Lessons of the month: Pyroglutamic acidosis: long-term paracetamol and a high anion gap.

An 84-year-old woman presented in extremis with confusion and Kussmaul respiration. She had a history of urosepsis, renal impairment and osteoarthrosis. The venous blood gas showed a marked metabolic acidosis with a high anion gap. Lactate and ketones were normal. Her medications included regular paracetamol via a dosette box. Lactic acidosis and ketoacidosis being excluded, it emerged that the most likely cause of a high anion-gap acidosis in the presence of chronic paracetamol therapy is pyroglutamic acidosis, caused by the build-up of an acidic intermediate in the gamma-glutamyl cycle, the function of which is to synthesise glutathione. Paracetamol was stopped and fluids administered; she recovered over 7 days and was sent home. The biochemical diagnosis was confirmed by a central laboratory after discharge. This case emphasises the importance of the anion gap in diagnosis, and one important danger of chronic paracetamol administration.

The benefit of evolving multidisciplinary care in ALS: a diagnostic cohort survival comparison.

BACKGROUND: Care for people with amyotrophic lateral sclerosis (ALS) has altered at King's College Hospital over the last 20 years. The clinic has been a multidisciplinary, specialist, tertiary referral centre since 1995 with a large team with integrated palliative and respiratory care since 2006. We hypothesised that these changes would improve survival. METHODS: In this retrospective observational study, patients diagnosed with El Escorial definite, probable and possible ALS between 1995-1998 and 2008-2011 were followed up. The primary outcome measure was a chi-square test for the proportion of each cohort surviving. Kaplan-Meier survival analysis and Cox multivariate regression were secondary analyses. RESULTS: There was low reporting of some interventions. Five hundred and forty-seven people were included. Survival between the cohorts was significantly different (p = 0.022) with a higher proportion surviving during 2008-2011. Survival time was 21.6 (95% CI 19.2-24.0) months in the 2008-2011 cohort compared to 19.2 years (15.6-21.6) in the 1995-1998 cohort (log rank p = 0.018). Four hundred and ninety-three cases were included in the Cox regression. Diagnostic cohort was a significant predictor variable (HR 0.79 (0.64-0.97) p = 0.023). CONCLUSIONS: These results support the hypothesis that integrated specialist clinics with multidisciplinary input improve survival in ALS.