Evidence around early induction of labor in women of advanced maternal age and those using assisted reproductive technology.

Worldwide, there has been a trend toward later motherhood. Concurrently, the incidence of subfertility has been on the rise, necessitating conception using assisted reproductive technologies (ARTs). These pregnancies are considered high risk due to fetal complications such as antepartum stillbirth and growth restriction and maternal complications such as increase in maternal morbidity and mortality. Early induction of labor can help to mitigate these risks. However, this has to be balanced against the iatrogenic harms of earlier delivery to both the baby, including respiratory distress and NICU stay, and the mother who might experience longer labor and other complications such as uterine hyperstimulation. Induction of labor at 39 weeks is the optimal timing for preventing antepartum stillbirth and avoiding iatrogenic harm. Delivery by elective cesarean section is not advocated as its benefits in these patients are unclear compared with the short- and long-term complications of a major abdominal surgery.

A Systematic Review of the Role of Prebiotics and Probiotics in Autism Spectrum Disorders.

Background: Autism spectrum disorder (ASD) is a complex developmental condition typically characterized by deficits in social and communicative behaviors as well as repetitive patterns of behaviors. Despite its prevalence (affecting 0.1% to 1.8% of the global population), the pathogenesis of ASD remains incompletely understood. Patients with ASD are reported to have more frequent gastrointestinal (GI) complaints. There is some anecdotal evidence that probiotics are able to alleviate GI symptoms as well as improve behavioral issues in children with ASD. However, systematic reviews of the effect of prebiotics/probiotics on ASD and its associated symptoms are lacking. Methods: Using the keywords (prebiotics OR probiotics OR microbiota OR gut) AND (autism OR social OR ASD), a systematic literature search was conducted on PubMed, EMBASE, Medline, Clinicaltrials.gov and Google Scholar databases. The inclusion criteria were original clinical trials, published in English between the period 1st January 1988 and 1st February 2019. Results: A total of eight clinical trials were systematically reviewed. Two clinical trials examined the use of prebiotic and/or diet exclusion while six involved the use of probiotic supplementation in children with ASD. Most of these were prospective, open-label studies. Prebiotics only improved certain GI symptoms; however, when combined with an exclusion diet (gluten and casein free) showed a significant reduction in anti-sociability scores. As for probiotics, there is limited evidence to support the role of probiotics in alleviating the GI or behavioral symptoms in children with ASD. The two available double-blind, randomized, placebo-controlled trials found no significant difference in GI symptoms and behavior. Conclusion: Despite promising preclinical findings, prebiotics and probiotics have demonstrated an overall limited efficacy in the management of GI or behavioral symptoms in children with ASD. In addition, there was no standardized probiotics regimen, with multiple different strains and concentrations of probiotics, and variable duration of treatments.

A Systematic Review of the Effect of Probiotic Supplementation on Schizophrenia Symptoms.

BACKGROUND: Derangements of the gut microbiome have been linked to increased systemic inflammation and central nervous system disorders, including schizophrenia. This systematic review thus aimed to investigate the hypothesis that probiotic supplementation improves schizophrenia symptoms. METHODS: By using the keywords (probiotic OR gut OR microbiota OR microbiome OR yogurt OR yoghurt OR lactobacillus OR bifidobacterium) AND (schizophrenia OR psychosis), a preliminary search of the PubMed, Medline, Embase, Google Scholar, ClinicalTrials.gov, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), and Cochrane Field for Complementary Medicine databases yielded 329 papers published in English between January 1, 1960 and May 1, 2018. Attempts were made to search grey literature as well. RESULTS: Three clinical studies were reviewed, comparing the use of probiotics to placebo controls. Applying per-protocol analysis and a fixed-effects model, there was no significant difference in schizophrenia symptoms between the group that received probiotic supplementation and the placebo group post-intervention as the standardized mean difference was -0.0884 (95% CI -0.380 to 0.204, p = 0.551). Separate analyses were performed to investigate the effect of probiotic supplementation on positive or negative symptoms of schizophrenia alone. In both instances, no significant difference was observed as well. CONCLUSION: Based on current evidence, limited inferences can be made regarding the efficacy of probiotics in schizophrenia. Although probiotics may have other benefits, for example to regulate bowel movement and ameliorate the metabolic effects of antipsychotic medications, the clinical utility of probiotics in the treatment of schizophrenia patients remains to be validated by future clinical studies.

A meta-analysis of the effectiveness of yoga-based interventions for maternal depression during pregnancy.

Prompt and effective treatment of maternal depression during pregnancy is important as it is an independent predictor of negative maternal and fetal outcomes. Yoga is an increasingly popular non-pharmacological modality. This study thus aimed to undertake a meta-analysis of the efficacy of yoga-based interventions for maternal depression during pregnancy. A total of 8 clinical studies were systematically reviewed, and 6 studies with a total of 405 pregnant mothers were included in the final meta-analysis. Applying per-protocol analysis and a random-effects model, the pooled standardized mean difference (SMD) from baseline depressive score was -0.452 (95% CI: -0.816 to -0.880, P = 0.015), supporting a statistically significant beneficial effect of yoga-based interventions on mood. Overall, yoga-based interventions are a promising non-pharmacological option, however, most trials examined were preliminary, recruited only participants with mild depression, did not blind study participants and had relatively small sample sizes. Larger randomized, controlled trials should be encouraged.

Systematic review with meta-analysis: The association between post-traumatic stress disorder and irritable bowel syndrome.

BACKGROUND AND AIM: Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by symptoms of hyperarousal and hypervigilance. Increasing research on the "gut-brain" axis (bidirectional signaling between the gut and the brain) has drawn links between PTSD and irritable bowel syndrome (IBS), an exceedingly common yet incompletely understood gastrointestinal condition. This meta-analysis thus aimed to examine the body of evidence and extent of association of PTSD with IBS. METHODS: Using the keywords [early abuse OR childhood abuse OR violence OR trauma OR PTSD] AND [irritable bowel syndrome or IBS], a preliminary search on the PubMed, Medline, Embase, ScienceDirect, PsychINFO, Web of Science, and Google Scholar databases yielded 11,257 papers published in English between January 1, 1988, and May 1, 2018. Of these, only eight studies were included in the final meta-analysis. RESULTS: The eight studies (four cross-sectional and four cohort) contained a total of 648,375 subjects. Most studies were from the USA and conducted on army veterans. The funnel plot revealed a roughly symmetrical distribution of studies, and Egger test was not significant for publication bias (P = 0.583). Random-effects meta-analysis found PTSD to be a significant risk factor for IBS (pooled odds ratio 2.80, 95% confidence interval: 2.06 to 3.54, P < 0.001). CONCLUSIONS: Overall, PTSD is associated with an increased likelihood of IBS. This is the first meta-analysis to specifically examine the association between PTSD and IBS, and it provides insights into the probable (patho)physiology and management of IBS, supporting a holistic consideration of the psychosocial aspects of IBS and further research into effective multi-modal therapeutics.

Selective Serotonin Reuptake Inhibitors and Persistent Pulmonary Hypertension of the Newborn: An Update Meta-Analysis.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition associated with substantial mortality and morbidity. Previous studies have suggested a possible link between maternal selective serotonin reuptake inhibitor (SSRI) use and the risk of PPHN. This study aimed to provide an up-to-date review and meta-analysis of the topic. METHODS: Using the search terms [SSRI OR SSRIs OR selective serotonin reuptake inhibitors OR antidepressant OR Prozac OR fluoxetine OR Lexapro OR escitalopram] AND [pregnancy OR maternal OR newborn OR persistent pulmonary hypertension OR PPHN OR neonat* OR fet*], a preliminary search on the PubMed, Medline, EMBASE, Web of Science, and Google Scholar database yielded 7327 articles published in English between January 1, 1960 and October 1, 2017. RESULTS: A total of 9 cohort and case-control studies, with a total of 7,540,265 subjects were systematically reviewed. Random-effects meta-analysis of eight studies revealed a significantly increased risk of PPHN with maternal SSRI use during pregnancy, with a pooled OR of 1.516 (95% confidence interval: 1.035-1.997, p < 0.001). Overall, the absolute increase in risk of PPHN with SSRI use appears small, with an absolute risk difference of 0.619 per 1000 livebirths and a number needed to harm of 1615 women. CONCLUSIONS: Current evidence suggests that there were significantly greater odds of PPHN with SSRI use during pregnancy. However, the clinical significance of this association remains modest and likely outweighed by the potential benefits of treatment of perinatal depression. The risk of PPHN associated with SSRI therapy might not warrant the recommendation to withdraw antidepressant therapy, as evidence from other studies show that untreated perinatal depression presents additional adverse maternal and fetal outcomes. Given the increasing prevalence of maternal depression and consequent use of antidepressant medications, further research with robust longitudinal or randomized, controlled studies and mechanistic investigations are needed.

A Meta-Analysis of the Clinical Use of Curcumin for Irritable Bowel Syndrome (IBS).

Irritable bowel syndrome (IBS) remains a prevalent and difficult-to-manage gastrointestinal condition. There is growing interest in the use of traditional medicine to manage IBS. In particular, curcumin, a biologically active phytochemical, has demonstrated anti-inflammatory and anti-oxidant properties and mucosal protective effects in rat models of colitis. This meta-analysis thus aimed to investigate the hypothesis that curcumin improves IBS symptoms. Using the keywords (curcumin OR turmeric OR Indian saffron OR diferuloylmethane OR curcuminoid) AND (irritable bowel syndrome OR IBS), a preliminary search on the PubMed, Medline, Embase, PsychINFO, Web of Science, and Google Scholar databases yielded 1080 papers published in English between 1 January 1988 and 1 May 2018. Five randomized, controlled trials were systematically reviewed and 3 were included in the final meta-analysis. Random-effects meta-analysis based on three studies and 326 patients found curcumin to have a beneficial albeit not statistically significant effect on IBS symptoms (pooled standardized mean difference from baseline IBS severity rating -0.466, 95% CI: -1.113 to 0.182, p = 0.158). This is the first meta-analysis to examine the use of curcumin in IBS. With its unique anti-oxidant and anti-inflammatory activities and ability to modulate gut microbiota, curcumin is a potentially useful addition to our armamentarium of agents for IBS. It also appears safe and well-tolerated, with no adverse events reported in the available trials. However, current findings are based on a considerably limited evidence base with marked heterogeneity. More robust clinical trials involving a standardized curcumin preparation and larger sample sizes should be encouraged.

A meta-analysis of cyclosporine treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are dermatologic emergencies with high morbidity and mortality risk. Cyclosporine, an immunomodulatory agent, is sometimes used off-label, and its role continues to be debated. This meta-analysis aimed to provide an update of current evidence and to clarify the role of cyclosporine in SJS/TEN treatment better. METHODS: Using the keywords [cyclosporine OR cyclosporine OR ciclosporin OR CsA] AND [Steven-Johnson OR SJS OR toxic epidermal OR epidermal necrolysis OR TEN OR hypersensitivity OR dermatologic OR burns], a preliminary search on the PubMed, Ovid, Web of Science, and Google Scholar Database yielded 615 papers published in English between January1, 1960 and July 1, 2017. The inclusion criteria for this review were: 1) published retrospective or prospective study (excluding single case reports); 2) patients with clinical diagnosis of SJS or TEN; 3) trial of cyclosporine treatment; and 4) available survival/mortality data. RESULTS: A total of 12 studies, with a total of 358 SJS/TEN patients were reviewed. Two studies were excluded from the meta-analysis as they did not report SCORe of toxic epidermal necrosis/predicted mortality data; one was excluded because of possible data irregularities. Meta-analysis of nine studies revealed a significant reduction in mortality risk with cyclosporine therapy (standardized mortality ratio 0.320; 95% CI: 0.119-0.522; P=0.002). Cyclosporine was also generally well tolerated with little adverse effects or increased infection, albeit the patients tended to be critically ill. Publication bias was observed in the funnel plot and Egger test (P=0.0467). CONCLUSION: Currently available evidence are predominantly open trials and retrospective studies with a significant risk of bias, perhaps owing to the rarity and life-threatening nature of the condition. Given its immunomodulatory actions, cyclosporine could be a potential treatment option for SJS/TEN in addition to best supportive measures. Further confirmation with robust randomized, controlled trials or larger case series is necessary and should be encouraged.

Use of Lactobacillus spp. to prevent recurrent urinary tract infections in females.

Urinary tract infections (UTIs) are the most common bacterial infections seen in the community, especially amongst females. The widespread use of antibiotics has led to the increased occurrence of E. coli resistant isolates worldwide. A promising non-antibiotic approach is the use of probiotic lactobacilli strains. This paper hypothesizes that Lactobacillus spp. containing products are able to prevent recurrent urinary tract infections in females. Using the keywords [lactobacillus OR lactobacilli OR probiotic] and [urinary tract infection OR UTI OR cystitis], a preliminary search on the PubMed, Ovid, Google Scholar and ClinicalTrials.gov database yielded 1,647 papers published in English between 1-Jan-1960 and 1-May-2017. 9 clinical trials with a total of 726 patients were reviewed. Different lactobacilli strains (in either oral or suppository formulation) were utilized and they demonstrated varying efficacy in the prevention of recurrent UTIs. Using a random-effects model, pooled risk ratio of at least one recurrent UTI episode during the entire study duration was 0.684 (95% CI 0.438 to 0.929, p < 0.001), per-protocol analysis. However, key limitations include significant inter-study variability and the limited duration of follow-up of most studies. Our hypothesis on the chemoprophylactic effects of probiotics for UTIs is plausible and supported by current data. Lactobacillus rhamnosus GR1 and Lactobacillus reuteri RC14 were the most commonly studied lactobacilli strains. Further and more robust randomized controlled trials with standardized lactobacilli strains and formulation are required for confirmation of effects.

A meta-analysis of the association between Helicobacter pylori (H. pylori) infection and hyperemesis gravidarum.

BACKGROUND: Hyperemesis gravidarum remains a common, distressing, and significant yet poorly understood disorder during pregnancy. The association between maternal Helicobacter pylori (H. pylori) infection and hyperemesis gravidarum has been increasingly recognized and investigated. This study thus aimed to provide an updated review and meta-analysis of the topic. METHODS: Using the search terms (H. pyloriOR Helicobacter ORHelicobacter pyloriOR infection) AND (pregnancy OR emesis OR hyperemesis gravidarum OR nausea OR vomiting), a preliminary search on the PubMed, Ovid, Web of Science, Google Scholar, and WanFang database yielded 372 papers published in English between January 1st, 1960 and June 1st, 2017. RESULTS: A total of 38 cross-sectional and case-control studies, with a total of 10 289 patients were eligible for review. Meta-analysis revealed a significant association between H. pylori infection and hyperemesis gravidarum during pregnancy, with a pooled odds ratio of 1.348 (95% CI: 1.156-1.539, P < .001). Subgroup analysis found that serologic and stool antigen tests were comparable methods of detecting H. pylori as they yielded similar odds ratios. LIMITATIONS: Although the studies did not have high heterogeneity (I2  = 28%), publication bias was observed, and interstudy discrepancies in the diagnostic criteria adopted for hyperemesis gravidarum limit the reliability of findings. Also, 15 of the included studies were from the same country (Turkey), which could limit the generalizability of current findings. The prevalence of H. pylori infection varies throughout the world, and there may also be pathogenic differences as most strains of H. pylori in East Asia carry the cytotoxin-associated gene A gene. CONCLUSION: H. pylori infection was associated with an increased likelihood of hyperemesis gravidarum during pregnancy. Given the high prevalence of H. pylori infections worldwide, detecting H. pylori infection and the eradication of maternal H. pylori infection could be part of maternal hyperemesis gravidarum management. Further confirmation with robust longitudinal studies and mechanistic investigations are needed.

A meta-analysis of the use of rifaximin to prevent travellers' diarrhoea.

BACKGROUND: Travellers' diarrhoea affects tens of millions of people travelling to less developed countries or regions annually. There are positive reports of the use of rifaximin, a non-absorbed, gut-selective antibiotic to prevent travellers' diarrhoea. This study will critically review and analyse clinical trials on the subject. METHODS: Using the keywords [diarrhoea OR diarrhoea OR travel*] AND [rifaximin OR xifaxan OR xifaxanta OR normix OR rifagut], a preliminary search on the PubMed and Ovid databases yielded 411 papers published in English between 1 January 1988 and 1 July 2016. Of these, there were only five relevant clinical trials. RESULTS: The clinical trials were double-blind, placebo-controlled, randomized trials with a total of 879 subjects. The meta-analysis found significant reduction in risk of travellers' diarrhoea with rifaximin use compared to placebo (pooled RR 0.478, 95% CI: 0.375-0.610, and P < 0.001). For the entire travel and follow-up period, the risk of developing travellers' diarrhoea was significantly greater in individuals receiving the placebo than those receiving rifaximin (daily doses of 400-600 mg). Overall, rifaximin offered significant protection rates of 48-72%, with lower protection rates for Asian than Latin American countries. In terms of tolerability, similar rates of adverse events were reported for the rifaximin and placebo group ( P > 0.05), with no clinically significant or serious adverse events related to rifaximin use. CONCLUSIONS: There is good evidence supporting the use of rifaximin as a chemoprophylactic agent against travellers' diarrhoea, especially in individuals who are at high risk of severe complications from acute infectious diarrhoea. Rifaximin has an excellent tolerability/safety profile and demonstrated efficacy against diarrhoeagenic Escherichia coli and even enteroinvasive bacteria such Campylobacter species. Future studies should study the most effective dosing regimen for rifaximin chemoprophylaxis, as well as profile local antimicrobial resistance/susceptibility data in less developed regions to further guide rifaximin use.

Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis.

INTRODUCTION: St John's wort is a popular herbal remedy recommended by Traditional Chinese Medicine (TCM) practitioners and licensed and widely prescribed for depression in many European countries. However, conflicting data regarding its benefits and risks exist, and the last large meta-analysis on St John's wort use for depression was done in 2008, with no updated meta-analysis available. METHODS: Using the keywords [St John's Wort OR Hypericum perforatum OR hypericin OR hyperforin OR johanniskraut OR] AND [depression OR antidepressant OR SSRI], a preliminary search (without language restriction) on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group, Cochrane Field for Complementary Medicine, China National Knowledge Infrastructure and WanFang database yielded 5428 papers between 1-Jan-1960 and 1-May-2016. RESULTS: 27 clinical trials with a total of 3808 patients were reviewed, comparing the use of St John's wort and SSRI. In patients with depression, St John's wort demonstrated comparable response (pooled RR 0.983, 95% CI 0.924-1.042, p<0.001) and remission (pooled RR 1.013, 95% CI 0.892-1.134, p<0.001) rate, and significantly lower discontinuation/dropout (pooled OR 0.587, 95% CI 0.478-0.697, p<0.001) rate compared to standard SSRIs. The pooled SMD from baseline HAM-D scores (pooled SMD -0.068, 95% CI -0.127 to 0.021, p<0.001) also support its significant clinical efficacy in ameliorating depressive symptoms. LIMITATIONS: Evidence on the long-term efficacy and safety of St. John's wort is limited as the duration of all available studies ranged from 4 to 12 weeks. It is also unclear if St John's wort would be beneficial for patients with severe depression, high suicidality or suicide risk. CONCLUSION: For patients with mild-to-moderate depression, St John's wort has comparable efficacy and safety when compared to SSRIs. Follow-up studies carried out over a longer duration should be planned to ascertain its benefits.

A Systematic Review and Meta-Analysis of the Efficacy of Cognitive Behavioral Therapy for the Management of Pediatric Migraine.

INTRODUCTION: Migraine headaches are common in children and adolescents. Current pharmacologic treatment options are limited despite the prevalence and debilitating effects of pediatric migraine. Cognitive behavioral therapy (CBT) is an evidence-based practice that focuses on the development of coping strategies and cognitive restructuring to alter the pain experience. Till date, no meta-analysis has been done to examine the use of CBT in pediatric migraine. METHODS: Using the keywords (cognitive behavioral therapy OR cognitive behavior therapy OR cognitive behavioral therapy OR cognitive behavior therapy OR CBT) AND (headache OR migraine), a preliminary search on the PubMed and Ovid database yielded 3841 articles published in English between 1 Jan 1980 and 1 May 2016. Full articles were also reviewed for references of interest. After data extraction, 14 studies were included in the meta-analysis. RESULTS: The results of the meta-analysis well-support the clinical role of CBT in the management of pediatric migraine. The pooled odds ratios of clinically significant improvement, that is, 50% or greater headache activity reduction post-treatment and at follow-up (3 months or later) were OR 9.11 (95% CI: 5.01 to 16.58, P < .001) and OR 9.18 (95% CI: 5.69 to 14.81, P < .001) respectively, demonstrating significant clinical improvement with CBT as compared with wait-list control, placebo, or standard medication. Furthermore, the clinical improvement was stable, even at a 1-year follow-up as evident in some of the studies. CONCLUSION: There is good evidence that CBT is beneficial to children suffering from migraine, and may also augment the efficacy of standard medications such as amitriptyline.