The incidence of potentially serious complications during non-obstetric anaesthetic practice in the United Kingdom: an analysis from the 7th National Audit Project (NAP7) activity survey.

Complications and critical incidents arising during anaesthesia due to patient, surgical or anaesthetic factors, may cause harm themselves or progress to more severe events, including cardiac arrest or death. As part of the 7th National Audit Project of the Royal College of Anaesthetists, we studied a prospective national cohort of unselected patients. Anaesthetists recorded anonymous details of all cases undertaken over 4 days at their site through an online survey. Of 416 hospital sites invited to participate, 352 (85%) completed the survey. Among 24,172 cases, 1922 discrete potentially serious complications were reported during 1337 (6%) cases. Obstetric cases had a high reported major haemorrhage rate and were excluded from further analysis. Of 20,996 non-obstetric cases, 1705 complications were reported during 1150 (5%) cases. Circulatory events accounted for most complications (616, 36%), followed by airway (418, 25%), metabolic (264, 15%), breathing (259, 15%), and neurological (41, 2%) events. A single complication was reported in 851 (4%) cases, two complications in 166 (1%) cases and three or more complications in 133 (1%) cases. In non-obstetric elective surgery, all complications were 'uncommon' (10-100 per 10,000 cases). Emergency (urgent and immediate priority) surgery accounted for 3454 (16%) of non-obstetric cases but 714 (42%) of complications with severe hypotension, major haemorrhage, severe arrhythmias, septic shock, significant acidosis and electrolyte disturbances all being 'common' (100-1000 per 10,000 cases). Based on univariate analysis, complications were associated with: younger age; higher ASA physical status; male sex; increased frailty; urgency and extent of surgery; day of the week; and time of day. These data represent the rates of potentially serious complications during routine anaesthesia care and may be valuable for risk assessment and patient consent.

Peri-operative cardiac arrest: management and outcomes of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. We report the results of the 12-month registry phase, from 16 June 2021 to 15 June 2022, focusing on management and outcomes. Among 881 cases of peri-operative cardiac arrest, the initial rhythm was non-shockable in 723 (82%) cases, most commonly pulseless electrical activity. There were 665 (75%) patients who survived the initial event and 384 (52%) who survived to hospital discharge. A favourable functional outcome (based on modified Rankin Scale score) was reported for 249 (88%) survivors. Outcomes varied according to arrest rhythm. The highest rates of survival were seen for bradycardic cardiac arrests with 111 (86%) patients surviving the initial event and 77 (60%) patients surviving the hospital episode. The lowest survival rates were seen for patients with pulseless electrical activity, with 312 (68%) surviving the initial episode and 156 (34%) surviving to hospital discharge. Survival to hospital discharge was worse in patients at the extremes of age with 76 (40%) patients aged > 75 y and 9 (45%) neonates surviving. Hospital survival was also associated with surgical priority, with 175 (88%) elective patients and 176 (37%) non-elective patients surviving to discharge. Outcomes varied with the cause of cardiac arrest, with lower initial survival rates for pulmonary embolism (5, 31%) and bone cement implantation syndrome (9, 45%), and hospital survival of < 25% for pulmonary embolism (0), septic shock (13, 24%) and significant hyperkalaemia (1, 20%). Overall care was rated good in 464 (53%) cases, and 18 (2%) cases had overall care rated as poor. Poor care elements were present in a further 245 (28%) cases. Care before cardiac arrest was the phase most frequently rated as poor (92, 11%) with elements of poor care identified in another 186 (21%) cases. These results describe the management and outcomes of peri-operative cardiac arrest in UK practice for the first time.

Peri-operative cardiac arrest: epidemiology and clinical features of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. Here we report the results of the 12-month registry, from 16 June 2021 to 15 June 2022, focusing on epidemiology and clinical features. We reviewed 881 cases of peri-operative cardiac arrest, giving an incidence of 3 in 10,000 anaesthetics (95%CI 3.0-3.5 per 10,000). Incidence varied with patient and surgical factors. Compared with denominator survey activity, patients with cardiac arrest: included more males (56% vs. 42%); were older (median (IQR) age 60.5 (40.5-80.5) vs. 50.5 (30.5-70.5) y), although the age distribution was bimodal, with infants and patients aged > 66 y overrepresented; and were notably more comorbid (73% ASA physical status 3-5 vs. 27% ASA physical status 1-2). The surgical case-mix included more weekend (14% vs. 11%), out-of-hours (19% vs. 10%), non-elective (65% vs. 30%) and major/complex cases (60% vs. 28%). Cardiac arrest was most prevalent in orthopaedic trauma (12%), lower gastrointestinal surgery (10%), cardiac surgery (9%), vascular surgery (8%) and interventional cardiology (6%). Specialities with the highest proportion of cases relative to denominator activity were: cardiac surgery (9% vs. 1%); cardiology (8% vs. 1%); and vascular surgery (8% vs. 2%). The most common causes of cardiac arrest were: major haemorrhage (17%); bradyarrhythmia (9%); and cardiac ischaemia (7%). Patient factors were judged a key cause of cardiac arrest in 82% of cases, anaesthesia in 40% and surgery in 35%.

The 7th National Audit Project (NAP7) baseline survey of individual anaesthetists: preparedness for and experiences of peri-operative cardiac arrest.

The Royal College of Anaesthetists' 7th National Audit Project baseline survey assessed knowledge, attitudes, practices and experiences of peri-operative cardiac arrests among UK anaesthetists and Anaesthesia Associates. We received 10,746 responses, representing a 71% response rate. In-date training in adult and paediatric advanced life support was reported by 9646 (90%) and 7125 (66%) anaesthetists, respectively. There were 8994 (84%) respondents who were confident in leading a peri-operative cardiac arrest, with males more confident than females, but only 5985 (56%) were confident in leading a debrief and 7340 (68%) communicating with next of kin. In the previous two years, 4806 (46%) respondents had managed at least one peri-operative cardiac arrest, of which 321 (7%) and 189 (4%) of these events involved a child or an obstetric patient, respectively. Respondents estimated the most common causes of peri-operative cardiac arrest to be hypovolaemia, hypoxaemia and cardiac ischaemia, with haemorrhage coming fifth. However, the most common reported causes for the most recently attended peri-operative cardiac arrest were haemorrhage; (927, 20%); anaphylaxis (474, 10%); and cardiac ischaemia (397, 9%). Operating lists or shifts were paused or stopped after 1330 (39%) cardiac arrests and 1693 (38%) respondents attended a debrief, with 'hot' debriefs most common. Informal wellbeing support was relatively common (2458, 56%) and formal support was uncommon (472, 11%). An impact on future care delivery was reported by 196 (4%) anaesthetists, most commonly a negative psychological impact. Management of a peri-operative cardiac arrest during their career was reported by 8654 (85%) respondents. The overall impact on professional life was more often judged positive (2630, 30%) than negative (1961, 23%), but impact on personal life was more often negative.

Organisation of UK hospitals and anaesthetic departments in the treatment of peri-operative cardiac arrest: an analysis from the 7th National Audit Project (NAP7) local co-ordinator baseline survey.

We report the results of the Royal College of Anaesthetists' 7th National Audit Project organisational baseline survey sent to every NHS anaesthetic department in the UK to assess preparedness for treating peri-operative cardiac arrest. We received 199 responses from 277 UK anaesthetic departments, representing a 72% response rate. Adult and paediatric anaesthetic care was provided by 188 (95%) and 165 (84%) hospitals, respectively. There was no paediatric intensive care unit on-site in 144 (87%) hospitals caring for children, meaning transfer of critically ill children is required. Remote site anaesthesia is provided in 182 (92%) departments. There was a departmental resuscitation lead in 113 (58%) departments, wellbeing lead in 106 (54%) and departmental staff wellbeing policy in 81 (42%). A defibrillator was present in every operating theatre suite and in all paediatric anaesthesia locations in 193 (99%) and 149 (97%) departments, respectively. Advanced airway equipment was not available in: every theatre suite in 13 (7%) departments; all remote locations in 103 (57%) departments; and all paediatric anaesthesia locations in 23 (15%) departments. Anaesthetic rooms were the default location for induction of anaesthesia in adults and children in 148 (79%) and 121 (79%) departments, respectively. Annual updates in chest compressions and in defibrillation were available in 149 (76%) and 130 (67%) departments, respectively. Following a peri-operative cardiac arrest, debriefing and peer support programmes were available in 154 (79%) and 57 (29%) departments, respectively. While it is likely many UK hospitals are very well prepared to treat anaesthetic emergencies including cardiac arrest, the survey suggests this is not universal.

Patient characteristics, anaesthetic workload and techniques in the UK: an analysis from the 7th National Audit Project (NAP7) activity survey.

Detailed contemporary knowledge of the characteristics of the surgical population, national anaesthetic workload, anaesthetic techniques and behaviours are essential to monitor productivity, inform policy and direct research themes. Every 3-4 years, the Royal College of Anaesthetists, as part of its National Audit Projects (NAP), performs a snapshot activity survey in all UK hospitals delivering anaesthesia, collecting patient-level encounter data from all cases under the care of an anaesthetist. During November 2021, as part of NAP7, anaesthetists recorded details of all cases undertaken over 4 days at their site through an online survey capturing anonymous patient characteristics and anaesthetic details. Of 416 hospital sites invited to participate, 352 (85%) completed the activity survey. From these, 24,177 reports were returned, of which 24,172 (99%) were included in the final dataset. The work patterns by day of the week, time of day and surgical specialty were similar to previous NAP activity surveys. However, in non-obstetric patients, between NAP5 (2013) and NAP7 (2021) activity surveys, the estimated median age of patients increased by 2.3 years from median (IQR) of 50.5 (28.4-69.1) to 52.8 (32.1-69.2) years. The median (IQR) BMI increased from 24.9 (21.5-29.5) to 26.7 (22.3-31.7) kg.m-2 . The proportion of patients who scored as ASA physical status 1 decreased from 37% in NAP5 to 24% in NAP7. The use of total intravenous anaesthesia increased from 8% of general anaesthesia cases to 26% between NAP5 and NAP7. Some changes may reflect the impact of the COVID-19 pandemic on the anaesthetic population, though patients with confirmed COVID-19 accounted for only 149 (1%) cases. These data show a rising burden of age, obesity and comorbidity in patients requiring anaesthesia care, likely to impact UK peri-operative services significantly.

Methods of the 7th National Audit Project (NAP7) of the Royal College of Anaesthetists: peri-operative cardiac arrest.

Cardiac arrest in the peri-operative period is rare but associated with significant morbidity and mortality. Current reporting systems do not capture many such events, so there is an incomplete understanding of incidence and outcomes. As peri-operative cardiac arrest is rare, many hospitals may only see a small number of cases over long periods, and anaesthetists may not be involved in such cases for years. Therefore, a large-scale prospective cohort is needed to gain a deep understanding of events leading up to cardiac arrest, management of the arrest itself and patient outcomes. Consequently, the Royal College of Anaesthetists chose peri-operative cardiac arrest as the 7th National Audit Project topic. The study was open to all UK hospitals offering anaesthetic services and had a three-part design. First, baseline surveys of all anaesthetic departments and anaesthetists in the UK, examining respondents' prior peri-operative cardiac arrest experience, resuscitation training and local departmental preparedness. Second, an activity survey to record anonymised details of all anaesthetic activity in each site over 4 days, enabling national estimates of annual anaesthetic activity, complexity and complication rates. Third, a case registry of all instances of peri-operative cardiac arrest in the UK, reported confidentially and anonymously, over 1 year starting 16 June 2021, followed by expert review using a structured process to minimise bias. The definition of peri-operative cardiac arrest was the delivery of five or more chest compressions and/or defibrillation in a patient having a procedure under the care of an anaesthetist. The peri-operative period began with the World Health Organization 'sign-in' checklist or first hands-on contact with the patient and ended either 24 h after the patient handover (e.g. to the recovery room or intensive care unit) or at discharge if this occured earlier than 24 h. These components described the epidemiology of peri-operative cardiac arrest in the UK and provide a basis for developing guidelines and interventional studies.

Distinct opposing associations of upper and lower body fat depots with metabolic and cardiovascular disease risk markers.

BACKGROUND: To examine the associations of total and regional adiposity with metabolic and cardiovascular disease (CVD) risk markers. METHODS: This cross-sectional study included 1080 (53.8% men, aged 39-44 years) individuals from South India. Anthropometry (height, weight, waist and hip circumference), body composition assessment using dual-energy X-ray absorptiometry (DXA), blood pressure (BP), and plasma glucose, insulin and lipids were measured. Regression analysis was used to examine associations of standardized fat measurements with type 2 diabetes (T2D), insulin resistance (IR), hypertension and hypertriglyceridemia and continuous measurements of BP, glucose, insulin, HOMA-IR and lipids. Contour plots were constructed to visualize the differential effect of upper and lower fat depots. RESULTS: DXA-measured fat depots were positively associated with metabolic and CVD risk markers. After adjusting for fat mass index, upper body fat remained positively, while lower body fat was negatively associated with risk markers. A one standard deviation (SD) increase in android fat showed higher odds ratios (ORs) for T2D (6.59; 95% CI 3.17, 13.70), IR (4.68; 95% CI 2.31, 9.50), hypertension (2.57; 95% CI 1.56, 4.25) and hypertriglyceridemia (6.39; 95% CI 3.46, 11.90) in men. A 1 SD increase in leg fat showed a protective effect with ORs for T2D (0.42; 95% CI 0.24, 0.74), IR (0.31; 95% CI 0.17, 0.57) and hypertriglyceridemia (0.61; 95% CI 0.38, 0.98). The magnitude of the effect was greater with DXA-measured fat compared with anthropometry. CONCLUSION: At any level of total body fat, upper and lower body fat depots demonstrate opposite risk associations with metabolic and CVD risk markers in Asian Indians.

Prevalence, incidence and predictors of cardiovascular risk factors: longitudinal data from rural and urban South India and comparison with global data.

INTRODUCTION: India has high mortality rates from cardiovascular disease (CVD). Understanding the trends and identifying modifiable determinants of CVD risk factors will guide preventive strategies and policy making. RESEARCH DESIGN AND METHODS: CVD risk factors (obesity, central obesity, and type 2 diabetes (T2D), hypertension, hypercholesterolemia and hypertriglyceridemia) prevalence and incidence were estimated in 962 (male 519) non-migrant adults from Vellore, South India, studied in: (1) 1998-2002 (mean age 28.2 years) and (2) 2013-2014 (mean age 41.7 years). Prevalence was compared with the Non-Communicable Disease Risk Collaboration (global) data. Incidence was compared with another Indian cohort from New Delhi Birth Cohort (NDBC). Regression analysis was used to test baseline predictors of incident CVD risk factors. RESULTS: The prevalence at 28 and 42 years was 17% (95% CI 14% to 19%) and 51% (95% CI 48% to 55%) for overweight/obesity, 19% (95% CI 17% to 22%) and 59% (95% CI 56% to 62%) for central obesity, 3% (95% CI 2% to 4%) and 16% (95% CI 14% to 19%) for T2D, 2% (95% CI 1% to 3%) and 19% (95% CI 17% to 22%) for hypertension and 15% (95% CI 13% to 18%) and 30% (95% CI 27% to 33%) for hypertriglyceridemia. The prevalence of T2D at baseline and follow-up and hypertension at follow-up was comparable with or exceeded that in high-income countries despite lower obesity rates. The incidence of most risk factors was lower in Vellore than in the NDBC. Waist circumference strongly predicted incident T2D, hypertension and hypertriglyceridemia. CONCLUSIONS: A high prevalence of CVD risk factors was evident at a young age among Indians compared with high and upper middle income countries, with rural rates catching up with urban estimates. Adiposity predicted higher incident CVD risk, but the prevalence of hypertension and T2D was higher given a relatively low obesity prevalence. Preventive efforts should target both rural and urban India and should start young.

Refinement of eDNA as an early monitoring tool at the landscape-level: study design considerations.

Natural resource managers use data on the spatial range of species to guide management decisions. These data come from survey or monitoring efforts that use a wide variety of tools. Environmental DNA (eDNA) is a surveillance tool that uses genetic markers for detecting species and holds potential as a tool for large-scale monitoring programs. Two challenges of eDNA-based studies are uncertainties created by imperfect capture of eDNA in collection samples (e.g., water field samples) and imperfect detection of eDNA using molecular methods (e.g., quantitative PCR). Occurrence models can be used to address these challenges, thus we use an occurrence model to address two objectives: first, to determine how many samples were required to detect species using eDNA; second, to examine when and where to take samples. We collected water samples from three different habitat types in the Upper Mississippi River when both Bighead Carp and Silver Carp were known to be present based on telemetry detections. Each habitat type (backwater, tributary, and impoundment) was sampled during April, May, and November. Detections of eDNA for both species varied across sites and months, but were generally low, 0-19.3% of samples were positive for eDNA. Overall, we found that eDNA-based sampling holds promise to be a powerful monitoring tool for resource managers; however, limitations of eDNA-based sampling include different biological and ecological characteristics of target species such as seasonal habitat usage patterns as well as aspects of different physical environments that impact the implementation of these methods such as water temperature.

IndEcho study: cohort study investigating birth size, childhood growth and young adult cardiovascular risk factors as predictors of midlife myocardial structure and function in South Asians.

INTRODUCTION: South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians. METHODS AND ANALYSIS: We propose to study approximately 3000 men and women aged 43-50 years from two birth cohorts established in 1969-1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes. ETHICS AND DISSEMINATION: The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13432279; Pre-results.

pRotective vEntilation with veno-venouS lung assisT in respiratory failure: A protocol for a multicentre randomised controlled trial of extracorporeal carbon dioxide removal in patients with acute hypoxaemic respiratory failure.

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO2R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO2R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO2R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO2R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

Weight Gain and Height Growth during Infancy, Childhood, and Adolescence as Predictors of Adult Cardiovascular Risk.

OBJECTIVES: To investigate independent relationships of childhood linear growth (height gain) and relative weight gain to adult cardiovascular disease (CVD) risk traits in Asian Indians. STUDY DESIGN: Data from 2218 adults from the Vellore Birth Cohort were examined for associations of cross-sectional height and body mass index (BMI) and longitudinal growth (independent conditional measures of height and weight gain) in infancy, childhood, adolescence, and adulthood with adult waist circumference (WC), blood pressure (BP), insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR]), and plasma glucose and lipid concentrations. RESULTS: Higher BMI/greater conditional relative weight gain at all ages was associated with higher adult WC, after 3 months with higher adult BP, HOMA-IR, and lipids, and after 15 years with higher glucose concentrations. Taller adult height was associated with higher WC (men ß = 2.32 cm per SD, women ß = 1.63, both P < .001), BP (men ß = 2.10 mm Hg per SD, women ß = 1.21, both P ≤ .001), and HOMA-IR (men ß = 0.08 log units per SD, women ß = 0.12, both P ≤ .05) but lower glucose concentrations (women ß = -0.03 log mmol/L per SD P = .003). Greater height or height gain at all earlier ages were associated with higher adult CVD risk traits. These positive associations were attenuated when adjusted for adult BMI and height. Shorter length and lower BMI at birth were associated with higher glucose concentration in women. CONCLUSIONS: Greater height or weight gain relative to height during childhood or adolescence was associated with a more adverse adult CVD risk marker profile, and this was mostly attributable to larger adult size.

Parental determinants of metabolic syndrome among adolescent Asian Indians: A cross-sectional analysis of parent-offspring trios.

BACKGROUND: The aim of the present study was to investigate the relationship between parental metabolic syndrome (MS) and the risk of MS and associated abnormalities in adolescent offspring. METHODS: This cross-sectional study was performed on 304 adolescents (12-16 years; 236 children with at least one parent and 124 father-mother-child trios) recruited from four schools representing different socioeconomic strata from Vellore, India. Anthropometric data was collected and blood pressure, blood glucose, and lipids were measured. RESULTS: The prevalence of MS in adolescent offspring, fathers, and mothers was 3.3%, 52.5%, and 48.7% respectively. The most commonly observed metabolic abnormality among adolescents was lower high-density lipoprotein. Maternal waist circumference (WC) was strongly correlated with adolescent body mass index (P = 0.007), WC (P < 0.001), serum triglycerides (P = 0.02), and systolic (P = 0.005) and diastolic (P = 0.01) blood pressure. Maternal MS status was significantly associated with a greater risk of central obesity (WC odds ratio [OR] 2.02; 95% confidence interval [CI] 1.21-3.17) in offspring. Both parents having MS conferred a significant effect on the child's WC (OR 1.21; 95% CI 1.72-2.07) and increased risk of MS (OR 6.19; 95% CI 1.64-23.26). CONCLUSIONS: This study highlights the possible heritable parental components that may contribute to the MS phenotype in offspring: MS in adolescent offspring is related to parental MS status, and maternal traits reflect offspring adiposity and metabolic traits more strongly than paternal factors. Therefore, adolescent children of parents with MS should be targets for primordial prevention of cardiometabolic disease.

Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians.

OBJECTIVE: The variant allele of rs3798220 in the apolipoprotein(a) gene (LPA) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians. METHODS: We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs. RESULTS: The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians. CONCLUSION: Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians.

Acute respiratory distress syndrome related to influenza A H1N1 infection: correlation of pulmonary computed tomography findings to extracorporeal membrane oxygenation treatment and clinical outcome.

PURPOSE: The aim of the present study was to correlate computed tomography appearances with clinical severity and outcome using a total lung disease (TLD) score in patients with acute respiratory distress syndrome (ARDS) related to influenza A H1N1 infection. MATERIALS AND METHODS: Chest computed tomographic scans of 33 patients admitted in the intensive care unit with ARDS related to influenza A H1N1 were retrospectively reviewed. Total lung disease was calculated from the combined extent of consolidation (TLC) and ground glass (TLGG) in the anterior, middle, and posterior segments of the lungs at 3 different levels (apex, hila, and base) using the method described by Goodman et al (Radiology. 213:545-552;1999). Total lung disease, TLC, and TLGG were statistically correlated with demographic characteristics, requirement for extracorporeal membrane oxygenation (ECMO) treatment, and patient outcome. RESULTS: Total lung disease is higher in patients who require ECMO treatment (P = .016). It is significantly higher (P = .003) in the posterior segments and significantly lower (P = .0001) in the anterior segments compared with TLGG. Total consolidation significantly increases (P = .0001), whereas TLGG significantly decreases (P = .0001) from the anterior toward the posterior segments. There is also a significant increase in TLD (P = .0001), TLC (P = .0001), and TLGG (P = .004) from the apices to the lung bases. There is a negative correlation between TLD and age (P = .01), and TLGG and body mass index (P = .014). Total consolidation is higher (P = .013) and TLGG is lower (P = .012) in patients with a body mass index greater than 30 kg/m(2). CONCLUSION: A greater extent of air-space disease in ARDS related to influenza A H1N1 infection is associated with progression to ECMO treatment and, therefore, clinical severity. The extent of total air-space disease is greater in younger patients, and obesity is related to a more extensive consolidation.

Associations of variants in FTO and near MC4R with obesity traits in South Asian Indians.

Recent genome-wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity-related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity- and type 2 diabetes (T2DM)-related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity-related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist-hip ratio. Consistent associations were observed for adipose tissue-specific measurements such as skinfold thickness reinforcing the association with obesity-related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity-related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity-related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian "thin-fat" phenotype.

Born with low birth weight in rural Southern India: what are the metabolic consequences 20 years later?

OBJECTIVE: Low birth weight (LBW) is common in the Indian population and may represent an important predisposing factor for type 2 diabetes (T2D) and the metabolic syndrome. Intensive metabolic examinations in ethnic LBW Asian Indians have been almost exclusively performed in immigrants living outside India. Therefore, we aimed to study the metabolic impact of being born with LBW in a rural non-migrant Indian population. SUBJECTS AND METHODS: One hundred and seventeen non-migrant, young healthy men were recruited from a birth cohort in a rural part of south India. The subjects comprised 61 LBW and 56 normal birth weight (NBW) men, with NBW men acting as controls. Subjects underwent a hyperinsulinaemic euglycaemic clamp, i.v. and oral glucose tolerance tests and a dual-energy X-ray absorptiometry scan. The parents' anthropometric status and metabolic parameters were assessed. RESULTS: Men with LBW were shorter (167±6.4 vs 172±6.0 cm, P<0.0001), lighter (51.9±9 vs 55.4±7 kg, P=0.02) and had a reduced lean body mass (42.1±5.4 vs 45.0±4.5 kg, P=0.002) compared with NBW controls. After adjustment for height and weight, the LBW subjects had increased diastolic blood pressure (77±6 vs 75±6 mmHg, P=0.01). Five LBW subjects had impaired glucose tolerance. In vivo insulin secretion and peripheral insulin action were similar in both the groups. Mothers of the LBW subjects were 3 cm shorter than the control mothers. CONCLUSION: Only subtle features of the metabolic syndrome and changes in body composition among LBW rural Indians were found. Whether other factors such as urbanisation and ageing may unmask more severe metabolic abnormalities may require a long-term follow-up.

Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians.

BACKGROUND: A feature of the Asian Indian phenotype is low birth weight with increased adult type 2 diabetes risk. Most populations show consistent associations between low birth weight and adult type 2 diabetes. Recently, two birth weight-lowering loci on chromosome 3 (near CCNL1 and ADCY5) were identified in a genome-wide association study, the latter of which is also a type 2 diabetes locus. We therefore tested the impact of these genetic variants on birth weight and adult glucose/insulin homeostasis in a large Indian birth cohort. METHODOLOGY/PRINCIPAL FINDINGS: Adults (n = 2,151) enrolled in a birth cohort (established 1969-73) were genotyped for rs900400 (near CCNL1) and rs9883204 (ADCY5). Associations were tested for birth weight, anthropometry from infancy to adulthood, and type 2 diabetes related glycemic traits. The average birth weight in this population was 2.79±0.47 kg and was not associated with genetic variation in CCNL1 (p = 0.87) or ADCY5 (p = 0.54). Allele frequencies for the 'birth weight-lowering' variants were similar compared with Western populations. There were no significant associations with growth or adult weight. However, the 'birth weight-lowering' variant of ADCY5 was associated with modest increase in fasting glucose (ß 0.041, p = 0.027), 2-hours glucose (ß 0.127, p = 0.019), and reduced insulinogenic index (ß -0.106, p = 0.050) and 2-hour insulin (ß -0.058, p = 0.010). CONCLUSIONS: The low birth weight in Asian Indians is not even partly explained by genetic variants near CCNL1 and ADCY5 which implies that non-genetic factors may predominate. However, the 'birth-weight-lowering' variant of ADCY5 was associated with elevated glucose and decreased insulin response in early adulthood which argues for a common genetic cause of low birth weight and risk of type 2 diabetes.