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European Journal of Preventive... Dec 2023There is good evidence showing that inactivity and walking minimal steps/day increase the risk of cardiovascular (CV) disease and general ill-health. The optimal number... (Meta-Analysis)
Meta-Analysis
AIMS
There is good evidence showing that inactivity and walking minimal steps/day increase the risk of cardiovascular (CV) disease and general ill-health. The optimal number of steps and their role in health is, however, still unclear. Therefore, in this meta-analysis, we aimed to evaluate the relationship between step count and all-cause mortality and CV mortality.
METHODS AND RESULTS
We systematically searched relevant electronic databases from inception until 12 June 2022. The main endpoints were all-cause mortality and CV mortality. An inverse-variance weighted random-effects model was used to calculate the number of steps/day and mortality. Seventeen cohort studies with a total of 226 889 participants (generally healthy or patients at CV risk) with a median follow-up 7.1 years were included in the meta-analysis. A 1000-step increment was associated with a 15% decreased risk of all-cause mortality [hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.81-0.91; P < 0.001], while a 500-step increment was associated with a 7% decrease in CV mortality (HR 0.93; 95% CI 0.91-0.95; P < 0.001). Compared with the reference quartile with median steps/day 3867 (2500-6675), the Quartile 1 (Q1, median steps: 5537), Quartile 2 (Q2, median steps 7370), and Quartile 3 (Q3, median steps 11 529) were associated with lower risk for all-cause mortality (48, 55, and 67%, respectively; P < 0.05, for all). Similarly, compared with the lowest quartile of steps/day used as reference [median steps 2337, interquartile range 1596-4000), higher quartiles of steps/day (Q1 = 3982, Q2 = 6661, and Q3 = 10 413) were linearly associated with a reduced risk of CV mortality (16, 49, and 77%; P < 0.05, for all). Using a restricted cubic splines model, we observed a nonlinear dose-response association between step count and all-cause and CV mortality (Pnonlineraly < 0.001, for both) with a progressively lower risk of mortality with an increased step count.
CONCLUSION
This meta-analysis demonstrates a significant inverse association between daily step count and all-cause mortality and CV mortality with more the better over the cut-off point of 3867 steps/day for all-cause mortality and only 2337 steps for CV mortality.
Topics: Humans; Walking; Cardiovascular Diseases; Cohort Studies; Health Status
PubMed: 37555441
DOI: 10.1093/eurjpc/zwad229 -
Drugs Oct 2023Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs).
OBJECTIVE
The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA).
METHODS
Studies were identified by conducting a systematic search (week 4, January 2023) of the MEDLINE (accessed by PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and US National Institutes of Health Clinical Trials Registry ( http://www.
CLINICALTRIALS
gov ) databases. Any randomized, controlled, double- or single-blinded, parallel-group study comparing at least one ASM therapy against placebo, another ASM, or a different dose of the same ASM in participants with a diagnosis of DS was identified. The efficacy outcomes were the proportions of participants with ≥ 50% (seizure response) and 100% reduction (seizure freedom) in baseline convulsive seizure frequency during the maintenance period. The tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and who experienced at least one adverse event (AE). Effect sizes were estimated by network meta-analyses within a frequentist framework.
RESULTS
Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n = 2), pharmaceutical-grade cannabidiol (n = 3), fenfluramine hydrochloride (n = 2), and soticlestat (n = 1). The studies recruited 680 participants, of whom 409 were randomized to active treatments (stiripentol = 33, pharmaceutical-grade cannabidiol = 228, fenfluramine hydrochloride = 122, and soticlestat = 26) and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07-0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57-76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Stiripentol was associated with a lower probability of drug discontinuation for any reason than pharmaceutical-grade cannabidiol (OR 0.45, 95% CI 0.04-5.69), and pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06-0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59-1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS.
CONCLUSIONS
There exists first-class evidence that documents the efficacy and tolerability of stiripentol, pharmaceutical-grade cannabidiol, fenfluramine hydrochloride, and soticlestat for the treatment of seizures associated with DS, and allows discussion about the expected outcomes regarding seizure frequency reduction and tolerability profiles.
Topics: Humans; Anticonvulsants; Cannabidiol; Network Meta-Analysis; Randomized Controlled Trials as Topic; Seizures; Epilepsies, Myoclonic; Fenfluramine; Pharmaceutical Preparations
PubMed: 37695433
DOI: 10.1007/s40265-023-01936-y -
Hypertension (Dallas, Tex. : 1979) Oct 2023Alcohol consumption may increase blood pressure but the details of the relationship are incomplete, particularly for the association at low levels of alcohol... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol consumption may increase blood pressure but the details of the relationship are incomplete, particularly for the association at low levels of alcohol consumption, and no meta-analyses are available for nonexperimental cohort studies.
METHODS
We performed a systematic search of longitudinal studies in healthy adults that reported on the association between alcohol intake and blood pressure. Our end points were the mean differences over time of systolic (SBP) and diastolic blood pressure (DBP), plotted according to baseline alcohol intake, by using a dose-response 1-stage meta-analytic methodology.
RESULTS
Seven studies, with 19 548 participants and a median follow-up of 5.3 years (range, 4-12 years), were included in the analysis. We observed a substantially linear positive association between baseline alcohol intake and changes over time in SBP and DBP, with no suggestion of an exposure-effect threshold. Overall, average SBP was 1.25 and 4.90 mm Hg higher for 12 or 48 grams of daily alcohol consumption, compared with no consumption. The corresponding differences for DBP were 1.14 and 3.10 mm Hg. Subgroup analyses by sex showed an almost linear association between baseline alcohol intake and SBP changes in both men and women, and for DBP in men while in women we identified an inverted -shaped association. Alcohol consumption was positively associated with blood pressure changes in both Asians and North Americans, apart from DBP in the latter group.
CONCLUSIONS
Our results suggest the association between alcohol consumption and SBP is direct and linear with no evidence of a threshold for the association, while for DBP the association is modified by sex and geographic location.
Topics: Adult; Female; Humans; Male; Alcohol Drinking; Blood Pressure; Cohort Studies; Hypertension
PubMed: 37522179
DOI: 10.1161/HYPERTENSIONAHA.123.21224 -
British Journal of Sports Medicine Oct 2023To identify the optimal dose and type of physical activity to improve functional capacity and reduce adverse events in acutely hospitalised older adults.
Optimal dose and type of physical activity to improve functional capacity and minimise adverse events in acutely hospitalised older adults: a systematic review with dose-response network meta-analysis of randomised controlled trials.
OBJECTIVE
To identify the optimal dose and type of physical activity to improve functional capacity and reduce adverse events in acutely hospitalised older adults.
DESIGN
Systematic review and Bayesian model-based network meta-analysis.
DATA SOURCES
Four databases were searched from inception to 20 June 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials that assessed the effectiveness of a physical activity-based intervention on at least one functional outcome in people aged ≥50 years hospitalised due to an acute medical condition were included. Pooled effect estimates (ie, standardised mean differences for functional capacity and the ratio of means for adverse events) were calculated using random treatment effects network meta-analysis models.
RESULTS
Nineteen studies (3842 participants) met the inclusion criteria. Approximately 100 Metabolic Equivalents of Task per day (METs-min/day) (~40 min/day of light effort or ~25 min/day of moderate effort activities) was the minimal dose to improve the functional capacity of acute hospitalised older adults (standardised mean difference (SMD)=0.28, 95% credible interval (CrI) 0.01 to 0.55). The optimal dose was estimated at 159 METs-min/day (~70 min/day of light effort or ~40 min/day of moderate effort activities; SMD=0.41, 95% CrI 0.08 to 0.72). Ambulation was deemed the most efficient intervention, and the optimal dose was reached at 143 METs-min/day (~50 min/day of slow-paced walking; SMD=0.76, 95% CrI 0.35 to 1.16), showing a high evidential power (87.68%). The minimal effective ambulation dose was estimated at 74 METs-min/day (~25 min/day of slow-paced walking; SMD=0.25, 95% CrI 0.01 to 0.41). Physical activity interventions resulted in a decrease in the rate of adverse events compared with usual care at discharge (ratio of means=0.96, 95% CrI 0.95 to 0.97; median time 7 days).
CONCLUSIONS
This meta-analysis yielded low to moderate evidence supporting the use of in-hospital supervised physical activity programmes in acutely hospitalised older adults. As little as ~25 min/day of slow-paced walking is sufficient to improve functional capacity and minimise adverse events in this population.
TRIAL REGISTRATION NUMBER
PROSPERO CRD42021271999.
PubMed: 37536984
DOI: 10.1136/bjsports-2022-106409 -
Archives of Pathology & Laboratory... Sep 2023To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2)...
PURPOSE.—
To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification.
METHODS.—
The Update Panel conducted a systematic literature review to identify signals for updating recommendations.
RESULTS.—
The search identified 173 abstracts. Of 5 potential publications reviewed, none constituted a signal for revising existing recommendations.
RECOMMENDATIONS.—
The 2018 ASCO-CAP recommendations for HER2 testing are affirmed.
DISCUSSION.—
HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, although it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines.
Topics: Humans; Female; Breast Neoplasms; In Situ Hybridization, Fluorescence; Receptor, ErbB-2; In Situ Hybridization; Biomarkers, Tumor
PubMed: 37303228
DOI: 10.5858/arpa.2023-0950-SA -
Current Environmental Health Reports Dec 2023We performed a systematic review and meta-analysis on the relation between fluoride exposure and skeletal fluorosis (SF) using a novel statistical methodology for... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
We performed a systematic review and meta-analysis on the relation between fluoride exposure and skeletal fluorosis (SF) using a novel statistical methodology for dose-response modeling.
RECENT FINDINGS
Skeletal fluorosis, a major health issue that is endemic in some regions, affects millions of people worldwide. However, data regarding the dose-response relation between fluoride exposure and SF are limited and outdated. We included twenty-three studies in the meta-analysis. When comparing the highest versus the lowest fluoride category, the summary risk ratio (RR) for SF prevalence was 2.05 (95% CI 1.60; 2.64), with a value of 2.73 (95% CI 1.92; 3.90) for drinking water and 1.40 (95% CI 0.90; 2.17) for urinary fluoride. The RR by the risk of bias (RoB) was 2.37 (95% CI 1.56; 3.58) and 1.78 (95% CI 1.34; 2.36) for moderate and high RoB studies, respectively. The dose-response curve based on a one-stage cubic spline regression model showed an almost linear positive relation between exposure and SF occurrence starting from relatively low concentrations up to 5 mg/L and 2.5 mg/L, respectively, for water and urinary fluoride, with no substantial increase above this threshold. The RR for developing moderate-severe forms increases at 5.00 mg/L and 2.5 mg/L of water and urinary fluoride, respectively. Better-quality studies are needed to confirm these results, but greater attention should be given to water fluoride levels to prevent SF, in addition to the other potential adverse effects of fluoride exposure.
Topics: Humans; Fluorides; Fluorosis, Dental; Drinking Water; Prevalence
PubMed: 37861949
DOI: 10.1007/s40572-023-00412-9 -
Journal of Investigative Medicine : the... Aug 2023The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which... (Review)
Review
The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which focuses on each patient, is justified. Metabolomics would decipher the molecular mechanisms underlying the therapeutic response heterogeneity. Identification of altered metabolic pathways would open new horizons in the therapeutic management of acromegaly. This research aimed to evaluate the metabolomic profile in acromegaly and metabolomics' contributions to understanding disease pathogenesis. A systematic review was carried out by querying four electronic databases and evaluating patients with acromegaly through metabolomic techniques. In all, 21 studies containing 362 patients were eligible. Choline, the ubiquitous metabolite identified in growth hormone (GH)-secreting pituitary adenomas (Pas) by in vivo magnetic resonance spectroscopy (MRS), negatively correlated with somatostatin receptors type 2 expression and positively correlated with magnetic resonance imaging T2 signal and Ki-67 index. Moreover, elevated choline and choline/creatine ratio differentiated between sparsely and densely granulated GH-secreting PAs. MRS detected low hepatic lipid content in active acromegaly, which increased after disease control. The panel of metabolites of acromegaly deciphered by mass spectrometry (MS)-based techniques mainly included amino acids (especially branched-chain amino acids and taurine), glyceric acid, and lipids. The most altered pathways in acromegaly were the metabolism of glucose (particularly the downregulation of the pentose phosphate pathway), linoleic acid, sphingolipids, glycerophospholipids, arginine/proline, and taurine/hypotaurine. Matrix-assisted laser desorption/ionization coupled with MS imaging confirmed the functional nature of GH-secreting PAs and accurately discriminated PAs from healthy pituitary tissue.
Topics: Humans; Acromegaly; Growth Hormone-Secreting Pituitary Adenoma; Magnetic Resonance Imaging; Metabolomics; Adenoma
PubMed: 37139720
DOI: 10.1177/10815589231169452 -
Journal of Psychiatric Research Aug 2023Rapid-cycling in bipolar disorder (RC-BD) is associated with greater illness morbidity and inferior treatment response but many aspects remain unclear, prompting this... (Review)
Review
Rapid-cycling in bipolar disorder (RC-BD) is associated with greater illness morbidity and inferior treatment response but many aspects remain unclear, prompting this systematic review of its definitions, prevalence, and clinical characteristics. We searched multiple literature databases through April 2022 for systematic reviews or meta-analyses on RC-BD and extracted associated definitions, prevalence, risk-factors, and clinical outcomes. We assessed study quality (NIH Quality Assessment Tool) and levels of evidence (Oxford criteria). Of 146 identified reviews, 22 fulfilling selection criteria were included, yielding 30 studies involving 13,698 BD patients, of whom 3777 (27.6% [CI: 26.8-28.3]) were considered RC-BD, as defined in 14 reports by ≥4 recurrences/year within the past 12 months or in any year, without considering responsiveness to treatment. Random-effects meta-analytically pooled one-year prevalence was 22.3% [CI: 14.4-32.9] in 12 reports and lifetime prevalence was 35.5% [27.6-44.3] in 18 heterogenous reports. Meta-regression indicated greater lifetime prevalence of RC-BD among women than men (p=0.003). Association of RC-BD with suicide attempts, and unsatisfactory response to mood-stabilizers was supported by strong evidence (Level 1); associations with childhood maltreatment, mixed-features, female sex, and type-II BD had moderate evidence (Level 2). Other factors: genetic predisposition, metabolic disturbances or hypothyroidism, antidepressant exposure, predominant depressive polarity (Level 3), along with greater illness duration and immune-inflammatory dysfunction (Level 4) require further study. RC-BD was consistently recognized as having high prevalence (22.3%-35.5% of BD cases) and inferior treatment response. Identified associated factors can inform clinical practice. Long-term illness-course, metabolic factors, and optimal treatment require further investigation.
Topics: Female; Humans; Male; Antidepressive Agents; Bipolar Disorder; Hypothyroidism; Prevalence; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 37429185
DOI: 10.1016/j.jpsychires.2023.06.021 -
Life Sciences Nov 2023A diverse and stable microbiota promotes a healthy state, nevertheless, an imbalance in gut or oral bacterial composition, called dysbiosis, can cause gastrointestinal... (Review)
Review
A diverse and stable microbiota promotes a healthy state, nevertheless, an imbalance in gut or oral bacterial composition, called dysbiosis, can cause gastrointestinal disorders, systemic inflammatory states and oxidative stress, among others. Recently, gut and oral dysbiosis has been linked to Alzheimer's disease (AD), which is considered the most common form of dementia and a public health priority due to its high prevalence and incidence. The aim of this review is to highlight the implications of gut and oral microbiota in the neuroinflammation characteristic of AD pathology and the subsequent cognitive impairment. It is a systematic review of the current literature obtained by searching the PubMed, Web of Science and Scopus databases. The characteristic intestinal dysbiosis in AD patients leads to increased permeability of the intestinal barrier and activates immune cells in the central nervous system due to translocation of microbiota-derived metabolites and/or bacteria into the circulation leading to increased neuroinflammation and neuronal loss, thus generating the cognitive impairment characteristic of AD. The presence in the central nervous system of Porphyromonas gingivalis can cause an increased neuroinflammation and beta-amyloid peptide accumulation.
Topics: Humans; Alzheimer Disease; Gastrointestinal Microbiome; Neuroinflammatory Diseases; Dysbiosis; Microbiota; Inflammation; Bacteria; Brain
PubMed: 37793482
DOI: 10.1016/j.lfs.2023.122132 -
PloS One 2023Whether food source or energy mediates the effect of fructose-containing sugars on blood pressure (BP) is unclear. We conducted a systematic review and meta-analysis of... (Meta-Analysis)
Meta-Analysis
Whether food source or energy mediates the effect of fructose-containing sugars on blood pressure (BP) is unclear. We conducted a systematic review and meta-analysis of the effect of different food sources of fructose-containing sugars at different levels of energy control on BP. We searched MEDLINE, Embase and the Cochrane Library through June 2021 for controlled trials ≥7-days. We prespecified 4 trial designs: substitution (energy matched substitution of sugars); addition (excess energy from sugars added); subtraction (excess energy from sugars subtracted); and ad libitum (energy from sugars freely replaced). Outcomes were systolic and diastolic BP. Independent reviewers extracted data. GRADE assessed the certainty of evidence. We included 93 reports (147 trial comparisons, N = 5,213) assessing 12 different food sources across 4 energy control levels in adults with and without hypertension or at risk for hypertension. Total fructose-containing sugars had no effect in substitution, subtraction, or ad libitum trials but decreased systolic and diastolic BP in addition trials (P<0.05). There was evidence of interaction/influence by food source: fruit and 100% fruit juice decreased and mixed sources (with sugar-sweetened beverages [SSBs]) increased BP in addition trials and the removal of SSBs (linear dose response gradient) and mixed sources (with SSBs) decreased BP in subtraction trials. The certainty of evidence was generally moderate. Food source and energy control appear to mediate the effect of fructose-containing sugars on BP. The evidence provides a good indication that fruit and 100% fruit juice at low doses (up to or less than the public health threshold of ~10% E) lead to small, but important reductions in BP, while the addition of excess energy of mixed sources (with SSBs) at high doses (up to 23%) leads to moderate increases and their removal or the removal of SSBs alone (up to ~20% E) leads to small, but important decreases in BP in adults with and without hypertension or at risk for hypertension. Trial registration: Clinicaltrials.gov: NCT02716870.
Topics: Adult; Humans; Fructose; Blood Pressure; Fruit; Sugars; Hypertension
PubMed: 37582096
DOI: 10.1371/journal.pone.0264802