The global epidemiology of upper and lower gastrointestinal bleeding in general population: A systematic review.

BACKGROUND: Gastrointestinal bleeding (GIB) is a common and potentially life-threatening clinical event. To date, the literature on the long-term global epidemiology of GIB has not been systematically reviewed. AIM: To systematically review the published literature on the worldwide epidemiology of upper and lower GIB. METHODS: EMBASE® and MEDLINE were queried from 01 January 1965 to September 17, 2019 to identify population-based studies reporting incidence, mortality, or case-fatality rates of upper GIB (UGIB) or lower GIB (LGIB) in the general adult population, worldwide. Relevant outcome data were extracted and summarized (including data on rebleeding following initial occurrence of GIB when available). All included studies were assessed for risk of bias based upon reporting guidelines. RESULTS: Of 4203 retrieved database hits, 41 studies were included, comprising a total of around 4.1 million patients with GIB worldwide from 1980-2012. Thirty-three studies reported rates for UGIB, four for LGIB, and four presented data on both. Incidence rates ranged from 15.0 to 172.0/100000 person-years for UGIB, and from 20.5 to 87.0/100000 person-years for LGIB. Thirteen studies reported on temporal trends, generally showing an overall decline in UGIB incidence over time, although a slight increase between 2003 and 2005 followed by a decline was shown in 5/13 studies. GIB-related mortality data were available from six studies for UGIB, with rates ranging from 0.9 to 9.8/100000 person-years, and from three studies for LGIB, with rates ranging from 0.8 to 3.5/100000 person-years. Case-fatality rate ranged from 0.7% to 4.8% for UGIB and 0.5% to 8.0% for LGIB. Rates of rebleeding ranged from 7.3% to 32.5% for UGIB and from 6.7% to 13.5% for LGIB. Two main areas of potential bias were the differences in the operational GIB definition used and inadequate information on how missing data were handled. CONCLUSION: Wide variation was seen in estimates of GIB epidemiology, likely due to high heterogeneity between studies however, UGIB showed a decreasing trend over the years. Epidemiological data were more widely available for UGIB than for LGIB.

Diagnostic and prognostic factors in patients with prostate cancer: a systematic review.

OBJECTIVES: As part of the PIONEER Consortium objectives, we have explored which diagnostic and prognostic factors (DPFs) are available in relation to our previously defined clinician and patient-reported outcomes for prostate cancer (PCa). DESIGN: We performed a systematic review to identify validated and non-validated studies. DATA SOURCES: MEDLINE, Embase and the Cochrane Library were searched on 21 January 2020. ELIGIBILITY CRITERIA: Only quantitative studies were included. Single studies with fewer than 50 participants, published before 2014 and looking at outcomes which are not prioritised in the PIONEER core outcome set were excluded. DATA EXTRACTION AND SYNTHESIS: After initial screening, we extracted data following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) criteria and discussed the identified factors with a multidisciplinary expert group. The quality of the included papers was scored for applicability and risk of bias using validated tools such as PROBAST, Quality in Prognostic Studies and Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS: The search identified 6604 studies, from which 489 DPFs were included. Sixty-four of those were internally or externally validated. However, only three studies on diagnostic and seven studies on prognostic factors had a low risk of bias and a low risk concerning applicability. CONCLUSION: Most of the DPFs identified require additional evaluation and validation in properly designed studies before they can be recommended for use in clinical practice. The PIONEER online search tool for DPFs for PCa will enable researchers to understand the quality of the current research and help them design future studies. ETHICS AND DISSEMINATION: There are no ethical implications.

The alpha-7 nicotinic acetylcholine receptor agonist GTS-21 engages the glucagon-like peptide-1 incretin hormone axis to lower levels of blood glucose in db/db mice.

AIM: To establish if alpha-7 nicotinic acetylcholine receptor (α7nAChR) agonist GTS-21 exerts a blood glucose-lowering action in db/db mice, and to test if this action requires coordinate α7nAChR and GLP-1 receptor (GLP-1R) stimulation by GTS-21 and endogenous GLP-1, respectively. MATERIALS AND METHODS: Blood glucose levels were measured during an oral glucose tolerance test (OGTT) using db/db mice administered intraperitoneal GTS-21. Plasma GLP-1, peptide tyrosine tyrosine 1-36 (PYY1-36), glucose-dependent insulinotropic peptide (GIP), glucagon, and insulin levels were measured by ELISA. A GLP-1R-mediated action of GTS-21 that is secondary to α7nAChR stimulation was evaluated using α7nAChR and GLP-1R knockout (KO) mice, or by co-administration of GTS-21 with the dipeptidyl peptidase-4 inhibitor, sitagliptin, or the GLP-1R antagonist, exendin (9-39). Insulin sensitivity was assessed in an insulin tolerance test. RESULTS: Single or multiple dose GTS-21 (0.5-8.0 mg/kg) acted in a dose-dependent manner to lower levels of blood glucose in the OGTT using 10-14 week-old male and female db/db mice. This action of GTS-21 was reproduced by the α7nAChR agonist, PNU-282987, was enhanced by sitagliptin, was counteracted by exendin (9-39), and was absent in α7nAChR and GLP-1R KO mice. Plasma GLP-1, PYY1-36, GIP, glucagon, and insulin levels increased in response to GTS-21, but insulin sensitivity, body weight, and food intake were unchanged. CONCLUSIONS: α7nAChR agonists improve oral glucose tolerance in db/db mice. This action is contingent to coordinate α7nAChR and GLP-1R stimulation. Thus α7nAChR agonists administered in combination with sitagliptin might serve as a new treatment for type 2 diabetes.