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Journal of the International AIDS... Feb 2023Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a... (Review)
Review
INTRODUCTION
Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV.
METHODS
We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009-March 2021. We included clinical trials and observational studies assessing the efficacy/effectiveness or safety of TAF through ≥6 months of treatment in participants aged 0-19 years.
RESULTS AND DISCUSSION
Overall 3626 abstracts and 371 full papers were screened. Four single-arm, innovator-funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment-experienced and virally suppressed children or adolescents. One trial also included treatment-naïve adolescents with baseline viral load >1000 copies/ml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (46/50) of treatment-naïve participants were virally suppressed (one trial). Among treatment-experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 3/4 adverse event was considered drug-related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis [drug-related] and grade 1 pulmonary tuberculosis [unrelated to treatment]). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z-score (height- and age-adjusted) from baseline to 48 weeks was -0.12 (interquartile range [IQR] -0.46, 0.17) to 0.05 (IQR not reported) for spine, and -0.09 (IQR -0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight-for-age z-scores increased by 0.25 from baseline to 48 weeks.
CONCLUSIONS
Four single-arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF-containing regimens over 24-48 weeks. However, further comparative and longer-term safety data are needed in children and adolescents, including on weight and metabolic changes.
Topics: Infant; Humans; Child; Adolescent; Tenofovir; HIV Infections; Anti-HIV Agents; HIV-1; Adenine; Emtricitabine
PubMed: 36823283
DOI: 10.1002/jia2.26037 -
Public Health Nov 2021This study aimed to summarise the effect of community-based intervention programmes on the prevention of cardiovascular disease (CVD) by reducing cardiometabolic risk... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aimed to summarise the effect of community-based intervention programmes on the prevention of cardiovascular disease (CVD) by reducing cardiometabolic risk factors.
STUDY DESIGN
This was a systematic review and meta-analysis.
METHODS
A systematic search in the PubMed database and screening of reference lists aimed to identify community-based CVD prevention programmes from inception up to April 2020. The mean differences and standard deviations for CVD risk factors, including blood pressure, lipid profile, blood glucose and body weight indices, were extracted and pooled using a random effects model.
RESULTS
Screening of 11,889 titles/abstracts and full texts resulted in 48 studies being included in this review. The meta-analysis showed that community-based programmes have led to considerable decreases in systolic blood pressure (weighted mean difference [WMD] = -2.90 mm Hg, 95% confidence interval [95% CI]: -3.63, -2.16), diastolic blood pressure (WMD = -2.21 mm Hg, 95% CI: -3.12, -1.29), serum levels of low-density lipoprotein cholesterol (LDL-C; WMD = -8.88 mg/dl, 95% CI: -12.84, -4.92), triglycerides (WMD = -8.40 mg/dl, 95% CI: -12.10, -4.70), total cholesterol (WMD = -2.96 mg/dl, 95% CI: -3.10, -2.81) and fasting blood glucose (WMD = -2.06 mg/dl, 95% CI: -3.02, -1.10). A moderate decrease in body weight was also found with community-based CVD prevention programmes. However, community-based CVD prevention programmes were not associated with any significant changes in serum levels of high-density lipoprotein.
CONCLUSIONS
The present study indicates that community-based strategies have successfully led to an improvement in CVD risk factors, particularly by reducing blood pressure, serum levels of LDL-C and triglycerides, obesity indices and blood glucose. The impact of these programmes on CVD is modified by the type of intervention and by different cultural and physical environments.
Topics: Blood Pressure; Cardiovascular Diseases; Cholesterol, LDL; Humans; Lipids; Risk Factors; Triglycerides
PubMed: 34700187
DOI: 10.1016/j.puhe.2021.09.006 -
Nutrition Journal Jan 2024Exercise training (Ex) and intermittent fasting (IF) are effective for improving body composition and cardiometabolic health overweight and obese adults, but whether... (Meta-Analysis)
Meta-Analysis Review
Combined versus independent effects of exercise training and intermittent fasting on body composition and cardiometabolic health in adults: a systematic review and meta-analysis.
INTRODUCTION AND AIM
Exercise training (Ex) and intermittent fasting (IF) are effective for improving body composition and cardiometabolic health overweight and obese adults, but whether combining Ex and IF induces additive or synergistic effects is less well established. We therefore, performed a systematic review and meta-analysis to compare the combined versus independent effects of Ex and IF on body composition and cardiometabolic health in adults.
METHOD
An electronic search was conducted in three main online databases including PubMed, Web of Science, and Scopus, from inception to March 9, 2023 for studies involving Ex plus IF trials versus standalone Ex and/or IF interventions in adults. Interventions had a duration of ≥ 2 weeks. Standardized (SMD) or weighted mean differences (WMD) and 95% confidence intervals were calculated in order to compare effects on body weight, body mass index (BMI), body fat lean body mass (LBM), visceral fat, and waist circumference. For cardiometabolic health, outcomes included fasting glucose, insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL), triglycerides (TG), high-density lipoprotein cholesterol (HDL), systolic (SBP) and diastolic (DBP) blood pressure, and VOmax/peak.
RESULTS
Ex plus IF decreased body weight [WMD: -3.03 kg (95% CI: -3.44 to -2.61), p = 0.001], BMI [WMD: -1.12 kg.m (95% CI: -1.28 to -0.95), p = 0.001], body fat [SMD: -0.72 (95% CI: -1.23 to -0.21), p = 0.005], visceral fat [SMD: -0.34 (95% CI: -0.63 to -0.05), p = 0.01], and waist circumference [WMD: -2.63 cm (95% CI: -4.16 to -1.11), p = 0.001] more than Ex alone. However, changes in body composition and cardiometabolic health markers were not significantly different for Ex plus IF when compared with IF alone, with the exception of VOmax/peak [SMD: 0.55 (95% CI: 0.14 to 0.97), p = 0.009].
CONCLUSION
We demonstrate that a combination of Ex and IF produces superior changes in body composition, but not in markers of cardiometabolic health when compared with Ex or IF alone. Ex plus IF could therefore be effective for weight and fat loss but has no additive or synergistic effects for other cardiometabolic health markers.
Topics: Adult; Humans; Intermittent Fasting; Body Composition; Exercise; Cholesterol, HDL; Obesity; Cardiovascular Diseases
PubMed: 38183054
DOI: 10.1186/s12937-023-00909-x -
Toxins Jul 2022Owing to their low minimal environmental risk and other ethical considerations, plant-derived sterilants are used to control rodent populations. However, the effects of... (Meta-Analysis)
Meta-Analysis Review
Owing to their low minimal environmental risk and other ethical considerations, plant-derived sterilants are used to control rodent populations. However, the effects of plant-derived sterilants are not immediate, and their efficacy on rodent control is controversial, which negatively affects sterilant research and application. Here, a meta-analysis of the available literature was conducted to evaluate the effects of two plant-derived sterilants, triptolide and curcumol, on rodent populations. Using a random-effects and a fixed-effects model, we calculated the weighted mean difference (WMD) and relative risk (RR) and their corresponding 95% confidence intervals (95% CIs). After the application of plant-derived sterilants, the rodent population density tended to decrease. Three outcome-related measures in rodents, i.e., capture rate (RR = 0.31, 95% CI [0.20, 0.47]), pregnancy rate (RR = 0.49, 95% CI [0.40, 0.61]), and sperm survival rate (WMD = -17.53, 95% CI [-28.96, -6.06]), significantly decreased, as shown by a significant reduction of ovarian, uterine, and testicular organ coefficients. However, the number of effective rodent holes did not change significantly after the interventions, indicating that the studied sterilants did not directly eradicate the rodent populations. This study provides a theoretical basis for elucidating the inhibitory mechanisms of plant-derived sterilants on rodent populations and for the rational use of these sterilants.
Topics: Animals; Female; Male; Pest Control; Population Dynamics; Pregnancy; Rodentia; Semen; Spermatozoa; Testis
PubMed: 35878225
DOI: 10.3390/toxins14070487 -
The Journal of Nutrition, Health & Aging 2021Osteosarcopenia is a geriatric syndrome defined by the concomitant presence of osteopenia/osteoporosis (loss of bone mineral density (BMD)) and sarcopenia (loss of...
BACKGROUND
Osteosarcopenia is a geriatric syndrome defined by the concomitant presence of osteopenia/osteoporosis (loss of bone mineral density (BMD)) and sarcopenia (loss of muscle mass and/or function), which increases the risk of falls, fractures, and premature mortality.
OBJECTIVE
To examine the efficacy of non-pharmacological (exercise and/or nutritional) interventions on musculoskeletal measures and outcomes in osteosarcopenic adults by reviewing findings from randomized controlled trials (RCTs).
METHODS
This review was registered at PROSPERO (registration number: CRD42020179292) and conducted in accordance with the PRISMA guidelines. Electronic databases were searched for RCTs assessing the effect of at least one non-pharmacological intervention (any form of exercise and/or supplementation with protein, vitamin D, calcium or creatine) on any musculoskeletal measure/outcome of interest (BMD, bone strength/turnover, muscle mass and strength, physical performance, falls/fractures) in adults with osteosarcopenia as defined by any proposed criteria.
RESULTS
Two RCTs (of n=106 older osteosarcopenic adults (≥65 years)) assessing the effects of progressive resistance training (RT) (via resistance bands or machines; 2-3 times/week; ~60 minutes in duration) were eligible for inclusion. The two RCTs demonstrated moderate quality evidence that RT increases muscle mass, strength, and quality, with changes in strength and quality occurring before muscle mass (12 vs 28 weeks). There was low quality evidence that RT increases lumbar spine BMD and maintains total hip BMD when performed for 12 and 18 months, respectively, and moderate quality evidence that RT has no effect on markers of bone turnover or physical performance. No major adverse effects were recorded in either of the RCTs. There were no eligible RCTs examining the impact of nutritional interventions.
CONCLUSION
Chronic RT is safe and effective at potentiating gains in muscle mass, strength, and quality, and increasing or maintaining BMD in older osteosarcopenic adults. No RCT has examined the effects of protein, vitamin D, calcium, or creatine against a control/placebo in this high-risk population.
Topics: Aged; Female; Humans; Male; Middle Aged; Osteoporosis; Sarcopenia
PubMed: 33367459
DOI: 10.1007/s12603-020-1537-7 -
Journal of Hypertension Dec 2021A hypertensive response to exercise (HRE) is associated with cardiovascular disease and high blood pressure (BP). A poor cardiovascular risk factor profile may underlie... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A hypertensive response to exercise (HRE) is associated with cardiovascular disease and high blood pressure (BP). A poor cardiovascular risk factor profile may underlie these associations, although this has not been systematically elucidated. Via systematic review and meta-analysis, we aimed to assess the relationship between exercise BP and cardiovascular risk factors, and determine if cardiovascular risk is higher in those with an HRE vs. no-HRE across different study populations (including those with/without high BP at rest).
METHODS
Three online databases were searched for cross-sectional studies reporting data on exercise BP, an HRE and cardiovascular risk factors (including arterial structure, lipid, metabolic, inflammatory and kidney function markers). Random-effects meta-analyses and meta-regression were used to calculate pooled correlations between exercise BP and each risk factor and pooled mean differences between those with/without an HRE.
RESULTS
Thirty-eight studies (38 295 participants, aged 50 ± 3years; 78% male) were included. Exercise SBP was associated with arterial, lipid and kidney function risk markers (P < 0.05). Those with an HRE had greater aortic stiffness (+0.80 ± 0.35 m/s), total (+0.14 ± 0.03 mmol/l) and low-density lipoprotein (+0.12 ± 0.03 mmol/l) cholesterol, triglycerides (+0.24 ± 0.04 mmol/l), glucose (+0.15 ± 0.05 mmol/l), white blood cell count (+0.49 ± 0.16 mmol/l) and albumin-to-creatinine ratio (standardized mean difference: +0.97 ± 0.34), and lower flow-mediated dilation (-4.13 ± 1.02%) and high-density lipoprotein cholesterol (-0.04 ± 0.01 mmol/l) vs. those with no-HRE (P < 0.05 all). Results were broadly similar across study populations.
CONCLUSION
Exercise SBP is associated with multiple cardiovascular risk factors, which appear worse in those with an HRE vs. no-HRE. As results were similar across population groups, an HRE should be considered an important indicator of cardiovascular risk.
Topics: Blood Pressure; Cardiovascular Diseases; Cross-Sectional Studies; Exercise; Female; Humans; Hypertension; Male
PubMed: 34738988
DOI: 10.1097/HJH.0000000000002962 -
Current Osteoporosis Reports Jun 2023To systematically review recent studies investigating the association between metabolites and bone mineral density (BMD) in humans. (Review)
Review
PURPOSE OF REVIEW
To systematically review recent studies investigating the association between metabolites and bone mineral density (BMD) in humans.
METHODS
Using predefined keywords, we searched literature published from Jan 1, 2019 to Feb 20, 2022 in PubMed, Web of Science, Embase, and Scopus. Studies that met the predefined exclusion criteria were excluded. Among the included studies, we identified metabolites that were reported to be associated with BMD by at least three independent studies.
RECENT FINDINGS
A total of 170 studies were retrieved from the databases. After excluding studies that did not meet our predefined inclusion criteria, 16 articles were used in this review. More than 400 unique metabolites in blood were shown to be significantly associated with BMD. Of these, three metabolites were reported by ≥ 3 studies, namely valine, leucine and glycine. Glycine was consistently shown to be inversely associated with BMD, while valine was consistently observed to be positively associated with BMD. Inconsistent associations with BMD was observed for leucine. With advances in metabolomics technology, an increasing number of metabolites associated with BMD have been identified. Two of these metabolites, namely valine and glycine, were consistently associated with BMD, highlighting their potential for clinical application in osteoporosis. International collaboration with a larger population to conduct clinical studies on these metabolites is warranted. On the other hand, given that metabolomics could be affected by genetics and environmental factors, whether the inconsistent association of the metabolites with BMD is due to the interaction between metabolites and genes and/or lifestyle warrants further study.
Topics: Humans; Leucine; Osteoporosis; Bone Density
PubMed: 37060383
DOI: 10.1007/s11914-023-00785-8 -
Obesity Reviews : An Official Journal... May 2021Sarcopenia and obesity are common conditions in older adults that may have differing effects on falls and fracture risk. This systematic review and meta-analysis aimed... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia and obesity are common conditions in older adults that may have differing effects on falls and fracture risk. This systematic review and meta-analysis aimed to determine whether older adults with sarcopenic obesity have increased risk of falls and fractures or lower bone mass compared with older adults with sarcopenia, obesity, or neither condition. Twenty-six studies (n = 37,124) were included in the systematic review and 17 (n = 31,540) were included in the meta-analysis. Older adults with sarcopenic obesity had lower femoral neck areal bone mineral density (aBMD) compared with those with obesity alone but had higher femoral neck aBMD compared with counterparts with sarcopenia alone (both P < 0.05). Older adults with sarcopenic obesity had higher nonvertebral fracture rates (incidence rate ratio: 1.88; 95% confidence intervals: 1.09, 3.23; based on two studies), compared with those with sarcopenia alone, and also had higher falls risk compared with controls (risk ratio: 1.30; 95% confidence intervals: 1.10, 1.54) and obesity alone (risk ratio: 1.17; 95% confidence intervals: 1.01, 1.36). In conclusion, this systematic review and meta-analysis has demonstrated that older adults with sarcopenic obesity are at increased risk of adverse musculoskeletal outcomes compared with individuals with obesity, sarcopenia, or neither condition. These data support the need for developing interventions to improve bone health and physical function in this population.
Topics: Accidental Falls; Aged; Bone Density; Fractures, Bone; Humans; Obesity; Sarcopenia
PubMed: 33491333
DOI: 10.1111/obr.13187 -
The Journal of Clinical Endocrinology... Dec 2020Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia. (Meta-Analysis)
Meta-Analysis
CONTEXT
Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia.
OBJECTIVE
The aim of this systematic review was to investigate the impact of therapy for overt and subclinical hyper- and hypothyroidism on serum lipids.
DATA SOURCES
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus from 1970 through April 5, 2018.
STUDY SELECTION
Pairs of independent reviewers selected randomized and observational studies evaluating lipid parameters in patients undergoing treatment for hyper- or hypothyroidism.
DATA EXTRACTION
Pairs of independent reviewers extracted data and appraised studies.
DATA SYNTHESIS
Treatment of overt hyperthyroidism showed a significant increase in total cholesterol (TC) by 44.50 mg/dL (95% confidence interval [CI]: 37.99, 51.02), low-density lipoprotein cholesterol (LDL-C) by 31.13 mg/dL (95% CI: 24.33, 37.93), high-density lipoprotein cholesterol (HDL-C) by 5.52 mg/dL (95% CI: 1.48, 9.56), apolipoprotein A (Apo A) by 15.6 mg/dL (95% CI: 10.38, 20.81), apolipoprotein B (apo B) by 26.12 mg/dL (95% CI: 22.67, 29.57), and lipoprotein (Lp[a]) by 4.18 mg/dL (95% CI: 1.65, 6.71). There was no significant change in triglyceride (TG) levels. Treatment of subclinical hyperthyroidism did not change any lipid parameters significantly. Levothyroxine therapy in overt hypothyroidism showed a statistically significant decrease in TC by -58.4 mg/dL (95% CI: -64.70, -52.09), LDL-C by -41.11 mg/dL (95% CI: -46.53, -35.69), HDL-C by -4.14 mg/dL (95% CI: -5.67, -2.61), TGs by -7.25 mg/dL (95% CI: -36.63, 17.87), apo A by -12.59 mg/dL (95% CI: -17.98, -7.19), apo B by -33.96 mg/dL (95% CI: 41.14, -26.77), and Lp(a) by -5.6 mg/dL (95% CI: -9.06, -2.14). Levothyroxine therapy in subclinical hypothyroidism showed similar changes but with a smaller magnitude. The studies contained varied population characteristics, severity of thyroid dysfunction, and follow-up duration.
CONCLUSIONS
Treatment of overt but not subclinical hyperthyroidism is associated with worsening of the lipid profile. Levothyroxine therapy in both overt and subclinical hypothyroidism leads to improvement in the lipid profile, with a smaller magnitude of improvement in subclinical hypothyroidism.
Topics: Cholesterol; Humans; Hyperthyroidism; Hypothyroidism; Lipids; Lipoprotein(a); Thyroid Diseases; Thyroid Gland; Thyroxine; Triglycerides
PubMed: 32954428
DOI: 10.1210/clinem/dgaa672 -
Osteoporosis International : a Journal... Dec 2021Due to the metabolic nature of osteoporosis, this study was conducted to identify metabolomic studies investigating the metabolic profile of low bone mineral density... (Review)
Review
Due to the metabolic nature of osteoporosis, this study was conducted to identify metabolomic studies investigating the metabolic profile of low bone mineral density (BMD) and osteoporosis. A comprehensive systematic literature search was conducted through PubMed, Web of Science, Scopus, and Embase databases up to April 08, 2020, to identify observational studies with cross-sectional or case-control designs investigating the metabolic profile of low BMD in adults using biofluid specimen via metabolomic platform. The quality assessment panel specified for the "omics"-based diagnostic research (QUADOMICS) tool was used to estimate the methodologic quality of the included studies. Ten untargeted and one targeted approach metabolomic studies investigating biomarkers in different biofluids through mass spectrometry or nuclear magnetic resonance platforms were included in the systematic review. Some metabolite panels, rather than individual metabolites, showed promising results in differentiating low BMD from normal. Candidate metabolites were of different categories including amino acids, followed by lipids and carbohydrates. Besides, certain pathways were suggested by some of the studies to be involved. This systematic review suggested that metabolic profiling could improve the diagnosis of low BMD. Despite valuable findings attained from each of these studies, there was great heterogeneity regarding the ethnicity and age of participants, samples, and the metabolomic platform. Further longitudinal studies are needed to validate the results and confirm the predictive role of metabolic profile on low BMD and fracture. It is also mandatory to address and minimize the heterogeneity in future studies by using reliable quantitative methods. Summary: Due to the metabolic nature of osteoporosis, researchers have considered metabolomic studies recently. This systematic review showed that metabolic profiling including different categories of metabolites could improve the diagnosis of low BMD. However, great heterogeneity was observed and it is mandatory to address and minimize the heterogeneity in future studies.
Topics: Adult; Biomarkers; Bone Density; Bone Diseases, Metabolic; Cross-Sectional Studies; Humans; Metabolomics
PubMed: 34309694
DOI: 10.1007/s00198-021-06037-8