Pretreatment with beta-blockers and the frequency of hypokalemia in patients with acute chest pain

Plasma potassium concentration was measured at admission in 1234 patients who presented with acute chest pain. One hundred and ninety five patients were on P blockers before admission. The potassium concentrations of patients admitted early (within four hours of onsetof symptoms) were compared with those admitted later (4-18 hours after onset of symptoms). There was a transient fall in plasma potassium concentrations in patients not pre-treated with , B blockers. This was not seen in patients who had been on P blockers before admission. Nonselective, B blockers were more effective than cardioselective agents in maintaining concentrationsof plasma potassium. These findings suggest a mechanism for the beneficial effects of ,B blockers on morbidity and mortality in acute myocardial infarction

Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project

Background: Current clinical testing methods used to uncover the genetic basis of rare disease have inherent limitations, which can lead to causative pathogenic variants being missed. Within the rare disease arm of the 100 000 Genomes Project (100kGP), families were recruited under the clinical indication ‘single autosomal recessive mutation in rare disease’. These participants presented with strong clinical suspicion for a specific autosomal recessive disorder, but only one suspected pathogenic variant had been identified through standard-of-care testing. Whole genome sequencing (WGS) aimed to identify cryptic ‘second-hit’ variants. Methods: To investigate the 31 families with available data that remained unsolved following formal review within the 100kGP, SVRare was used to aggregate structural variants present in <1% of 100kGP participants. Small variants were assessed using population allele frequency data and SpliceAI. Literature searches and publicly available online tools were used for further annotation of pathogenicity. Results: Using these strategies, 8/31 cases were solved, increasing the overall diagnostic yield of this cohort from 10/41 (24.4%) to 18/41 (43.9%). Exemplar cases include a patient with cystic fibrosis harbouring a novel exonic LINE1 insertion in CFTR and a patient with generalised arterial calcification of infancy with complex interlinked duplications involving exons 2–6 of ENPP1. Although ambiguous by short-read WGS, the ENPP1 variant structure was resolved using optical genome mapping and RNA analysis. Conclusion: Systematic examination of cryptic variants across a multi-disease cohort successfully identifies additional pathogenic variants. WGS data analysis in autosomal recessive rare disease should consider complex structural and small intronic variants as potentially pathogenic second hits

Modelling critical illness claim diagnosis rates II: results

This is Paper II in a series of two papers. In Paper I we developed a methodology for estimating and graduating Critical Illness (CI) insurance diagnosis rates. In this paper we use data from the UK for 1999–2005 supplied by the Continuous Mortality Investigation (CMI) to illustrate our methodology by deriving and discussing all causes and cause specific critical illness diagnosis rate

Modelling critical illness claim diagnosis rates II: results

This is Paper II in a series of two papers. In Paper I we developed a methodology for estimating and graduating Critical Illness (CI) insurance diagnosis rates. In this paper we use data from the UK for 1999–2005 supplied by the Continuous Mortality Investigation (CMI) to illustrate our methodology by deriving and discussing all causes and cause specific critical illness diagnosis rate

Market Valuation, Pension Fund Policy and Contribution Volatility

asset and liability management, conditional indexation, defined benefit pension funds, fair value versus actuarial discounting, Monte Carlo simulation, pension liabilities, G23, C15, C59, J18,