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BMC Geriatrics Jun 2024Depression is a prevalent issue among older adults, affecting their quality of life and overall well-being. Exercise is an effective means of relieving depressive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Depression is a prevalent issue among older adults, affecting their quality of life and overall well-being. Exercise is an effective means of relieving depressive symptoms in older adults, but the optimal dose for different exercise types remains unclear. As such, the aim of this meta-analysis was to examine the dose-response relationship between overall and specific types of exercise with depression symptoms in older adults.
METHODS
This systematic review and network meta-analysis included a search of PubMed, Medline, Embase, PsycINFO, Cochrane library, and Web of Science for randomized controlled trials of exercise in older adults with depression symptoms from inception to 15 July 2023. Comprehensive data extraction covered dose, treatment regimen, demographics and study duration. Dosage metrics, encompassing METs-min/week, were scrutinized in correlation with the Minimal Clinically Importance Difference (MCID).
RESULTS
A total of 47 studies involving 2895 participants and 7 kinds of exercise were included in the review. Without considering the dose, the results of our network meta-analysis indicated that Walking was the most effective in alleviating depression in older adults, in addition to Aerobic exercise (AE), Yoga, Qigong, Resistance training (RT), and Tai Chi (TC), which were equally effective. However, the results of the dose-response analysis found that Aerobic exercise was most effective at a dose of 1000 METs-min/week. It is noteworthy that Walking is significantly effective in alleviating depressive symptoms in older adults at very low doses. In terms of clinical benefits, we found that overall exercise doses in the range of 600 ~ 970 METs-min/week were clinically effective. Considering the specific types of exercise, Aerobic exercise, Resistance training, Walking, and Yoga were found to be effective at doses ranging from 820 ~ 1000 METs-min/week, 520 ~ 1000 METs-min/week, 650 ~ 1000 METs-min/week, 680 ~ 1000 METs-min/week, respectively. At the same time, we found that when the age exceeded 81 years, even when participating in exercise, it did not achieve the effect of alleviating depressive symptoms in older adults.
CONCLUSIONS
In conclusion, including Walking, AE, Yoga, Qigong, RT, and TC, effectively alleviate depressive symptoms in older adults. Furthermore, we established statistically and clinically significant threshold doses for various exercise types. Early initiation of exercise is beneficial, but its efficacy diminishes from the age of 80, and beyond 81, exercise no longer significantly alleviates depressive symptoms.
Topics: Humans; Aged; Depression; Network Meta-Analysis; Exercise Therapy; Exercise; Randomized Controlled Trials as Topic
PubMed: 38849780
DOI: 10.1186/s12877-024-05118-7 -
Frontiers in Oncology 2024[This corrects the article DOI: 10.3389/fonc.2024.1363812.].
[This corrects the article DOI: 10.3389/fonc.2024.1363812.].
PubMed: 38846979
DOI: 10.3389/fonc.2024.1433346 -
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 -
Frontiers in Immunology 2024A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied.... (Meta-Analysis)
Meta-Analysis
Clinical outcomes of immune checkpoint inhibitor combined with other targeted or immunological therapy regimens for the treatment of advanced bile tract cancer: a systematic review and meta-analysis.
BACKGROUND AND AIMS
A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied. This meta-analysis aimed to evaluate the effectiveness and safety of ICI combination therapy for advanced BTC.
METHODS
The study protocol was registered on PROSPERO (CRD42023452422). Data on the median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade ≥3 adverse events (AEs) reported in relevant studies were pooled and analyzed to determine the efficacy and safety of ICI combination therapy.
RESULTS
In total, 15 studies with 665 patients were included in this meta-analysis. The overall ORR and DCR were 34.6% and 77.6%, respectively. The overall median PFS and OS were 6.06 months [95% confidence interval (CI): 4.91-7.21] and 12.11 months (95% CI: 10.66-13.55), respectively. Patients receiving ICI combination therapy in addition to other therapies had a considerably prolonged median PFS and OS (z=9.69, <0.001 and z=16.17, <0.001). Patients treated as first-line treatment had a substantially longer median PFS and OS compared to patients treated as non-first-line treatment (z=11.19, <0.001 and z=49.17, <0.001). The overall pooled grade ≥3 AEs rate was 38.2% (95% CI: 0.268-0.497) and was not influenced by whether ICI therapy was combined with other treatments or not or the treatment line.
CONCLUSION
Advanced BTC patients may benefit from ICI combination treatment without additional AEs. However, concurrent chemotherapy or radiotherapy is still needed to achieve better outcomes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023452422.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Biliary Tract Neoplasms; Immunotherapy
PubMed: 38840927
DOI: 10.3389/fimmu.2024.1378760 -
BMC Public Health Jun 2024Out-of-pocket (OOP) payment is one of many countries' main financing options for health care. High OOP payments push them into financial catastrophe and the resultant...
BACKGROUND
Out-of-pocket (OOP) payment is one of many countries' main financing options for health care. High OOP payments push them into financial catastrophe and the resultant impoverishment. The infrastructure, society, culture, economic condition, political structure, and every element of the physical and social environment influence the intensity of financial catastrophes in health expenditure. Hence, the incidence of Catastrophic Health Expenditure (CHE) must be studied more intensively, specifically from regional aspects. This systematic review aims to make a socio-ecological synthesis of the predictors of CHE.
METHOD
We retrieved data from Scopus and Web of Science. This review followed PRISMA guidelines. The interest outcomes of the included literature were the incidence and the determinants of CHE. This review analyzed the predictors in light of the socio-ecological model.
RESULTS
Out of 1436 screened documents, fifty-one met the inclusion criteria. The selected studies were quantitative. The studies analyzed the socioeconomic determinants from the demand side, primarily focused on general health care, while few were disease-specific and focused on utilized care. The included studies analyzed the interpersonal, relational, and institutional predictors more intensively. In contrast, the community and policy-level predictors are scarce. Moreover, neither of the studies analyzed the supply-side predictors. Each CHE incidence has different reasons and different outcomes. We must go with those case-specific studies. Without the supply-side response, it is difficult to find any effective solution to combat CHE.
CONCLUSION
Financial protection against CHE is one of the targets of sustainable development goal 3 and a tool to achieve universal health coverage. Each country has to formulate its policy and enact laws that consider its requirements to preserve health rights. That is why the community and policy-level predictors must be studied more intensively. Proper screening of the cause of CHE, especially from the perspective of the health care provider's perspective is required to identify the individual, organizational, community, and policy-level barriers in healthcare delivery.
Topics: Humans; Health Expenditures; Catastrophic Illness; Socioeconomic Factors; Financing, Personal
PubMed: 38840231
DOI: 10.1186/s12889-024-18579-7 -
Frontiers in Pharmacology 2024The efficacy of Chinese herbal medicine (CHM) in managing irritable bowel syndrome with diarrhea (IBS-D) accompanied by anxiety and depression remains uncertain. Thus, a...
Exploration of the mechanism of Traditional Chinese Medicine for anxiety and depression in patients with diarrheal irritable bowel syndrome based on network pharmacology and meta-analysis.
BACKGROUND
The efficacy of Chinese herbal medicine (CHM) in managing irritable bowel syndrome with diarrhea (IBS-D) accompanied by anxiety and depression remains uncertain. Thus, a systematic review was carried out employing meta-analysis and network pharmacology to ascertain the efficacy and underlying mechanisms of CHM therapy.
METHODS
By conducting a systematic review, including literature search, screening, and data extraction, we identified 25 randomized controlled trials to assess CHM's effectiveness in treating irritable bowel syndrome alongside anxiety and depression. Network pharmacology was utilized to scrutinize the metabolite utility of CHM in addressing this condition. Potential primary mechanisms were synthesized using information sourced from the PubMed database.
RESULTS
Twenty-five studies, including 2055 patients, were analyzed, revealing significant treatment efficacy for IBS-D in the trial group compared to controls [OR = 4.01, 95% CI (2.99, 5.36), I = 0%] Additionally, treatment for depression [SMD = -1.08, 95% CI (-1.30, -0.86), < 0.00001, I = 68%; SDS: SMD = -1.69, 95% CI (-2.48, -0.90), < 0.0001, I = 96%] and anxiety [HAMA: SMD = -1.29, 95% CI (-1.68, -0.91), < 0.00001, I = 89%; SAS: SMD = -1.75, 95% CI (-2.55, -0.95), < 0.00001, I = 96%] significantly improved in the trial group. Furthermore, the trial group exhibited a significantly lower disease relapse rate [OR = 0.30, 95% CI (0.20, 0.44), < 0.00001, I = 0%]. CHM treatment consistently improved IBS severity (IBS-SSS) and symptom scores. Network pharmacology analysis identified key chemical metabolites in traditional Chinese medicine formulations, including Beta-sitosterol, Stigmasterol, Quercetin, Naringenin, Luteolin, Kaempferol, Nobiletin, Wogonin, Formononetin, and Isorhamnetin. Utilizing the STRING database and Cytoscape v3.9.0 software, a protein-protein interaction (PPI) network revealed the top eight key targets: IL-6, TNF, PPARG, PTGS2, ESR1, NOS3, MAPK8, and AKT1, implicated in anti-inflammatory responses, antioxidant stress modulation, and neurotransmitter homeostasis maintenance.
CONCLUSION
Chinese Herbal Medicine (CHM) offers a promising and safe treatment approach for patients dealing with Diarrheal Irritable Bowel Syndrome (IBS-D) accompanied by anxiety and depression; thus, indicating its potential for practical implementation. The most active metabolites of CHM could simultaneously act on the pathological targets of IBS-D, anxiety, and depression.The diverse scope of CHM's therapeutic role includes various aspects and objectives, underscoring its potential for broad utilization.
PubMed: 38835657
DOI: 10.3389/fphar.2024.1404738 -
Cureus Jun 2024Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One... (Review)
Review
Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One of the most successful lines for inducing and maintaining clinical remission in subjects with UC is biological therapy with anti-tumor necrosis factor α (anti-TNF) agents, including adalimumab (ADA) and infliximab (IFX). This meta-analysis is an attempt to obtain complementary information driven by real-world experience (RWE) concerning the efficacy and safety of two of the most popular anti-TNFs in treating UC. This is a systematic review and meta-analysis of RWE studies comparing ADA and IFX as naïve anti-TNF agents for the treatment of subjects with UC. Studies were obtained by searching Scopus, Google Scholar, the Cochrane Central Register of Controlled Trials, Embase, and the PubMed Central databases. Patients treated with IFX showed significantly higher induction responses. No statistically significant difference was found in the comparison of response in the maintenance treatment period. Higher overall adverse events were related to IFX treatment, with serious adverse events that were nonsignificantly higher in the ADA-treated group. In conclusion, IFX demonstrated significantly higher induction responses compared to ADA in patients with moderate-to-severe UC. IFX was associated with higher overall adverse events, whereas serious adverse events were non-significantly higher in the ADA-treated group. IFX may be favored as a first-line agent for its induction efficacy, and the choice between IFX and ADA should be individualized based on comprehensive clinical evaluation.
PubMed: 38835557
DOI: 10.7759/cureus.61547 -
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 -
JAMA Network Open Jun 2024Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates.
OBJECTIVE
To assess the efficacy and tolerability of TNT protocols for LARC.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024.
STUDY SELECTION
Randomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria.
DATA EXTRACTION AND SYNTHESIS
Two authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach.
MAIN OUTCOMES AND MEASURES
The primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival.
RESULTS
Of 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63).
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments.
Topics: Rectal Neoplasms; Humans; Neoadjuvant Therapy; Network Meta-Analysis; Female; Middle Aged; Male; Randomized Controlled Trials as Topic; Adult
PubMed: 38833249
DOI: 10.1001/jamanetworkopen.2024.14702 -
Heliyon Jun 2024In recent years, the combination of targeted drugs, such as Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, with endocrine therapy (ET), has emerged as a new research...
BACKGROUND
In recent years, the combination of targeted drugs, such as Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, with endocrine therapy (ET), has emerged as a new research focus in the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer. This network meta-analysis aimed to systematically evaluate the efficacy and safety of CDK4/6 inhibitors combined with ET for HR+/HER2-breast cancer.
METHODS
A systematic search was conducted across PubMed, Web of Science, Cochrane Library, and GeenMedical databases to identify randomized controlled trials investigating the use of CDK4/6 inhibitors in combination with endocrine therapy for the treatment of HR+/HER2-breast cancer. The search period spanned from the inception of each database up to February 29, 2024. Data analysis was conducted using Stata 14.0 and R 4.1.0 software.
RESULTS
A total of 20 randomized controlled trials (RCTs) were included in this study, investigating the effectiveness of four CDK4/6 inhibitors-Abemaciclib, Dalpiciclib, Ribociclib, and Palbociclib-when combined with ET for the treatment of HR+/HER2-breast cancer. The results indicated that Abemaciclib + ET, Dalpiciclib + ET, Palbociclib + ET, and Ribociclib + ET exhibited similar therapeutic effects in terms of improving objective response rate (ORR), disease control rate (DCR) and reducing the occurrence of fatigue, all of which were superior to ET alone. However, in terms of prolonging progression-free survival (PFS) and overall survival (OS), Dalpiciclib + ET significantly improved PFS compared to Ribociclib + ET, Palbociclib + ET, Abemaciclib and Palbociclib. Ribociclib + ET significantly improved OS compared to Palbociclib + ET. Regarding overall adverse reaction events (AREs), Dalpiciclib + ET had a higher incidence compared to Ribociclib + ET. The incidence of neutropenia caused by Dalpiciclib + ET was significantly higher compared to Palbociclib + ET, Ribociclib + ET, Abemaciclib, and Palbociclib. Abemaciclib + ET demonstrated the worst safety profile concerning diarrhea.
CONCLUSION
Abemaciclib + ET likely represents the most effective option in terms of therapeutic effects, but it is prone to causing diarrhea and fatigue. On the other hand, Dalpiciclib + ET likely demonstrates the best efficacy in terms of PFS but exhibits the poorest safety profile, particularly in relation to neutropenia. Therefore, clinicians should exercise increased vigilance in monitoring and managing adverse effects when prescribing Abemaciclib + ET and Dalpiciclib + ET.
PubMed: 38832268
DOI: 10.1016/j.heliyon.2024.e31583