Factors Associated With Loneliness: An Umbrella Review Of Observational Studies.

BACKGROUND: Evidence provides inconsistent findings on risk factors and health outcomes associated with loneliness. The aim of this work was to grade the evidence on risk factors and health outcomes associated with loneliness, using an umbrella review approach. METHODS: For each meta-analytic association, random-effects summary effect size, 95% confidence intervals (CIs), heterogeneity, evidence for small-study effect, excess significance bias and 95% prediction intervals were calculated, and used to grade significant evidence (p<0.05) from convincing to weak. For narrative systematic reviews, findings were reported descriptively. RESULTS: From 210 studies initially evaluated, 14 publications were included, reporting on 18 outcomes, 795 studies, and 746,706 participants. Highly suggestive evidence (class II) supported the association between loneliness and incident dementia (relative risk, RR=1.26; 95%CI: 1.14-1.40, I2 23.6%), prevalent paranoia (odds ratio, OR=3.36; 95%CI: 2.51-4.49, I2 92.8%) and prevalent psychotic symptoms (OR=2.33; 95%CI: 1.68-3.22, I2 56.5%). Pooled data supported the longitudinal association between loneliness and suicide attempts and depressive symptoms. In narrative systematic reviews, factors cross-sectionally associated with loneliness were age (in a U-shape way), female sex, quality of social contacts, low competence, socio-economic status and medical chronic conditions. LIMITATIONS: Low quality of the studies included; mainly cross-sectional evidence. CONCLUSIONS: This work is the first meta-evidence synthesis showing that highly suggestive and significant evidence supports the association between loneliness and adverse mental and physical health outcomes. More cohort studies are needed to disentangle the direction of the association between risk factors for loneliness and its related health outcomes.

Including Relative Adrenal Insufficiency in Definition and Classification of Acute-on-Chronic Liver Failure.

BACKGROUND & AIMS: Relative adrenal insufficiency (RAI) is defined by insufficient production of cortisol relative to organ demand. RAI is observed frequently in hospitalized patients with cirrhosis, but there is disagreement over the clinical effects of RAI in these patients. We evaluated the prevalence and the clinical effects of RAI in hospitalized patients with cirrhosis. METHODS: We performed a prospective study of 160 patients admitted to a hospital in Italy for acute decompensation of cirrhosis from May 2011 through September 2016. Patients were followed up until death, liver transplantation, or a maximum of 90 days. Serum and salivary levels of cortisol were measured before and after a 1-hour Short Synacthen Test. A diagnosis of RAI was given to patients with an increase in serum cortisol of less than 9 µg/dL, after Synacthen administration, in patients with baseline serum levels of cortisol less than 35 µg/dL. We collected blood samples before the Synacthen test and analyzed them for blood cell counts, liver and renal function, levels of C-reactive protein, and lipid profiles (total cholesterol, high-density lipoprotein cholesterol, apolipoprotein-A1). RESULTS: A diagnosis of RAI was made for 78 patients (49%). Age (odds ratio [OR], 0.95; P = .030), number of leukocytes (OR, 3.10; P = .006), and levels of high-density lipoprotein cholesterol (OR, 0.30; P = .039) were associated independently with RAI. Patients with RAI had a significantly higher risk of developing bacterial infections (hazard ratio [HR], 1.60; P = .038), sepsis (HR, 2.95; P = .001), septic shock (HR, 4.94; P = .038), new organ failures (HR, 2.45; P = .014), and acute-on-chronic liver failure (HR, 2.27; P = .037) than patients without RAI. RAI was associated independently with death within 90 days of diagnosis (subdistribution HR, 4.83; P = .001). Patients with RAI and mild renal dysfunction or hepatic encephalopathy had no significant difference in cumulative incidence of 28-day mortality vs patients with acute-on-chronic liver failure grade 1 (25% vs 22%). CONCLUSIONS: We found RAI to occur in almost half of patients admitted to a hospital for acute decompensation of cirrhosis. RAI was associated with a deficit of substrates for steroidogenesis and an increase in markers of inflammation. Patients with RAI have a high risk of developing sepsis, septic shock, organ failure, and death within 90 days. RAI has similar prognostic value to nonrenal organ failures.