The Evolution of Science and Regulation of Dietary Supplements: Past, Present, and Future.

Dietary supplement use in the United States is widespread and increasing, especially among certain population groups, such as older Americans. The science surrounding dietary supplements has evolved substantially over the last few decades since their formal regulation in 1994. Much has been learned about the mechanisms of action of many dietary supplement ingredients, but the evidence on their health effects is still building. As is true of much nutrition research, there are many studies that point to health effects, but not all are at the level of scientific evidence (e.g., randomized controlled interventions), rigor, or quality needed for definitive statements of efficacy regarding clinical end points. New technologies and approaches are being applied to the science of dietary supplements, including nutrigenomics and microbiome analysis, data science, artificial intelligence (AI), and machine learning-all of which can elevate the science behind dietary supplements. Products can contain an array of bioactive compounds derived from foods as well as from medicinal plants, which creates enormous challenges in data collection and management. Clinical applications, particularly those aimed at providing personalized nutrition options for patients, have become more sophisticated as dietary supplements are incorporated increasingly into clinical practice and self-care. The goals of this article are to provide historical context for the regulation and science of dietary supplements, identify research resources, and suggest some future directions for science in this field.

The Cumulative Incidence of Post-Traumatic Epilepsy After Mild Traumatic Brain Injury: A Systematic Review and Individual Participant Data Meta-Analysis Protocol.

A precise understanding of the latency to post-traumatic epilepsy (PTE) following a traumatic brain injury (TBI) is necessary for optimal patient care. This precision is currently lacking despite a surprising number of available data sources that could address this pressing need. Following guidance from the Cochrane Collaboration and Joanna Briggs Institute, we conduct a systematic review to address the research questions: What is the cumulative incidence of PTE following mild TBI (mTBI; concussion), and what is the distribution of the latency to onset? We designed a comprehensive search of medical databases and gray literature sources. Citations will be screened on both abstract and full-text levels, independently and in duplicate. Studies will be evaluated for risk of bias independently and in duplicate using published instruments specific to incidence/prevalence studies. Data will be abstracted independently and in duplicate using piloted extraction forms. Disagreements will be resolved by consensus or third-party adjudication. Evidence synthesis will involve pairwise and individual participant data meta-analysis with heterogeneity explored via a set of predetermined subgroups. The robustness of the findings will be subjected to sensitivity analyses based on the risk of bias, outlier studies, and mTBI definitional criteria. The overall certainty in the estimates will be reported using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations). This protocol presents an innovative and impactful approach to build on the growing body of knowledge surrounding post-mTBI PTE. Through a precise understanding of the latency period, this study can contribute to early detection, tailored interventions, and improved outcomes, leading to a substantial impact on patient care and quality of life.

What is the association between the microbiome and cognition? An umbrella review protocol.

INTRODUCTION: Cognitive impairment is reported in a variety of clinical conditions including Alzheimer's disease, Parkinson's and 'long-COVID'. Interestingly, many of these clinical conditions are also associated with microbial dysbiosis. This comanifestation of cognitive and microbiome findings in seemingly unrelated maladies suggests that they could share a common mechanism and potentially presents a treatment target. Although a rapidly growing body of literature has documented this comorbid presentation within specific conditions, an overview highlighting potential parallels across healthy and clinical populations is lacking. The objective of this umbrella review, therefore, is to summarise and synthesise the findings of these systematic reviews. METHODS AND ANALYSIS: On 2 April 2023, we searched MEDLINE (Pubmed), Embase (Ovid), the Web of Science (Core Collection), the Cochrane Library of Systematic Reviews and Epistemonikos as well as grey literature sources, for systematic reviews on clinical conditions and interventions where cognitive and microbiome outcomes were coreported. An updated search will be conducted before completion of the project if the search-to-publication date is >1 year old. Screening, data abstraction and quality assessment (AMSTAR 2, A MeaSurement Tool to Assess systematic Reviews) will be conducted independently and in duplicate, with disagreements resolved by consensus. Evidence certainty statements for each review's conclusions (eg, Grading of Recommendations Assessment, Development and Evaluation (GRADE)) will be extracted or constructed de novo. A narrative synthesis will be conducted and delineated by the review question. Primary study overlap will be visualised using a citation matrix as well as calculated using the corrected covered area method. ETHICS AND DISSEMINATION: No participant-identifying information will be used in this review. No ethics approval was required due to our study methodology. Our findings will be presented at national and international conferences and disseminated via social media and press releases. We will recruit at least one person living with cognitive impairment to collaborate on writing the plain language summary for the review. PROSPERO REGISTRATION NUMBER: CRD42023412903.

Saturated fat, the estimated absolute risk and certainty of risk for mortality and major cancer and cardiometabolic outcomes: an overview of systematic reviews.

OBJECTIVE: To assess the impact of reducing saturated fat or fatty foods, or replacing saturated fat with unsaturated fat, carbohydrate or protein, on the risk of mortality and major cancer and cardiometabolic outcomes in adults. METHODS: We searched MEDLINE, EMBASE, CINAHL, and references of included studies for systematic reviews and meta-analyses (SRMAs) of randomized controlled trials (RCTs) and observational studies in adults published in the past 10 years. Eligible reviews investigated reducing saturated fat or fatty foods or replacing saturated fat with unsaturated fat, carbohydrate or protein, on the risk of cancer and cardiometabolic outcomes and assessed the certainty of evidence for each outcome using, for example, the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. We assessed the quality of SRMAs using a modified version of AMSTAR-2. Results were summarized as absolute estimates of effect together with the certainty of effects using a narrative synthesis approach. RESULTS: We included 17 SRMAs (13 reviews of observational studies with follow-up 1 to 34 years; 4 reviews of RCTs with follow-up 1 to 17 years). The quality of two-thirds of the SRMAs was critically low to moderate; the main limitations included deficient reporting of study selection, absolute effect estimates, sources of funding, and a priori subgroups to explore heterogeneity. Our included reviews reported > 100 estimates of effect across 11 critically important cancer and cardiometabolic outcomes. High quality SRMAs consistently and predominantly reported low to very low certainty evidence that reducing or replacing saturated fat was associated with a very small risk reduction in cancer and cardiometabolic endpoints. The risk reductions where approximately divided, some being statistically significant and some being not statistically significant. However, based on 2 moderate to high quality reviews, we found moderate certainty evidence for a small but important effect that was statistically significant for two outcomes (total mortality events [20 fewer events per 1000 followed] and combined cardiovascular events [16 fewer per 1000 followed]). Conversely, 4 moderate to high quality reviews showed very small effects on total mortality, with 3 of these reviews showing non-statistically significant mortality effects. CONCLUSION: Systematic reviews investigating the impact of SFA on mortality and major cancer and cardiometabolic outcomes almost universally suggest very small absolute changes in risk, and the data is based primarily on low and very low certainty evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020172141.

Comparison of seven popular structured dietary programmes and risk of mortality and major cardiovascular events in patients at increased cardiovascular risk: systematic review and network meta-analysis.

OBJECTIVE: To determine the relative efficacy of structured named diet and health behaviour programmes (dietary programmes) for prevention of mortality and major cardiovascular events in patients at increased risk of cardiovascular disease. DESIGN: Systematic review and network meta-analysis of randomised controlled trials. DATA SOURCES: AMED (Allied and Complementary Medicine Database), CENTRAL (Cochrane Central Register of Controlled Trials), Embase, Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and ClinicalTrials.gov were searched up to September 2021. STUDY SELECTION: Randomised trials of patients at increased risk of cardiovascular disease that compared dietary programmes with minimal intervention (eg, healthy diet brochure) or alternative programmes with at least nine months of follow-up and reporting on mortality or major cardiovascular events (such as stroke or non-fatal myocardial infarction). In addition to dietary intervention, dietary programmes could also include exercise, behavioural support, and other secondary interventions such as drug treatment. OUTCOMES AND MEASURES: All cause mortality, cardiovascular mortality, and individual cardiovascular events (stroke, non-fatal myocardial infarction, and unplanned cardiovascular interventions). REVIEW METHODS: Pairs of reviewers independently extracted data and assessed risk of bias. A random effects network meta-analysis was performed using a frequentist approach and grading of recommendations assessment, development and evaluation (GRADE) methods to determine the certainty of evidence for each outcome. RESULTS: 40 eligible trials were identified with 35 548 participants across seven named dietary programmes (low fat, 18 studies; Mediterranean, 12; very low fat, 6; modified fat, 4; combined low fat and low sodium, 3; Ornish, 3; Pritikin, 1). At last reported follow-up, based on moderate certainty evidence, Mediterranean dietary programmes proved superior to minimal intervention for the prevention of all cause mortality (odds ratio 0.72, 95% confidence interval 0.56 to 0.92; patients at intermediate risk: risk difference 17 fewer per 1000 followed over five years), cardiovascular mortality (0.55, 0.39 to 0.78; 13 fewer per 1000), stroke (0.65, 0.46 to 0.93; 7 fewer per 1000), and non-fatal myocardial infarction (0.48, 0.36 to 0.65; 17 fewer per 1000). Based on moderate certainty evidence, low fat programmes proved superior to minimal intervention for prevention of all cause mortality (0.84, 0.74 to 0.95; 9 fewer per 1000) and non-fatal myocardial infarction (0.77, 0.61 to 0.96; 7 fewer per 1000). The absolute effects for both dietary programmes were more pronounced for patients at high risk. There were no convincing differences between Mediterranean and low fat programmes for mortality or non-fatal myocardial infarction. The five remaining dietary programmes generally had little or no benefit compared with minimal intervention typically based on low to moderate certainty evidence. CONCLUSIONS: Moderate certainty evidence shows that programmes promoting Mediterranean and low fat diets, with or without physical activity or other interventions, reduce all cause mortality and non-fatal myocardial infarction in patients with increased cardiovascular risk. Mediterranean programmes are also likely to reduce stroke risk. Generally, other named dietary programmes were not superior to minimal intervention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016047939.

Functional genomics of human clear cell sarcoma: genomic, transcriptomic and chemical biology landscape for clear cell sarcoma.

BACKGROUND: Systemic therapy for metastatic clear cell sarcoma (CCS) bearing EWSR1-CREB1/ATF1 fusions remains an unmet clinical need in children, adolescents, and young adults. METHODS: To identify key signaling pathway vulnerabilities in CCS, a multi-pronged approach was taken: (i) genomic and transcriptomic landscape analysis, (ii) integrated chemical biology interrogations, (iii) development of CREB1/ATF1 inhibitors, and (iv) antibody-drug conjugate testing (ADC). The first approach encompassed DNA exome and RNA deep sequencing of the largest human CCS cohort yet reported consisting of 47 patient tumor samples and 8 cell lines. RESULTS: Sequencing revealed recurrent mutations in cell cycle checkpoint, DNA double-strand break repair or DNA mismatch repair genes, with a correspondingly low to intermediate tumor mutational burden. DNA multi-copy gains with corresponding high RNA expression were observed in CCS tumor subsets. CCS cell lines responded to the HER3 ADC patritumab deruxtecan in a dose-dependent manner in vitro, with impaired long term cell viability. CONCLUSION: These studies of the genomic, transcriptomic and chemical biology landscape represent a resource 'atlas' for the field of CCS investigation and drug development. CHK inhibitors are identified as having potential relevance, CREB1 inhibitors non-dependence of CCS on CREB1 activity was established, and the potential utility of HER3 ADC being used in CCS is found.

Auditory hallucinations, childhood sexual abuse, and limbic gray matter volume in a transdiagnostic sample of people with psychosis.

Childhood sexual abuse (CSA) is a potentially unique risk factor for auditory hallucinations (AH), but few studies have examined the moderating effects of sex or the association of CSA with limbic gray matter volume (GMV) in transdiagnostic samples of people with psychotic disorders. Here we found that people with psychotic disorders reported higher levels of all surveyed maltreatment types (e.g., physical abuse) than healthy controls, but people with psychotic disorders with AH (n = 41) reported greater CSA compared to both those without AH (n = 37; t = -2.21, p = .03) and controls (n = 37; t = -3.90, p < .001). Among people with psychosis, elevated CSA was most pronounced among females with AH (sex × AH status: F = 4.91, p = .009), held controlling for diagnosis, medications, and other maltreatment (F = 3.88, p = .02), and correlated with the current severity of AH (r = .26, p = .03) but not other symptoms (p's > .16). Greater CSA among patients related to larger GMV of the left amygdala accounting for AH status, diagnosis, medications, and other maltreatment (t = 2.12, p = .04). Among people with psychosis, females with AH may represent a unique subgroup with greater CSA. Prospective high-risk studies integrating multiple measures of maltreatment and brain structure/function may help elucidate the mechanisms linking CSA with amygdala alterations and AH.

International prevalence of consultation with a naturopathic practitioner: a systematic review and meta-analysis.

OBJECTIVES: Naturopathy is a traditional medicine system informed by codified philosophies and principles, and an emphasis on non-pharmacologic therapeutic interventions. While naturopathy is practised by approximately 75 000-100 000 000 naturopathic practitioners in at least 98 countries, little is known about the international prevalence of history of consultation with a naturopathic practitioner. This study reports a systematic review and meta-analysis of studies describing the global prevalence of history of consultation with a naturopathic practitioner by the general population. SETTING: The included literature was identified through a systematic search of eight databases between September and October 2019, as well as the grey literature. PARTICIPANTS: Studies were included if they reported the prevalence rate of consultations with a naturopathic practitioner by the general population. INTERVENTIONS: Survey items needed to report consultations with a naturopathic practitioner as defined in the country where data was collected, and not combine naturopathic consultations with other health services or only report consulations for illness populations. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary measures used for the analysis was consultations in the previous 12 months. Other prevalence timeframes were reported as secondary measures. METHODS: Meta-analysis of prevalence data was conducted using random effects models based on individual countries and WHO world regions. RESULTS: The literature search identified eight manuscripts summarising 14 studies reporting prevalence for inclusion in the review. All included studies had a low risk of bias. Meta-analysis of the included studies by world region found the 12-month prevalence of history of naturopathy consultations ranged from 1% in the Region of the Americas to 6% in the European and Western Pacific Regions. CONCLUSIONS: There are up to sixfold differences in the prevalence of naturopathy consults over 12 months between and within world regions, which may be driven by a range of policy, legislative and social factors. PROSPERO REGISTRATION NUMBER: CRD42020145529.

Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate the benefits and risks of zinc formulations compared with controls for prevention or treatment of acute viral respiratory tract infections (RTIs) in adults. METHOD: Seventeen English and Chinese databases were searched in April/May 2020 for randomised controlled trials (RCTs), and from April/May 2020 to August 2020 for SARS-CoV-2 RCTs. Cochrane rapid review methods were applied. Quality appraisals used the Risk of Bias 2.0 and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-eight RCTs with 5446 participants were identified. None were specific to SARS-CoV-2. Compared with placebo, oral or intranasal zinc prevented 5 RTIs per 100 person-months (95% CI 1 to 8, numbers needed to treat (NNT)=20, moderate-certainty/quality). Sublingual zinc did not prevent clinical colds following human rhinovirus inoculations (relative risk, RR 0.96, 95% CI 0.77 to 1.21, moderate-certainty/quality). On average, symptoms resolved 2 days earlier with sublingual or intranasal zinc compared with placebo (95% CI 0.61 to 3.50, very low-certainty/quality) and 19 more adults per 100 were likely to remain symptomatic on day 7 without zinc (95% CI 2 to 38, NNT=5, low-certainty/quality). There were clinically significant reductions in day 3 symptom severity scores (mean difference, MD -1.20 points, 95% CI -0.66 to -1.74, low-certainty/quality), but not average daily symptom severity scores (standardised MD -0.15, 95% CI -0.43 to 0.13, low-certainty/quality). Non-serious adverse events (AEs) (eg, nausea, mouth/nasal irritation) were higher (RR 1.41, 95% CI 1.17 to 1.69, NNHarm=7, moderate-certainty/quality). Compared with active controls, there were no differences in illness duration or AEs (low-certainty/quality). No serious AEs were reported in the 25 RCTs that monitored them (low-certainty/quality). CONCLUSIONS: In adult populations unlikely to be zinc deficient, there was some evidence suggesting zinc might prevent RTIs symptoms and shorten duration. Non-serious AEs may limit tolerability for some. The comparative efficacy/effectiveness of different zinc formulations and doses were unclear. The GRADE-certainty/quality of the evidence was limited by a high risk of bias, small sample sizes and/or heterogeneity. Further research, including SARS-CoV-2 clinical trials is warranted. PROSPERO REGISTRATION NUMBER: CRD42020182044.

Honeybee products for the treatment and recovery from viral respiratory infections including SARS-COV-2: A rapid systematic review.

BACKGROUND: This rapid review systematically evaluated the effects of honeybee products compared to controls for the prevention, duration, severity, and recovery of acute viral respiratory tract infections (RTIs), including SARS-CoV-2, in adults and children. METHODS: Cochrane rapid review methods were applied. Four English databases plus preprint servers and trial registries were searched for randomized controlled trials (RCTs). The evidence was appraised and synthesized using RoB 2.0 and GRADE. RESULTS: 27 results were derived from 9 RCTs that included 674 adults and 781 children. In hospitalized adults with SARS-CoV-2, propolis plus usual-care compared to usual-care alone reduced the risk of shock, respiratory failure and kidney injury and duration of hospital admission. Honey was less effective than Guaifenesin for reducing cough severity at 60-minutes in adults with non-specific acute viral RTIs. Compared to coffee, honey plus coffee, and honey alone reduced the severity of post-infectious cough in adults. Honey reduced the duration of cough in children compared to placebo and salbutamol; and the global impact of nocturnal cough after one night compared to usual-care alone and pharmaceutical cough medicines. CONCLUSION: More studies are needed to robustly assess honeybee's role in SARS-CoV-2 and non-specific viral respiratory infections. PROTOCOL REGISTRATION: PROSPERO: CRD42020193847.

Inflammatory Bowel Disease and Neutrophil-Lymphocyte Ratio: A Systematic Scoping Review.

Neutrophil-lymphocyte ratio (NLR) is a biomarker of the systemic inflammatory response. The objective of this systematic scoping review was to examine the literature on NLR and inflammatory bowel disease (IBD). PubMed, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, Cochrane Specialized Register, DOAJ, PDQT, Biosis Citation Index, Scopus, and Web of Science were systematically searched. A total of 2621 citations yielding 62 primary studies were synthesized under four categories: distinguishing patients with IBD from controls, disease activity differentiation, clinical outcome prediction, and association of NLR with other IBD biomarkers. Thirty-eight studies employed receiver operating characteristic (ROC) curve analysis to generate optimal NLR cutpoints for applications including disease activity differentiation and prediction of response to treatment. Among the most promising findings, NLR may have utility for clinical and endoscopic disease activity differentiation and prediction of loss of response to infliximab (IFX). Overall findings suggest NLR may be a promising IBD biomarker. Assessment of NLR is non-invasive, low cost, and widely accessible given NLR is easily calculated from blood count data routinely and serially monitored in patients with IBD. Further research is justified to elucidate how evaluation of NLR in research and clinical practice would directly impact the quality and cost of care for patients living with IBD.

Cellular and Extracellular White Matter Abnormalities in Obsessive-Compulsive Disorder: A Diffusion Magnetic Resonance Imaging Study.

BACKGROUND: While previous studies have implicated white matter (WM) as a core pathology of obsessive-compulsive disorder (OCD), the underlying neurobiological processes remain elusive. This study used free-water (FW) imaging derived from diffusion magnetic resonance imaging to identify cellular and extracellular WM abnormalities in patients with OCD compared with control subjects. Next, we investigated the association between diffusion measures and clinical variables in patients. METHODS: We collected diffusion-weighted magnetic resonance imaging and clinical data from 83 patients with OCD (56 women/27 men, age 37.7 ± 10.6 years) and 52 control subjects (27 women/25 men, age 32.8 ± 11.5 years). Fractional anisotropy (FA), FA of cellular tissue, and extracellular FW maps were extracted and compared between patients and control subjects using tract-based spatial statistics and voxelwise comparison in FSL Randomise. Next, we correlated these WM measures with clinical variables (age of onset and symptom severity) and compared them between patients with and without comorbidities and patients with and without psychiatric medication. RESULTS: Patients with OCD demonstrated lower FA (43.4% of the WM skeleton), lower FA of cellular tissue (31% of the WM skeleton), and higher FW (22.5% of the WM skeleton) compared with control subjects. We did not observe significant correlations between diffusion measures and clinical variables. Comorbidities and medication status did not influence diffusion measures. CONCLUSIONS: Our findings of widespread FA, FA of cellular tissue, and FW abnormalities suggest that OCD is associated with microstructural cellular and extracellular abnormalities beyond the corticostriatothalamocortical circuits. Future multimodal longitudinal studies are needed to understand better the influence of essential clinical variables across the illness trajectory.

Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data.

OBJECTIVE: To determine the efficacy and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Searches of CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception to 25 August 2020. STUDY SELECTION: Randomized clinical trials evaluating LCDs (<130 g/day or <26% of a 2000 kcal/day diet) and VLCDs (<10% calories from carbohydrates) for at least 12 weeks in adults with type 2 diabetes were eligible. DATA EXTRACTION: Primary outcomes were remission of diabetes (HbA1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA1c, fasting glucose, and adverse events. Secondary outcomes included health related quality of life and biochemical laboratory data. All articles and outcomes were independently screened, extracted, and assessed for risk of bias and GRADE certainty of evidence at six and 12 month follow-up. Risk estimates and 95% confidence intervals were calculated using random effects meta-analysis. Outcomes were assessed according to a priori determined minimal important differences to determine clinical importance, and heterogeneity was investigated on the basis of risk of bias and seven a priori subgroups. Any subgroup effects with a statistically significant test of interaction were subjected to a five point credibility checklist. RESULTS: Searches identified 14 759 citations yielding 23 trials (1357 participants), and 40.6% of outcomes were judged to be at low risk of bias. At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA1c <6.5%) (76/133 (57%) v 41/131 (31%); risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264, I2=58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA1c <6.5% without medication was used. Subgroup assessments determined as meeting credibility criteria indicated that remission with LCDs markedly decreased in studies that included patients using insulin. At 12 months, data on remission were sparse, ranging from a small effect to a trivial increased risk of diabetes. Large clinically important improvements were seen in weight loss, triglycerides, and insulin sensitivity at six months, which diminished at 12 months. On the basis of subgroup assessments deemed credible, VLCDs were less effective than less restrictive LCDs for weight loss at six months. However, this effect was explained by diet adherence. That is, among highly adherent patients on VLCDs, a clinically important reduction in weight was seen compared with studies with less adherent patients on VLCDs. Participants experienced no significant difference in quality of life at six months but did experience clinically important, but not statistically significant, worsening of quality of life and low density lipoprotein cholesterol at 12 months. Otherwise, no significant or clinically important between group differences were found in terms of adverse events or blood lipids at six and 12 months. CONCLUSIONS: On the basis of moderate to low certainty evidence, patients adhering to an LCD for six months may experience remission of diabetes without adverse consequences. Limitations include continued debate around what constitutes remission of diabetes, as well as the efficacy, safety, and dietary satisfaction of longer term LCDs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020161795.

Corrigendum to "Choose your shortcuts wisely: COVID-19 rapid reviews of traditional, complementary and integrative medicine" [Integr Med Res 2020; 9: 100484].

[This corrects the article DOI: 10.1016/j.imr.2020.100484.].

Corrigendum to "Rapid review protocol: Zinc for the prevention or treatment of COVID-19 and other coronavirus-related respiratory tract infections" [Integr Med Res 9 (2020): 100457].

[This corrects the article DOI: 10.1016/j.imr.2020.100457.].

Multinutrients for the Treatment of Psychiatric Symptoms in Clinical Samples: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis focused on randomized controlled trials (RCT) of multinutrients consisting of at least four vitamins and/or minerals as interventions for participants with psychiatric symptoms. A systematic search identified 16 RCTs that fit the inclusion criteria (n = 1719 participants) in six psychiatric categories: depression, post-disaster stress, antisocial behavior, behavioral deficits in dementia, attention-deficit/hyperactivity disorder, and autism. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to rate the evidence base. Significant clinical benefit was assessed using minimal clinically important differences (MIDs). Due to heterogeneity in participants, multinutrient formulas, outcome measures, and absence of complete data, only the Attention-Deficit/Hyperactivity Disorder (ADHD) category was eligible for meta-analyses. In ADHD populations, statistically and clinically significant improvements were found in global functioning, Mean Difference (MD) -3.3, p = 0.001, MID -3.26; Standardized Mean Difference (SMD) -0.49 p = 0.001 MD -0.5), clinician ratings of global improvement (MD -0.58, p = 0.001, MID -0.5) and ADHD improvement (MD -0.54, p = 0.002, MID -0.5), and clinician (but not observer) measures of ADHD inattentive symptoms (MD -1.53, p = 0.05, MID -0.5). Narrative synthesis also revealed a pattern of benefit for global measures of improvement, for example: in autism, and in participants with behavioral deficits in dementia. Post-natural disaster anxiety and the number of violent incidents in prison populations also improved. Broad-spectrum formulas (vitamins + minerals) demonstrated more robust effects than formulas with fewer ingredients. This review highlights the need for robust methodology-RCTs that report full data, including means and standard deviations for all outcomes-in order to further elucidate the effects of multinutrients for psychiatric symptoms.

Interindividual differences in memory system local field potential activity predict behavioral strategy on a dual-solution T-maze.

Individuals can use diverse behavioral strategies to navigate their environment including hippocampal-dependent place strategies reliant upon cognitive maps and striatal-dependent response strategies reliant upon egocentric body turns. The existence of multiple memory systems appears to facilitate successful navigation across a wide range of environmental and physiological conditions. The mechanisms by which these systems interact to ultimately generate a unitary behavioral response, however, remain unclear. We trained 20 male, Sprague-Dawley rats on a dual-solution T-maze while simultaneously recording local field potentials that were targeted to the dorsolateral striatum and dorsal hippocampus. Eight rats spontaneously exhibited a place strategy while the remaining 12 rats exhibited a response strategy. Interindividual differences in behavioral strategy were associated with distinct patterns of LFP activity between the dorsolateral striatum and dorsal hippocampus. Specifically, striatal-hippocampal theta activity was in-phase in response rats and out-of-phase in place rats and response rats exhibited elevated striatal-hippocampal coherence across a wide range of frequency bands. These contrasting striatal-hippocampal activity regimes were (a) present during both maze-learning and a 30 min premaze habituation period and (b) could be used to train support vector machines to reliably predict behavioral strategy. Distinct patterns of neuronal activity across multiple memory systems, therefore, appear to bias behavioral strategy selection and thereby contribute to interindividual differences in behavior.

Zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections: a rapid review.

BACKGROUND: The global COVID-19 pandemic has prompted an urgent search for interventions to prevent and treat SARS-CoV-2. Higher risk of infection and adverse outcomes coincide with populations with chronic diseases and elderly who are at risk of zinc deficiency. Through several mechanisms zinc may prevent, reduce severity and duration of symptoms. METHOD: An a priori protocol was registered with PROSPERO on 27th April 2020 (CRD42020182044). Eight databases (one Chinese) and four clinical trial registries (one Chinese) were searched for randomised and quasi-randomised controlled trials (RCTs), evaluating single or adjunct zinc against placebo or active controls, for prevention and/or treatment of SARS-CoV-2, other coronaviruses or related infections. RR constraints included not searching bibliographies or contacting authors, single reviewers with calibration and second reviewer checking, meta-analyses and quality appraisal of critical and study primary outcomes only and reporting results as they became available. RESULTS: 118 publications of 1,627 records met the inclusion criteria (35 Chinese and 83 English publications), 32 for prevention, 78 for treatment and 8 for both. Four RCTs specific to SARS-CoV-2 are ongoing; two are investigating zinc for prevention and two for treatment. As of 7 July 2020, no results were available. A wide range of zinc forms, including nasal spray/gel, lozenges, liquid, tablets and intramuscular were investigated. CONCLUSION: Currently, indirect evidence suggests zinc may potentially reduce the risk, duration and severity of SARS-CoV-2 infections, particularly for populations at risk of zinc deficiency including people with chronic disease co-morbidities and older adults. Direct evidence to determine if zinc is effective for either prevention or treatment of SARS-CoV-2 is pending. In the interim, assessing zinc status of people with chronic diseases and older adults, as part of a SARS-CoV-2 clinical work-up, is reasonable as both groups have a higher risk of zinc deficiency/insufficiency and poorer outcomes from SARS-CoV-2.

Choose your shortcuts wisely: COVID-19 rapid reviews of traditional, complementary and integrative medicine.

Background: The COVID-19 pandemic has led to an explosion of rapid reviews geared towards providing time sensitive answers for clinical and policy decision-makers. Rapid reviews (RRs) strike a balance between rigour and rapidity to minimise bias and optimise transparency within specified constraints. Methods: This review article appraised the methods and reporting standards of a convenience sample of RR protocols and RRs of COVID-19 clinical management questions, published in the first six-months of 2020. Inclusion criteria were all RR protocols evaluating traditional, complementary, and integrative medicine (TCIM) registered on PROSPERO, and all RRs indexed on PubMed or published on the Oxford COVID-19 Evidence Service. A purpose-specific 9-item reporting checklist reflecting recommended minimum requirements for RRs was applied. Findings were synthesised and narrated in the context of methodological considerations for conducting and reporting RRs of TCIM. Results: Included studies were five RR protocols of TCIM and 16 RRs, of which five considered TCIM. Wide variations in RR methods were proposed or applied, as were the reporting standards. All five RRs that evaluated TCIM had the lowest reporting standards that limited reproducibility and transparency. Despite accepted recommendations, most RRs did not publish a protocol. Conclusions: We propose that specific research disciplines, such as TCIM, have a uniqueness that may lead to unacceptable outputs if minimum methodological standards are not applied. The recommended minimum requirements will optimise the credibility of rapid reviews of TCIM and limit the risk of prematurely disregarding a potentially effective intervention.