The Efficacy of COPD Outreach in Reducing Length of Stay and Improving Quality of Life.

COPD exacerbations results in prolonged hospitalisation, re-admissions, reduces health-related quality of life (HRQoL) and increases mortality. The study aimed to assess the efficacy of a COPD Outreach service in reducing average length of stay (ALOS), reducing readmissions within 90 days of admission, improving HRQoL and reducing mortality among COPD patients with acute exacerbations (AECOPD). AECOPD data for a 2 year period commencing September 2011 was analysed. The COPD Assessment test (CAT) quantified HRQoL at enrolment and 6 weeks post Outreach. COPD Outreach had an ALOS of 2.47 days compared to ALOS 8.59 days and 8.5 days for all AECOPD before and during an operational COPD Outreach. Re-admission rates among patients enrolled in COPD Outreach were 36.3%. CAT improved from mean 19.3 to 13.5. Mortality was 4.9% among Outreach patients and 2.5% for overall AECOPD in 2012-2013. COPD Outreach reduced ALOS and improved HRQoL for selected patients with AECOPD. It did not reduce re-admissions or mortality.

Metabolic inflexibility and protein lysine acetylation in heart mitochondria of a chronic model of type 1 diabetes.

Diabetic cardiomyopathy refers to the changes in contractility that occur to the diabetic heart that can arise in the absence of vascular disease. Mitochondrial bioenergetic deficits and increased free radical production are pathological hallmarks of diabetic cardiomyopathy, but the mechanisms and causal relationships between mitochondrial deficits and the progression of disease are not understood. We evaluated cardiac mitochondrial function in a rodent model of chronic Type 1 diabetes (OVE26 mice) before the onset of contractility deficits. We found that the most pronounced change in OVE26 heart mitochondria is severe metabolic inflexibility. This inflexibility is characterized by large deficits in mitochondrial respiration measured in the presence of non-fatty acid substrates. Metabolic inflexibility occurred concomitantly with decreased activities of PDH (pyruvate dehydrogenase) and complex II. Hyper-acetylation of protein lysine was also observed. Treatment of control heart mitochondria with acetic anhydride (Ac2O), an acetylating agent, preferentially inhibited respiration by non-fatty acid substrates and increased superoxide production. We have concluded that metabolic inflexibility, induced by discrete enzymatic and molecular changes, including hyper-acetylation of protein lysine residues, precedes mitochondrial defects in a chronic rodent model of Type 1 diabetes.

Inhibition of mitochondrial respiration by phosphoenolpyruvate.

The cytosolic factors that influence mitochondrial oxidative phosphorylation rates are relatively unknown. In this report, we examine the effects of phosphoenolpyruvate (PEP), a glycolytic intermediate, on mitochondrial function. It is reported here that in rat heart mitochondria, PEP delays the onset of state 3 respiration in mitochondria supplied with either NADH-linked substrates or succinate. However, the maximal rate of state 3 respiration is only inhibited when oxidative phosphorylation is supported by NADH-linked substrates. The capacity of PEP to delay and/or inhibit state 3 respiration is dependent upon the presence or absence of ATP. Inhibition of state 3 is exacerbated in uncoupled mitochondria, with a 40% decrease in respiration seen with 0.1mM PEP. In contrast, ATP added exogenously or produced by oxidative phosphorylation completely prevents PEP-mediated inhibition. Mechanistically, the results support the conclusion that the main effects of PEP are to impede ADP uptake and inhibit NADH oxidation. By altering the NADH/NAD(+) status of mitochondria, it is demonstrated that PEP enhances succinate dehydrogenase activity and increase free radical production. The results of this study indicate PEP may be an important modulator of mitochondrial function under conditions of decreased ATP.

Lymphocytic meningitis: incidence, causes and outcomes over five years.

Over a five-year period 114 cases of lymphocytic meningitis were admitted to a general hospital. Case notes were reviewed to determine incidence, causes and outcomes and to identify what clinical features, cerebrospinal fluid (CSF) parameters or other tests were useful in elucidating a cause. Of 114 patients with lymphocytic meningitis 44 had viral meningitis, six viral encephalitis, and seven had other infective meningo-encephalitis. Seven patients had carcinomatous meningitis, nine had an autoimmune/inflammatory process, thirteen had a demyelinating central nervous system (CNS) disorder, and two had an inflammatory neuropathy. In 26 patients no diagnosis was reached. Six of these showed clear steroid responsiveness. Overall lymphocytic meningitis had a good prognosis. Clinical and CSF characteristics were important in diagnosis and prognosis. Recommendations on management of these cases are presented.