Systematic review and meta-analysis of global prevalence of neurotoxic and hemotoxic snakebite envenomation.

Background: The World Health Organization estimates that there are approximately 5.4 million snakebites and 1.8-2.7 million cases of envenomation, with 81 410-137 880 deaths each year worldwide. Aims: To estimate the prevalence of neurotoxic and haemotoxic snakebite envenomation through a comprehensive systematic review and meta-analysis. Methods: We searched Medline/PubMed, Scopus and Cochrane Library up to January 2021 using keywords such as snakebite and snake envenomation. Bibliographic and random searches were also performed. Prospective or retrospective observational studies and randomized controlled trials were included for the review. Results: We included 271 of 9711 studies published between 1963 and 2020. The pooled prevalence of snakebite from 188 studies with a total of 207 235 participants showed the highest prevalence in North America (69.20%; 95% confidence interval, CI: 57.06-81.34%) and lowest in Africa (28.10%; 95% CI: 22.22-33.98%). There was a pooled prevalence of 24.94% (95% CI: 22.84-27.03%) for haemotoxicity, with a highest prevalence of coagulopathy (43.76%; 95% CI: 33.15-54.37%). The overall prevalence of neurotoxicity was 38.20% (95% CI: 31.88-44.53%), with a highest prevalence of ptosis (53.57%; 95% CI: 38.51-68.62%). Conclusion: There was a higher prevalence of snakebites in North America. The most prevalent haemotoxicity and neurotoxicity were coagulopathy and ptosis, respectively. The overall quality of evidence was good with a non-significant publication bias.

Proton pump inhibitors use and risk of inflammatory bowel diseases: a meta-analysis of observational studies.

Background and objective: Proton Pump Inhibitors (PPIs) reduce gastric acid production and they are indicated for myriad gastrointestinal conditions. Prolonged use of PPI has been linked to the risk of inflammatory bowel disease (IBD) though this fact is not well established. We aimed to conduct a systematic review and meta-analysis to estimate the risk of IBD occurrence with PPI use. Methodology: The databases such as PubMed, Scopus, and Cochrane Library were accessed from inception to December 2020. Additionally, the bibliographic search and a random search in Google, Google Scholar, and ResearchGate were performed to find additional sources. The observational studies estimating the risk of IBD following the use of PPI, published in the English language were considered for this review. The methodological quality of included studies was assessed using the Modified Downs and Black checklist. Results: Eight out of 2038 studies with 157,758 participants were included in this meta-analysis. A significantly higher risk of IBD (adjusted odds ratio [aOR] 2.43; 95% Confidence Interval [CI] 1.18-5.02; P=0.02; n=6) was observed in participants taking PPIs for any indication. Moreover, a significant association was observed between PPI exposure on the different types of IBD such as ulcerative colitis and Crohn's disease together (aOR: 3.60; 95% CI: 1.10-11.74), collagenous colitis (OR: 4.73; 95% CI: 1.99-11.22) and lymphocytic Colitis (OR: 3.77; 95% CI: 2.91-4.87), but not with ulcerative colitis (P=0.47) and microscopic colitis (P=0.07) alone. Similarly, a significant association was observed among Europeans (aOR: 3.98; 95% CI: 2.36-6.71), but not with North American (aOR: 0.48; 95% CI: 0.01-26.71) studies. Overall the study quality was good. Conclusion: The current evidence indicates that exposure to PPI is significantly associated with increased risk of IBD. Further, adequately powered studies from various parts of the world are needed for better quantification and generalizability of our findings. PROSPERO Protocol Registration Number: CRD42020209674.

Integration of liquid biopsy and pharmacogenomics for precision therapy of EGFR mutant and resistant lung cancers.

The advent of molecular profiling has revolutionized the treatment of lung cancer by comprehensively delineating the genomic landscape of the epidermal growth factor receptor (EGFR) gene. Drug resistance caused by EGFR mutations and genetic polymorphisms of drug metabolizing enzymes and transporters impedes effective treatment of EGFR mutant and resistant lung cancer. This review appraises current literature, opportunities, and challenges associated with liquid biopsy and pharmacogenomic (PGx) testing as precision therapy tools in the management of EGFR mutant and resistant lung cancers. Liquid biopsy could play a potential role in selection of precise tyrosine kinase inhibitor (TKI) therapies during different phases of lung cancer treatment. This selection will be based on the driver EGFR mutational status, as well as monitoring the development of potential EGFR mutations arising during or after TKIs treatment, since some of these new mutations may be druggable targets for alternative TKIs. Several studies have identified the utility of liquid biopsy in the identification of EGFR driver and acquired resistance with good sensitivities for various blood-based biomarkers. With a plethora of sequencing technologies and platforms available currently, further evaluations using randomized controlled trials (RCTs) in multicentric, multiethnic and larger patient cohorts could enable optimization of liquid-based assays for the detection of EGFR mutations, and support testing of CYP450 enzymes and drug transporter polymorphisms to guide precise dosing of EGFR TKIs.