Epilepsy related multimorbidity,polypharmacy and risks in adults with intellectual disabilities: a national study

Journal of Neurology - A quarter of people with Intellectual Disability (ID) in the UK have epilepsy compared to 0.6% in the general population and die much younger. Epilepsy is associated with...     

Associations between loneliness and acute hospitalisation outcomes among patients receiving mental healthcare in South London: a retrospective cohort study

Purpose

It is well known that loneliness can worsen physical and mental health outcomes, but there is a dearth of research on the impact of loneliness in populations receiving mental healthcare. This study aimed to investigate cross-sectional correlates of loneliness among such patients and longitudinal risk for acute general hospitalisations.

Method

A retrospective observational study was conducted on the data from patients aged 18 + receiving assessment/care at a large mental healthcare provider in South London. Recorded loneliness status was ascertained among active patients on the index date, 30th Jun 2012. Acute general hospitalisation (emergency/elective) outcomes were obtained until 31st Mar 2018. Length of stay was modelled using Poisson regression models and time-to hospitalisation and time-to mortality were modelled using Cox proportional hazards regression models.

Results

The data from 26,745 patients were analysed. The prevalence of patients with recorded loneliness was 16.4% at the index date. In the fully adjusted model, patients with recorded loneliness had higher hazards of emergency (HR 1.15, 95% CI 1.09–1.22) and elective (1.05, 1.01–1.12) hospitalisation than patients who were not recorded as lonely, and a longer duration of both emergency (IRR 1.06, 95% CI 1.05–1.07) and elective (1.02, 1.01–1.03) general hospitalisations. There was no association between loneliness and mortality. Correlates of loneliness included having an eating disorder (OR 1.67, 95% CI 1.29–2.25) and serious mental illnesses (OR 1.44, 1.29–1.62).

Conclusion

Loneliness in patients receiving mental healthcare is associated with higher use of general hospital services. Increased attention to the physical healthcare of this patient group is therefore warranted.

     

Gestational diabetes and cardiovascular risk factors and disease in U.S. Hispanics/Latinas in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

To compare cardiovascular risk and disease prevalence in U.S. Hispanics/Latinas with and without a history of gestational diabetes mellitus (GDM). Cross-sectional data from 2008 to 2011 were analyzed for 8,262 (305 with GDM history) parous women, aged 20–73 years, from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Women with and without a history of GDM were compared on sociodemographic, cardiovascular risk factor, and disease data from standardized interviews and fasting blood tests, using chi-square tests, t-tests, and logistic regressions to determine odds ratios (ORs) and 95 percent confidence intervals (CIs). Adjusting for covariates, compared to those without a history of GDM, women with a history of GDM were younger (M = 39.1 years [95 percent CI = 37.8, 41.6] vs. 45.5 years [95 percent CI = 44.9, 46.1]) and more likely to have health insurance (68.1 percent [95 percent CI = 60.3 percent, 76.0 percent] vs. 54.9 percent [95 percent CI = 52.8 percent, 57.1 percent]), had greater waist circumference (M = 102.3 cm, [95 percent CI = 100.2, 104.3] vs. 98.1 cm [95 percent CI = 97.4, 98.5]) and higher fasting glucose (116.0 mg/dL [95 percent CI = 107.8, 124.3] vs. 104.2 mg/dL [95 percent CI = 103.4, 105.1]), and had higher odds of having metabolic syndrome (OR = 1.7 [95 percent CI = 1.2, 2.6]) or diabetes (OR = 3.3 [95 percent CI = 2.2, 4.8]). Prevalences of heart and cerebrovascular disease were similar. GDM history was positively associated with diabetes but not with cardiovascular disease.     

The chemotherapeutic agent DMXAA potently and specifically activates the TBK1-IRF-3 signaling axis

Vascular disrupting agents (VDAs) represent a novel approach to the treatment of cancer, resulting in the collapse of tumor vasculature and tumor death. 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a VDA currently in advanced phase II clinical trials, yet its precise mechanism of action is unknown despite extensive preclinical and clinical investigations. Our data demonstrate that DMXAA is a novel and specific activator of the TANK-binding kinase 1 (TBK1)-interferon (IFN) regulatory factor 3 (IRF-3) signaling pathway. DMXAA treatment of primary mouse macrophages resulted in robust IRF-3 activation and approximately 750-fold increase in IFN-beta mRNA, and in contrast to the potent Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS), signaling was independent of mitogen-activated protein kinase (MAPK) activation and elicited minimal nuclear factor kappaB-dependent gene expression. DMXAA-induced signaling was critically dependent on the IRF-3 kinase, TBK1, and IRF-3 but was myeloid differentiation factor 88-, Toll-interleukin 1 receptor domain-containing adaptor inducing IFN-beta-, IFN promoter-stimulator 1-, and inhibitor of kappaB kinase-independent, thus excluding all known TLRs and cytosolic helicase receptors. DMXAA pretreatment of mouse macrophages induced a state of tolerance to LPS and vice versa. In contrast to LPS stimulation, DMXAA-induced IRF-3 dimerization and IFN-beta expression were inhibited by salicylic acid. These findings detail a novel pathway for TBK1-mediated IRF-3 activation and provide new insights into the mechanism of this new class of chemotherapeutic drugs.