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Pediatric Pulmonology Jul 2024Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter... (Review)
Review
BACKGROUND
Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet.
METHODS
A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts.
RESULTS
Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children.
CONCLUSION
A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required.
PubMed: 38953717
DOI: 10.1002/ppul.27112 -
Clinical Cardiology Jul 2024Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown encouraging results regarding cardiovascular outcomes mainly in patients with diabetes. In the present... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown encouraging results regarding cardiovascular outcomes mainly in patients with diabetes. In the present study, we compared the efficacy of GLP-1 RAs in cardiovascular events between patients with and without diabetes.
METHODS
After finding eligible studies assessing the impact of GLP-1 RAs on cardiovascular events in patients with and without diabetes using a systematic search, we performed a meta-analysis on randomized-controlled trials (RCTs) comparing cardiovascular outcomes between patients taking GLP-1 RAs and placebo stratified by the presence or absence of diabetes. Relative risk (RR) and its 95% confidence interval (CI) were set as the reporting effect size using the random-effects model.
RESULTS
A total of 24 RCTs (50 033 with GLP-1 RAs and 44 514 with placebo) were included. Patients on GLP-1 RAs had lower risk of major adverse cardiovascular events (MACE) (RR 0.87, 95% CI 0.82-0.93), cardiovascular death (RR 0.88, 95% CI 0.82-0.94), myocardial infarction (MI) (RR 0.87, 95% CI 0.77-0.97), stroke (RR 0.86, 95% CI 0.80-0.92), and hospitalization for heart failure (RR 0.90, 95% CI 0.83-0.98). Both subgroups were shown to be effective in terms of MACE and mortality. Nondiabetic patients had decreased risk of hospitalization for heart failure and MI, whereas the diabetic subgroup had marginally nonsignificant efficacy.
CONCLUSION
The findings of this meta-analysis indicated that patients who are overweight/obese but do not have diabetes have a comparable reduction in the risk of adverse cardiovascular events as those with diabetes. These results need to be confirmed further by large-scale randomized trials in the future.
Topics: Humans; Glucagon-Like Peptide-1 Receptor; Randomized Controlled Trials as Topic; Cardiovascular Diseases; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Risk Factors; Risk Assessment; Treatment Outcome; Incretins; Glucagon-Like Peptide-1 Receptor Agonists
PubMed: 38953365
DOI: 10.1002/clc.24314 -
Frontiers in Pediatrics 2024Two significant etiological factors contributing to iron deficiency anemia, and undernutrition posing substantial public health challenges in Sub-Saharan Africa, are...
Impact of weekly iron-folic acid supplementation on nutritional status and parasitic reinfection among school-age children and adolescents in Sub-Saharan Africa: a systematic review and meta-analysis.
BACKGROUND
Two significant etiological factors contributing to iron deficiency anemia, and undernutrition posing substantial public health challenges in Sub-Saharan Africa, are soil-transmitted helminths and malaria. This study carried out the effect of weekly iron-folic acid supplementation (WIFAS) on the nutrition and general health of school-age children and adolescents in Sub-Saharan Africa, a systematic review and meta-analysis have been conducted.
METHODS
To find pertinent publications for this study, a thorough search was carried out on May 20, 2023, across five databases: Pubmed (MEDLINE), Web of Science, Scopus, Cochrane Library, and Google Scholar. In addition, a search was conducted on August 23, 2023, to capture any new records. The inclusion criteria for the studies were based on school-age children and adolescent populations, randomized controlled trials, and investigations into the effects of WIFAS. The outcomes of interest were measured through anthropometric changes, malaria, and helminthic reinfection
RESULTS
A systematic review of 11 articles revealed that WIFAS significantly decreased the risk of schistosomiasis reinfection by 21% among adolescents (risk ratio = 0.79, 95%CI: 0.66, 0.97; heterogeneity = 0.00%, = 0.02). However, no significant impact was observed on the risk of malaria reinfection (risk ratio = 1.02, 95%CI: 0.92, 1.13; heterogeneity = 0.00%, = 0.67) or A. Lumbricoides reinfection (risk ratio = 0.95, 95%CI: 0.75, 1.19; heterogeneity = 0.00%, = 0.65). Moreover, the analysis demonstrated that there is no significant effect of iron-folic acid supplementation in measured height and height for age -score (HAZ) of the school-age children (Hedge's g -0.05, 95%CI: -0.3, 0.2; test for heterogeneity = 0.00%, = 0.7) and (Hedge's g 0.12, 95%CI: -0.13, 0.37; test for heterogeneity = 0.00%, = 0.36) respectively.
CONCLUSION
The effectiveness of WIFAS in reducing the risk of schistosomiasis reinfection in adolescents has been demonstrated to be greater than that of a placebo or no intervention. Additionally, the narrative synthesis of iron-folic acid supplementation has emerged as a potential public health intervention for promoting weight change. However, there was no significant association between WIFAS and Ascariasis, trichuriasis, and hookworm. Moreover, the certainty of the evidence for the effects of WIFAS on height and malaria is low and therefore inconclusive. Whereas, the certainty of the evidence for the effectiveness of WIFAS on Schistosomiasis is moderate. Even though the mechanisms need further research WIFAS may be implemented as part of a comprehensive public health strategy to address schistosomiasis in adolescents.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023397898, PROSPERO (CRD42023397898).
PubMed: 38952434
DOI: 10.3389/fped.2024.1366540 -
Seminars in Thrombosis and Hemostasis Jul 2024The optimal pharmacological prophylaxis for venous thromboembolism (VTE) after hip or knee arthroplasty is uncertain. We conducted a systematic review and network...
The optimal pharmacological prophylaxis for venous thromboembolism (VTE) after hip or knee arthroplasty is uncertain. We conducted a systematic review and network meta-analysis to compare the efficacy and safety of various medications. We searched multiple databases for randomized clinical trials (RCTs) comparing medications (including factor Xa inhibitors, factor IIa inhibitor, warfarin, unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], aspirin, pentasaccharide) for VTE prophylaxis post-arthroplasty. Outcomes included any postoperative VTE identified with screening, major bleeding, and death. We used LMWH as the main comparator for analysis and performed trial sequential analysis (TSA) for each pairwise comparison. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessments, Developments and Evaluations). We analyzed 70 RCTs (55,841 participants). Factor Xa inhibitors decreased postoperative VTE significantly compared with LMWH (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.44-0.68, high certainty). Pentasaccharides probably reduce VTE (OR: 0.61, 95% CI: 0.36-1.02, moderate certainty), while the factor IIa inhibitor dabigatran may reduce VTE (OR: 0.75, 95% CI: 0.40-1.42, low certainty). UFH probably increases VTE compared with LMWH (OR: 1.31, 95% CI: 0.91-1.89, moderate certainty), and other agents like warfarin, aspirin, placebo, and usual care without thromboprophylaxis increase VTE (high certainty). Factor Xa inhibitors may not significantly affect major bleeding compared with LMWH (OR: 1.06, 95% CI: 0.81-1.39, low certainty). No medications had a notable effect on mortality compared with LMWH (very low certainty). TSA suggests sufficient evidence for the benefit of factor Xa inhibitors over LMWH for VTE prevention. Compared with LMWH and aspirin, factor Xa inhibitors are associated with reduced VTE after hip or knee arthroplasty, without an increase in bleeding and likely no impact on mortality.
PubMed: 38950598
DOI: 10.1055/s-0044-1787996 -
Nutrition Reviews Jul 2024Previous research linked vitamin D deficiency in pregnancy to adverse pregnancy outcomes.
CONTEXT
Previous research linked vitamin D deficiency in pregnancy to adverse pregnancy outcomes.
OBJECTIVE
Update a 2017 systematic review and meta-analysis of randomized controlled trials (RCTs) on the effect of vitamin D supplementation during pregnancy, identify sources of heterogeneity between trials, and describe evidence gaps precluding a clinical recommendation.
DATA SOURCES
The MEDLINE, PubMed, Europe PMC, Scopus, Cochrane Database of Systematic Reviews, Web of Science, and CINAHL databases were searched. Articles were included that reported on RCTs that included pregnant women given vitamin D supplements as compared with placebo, no intervention, or active control (≤600 IU d-1). Risk ratios (RRs) and mean differences were pooled for 38 maternal, birth, and infant outcomes, using random effects models. Subgroup analyses examined effect heterogeneity. The Cochrane risk of bias tool was used.
DATA EXTRACTION
Included articles reported on a total of 66 trials (n = 17 276 participants).
DATA ANALYSIS
The median vitamin D supplementation dose was 2000 IU d-1 (range: 400-60 000); 37 trials used placebo. Antenatal vitamin D supplementation had no effect on the risk of preeclampsia (RR, 0.81 [95% CI, 0.43-1.53]; n = 6 trials and 1483 participants), potentially protected against gestational diabetes mellitus (RR, 0.65 [95% CI, 0.49-0.86; n = 12 trials and 1992 participants), and increased infant birth weight by 53 g (95% CI, 16-90; n = 40 trials and 9954 participants). No effect of vitamin D on the risk of preterm birth, small-for-gestational age, or low birth weight infants was found. A total of 25 trials had at least 1 domain at high risk of bias.
CONCLUSION
Additional studies among the general pregnant population are not needed, given the many existing trials. Instead, high-quality RCTs among populations with low vitamin D status or at greater risk of key outcomes are needed. Benefits of supplementation in pregnancy remain uncertain because current evidence has high heterogeneity, including variation in study context, baseline and achieved end-line 25-hydroxyvitamin D level, and studies with high risk of bias.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42022350057.
PubMed: 38950419
DOI: 10.1093/nutrit/nuae065 -
Annals of Internal Medicine Jul 2024In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or... (Review)
Review
Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease : A Systematic Review and Retrospective Individual Participant-Level Meta-analysis of Clinical Trials.
BACKGROUND
In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear.
PURPOSE
To examine the association of ACEi or ARB treatment initiation, relative to a non-ACEi or ARB comparator, with rates of KFRT and death.
DATA SOURCES
Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023.
STUDY SELECTION
Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m.
DATA EXTRACTION
The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m), albuminuria (urine albumin-creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes.
DATA SYNTHESIS
A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes ( for interaction > 0.05 for all).
LIMITATION
Individual participant-level data for hyperkalemia or acute kidney injury were not available.
CONCLUSION
Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD.
PRIMARY FUNDING SOURCE
National Institutes of Health. (PROSPERO: CRD42022307589).
PubMed: 38950402
DOI: 10.7326/M23-3236 -
Journal of Anxiety Disorders Jun 2024This review evaluates randomized controlled trials (RCTs) intervening on adult state anxiety (fear and emotional distress during dental treatment), chronic dental... (Review)
Review
This review evaluates randomized controlled trials (RCTs) intervening on adult state anxiety (fear and emotional distress during dental treatment), chronic dental (trait) anxiety or dental phobia (disproportionately high trait anxiety; meeting diagnostic criteria for specific phobia). Seven online databases were systematically searched. 173 RCTs met inclusion criteria, of which 67 qualified for 14 pooled analyses. To alleviate state anxiety during oral surgery, moderate-certainty evidence supports employing hypnosis (SMD=-0.31, 95 %CI[-0.56,-0.05]), and low-certainty evidence supports prescribing benzodiazepines (SMD=-0.43, [-0.74,-0.12]). Evidence for reducing state anxiety is inconclusive regarding psychotherapy, and does not support virtual reality exposure therapy (VRET), virtual reality distraction, music, aromatherapy, video information and acupuncture. To reduce trait anxiety, moderate-certainty evidence supports using Cognitive Behavioral Therapy (CBT; SMD=-0.65, [-1.06, -0.24]). Regarding dental phobia, evidence with low-to-moderate certainty supports employing psychotherapy (SMD=-0.48, [-0.72,-0.24]), and CBT specifically (SMD=-0.43, [-0.68,-0.17]), but not VRET. These results show that dental anxieties are manageable and treatable. Clinicians should ensure that interventions match their purpose-managing acute emotions during treatment, or alleviating chronic anxiety and avoidance tendencies. Existing research gaps underscore the necessity for future trials to minimize bias and follow CONSORT reporting guidelines.
PubMed: 38945067
DOI: 10.1016/j.janxdis.2024.102891 -
Journal of the European Academy of... Jun 2024Acne is a common skin condition, but little data exist on the comparative efficacy of topical acne therapies. We conducted a systematic review and network meta-analysis... (Review)
Review
Acne is a common skin condition, but little data exist on the comparative efficacy of topical acne therapies. We conducted a systematic review and network meta-analysis to evaluate the efficacy of topical therapies for mild-to-moderate acne. Searches in PubMed/MEDLINE, Cochrane CENTRAL via Ovid, Embase via Ovid and Web of Science were conducted on 29 November 2021. Randomized controlled trials examining ≥12 weeks of topical treatments for acne vulgaris in subjects aged 12 and older were included. Main outcomes were absolute or percent change in acne lesion count and treatment success on the Investigator's Global Assessment scale. Thirty-five randomized clinical trials with 33,472 participants comparing nine different topical agents were included. Adapalene-benzoyl peroxide (BPO), clindamycin-BPO and clindamycin-tretinoin demonstrated the greatest reduction in non-inflammatory (ratio of means [RoM] 1.76; 95% CI [1.46; 2.12], RoM 1.70; 95% CI [1.44; 2.02] and RoM 1.87; 95% CI [1.53; 2.30], respectively), inflammatory (RoM 1.56; 95% CI [1.44; 1.70], RoM 1.49; 95% CI [1.39; 1.60] and RoM 1.48; 95% CI [1.36; 1.61], respectively) and total lesion count (ROM 1.67; 95% CI [1.47; 1.90], RoM 1.59; 95% CI [1.42; 1.79] and RoM 1.64; 95% CI [1.42; 1.89], respectively) compared to placebo. All single agents outperformed placebo except tazarotene, which did not significantly outperform placebo for inflammatory and non-inflammatory lesion count reduction. Most combination agents significantly outperformed their individual components in lesion count reduction and global assessment scores, except for clindamycin-tretinoin and clindamycin-BPO, which did not significantly outperform tretinoin (RoM 1.13; 95% CI [0.94; 1.36]) and BPO (RoM = 1.15, 95% CI [0.98; 1.36]), respectively, for non-inflammatory lesion reduction. There was no significant difference amongst most single agents when evaluating lesion count reduction. Combination agents are generally most effective for mild-to-moderate acne; however for non-inflammatory acne, the addition of clindamycin in topical regimens is unnecessary and should be avoided.
PubMed: 38943431
DOI: 10.1111/jdv.20154 -
Journal of Affective Disorders Jun 2024Cariprazine has emerged as a promising augmenting treatment agent for unipolar depression and as a monotherapy option for bipolar depression. We evaluated cariprazine's...
BACKGROUND
Cariprazine has emerged as a promising augmenting treatment agent for unipolar depression and as a monotherapy option for bipolar depression. We evaluated cariprazine's efficacy in treating acute major depressive episodes in individuals with major depressive disorder (MDD) or bipolar disorder.
METHODS
A systematic review was conducted on MEDLINE, Embase, PyscInfo, Scopus and Web of Science, ClinicalTrials.gov and ScanMedicine. Study quality was assessed using the RoB 2 tool. Pairwise and dose-response meta-analyses were conducted with RStudio. Evidence quality was assessed with GRADE.
RESULTS
Nine RCTs meeting inclusion criteria encompassed 4877 participants. Cariprazine, compared to placebo, significantly reduced the MADRS score (MD = -1.49, 95 % CI: -2.22 to -0.76) and demonstrated significantly higher response (RR = 1.21, 95 % CI: 1.12 to 1.30) and remission (RR = 1.19, 95 % CI: 1.06 to 1.34) rates. Subgroup analysis unveiled statistically significant reductions in MADRS score in MDD (MD = -1.15, 95 % CI: -2.04 to -0.26) and bipolar I disorder (BDI) (MD = -2.53, 95 % CI: -3.61 to -1.45), higher response rates for both MDD (RR = 1.19, 95 % CI: 1.08 to 1.31) and BDI (RR = 1.27, 95 % CI: 1.10 to 1.46), and higher remission rates only for BDI (RR = 1.41, 95 % CI: 1.24 to 1.60). A higher rate of treatment discontinuation due to adverse events was observed.
LIMITATIONS
Reliance solely on RCTs limits generalisability; strict criteria might not reflect real-world diversity.
CONCLUSIONS
Cariprazine demonstrates efficacy in treating major depressive episodes, although variations exist between MDD and BDI and tolerability may be an issue.
PubMed: 38942207
DOI: 10.1016/j.jad.2024.06.099 -
JACC. Advances Nov 2023Guideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor...
BACKGROUND
Guideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i) monoclonal antibodies can help further reduce LDL-C and major adverse cardiovascular events (MACE) although differences in efficacy by sex and type are less understood.
OBJECTIVES
The authors sought to determine if there are differences in the efficacy of LDL-C lowering and reduction in the risk of MACE by sex and type of PCSK9i.
METHODS
A comprehensive literature search was done through October 17, 2022, for published trials comparing PCSK9i vs control. Outcomes assessed were LDL-C reduction and incidence of MACE following the use of PCSK9i vs placebo, stratified by sex and type of PCSK9i used.
RESULTS
We identified 16 trials with 54,996 adults, and 15,143 (27.5%) of them were female. PCSK9i significantly reduced MACE compared to placebo in both women (HR: 0.86, 95% CI: 0.74-0.97, < 0.001) and men (HR: 0.85, 95% CI: 0.79-0.91, < 0.001) with no significant sex difference (MD -0.01, 95% CI: -0.14 to -0.13, = 0.930). PCSK9i also significantly reduced LDL-C levels in both sexes at 12 weeks (females: MD -62.57, 95% CI: -70.24 to -54.91, < 0.001; males: MD -66.19, 95% CI: -72.03 to -60.34, < 0.001) and 24 weeks (females: MD -47.52, 95% CI: -52.94 to -42.09, < 0.001; males: MD -54.07, 95% CI: -59.46 to -48.68, < 0.001). Significant sex difference was seen in the LDL reduction of PCSK9i for both 12 weeks (males vs females: MD -4.55, 95% CI: -7.34 to -1.75, < 0.01) and 24 weeks (males vs females: MD -7.11, 95% CI: -9.99 to -4.23, < 0.001).
CONCLUSIONS
The use of PCSK9i results in significant LDL-C and MACE reduction in both males and females. While there is no significant sex difference in MACE reduction, LDL-C reduction is greater in males than in females. Our data support the equal use of PCSK9i in all eligible patients, regardless of sex.
PubMed: 38938736
DOI: 10.1016/j.jacadv.2023.100669