UNASSIGNED: The optimal first-line immunotherapy regimen for patients with PD-L1 expression ≥50% in squamous non-small cell lung cancer (Sq-NSCLC) remains uncertain. This study utilized net-work meta-analysis (NMA) to indirectly compare the efficacy of various first-line immuno-therapy regimens in this patient subset.
UNASSIGNED: Systematic searches were conducted across PubMed, the Cochrane Library, Web of Science, and Embase databases for randomized controlled trials reporting overall survival (OS) and progression-free survival (PFS) outcomes. The search spanned from database inception to November 3, 2023. Bayesian network meta-analysis was employed for a comprehen-sive analysis. To ensure scientific rigor and transparency, this study is registered in the Interna-tional Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42022349712.
UNASSIGNED: The NMA encompassed 9 randomized controlled trials (RCTs), involving 2170 patients and investigating 9 distinct immunotherapy regimens. For OS, the combination of camrelizumab and chemotherapy demonstrated the highest probability (36.68%) of efficacy, fol-lowed by cemiplimab (33.86%) and atezolizumab plus chemotherapy (23.87%). Regarding PFS, the camrelizumab and chemotherapy combination had the highest probability (39.70%) of efficacy, followed by pembrolizumab (22.88%) and pembrolizumab plus chemotherapy (17.69%). Compared to chemotherapy, first-line treatment with immune checkpoint inhibitors (ICIs) in Sq-NSCLC pa-tients exhibited significant improvements in OS (HR 0.59, 95% CI 0.47-0.75) and PFS (HR 0.44, 95% CI 0.37-0.52).
UNASSIGNED: This study suggests that, for Sq-NSCLC patients with PD-L1 expression ≥50%, the first-line immunotherapy regimen of camrelizumab plus chemotherapy provides superior OS and PFS outcomes. Furthermore, ICIs demonstrate enhanced efficacy compared to chemotherapy in this patient population.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier: CRD 42022349712.

OBJECTIVE: To investigate the impact of potential risk of bias elements on effect estimates in randomized trials.
METHODS: We conducted a systematic survey of meta-epidemiological studies examining the influence of potential risk of bias elements on effect estimates in randomized trials. We included only meta-epidemiological studies that either preserved the clustering of trials within meta-analyses (compared effect estimates between trials with and without the potential risk of bias element within each meta-analysis, then combined across meta-analyses; between-trial comparisons), or preserved the clustering of substudies within trials (compared effect estimates between substudies with and without the element, then combined across trials; within-trial comparisons). Separately for studies based on between- and within-trial comparisons, we extracted ratios of odds ratios (RORs) from each study and combined them using a random-effects model. We made overall inferences and assessed certainty of evidence based on Grading of Recommendations, Assessment, development, and Evaluation and Instrument to assess the Credibility of Effect Modification Analyses.
RESULTS: Forty-one meta-epidemiological studies (34 of between-, 7 of within-trial comparisons) proved eligible. Inadequate random sequence generation (ROR 0.94, 95% confidence interval [CI] 0.90-0.97) and allocation concealment (ROR 0.92, 95% CI 0.88-0.97) probably lead to effect overestimation (moderate certainty). Lack of patients blinding probably overestimates effects for patient-reported outcomes (ROR 0.36, 95% CI 0.28-0.48; moderate certainty). Lack of blinding of outcome assessors results in effect overestimation for subjective outcomes (ROR 0.69, 95% CI 0.51-0.93; high certainty). The impact of patients or outcome assessors blinding on other outcomes, and the impact of blinding of health-care providers, data collectors, or data analysts, remain uncertain. Trials stopped early for benefit probably overestimate effects (moderate certainty). Trials with imbalanced cointerventions may overestimate effects, while trials with missing outcome data may underestimate effects (low certainty). Influence of baseline imbalance, compliance, selective reporting, and intention-to-treat analysis remain uncertain.
CONCLUSIONS: Failure to ensure random sequence generation or adequate allocation concealment probably results in modest overestimates of effects. Lack of patients blinding probably leads to substantial overestimates of effects for patient-reported outcomes. Lack of blinding of outcome assessors results in substantial effect overestimation for subjective outcomes. For other elements, though evidence for consistent systematic overestimate of effect remains limited, failure to implement these safeguards may still introduce important bias.

Parkinson\'s disease-related constipation (PDC) is commonly associated with impaired dopamine transmission and gastrointestinal dysfunction. Current pharmacological treatments have limited efficacy and potential side effects. Acupuncture has shown promise as an alternative or adjunct therapy by modulating the brain-gut axis, gastrointestinal hormones, and autonomic function. Preliminary randomized trials have shown that acupuncture significantly improves constipation symptoms, bowel movements, and comfort compared to sham or drug treatments and is well-tolerated. The mechanisms of action may involve regulating the gut microbiota and mucosal immunity to improve dysbiosis and gastrointestinal motility. However, more rigorous studies are required to optimize acupuncture protocols and determine long-term efficacy and safety. In summary, acupuncture shows promise as an adjunct therapy for PDC, but further research is needed to confirm its efficacy and safety.

Currently, only a few specific blood pressure-lowering medications are recommended for migraine prevention. Whether benefits extend to other classes or drugs is uncertain.
Embase, MEDLINE, and the Cochrane Central Registry of Controlled Trials were searched for randomized control trials on the effect of blood pressure-lowering medications compared with placebo in participants with episodic migraine. Data were collected on four outcomes - monthly headache or migraine days, and monthly headache or migraine attacks, with a standardised mean difference calculated for overall. Random effect meta-analysis was performed.
In total, 50 trials (70% of which were crossover) were included, comprising 60 comparisons. Overall mean age was 39 years, and 79% were female. Monthly headache days were fewer in all classes compared to placebo, and this was statistically significant for all but one class: alpha-blockers -0.7 (95% CI: -1.2, -0.1), angiotensin-converting enzyme inhibitors -1.3 (95% CI: -2.9, 0.2), angiotensin II receptor blockers -0.9 (-1.6, -0.1), beta-blocker -0.4 (-0.8, -0.0) and calcium channel blockers -1.8 (-3.4, -0.2). Standardised mean difference was significantly reduced for all drug classes and was separately significant for numerous specific drugs: clonidine, candesartan, atenolol, bisoprolol, metoprolol, propranolol, timolol, nicardipine and verapamil.
Among people with episodic migraine, a broader number of blood pressure-lowering medication classes and drugs reduce headache frequency than those currently included in treatment guidelines.Trial Registration: The study was registered at PROSPERO (CRD42017079176).

UNASSIGNED: Vitamin D supplements may only be beneficial for the prevention of osteoporotic fractures when administered with calcium and in individuals with low blood levels of 25(OH)D, but possible hazards of calcium supplements on CVD cannot be excluded.
UNASSIGNED: We conducted a meta-analysis of all placebo-controlled randomized trials assessing the effects of calcium supplements alone or with vitamin D on CHD, stroke, and all-cause mortality.
UNASSIGNED: A meta-analysis of 11 trials included 7 comparisons of calcium alone compared with control (n = 8634) and 6 comparisons of calcium plus vitamin D compared with control (n = 46,804). Aggregated study-level data were obtained from individual trials and combined using a fixed-effects meta-analysis. The main outcomes included MI, CHD death, any CHD, stroke, and all-cause mortality.
UNASSIGNED: Among trials of calcium alone (mean daily dose 1 g), calcium was not significantly associated with any excess risk of MI (RR, 1.15; 95% CI: 0.88, 1.51; n = 219 events), CHD death (RR, 1.24; 95% CI: 0.89, 1.73; n = 142), any CHD (RR, 1.01; 95% CI: 0.75, 1.37; n = 177), or stroke (RR, 1.15; 95% CI, 0.90, 1.46, n = 275). Among 6 trials of combined treatment, supplementation with calcium plus vitamin D was not significantly associated with any excess risk of MI (RR, 1.09; 95% CI: 0.95, 1.25; n = 854), CHD death (RR, 1.04; 95% CI: 0.85, 1.27; n = 391), any CHD (RR, 1.05; 95% CI: 0.93, 1.19; n = 1061), or stroke (RR, 1.02; 95% CI: 0.89, 1.17; n = 885). Likewise, calcium alone, or with vitamin D had no significant associations with all-cause mortality.
UNASSIGNED: This meta-analysis demonstrated that calcium supplements were not associated with any significant hazard for CHD, stroke, or all-cause mortality and excluded excess risks above 0.3%-0.5% per year for CHD or stroke. Further trials of calcium and vitamin D are required in individuals with low blood levels of 25(OH)D for the prevention of fracture and other disease outcomes.

UNASSIGNED: Appropriate analyses and reporting are essential to the reproducibility and interpretation of clinical trials. However, the coronavirus disease 19 (COVID-19) pandemic and other force majeure events, like the war in Ukraine, have impacted the conduct of clinical trials.
UNASSIGNED: The number of clinical trials potentially impacted were estimated from clinicaltrials.gov. To identify reporting items considered vital for assessing the impact of COVID-19, we reviewed 35 randomized phase III trials from three top oncology journals published between July and December 2020. For validation, we reviewed 29 phase III trials published between January and December 2021.
UNASSIGNED: Our results show that the number of clinical trials being potentially impacted in cancer, cardiovascular diseases, and diabetes is at least 1,484, 535, and 145, respectively. The magnitude of disruption is most significant in oncology trials. Based on the review of 35 trials, a modified checklist with ten new and four modified items covering pandemic\'s impact on trial conduct, protocol changes, delays, data capture, analysis and interpretation was developed to ensure comprehensive and transparent reporting. Our validation shows that six out of seven applicable reporting items were reported in less than 21% of the articles.
UNASSIGNED: Our recommendations were proposed to improve the reporting of randomized clinical trials impacted by COVID-19 and force majeure events that are broadly applicable to different areas of medical research.

OBJECTIVE: This study aimed at quantifying and ranking the effects of different foods or food groups on weight loss.
METHODS: We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Embase to April 2021. We included randomized trials evaluating the comparative effects of two or more food groups, or compared a food group against a control group (usual diet, no intervention) for weight loss in adults. We conducted random-effects network meta-analysis with Bayesian framework to estimate mean difference [MD] and 95% credible interval [CrI] of the effect of food groups on weight loss.
RESULTS: 152 RCTs with 9669 participants were eligible. Increased consumption of fish (MD - 0.85 kg, 95% CrI - 1.66, - 0.02; GRADE = low), whole grains (MD - 0.44 kg, 95% CrI - 0.88, 0.0; GRADE = very low), and nuts (MD - 0.37 kg, 95% CI - 0.72, - 0.01; GRADE = low) demonstrated trivial weight loss, well below minimal clinically important threshold (3.9 kg), when compared with the control group. Interventions with other food groups led to no weight loss when compared with either the control group or other food groups. The certainty of the evidence was rated low to very low with the point estimates for all comparisons less than 1 kg. None of the food groups showed an important reduction in body weight when restricted to studies conducted in participants with overweight or obesity.
CONCLUSIONS: Interventions with a single food or food group resulted in no or trivial weight loss, especially in  individuals with overweight or obesity. Further trials on single foods or food groups for weight loss should be highly discouraged.

OBJECTIVE: Chemotherapy, when added to radiotherapy, improves survival in locally advanced nasopharyngeal carcinoma (NPC). This article presents the second update of the Meta-Analysis of Chemotherapy in NPC.
METHODS: Published or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified. Updated data were sought for studies included in the previous rounds of the meta-analysis. The primary endpoint was overall survival. All trials were analyzed following the intent-to-treat principle using a fixed-effects model. Treatments were classified in five subsets according to chemotherapy timing. The statistical analysis plan was pre-specified.
RESULTS: Eighteen new trials were identified. Individual patient data were available for seven. In total, the meta-analysis now included 26 trials and 7,080 patients. The addition of chemotherapy reduced the risk of death, with a hazard ratio (HR) of 0.79 (95% confidence interval (CI) [0.73; 0.85]), and an absolute survival increase at 5 and 10 years of 6.1% [+3.9; +8.3] and + 8.4% [+5.7; +11.1], respectively. The largest effect was observed for concomitant + adjuvant, induction (with concomitant in both arms) and concomitant chemotherapy, with respective HR [95%CI] of 0.68 [0.59; 0.79] (absolute survival increase at 5 years: 12.3% (7.0%;17.6%)), 0.73 [0.63; 0.86] (6.0% (2.5%;9.5%)) and 0.81 [0.70; 0.92] (5.2% (0.8%;9.6%)). The benefit of chemotherapy was also demonstrated by improvement in progression-free survival, cancer mortality, locoregional control and distant control. There was a significant interaction between patient age and chemotherapy effect.
CONCLUSIONS: This updated meta-analysis confirms the benefit of concomitant chemotherapy and concomitant + adjuvant chemotherapy, and suggests that addition of induction or adjuvant chemotherapy to concomitant chemotherapy improves tumor control and survival. The benefit of chemotherapy decreases with increasing patient age.

UNASSIGNED: Compound glycyrrhizin injection (CGI) is a preparation with glycyrrhizin as the main active ingredient extracted from licorice. As clinical trials suggest that CGI is effective in improving liver function for acute icteric hepatitis in children (AIHC), this systematic review aimed to evaluate and verify its therapeutic effects and safety.
UNASSIGNED: Six electronic databases were searched from their inception to 15 May 2021. Randomized controlled trials (RCTs) assessing therapeutic effects and safety of CGI for AIHC were included. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. Primary outcomes were indexes related to liver function, including total bilirubin (TBiL), alanine aminotransferase (ALT) and aspartate transaminase (AST). RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool.
UNASSIGNED: Six RCTs involving 608 children were included. The overall bias was assessed as having \"high risk of bias\" in all trials. All trials compared the combination of CGI and conventional western medicine (CWM) with CWM alone. Regarding the effects of CGI for AIHC, results showed that CGI plus CWM was superior to CWM alone in reducing the levels of TBiL (mean difference (MD) = -8.19 mmol/L, 95% CI -9.86 to -6.53), ALT (MD = -24.09 U/L, 95% CI -30.83 to -17.34) and AST (MD = -18.67 U/L, 95% CI -21.88 to -15.45). No trial reported adverse events. The certainty of the evidence for outcomes were all evaluated as low or very low.
UNASSIGNED: CGI may have adjuvant therapeutic effects on improving the liver function of children with AIHC. There is no evidence to determine the safety of CGI for AIHC. As current evidence is weak, further well-designed RCTs are required for verification of the therapeutic effects of CGI.

Women who are in the pregnancy-puerperal cycle or are lactating have been deliberately excluded from participating in COVID-19 vaccine clinical trials that aimed to evaluate either the efficacy of the vaccines in inducing the formation of neutralizing antibodies or the investigational products\' safety profile. The exclusion of pregnant and lactating women from such studies certainly and inequitably denies these women access to COVID-19 vaccines, since these products have become increasingly available to nonpregnant people and even to those who are pregnant and are in high-income settings. In this clinical opinion article, we discuss some aspects of the prolonged pandemic, the emergence of viral variants, the risks of severe complications of COVID-19 in pregnant women, and the disproportionate impact of the above on low- and middle-income countries. We argue that the decision to receive the COVID-19 vaccine should be a joint decision between the pregnant or lactating women and the healthcare providers, while considering the available data on vaccine efficacy, safety, the risks of SARS-CoV-2 infection in pregnant women, and the women\'s individual risks for infection and serious illness. The various types of vaccines that are already in use and their safety, effectiveness, and the potential risks and benefits of their administration to pregnant or lactating women are also reviewed.