Glucagon-like peptide-1 receptor agonists in adolescents with overweight or obesity with or without type 2 diabetes multimorbidity-a systematic review and network meta-analysis.

AIM: To synthesize the evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adolescents with overweight or obesity. MATERIALS AND METHODS: For this systematic review and network meta-analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta-analysis to compare GLP-1RAs and placebo, followed by a drug-wise network meta-analysis (NMA) to compare GLP-1RAs against each other. RESULTS: We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP-1RAs reduced weight (mean difference -4.21 kg, 95% confidence interval [CI] -7.08 to -1.35) and body mass index (BMI; mean difference -2.11 kg/m2, 95% CI -3.60 to -0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide. CONCLUSIONS: The evidence suggests that GLP-1RAs reduce most weight-related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head-to-head comparisons, pragmatic design, adiposity-related outcomes, and economic evaluation can further guide the use and choice of GLP-1RAs.

Prevalence of Acute on Chronic Liver Failure in Autoimmune Hepatitis, Treatment Response and Mortality Burden Assessment: A Region-Predominant Systematic Review and Meta-Analysis.

Acute-on-chronic liver failure (ACLF) is a global health problem. Little scientific evidence exists on its prevalence in autoimmune hepatitis. Treatment response and mortality outcomes have also been reported differently. The study was conducted to estimate the overall prevalence of ACLF among patients with autoimmune hepatitis (AIH) and determine the associated treatment response and mortality. We scrutinized wide literature in Scopus, PubMed, Embase, Web of Science, and Cochrane, and assessed published articles completely, studies performed and reported from around the globe, until December 07, 2023, according to the PROSPERO registered protocol (CRD42023412176). Studies (retrospective and prospective cohort study type) that stated the ACLF development among established AIH cases were considered. Features of the study, duration of follow-up, and numeric patient information were retrieved from the studies included. The research paper quality was checked for risk of bias. Random effect meta-analysis with metaregression and subsection scrutinies were performed with R. The main outcome was the collective prevalence of ACLF in the AIH patients, whereas treatment response and mortality in AIH-associated ACLF were secondary outcomes. Six studies were involved with confirmed diagnoses in 985 AIH patients for the data synthesis. The pooled prevalence of ACLF in the explored patients was 12% (95% CI: 8-17) ( P =0.01). Heterogeneity was found to be high in the present meta-analysis ( I2 =72%; P < 0.01). For the secondary endpoint analysis, the pooled prevalence of complete remission at 1-year follow-up was 71% (0.52; 0.85), and mortality from the ACLF-AIH patient population was 32% (95% CI: 18-50). Sensitivity analysis showed no influence on the overall estimations of the pooled prevalence of ACLF by omitting studies one by one. One in 10 AIH patients likely present with ACLF. The response to treatment is seen in two-thirds of patients, and mortality is high.

A meta-analysis and mapping of global mpox infection among children and adolescents.

Monkeypox (mpox) is a significant health concern affecting children and adolescents globally. This systematic review and meta-analysis aims to synthesise the available evidence on the proportion of children and adolescents affected by the mpox virus. A comprehensive search was conducted in seven electronic databases (PubMed, Scopus, Web of Science, EMBASE, ProQuest, EBSCOHost, and Cochrane) to identify the original reports on mpox cases in children and adolescents till 15 January 2023. Descriptive reports on probable or laboratory-confirmed mpox in children and adolescents (0-17 years old) were considered eligible. Studies not providing separate data for the above age group and case-control studies were excluded. The primary outcome was pooled proportion of mpox cases among children and adolescents. Proportion meta-analysis and heterogeneity between studies were determined using a restricted maximum likelihood estimator, and a random-effects model was fitted to the data. Sensitivity analysis and subgroup analysis were also conducted. A drapery plot was also provided as a complementary figure to the forest plot. The protocol was prospectively registered with PROSPERO (CRD42023392475). A total of 440 studies were identified, of which 37 were included in the review and 25 in the meta-analysis (62,701 participants with 3306 children and adolescents). The pooled proportion of children and adolescents was 0.46 (95% CI: 0.30-0.63, I2 :100%). The proportion of children and adolescents was significantly lower (p < 0.001) in the ongoing pandemic 0.04 (95% CI: 0.00-0.32) than before 2022 0.62 (95% CI: 0.49-0.74). The meta-regression showed that the higher the study's sample size, the lower the proportion of children among the mpox cases. Both overall and subgroup heterogeneity were high. Adolescents and children below 5 years are commonly affected by the ongoing pandemic. In conclusion, the high proportion of children affected by the mpox virus highlights the need for increased research and targeted interventions to prevent and control the spread of the virus in this population.

Menstrual cup adoption among reproductive age women in India: a systematic review and meta-analysis.

This systematic review and meta-analysis aim to synthesize the information on menstrual cup adoption among reproductive-age women in India. A comprehensive search was conducted in four databases following PRISMA 2020 guidelines. A total of 18 articles were included in this review. The findings of the studies were described narratively, and meta-analysis and sensitivity analysis were also performed. The pooled prevalence of knowledge regarding menstrual cups among women in the included studies was 35 percent (CI: 0.23-.49). Just 5 percent (CI: 0.02-0.12) of women use menstrual cups. Only 24 percent (CI: 0.17-0.33) of the women who used menstrual cups reported leakage as one of the key barriers or issues to menstrual cup use. Nevertheless, 62 percent (CI: 0.42-0.78) of non-users have a pooled prevalence expressing willingness to use in the future. The price was found to be both a motivating and discouraging factor for using menstruation cups. Currently, menstrual cup use among Indian women and girls is very low. However, user reviews suggest that menstrual cups are an appealing and safer replacement for conventional period supplies. To fully realize the potential of menstruation cups, significant education, and awareness efforts are required to ensure proper usage. Furthermore, initiatives to lower the initial cost of menstruation cups are critical.

Drug metabolizing enzymes pharmacogenetic variation-informed antidepressant therapy approach for common mental disorders: A systematic review and meta-analysis.

IMPORTANCE: Currently, 30-50 % of individuals with depression and 40 % with anxiety-collectively referred to as common mental disorders (CMDs), exhibit inadequate responses to antidepressant treatments. OBJECTIVE: To assess the effectiveness and safety of drug-metabolizing enzyme pharmacogenetic variation informed treatment (PGxIT) versus usual antidepressant treatment (UT) in patients with CMDs. DATA SOURCES: A literature search was conducted in the MEDLINE, Scopus, and Cochrane Library databases from inception until January 30, 2024. STUDY SELECTION: Studies were selected based on CMD diagnoses, reporting on the genetic variations of drug-metabolizing enzyme (DME) genes in relation to antidepressants, involving PGxIT and UT groups with human subjects, and published in English. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment were performed independently by two authors. A pooled risk ratio (RR) with 95 % CI was estimated using both random and fixed-effect models, and heterogeneity was assessed using Cochran's Q test and the I2 statistic. The publication bias of eligible studies was assessed using post hoc Doi plots and the LFK index. RESULTS: This systematic review included 18 studies (n = 7021). The PGxIT demonstrated greater efficacy in the remission of symptoms of depressive disorder at 8 weeks (RR 1.523 [95 % CI: 1.255-1.843]; I2 = 48 %) and 12 weeks (RR 1.631 [95 % CI: 1.001-2.657]; I2 = 86 %; p < 0.01), and symptoms of anxiety disorder compared to UT. Additionally, the risk of adverse drug events (ADEs) was significantly lower in the PGxIT group (RR = 0.65 [95 % CI: 0.52-0.82]; I2 = 0 %) than in the UT group. The certainty of evidence for both outcomes was moderate. CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis suggest that pharmacogenetically guided antidepressant treatment, based on genetic variation in drug-metabolizing enzymes, is associated with superior efficacy in the remission of symptoms for patients with depressive disorders and a reduction in ADEs compared to usual treatment and the findings of the systematic review for remission in anxiety disorders indicate that, PGx guided treatment is also associated with increased remission of symptoms in anxiety disorders compared to usual treatment.

Oral health status among the transgender population of India: A systematic review and meta-analysis.

BACKGROUND: The invisibility of the transgender population within official records, combined with other socio-economic factors, impacts oral health status among transgender people. Hence, our systematic review and meta-analysis aim to generate a pooled estimate of the oral health status of the transgender community in India. MATERIAL AND METHODS: A systematic search was performed across four databases. The studies included a quantitative research design conducted in India and involved self-identified transgender individuals. The pooled prevalence was determined at a 95% confidence interval (CI). Q-statistics and the I2 test were utilized to evaluate the source of heterogeneity. Leave-one-out analysis and Baujat plots were used to detect outliers within the studies. A Doi plot and LFK index were employed to assess the publication bias. RESULTS: A total of 12 studies comprising 1566 transgender participants were included. The pooled prevalence of toothbrush use among transgenders in India was found at 83% (95% CI: 0.73-0.91), smoking = 12% (CI: 0.03-0.26), smokeless tobacco = 53% (CI = 0.38-0.68), dental caries = 78% (CI: 67%-88%), calculus = 65% (CI: 0.4-0.86), and bleeding 18% (CI:0.08-0.32). CONCLUSION: Oral health disparities among Indian transgender individuals are evident in the low toothbrush usage, an elevated prevalence of tobacco use, and dental disorders such as calculus, cavities, and bleeding. Tailored dental health programs that include inclusive healthcare services and awareness are essential. PROSPERO REGISTRATION: CRD42023468872.

Intraoperative goal-directed fluid therapy in adult patients undergoing craniotomies under general anaesthesia: A systematic review and meta-analysis with trial sequential analysis.

Background and Aims: Goal-directed fluid therapy (GDFT) has conflicting evidence regarding outcomes in neurosurgical patients. This meta-analysis aimed to compare the effect of GDFT and conventional fluid therapy on various perioperative outcomes in patients undergoing neurosurgical procedures. Methods: A comprehensive literature search was conducted using PubMed, EMBASE, Scopus, ProQuest, Web of Science, EBSCOhost, Cochrane and preprint servers. The search was conducted up until 16 October 2023, following PROSPERO registration. The search strategy included terms related to GDFT, neurosurgery and perioperative outcomes. Only randomised controlled trials involving adult humans and comparing GDFT with standard/liberal/traditional/restricted fluid therapy were included. The studies were evaluated for risk of bias (RoB), and pooled estimates of the outcomes were measured in terms of risk ratio (RR) and mean difference (MD). Results: No statistically significant difference was observed in neurological outcomes between GDFT and conventional fluid therapy [RR with 95% confidence interval (CI) was 1.10 (0.69, 1.75), two studies, 90 patients, low certainty of evidence using GRADEpro]. GDFT reduced postoperative complications [RR = 0.67 (0.54, 0.82), six studies, 392 participants] and intensive care unit (ICU) and hospital stay [MD (95% CI) were -1.65 (-3.02, -0.28) and -0.94 (-1.47, -0.42), respectively] with high certainty of evidence. The pulmonary complications were significantly lower in the GDFT group [RR (95% CI) = 0.55 (0.38, 0.79), seven studies, 442 patients, high certainty of evidence]. Other outcomes, including total intraoperative fluids administered and blood loss, were comparable in GDFT and conventional therapy groups [MD (95% CI) were -303.87 (-912.56, 304.82) and -14.79 (-49.05, 19.46), respectively]. Conclusion: The perioperative GDFT did not influence the neurological outcome. The postoperative complications and hospital and ICU stay were significantly reduced in the GDFT group.

Zavegepant for Acute Treatment of Migraine: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: Evaluate the safety and efficacy of zavegepant (BHV-3500), a recently approved nasal spray containing a third-generation calcitonin gene-related peptide receptor antagonist, for treating acute migraine attacks. METHODS: A comprehensive search was conducted across various databases up to 06/26/2023 to identify relevant randomized clinical trials (RCTs) on zavegepant's efficacy and safety in treatment of acute migraine attacks. Primary outcome: freedom from pain at 2 hours postdose. Safety outcomes were evaluated based on adverse events (AEs), with zavegepant 10 mg and placebo groups compared for incidence of AEs. RESULTS: Two RCTs, involving 2061 participants (1014 receiving zavegepant and 1047 receiving placebo), were quantitatively analyzed. An additional trial was included for qualitative synthesis. Zavegepant 10 mg exhibited a significantly higher likelihood of achieving freedom from pain at 2 hours postdose compared with the placebo group (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.28 to 1.84). It also showed superior relief from the most bothersome symptoms at 2 hours postdose compared with placebo (RR 1.26, 95% CI 1.13 to 1.42). However, the zavegepant 10 mg group experienced a higher incidence of AEs compared with placebo (RR 1.78, 95% CI 1.5 to 2.12), with dysgeusia being the most reported AE (RR 4.18, 95% CI 3.05 to 5.72). CONCLUSION: Zavegepant 10 mg is more effective than placebo in treating acute migraine attacks, providing compelling evidence of its efficacy in relieving migraine pain and most bothersome associated symptoms. Further trials are necessary to confirm its efficacy, tolerability, and safety in diverse clinic-based settings with varied patient populations.

Maternal and Child Health Training of Traditional Birth Attendants and Pregnancy Outcomes: A Systematic Review and Meta-analysis.

INTRODUCTION: In remote communities, maternal and child health is often compromised due to limited access to healthcare. Simultaneously, these communities historically rely greatly on traditional birth attendants (TBAs). However, optimal integration of these traditional methods with modern healthcare practices remains a topic of debate. We assessed the effect of maternal and child health training of traditional birth attendants on adverse pregnancy outcomes. METHODS: We conducted a systematic review and meta-analysis to answer the above research question. We independently screened studies using databases like PubMed, Scopus, and CENTRAL, extracted data, and assessed the study quality. Due to fewer original studies in this field, we considered both pre-post and between-group differences to assess the effect of differences. These were synthesised separately, assessed against a p-value function, and subjected to sensitivity analyses. RESULTS: We included six interventional studies. Training TBAs reduced the risk of perinatal mortality [0.69, 0.61-0.78] and 7-day neonatal mortality [0.65, 0.53-0.80] but not stillbirth [0.70, 0.39-1.26]. In randomized controlled trials, there is a lower risk of perinatal mortality [0.73, 0.67-0.79] and neonatal mortality [0.70, 0.62-0.80] but not stillbirth [0.81, 0.56-1.18] with trained traditional birth attendants. There are methodological concerns with most existing studies, including domains like allocation concealment. DISCUSSION: There is some evidence of the benefit of training TBAs, though of a low to very low certainty. Due to fewer studies, inconsistent estimates for different critical outcomes, and concerns with the existing studies, further well-designed studies can give more insights. They can also help optimize the contents of TBA training interventions. PROTOCOL: CRD42023412935 (PROSPERO).

Oral health status of prisoners in India: A systematic review and meta-analysis.

AIMS: Given the high prevalence of oral health problems among prisoners, the goal of this systematic review is to provide a better knowledge of the scope of this problem. METHODS: Electronic searches of PubMed/MEDLINE, Embase, Scopus, and Google Scholar were performed. Studies that investigated inmates aged 18 or older with oral health problems were eligible. Variables reported in four or less studies were described narratively. Conversely, for variables reported in more than four studies, a meta-analysis was performed using random effect model. Furthermore, meta-regression and sensitivity analysis is also performed to evaluate moderator effect on outcome. Doi and LFT index is applied to assess publication bias. RESULTS: Out of 494 results, 12 studies were included. The pooled prevalence of caries among prisoners is 78.42% (59.48%-92.58%). On meta-regression, the prevalence of caries appears to be lower in studies with a higher male percentage; however, non-significant (p = .079) due to small sample size. Community periodontal index (CPI) scores revealed periodontal disease, with scores of 3 and 4. Moreover, a significant need for oral hygiene instruction, prosthesis, extraction, and tooth ache, periodontal disease, oral mucosal lesions, leucoplakia, attrition, abrasion, bruxism, and smoking behaviors were also reported. CONCLUSION: Poor oral health status in the incarcerated population highlights the urgent need for comprehensive oral health intervention in prisons.

Effect of maternal obsessive-compulsive disorder (OCD) on feto-maternal outcomes: A systematic review and meta-analysis.

BACKGROUND: Mental health disorders in pregnant women have been related to unfavorable obstetric and neonatal outcomes. Obsessive-compulsive disorder (OCD) significantly distresses mothers and affects the maternal-infant bond. OBJECTIVES: The present meta-analysis and systematic review aimed to assess the association of maternal OCD with adverse feto-maternal outcomes. SEARCH STRATEGY: A systematic search was undertaken in the five databases-Cochrane, Embase, ProQuest, Web of Science, and PubMed-on September 5, 2023. SELECTION CRITERIA: Studies that included pregnant women with OCD in whom the feto-maternal outcomes were reported were included in the systematic review. DATA COLLECTION AND ANALYSIS: Two pass screening ("title-abstract screening" followed by "full-text review"), and data extraction by two authors independently using the Nested-Knowledge Auto living semi-automated systematic review platform was carried out. The decision for selected studies was reviewed by a third author. Of the 360 studies identified, eight were included for the meta-analysis. Meta-analysis was conducted using R software. MAIN RESULTS: Of the 24 maternal and neonatal adverse outcomes assessed, 11 were found to be associated with maternal OCD, notably pre-eclampsia (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.19-1.57), antepartum hemorrhage or placental abruption (OR 1.32, 95% CI 1.13-1.54), postpartum hemporrhage (OR 1.19, 95% CI 1.08-1.31), cesarean section delivery (OR 1.32, 95% CI 1.23-1.41), emergency cesarean section (OR 1.22, 95% CI 1.15-1.30), preterm birth (OR 1.41, 95% CI 1.21-1.64), low birth weight (OR 1.41, 95% CI 1.28-1.54), low Apgar score at 5 min (OR 2.37, 95% CI 1.32-4.27), neonatal hypoglycemia (OR 1.37, 95% CI 1.23-1.53), neonatal respiratory distress (OR 1.77, 95% CI 1.44-2.16), and major congenital malformations (OR 1.37, 95% CI 1.08-1.74). CONCLUSION: OCD in pregnant women might be associated with multiple adverse feto-maternal outcomes.

Serum copper status of patients with colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and a public health problem. Several clinical studies have shown that copper (Cu) is involved in carcinogenesis, possibly via cuproptosis, a new form of programmed cell death, but the conclusions from published reports are inconsistent. This study aimed at evaluating the potential of Cu dysregulation as a CRC susceptibility factor. METHODS: In this systematic review and meta-analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum Cu concentrations in CRC patients and controls from articles published till June 2023. The studies included reported measurements of serum/plasma/blood Cu levels. Meta-analyses were performed as well as study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary standardized mean differences (SMDs) and the corresponding 95% confidence intervals (95% CIs) were applied to compare the levels of Cu between CRC patients and controls. RESULTS: 26 studies with a pooled total of9628 participants and 2578 CRC cases were included. The pooled SMD was equal to 0.85 (95% CIs -0.44; 2.14) showing that the CRC patients had higher mean Cu levels than the control subjects, but the difference was not significant (p = 0.185) and the heterogeneity was very high, I2 = 97.9% (95% CIs: 97.5-98.3%; p < 0.001). CONCLUSION: The pooled results were inconclusive, likely due to discordant results and inaccuracy in reporting data of some studies; further research is needed to establish whether Cu dysregulation might contribute to the CRC risk and whether it might reflect different CRC grades.

Electronic-PRO Measures for adverse events Of Treatment In ONcology (E-PROMOTION).

PURPOSE: Cancer patients struggle with the trauma of the disease and its treatment. PRO-CTCAE was developed to improve the recording of underreported symptomatic toxicities. We evaluated the improvement and ease in reporting symptomatic adverse events through add-on PRO-CTCAE (via a mobile application) compared to standard clinician-reported outcomes in routine clinical practice. We also evaluated changes in the health-related quality of life (HRQoL). METHODS: 110 cancer patients were studied for three weeks between their first and second chemotherapy session. HRQoL was assessed using EORTC QLQ-c30. RESULTS: Fifty-three patients self-reported their symptomatic adverse events on the day 7th & day 14th after the first cycle of chemotherapy. For the other fifty-seven patients, recording of adverse events was done by standard clinician-reported outcomes. All the patients in the study group reported adverse events compared to only 21 % in the standard reporting group. All 15 domains of adverse events were reported in the self-reporting group compared to only 5 in the standard reporting group. The self-reporting group had a significantly better overall quality of life. CONCLUSIONS: Self-reporting of adverse events using mobile app-based PRO-CTCAE helps patients and clinicians with better documentation of symptomatic toxicities of chemotherapy, reducing the burden on physicians and improving patient satisfaction. Mobile app-based self-reporting empowers cancer patients undergoing treatment, improves their quality of life, and should be implemented in routine clinical practice. Wider implementation can lead to further optimised solutions.

Targeting self-care adherence for glycaemic control in multimorbid type 2 diabetes mellitus with depression using bupropion: a protocol for cross-over randomised controlled trial.

INTRODUCTION: Diabetes and depression are among the 10 biggest health burdens globally. They often coexist and exhibit a strong bidirectional relationship. Depression leads to decreased adherence to self-care activities. This impacts glycaemic control and worsens type 2 diabetes mellitus (T2D). Both conditions have a synergistic effect and lead to greater complications, hospitalisations, healthcare expenditure and a worse quality of life. There is no consensus on managing people with comorbid T2D and depression. Bupropion is an efficacious antidepressant with many properties suitable for T2D with depression, including a favourable metabolic profile, persistent weight loss and improvement in sexual dysfunction. We will assess the efficacy and safety of add-on bupropion compared with standard care in people with T2D and mild depression. This study can give valuable insights into managing the multimorbidity of T2D and depression. This can help mitigate the health, social and economic burden of both these diseases. RESEARCH DESIGN AND METHODS: This cross-over randomised controlled trial will recruit people with T2D (for 5 years or more) with mild depression. They will be randomised to add-on bupropion and standard care. After 3 months of treatment, there will be a washout period of 1 month (without add-on bupropion while standard treatment will continue). Following this, the two arms will be swapped. Participants will be assessed for glycosylated haemoglobin, adherence to diabetes self-care activities, lipid profile, urine albumin-to-creatinine ratio, autonomic function, sexual function, quality of life and adverse events. ETHICS AND DISSEMINATION: The Institutional Ethics Committee at All India Institute of Medical Sciences, Jodhpur has approved this study (AIIMS/IEC/2022/4172, 19 September 2022). We plan to disseminate the research findings via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts and social media. TRIAL REGISTRATION NUMBER: CTRI/2022/10/046411.

Identification of Putative Biomarkers in Cerebral Palsy: A Meta-Analysis and Meta-Regression.

BACKGROUND: Cerebral palsy (CP) is a neurological disorder that impairs motor abilities. Identifying maternal biomarker derangements can facilitate further evaluation for early diagnosis, potentially leading to improved clinical outcomes. This study investigates the association between maternal biomarker derangements and CP development during the antenatal period. METHODS: A systematic search was conducted in MEDLINE, EMBASE, and Cochrane databases, following MOOSE guidelines. Data on participants exceeding biomarker thresholds (95th and 5th percentiles) were extracted for combined odds ratio estimation. Geometric mean differences, reported as multiples of the median (MoMs), were used to analyze changes in marker levels. Trimesterwise subgroup analysis and metaregression assessed the impact of variables on outcomes. RESULTS: Five observational studies (1552 cases, 484,985 controls) revealed lower maternal pregnancy-associated plasma protein A levels were associated with CP (pooled odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.22 to 2.09; I = 0%), with a -0.04 MoM geometric mean difference. Lower maternal beta-human chorionic gonadotropin (HCG) levels in first and second trimesters indicated a pooled OR = 1.18 (95% CI = 0.85 to 1.63; I = 57%). Sensitivity analysis showed an OR = 1.40 (95% CI = 1.08 to 1.82; I = 0%), with a -0.07 MoM geometric mean difference. Metaregression identified primigravida status as negatively influencing beta-HCG levels. Elevated nuchal translucency values and CP presented a pooled OR = 1.06 (95% CI = 0.77 to 1.44; I = 0%). CONCLUSION: Lower maternal pregnancy-associated plasma protein A levels during the first trimester and lower beta-HCG levels in the first and second trimesters are associated with CP development in children. Future research should validate the predictive utility of these biomarkers and explore novel ones through large-scale cohort studies.

Selenium levels in colorectal cancer: A systematic review and meta-analysis of serum, plasma, and colorectal specimens.

BACKGROUND: Colorectal cancer (CRC) is a growing public health problem. Several clinical studies have shown a potentially protective effect of selenium (Se), but the reports are inconsistent. The objective of the study was to examine the evidence for relation between serum/tissue Se status and CRC. METHOD AND MATERIALS: In this Systematic Review and Meta-Analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum/plasma/whole blood/tissue Se concentrations in CRC patients and controls for articles published till August 2023. Meta-analysis was performed, and study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary mean differences in serum levels of Se between CRC patients and healthy controls, and Se levels between malignant and matched non-malignant tissue specimens were assessed. RESULTS: After initial screening, a total of 24 studies (18 serum and 6 tissue studies) with a pooled total of 2640 participants were included in the meta-analysis. CRC patients had significantly lower serum Se levels than healthy controls, being the difference between the two equal to 3.73 µg/dl (95% CI: 6.85-0.61). However, the heterogeneity was very high, I2= 99% (p < 0.01). Our meta-analysis showed higher Se levels in CRC cancerous specimens than in matched healthy colon tissue: the increase was equal to 0.07 µg/g wet tissue weight (95% CI: 0.06-0.09; p= 0.02). CONCLUSIONS: CRC patients have lower serum and higher colon cancerous tissue Se levels. Some factors, such as Se levels in different tumor grades of CRC need to be further considered for a more conclusive association between Se levels and risk of CRC.

Exploring the role of Orexin-A neuropeptide in Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Parkinson's disease (PD) is a progressive neurological condition that affects movement and coordination. Orexin-A (OXA) is an excitatory neuropeptide that is found throughout the central nervous system. There is growing interest in investigating the potential diagnostic and therapeutic utility of OXA in PD. To date, studies have reported a wide range of OXA concentrations in patients with PD. In this review, we discuss the current understanding of the dysregulation of OXA in PD and analyze its levels in the CSF. METHODS: We searched six databases (PubMed, Scopus, Web of Science, EMBASE, ProQuest, and EBSCOHost) and preprint servers using a predetermined search strategy through 4th March 4, 2023. The search keywords included "Parkinson's disease", "Orexin-A", "Hypocretin-1", "cerebrospinal fluid", and "CSF". Studies that reported OXA/Hypocretin-1 levels in the CSF of patients with PD were included. Two researchers independently reviewed the records and extracted data. FINDINGS: Eighteen studies involving 244 patients were analyzed. CSF Orexin-A concentrations were lower in patients with Parkinson's disease than in controls, with a mean difference of -59.21 (95 % CI: -89.10 to -29.32). The mean OXA levels were 281.52 (95 % CI: 226.65-336.40). CONCLUSION: Our analysis reveals lower concentrations of orexin-A in the cerebrospinal fluid of Parkinson's disease patients compared to controls, but within the normal range. These findings suggest a potential, but not significant, disruption in the orexinergic system associated with the disease.

Association between homocysteine and coronary artery disease-trend over time and across the regions: a systematic review and meta-analysis.

BACKGROUND: The association of homocysteine with coronary artery disease (CAD) has been explored previously with mixed findings. The present Systematic Review and Meta-Analysis (SRMA) has assessed the pooled estimate of association between homocysteine (Hcy) and CAD, and its variation over the period and geography. METHODS: Systematic literature search was done in PubMed, Scopus and Cochrane to identify the observational studies that have reported mean Hcy among cases (CAD) and control. The SRMA was registered in PROSPERO (ID-CRD42023387675). RESULTS: Pooled standardized mean difference (SMD) of Hcy levels between the cases and controls was 0.73 (95% CI 0.55-0.91) from 59 studies. Heterogeneity was high (I2 94%). The highest SMD was found among the Asian studies (0.85 [95% CI 0.60-1.10]), while the European studies reported the lowest SMD between the cases and controls (0.32 [95% CI 0.18-0.46]). Meta-regression revealed that the strength of association was increasing over the years (Beta = 0.0227, p = 0.048). CONCLUSIONS: Higher homocysteine levels might have a significant association with coronary artery diseases, but the certainty of evidence was rated low, owing to the observational nature of the studies, high heterogeneity, and publication bias. Within the population groups, Asian and African populations showed a greater strength of association than their European and American counterparts, and it also increased over the years.

PeRinatal, neOnatal, and Maternal OuTcomEs with azithromycin prophylaxis in pregnancy and labour (PROMOTE-PROPHYLAXIS): systematic review and meta-analysis.

Background: Initial randomised controlled trials (RCTs) showed that prophylactic azithromycin in pregnant women improved maternal and neonatal outcomes; however, the recent evidence did not show any benefit to neonatal survival. There is conflicting evidence over the role of azithromycin prophylaxis in antenatal and intrapartum periods. We explored whether azithromycin prophylaxis in pregnant women improves maternal and neonatal outcomes. Methods: For this systematic review and meta-analysis registered on PROSPERO [CRD42023411093], we searched seven databases (PubMed, Scopus, Embase, Cochrane Library, EBSCOHost, ProQuest, and Web of Science) and clinical trial registries until 04/23/2024, for RCTs evaluating antenatal/intrapartum azithromycin prophylaxis against placebo/routine care in pregnant women. The primary outcome was neonatal mortality. Intrapartum and antenatal administration were assessed separately. We used random-effects meta-analysis. The risk of bias was assessed using the Cochrane RoB 2 tool. The GRADE approach was used to evaluate the certainty of the evidence. Findings: Screening 2161 records retrieved 20 RCTs (56,381 participants). Intrapartum azithromycin may make little or no difference to neonatal mortality [5 RCTs, 44,436 participants; Risk Ratio (RR): 1.02, 95% CI 0.86-1.20, I 2  = 0%, very low certainty], and maternal mortality [3 RCTs, 44,131 participants, RR: 1.26, 0.65-2.42, I 2  = 0%, low certainty]. Similarly, antenatal azithromycin may have little or no effect on neonatal mortality [3 RCTs; 5304 participants; RR: 0.74, 0.35-1.56, I 2  = 43%, very-low certainty] and maternal mortality [3 RCTs; 8167 participants RR: 1.62, 0.67-3.91, I 2  = 0%, low certainty]. There is no data on long-term adverse outcomes and antimicrobial resistance. Interpretation: Low to very low certainty evidence suggests that intrapartum or antenatal azithromycin prophylaxis in pregnant women might not reduce maternal or neonatal mortality. Funding: None.