Jill P. Pell

Parachute use to prevent death and major trauma related to gravitational challenge: Systematic review of randomised controlled trials

Abstract Objectives To determine whether parachutes are effective in preventing major trauma related to gravitational challenge. Design Systematic review of randomised controlled trials. Data sources: Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists. Study selection: Studies showing the effects of using a parachute during free fall. Main outcome measure Death or major trauma, defined as an injury severity score > 15. Results We were unable to identify any randomised controlled trials of parachute intervention. Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.

Evidence of Improving Prognosis in Heart Failure Trends in Case Fatality in 66 547 Patients Hospitalized Between 1986 and 1995

BackgroundContemporary survival in unselected patients with heart failure and the population impact of newer therapies have not been widely studied. Therefore, we have documented case-fatality rates (CFRs) over a recent 10-year period. Methods and ResultsIn Scotland, all hospitalizations and deaths are captured on a single database. We have studied case fatality in all patients admitted with a principal diagnosis of heart failure from 1986 to 1995. A total of 66 547 patients (47% male) were studied. Median age was 72 years in men and 78 years in women. Crude CFRs at 30 days and at 1, 5, and 10 years were 19.9%, 44.5%, 76.5%, and 87.6%, respectively. Median survival was 1.47 years in men and 1.39 years in women (2.47 and 2.36 years, respectively, in those surviving 30 days). Age had a powerful effect on survival, and sex, comorbidity, and deprivation had modest effects. One-year CF was 24.2% in those aged <55 years and 58.1% in those aged >84 years. After adjustment, 30-day CFRs fell between 1986 and 1995, by 26% (95% CI 15 to 35, P <0.0001) in men and 17% (95% CI 6 to 26, P <0.0001) in women. Longer term CFRs fell by 18% (95% CI 13 to 24, P <0.0001) in men and 15% (95% CI 10 to 20, P <0.0001) in women. Median survival increased from 1.23 to 1.64 years. ConclusionsHeart failure CF is much higher in the general population than in clinical trials, especially in the elderly. Although survival has increased significantly over the last decade, there is still much room for improvement.

UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age

Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.

Smoke-free Legislation and Hospitalizations for Acute Coronary Syndrome

BACKGROUND Previous studies have suggested a reduction in the total number of hospital admissions for acute coronary syndrome after the enactment of legislation banning smoking in public places. However, it is unknown whether the reduction in admissions involved nonsmokers, smokers, or both. METHODS Since the end of March 2006, smoking has been prohibited by law in all enclosed public places throughout Scotland. We collected information prospectively on smoking status and exposure to secondhand smoke based on questionnaires and biochemical findings from all patients admitted with acute coronary syndrome to nine Scottish hospitals during the 10-month period preceding the passage of the legislation and during the same period the next year. These hospitals accounted for 64% of admissions for acute coronary syndrome in Scotland, which has a population of 5.1 million. RESULTS Overall, the number of admissions for acute coronary syndrome decreased from 3235 to 2684--a 17% reduction (95% confidence interval, 16 to 18)--as compared with a 4% reduction in England (which has no such legislation) during the same period and a mean annual decrease of 3% (maximum decrease, 9%) in Scotland during the decade preceding the study. The reduction in the number of admissions was not due to an increase in the number of deaths of patients with acute coronary syndrome who were not admitted to the hospital; this latter number decreased by 6%. There was a 14% reduction in the number of admissions for acute coronary syndrome among smokers, a 19% reduction among former smokers, and a 21% reduction among persons who had never smoked. Persons who had never smoked reported a decrease in the weekly duration of exposure to secondhand smoke (P<0.001 by the chi-square test for trend) that was confirmed by a decrease in their geometric mean concentration of serum cotinine from 0.68 to 0.56 ng per milliliter (P<0.001 by the t-test). CONCLUSIONS The number of admissions for acute coronary syndrome decreased after the implementation of smoke-free legislation. A total of 67% of the decrease involved nonsmokers. However, fewer admissions among smokers also contributed to the overall reduction.

Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%–2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5′ region of Uromodulin (UMOD; rs13333226, combined P value of 3.6×10−11). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84–0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860–0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83–0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83–0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

Smoke-free Legislation and Hospitalizations for Childhood Asthma

BACKGROUND Previous studies have shown that after the adoption of comprehensive smoke-free legislation, there is a reduction in respiratory symptoms among workers in bars. However, it is not known whether respiratory disease is also reduced among people who do not have occupational exposure to environmental tobacco smoke. The aim of our study was to determine whether the ban on smoking in public places in Scotland, which was initiated in March 2006, influenced the rate of hospital admissions for childhood asthma. METHODS Routine hospital administrative data were used to identify all hospital admissions for asthma in Scotland from January 2000 through October 2009 among children younger than 15 years of age. A negative binomial regression model was fitted, with adjustment for age group, sex, quintile of socioeconomic status, urban or rural residence, month, and year. Tests for interactions were also performed. RESULTS Before the legislation was implemented, admissions for asthma were increasing at a mean rate of 5.2% per year (95% confidence interval [CI], 3.9 to 6.6). After implementation of the legislation, there was a mean reduction in the rate of admissions of 18.2% per year relative to the rate on March 26, 2006 (95% CI, 14.7 to 21.8; P<0.001). The reduction was apparent among both preschool and school-age children. There were no significant interactions between hospital admissions for asthma and age group, sex, urban or rural residence, region, or quintile of socioeconomic status. CONCLUSIONS In Scotland, passage of smoke-free legislation in 2006 was associated with a subsequent reduction in the rate of respiratory disease in populations other than those with occupational exposure to environmental tobacco smoke. (Funded by NHS Health Scotland.)

Acute upper gastrointestinal haemorrhage in west of Scotland: case ascertainment study.

Abstract Objectives: To determine the incidence and case fatality of acute upper gastrointestinal haemorrhage in the west of Scotland and to identify associated factors. Design: Case ascertainment study. Setting: All hospitals treating adults with acute upper gastrointestinal haemorrhage in the west of Scotland. Subjects: 1882 patients aged 15 years and over treated in hospitals for acute upper gastrointestinal haemorrhage during a six month period. Main outcome measures: Incidence of acute upper gastrointestinal haemorrhage per 100 000 population per year, and case fatality. Results: The annual incidence was 172 per 100 000 people aged 15 and over. The annual population mortality was 14.0 per 100 000. Both were higher among elderly people, men, and patients resident in areas of greater social deprivation. Overall case fatality was 8.2%. This was higher among those who bled as inpatients after admission for other reasons (42%) and those admitted as tertiary referrals (16%). Factors associated with increased case fatality were age, uraemia, pre-existing malignancy, hepatic failure, hypotension, cardiac failure, and frank haematemesis or a history of syncope at presentation. Social deprivation, sex, and anaemia were not associated with increased case fatality after adjustment for other factors. Conclusions: The incidence of acute upper gastrointestinal haemorrhage was 67% greater than the highest previously reported incidence in the United Kingdom, which may be partially attributable to the greater social deprivation in the west of Scotland and may be related to the increased prevalence of Helicobacter pylori. Fatality after acute upper gastrointestinal haemorrhage was associated with age, comorbidity, hypotension, and raised blood urea concentrations on admission. Although deprivation was associated with increased incidence, it was not related to the risk of fatality. Key messages The incidence of upper gastrointestinal haemorrhage in the west of Scotland was 67% higher than the highest incidence previously reported in the United Kingdom A substantial part of this excess incidence may be attributable to socioeconomic deprivation The overall population mortality from upper gastrointestinal haemorrhage may increase as the elderly population increases because both incidence and case fatality rise steeply with age A reduction in the overall case fatality from acute upper gastrointestinal haemorrhage will be best achieved by reducing case fatality among elderly patients

Teenage pregnancy and risk of adverse perinatal outcomes associated with first and second births: population based retrospective cohort study

Abstract Objective: To determine whether first and second births among teenagers are associated with increased risk of adverse perinatal outcomes after confounding variables have been taken into account. Design: Population based retrospective cohort study using routine discharge data for 1992-8. Setting: Scotland. Main outcome measures: Stillbirth, preterm delivery, emergency caesarean section, and small for gestational age baby among non-smoking mothers aged 15-19 and 20-29. Results: The 110 233 eligible deliveries were stratified into first and second births. Among first births, the only significant difference in adverse outcomes by age group was for emergency caesarean section, which was less likely among younger mothers (odds ratio 0.5, 95% confidence interval 0.5 to 0.6). Second births in women aged 15-19 were associated with an increased risk of moderate (1.6, 1.2 to 2.1) and extreme prematurity (2.5, 1.5 to 4.3) and stillbirth (2.6, 1.3 to 5.3) but a reduced risk of emergency caesarean section (0.7, 0.5 to 1.0). Conclusions: First teenage births are not independently associated with an increased risk of adverse pregnancy outcome and are at decreased risk of delivery by emergency caesarean section. However, second teenage births are associated with an almost threefold risk of preterm delivery and stillbirth. What is already known on this topic Teenage mothers are more likely to deliver prematurely and to have a perinatal death than older women Teenage mothers are also more likely to smoke, be having a first baby, and live in adverse social circumstances What this study adds Non-smoking women aged 15-19 having a first birth were not at increased risk of adverse obstetric outcomes compared with women aged 20-29 after potential confounding variables were adjusted for Non-smoking women aged 15-19 having a second birth were at significantly increased risk of both premature delivery and stillbirth compared with women aged 20-29

Gestational Age at Delivery and Special Educational Need: Retrospective Cohort Study of 407,503 Schoolchildren

A retrospective cohort study of 407,503 schoolchildren by Jill Pell and colleagues finds that gestational age at delivery has a dose-dependent relationship with the risk of special educational needs that extends across the full gestational range.

Interpregnancy interval and risk of preterm birth and neonatal death: retrospective cohort study

Abstract Objective To determine whether a short interval between pregnancies is an independent risk factor for adverse obstetric outcome. Design Retrospective cohort study. Setting Scotland. Subjects 89 143 women having second births in 1992-8 who conceived within five years of their first birth. Main outcome measures Intrauterine growth restriction (birth weight less than the 5th centile for gestational age), extremely preterm birth (24-32 weeks), moderately preterm birth (33-36 weeks), and perinatal death. Results Women whose subsequent interpregnancy interval was less than six months were more likely than other women to have had a first birth complicated by intrauterine growth restriction (odds ratio 1.3, 95% confidence interval 1.1 to 1.5), extremely preterm birth (4.1, 3.2 to 5.3), moderately preterm birth (1.5, 1.3 to 1.7), or perinatal death (24.4, 18.9 to 31.5). They were also shorter, less likely to be married, and more likely to be aged less than 20 years at the time of the second birth, to smoke, and to live in an area of high socioeconomic deprivation. When the outcome of the second birth was analysed in relation to the preceding interpregnancy interval and the analysis confined to women whose first birth was a term live birth (n = 69 055), no significant association occurred (adjusted for age, marital status, height, socioeconomic deprivation, smoking, previous birth weight vigesimal, and previous caesarean delivery) between interpregnancy interval and intrauterine growth restriction or stillbirth. However, a short interpregnancy interval (< 6 months) was an independent risk factor for extremely preterm birth (adjusted odds ratio 2.2, 1.3 to 3.6), moderately preterm birth (1.6, 1.3 to 2.0), and neonatal death unrelated to congenital abnormality (3.6, 1.2 to 10.7). The adjusted attributable fractions for these associations were 6.1%, 3.9%, and 13.8%. The associations were very similar when the analysis was confined to married non-smokers aged 25 and above. Conclusions A short interpregnancy interval is an independent risk factor for preterm delivery and neonatal death in the second birth.