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Cannabis and Cannabinoid Research Aug 2022The endocannabinoid (eCB) system plays a key role in maintaining homeostasis, including the regulation of metabolism and stress responses. Chronic stress may blunt eCB... (Meta-Analysis)
Meta-Analysis
The endocannabinoid (eCB) system plays a key role in maintaining homeostasis, including the regulation of metabolism and stress responses. Chronic stress may blunt eCB signaling, and disruptions in eCB signaling have been linked to stress-related psychiatric disorders and physical health conditions, including anxiety, depression, post-traumatic stress disorder (PTSD), diabetes, and obesity. Pharmacological and nonpharmacological behavioral interventions (e.g., exercise) that target the eCB system may be promising therapeutic approaches for the prevention and treatment of stress-related diseases. In this study, we perform a systematic review and the first meta-analysis to examine the impact of exercise on circulating eCB concentrations. We performed a review of the MEDLINE (PubMed) database for original articles examining the impact of exercise on eCBs in humans and animal models. A total of 262 articles were screened for initial inclusion. Thirty-three articles (reporting on 57 samples) were included in the systematic review and 10 were included in the meta-analysis. The majority of samples that measured anandamide (AEA) showed a significant increase in AEA concentrations following acute exercise (74.4%), whereas effects on 2-arachidonoylglycerol (2-AG) were inconsistent. The meta-analysis, however, revealed a consistent increase in both AEA and 2-AG following acute exercise across modalities (e.g., running, cycling), species (e.g., humans, mice), and in those with and without pre-existing health conditions (e.g., PTSD, depression). There was substantial heterogeneity in the magnitude of the effect across studies, which may relate to exercise intensity, physical fitness, timing of measurement, and/or fasted state. Effects of chronic exercise were inconsistent. Potential interpretations and implications of exercise-induced mobilization of eCBs are discussed, including refilling of energy stores and mediating analgesic and mood elevating effects of exercise. We also offer recommendations for future work and discuss therapeutic implications for exercise in the prevention and treatment of stress-related psychopathology.
Topics: Affect; Animals; Anxiety; Endocannabinoids; Humans; Mice; Running; Stress Disorders, Post-Traumatic
PubMed: 34870469
DOI: 10.1089/can.2021.0113 -
The Lancet. Psychiatry Apr 2020Approximately 188 million people use cannabis yearly worldwide, and it has recently been legalised in 11 US states, Canada, and Uruguay for recreational use. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 188 million people use cannabis yearly worldwide, and it has recently been legalised in 11 US states, Canada, and Uruguay for recreational use. The potential for increased cannabis use highlights the need to better understand its risks, including the acute induction of psychotic and other psychiatric symptoms. We aimed to investigate the effect of the cannabis constituent Δ-tetrahydrocannabinol (THC) alone and in combination with cannabidiol (CBD) compared with placebo on psychiatric symptoms in healthy people.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published in English between database inception and May 21, 2019, with a within-person, crossover design. Inclusion criteria were studies reporting symptoms using psychiatric scales (the Brief Psychiatric Rating Scale [BPRS] and the Positive and Negative Syndrome Scale [PANSS]) following the acute administration of intravenous, oral, or nasal THC, CBD, and placebo in healthy participants, and presenting data that allowed calculation of standardised mean change (SMC) scores for positive (including delusions and hallucinations), negative (such as blunted affect and amotivation), and general (including depression and anxiety) symptoms. We did a random-effects meta-analysis to assess the main outcomes of the effect sizes for total, positive, and negative PANSS and BPRS scores measured in healthy participants following THC administration versus placebo. Because the number of studies to do a meta-analysis on CBD's moderating effects was insufficient, this outcome was only systematically reviewed. This study is registered with PROSPERO, CRD42019136674.
FINDINGS
15 eligible studies involving the acute administration of THC and four studies on CBD plus THC administration were identified. Compared with placebo, THC significantly increased total symptom severity with a large effect size (assessed in nine studies, with ten independent samples, involving 196 participants: SMC 1·10 [95% CI 0·92-1·28], p<0·0001); positive symptom severity (assessed in 14 studies, with 15 independent samples, involving 324 participants: SMC 0·91 [95% CI 0·68-1·14], p<0·0001); and negative symptom severity with a large effect size (assessed in 12 studies, with 13 independent samples, involving 267 participants: SMC 0·78 [95% CI 0·59-0·97], p<0·0001). In the systematic review, of the four studies evaluating CBD's effects on THC-induced symptoms, only one identified a significant reduction in symptoms.
INTERPRETATION
A single THC administration induces psychotic, negative, and other psychiatric symptoms with large effect sizes. There is no consistent evidence that CBD induces symptoms or moderates the effects of THC. These findings highlight the potential risks associated with the use of cannabis and other cannabinoids that contain THC for recreational or therapeutic purposes.
FUNDING
UK Medical Research Council, Maudsley Charity, Brain and Behavior Research Foundation, Wellcome Trust, and the UK National Institute for Health Research.
Topics: Administration, Inhalation; Cannabidiol; Dronabinol; Drug Combinations; Drug Interactions; Hallucinogens; Humans; Marijuana Smoking; Psychoses, Substance-Induced
PubMed: 32197092
DOI: 10.1016/S2215-0366(20)30074-2 -
Sports Medicine (Auckland, N.Z.) Feb 2024Many sports require maximal strength and endurance performance. Concurrent strength and endurance training can lead to suboptimal training adaptations. However, how... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many sports require maximal strength and endurance performance. Concurrent strength and endurance training can lead to suboptimal training adaptations. However, how adaptations differ between males and females is currently unknown. Additionally, current training status may affect training adaptations.
OBJECTIVE
We aimed to assess sex-specific differences in adaptations in strength, power, muscle hypertrophy, and maximal oxygen consumption ( O) to concurrent strength and endurance training in healthy adults. Second, we investigated how training adaptations are influenced by strength and endurance training status.
METHODS
A systematic review and meta-analysis was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and a Cochrane risk of bias was evaluated. ISI Web of science, PubMed/MEDLINE, and SPORTDiscus databases were searched using the following inclusion criteria: healthy adults aged 18-50 years, intervention period of ≥ 4 weeks, and outcome measures were defined as upper- and lower-body strength, power, hypertrophy, and/or O. A meta-analysis was performed using a random-effects model and reported in standardized mean differences.
RESULTS
In total, 59 studies with 1346 participants were included. Concurrent training showed blunted lower-body strength adaptations in males, but not in females (male: - 0.43, 95% confidence interval [- 0.64 to - 0.22], female: 0.08 [- 0.34 to 0.49], group difference: P = 0.03). No sex differences were observed for changes in upper-body strength (P = 0.67), power (P = 0.37), or O (P = 0.13). Data on muscle hypertrophy were insufficient to draw any conclusions. For training status, untrained but not trained or highly trained endurance athletes displayed lower O gains with concurrent training (P = 0.04). For other outcomes, no differences were found between untrained and trained individuals, both for strength and endurance training status.
CONCLUSIONS
Concurrent training results in small interference for lower-body strength adaptations in males, but not in females. Untrained, but not trained or highly trained endurance athletes demonstrated impaired improvements in O following concurrent training. More studies on females and highly strength-trained and endurance-trained athletes are warranted.
CLINICAL TRIAL REGISTRATION
PROSPERO: CRD42022370894.
Topics: Adult; Humans; Male; Female; Endurance Training; Physical Endurance; Athletes; Sports; Hypertrophy; Muscle Strength; Resistance Training
PubMed: 37847373
DOI: 10.1007/s40279-023-01943-9 -
Journal of Managed Care & Specialty... Jan 2023US health plans are adopting benefit designs that shift greater financial burden to patients through higher deductibles, additional copay tiers, and coinsurance. Prior... (Review)
Review
US health plans are adopting benefit designs that shift greater financial burden to patients through higher deductibles, additional copay tiers, and coinsurance. Prior systematic reviews found that higher cost was associated with reductions in both appropriate and inappropriate medications. However, these reviews were conducted prior to contemporary benefit design and medication utilization. To assess the relationship and factors associated with cost-sharing and (1) medication adherence, (2) clinical outcomes, (3) health care resource utilization (HRU), and (4) costs. A systematic review of literature published between January 2010 and August 2020 was conducted to identify the relationship between cost-sharing and medication adherence, clinical outcomes, HRU, and health care costs. Data were extracted using a standardized template and were synthesized by key questions of interest. From 1,995 records screened, 79 articles were included. Most studies, 71 of 79 (90%), reported the relationship between cost-sharing and treatment adherence, persistence and/or discontinuation; 16 (20%) reported data on cost-sharing and HRU or medication initiation, 11 (14%) on costsharing and health care costs, and 6 (8%) on cost-sharing and clinical outcomes. The majority of publications found that, regardless of disease area, increased cost-sharing was associated with worse adherence, persistence, or discontinuation. The aggregate data suggested the greater the magnitude of cost-sharing, the worse the adherence. Among studies examining clinical outcomes, cost-sharing was associated with worse outcomes in 1 study and the remaining 3 found no significant differences. Regarding HRU, higher-cost-sharing trended toward decreased outpatient and increased inpatient utilization. The available evidence suggested higher cost-sharing has an overall neutral to negative impact on total costs. Studies evaluating elimination of copays found either decreased or no impact in total costs. The published literature shows consistent impacts of higher cost sharing on initiation and continuation of medications, and the greater the cost-sharing, the worse the medication adherence. The evidence is limited regarding the impact of cost-sharing on clinical outcomes, HRU, and costs. Limited evidence suggests increased cost-sharing is associated with more inpatient care and less outpatient care; however, a neutral to no difference was suggested for other outcomes. Although increased costsharing is intended to decrease total costs, studies evaluating reducing or eliminating cost-sharing found that total costs did not rise. Today's growing cost-containment environment should carefully consider the broader impact cost-sharing has on treatment adherence, clinical outcomes, resource use, and total costs. It may be that cost-sharing is a blunt, rather than precise, tool to curb health care costs, affecting both necessary and unnecessary health care use. This study and the development of this article were funded by the National Pharmaceutical Council. Mr Sils is an employee of the National Pharmaceutical Council. Dr Graff is a former employee of the National Pharmaceutical Council. Drs Fusco and Kistler and Ms Ruiz are employees of Xcenda. Xcenda received funding to conduct the literature review.
Topics: Humans; Patient Acceptance of Health Care; Health Care Costs; Cost Sharing; Pharmacy; Pharmaceutical Preparations; Retrospective Studies; Medication Adherence
PubMed: 35389285
DOI: 10.18553/jmcp.2022.21270 -
Harvard Review of Psychiatry 2020After participating in this activity, learners should be better able to:• Evaluate the relationship between negative symptoms and functioning in youth at clinical high... (Meta-Analysis)
Meta-Analysis
LEARNING OBJECTIVE
After participating in this activity, learners should be better able to:• Evaluate the relationship between negative symptoms and functioning in youth at clinical high risk for psychosis.
AIM
Youth at CHR for psychosis often demonstrate significant negative symptoms and poor functioning, though the magnitude and direction of the relationship between the two remains unknown. The objective of this systematic review is to summarize the relationship between negative symptoms and functioning in CHR samples.
METHOD
Electronic databases CINAHL, EBM, Embase, MEDLINE, and PsycINFO were searched from inception. Studies were selected if they included any study that reported a relationship between negative symptoms and functioning in youth at clinical high risk (CHR). The correlation coefficient r was converted to Cohen's d, and all random-effects meta-analyses were performed using the transformed values.
RESULTS
Forty-one studies met the inclusion criteria, including a total of 4574 individuals at CHR for psychosis. Negative symptom total scores were significantly associated with poorer global functioning (d, -1.40; 95% CI, -1.82 to -0.98; I = 79.4%; p < .001 [9 studies, n = 782]), social functioning (d, -1.10; 95% CI, -1.27 to -0.93; I = 10.40%; p < .001 [12 studies, n = 811]), and role functioning (d, -0.96; 95% CI, -1.17 to -0.76; I = 41.1%; p < .001 [9 studies, n = 881]). In addition, negative symptoms were consistently associated with poor premorbid functioning. When examining negative symptom domains, avolition, anhedonia, and blunted affect were each significantly and independently associated with poorer social functioning and role functioning. In terms of prediction models, negative symptoms contributed to the prediction of lower functioning across multiple studies.
CONCLUSION
This meta-analysis demonstrates a strong relationship between negative symptoms and functioning in youth at clinical high risk for psychosis.
Topics: Humans; Psychotic Disorders; Risk Assessment; Social Adjustment; Social Behavior Disorders; Young Adult
PubMed: 33156155
DOI: 10.1097/HRP.0000000000000273 -
CNS Neuroscience & Therapeutics Mar 2024Noninvasive brain stimulation (NIBS) techniques are a promising tool for treating the negative symptoms of schizophrenia. Growing evidence suggests that different... (Meta-Analysis)
Meta-Analysis
Is it more effective for anhedonia and avolition? A systematic review and meta-analysis of non-invasive brain stimulation interventions for negative symptoms in schizophrenia.
BACKGROUND
Noninvasive brain stimulation (NIBS) techniques are a promising tool for treating the negative symptoms of schizophrenia. Growing evidence suggests that different dimensions of negative symptoms have partly distinct underlying pathophysiological mechanisms. Previous randomized controlled trials (RCTs) have shown inconsistent impacts of NIBS across dimensions.
OBJECTIVE
This systematic review and meta-analysis evaluated the effects of NIBS on general negative symptoms, and on specific domains, including blunted affect, alogia, asociality, anhedonia, and avolition.
DATA SOURCES
PubMed, Web of Science, Embase, Cochrane CENTRAL, PsycINFO, OpenGrey, and Clinicaltrials.gov from the first date available to October, 2023.
RESULTS
Among 1049 studies, we identified eight high-quality RCTs. NIBS significantly affects general negative symptoms (SMD = -0.54, 95% CI [-0.88, -0.21]) and all five domains (SMD = -0.32 to -0.63). Among dimensions, better effects have been shown for improvement of avolition (SMD = -0.47, 95% CI [-0.81, -0.13]) and anhedonia (SMD = -0.63, 95% CI [-0.98, -0.28]). Subgroup analyses of studies that applied once daily stimulation or >10 sessions showed significantly reduced negative symptom severity.
CONCLUSION
NIBS exerts distinct effects across multiple dimensions of negative symptom, with treatment effects related to stimulation frequency and total sessions. These results need to be confirmed in dedicated studies.
Topics: Humans; Anhedonia; Brain; PubMed; Schizophrenia; Electric Stimulation Therapy
PubMed: 38432851
DOI: 10.1111/cns.14645 -
Nutrients May 2023Dietary fiber (DF) consumption has been associated with improved glycemic control in epidemiological and long-term interventional studies. However, its acute effects are... (Review)
Review
Dietary fiber (DF) consumption has been associated with improved glycemic control in epidemiological and long-term interventional studies. However, its acute effects are not yet clear. This systematic review aims to elucidate the postprandial effects of DF in starchy products on glycemia and insulinemia. An electronic search of databases was conducted, and forty-one records met the inclusion criteria and underwent a risk-of-bias assessment. It was shown that soluble DF does not clearly affect glycemia in individuals with normal weight, while resistant starch may be more effective in flattening glycemic responses. Concerning insulinemia, both soluble DF and resistant starch have mixed results, with either favorable or no effects. Data on insoluble DF and glucose metabolism are scarce. The same mixed results for glycemia can be seen in healthy volunteers with overweight/obesity, while resistant starch seems to improve insulinemic responses. Finally, more studies need to examine the acute effects of DF in starchy foods on glucose metabolism and insulin secretion in individuals facing glucose abnormalities. Additionally, more studies are needed to prove whether ingesting high-fiber carbohydrate-containing products per se can result in blunted glycemic and insulinemic responses and which DF type and amount are more effective.
Topics: Humans; Blood Glucose; Dietary Carbohydrates; Insulin; Resistant Starch; Cross-Over Studies; Glucose; Dietary Fiber; Postprandial Period; Glycemic Index
PubMed: 37242267
DOI: 10.3390/nu15102383 -
Vaccine May 2021In North America, the first dose of a measles-containing vaccine (MCV1) is administered at ≥12 months of age. However, MCV1 may be given to infants <12 months living... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In North America, the first dose of a measles-containing vaccine (MCV1) is administered at ≥12 months of age. However, MCV1 may be given to infants <12 months living in highly endemic areas or traveling to these areas. Although an early dose of MCV1 leads to immediate protection, it remains unclear how this impacts long-term immunity.
METHODS
This systematic review and meta-analysis evaluates the impact of MCV1 given at <12 months vs. ≥12 months of age on long-term immunogenicity and vaccine effectiveness, with long-term defined as at least one-year post-vaccination. PubMed, EMBASE, Global Health, Web of Science and Scopus were searched on October 31st, 2019. Studies were included if they included a cohort of infants vaccinated <12 months of age and evaluated long-term immunogenicity, vaccine efficacy, or effectiveness.
RESULTS
A total of 51 texts were identified: 23 reported outcomes related to vaccine effectiveness and 30 to immunogenicity. Infants vaccinated with MCV1 < 12 months of age showed an overall higher risk of measles compared to ≥12 months of age (RR = 3.16, 95% CI: 2.00, 5.01; OR = 2.46, 95% CI: 1.40, 4.32). Risk of measles decreased with increasing age at first vaccination, with those vaccinated with one dose ≥15 months at a lesser risk compared to 12-14 months or <12 months. Measles seroconversion and seropositivity was not affected by age at first vaccination, but antibody levels were significantly lower in the MCV1 < 12-month group (MD = -0.40, 95% CI: -0.71, -0.09).
CONCLUSION
Long-term measles seroconversion and seropositivity did not appear to be affected by age at MCV1, while vaccine effectiveness decreased with younger age. There was not enough evidence to look at the effect of age at MCV1 on immune blunting.
Topics: Antibodies, Viral; Humans; Immunization Schedule; Infant; Measles; Measles Vaccine; Measles virus; North America; Vaccination
PubMed: 33926750
DOI: 10.1016/j.vaccine.2021.04.012 -
Non-steroidal anti-inflammatory drugs on core body temperature during exercise: A systematic review.Journal of Exercise Science and Fitness Apr 2021Because of their anti-pyretic effects, some individuals prophylactically use non-steroidal anti-inflammatory drugs (NSAIDs) to blunt core temperature (Tc) increases... (Review)
Review
BACKGROUND
Because of their anti-pyretic effects, some individuals prophylactically use non-steroidal anti-inflammatory drugs (NSAIDs) to blunt core temperature (Tc) increases during exercise, thus, potentially improving performance by preventing hyperthermia and/or exertional heat illness. However, NSAIDs induce gastrointestinal damage, alter renal function, and decrease cardiovascular function, which could compromise thermoregulation and increase Tc. The aim of this systematic review was to evaluate the effects of NSAIDs on Tc in exercising, adult humans.
METHODS
We conducted searches in MEDLINE, PubMed, Cochrane Reviews, and Google Scholar for literature published up to November 2020. We conducted a quality assessment review using the Physiotherapy Evidence Database scale. Nine articles achieved a score ≥ seven to be included in the review.
RESULTS
Seven studies found aspirin, ibuprofen, and naproxen had no effect (p > .05) on Tc during walking, running, or cycling for ≤ 90 min in moderate to hot environments. Two studies found significant Tc changes. In one investigation, 81 mg of aspirin for 7-10 days prior to exercise significantly increased Tc during cycling (p < .001); final Tc at the end of exercise = 38.3 ± 0.1 °C vs. control = 38.1 ± 0.1 °C. In contrast, participants administered 50 mg rofecoxib for 6 days experienced significantly lower Tc during 45 min of cycling compared to placebo (NSAID Tc range ≈ 36.7-37.2 °C vs control ≈ 37.3-37.8 °C, p < 0.05).
CONCLUSIONS
There are limited quality studies examining NSAID effects on Tc during exercise in humans. The majority suggest taking non-selective NSAIDs (e.g., aspirin) 1-14 days before exercise does not significantly affect Tc during exercise. However, it remains unclear whether Tc increases, decreases, or does not change during exercise with other NSAID drug types (e.g., naproxen), higher dosages, chronic use, greater exercise intensity, and/or greater environmental temperatures.
PubMed: 33552178
DOI: 10.1016/j.jesf.2020.12.003 -
Therapeutic Advances in Respiratory... 2020Angiopoietin-2 (Ang-2), as one of the ligands of endothelial receptor Tie2, is known to be significant for vessel maturation and stabilization after birth. Previous... (Meta-Analysis)
Meta-Analysis
Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies.
BACKGROUND
Angiopoietin-2 (Ang-2), as one of the ligands of endothelial receptor Tie2, is known to be significant for vessel maturation and stabilization after birth. Previous studies showed the relationship between Ang-2 level and the risk of mortality in patients with acute respiratory distress syndrome (ARDS). However, the link between circulating Ang-2 and the risk of mortality in patients with ARDS varied in different investigations.
RESULTS
We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating Ang-2 and mortality in patients with ARDS. Among the 10 eligible studies, pooled odds ratio (OR) showed that high Ang-2 level contributed to ARDS mortality [OR = 1.56, 95% confidence interval (CI): 1.30-1.89, = 76.2%]. Stratified analysis revealed that higher circulating Ang-2 was related to a 30% higher risk in the high-quality scores group (OR = 1.68, 95% CI: 1.33-2.68, = 62.4%). The of the bad compliance group decreased from 76.2% to 8.5%, which suggested that compliance is a significant source of heterogeneity. This association may be blunted by potential bias, although the results was not meaningfully changed by omitting only one study at a time. Further subgroup analysis and meta-regression support that compliance of patients also affects the results significantly, compared with the publication year, follow-up duration, the samples, or population characteristics.
CONCLUSION
Participants with higher baseline Ang-2 were at a higher risk for future risk of mortality in patients with ARDS. Higher circulating Ang-2 levels could independently predict the risk of mortality in patients with ARDS. However, further large scale prospective cohorts or even interventional studies are warranted to evaluate the diagnostic power of Ang-2 and its causative role on ARDS outcome.
Topics: Adolescent; Adult; Angiopoietin-2; Biomarkers; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Predictive Value of Tests; Prognosis; Respiratory Distress Syndrome; Risk Assessment; Risk Factors; Up-Regulation; Young Adult
PubMed: 32043429
DOI: 10.1177/1753466620905274