Running title: Network meta-analysis of pharmacological agents for treatment of CIC Word count: 3745 (excluding abstract, summary box, acknowledgements, disclosures, references, table and figure legends) Key words: bisacodyl, elobixibat, linaclotide, lubiprostone, picosulfate, polyethylene glycol, prucalopride, tegaserod, velusetrag Abbreviations: chronic idiopathic constipation (CIC) numbers needed to treat (NNT) sodium picosulfate (NaP) polyethylene glycol (PEG) complete spontaneous bowel movements (CSBM) spontaneous bowel movements (SBM) weighted mean difference (WMD) confidence interval (CI) Study Selection: Phase IIB and phase III randomized, placebo-controlled trials (RCT) of ≥4weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least 1 of 4 endpoints. Data Extraction and Synthesis:Two investigators independently evaluated all full text articles that met inclusion criteria and extracted data for primary and secondary endpoints, risk of bias and quality of evidence.Outcomes: Primary endpoints were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary endpoints were change from baseline (∆ b ) in the number of SBM/week and ∆ b CSBM/week.Results: Twenty-one RCTs (9189 patients) met inclusion and endpoint criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All pre-specified endpoints were unavailable in 4 polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week endpoint. No drug was superior at improving the primary endpoints on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary endpoint, ∆ b in number of SBM/week.

Both short (<7 hours) and long sleep durations (>9 hours) can increase the risk of overall cardiovascular disease mortality, particularly in Asian populations and elderly individuals. Future epidemiological studies would ideally include objective sleep measurements, rather than self-report measures, and all potential confounders, such as genetic variants.

We examined risks for first hospitalization and the rate, risk factors, costs, and 1‐year outcome of 30‐day readmission among patients admitted for complications of cirrhosis. Data were retrospectively analyzed for adult patients with cirrhosis residing in Minnesota, Iowa, or Wisconsin and admitted from 2010 through 2013 at both campuses of the Mayo Clinic Hospital in Rochester, MN. Readmission was captured at the two hospitals as well as at community hospitals in the tristate area within the Mayo Clinic Health System. The incidence of hospitalization for complications of cirrhosis was 100/100,000 population, with increasing age and male sex being the strongest risks for hospitalization. For the 2,048 hospitalized study patients, the overall 30‐day readmission rate was 32%; 498 (24.3%) patients were readmitted to Mayo Clinic hospitals and 157 (7.7%) to community hospitals, mainly for complications of portal hypertension (52%) and infections (30%). Readmission could not be predicted accurately. There were 146 deaths during readmission and an additional 105 deaths up to 1 year of follow‐up (50.4% total mortality). Annual postindex hospitalization costs for those with a 30‐day readmission were substantially higher ($73,252) than those readmitted beyond 30 days ($62,053) or those not readmitted ($5,719). At 1‐year follow‐up, only 20.4% of patients readmitted within 30 days were at home. In conclusion, patients with cirrhosis have high rates of hospitalization, especially among men over 65 years, and of unscheduled 30‐day readmission. Readmission cannot be accurately predicted. Postindex hospitalization costs are high; nationally, the annual costs are estimated to be more than $4.45 billion. Only 20% of patients readmitted within 30 days are home at 1 year. (Hepatology Communications 2018;2:188–198)

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