Large-scale Randomized Controlled Trials Research Articles

Impact of allogenic Fecal Microbiota Transplantation (FMT) on lipid parameters in patients with metabolic syndrome (MetS): a meta-analysis

Abstract Background Metabolic Syndrome (MetS) has long been considered a formidable global health concern, and impaired lipid metabolism has been one of its crucial clinical manifestations. Fecal Microbiota Transplantation (FMT) has emerged as a potential therapeutic strategy for MetS, nevertheless, prior meta-analyses have not only yielded conflicting outcomes, but as well predominantly centered on glycemic parameters, leaving the potential impact of FMT on lipid metabolism remained unexplored. Purpose This meta-analysis systematically assessed the influence of allogenic FMT on lipid parameters in MetS patients, unraveling its potential as an innovative therapeutic modality for MetS. Methods A meta-analysis was performed to explore the impact of allogenic FMT on lipid parameters (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TCHO] and triglycerides [TG]) in patients with MetS. Terms regarding FMT and metabolic syndrome were searched in PubMed/Medline, EMBASE, Web of Science, the Cochrane Library, and Scopus from the inception of the databases until 31 August 2023. Ten randomized controlled trials (RCTs) were included and mean difference (MD) of parameters were pooled using a fixed effects model. Subgroup analyses according to follow-up durations were performed, and this study was registered in PROSPERO. Results A total of 532 patients in 10 studies were included. Patients undergoing allogenic FMT manifested significantly higher HDL-c level compared with control group (receiving placebo or autologous FMT, pooled MD 0.06 [95% CI: 0.02, 0.10]), and the result remained consistent in the subgroup with 4 to 6 weeks of follow-up (MD 0.07 [95% CI: 0.02, 0.10]). Though overall pooled result did not manifest a significant LDL lowering effect (MD -0.08 [95% CI: -0.21, 0.05]), in subgroup analyses, a significantly lowered LDL level was observed at 12 weeks of follow-up (MD -0.34 [95% CI: -0.60, -0.08]). No significant difference was observed between allogenic FMT and control group concerning TCHO ant TG levels regardless of lengths of follow-up. Conclusions An overall higher level of HDL-C and lowered LDL-C at 12 weeks of follow-up was observed in MetS patients receiving allogenic FMT. The results indicated that gut microbiota from lean, healthy donors may display a beneficial effect on modulating lipid metabolism in patients with MetS. Allogenic FMT manifested promising therapeutic impact and could serve as a viable intervention for MetS patients. Future large-scale RCTs are required for further validation.

Interventions to reduce opioid use for patients with chronic non-cancer pain in primary care settings: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to assess interventions to reduce opioid use for patients with chronic non-cancer pain (CNCP) versus usual care or active controls in primary care settings. In this registered study (PROSPERO: CRD42022338458), we searched MEDLINE, Embase PsycInfo, CINAHL, and Cochrane Library from inception to December 28th 2021, and updated on Dec 14th 2023 for randomized controlled trials (RCTs) and cohort studies with no restrictions. Methodological quality was assessed using the Cochrane Risk of Bias tool for RCTs and Newcastle Ottawa Scale for cohort studies. Primary outcomes included mean reduction in morphine equivalent daily dose (reported as mean differences [MDs] mg/day; 95% confidence intervals [95%CIs]) and/or opioid cessation proportion. Secondary outcomes were mean changes in pain severity (reported as standardized mean difference [SMDs]; 95%CIs) and (serious) adverse events. Meta-analyses were performed using random-effects models. We identified 3,826 records, of which five RCTs (953 participants) and five cohort studies (901 participants) were included. Overall, opioid dosage was significantly reduced in intervention groups compared to controls (MD: -28.63 mg/day, 95%CI: -39.77 to -17.49; I2 = 31.25%; eight studies). Subgroup analyses revealed significant opioid dose reductions with mindfulness (MD: -29.36 mg/day 95%CI: -40.55 to -18.17; I2 = 0.00%; two trials) and CBT-based multimodalities (MD: -41.68 mg/day; 95%CI: -58.47 to -24.89; I2 = 0.00%; two cohort studies), respectively, compared to usual care. No significant differences were observed in opioid cessation (Odds ratio: 1.10, 95%CI: -0.48 to 2.67, I2 = 58.59%; two trials) or pain severity (SMD: -0.13, 95%CI: -0.37 to 0.11; I2 = 33.51%; three trials). Adverse events were infrequently examined, with withdrawal symptoms commonly reported. The studied interventions were effective in reducing opioid dosage for people with CNCP in primary care. They highlighted the importance of multidisciplinary collaboration. Large-scale RCTs measuring the long-term effects and cost of these interventions are needed before their implementation.

The efficacy and safety of intravenous tocilizumab to treat Graves' ophthalmopathy: A systematic review and single-arm meta-analysis.

This study aims to evaluate the efficacy and safety of intravenous tocilizumab (TCZ) in the treatment of Graves' ophthalmopathy (GO). A comprehensive search was conducted across the Web of Science, PubMed, Embase, Cochrane Library, World Health Organization International Clinical Trials Registry Platform, and https://ClinicalTrials.gov databases from inception to April 2024. Randomized controlled trials (RCTs) and cohort studies that utilized intravenous TCZ for treating GO were included. Twelve studies encompassing 219 patients with active, steroid-resistant GO were analyzed. The meta-analysis demonstrated significant improvements in Clinical Activity Score (CAS) response (effect size [ES] = 0.98, 95% confidence interval [CI]: 0.93-1.00), proptosis response (ES = 0.50, 95% CI: 0.27-0.73), and diplopia response (ES = 0.48, 95% CI: 0.24-0.74). The ES for adverse events was 0.27 (95% CI: 0.22-0.33), with only three severe cases necessitating treatment discontinuation, and a low reactivation rate (ES = 0.01, 95% CI: 0.00-0.04). TCZ treatment led to a mean CAS reduction of 4.60 points (95% CI: 3.88-5.32) across 10 studies, a mean proptosis reduction of 2.04 mm (95% CI: 1.42-2.65) across 7 studies, and a mean decrease in thyroid-stimulating hormone receptor antibodies (TRAb) levels of 10.62 IU (95% CI: 4.67-10.62) across 5 studies. This meta-analysis provides robust evidence supporting the efficacy and safety of intravenous TCZ in patients with GO who are resistant to glucocorticoid therapy. The results highlight TCZ's comparable efficacy to glucocorticoids and suggest that TCZ could significantly expand clinical management options for GO. In the future, more high-quality, large-scale RCTs are still needed to confirm these findings.

Functional Role of Extracellular Vesicles in Skeletal Muscle Physiology and Sarcopenia: The Importance of Physical Exercise and Nutrition.

Extracellular vesicles (EVs) play a key role in intercellular communication by transferring miRNAs and other macromolecules between cells. Understanding how diet and exercise modulate the release and content of skeletal muscle (SM)-derived EVs could lead to novel therapeutic strategies to prevent age-related muscle decline and other chronic diseases, such as sarcopenia. This review aims to provide an overview of the role of EVs in muscle function and to explore how nutritional and physical interventions can optimise their release and function. A literature review of studies examining the impact of exercise and nutritional interventions on MS-derived EVs was conducted. Major scientific databases, including PubMed, Scopus and Web of Science, were searched using keywords such as 'extracellular vesicles', 'muscle', 'exercise', 'nutrition' and 'sarcopenia'. The selected studies included randomised controlled trials (RCTs), clinical trials and cohort studies. Data from these studies were synthesised to identify key findings related to the release of EVs, their composition and their potential role as therapeutic targets. Dietary patterns, specific foods and supplements were found to significantly modulate EV release and composition, affecting muscle health and metabolism. Exercise-induced changes in EV content were observed after both acute and chronic interventions, with a marked impact on miRNAs and proteins related to muscle growth and inflammation. Nutritional interventions, such as the Mediterranean diet and omega-3 fatty acids, have also shown the ability to alter EV profiles, suggesting their potential to improve cardiovascular health and reduce inflammation. EVs are emerging as critical mediators of the beneficial effects of diet and exercise on muscle health. Both exercise and nutritional interventions can modulate the release and content of MS-derived EVs, offering promising avenues for the development of novel therapeutic strategies targeting sarcopenia and other muscle diseases. Future research should focus on large-scale RCT studies with standardised methodologies to better understand the role of EVs as biomarkers and therapeutic targets.

Compression-only versus standard cardiopulmonary resuscitation in out-of-hospital cardiac arrest: A meta-analysis of randomized controlled trials.

Bystander-initiated cardiopulmonary resuscitation (CPR) can improve survival rates in individuals with out-of-hospital cardiac arrest (OHCA). Two CPR approaches are commonly utilized, standard (S-CPR) with mouth-to-mouth breathing and compression-only (CO-CPR). We conducted a systematic review and meta-analysis to compare clinical outcomes associated with S-CPR versus CO-CPR in OHCA. A systematic literature search was conducted using PubMed, EMBASE, and the Cochrane Library. Eligible studies included randomized controlled trials (RCTs) focused on adult OHCA patients receiving CO-CPR or S-CPR. Forest plots were generated for pooled data analysis using Review Manager version 5.4. Random-effect analyses were used, and statistical significance was set at p < .05. Four randomized controlled trials were included in the final analysis, encompassing a total sample size of 4987 patients (2482 in the CO-CPR group and 2505 in the S-CPR group). CO-CPR was associated with significantly improved 1-day survival compared with S-CPR (OR = 1.15; 95% CI: 1.02-1.31; p = .03) and survival to hospital discharge (OR = 1.25; 95% CI: 1.01-1.55; p = .04). No heterogeneity was observed among the studies for either outcome. CO-CPR emerges as a promising strategy for improving outcomes in OHCA compared to S-CPR. However, further large-scale RCTs are required to generate more robust evidence.

Translational Cardiology: Practical Insights into the Coenzyme Q10 Role as Potential Therapeutic Agent for Cardiovascular Disease Treatment via Systematic Review and Meta-Analysis of Prospective Cohort Studies

Background and Objectives: As clinicians seek novel treatment strategies for CVDs, personalized nutrient recommendations are becoming essential. CoQ10, a key component of the mitochondrial electron transport chain, shows promise with proven cardioprotective effects. This systematic review and meta-analysis evaluates the efficacy of CoQ10 supplementation in improving mitochondrial function, systolic performance, and other parameters in CVD. Methods: Analysis included data from PubMed, Embase, and the Cochrane Library up to January 2024. It focused on randomized controlled trials (RCTs) involving adults with cardiovascular diseases (CVDs), comparing CoQ10 with placebo or standard care. Data extraction and quality assessment followed PRISMA guidelines, the Cochrane Collaboration's RoB2 tool, AMSTAR 2, and GRADE. The primary outcome was mitochondrial function (ATP production, respiratory capacity), and the secondary outcome was systolic function (ejection fraction). Findings: CoQ10 supplementation improved ejection fraction (mean difference: 5.6%, 95% CI: 3.2% to 8.0%, p&lt;0.001, I²=25%). The I² statistic for ejection fraction was 25%, indicating low heterogeneity. Mitochondrial function showed increased ATP production (SMD: 0.82, 95% CI: 0.60 to 1.04, p&lt;0.001, I²=30%) and enhanced respiratory capacity (SMD: 0.75, 95% CI: 0.53 to 0.97, p&lt;0.001, I²=28%). The I² statistics for ATP production and mitochondrial respiratory capacity were 30% and 28%, respectively, suggesting low to moderate heterogeneity. Sensitivity analyses confirmed the robustness of the results, with consistent effect sizes and confidence intervals across both fixed-effect and random-effects models, and no significant changes upon excluding high-risk studies. Publication bias was low, as indicated by funnel plots and Egger's test (p=0.12). Limitations: Larger-scale RCTs are needed to confirm findings and determine the optimal dosage and duration of CoQ10 therapy. Conclusion: CoQ10 has been consistently shown to improve mitochondrial function, systolic performance, and other key cardiovascular health parameters in CVD patients. The evidence here presented strongly bridges the gaps between the current research and clinical applications and supports clinicians in implementing the prescription of CoQ10 supplementation as an intervention evidence-based therapeutic agent that effectively improves cardiovascular health outcomes

The impact of yoga therapy on lumbar intervertebral disc prolapse: A systematic review

ABSTRACT This systematic review is aimed to evaluate the effect of yoga therapy on lumbar intervertebral disc prolapse (LIVDP) also known as lumbar disc herniation (LDH). Databases such as PubMed/Medline, Cochrane Library, Science Direct, and search engine Google Scholar were searched from 2007 to 2024. Randomized control trials (RCTs), case studies, and quasi-experimental studies involving yoga therapy and LIVDP/LDH were included in the study. The PRISMA guidelines were followed to extract the 10 articles for the study. The primary outcomes included disability scores, pain intensity, nerve conduction, and structural changes. 10 studies involving 546 patients were included in the study. The average sample size of the studies was 54.6 patients. The length of intervention varied from 3 weeks to 4 months with an average of 2 sessions/week. This study demonstrated that yoga therapy is an effective, affordable, and preventive treatment for LIVDP and low back pain. However, additional high-quality, large-scale RCTs and studies are needed for clinically significant results.

Minimally invasive vs. conventional mitral valve surgery: a meta-analysis of randomised controlled trials.

The evidence underlying the efficacy and safety of minimally invasive mitral valve surgery (MIMVS) is inconclusive. We conducted a meta-analysis to evaluate whether MIMVS improves clinical outcomes compared with conventional sternotomy. We searched MEDLINE (via PubMed), Embase, the Cochrane Library, and ClinicalTrials.gov from inception to January 2024 for all randomised controlled trials (RCTs), comparing MIMVS with conventional mitral valve surgery. RevMan 5.4 was used to analyse the data with risk ratio (RR) and mean difference (MD) as the effect measures. Eight studies reporting data on 7 RCTs were included in our review. There was no significant difference in all-cause mortality, the number of patients requiring blood product transfusion, and the change from baseline in the SF-36 physical function scores between the MIMVS and conventional sternotomy groups. MIMVS reduced the length of hospital stay (MD -2.02 days, 95% CI: -3.66, -0.39) but did not affect the length of ICU stay, re-operation for bleeding, and the incidence of renal injury, wound infection, neurological events, and postoperative moderate or severe mitral regurgitation. MIMVS was associated with a trend toward lower postoperative pain scores (MD -1.06; 95% CI: -3.96 to 0.75). MIMVS reduced the number of days spent in the hospital and showed a trend toward lower postoperative pain scores, but it did not decrease the risk of all-cause mortality or the number of patients needing blood product transfusions. Further large-scale RCTs are required to inform definitive conclusions, particularly with regard to quality-of-life outcomes investigating functional recovery. PROSPERO (CRD42023482122).

Long COVID Brain Fog Treatment: Findings from a Pilot Randomized Controlled Trial of Constraint-Induced Cognitive Therapy.

Long COVID brain fog is often disabling. Yet, no empirically-supported treatments exist. This study's objectives were to evaluate feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae. Sixteen community-residents ≥ 3-months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment-as-usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive-training program. CICT was deemed feasible if (a) ≥80% of participants completed treatment, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) <2 study-related, serious adverse-events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed. Fourteen completed Immediate-CICT (n=7) or TAU (n=7); two withdrew from TAU before their second testing session. Completers were [M (SD)]: 10 (7) months post-COVID; 51 (13) years old; 10 females, 4 males; 1 African American, 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M=3.7 points, p<.001, d=2.6) and brain fog (M=-4 points, p<.001, d=-2.9). Four of five non-retired Immediate-CICT participants returned-to-work post-treatment; no TAU participants did, p=.048. CICT has promise for reducing brain fog, improving IADL, and promoting returning-to-work in adults with Long COVID. Findings warrant a large-scale RCT with an active-comparison group.

The Role of Dietary Patterns and Nutritional Supplements in the Management of Mental Disorders in Children and Adolescents: An Umbrella Review of Meta-Analyses: Le rôle des habitudes alimentaires et des suppléments nutritionnels dans la prise en charge des troubles mentaux chez les enfants et les adolescents : une méta-revue de méta-analyses.

In recent years, the relationship between nutrition and mental health has gained considerable interest. We identified, synthesized, and appraised all meta--analyses of randomized controlled trials (RCTs) and observational studies reporting on the efficacy of dietary patterns and nutrient supplements in the prevention and treatment of mental disorders in children and adolescents. Systematic research in MEDLINE, PsycINFO, Scopus, and Cochrane Database of Systematic Reviews was completed on 8 January 2024. Our research found 24 meta-analyses: 14 on RCTs, 8 on observational studies, and 2 combining both. Emerging evidence suggests that omega-3, in particular eicosapentaenoic acid, and Vitamin D may have adjunctive benefits in the treatment of attention deficit hyperactivity disorder (ADHD), while no evidence was found for autism spectrum disorder (ASD). Observational data also indicated that prenatal folic acid supplementation (>400 μg daily) was associated with a reduced risk of ASD in offspring. In terms of dietary habits, several meta-analyses of observational data revealed that healthy dietary patterns (rich in fruits, vegetables, and fibre, low in saturated fats) during the prenatal period, childhood, and adolescence were linked to a significantly reduced risk of internalizing disorders and externalizing disorders. Conversely, unhealthy dietary habits (high in sugars, saturated animal fats, and industrial foods, low in fruits, vegetables, and fibre) are associated with an elevated risk of these mental health issues. However, the number of available studies on dietary interventions for the treatment of depression, ASD, and ADHD was limited, and the results obtained were either nonsignificant or contradictory. Our findings emphasize the need to establish clear causal relationships between dietary habits and the risk of mental illness in children and adolescents. Moreover, further investigation of the benefits observed with some nutrient supplements (such as omega-3 and vitamin D for ADHD) through larger-scale RCTs is imperative to establish more robust conclusions.

Lipid-lowering therapies and long-term stroke prevention in East Asians: A systematic review and meta-analysis of randomized controlled trials.

Stroke prevention is a pressing global health priority, with reducing elevated lipids recognized as a key strategy. East Asians, constituting more than 1.6 billion individuals and the largest racial group worldwide, are a key demographic in this effort. Yet, the effectiveness of lipid-lowering therapies for stroke prevention in this population remains uncertain. We conducted a systematic review and meta-analysis of large-scale randomized controlled trials (RCTs) with at least 3 years of follow-up to evaluate the long-term impact of lipid-lowering therapies on stroke incidence in East Asians. We systematically searched four electronic databases up to 11 January 2024. The association was quantified using relative risk (RR) with a 95% confidence interval (CI), and between-study heterogeneity was evaluated using the I2 statistic. In addition, we utilized the Cochrane Risk of Bias Tool to assess the risk of bias in each included RCT and applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to evaluate the certainty of the evidence. This study incorporated data from nine large-scale RCTs involving 54,354 participants. Our findings of overall analyses revealed that lipid-lowering therapies did not significantly affect the long-term incidence of all strokes (9 RCTs; 54,354 participants; RR = 0.98 (95% CI = 0.87-1.10); P = 0.75), ischemic stroke (7 RCTs; 52,059 participants; RR = 0.91 (95% CI, = 0.79-1.04); P = 0.16), or hemorrhage stroke (7 RCTs; 52,059 participants; RR = 1.24 (95% CI = 0.97-1.59); P = 0.09) in East Asians. Notably, there was no evidence of heterogeneity or publication bias, and the quality of evidence assessed using GRADE methodologies was rated as high. Sensitivity analyses confirmed the robustness of our results, with no single study significantly affecting the overall findings. Furthermore, subgroup analyses consistently supported the conclusions, further bolstering the reliability of our study. Lipid-lowering therapies did not demonstrate any beneficial effects on long-term stroke prevention among East Asians.

The recombinant shingles vaccine is associated with lower risk of dementia

There is emerging evidence that the live herpes zoster (shingles) vaccine might protect against dementia. However, the existing data are limited and refer only to the live vaccine, which is now discontinued in the United States and many other countries in favor of a recombinant vaccine. Whether the recombinant shingles vaccine protects against dementia remains unknown. Here we used a natural experiment opportunity created by the rapid transition from the use of live to the use of recombinant vaccines to compare the risk of dementia between vaccine types. We show that the recombinant vaccine is associated with a significantly lower risk of dementia in the 6 years post-vaccination. Specifically, receiving the recombinant vaccine is associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected. The recombinant shingles vaccine was also associated with lower risks of dementia than were two other vaccines commonly used in older people: influenza and tetanus–diphtheria–pertussis vaccines. The effect was robust across multiple secondary analyses, and was present in both men and women but was greater in women. These findings should stimulate studies investigating the mechanisms underpinning the protection and could facilitate the design of a large-scale randomized control trial to confirm the possible additional benefit of the recombinant shingles vaccine.

Liver resection had better disease-free survival rates compared with radiofrequency ablation in hepatocellular carcinoma: A meta-analysis based on randomized clinical trials.

Liver resection (LR) and radiofrequency ablation (RFA) are the most commonly used treatment modalities for early-stage hepatocellular carcinoma (ES-HCC). The comparative efficacy of LR and RFA in ES-HCC remains debated. We conducted a meta-analysis based on randomized trials to compare the outcomes of LR and RFA. We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing RFA and LR interventions for the treatment of ES-HCC. The primary outcomes were overall survival (OS) and disease-free survival (DFS). We used meta-regression to determine the source of heterogeneity and conducted a trial sequential analysis to examine whether the outcome was statistically reliable. Our meta-analysis included nine RCTs with a total of 1,516 HCC patients. Compared with patients receiving RFA, those receiving LR did not have significantly different 2-year OS (HR=1.28, 95% CI: 0.73-2.23) and 5-year OS (HR=1.49, 95% CI: 0.99-2.24). However, patients receiving LR showed a favorable trend in 2-year DFS (HR=1.40, 95% CI: 1.16-1.69) and 5-year DFS (HR=1.37; 95% CI: 1.05-1.77), although these results are not conclusive due to underpowered significance. The heterogeneity was low, and the outcomes were statistically reliable. Meta-analysis suggests that while LR shows a favorable trend in DFS compared to RFA for ES-HCC, the present evidence does not thoroughly support recommending LR over RFA. The inconclusive nature of these findings highlights the need for further large-scale RCTs to establish definitive comparative efficacy.

Efficacy and safety of direct oral anticoagulants versus warfarin in the treatment of cerebral venous sinus thrombosis.

Given the evolving application and promising outcomes of direct oral anticoagulants (DOACs) in various thromboembolic conditions, we aimed to compare the efficacy and safety of DOACs with warfarin in the post-acute treatment of cerebral venous sinus thrombosis (CVST) using clinical and radiological parameters. A total of 140 CVST patients were enrolled, with 95 receiving warfarin and 45 receiving DOACs as post-acute treatment. Clinical and imaging parameters of the patients in follow-up visits were investigated, including the last modified Rankin Scale (mRS), venousthromboembolic events, CVST recurrence, mortality rate, recanalization status, and hemorrhagic events, to compare the efficacy and safety of treatment between the two groups. At baseline, patients' assessments using two prognostic scores, ISCVT-RS and IN-REvASC, revealed that there was no statistically significant difference in the distribution of prognostic risk categories between the warfarin and DOACs groups. Following acute therapy, patients in the warfarin and DOACs groups were followedup forthemedian of359 and325days, respectively. Analysis to compare the efficacy of warfarin and DOACs revealed no significant difference in last mRS scores, CVST recurrencerate, venousthromboembolic events, and recanalizationstatus between the two groups. Additionally, there was no statistically significant difference in the risk of hemorrhagic events between warfarin and DOACsgroups. Our findings show that DOACs have comparable safety and efficacy in the post-acute treatment of CVST patients; however, large-scalerandomized controlled trials are required to validate our findings.

Medical Assistant Health Coaching for Type 2 Diabetes in Primary Care: Results From a Pragmatic Cluster Randomized Controlled Trial.

This cluster (clinic-level) randomized controlled trial (RCT) compared medical assistant (MA) health coaching (MAC) with usual care (UC) among at-risk adults with type 2 diabetes in two diverse real-world primary care environments: a federally qualified health center (FQHC; Neighborhood Healthcare) and a large nonprofit private insurance-based health system (Scripps Health). A total of 600 adults with type 2 diabetes who met one or more of the following criteria in the last 90 days were enrolled: HbA1c ≥8% and/or LDL cholesterol ≥100 mg/dL and/or systolic blood pressure (SBP) ≥140 mmHg. Participants at MAC clinics received in-person and telephone self-management support from a specially trained MA health coach for 12 months. Electronic medical records were used to examine clinical outcomes in the overall sample. Behavioral and psychosocial outcomes were evaluated in a subsample (n = 300). All clinical outcomes improved significantly over 1 year in the overall sample (P < 0.001). The reduction in HbA1c was significantly greater in the MAC versus UC group (unstandardized Binteraction = -0.06; P = 0.002). A significant time by group by site interaction also showed that MAC resulted in greater improvements in LDL cholesterol than UC at Neighborhood Healthcare relative to Scripps Health (Binteraction = -1.78 vs. 1.49; P < 0.05). No other statistically significant effects were observed. This was the first large-scale pragmatic RCT supporting the real-world effectiveness of MAC for type 2 diabetes in U.S. primary care settings. Findings suggest that this team-based approach may be particularly effective in improving diabetes outcomes in FQHC settings.

Effect of exercise on postoperative recovery of patients with non-small cell lung cancer: a systematic review and meta-analysis

Patients with non-small cell lung cancer (NSCLC) in the postoperative recovery period often experience reduced exercise capacity and impaired lung function, which affects their overall quality of life. This paper investigated the effect of exercise interventions on exercise capacity, lung function, quality of life, and symptoms in these patients. Methods: We performed a literature search across Cochrane, Embase, PubMed, Web of Science, and EBSCO databases were comprehensively searched for randomized controlled trials (RCTs) from inception to September 2023, all English RCTs were eligible if they assessed the effects of exercise interventions on postoperative NSCLC patients. Results: Twelve articles met our inclusion criteria, evidencing that exercise interventions could significantly improve the functional capacity of NSCLC patients in postoperative recovery. Notably, Forced Expiratory Volume in 1 s (FEV1) was improved, indicating enhanced lung function. Furthermore, exercise improved the physical and mental health scores of SF-36, along with increased quadriceps strength and relieved dyspnea. However, fatigue levels were not significantly changed. Conclusions: Exercise interventions of NSCLC patients in the postoperative recovery are associated with improved functional capacity, lung function, quality of life, and quadriceps strength, as well as alleviated symptoms of dyspnea. These findings underscore the potential benefits of incorporating exercise into postoperative care for NSCLC patients. Nonetheless, further large-scale RCTs are required to solidify the evidence base on the clinical outcomes of exercise following pneumonectomy.

The efficacy and safety of Xiao-Ban-Xia-Tang in the treatment of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent and critical side effects due to chemotherapeutics. In China, Xiao-Ban-Xia-Tang (XBXT) has already been applied extensively to prevent and treat CINV. However, there is limited testimony on the effectiveness and safety of this purpose, and there was no correlative systematic review. The aim of this review was to systematically evaluate the effectiveness and safety of XBXT in preventing and treating CINV. The systematic search was conducted in eight databases to acquire randomized controlled trials (RCTs) that appraised the effect of XBXT in treating CINV. The vomiting and nausea relief efficiency, eating efficiency, quality of life, and adverse reactions were explored for efficacy assessment. Bias risk was rated by manipulating the Cochrane risk of bias tool 2.0 (RoB 2). The retrieved investigations were analyzed by utilizing ReviewManager 5.4 and Stata 17.0. The quality of evidence was evaluated adopting the GRADE tool. A total of 16 clinical RCTs of XBXT in the treatment of CINV were incorporated into the investigation, with a total of 1246 participants. The meta-analysis showed that compared with conventional antiemetic drugs, XBXT and antiemetics improved the vomiting relief efficiency (RR 1.35, 95% confidence interval: 1.25-1.46, p < 0.00001), nausea relief efficiency (N = 367, RR 1.23, 95% CI: 1.09-1.38, p < 0.00001), and quality of life (RR = 1.37, 95% CI: 1.14-1.65, p = 0.0009) and reduced the adverse events (N = 370, RR 0.53, 95% CI: 0.29-0.96, p = 0.04). XBXT and DARAs raised eating efficiency compared with DARAs (N = 208, RR 1.30, 95% CI: 1.07-1.57, p = 0.007). The data existed as statistically significant, and the publication bias was identified as relatively low from the funnel plot and trim and fill analysis. In addition, sensitivity analysis demonstrated robust outcomes. The quality of evidence for each outcome ranged from moderate to high. There is some encouraging evidence that XBXT and antiemetics had better therapeutic effects and safety in treating CINV than antiemetic drugs alone. The quality assessment and low publication bias indicated that the overall criterion was scientific. Better research is required to verify the evidence designed with large-scale RCTs and rigorous methods.

Effect of JAK Inhibitors on the Risk of Death in Patients with Moderate to Severe COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The pathophysiology of COVID-19 involves a signalling pathway based on the Janus kinases (JAKs) and the signal transducer and activator of transcription (STAT) family of proteins. As such, there has been growing interest in exploring JAK inhibitors as potential therapeutic agents for this disease. To provide a comprehensive summary of the efficacy of JAK inhibitors in the treatment of COVID-19 through a systematic review and meta-analysis. A systematic literature search was conducted in multiple electronic databases (PubMed, Scopus, and the Cochrane Central Register of Controlled Trials) and preprint repositories, without language restrictions, to identify relevant studies published up to December 31, 2023. The primary outcome of interest was all-cause mortality. Randomized controlled trials (RCTs) investigating the administration of JAK inhibitors in patients with COVID-19 were included. Through the systematic literature search, a total of 20 RCTs meeting the inclusion criteria were identified. A random-effects model was employed to estimate the pooled odds ratio for death with administration of a JAK inhibitor relative to non-administration of such an agent, with 95% confidence interval. Meta-analysis of these trials revealed a significant reduction in mortality among patients with COVID-19 who received JAK inhibitors relative to those who did not receive these agents (pooled odds ratio 0.70, 95% confidence interval 0.58-0.84). The results of this systematic review and meta-analysis suggest that JAK inhibitors, specifically baricitinib, may address the urgent need for effective treatments in the ongoing COVID-19 pandemic by reducing the risk of death among affected patients. However, further research, including larger-scale RCTs, is needed to establish the efficacy and safety of other JAK inhibitors in the treatment of COVID-19 and to generate more robust evidence regarding their use in this specific patient population.

Benchmarking the transcriptomic predictive biomarkers for immunotherapy plus chemotherapy: Results from phase III RATIONALE-309 and ORIENT-11 randomized trials.

e14624 Background: The combination of PD-(L)1 inhibitors and chemotherapy (IO+Chemo) has become the standard first-line treatment for multiple types of cancer. In contrast to PD-(L)1 monotherapy, there is a lack of established biomarkers to distinguish the outcomes of IO+Chemo. The paucity of high-quality omics data in this setting has not allowed for deep biomarker exploration. We utilized RNA-seq data from two in-house randomized controlled trials (RCTs), RATIONALE-309 and ORIENT-11, with the goal to find transcriptomic biomarkers to identify patients who may not derive benefit from IO+Chemo. Methods: RATIONALE-309 (NCT03924986) was a phase 3 study conducted at 42 sites in Asia. Treatment-naive recurrent/metastatic nasopharyngeal cancer patients were randomly allocated to either PD-1 inhibitor tislelizumab or placebo plus gemcitabine and cisplatin. ORIENT-11 (NCT03607539) was a phase 3 study that enrolled patients from 47 centers in China who had previously untreated locally advanced/metastatic nonsquamous non-small cell lung cancer. Patients were randomized to PD-1 inhibitor sintilimab or placebo plus pemetrexed and platinum. We compared several immune-related biomarkers, including IFN-γ signature, PD-L1, cytolytic score (CYT), T-cell inflamed gene expression profile, B cell infiltration, and ESTIMATE immune score, and explored the optimal predictive threshold. Results: In the RATIONALE-309 and ORIENT-11 trials, 247 and 171 patients with RNA-seq data were analyzed, respectively. Although the addition of Chemo to IO could theoretically benefit tumors with low immune activation, we hypothesized that patients might not benefit from IO+Chemo if their activation level is extremely low. We first tested the predictiveness of several thresholds (20-50th quantiles) for each selected biomarker in the two RCTs. We found that low CYT and B cell are the two best indicators for identifying a lack of survival benefits from IO+Chemo versus Chemo, especially when using 20-30th quantile as threshold. To incorporate their distinct biological information and predictive value, we combined their genes into a single gene signature to represent immune activation. We found that patients in the lower quantile (&lt;20th) showed no benefit of IO+Chemo over Chemo in terms of overall survival (OS) (RATIONALE-309: HR=1.01, P=0.99; ORIENT-11: HR=1.54, P=0.31) and progression-free survival (PFS) (RATIONALE-309: HR=0.76, P=0.42; ORIENT-11: HR=1.30, P=0.52). Moreover, this lack of advantage was maintained in key subgroups such as PD-L1-positive patients and former/current smokers across the two RCTs. Conclusions: Based on the two large-scale RCTs, our findings have implications for the selection of biomarkers when identifying suitable candidates for IO+Chemo treatment. B cells and CYT are crucial components required for the efficacy of IO+Chemo.

Effect of probiotics on cognitive function in adults with mild cognitive impairment or Alzheimer's disease: A meta-analysis of randomized controlled trials

BackgroundRecent clinical studies have yielded controversial results regarding the effect of probiotics on cognitive function in Alzheimer's disease (AD) or mild cognitive impairment (MCI) subjects. To clarify the efficacy of probiotics on cognition, we conducted a meta-analysis of randomized controlled trials (RCTs). MethodsInstructions of the PRISMA 2020 statement were followed. Literature from the PubMed, Embase and Cochrane databases were systematically searched and manually screened for relevant published RCTs. We performed statistical analysis using RevMan, and assessed the risk of bias using the R software. ResultsA total of 12 studies comprising 852 patients with MCI or AD were identified. The results of meta-analysis showed that probiotics improved global cognitive function (SMD=0.67; 95% CI, 0.32, 1.02), recall/delayed memory (SMD=0.67; 95% CI: 0.32, 1.02), attention (SMD=0.31; 95% CI: 0.04, 0.58) and visuospatial/constructional (SMD=0.24; 95% CI: 0.06, 0.42) cognitive domain. ConclusionThis meta-analysis found that probiotic supplementation is associated with an improvement in cognitive performance among patients with AD and MCI. However, current evidence is limited, and more reliable large-scale RCTs with higher methodological quality are needed.