Renin-angiotensin system inhibitor use and risk of Parkinson's disease: a meta-analysis.

BACKGROUND: Hypertension is a recognized risk factor for Parkinson's disease (PD). The renin-angiotensin system (RAS) inhibitors are widely used to treat hypertension. However, the association of RAS inhibitor use with PD has still been an area of controversy. METHODS: Thus, we conducted a meta-analysis to investigate the relationship between RAS inhibitor use and PD. PUBMED and EMBASE databases were searched for articles published up to Oct 2023. All studies that examined the relationship between RAS inhibitor use and the incidence of PD were included. RESULTS: Seven studies with total 3,495,218 individuals met our inclusion criteria for this meta-analysis. Overall, RAS inhibitor use was associated with a reduction in PD risk (OR = 0.88, 95%CI = 0.79-0.98) compared with the controls. When restricted the analysis to individuals with RAS inhibitor use indication, RAS inhibitor exposure was also associated with a decreased risk of PD (OR = 0.76, 95%CI = 0.62-0.92). Pooled results of cohort studies also did support a protective role of angiotensin converting enzyme inhibitors (ACEIs) (OR = 0.97, 95%CI = 0.89-1.07) users and angiotensin II receptor blockers (ARBs) (OR = 0.8, 95%CI = 0.63-1.02) in PD. CONCLUSION: Overall, RAS inhibitor use as a class is associated with a reduction in PD risk. However, the findings of ACEIs and ARBs may be limited by small sample size. Future well-designed studies considering the classification by inhibitor type, duration, dose, or property of BBB penetration of RAS inhibitors are needed to clarify the contribution of these exposure parameters on the risk of PD.

Association of atopic dermatitis and headache disorder: a systematic review and meta-analyses.

Background: Growing evidence suggests that headache disorders and atopic dermatitis share similar pathological mechanisms and risk factors. The aim of this study was to assess the risk for headache disorders in patients with atopic dermatitis. Methods: We systematically searched the PubMed and Embase databases from inception to December 1, 2023, for observational studies that examined risk of migraine in subjects with atopic dermatitis. Risk estimates from individual studies were pooled using random-effects models. Results: Ten studies with 12,717,747 subjects were included in the meta-analysis. Our results showed that patients with atopic dermatitis were associated with a higher risk of headache disorder (OR, 1.46, 95% CI = 1.36-1.56; P < 0.001; I2 = 98%) or migraine (OR, 1.32, 95% CI = 1.18-1.47; P < 0.001; I2 = 98.9%). Most of the results of the subgroup analyses were consistent with the overall results. Conclusion: The findings of this meta-analysis suggest that atopic dermatitis is a potential risk indicator for headache disorder or migraine. Further studies are still needed to verify our findings due to the substantial heterogeneity in our analyses.

Antidepressant use and the risk of seizure: a meta-analysis of observational studies.

PURPOSE: The association between antidepressant use and the risk of seizures remains controversial. Therefore, this meta-analysis examined whether antidepressant use affects the risk of seizures. METHODS: To identify relevant observational studies, we conducted systematic searches in PubMed and Embase of studies published through May 2023. Random-effects models were used to estimate overall relative risk. RESULTS: Our meta-analysis included eight studies involving 1,709,878 individuals. Our results showed that selective serotonin reuptake inhibitors (SSRI) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.32-1.66; P < 0.001) and selective noradrenalin reuptake inhibitors (SNRI) (OR 1.65, 95% CI 1.24-2.19; P = 0.001), but not tricyclic antidepressants (TCA) (OR 1.27, 95% CI 0.84-1.92; P = 0.249), were associated with an increased risk of seizures. Subgroup analyses revealed an OR of 2.35 (95% CI 1.7, 3.24; P < 0.001) among short-term (< 30 days) antidepressant users. CONCLUSIONS: The findings of this meta-analysis support an increased risk of seizures in new-generation antidepressant users, expanding previous knowledge by demonstrating a more pronounced risk in short-term users.

Effects of herpes zoster vaccination and antiviral treatment on the risk of stroke: a systematic review and meta-analysis.

Background: Evidence suggests that there is an increased risk of stroke after herpes zoster (HZ). However, reports on the effects of HZ vaccination (HZV) and antiviral treatment on stroke risk are inconsistent. Thus, we examined these associations in a meta-analysis. Methods: To identify relevant studies, we searched three databases for articles published up to January 2023. Random-effect models were examined to determine overall pooled estimates and 95% confidence intervals (CIs). Results: This review included 12 observational studies (six on HZV and seven on antiviral treatment). When comparing vaccinated and unvaccinated patients, vaccination was found to be associated with a lower risk of stroke (OR, 0.78; 95% CI 0.68-0.9; P = 0.001). A meta-analysis of self-controlled case series (SCCS) revealed evidence of a reduced OR in individuals who received the vaccine (OR, 1.14; 95% CI 0.94-1.37; P = 0.181) compared with unvaccinated individuals (OR, 1.36; 95% CI 1.15-1.61; P < 0.001). Compared with untreated patients, antiviral therapy was not associated with a reduced risk of stroke (OR, 1.13; 95% CI 0.94-1.36; P = 0.201). The meta-analysis of the SCCS showed no evidence of a reduced OR in individuals who received antiviral therapy (OR, 1.33; 95% CI 1.17-1.51; P < 0.001) compared to untreated individuals (OR, 1.45; 95% CI 1.25-1.69; P < 0.001). Conclusions: This meta-analysis suggests that the HZV, but not antiviral treatment, decreases the odds of developing stroke.

Gut microbiome profiles may be related to atypical antipsychotic associated overweight in Asian children with psychiatric disorder: a preliminary study.

Objective: Atypical antipsychotics (APs) modify the gut microbiome, and weight gain in response to AP could be mediated by the gut microbiome. Thus, the present study aimed to explore the changes in the gut bacterial microbiome in AP-exposed children with obesity. Methods: To rule out the confounder of AP indication, the gut bacterial microbiome was compared between healthy controls (Con) and AP-exposed individuals with overweight (APO) or normal weight (APN). Fifty-seven AP-treated outpatients (21 APO and 36 APN) and 25 Con were included in this cross-sectional microbiota study. Results: AP users, regardless of body mass index, exhibited decreased microbial richness and diversity and a distinct metagenomic composition compared to the Con. Although no differences in the microbiota structure were observed between APO and APN groups, the APO group was characterised by a higher abundance of Megamonas and Lachnospira. Additionally, the differences in the microbial functions were observed between APO and APN groups. Conclusions: The gut bacterial microbiota of APO children revealed taxonomic and functional differences compared to Con and APN. Further studies are needed to verify these findings and to explore the temporal and causal relationships between these variables.

Altered gut bacterial-fungal interkingdom networks in children and adolescents with depression.

BACKGROUND: Most studies of the gut-brain axis have focused on bacteria; little is known about commensal fungi. Children and adolescents with depression were reported to have gut bacterial microbiota dysbiosis, but the role of the mycobiota has not been evaluated. METHODS: Faecal samples were obtained from 145 children and adolescents with depression and 110 age- and gender-matched healthy controls. We analysed the fungal microbiota, including in terms of their associations with the gut microbiota, and subjected the internal transcribed spacer 2 (ITS2) rRNA gene to mitochondrial sequencing. RESULTS: Our findings revealed unaltered fungal diversity, but altered taxonomic composition, of the faecal fungal microbiota in the children and adolescents with depression. Key fungi such as Saccharomyces and Apiotrichum were enriched in the depressed patients, while Aspergillus and Xeromyces showed significantly decreased abundance. Interestingly, the bacterial-fungal interkingdom network was markedly altered in the children and adolescents with depression, and mycobiome profiles were associated with different bacterial microbiomes. LIMITATION: The cross-sectional design precluded the establishment of a causal relationship between the gut mycobiota and the children and adolescents with depression. CONCLUSIONS: The gut mycobiome is altered in the children and adolescents with depression. Our findings suggest that fungi play an important role in the balance of the gut microbiota and may help identify novel therapeutic targets for depression.

Anti-seizure medication exposure and the risk of dementia: A meta-analysis of observational studies.

Objective: There is growing evidence of a relationship between anti-seizure medication (ASM) use and the risk of dementia. This study examined this association using a meta-analysis approach. Methods: PubMed, EMBASE, and Cochrane Library were systematically searched for peer-reviewed observational studies published up to February 2023. Study quality was evaluated using the Newcastle-Ottawa Scale, and an overall odds ratio (OR) was pooled using fixed or random-effects models. Results: The analysis included 9 publications with 10 studies. The results showed that overall ASM exposure was associated with an increased risk of dementia [OR: 1.09, 95% confidence interval (CI): 1.03-1.15; P = 0.003] in general population. However, this association disappeared (OR: 1.02, 95% CI: 0.97-1.07; P = 0.361) when the study data adjusted for drug indications were pooled. Subgroup analysis based on individual drugs found only a positive association among those exposed to valproate, carbamazepine, and clonazepam. Furthermore, an increased risk was found in patients with bipolar disorder exposed to ASMs (OR: 1.43, 95% CI: 1.07-1.92; P = 0.015). Conclusions: The statistically significant association between ASM and dementia in general population may be driven by unmeasured confounding or several individual first-generation ASMs. However, a higher risk of dementia was observed among bipolar disorder patients treated with ASMs. Given the few included studies and evidence of high heterogeneity, further larger, prospective studies that control for important confounders are needed to verify our findings.

Antidepressant use during pregnancy and the risk for gestational diabetes: a systematic review and meta-analysis.

OBJECTIVE: Antidepressant medications are used by increasing numbers of pregnant women. The evidence on the relationship between antidepressant use during pregnancy and the risk for gestational diabetes mellitus (GDM) is inconsistent. We perform a systematic review and meta-analysis to assess the GDM risk associated with antidepressant exposure during pregnancy. METHODS: We systematically searched the PubMed and EMBASE databases until December 2021. We sought observational studies assessing the association between gestational antidepressant use and GDM. RESULTS: Five observational studies were included in the analysis. Mothers exposed to antidepressants during pregnancy were at a significantly increased risk for GDM (relative risk [RR] 1.20, 95% confidence interval [CI] 1.11-1.30; p < .001). However, after considering confounding by indication, we observed no significant effect of antidepressant use during pregnancy on the risk of GDM (RR 1.13, 95% CI 1-1.28; p = .054; I2 = 0%). Independent of clinical indication, subgroup analysis based on individual antidepressants suggested that the risk was increased by venlafaxine or amitriptyline use, but not by selective serotonin reuptake inhibitors. CONCLUSIONS: The significant association between antidepressant exposure during pregnancy and GDM may be overestimated due to confounding by indication. However, the evidence remains insufficient, particularly for specific drug classes.

Maternal Common Cold or Fever During Pregnancy and the Risk of Orofacial Clefts in the Offspring: A Systematic Review and Meta-analysis.

The common cold and/or an associated fever during pregnancy have/has been suspected to harm the developing fetus. We sought possible correlations between a maternal common cold or fever during pregnancy and the risk of orofacial clefts in the offspring.We systematically searched PubMed and Embase using appropriate keywords, and we checked the reference lists of retrieved articles. We used random-effects models to estimate overall relative risks.Incidence of orofacial clefts.We included 13 case-control studies. Modest but statistically significant associations were found between a maternal common cold and cleft lip with or without a cleft palate (CL/CP) (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.66-2.83) and a cleft palate only (CPO) (OR 3.08; 95% CI 1.5-6.34). Furthermore, maternal fever was also associated with an increased risk of CL/CP (OR 1.91, 95% CI 1.3-2.8) and CPO (OR 1.48, 95% CI 0.83-2.63) in the offspring. Further analyses of maternal influenza (alone) yielded similar results.Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal common cold or fever during pregnancy may be associated with a greater risk of CL/CP or CPO in the offspring. Future cohort studies using valid assessments of maternal common cold exposure during pregnancy that consider the severity of fever are needed to clarify the contribution of maternal common cold or fever status to the risk of orofacial clefts in children.

Exposure to selective noradrenalin reuptake inhibitors during the first trimester of pregnancy and risk of congenital malformations: A meta-analysis of cohort studies.

Selective serotonin-noradrenalin reuptake inhibitors (SNRIs) are used to treat depression and anxiety during pregnancy; however, information regarding their foetal safety is limited. Cohort studies concerning congenital malformations in infants born to mothers exposed to SNRIs during the first trimester of pregnancy were identified. Eight studies were included in the analysis. In general, the use of SNRIs was not associated with an increased risk of overall congenital malformations when compared with no exposure (rate ratio [RR] = 1.07, 95% confidence interval [CI] = 0.94-1.22; P = 0.31), exposure to SSRIs (RR = 1.12, 95% CI = 0.97-1.31; P = 0.12) and no exposure with clinical indication (RR = 1.04, 95% CI = 0.9-1.2; P = 0.564). A significantly increased risk of cardiac malformations was observed (RR = 1.33, 95% CI = 1.15-1.53; P < 0.001); however, this association was not statistically significant when the reference group comprised mothers exposed to SSRIs (RR = 1.1, 95% CI = 0.85-1.43; P = 0.47) or no exposure with clinical indication (RR = 1.17, 95% CI = 0.95-1.42; P = 0.13). The evidence shows no increased risk of congenital malformations and argues against a substantial cardiac teratogenic effect of SNRIs.

Gut microbiota is associated with weight gain in children treated with atypical antipsychotic: A pilot longitudinal study.

We studied longitudinal changes in the microbiome with weight gain during atypical antipsychotics (APs) treatment. 43 inpatients naive to AP paediatric medication were included in the longitudinal microbiota study. The baseline composition of the gut microbiome in the case group was characterised by an increase in Parabacteroides and Eubacterium_hallii_group. During the follow-up, the relative abundances of Romboutsia and Klebsiella increased significantly after 3 months of AP treatment; however, no significant changes in these two gut bacteria were observed in the control group. The baseline composition of the gut microbiome contributed to the risk of AP-associated weight gain.

Fecal microbiota in pediatric depression and its relation to bowel habits.

Although gut microbiota dysbiosis has been observed in the fecal samples of depressive adult patients, the detailed structure and composition of microbiota in pediatric depression remain unclear. To enhance our understanding of gut microbiota structure in depressive children, as well as the relationship between gut microbiota and bowel habits, we performed 16S rRNA sequencing to evaluate the gut microbial population in a cohort of 171 children (101 depressive patients and 70 controls) aged 12-18 years. Further analysis consisting of 30 drug-naive patients and 23 controls was performed to validate the results. Compared to controls, we found markedly decreased microbial richness and diversity, a distinct metagenomic composition with reduced short-chain fatty acid-producing bacteria (associated with healthy status), and overgrowth of bacteria such as Escherichia-Shigella and Flavonifractor in pediatric depression. Further analyses limited to drug-naive patients found similar results. Notably, we also observed that several taxa may be involved in the pathogenesis of disordered bowel habits in pediatric depression. Our findings suggest could inform future pediatric depression interventions specifically targeting the bacteria associated with bowel movements.

The risk of dementia in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Growing evidence indicates that inflammatory bowel disease (IBD) and dementia share similar pathological mechanisms, but no consensus has yet emerged on the effect that IBD and dementia are associated. To explore such a possible correlation, we summarize herein the epidemiological evidence. We subject relevant studies to meta-analysis. METHODS: We comprehensively searched Pubmed and Embase for relevant articles published to Dec 2021. The pooled risk ratio (RR) with the 95% confidence interval (CI) was used to estimate the effect; we calculated the generic inverse variance using a random-effects model. RESULTS: Seven studies involving 65,454 patients with dementia were included in the meta-analysis. The overall risk of dementia in IBD patients was significantly higher than that in the general population (risk ratio [RR], 1.35; 95% confidence interval [CI], 1.08-1.68; P = 0.008). The results of subgroup analyses were consistent with the overall results. The risk of Alzheimer's disease was higher in IBD patients (RR = 2.79, 95% CI = 1.1, 7.04; P < 0.001). CONCLUSIONS: Our results revealed that IBD may be a potential risk indicator for dementia.

Cesarean section is not associated with increased risk of celiac disease in the offspring: a meta-analysis.

OBJECTIVE: Epidemiologic findings are inconsistent concerning the association between cesarean section (C-section) and celiac disease in offspring. METHODS: We performed a systematic literature search of PubMed and Embase databases until July 2021. A meta-analysis was performed for each outcome in which a summary odds ratio (OR) was calculated while taking heterogeneity into account. RESULTS: A total of 11 observational were identified for the literature review. We found that C-section was not associated with an increase in the risk of CD (OR = 1.03, 95% CI, 0.95-1.12; p = .501). In subgroup analyses, the association remained insignificant for both infants born after elective C-section (OR 1.05; 0.95-1.16; p = .329) and emergency C-section (OR 1.06; 1-1.13; p = .051). CONCLUSIONS: Our results indicate that C-section is not associated with CD in offspring.

Labor epidural analgesia and risk of autism Spectrum disorders in offspring: A systematic review and meta-analysis.

Background: The effect of labor epidural anesthesia (LEA) on the risk of autism spectrum disorder (ASD) in offspring has been investigated recently, and available results are inconsistent. Methods: We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. Subgroup analyses were conducted to assess the sources of heterogeneity. Both fixed and random effects models were used was used to estimate overall relative risk. Results: Our results showed that LEA was associated with an increased risk of ASD in offspring [HR = 1.3, 95% confidence interval (CI): 1.25-1.35; P < 0.001] after combining crude estimates from the included studies. This association was gradually reduced, but still statistically significant, when potential confounding factors were considered (HR 1.13, 95% CI 1.03-1.25, P = 0.014). However, there was no significant association when we combined data of siblings from other pregnancies (HR = 1.07, 95% CI: 0.99-1.16, P = 0.076), implying that the association was due to confounding factors. Conclusion: The statistically significant association between LEA and ASD in the offspring can be partially explained by unmeasured confounding. Systematic Review Registration: Identifier CRD42022302892.

Association between irritable bowel syndrome and Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that irritable bowel syndrome (IBS) and Parkinson's disease (PD) share similar pathological mechanisms and risk factors. METHODS: We performed a systematic review and meta-analysis of the evidence for a relationship between IBS and PD. Risk estimates from individual studies were pooled using random-effects models. RESULTS: Six articles involving 58,645 patients with PD were included in our meta-analysis. The overall risk for PD in IBS patients was significantly higher than that in the general population (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.29-1.75; p < .001). Subgroup analysis revealed no significant differences in risk between men (OR = 1.47, 95% CI: 1.3-1.67; p < .001) and women (OR = 1.51, 95% CI: 1.29-1.75; p < .001); however, older (≥65 years) IBS patients (OR = 1.44, 95% CI: 1.3-1.59; p < .001) may be at higher risk for PD than younger (40-64 years) patients (OR = 1.32, 95% CI: 1.05-1.64; p = .017). CONCLUSION: Overall, the PD risk was higher in IBS patients than others, indicating that the intestinal disorder may serve as a warning sign for PD.

Maternal infection during pregnancy and the risk of attention-deficit/hyperactivity disorder in the offspring: A systematic review and meta-analysis.

BACKGROUND: The effects of maternal infection during pregnancy on the risk of attention-deficit/hyperactivity disorder (ADHD) in the offspring are unclear, and no overview is available. METHODS: We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. RESULTS: We found that that maternal infection during pregnancy was associated with a small increase in the risk of ADHD (OR 1.25, 95% CI 1.09, 1.44, P < 0.0001; I2 = 92.9%, p < 0.0001) in the offspring. In subgroup analyses, the association remained for maternal genitourinary (GU) infection (OR, 1.19, 1.12, 1.27, P < 0.001; I2 = 0%; p = 0.517). However, there was no significant association when we pooled data from siblings from other pregnancies (OR = 1.06, 95% CI, 0.99-1.13, P = 0.084; I2 = 0%; p = 0.859), implying that the association was due to confounding. CONCLUSIONS: The statistically significant association between maternal infection during pregnancy and ADHD in the offspring can be partially explained by unmeasured confounding.

Efficacy and safety of antiviral therapy in critically ill patients with mechanical ventilation: a meta-analysis with trial sequential analysis of randomized controlled trials.

OBJECTIVES: Viral reactivation is frequently detected in critically ill patients undergoing mechanical ventilation and is associated with worse outcomes. However, the efficacy and safety of antiviral therapy in these patients remain unknown. This review aims to assess the effects of antiviral therapy on mortality, viral reactivation, and adverse events in critically ill patients undergoing mechanical ventilation. METHODS: Data sources were Medline, Embase, the Cochrane Library, and reference lists. The study included randomized controlled trials that compared antiviral therapy with placebo, standard care, or no treatment. Participants were critically ill patients undergoing mechanical ventilation. Intervention was antiviral therapy. Assessment of risk of bias used the Cochrane risk of bias tool. For methods of data synthesis, risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model for meta-analysis with trial sequential analysis. RESULTS: Nine trials with a broad spectrum of critically ill patients were included. No association was found between antiviral therapy and all-cause mortality at the longest follow-up (nine trials, 1790 patients, RR 0.93, 95%CI 0.79-1.11, I2 3%). Trial sequential analysis showed that the cumulative Z curve crossed the futility boundary establishing sufficient evidence. No association was also found between antiviral therapy and 28-day mortality, in-hospital mortality, 60-day mortality, or 90-day mortality. However, antiviral therapy was associated with a reduction in viral reactivation (five trials, 644 patients, RR 0.23, 95%CI 0.14-0.37, I2 0%). Trial sequential analysis showed that the cumulative Z curve crossed the trial sequential monitoring boundary for benefit establishing sufficient evidence. Antiviral therapy was not associated with an increased risk of renal insufficiency (eight trials, 1574 patients, RR 0.88, 95%CI 0.73-1.05, I2 0%). CONCLUSIONS: No association between antiviral therapy and mortality was found, but antiviral therapy reduced viral reactivation without increasing the risk of renal insufficiency in critically ill patients with mechanical ventilation.

Early Life Antibiotic Exposure and the Subsequent Risk of Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis.

This study was conducted to assess this association between early life antibiotic exposure and the risk of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in later life. The results showed that early life antibiotic exposure was associated with an increased risk of ASD (OR = 1.13, 95% confidence interval (CI): 1.07-1.21) or ADHD (OR = 1.18, 95% CI: 1.1-1.27). However, this association for ASD (OR = 1.04, 95% CI: 0.97-1.11) or ADHD (OR = 0.98, 95% CI: 0.94-1.02) disappeared when data from sibling-matched studies were pooled. The statistically significant association between early life antibiotic exposure and ASD or ADHD in later life can be partially explained by unmeasured genetic and familial confounding factors.

Maternal non-steroidal anti-inflammatory drug exposure during pregnancy and risk of miscarriage: a systematic review and meta-analysis.

BACKGROUND: Numerous studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) might be associated with increased risk of miscarriage. However, these results are conflicting and inconclusive. METHODS: We performed this systematic review and meta-analysis to assess the relationship between NSAIDs exposure and risk of miscarriage. A systematic literature search was conducted to identify relevant studies published from the time of database inception until June 2021. RESULTS: A total of ten studies involving 207,341 pregnant women were subjected to meta-analysis. There was no statistically significantly increased risk of miscarriage with the use of NSAIDs during pregnancy (OR = 1.37, 95% CI 0.99-1.88, p = 0.057). However, our findings showed that women exposed to NSAIDs around the time of conception were at increased risk of miscarriage (OR 2.32, 95% CI 1.16-4.66, p = 0.018). Furthermore, no significant association between NSAID use and miscarriage was evident during the first trimester of pregnancy (OR = 1, 95% CI = 0.83-1.2, p = 0.996), possibly attributable to the small sample size. CONCLUSION: Our findings indicate that NSAID exposure around the time of conception might be a risk factor for miscarriage. Further studies are needed to evaluate whether the risk varies by the type, dosage, or timing of NSAID exposure.