There is accumulating evidence on the beneficial effects of probiotic supplementation for patients with depressive disorders. However, prior reviews on the topic have largely focused on clinical effectiveness with limited emphasis on the underlying mechanisms of action and effects of probiotics on gut microbiota. In accordance with PRISMA guidelines, a systematic literature search of Medline, EMBASE and the Cochrane Library using combinations of the key words, (“depress*” OR “MDD” OR “suicide”), (“probiotic” OR “Lactobacillus” OR “Bifidobacterium”) AND (“gut” OR “gut micr*” OR “microbiota”), as well as grey literature was performed. We found seven clinical trials involving patients with major depressive disorder (MDD). The small number of studies and heterogeneous sources of data precluded meta-analysis. Most trials (other than one open-label trial) had a low-to-moderate risk of bias, which was largely due to a lack of control for the effects of diet on gut microbiota. Probiotic supplementation yielded only modest effects on depressive symptoms and there were no consistent effects on gut microbiota diversity, and in most instances, no significant alterations in gut microbiota composition were observed after four to eight weeks of probiotic intervention. There is also a lack of systematic reporting on adverse events and no good longer-term data. Patients with MDD may require a longer time to show clinical improvement and the microbial host environment may also need longer than eight weeks to produce significant microbiota alterations. To advance this field, further larger-scale and longer-term studies are required.
Irritable bowel syndrome is a prototypical disorder of the brain–gut–microbiome axis, although the underlying pathogenesis and mechanisms remain incompletely understood. With the recent advances in ‘omics’ technologies, studies have attempted to uncover IBS-specific variations in the host–microbiome profile and function. However, no biomarker has been identified to date. Given the high inter-individual and day-to-day variability of the gut microbiota, and a lack of agreement across the large number of microbiome studies, this review focused on omics studies that had sampling at more than one time point. A systematic literature search was performed using various combinations of the search terms “Irritable Bowel Syndrome” and “Omics” in the Medline, EMBASE, and Cochrane Library up to 1 December 2022. A total of 16 original studies were reviewed. These multi-omics studies have implicated Bacteroides, Faecalibacterium prausnitzii, Ruminococcus spp., and Bifidobacteria in IBS and treatment response, found altered metabolite profiles in serum, faecal, or urinary samples taken from IBS patients compared to the healthy controls, and revealed enrichment in the immune and inflammation-related pathways. They also demonstrated the possible therapeutic mechanisms of diet interventions, for example, synbiotics and low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol (FODMAP) diets on microbial metabolites. However, there was significant heterogeneity among the studies and no uniform characteristics of IBS-related gut microbiota. There is a need to further study these putative mechanisms and also ensure that they can be translated to therapeutic benefits for patients with IBS.
Cancer-related anorexia/cachexia is known to be associated with worsened quality of life and survival; however, limited treatment options exist. Although megestrol acetate (MA) is often used off-label to stimulate appetite and improve anorexia/cachexia in patients with advanced cancers, the benefits are controversial. The present meta-analysis aimed to better elucidate the clinical benefits of MA in patients with cancer-related anorexia/cachexia. A systematic search of PubMed, EMBASE, OVID Medline, Clinicaltrials.gov, and Google Scholar databases found 23 clinical trials examining the use of MA in cancer-related anorexia. The available randomized, controlled trials were appraised using Version 2 of the Cochrane risk-of-bias tool (RoB 2) and they had moderate-to-high risk of bias. A total of eight studies provided sufficient data on weight change for meta-analysis. The studies were divided into high-dose treatment (>320 mg/day) and low-dose treatment (≤320 mg/day). The overall pooled mean change in weight among cancer patients treated with MA, regardless of dosage was 0.75 kg (95% CI = −1.64 to 3.15, τ2 = 9.35, I2 = 96%). Patients who received high-dose MA tended to have weight loss rather than weight gain. There were insufficient studies to perform a meta-analysis for the change in tricep skinfold, midarm circumference, or quality of life measures. MA was generally well-tolerated, except for a clear thromboembolic risk, especially with higher doses. On balance, MA did not appear to be effective in providing the symptomatic improvement of anorexia/cachexia in patients with advanced cancer.
Background and Objectives: Acute cholecystitis (AC) is a common surgical emergency. Recent evidence suggests that serum procalcitonin (PCT) is superior to leukocytosis and serum C-reactive protein in the diagnosis and severity stratification of acute infections. This review evaluates the role of PCT in AC diagnosis, severity stratification, and management. Materials and Methods: PubMed, Embase, and Scopus were searched from inception till 21 August 2022 for studies reporting the role of PCT in AC. A qualitative analysis of the existing literature was conducted. Results: Five articles, including 688 patients, were included. PCT ≤ 0.52 ng/mL had fair discriminative ability (Area under the curve (AUC) 0.721, p < 0.001) to differentiate Grade 1 from Grade 2–3 AC, and PCT > 0.8 ng/mL had good discriminatory ability to differentiate Grade 3 from 1–2 AC (AUC 0.813, p < 0.001). PCT cut-off ≥ 1.50 ng/mL predicted difficult laparoscopic cholecystectomy (sensitivity 91.3%, specificity 76.8%). The incidence of open conversion was higher with PCT ≥ 1 ng/mL (32.4% vs. 14.6%, p = 0.013). A PCT value of >0.09 ng/mL could predict major complications (defined as open conversion, mechanical ventilation, and death). Conclusions: Current evidence is plagued by the heterogeneity of small sample studies. Though PCT has some role in assessing severity and predicting difficult cholecystectomy, and postoperative complications in AC patients, more evidence is necessary to validate its use.
Long-term outcomes after non-traumatic pediatric out-of-hospital cardiac arrest (OHCA) are not well understood. This systematic review aimed to summarize long-term outcomes (1 year and beyond), including overall survival, survival with favorable neurological outcomes, and health-related quality of life (HRQoL) outcomes) amongst pediatric OHCA patients who survived to discharge. Embase, Medline, and The Cochrane Library were searched from inception to October 6, 2021. Studies were included if they reported outcomes at 1 year or beyond after pediatric OHCA. Data abstraction and quality assessment was conducted by three authors independently. Qualitative outcomes were reported systematically. Seven studies were included, and amongst patients that survived to hospital discharge or to 30 days, longer-term survival was at least 95% at 24 months of follow up. A highly variable proportion (range 10–71%) of patients had favorable neurological outcomes at 24 months of follow up. With regard to health-related quality of life outcomes, at a time point distal to 1 year, at least 60% of pediatric non-traumatic OHCA patients were reported to have good outcomes. Our study found that at least 95% of pediatric OHCA patients, who survived to discharge, survived to a time point distal to 1 year. There is a general paucity of data surrounding the pediatric OHCA population.
Despite its prevalence and disease burden, several chasms still exist with regard to the pharmacotherapy of bipolar disorder (BD). Polypharmacy is commonly encountered as a significant proportion of patients remain symptomatic, and the management of the depressive phase of the illness is a particular challenge. Gabapentin and pregabalin have often been prescribed off-label in spite of a paucity of evidence and clinical practice guidelines to support its use. This systematic review aimed to synthesize the available human clinical trials and inform evidence-based pharmacological approaches to BD management. A total of six randomized, controlled trials (RCTs) and 13 open-label trials involving the use of gabapentin and pregabalin in BD patients were reviewed. Overall, the studies show that gabapentin and its related drug pregabalin do not have significant clinical efficacy as either monotherapy or adjunctive therapy for BD. Gabapentin and pregabalin are probably ineffective for acute mania based on the findings of RCT, with only small open-label trials to support its potential adjunctive role. However, its effects on the long-term outcomes of BD remain to be elucidated. The evidence base was significantly limited by the generally small sample sizes and the trials also had heterogeneous designs and generally high risk of bias.