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BMJ Paediatrics Open Jun 2024Knowledge about multisystem inflammatory syndrome in children (MIS-C) is evolving, and evidence-based standardised diagnostic and management protocols are lacking. Our...
BACKGROUND
Knowledge about multisystem inflammatory syndrome in children (MIS-C) is evolving, and evidence-based standardised diagnostic and management protocols are lacking. Our review aims to summarise the clinical and diagnostic features, management strategies and outcomes of MIS-C and evaluate the variances in disease parameters and outcomes between high-income countries (HIC) and middle-income countries (MIC).
METHODS
We searched four databases from December 2019 to March 2023. Observational studies with a sample size of 10 or more patients were included. Mean and prevalence ratios for various variables were pooled by random effects model using R. A mixed generalised linear model was employed to account for the heterogeneity, and publication bias was assessed via funnel and Doi plots. The primary outcome was pooled mean mortality among patients with MIS-C. Subgroup analysis was conducted based on the income status of the country of study.
RESULTS
A total of 120 studies (20 881 cases) were included in the review. The most common clinical presentations were fever (99%; 95% CI 99.6% to 100%), gastrointestinal symptoms (76.7%; 95% CI 73.1% to 79.9%) and dermatological symptoms (63.3%; 95% CI 58.7% to 67.7%). Laboratory investigations suggested raised inflammatory, coagulation and cardiac markers. The most common management strategies were intravenous immunoglobulins (87.5%; 95% CI 82.9% to 91%) and steroids (74.7%; 95% CI 68.7% to 79.9%). Around 53.1% (95% CI 47.3% to 58.9%) required paediatric intensive care unit admissions, and overall mortality was 3.9% (95% CI 2.7% to 5.6%). Patients in MIC were younger, had a higher frequency of respiratory distress and evidence of cardiac dysfunction, with a longer hospital and intensive care unit stay and had a higher mortality rate than patients in HIC.
CONCLUSION
MIS-C is a severe multisystem disease with better mortality outcomes in HIC as compared with MIC. The findings emphasise the need for standardised protocols and further research to optimise patient care and address disparities between HIC and MIC.
PROSPERO REGISTRATION NUMBER
CRD42020195823.
Topics: Humans; Systemic Inflammatory Response Syndrome; Child; COVID-19
PubMed: 38844384
DOI: 10.1136/bmjpo-2023-002344 -
Cancer Immunology, Immunotherapy : CII Jun 2024Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of anti-PD-1/PD-L1-based dual immunotherapies versus PD-1/PD-L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta-analysis.
INTRODUCTION
Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical benefits of combination of two immune-oncology (IO) therapies for cancer patients persists.
METHODS
Both published and grey sources of randomized clinical trials that compared anti-PD-1/PD-L1-based immunotherapy combinations with monotherapy in patients with advanced or metastatic solid tumors were encompassed. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs).
RESULTS
Our analysis encompassed 31 studies comprising 10,341 patients, which covered 12 distinct immune-oncology combination regimens. Across all patients, the immunotherapy combinations exhibited the capability to enhance the ORR (OR = 1.23 [95% CI 1.13-1.34]) and extend PFS (HR = 0.91 [95% CI 0.87-0.95]). However, the observed enhancement in OS (HR = 0.96 [95% CI 0.91-1.01]) was of no significance. Greater benefits in terms of PFS (HR = 0.82 [95% CI 0.72 to 0.93]) and OS (HR = 0.85 [95% CI 0.73 to 0.99]) may be particularly pronounced in cases where PD-L1 expression is negative. Notably, despite a heightened risk of any-grade TRAEs (OR = 1.72 [95% CI 1.40-2.11]) and grade greater than or equal to 3 TRAEs (OR = 2.01 [95% CI 1.67-2.43]), toxicity was generally manageable.
CONCLUSIONS
This study suggests that incorporating an additional immunotherapy agent with PD-1/PD-L1 inhibitors can elevate the response rate and reduce the risk of disease progression, all while maintaining manageable toxicity. However, there remains a challenge in translating these primary clinical benefits into extended overall survival.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 38834888
DOI: 10.1007/s00262-024-03734-1 -
BMC Geriatrics Jun 2024Assessing and monitoring intrinsic capacity (IC) is an effective strategy to promote healthy ageing by intervening early in high-risk populations. This review... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Assessing and monitoring intrinsic capacity (IC) is an effective strategy to promote healthy ageing by intervening early in high-risk populations. This review systematically analyzed the global detection rates of IC deficits and explored variations across diverse populations and data collection methods.
METHODS
This study was preregistered with PROSPERO, CRD42023477315. In this systematic review and meta-analysis, we systematically searched ten databases from January 2015 to October 2023, for peer-reviewed, observational studies or baseline survey of trials that assessed IC deficits among older adults aged 50 and above globally following the condition, context and population approach. The main outcome was intrinsic capacity deficits which could be assessed by any tools. Meta-analyses were performed by a random-effect model to pool the detection rates across studies and subgroup analyses were conducted by populations and data collection methods.
RESULTS
Fifty-six studies conducted in 13 countries were included in the review and 44 studies with detection rates of IC were included in the meta-analysis. The pooled detection rate of IC deficits was 72.0% (65.2%-78.8%) and deficits were most detected in sensory (49.3%), followed by locomotion (40.0%), cognition (33.1%), psychology (21.9%), and vitality (20.1%). Variations in detection rates of IC deficits were observed across studies, with higher rates observed in low- and middle-income countries (74.0%) and hyper-aged societies (85.0%). Study population and measurement tools also explained the high heterogeneity across studies.
CONCLUSION
IC deficits are common among older adults, while heterogeneity exists across populations and by measurement. Early monitoring with standardized tools and early intervention on specific subdomains of IC deficits are greatly needed for effective strategies to promote healthy ageing.
Topics: Humans; Aged; Geriatric Assessment; Middle Aged; Healthy Aging; Aged, 80 and over
PubMed: 38831281
DOI: 10.1186/s12877-024-05088-w -
Sports Health Jun 2024The Olympic sport of diving involves the competitive disciplines of 3 m springboard and 10 m platform. Although it is generally accepted that lumbar spine injuries are... (Review)
Review
CONTEXT
The Olympic sport of diving involves the competitive disciplines of 3 m springboard and 10 m platform. Although it is generally accepted that lumbar spine injuries are common in diving athletes, the existing literature of health problems in diving athletes remains scarce.
OBJECTIVE
To identify the incidence, prevalence, and type of health problems that occur in competitive diving athletes.
DATA SOURCES
Medline, EMBASE, SportsDiscus, PsycINFO, and Google Scholar.
STUDY SELECTION
Studies written in English investigating elite or pre-elite competitive diving (springboard, platform) injuries and/or illnesses were eligible. Two independent reviewers screened for inclusion by title, abstract, and full text in accordance with the eligibility criteria.
STUDY DESIGN
Systematic review.
LEVEL OF EVIDENCE
Level 4.
DATA EXTRACTION
Data extraction was completed by 1 author using a structured form. A second author then independently reviewed and verified the extracted data, any discrepancies were resolved through consensus.
RESULTS
The search identified 2554 potential articles, with 28 studies meeting eligibility criteria. The surveillance setting of most studies was restricted to competition-based events, with the reported injury incidence proportion ranging from 2.1% to 22.2%. The reported injury incidence rate ranged from 1.9 to 15.5 per 1000 athlete-exposures. Injuries to the shoulder, lower back/lumbar spine, trunk, and wrist/hand were reported most frequently. The prevalence of low back pain was reported as high as 89% (lifetime), 43.1% (period), and 37.3% (point). The illness incidence proportion ranged from 0.0% to 22.2%, with respiratory and gastrointestinal illness reported most frequently.
CONCLUSION
Up to 1 in 5 diving athletes sustain an injury and/or illness during periods of competition. A reporting bias was observed, with most cohort studies limiting surveillance to short competition-based periods only. This limits the current understanding of the health problems experienced by diving athletes to competition periods only and requires expansion to whole-of-year surveillance.
PubMed: 38828690
DOI: 10.1177/19417381241255329 -
Heliyon Jun 2024There is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell...
BACKGROUND
There is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell lung cancer (NSCLC). We carried out a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy with different treatment cycles in order to provide valuable information for clinical decision-making.
METHODS
PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were systematically searched before May 2023. The included studies were categorized based on different treatment cycles of neoadjuvant immunotherapy to assess their respective efficacy and safety in patients with resectable NSCLC.
RESULTS
Incorporating data from 29 studies with 1331 patients, we found major pathological response rates of 43 % (95%CI, 34-52 %) with two cycles and 33 % (95%CI, 22-45 %) with three cycles of neoadjuvant immunotherapy. Radiological response rates were 39 % (95%CI, 28-50 %) and 56 % (95%CI, 44-68 %) for two and three cycles, respectively, with higher incidence rates of severe adverse events (SAEs) in the three-cycle group (32 %; 95%CI, 21-50 %). Despite similar rates of R0 resection between two and three cycles, the latter showed a slightly higher surgical delay rate (1 % vs. 7 %). Neoadjuvant treatment modes significantly affected outcomes, with the combination of immunotherapy and chemotherapy demonstrating superiority in improving pathological and radiological response rates, while the incidence of SAEs in patients receiving combination therapy remained within an acceptable range (23 %; 95%CI, 15-35 %). However, regardless of the treatment mode administered, an increase in the number of treatment cycles did not result in substantial improvement in pathological response rates.
CONCLUSION
There are clear advantages of combining immunotherapy and chemotherapy in neoadjuvant settings. Increasing the number of cycles of neoadjuvant immunotherapy from two to three primarily may not substantially improve the overall efficacy, while increasing the risk of adverse events. Further analysis of the outcomes of four cycles of neoadjuvant immunotherapy is necessary.
PubMed: 38828349
DOI: 10.1016/j.heliyon.2024.e31549 -
International Journal of Chronic... 2024Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese patent medicine, has been commonly used for treating COPD. This study evaluated the clinical efficacy of CKZ injections in COPD patients and explored potential underlying mechanisms by integrating meta-analysis and network pharmacology.
RESEARCH METHODS
Randomized controlled trials (RCTs) were search in database by Web of Science, Cochrane Library and PubMed as of November 2022 for literature collection, and the Review Manager 5.4 was used to analyze the data. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed.
RESULTS
A total of 15 RCTs including 1212 patients were included. The results of meta-analysis showed that CKZ injection can significantly improve the clinical effective rate (RR = 1.25, 95% CI: 1.14 to 1.36), and the clinical advantage was that it can significantly reduced acute exacerbation rate (RR = 0.29, 95% CI: 0.12 to 0.70) and COPD assessment test (CAT) scores (MD =-4.62, 95% CI:-8.966 to-0.28). A total of 31 chemical compounds and 178 potential targets for CKZ injection were obtained from the online databases. Molecular docking revealed that most key components and targets could form stable structure.
CONCLUSION
This systematic review with meta-analysis and network pharmacology demonstrates that CKZ could effectively improve the clinical efficacy and safety in the treatment of COPD. Such efficacy may be related to an anti-inflammatory effect and immunoregulation of CKZ via multiple components, multiple targets and multiple pathways.
Topics: Pulmonary Disease, Chronic Obstructive; Humans; Drugs, Chinese Herbal; Network Pharmacology; Treatment Outcome; Randomized Controlled Trials as Topic; Lung; Anti-Inflammatory Agents; Middle Aged; Male; Aged; Female; Injections
PubMed: 38826697
DOI: 10.2147/COPD.S442281 -
Frontiers in Immunology 2024Due to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges.
IMPORTANCE
Due to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges.
OBJECTIVE
To examine the efficacy and safety of systemic therapies for the treatment of moderate-to-severe atopic dermatitis in children and adolescents.
EVIDENCE REVIEW
On Feb 29, 2024, a systematic literature search was conducted in Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Central). No date restrictions were applied. Randomized clinical trials, cohort studies, large case series, and meta-analyses were assessed to evaluate the efficacy (or effectiveness) and/or safety of systemic treatments for moderate-to-severe atopic dermatitis in children and adolescents.
FINDINGS
A preliminary search yielded 1457 results, from which 19 unique articles with a total of 3741 patients were included in the analysis. Overall, the available data for each systemic medication are limited, and the overall quality of the included studies on conventional systemic treatments is relatively low. When Dupilumab was used as a standalone treatment, 30%-40% of infants and toddlers aged 6 months to 2 years achieved EASI-75, while 50% of patients aged 2 to 6 years achieved EASI-75. In children aged 6 to 12 years, 33.0%-59.0% of atopic dermatitis patients achieved EASI-75, and when combined with topical corticosteroids (TCS), 69.7%-74.6% achieved EASI-75. Long-term data showed EASI-75 rates ranging from 75.0% to 94.0% for this age group. For adolescents aged 12 to 18 years, 40%-71% of patients achieved EASI-75 within 12 to 16 weeks, and by week 52, 80.8% of patients achieved EASI-75.Abrocitinib treatment resulted in 68.5%-72.0% of patients achieving EASI-75. Omalizumab treatment at week 24 showed a percentage change in SCORAD scores of -12.4%. In the Methotrexate treatment group, there was a SCORAD change of -26.25% at week 12, while the Cyclosporine A group had a SCORAD change of -25.01%. Patients treated with IVIG (Intravenous Immunoglobulin) showed a -34.4% change in SCORAD percentage scores at week 4, which further decreased by 47.12% at week 24. Patients receiving 4mg of Baricitinib and TCS had a 52.5% rate of EASI-75 at 16 weeks, and patients receiving different doses of upadacitinib had a 63-75% rate of EASI-75 at 16 weeks. The rate of EASI-75 at 16 weeks was around 28% in patients who received various doses of Tralokinumab.The most common adverse events observed were nasopharyngitis, respiratory events and dermatitis atopic.
CONCLUSIONS AND RELEVANCE
Awareness of adverse events and concomitant medications is crucial, and appropriate dosing and frequent laboratory and clinical monitoring are also essential. More real-world evidence and prospective cohort studies analyzing the effectiveness and safety of systemic therapies in children and adolescents are of paramount importance for optimizing personalized, effective, and safe management of the growing population of patients with atopic dermatitis in this age group.
Topics: Humans; Dermatitis, Atopic; Child; Adolescent; Child, Preschool; Treatment Outcome; Severity of Illness Index; Infant; Female; Male; Dermatologic Agents; Antibodies, Monoclonal, Humanized
PubMed: 38812522
DOI: 10.3389/fimmu.2024.1367099 -
Journal of Clinical Medicine May 2024: High-flow nasal cannula (HFNC) therapy has emerged as a promising treatment modality for interstitial lung disease (ILD)-related respiratory failure. This systematic... (Review)
Review
: High-flow nasal cannula (HFNC) therapy has emerged as a promising treatment modality for interstitial lung disease (ILD)-related respiratory failure. This systematic review aims to evaluate the efficacy and safety of HFNC therapy in patients with ILDs. A comprehensive literature search was conducted using major electronic databases to identify relevant studies investigating the use of HFNC therapy in ILD patients with respiratory failure. Outcome measures of interest included improvements in oxygenation, dyspnea relief, respiratory rate control, hospital length of stay, and mortality. Twelve studies were analyzed with an overall population of 715 patients included. Idiopathic Pulmonary Fibrosis (IPF) was the most prevalent type of ILD. Evaluated clinical settings were acute (7 studies), chronic (2 studies), and end-stage (3 studies) ILDs. The HFNC as a support for acute respiratory failure seems not inferior to non-invasive ventilation while offering better comfort and patient's perception. Poor data are available about use in chronic/long-term or rehabilitative settings. In end of life/palliative care, an HFNC might improve quality of life. Despite the promising results, further research is warranted to establish optimal HFNC protocols, identify patient subgroups most likely to benefit, and explore long-term outcomes. Overall, the HFNC appears to be a valuable therapeutic option for managing respiratory failure in ILD patients, offering potential improvements in oxygenation and symptom relief.
PubMed: 38792497
DOI: 10.3390/jcm13102956 -
BMJ Paediatrics Open May 2024To review the efficacy of nebulised magnesium sulfate (MgSO) in acute asthma in children. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To review the efficacy of nebulised magnesium sulfate (MgSO) in acute asthma in children.
METHODS
The authors searched Medline, Embase, Web of Science and Cochrane Library for randomised controlled trials (RCTs) published until 15 December 2023. RCTs were included if they compared the efficacy and safety of nebulised MgSO as a second-line agent in children presenting with acute asthma exacerbation. A random-effects meta-analysis was performed, and the Risk of Bias V.2 tool was used to assess the biases among them.
RESULTS
10 RCTs enrolling 2301 children with acute asthma were included. All trials were placebo controlled and administered nebulised MgSO/placebo and salbutamol (±ipratropium bromide). There was no significant difference in Composite Asthma Severity Score between the two groups (6 RCTs, 1953 participants; standardised mean difference: -0.09; 95% CI: -0.2 to +0.02, I=21%). Children in the MgSO group have significantly better peak expiratory flow rate (% predicted) than the control group (2 RCTs, 145 participants; mean difference: 19.3; 95% CI: 8.9 to 29.8; I=0%). There was no difference in the need for hospitalisation, intensive care unit admission or duration of hospital stay. Adverse events were minor, infrequent (7.3%) and similar among the two groups.
CONCLUSIONS
There is low-certainty evidence that nebulised MgSO as an add-on second-line therapy for acute asthma in children does not reduce asthma severity or a need for hospitalisation. However, it was associated with slightly better lung functions. The current evidence does not support the routine use of nebulised MgSO in paediatric acute asthma management.
PROSPERO REGISTRATION NUMBER
CRD42022373692.
Topics: Humans; Magnesium Sulfate; Asthma; Child; Nebulizers and Vaporizers; Acute Disease; Administration, Inhalation; Bronchodilator Agents; Randomized Controlled Trials as Topic; Anti-Asthmatic Agents
PubMed: 38782483
DOI: 10.1136/bmjpo-2024-002638 -
Role of probiotic as adjuvant in treating various infections: a systematic review and meta-analysis.BMC Infectious Diseases May 2024Research on the advantages of probiotics has attracted increasing interest based on the number of publications, products, and public awareness of their benefits. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Research on the advantages of probiotics has attracted increasing interest based on the number of publications, products, and public awareness of their benefits. This review evaluated the role of probiotics (single and multiple regimens) as an additional regimen to treat common infectious diseases, including Helicobacter. pylori, diarrheal infections, urinary tract infections (UTIs), upper respiratory tract infections (URTIs), and HIV infections.
METHODS
We searched randomized controlled trials from PubMed, Scopus, Embase, and Cochrane and identified 6,950 studies. Duplicates were removed, and titles and abstracts were filtered. Bias was evaluated using the Cochrane Risk of Bias Tool for Randomized Trials (ROB 1.0 and 2.0). The certainty of the evidence was evaluated using GRADE. Data were extracted and meta-analysis was performed using RevMan.
RESULTS
A total of 32 studies were included in this study (22 H. pylori studies, 2 diarrheal infection studies, 6 UTI studies, and 2 HIV infection studies). There was no study on URTI. Probiotics, in addition to primary treatment, could improve the eradication of H. pylori versus the control (RR: 1.09; 95% CI:1.04 - 1.13, p value = 0.001) and achieve a cure range of Nugent score in UTI patients (RR 1.38; 95% CI: 1.01 - 1.89, p value = 0.04). For eradicating H. pylori infection, subgroup analysis based on the therapy regimen showed that standard triple therapy was slightly superior compared to quadruple therapy in eradicating H. pylori (RR: 1.14 vs. 1.01, respectively). Single strain probiotics showed a similar effect to multiple strain probiotic regimens (both had an RR of 1.09). The effect estimates of the use of single strain probiotics as adjuvant therapy in eradicating H. pylori and the use of probiotics in UTI had a high certainty of evidence. Meta-analysis was not performed for infectious diarrheal because there were only two eligible studies with different probiotic supplementations and outcome parameters. Nonetheless, they showed that the diarrheal incidence was lower and complete remission of diarrheal was higher after the regimen of probiotics. Similarly, a meta-analysis was not performed for HIV infection because the two eligible studies used different designs and comparators with contradicting findings.
CONCLUSION
This meta-analysis showed beneficial use of single strain probiotics as adjuvant therapy in eradicating H. pylori and the use of probiotics in UTI. Probiotic supplementation might not be beneficial for patients given a quadruple therapy. Single-strain and multi-strain probiotic regimens had similar effects in increasing the eradication rate of H. pylori. Our study also suggested that the benefits of probiotics as an additional regimen in infectious diarrheal and HIV infections remain unclear; more studies are needed to confirm the benefits.
Topics: Probiotics; Humans; Diarrhea; Helicobacter Infections; Urinary Tract Infections; Respiratory Tract Infections; HIV Infections; Randomized Controlled Trials as Topic; Treatment Outcome; Helicobacter pylori
PubMed: 38773400
DOI: 10.1186/s12879-024-09259-3