenem-resistant (CR)/non-susceptible Gram-negative (GN) infections has become an important public health objective. We conducted a systematic review and meta-analysis of published literature to evaluate the burden of CR GN infections, focusing on high-risk patients such as transplant recipients, or patients with cancer, renal impairment, or sepsis. METHODS: MEDLINE®, Cochrane Central, and Embase® were searched between 2010 and March 2019. Abstracts and full-text articles were screened in duplicate. Random effects meta-analysis was conducted when reported outcomes were sufficiently similar. RESULTS: Twenty-six publications were eligible. Meta-analyses found increased mortality associated with CR infections among high-risk patients in both unadjusted analysis (8 studies; summary unadjusted odds ratio [OR]: 5.85; 95% confidence interval [CI]: 3.69, 9.26; I2 = 19.8%) and adjusted analysis (5 studies; summary hazard ratio [HR]: 4.67; 95% CI: 2.18, 9.99; I2 = 77.7%), compared to patients with carbapenem-susceptible (CS) infections or no infection. Increased mortality was also seen in subgroup analyses by length of follow-up (either short-term or long-term) or causative pathogen. A limited number of studies found that CR GN infections increased the risk for mechanical ventilation, adverse events such as graft failure or acute rejection in solid organ transplant recipients, increased renal failure or nephrotoxicity, and an increase in readmissions and costs, though the findings reported in the literature were not consistent. CONCLUSION: This systematic literature review and meta-analysis indicates that CR GN infections in high-risk patients are associated with increased mortality, emphasizing the need for antimicrobial stewardship and infection control in hospitals which treat high-risk patients and for the development of effective antimicrobials with favorable efficacy and safety profiles for the treatment of CR GN infections.

Almond Consumption and Risk Factors for Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Evidence suggests that eating nuts may reduce the risk of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating almond consumption and risk factors for CVD. MEDLINE, Cochrane Central, Commonwealth Agricultural Bureau, and previous systematic reviews were searched from 1990 through June 2017 for RCTs of ≥3 wk duration that evaluated almond compared with no almond consumption in adults who were either healthy or at risk for CVD. The most appropriate stratum was selected with an almond dose closer to 42.5 g, with a control most closely matched for macronutrient composition, energy intake, and similar intervention duration. The outcomes included risk factors for CVD. Random-effects model meta-analyses and subgroup meta-analyses were performed. Fifteen eligible trials analyzed a total of 534 subjects. Almond intervention significantly decreased total cholesterol (summary net change: -10.69 mg/dL; 95% CI: -16.75, -4.63 mg/dL), LDL cholesterol (summary net change: -5.83 mg/dL; 95% CI: -9.91, -1.75 mg/dL); body weight (summary net change: -1.39 kg; 95% CI: -2.49, -0.30 kg), HDL cholesterol (summary net change: -1.26 mg/dL; 95% CI: -2.47, -0.05 mg/dL), and apolipoprotein B (apoB) (summary net change: -6.67 mg/dL; 95% CI: -12.63, -0.72 mg/dL). Triglycerides, systolic blood pressure, apolipoprotein A1, high-sensitivity C-reactive protein, and lipoprotein (a) showed no difference between almond and control in the main and subgroup analyses. Fasting blood glucose, diastolic blood pressure, and body mass index significantly decreased with almond consumption of >42.5 g compared with ≤42.5 g. Almond consumption may reduce the risk of CVD by improving blood lipids and by decreasing body weight and apoB. Substantial heterogeneity in eligible studies regarding almond interventions and dosages precludes firmer conclusions.

Effects of Intake of Apples, Pears, or Their Products on Cardiometabolic Risk Factors and Clinical Outcomes: A Systematic Review and Meta-Analysis.

Apples and pears contain nutrients that have been linked to cardiovascular health. We conducted a systematic review and meta-analysis to summarize related research. Medline, Cochrane Central, and Commonwealth Agricultural Bureau databases were searched for publications on apple or pear intake and cardiovascular disease (CVD)/ cardiometabolic disease (CMD). Studies in adults (healthy or at risk for CVD) that quantified apple or pear intake were included. Random-effects models meta-analysis was used when ≥3 studies reported the same outcome. In total, 22 studies were eligible including 7 randomized controlled trial, 1 nonrandomized trial, and 14 prospective observational studies. In RCTs, apple intake significantly decreased BMI, but made no difference in body weight, serum lipids, blood glucose, or blood pressure. In observational studies, apple or pear intake significantly decreased risk of cerebrovascular disease, cardiovascular death, type 2 diabetes mellitus, and all-cause mortality. No association was reported for cerebral infarction or intracerebral hemorrhage. In conclusion, apple or pear intake significantly decreased BMI and risk for CVD outcomes.

Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies.

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.

Avocado consumption and risk factors for heart disease: a systematic review and meta-analysis.

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 α, 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.

Risk factors for hospitalized patients with resistant or multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis.

Background: Identifying risk factors predicting acquisition of resistant Pseudomonas aeruginosa will aid surveillance and diagnostic initiatives and can be crucial in early and appropriate antibiotic therapy. We conducted a systematic review examining risk factors of acquisition of resistant P. aeruginosa among hospitalized patients. Methods: MEDLINE®, EMBASE®, and Cochrane Central were searched between 2000 and 2016 for studies examining independent risk factors associated with acquisition of resistant P. aeruginosa, among hospitalized patients. Random effects model meta-analysis was conducted when at least three or more studies were sufficiently similar. Results: Of the 54 eligible articles, 28 publications (31studies) examined multi-drug resistant (MDR) or extensively drug resistant (XDR) P. aeruginosa and 26 publications (29 studies) examined resistant P. aeruginosa. The acquisition of MDR P. aeruginosa, as compared with non-MDR P. aeruginosa, was significantly associated with intensive care unit (ICU) admission (3 studies: summary adjusted odds ratio [OR] 2.2) or use of quinolones (4 studies: summary adjusted OR 3.59). Acquisition of MDR or XDR compared with susceptible P. aeruginosa was significantly associated with prior hospital stay (4 studies: summary adjusted OR 1.90), use of quinolones (3 studies: summary adjusted OR 4.34), or use of carbapenems (3 studies: summary adjusted OR 13.68). The acquisition of MDR P. aeruginosa compared with non-P. aeruginosa was significantly associated with prior use of cephalosporins (3 studies: summary adjusted OR 3.96), quinolones (4 studies: summary adjusted OR 2.96), carbapenems (6 studies: summary adjusted OR 2.61), and prior hospital stay (4 studies: summary adjusted OR 1.74). The acquisition of carbapenem-resistant P. aeruginosa compared with susceptible P. aeruginosa, was statistically significantly associated with prior use of piperacillin-tazobactam (3 studies: summary adjusted OR 2.64), vancomycin (3 studies: summary adjusted OR 1.76), and carbapenems (7 studies: summary adjusted OR 4.36). Conclusions: Prior use of antibiotics and prior hospital or ICU stay was the most significant risk factors for acquisition of resistant P. aeruginosa. These findings provide guidance in identifying patients that may be at an elevated risk for a resistant infection and emphasize the importance of antimicrobial stewardship and infection control in hospitals.

Dietary intakes of flavan-3-ols and cardiovascular health: a field synopsis using evidence mapping of randomized trials and prospective cohort studies.

BACKGROUND: There is considerable interest in the impact of increased flavan-3-ol intake on cardiovascular disease (CVD) and diabetes outcomes. Through evidence mapping, we determined the extent of the evidence base to initiate a future systematic review investigating the impact of flavan-3-ol intake on CVD and diabetes outcomes. METHODS: We developed a research protocol, convened a technical expert panel (TEP) to refine the specific research questions, conducted a systematic search in multiple databases, double-screened abstracts and full-text articles, performed data extractions, and synthesized the data. We focused on randomized controlled trials (RCTs) and prospective cohort studies which assessed intakes of flavan-3-ol from foods, beverages, and supplement/extract sources on biomarkers and clinical outcomes of CVD and diabetes. RESULTS: Of 257 eligible articles, 223 and 34 publications contributed to 226 RCTs and 39 prospective cohort studies, respectively. In RCTs, the most frequently studied interventions were cocoa-based products (23.2%); berries (16.1%); tea in the form of green tea (13.9%), black tea (7.2%), or unspecified tea (3.6%); and red wine (11.2%). Mean total flavan-3-ol intake was highest in the cocoa-based trials (618.7 mg/day) and lowest in the interventions feeding red wine (123.7 mg/day). The most frequently reported outcomes were intermediate biomarkers including serum lipid levels (63.4%), blood glucose (50.9%), blood pressure (50.8%), flow-mediated dilation (21.9%), and high-sensitivity C-reactive protein (21.9%). The included 34 prospective cohort studies predominantly examined exposures to flavan-3-ols (26%), cocoa-based products (23.2%), berries (16.1%), and green tea (13.9%) and CVD incidence and mortality. CONCLUSION: Through a systematic, evidence-based approach, evidence mapping on flavan-3-ol intake and CVD outcomes demonstrated sufficient data relating to flavan-3ol intake and biomarkers and clinical outcomes of CVD and diabetes. The current evidence base highlights the distribution of available data which both support the development of a future systematic review and identified the research need for future long-term RCTs. SYSTEMATIC REVIEW REGISTRATION: At present, evidence mapping is not eligible for registration on the international prospective register of systematic reviews (i.e., PROSPERO).

Opportunities and challenges in using studies without a control group in comparative effectiveness reviews.

When examining the evidence on therapeutic interventions to answer a comparative effectiveness research question, one should consider all studies that are informative on the interventions' causal effects. "Single group studies" evaluate outcomes longitudinally in cohorts of subjects who are managed with a single treatment strategy. Because these studies are "missing" a direct, concurrent comparison group, they are typically deemed non-informative on comparative effectiveness. However, in principle, single group studies can provide information on causal treatment effects by extrapolating expected outcomes in the "missing" untreated arm. Single group studies rely on before-after, implicit, or historical comparisons as a proxy for an ideal comparison group. The validity of these comparisons must be carefully examined on a case-by-case basis. While in many cases, researchers will disagree on whether such extrapolations are reasonable; circumstances exist where such studies are generally acceptable as a source of evidence. This article provides an overview of issues related to the interpretation of single group studies with a focus on the assumptions required to support their consideration in comparative effectiveness reviews. We discuss the various settings in which single group studies are employed, common research designs that systematic reviewers need to interpret, and challenges associated with using these designs to inform comparative effectiveness questions.