Catherine Welch

BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: , fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: , -0·09 to 0·30). INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins. FUNDING: British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.

Using a retrospective analysis of the Intensive Care National Audit and Research Centre Case Mix Programme Database (ICNARC CMPD), we have summarised the characteristics and outcomes for mechanically ventilated patients admitted to UK intensive care units (ICUs) after cardiac arrest. Descriptive statistics on case mix, physiology, treatment, service delivery, outcome and activity were described separately for community cardiac arrest, in-hospital cardiac arrest (peri-operative) and in-hospital cardiac arrest (not peri-operative). The impact on outcome of several patient characteristics and physiological values were analysed using multivariable logistic regression. Mechanically ventilated survivors of cardiac arrest accounted for 24,132 (5.8%) of all admissions to the 174 ICUs in the ICNARC CMP. Of these, 10,347 (42.9%) survived to leave the ICU and 6778 (28.6%) survived to acute hospital discharge. The ICNARC model gives much better discrimination than APACHE II for predicting hospital mortality after admission to ICU following cardiac arrest: the predicted hospital mortality based on the APACHE II and ICNARC model was 41.9% and 79.7%, respectively.

INTRODUCTION: To evaluate the impact of recent evidence-based treatments for severe sepsis in routine clinical care requires an understanding of the underlying epidemiology, particularly with regard to trends over time. We interrogated a high quality clinical database to examine trends in the incidence and mortality of severe sepsis over a nine-year period. METHODS: Admissions with severe sepsis occurring at any time within 24 hours of admission to critical care were identified to an established methodology using raw physiological data from the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, containing data from 343,860 admissions to 172 adult, general critical care units in England, Wales and Northern Ireland between December 1995 and January 2005. Generalised linear models were used to assess changes in the incidence, case mix, outcomes and activity of these admissions. RESULTS: In total, 92,672 admissions (27.0%) were identified as having severe sepsis in the first 24 hours following admission. The percentage of admissions with severe sepsis during the first 24 hours rose from 23.5% in 1996 to 28.7% in 2004. This represents an increase from an estimated 18,500 to 31,000 admissions to all 240 adult, general critical care units in England, Wales and Northern Ireland. Hospital mortality for admissions with severe sepsis decreased from 48.3% in 1996 to 44.7% in 2004, but the total number of deaths increased from an estimated 9,000 to 14,000. The treated incidence of severe sepsis per 100,000 population rose from 46 in 1996 to 66 in 2003, with the associated number of hospital deaths per 100,000 population rising from 23 to 30. CONCLUSION: The population incidence of critical care admission with severe sepsis during the first 24 hours and associated hospital deaths are increasing. These baseline data provide essential information to those wishing to evaluate the introduction of the Surviving Sepsis Campaign care bundles in UK hospitals.

INTRODUCTION: This paper describes the case mix, outcome and activity for admissions to intensive care units (ICUs) with community-acquired pneumonia (CAP). METHODS: We conducted a secondary analysis of a high quality clinical database, the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, of 301,871 admissions to 172 adult ICUs across England, Wales and Northern Ireland, 1995 to 2004. Cases of CAP were identified from pneumonia admissions excluding nosocomial pneumonias and the immuno-compromised. It was not possible to review data from the time of hospital admission; therefore, some patients who developed hospital-acquired/nosocomial pneumonia may have been included. RESULTS: We identified 17,869 cases of CAP (5.9% of all ICU admissions). There was a 128% increase in admissions for CAP from 12.8 per unit to 29.2 per unit during the study period compared to only a 24% rise in total ICU admissions (p < 0.001). Eighty-five percent of admissions were from within the same hospital. Fifty-nine percent of cases were admitted to the ICU < 2 days, 21.5% between 2 and 7 days, and 19.5% > 7 days after hospital admission. Between 1995 and 1999 and 2000 and 2004 there was a rise in admissions from accident and emergency (14.8% to 16.8%; p < 0.001) and high dependency units (6.9% to 11.9%; p < 0.001) within the same hospital, those aged > 74 (18.5 to 26.1%; p < 0.001), and mean APACHE II score (6.83 to 6.91; p < 0.001). There was a fall in past history of severe respiratory problems (8.7% to 6.4%; p < 0.001), renal replacement therapy (1.6% to 1.2%; p < 0.01), steroid treatment (3.4% to 2.8%; p < 0.05), sedation/paralysis (50.2% to 40.4%; p < 0.001), cardiopulmonary resuscitation prior to admission (7.5% to 5.5%; p < 0.001), and septic shock (7.3% to 6.6%; p < 0.001). ICU mortality was 34.9% and ultimate hospital mortality 49.4%. Mortality was 46.3% in those admitted to the ICU within 2 days of hospital admission rising to 50.4% in those admitted at 2 to 7 days and 57.6% in those admitted after 7 days following hospital admission. CONCLUSION: CAP makes up a small, but important and rising, proportion of adult ICU admissions. Survival of over half of all cases vindicates the use of ICU facilities in CAP management. Nevertheless, overall mortality remains high, especially in those admitted later in their hospital stay.