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1.  Tea drinking habits and oesophageal cancer in a high risk area in northern Iran: population based case-control study 
Objective To investigate the association between tea drinking habits in Golestan province, northern Iran, and risk of oesophageal squamous cell carcinoma.
Design Population based case-control study. In addition, patterns of tea drinking and temperature at which tea was drunk were measured among healthy participants in a cohort study.
Setting Golestan province, northern Iran, an area with a high incidence of oesophageal squamous cell carcinoma.
Participants 300 histologically proved cases of oesophageal squamous cell carcinoma and 571 matched neighbourhood controls in the case-control study and 48 582 participants in the cohort study.
Main outcome measure Odds ratio of oesophageal squamous cell carcinoma associated with drinking hot tea.
Results Nearly all (98%) of the cohort participants drank black tea regularly, with a mean volume consumed of over one litre a day. 39.0% of participants drank their tea at temperatures less than 60°C, 38.9% at 60-64°C, and 22.0% at 65°C or higher. A moderate agreement was found between reported tea drinking temperature and actual temperature measurements (weighted κ 0.49). The results of the case-control study showed that compared with drinking lukewarm or warm tea, drinking hot tea (odds ratio 2.07, 95% confidence interval 1.28 to 3.35) or very hot tea (8.16, 3.93 to 16.9) was associated with an increased risk of oesophageal cancer. Likewise, compared with drinking tea four or more minutes after being poured, drinking tea 2-3 minutes after pouring (2.49, 1.62 to 3.83) or less than two minutes after pouring (5.41, 2.63 to 11.1) was associated with a significantly increased risk. A strong agreement was found between responses to the questions on temperature at which tea was drunk and interval from tea being poured to being drunk (weighted κ 0.68).
Conclusion Drinking hot tea, a habit common in Golestan province, was strongly associated with a higher risk of oesophageal cancer.
PMCID: PMC3269898  PMID: 19325180
2.  Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort 
Objectives To assess the incidence of and risks for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities among adult survivors of childhood and adolescent cancers.
Design Retrospective cohort study.
Setting 26 institutions that participated in the Childhood Cancer Survivor Study.
Participants 14 358 five year survivors of cancer diagnosed under the age of 21 with leukaemia, brain cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, kidney cancer, neuroblastoma, soft tissue sarcoma, or bone cancer between 1970 and 1986. Comparison group included 3899 siblings of cancer survivors.
Main outcome measures Participants or their parents (in participants aged less than 18 years) completed a questionnaire collecting information on demographic characteristics, height, weight, health habits, medical conditions, and surgical procedures occurring since diagnosis. The main outcome measures were the incidence of and risk factors for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities in survivors of cancer compared with siblings.
Results Survivors of cancer were significantly more likely than siblings to report congestive heart failure (hazard ratio (HR) 5.9, 95% confidence interval 3.4 to 9.6; P<0.001), myocardial infarction (HR 5.0, 95% CI 2.3 to 10.4; P<0.001), pericardial disease (HR 6.3, 95% CI 3.3 to 11.9; P<0.001), or valvular abnormalities (HR 4.8, 95% CI 3.0 to 7.6; P<0.001). Exposure to 250 mg/m2 or more of anthracyclines increased the relative hazard of congestive heart failure, pericardial disease, and valvular abnormalities by two to five times compared with survivors who had not been exposed to anthracyclines. Cardiac radiation exposure of 1500 centigray or more increased the relative hazard of congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities by twofold to sixfold compared to non-irradiated survivors. The cumulative incidence of adverse cardiac outcomes in cancer survivors continued to increase up to 30 years after diagnosis.
Conclusion Survivors of childhood and adolescent cancer are at substantial risk for cardiovascular disease. Healthcare professionals must be aware of these risks when caring for this growing population.
PMCID: PMC3266843  PMID: 19996459
3.  Adiposity and weight change in mid-life in relation to healthy survival after age 70 in women: prospective cohort study 
Objective To examine the hypothesis that mid-life adiposity is associated with a reduced probability of maintaining an optimal health status among those who survive to older ages.
Design Prospective cohort study.
Setting The Nurses’ Health Study, United States.
Participants 17 065 women who survived until at least the age of 70, provided information on occurrence of chronic disease, cognitive function, physical function, and mental health at older ages, and were free from major chronic diseases at mid-life (mean age was 50 at baseline in 1976).
Main outcome measures Healthy survival to age 70 and over was defined as having no history of 11 major chronic diseases and having no substantial cognitive, physical, or mental limitations.
Results Of the women who survived until at least age 70, 1686 (9.9%) met our criteria for healthy survival. Increased body mass index (BMI) at baseline was significantly associated with linearly reduced odds of healthy survival compared with usual survival, after adjustment for various lifestyle and dietary variables (P<0.001 for trend). Compared with lean women (BMI 18.5-22.9), obese women (BMI ≥30) had 79% lower odds of healthy survival (odds ratio 0.21, 95% confidence interval 0.15 to 0.29). In addition, the more weight gained from age 18 until mid-life, the less likely was healthy survival after the age of 70. The lowest odds of healthy survival were among women who were overweight (BMI ≥25) at age 18 and gained ≥10 kg weight (0.18, 0.09 to 0.36), relative to women who were lean (BMI 18.5-22.9) and maintained a stable weight.
Conclusions These data provide evidence that adiposity in mid-life is strongly related to a reduced probability of healthy survival among women who live to older ages, and emphasise the importance of maintaining a healthy weight from early adulthood.
PMCID: PMC3230231  PMID: 19789407
5.  Common mental disorder and obesity: insight from four repeat measures over 19 years: prospective Whitehall II cohort study 
To examine potential reciprocal associations between common mental disorders and obesity, and to assess whether there are dose-response relationships.
Prospective cohort study with four measures of common mental disorders and obesity over 19 years (Whitehall II study).
Civil service departments in London.
4363 adults (28% female, mean age 44 years at baseline).
Main outcome
Common mental disorder defined as General Health Questionnaire ‘caseness’; overweight and obesity based on Word Health Organization definitions.
In models adjusted for age, sex and body mass index at baseline, odds ratios for obesity at the fourth screening were 1.33 (95% confidence interval 1.00 to 1.77), 1.64 (1.13 to 2.36) and 2.01 (1.21 to 3.34) for participants with common mental disorder at one, two or three preceding screenings compared to individuals free from common mental disorder (ptrend<0.0001). The corresponding mean differences in body mass index at the last screening were 0.20, 0.31, 0.50 kg/m2, respectively (ptrend<0.0001). These associations remained after adjustments for baseline characteristics related to mental health and the exclusion of participants who were obese at baseline. In addition, obesity predicted future risk of common mental disorder, again with evidence of a dose-response relationship (ptrend=0.02, multivariable model). However, this association was lost when individuals with common mental disorder at baseline were excluded (ptrend=0.33).
These findings suggest that in British adults the direction of association between common mental disorders and obesity is from common mental disorder to increased future risk of obesity. This association is cumulative such that individuals with chronic or repeat episodes of common mental disorder are particularly at risk of weight gain.
PMCID: PMC2758338  PMID: 19808765
Adult; Epidemiologic Methods; Female; Humans; London; epidemiology; Male; Mental Disorders; complications; epidemiology; Middle Aged; Obesity; epidemiology; psychology
6.  The association between BMI and mortality using offspring BMI as an indicator of own BMI: large intergenerational mortality study 
Objectives To obtain valid estimates of the association between body mass index (BMI) and mortality by using offspring BMI as an instrumental variable for own BMI.
Design Cohort study based on record linkage, with 50 years of follow-up for mortality. Associations of offspring BMI with all cause and cause specific maternal and paternal mortality were estimated as hazard ratios per standard deviation of offspring BMI.
Setting A large intergenerational prospective population based database covering the general population of Sweden.
Participants More than one million Swedish parent-son pairs.
Results The final dataset analysed contained information on 1 018 012 mother-son pairs (122 677 maternal deaths) and 1 004 617 father-son pairs (242 126 paternal deaths). For some causes of death, the patterns of associations between offspring BMI and mortality were similar to those seen for own BMI and mortality in previous studies. Parental mortality from diabetes, coronary heart disease, and kidney cancer had the strongest positive associations with offspring BMI (for example, hazard ratio (HR) for coronary heart disease per standard deviation increase in offspring BMI for mothers 1.15, 95% CI 1.14 to 1.17 and for fathers 1.10, 1.09 to 1.11). However, in contrast to the inverse association of own BMI with lung cancer and respiratory disease mortality seen in other studies, there was a positive association between offspring BMI and lung cancer mortality in mothers (1.12, 1.09 to 1.15) and fathers (1.03, 1.02 to 1.05) and between offspring BMI and respiratory mortality in mothers (1.05, 1.02 to 1.08) and fathers (1.02, 1.00 to 1.04). Associations of own BMI and offspring BMI with all cause, cardiovascular disease related, and non-cardiovascular disease related mortality were compared in a subset of father-son pairs (n=72 815). When offspring BMI was used as an instrumental variable for paternal BMI, the causal association between BMI and paternal cardiovascular disease mortality (HR per standard deviation of BMI 1.82, 95% CI 1.17 to 2.83) was stronger than that indicated by the directly observed association between own BMI and cardiovascular disease mortality (1.45, 1.31 to 1.61).
Conclusions Use of offspring BMI as a predictor of own BMI, a technique that avoids problems of reverse causality, suggests that positive associations of BMI with all cause and cardiovascular mortality may be underestimated in conventional observational studies. Use of offspring BMI instead of own BMI in analyses of respiratory disease and lung cancer mortality, for which previous studies have reported consistent and strong inverse associations with own BMI, suggests that such studies have overstated the apparent adverse consequences of lower BMI with respect to these outcomes.
PMCID: PMC2797052  PMID: 20028778
7.  Health and disease in 85 year olds: baseline findings from the Newcastle 85+ cohort study 
Objectives The Newcastle 85+ Study aims to systematically study the clinical, biological, and psychosocial attributes of an unselected cohort of 85 year olds and to examine subsequent health trajectories as the cohort ages; health at baseline is reported.
Design Cross sectional analysis of baseline data from a cohort study.
Setting Newcastle upon Tyne and North Tyneside primary care trusts, United Kingdom.
Participants 1042 people born in 1921 and registered with the participating general practices.
Main outcome measures Detailed health assessment and review of general practice records (disease, medication, and use of general practice services); participants could decline elements of the protocol.
Results Of the 1453 eligible people, 851 (58.6%) were recruited to health assessment plus record review, 188 (12.9%) to record review only, and 3 (0.2%) to health assessment only. Data from record review are reported on a maximum of 1030 and from health assessment on a maximum of 853; individual denominators differ owing to withdrawal and missing values. Of the health assessment sample (n=853), 62.1% (n=530) were women and 10.4% (n=89) were in institutional care. The most prevalent diseases were hypertension (57.5%, 592/1030) and osteoarthritis (51.8%, 534/1030). Moderate or severe cognitive impairment was present in 11.7% (96/824) of participants, severe or profound urinary incontinence in 21.3% (173/813), hearing impairment in 59.6% (505/848), and visual impairment in 37.2% (309/831). Health assessment identified participants with possible disease but without a previous diagnosis in their medical record for hypertension (25.1%, 206/821), ischaemic heart disease (12.6%, 99/788), depression (6.9%, 53/772), dementia (6.7%, 56/840), and atrial fibrillation (3.8%, 30/788). Undiagnosed diabetes mellitus and thyroid disease were rare (1%, 7/717 and 6/762, respectively). A median of 3 (interquartile range 1-8) activities of daily living were undertaken with difficulty. Overall, 77.6% (646/832) of participants rated their health compared with others of the same age as good, very good, or excellent. High contact rates in the previous year with general practitioners (93.8%, 960/1024) were recorded. Women had significantly higher disease counts (medians: women 5, men 4; P=0.033) and disability scores (medians: women 4, men 2; P=0.0006) than men, but were less likely to have attended outpatient clinics in the previous three months (women 29% (150/524), men 37% (118/320), odds ratio 0.7, 95% confidence interval 0.5 to 0.9).
Conclusions This large cohort of 85 year olds showed good levels of both self rated health and functional ability despite significant levels of disease and impairment. Hypertension, ischaemic heart disease, atrial fibrillation, depression, and dementia may be underdiagnosed. Notable differences were found between the sexes: women outnumbered men and had more disease and disability.
PMCID: PMC2797051  PMID: 20028777
8.  Screening for postnatal depression in primary care: cost effectiveness analysis 
Objective To evaluate the cost effectiveness of routine screening for postnatal depression in primary care.
Design Cost effectiveness analysis with a decision model of alternative methods of screening for depression, including standardised postnatal depression and generic depression instruments. The performance of screening instruments was derived from a systematic review and bivariate meta-analysis at a range of instrument cut points; estimates of other relevant parameters were derived from literature sources and relevant databases. A decision tree considered the full treatment pathway from the possible onset of postnatal depression through identification, treatment, and possible relapse.
Setting Primary care.
Participants A hypothetical population of women assessed for postnatal depression either via routine care only or supplemented by use of formal identification methods six weeks postnatally, as recommended in recent guidelines.
Main outcome measures Costs expressed in 2006-7 prices and impact on health outcomes expressed in terms of quality adjusted life years (QALYs). The time horizon of the analysis was one year.
Results The routine application of either postnatal or general depression questionnaires did not seem to be cost effective compared with routine care only. The Edinburgh postnatal depression scale (at a cut point of 16) had an incremental cost effectiveness ratio (ICER) of £41 103 (€45 398, $67 130) per QALY compared with routine care only. The ICER for all other strategies ranged from £49 928 to £272 463 per QALY versus routine care only, while the probability that no formal identification strategy was cost effective was 88% (59%) at a cost effectiveness threshold of £20 000 (£30 000) per QALY. While sensitivity analysis indicated that the cost of managing incorrectly identified depression (false positive result) was an important driver of the model, formal identification approaches did not seem to be cost effective at any feasible estimate of this cost.
Conclusions Formal identification methods for postnatal depression do not seem to represent value for money for the NHS. The major determinant of cost effectiveness seems to be the potential additional costs of managing women incorrectly diagnosed as depressed. Formal identification methods for postnatal depression do not currently satisfy the National Screening Committee’s criteria for the adoption of a screening strategy as part of national health policy.
PMCID: PMC2797050  PMID: 20028779
9.  Topical intranasal corticosteroids in 4-11 year old children with persistent bilateral otitis media with effusion in primary care: double blind randomised placebo controlled trial 
Objective To determine the clinical effectiveness of topical intranasal corticosteroids in children with bilateral otitis media with effusion.
Design Double blind randomised placebo controlled trial.
Setting 76 Medical Research Council General Practice Research Framework practices throughout the United Kingdom, between 2004 and 2007.
Participants 217 children aged 4-11 years who had at least one practice recorded episode of otitis media or a related ear problem in the previous 12 months, and with bilateral otitis media with effusion confirmed by a research nurse using otoscopy plus micro-tympanometry (B/B or B/C2, modified Jerger types).
Intervention Mometasone furoate 50 µg or placebo spray given once daily into each nostril for three months.
Main outcome measures Proportions of children cured of bilateral otitis media with effusion assessed with tympanometry (C1 or A type) at one month (primary end point), three months, and nine months; adverse events; three month diary symptoms.
Results 41% (39/96) of the topical steroid group and 45% (44/98) of the placebo group were cured in one or both ears at one month (difference favouring placebo 4.3% (95% confidence interval −9.3% to 18.1%). Poisson regression was done with adjustment for four pre-specified covariates (clinical severity, P=0.003; atopy, P=0.67; age, P=0.92; season, P=0.71). The adjusted relative risk at one month was 0.97 (95% confidence interval 0.74 to 1.26). At three months, 58% of the topical steroid group and 52% of the placebo group were cured (relative risk 1.23, 0.84 to 1.80). Diary symptoms did not differ between the two groups, and no significant harms were reported.
Conclusions Topical steroids are unlikely to be an effective treatment for otitis media with effusion in general practice. High rates of natural resolution occurred by 1-3 months.
Trial registration Current Controlled Trials ISRCTN38988331; National Research Register NO575123823; MREC 03/11/073.
PMCID: PMC2795136  PMID: 20015903
10.  Lying obliquely—a clinical sign of cognitive impairment: cross sectional observational study 
Objective To determine if failure to spontaneously orient the body along the longitudinal axis of a hospital bed when asked to lie down is associated with cognitive impairment in older patients.
Design Cross sectional observational study.
Setting Neurology department of a university hospital in Germany.
Participants Convenience sample of 110 older (≥60 years) inpatients with neurological conditions and 23 staff neurologists.
Main outcome measures The main outcome measure was the association between the angle of the body axis and the results of three cognitive screening tests (mini-mental state examination, DemTect, and clock drawing test). Staff doctors were shown photographs of a model taken at a natural viewing able to determine their subjective perspective of what constitutes oblique.
Results 110 neurological inpatients (mean age 70.9 (SD 6.8) years) were included after exclusions. Evidence of cognitive impairment was found in 34, with scores indicating dementia in eight, according to the mini-mental state examination, and in 11 according to the DemTect. Across all patients, the mean angular deviation of the body axis from the longitudinal axis of the bed (range 0-23°) correlated linearly with the mini-mental state examination (r=−0.480), DemTect (r=−0.527), and the clock drawing test (r=−0.552) scores (P<0.001 for all), even after removing age as a covariate. Overall, 90% of staff neurologists considered a minimal body angle of 7° to be oblique. Angular deviation of at least 7° predicted cognitive impairment according to the three different tests, with specificities between 89% and 96% and sensitivities between 27% and 50%.
Conclusion Clinicians might suspect cognitive impairment in mobile older inpatients with neurological disorders who spontaneously position themselves obliquely when asked to lie on a bed.
PMCID: PMC2795135  PMID: 20015907
11.  Perceived age as clinically useful biomarker of ageing: cohort study 
Objective To determine whether perceived age correlates with survival and important age related phenotypes.
Design Follow-up study, with survival of twins determined up to January 2008, by which time 675 (37%) had died.
Setting Population based twin cohort in Denmark.
Participants 20 nurses, 10 young men, and 11 older women (assessors); 1826 twins aged ≥70.
Main outcome measures Assessors: perceived age of twins from photographs. Twins: physical and cognitive tests and molecular biomarker of ageing (leucocyte telomere length).
Results For all three groups of assessors, perceived age was significantly associated with survival, even after adjustment for chronological age, sex, and rearing environment. Perceived age was still significantly associated with survival after further adjustment for physical and cognitive functioning. The likelihood that the older looking twin of the pair died first increased with increasing discordance in perceived age within the twin pair—that is, the bigger the difference in perceived age within the pair, the more likely that the older looking twin died first. Twin analyses suggested that common genetic factors influence both perceived age and survival. Perceived age, controlled for chronological age and sex, also correlated significantly with physical and cognitive functioning as well as with leucocyte telomere length.
Conclusion Perceived age—which is widely used by clinicians as a general indication of a patient’s health—is a robust biomarker of ageing that predicts survival among those aged ≥70 and correlates with important functional and molecular ageing phenotypes.
PMCID: PMC2792675  PMID: 20008378
12.  Effect of listening to Nellie the Elephant during CPR training on performance of chest compressions by lay people: randomised crossover trial 
Objectives To determine whether listening to music during cardiopulmonary resuscitation (CPR) training increases the proportion of lay people delivering chest compressions of 100 per minute.
Design Prospective randomised crossover trial.
Setting Large UK university.
Participants 130 volunteers (81 men) recruited on an opportunistic basis. Exclusion criteria included age under 18, trained health professionals, and cardiopulmonary resuscitation (CPR) training within the past three months.
Interventions Volunteers performed three sequences of one minute of continuous chest compressions on a skill meter resuscitation manikin accompanied by no music, repeated choruses of Nellie the Elephant (Nellie), and That’s the Way (I like it) (TTW) according to a pre-randomised order.
Main outcome measures Rate of chest compressions delivered (primary outcome), depth of compressions, proportion of incorrect compressions, and type of error.
Results Median (interquartile range) compression rates were 110 (93-119) with no music, 105 (98-107) with Nellie, and 109 (103-110) with TTW. There were significant differences within groups between Nellie v no music and Nellie v TTW (P<0.001) but not no music v TTW (P=0.055). A compression rate of between 95 and 105 was achieved with no music, Nellie, and TTW for 15/130 (12%), 42/130 (32%), and 12/130 (9%) attempts, respectively. Differences in proportions were significant for Nellie v no music and Nellie v TTW (P<0.001) but not for no music v TTW (P=0.55). Relative risk for a compression rate between 95 and 105 was 2.8 (95% confidence interval 1.66 to 4.80) for Nellie v no music, 0.8 (0.40 to 1.62) for TTW v no music, and 3.5 (1.97 to 6.33) for Nellie v TTW. The number needed to treat for listening to Nellie v no music was 5 (4 to 10)—that is, the number of cardiac arrests required during which lay responders listen to Nellie to facilitate one patient receiving compressions at the correct rate (v no music) would be between four and 10. A greater proportion of compressions were too shallow when participants listened to Nellie v no music (56% v 47%, P=0.022).
Conclusions Listening to Nellie the Elephant significantly increased the proportion of lay people delivering compression rates at close to 100 per minute. Unfortunately it also increased the proportion of compressions delivered at an inadequate depth. As current resuscitation guidelines give equal emphasis to correct rate and depth, listening to Nellie the Elephant as a learning aid during CPR training should be discontinued. Further research is required to identify music that, when played during CPR training, increases the proportion of lay responders providing chest compressions at both the correct rate and depth.
PMCID: PMC2792674  PMID: 20008376
13.  The association of early IQ and education with mortality: 65 year longitudinal study in Malmö, Sweden 
Objectives To establish whether differences in early IQ explain why people with longer education live longer, or whether differences in father’s or own educational attainment explain why people with higher early IQ live longer.
Design Population based longitudinal study. Mortality risks were estimated with Cox proportional hazards regressions.
Setting Malmö, Sweden.
Participants 1530 children who took IQ tests at age 10 and were followed up until age 75.
Results Own educational attainment was negatively associated with all cause mortality in both sexes, even when early IQ and father’s education were adjusted for (hazard ratio (HR) for each additional year in school 0.91 (95% CI 0.85 to 0.97) for men and HR 0.88 (95 % CI 0.78 to 0.98) for women). Higher early IQ was linked with a reduced mortality risk in men, even when own educational attainment and father’s education were adjusted for (HR for one standard deviation increase in IQ 0.85 (95 % CI 0.75 to 0.96)). In contrast, there was no crude effect of early IQ for women, and women with above average IQ had an increased mortality risk when own educational attainment was adjusted for, but only after the age of 60 (HR 1.60 (95 % CI 1.06 to 2.42)). Adding measures of social career over and above educational attainment to the model (for example, occupational status at age 36 and number of children) only marginally affected the hazard ratio for women with above average IQ (<5%).
Conclusions Mortality differences by own educational attainment were not explained by early IQ. Childhood IQ was independently linked, albeit differently, to male adult mortality and to female adult mortality even when father’s education and own educational attainment was adjusted for, thus social background and own social career seem unlikely to be responsible for mortality differences by childhood IQ. The clear difference in the effect of IQ between men and women suggests that the link between IQ and mortality involves the social and physical environment rather than simply being a marker of a healthy body to begin with. Cognitive skills should, therefore, be addressed in our efforts to create childhood environments that promote health.
PMCID: PMC2792333  PMID: 20008007
14.  Kidney Function and Risk of Cardiovascular Disease and Mortality in Women: a Prospective Cohort Study 
Studies suggest that impaired kidney function is associated with cardiovascular disease (CVD) and mortality, particularly CVD death, among patients with existing kidney disease or CVD. Data in primary prevention are sparse. We aimed to evaluate the association of kidney function with CVD and mortality among apparently healthy women.
Prospective cohort study among 27,939 female health professionals aged ≥45 who were free of CVD and provided a blood sample at study entry.
Women's health study, United States.
Main outcome measures
Time to CVD (nonfatal stroke, nonfatal myocardial infarction, coronary revascularization procedures, or death from cardiovascular cause), specific CVD events, and all-cause mortality. Endpoints were confirmed after medical record and death certificate review.
We estimated glomerular filtration rate (GFR) using the abbreviated Modification-of-Diet-in-Renal-Disease-Study equation. At baseline, 1,315 (4.7%) women had GFR <60 ml/min/1.73m2. During 12 years of follow-up, 1,199 incident CVD events and 856 deaths (179 from CVD) occurred. Compared with women with GFR ≥90 ml/min/1.73m2, the multivariable-adjusted hazard ratios (HRs) (95% confidence intervals) were 0.95 (0.83−1.08), 0.84 (0.70−1.00), and 1.00 (0.79−1.27) for any first CVD and 0.93 (0.79−1.09), 1.03 (0.85−1.26), and 1.09 (0.83−1.45) for all-cause mortality among women with GFR levels of 75−89.9, 60−74.9, and <60 ml/min/1.73 m2, respectively. Similar null findings were observed for myocardial infarction, stroke, coronary revascularization, and non-cardiovascular death. In contrast, we observed an increased risk of CVD death (HR=1.68; 1.02−2.79) for women with GFR <60 ml/min/1.73m2.
In this large cohort of women, GFR <60 ml/min/1.73m2 appeared to be associated with increased risk of CVD death but not other CVD events or non-CVD mortality. We observed no increase in risk of any of the outcomes among women with less severe impairment of kidney function.
PMCID: PMC2704981  PMID: 19564178
kidney; cardiovascular disease; women; epidemiology
15.  Mortality from pandemic A/H1N1 2009 influenza in England: public health surveillance study 
Objective To establish mortality from pandemic A/H1N1 2009 influenza up to 8 November 2009.
Design Investigation of all reported deaths related to pandemic A/H1N1 in England.
Setting Mandatory reporting systems established in acute hospitals and primary care.
Participants Physicians responsible for the patient.
Main outcome measures Numbers of deaths from influenza combined with mid-range estimates of numbers of cases of influenza to calculate age specific case fatality rates. Underlying conditions, time course of illness, and antiviral treatment.
Results With the official mid-range estimate for incidence of pandemic A/H1N1, the overall estimated case fatality rate was 26 (range 11-66) per 100 000. It was lowest for children aged 5-14 (11 (range 3-36) per 100 000) and highest for those aged ≥65 (980 (range 300-3200) per 100 000). In the 138 people in whom the confirmed cause of death was pandemic A/H1N1, the median age was 39 (interquartile range 17-57). Two thirds of patients who died (92, 67%) would now be eligible for the first phase of vaccination in England. Fifty (36%) had no, or only mild, pre-existing illness. Most patients (108, 78%) had been prescribed antiviral drugs, but of these, 82 (76%) did not receive them within the first 48 hours of illness.
Conclusions Viewed statistically, mortality in this pandemic compares favourably with 20th century influenza pandemics. A lower population impact than previous pandemics, however, is not a justification for public health inaction. Our data support the priority vaccination of high risk groups. We observed delayed antiviral use in most fatal cases, which suggests an opportunity to reduce deaths by making timely antiviral treatment available, although the lack of a control group limits the ability to extrapolate from this observation. Given that a substantial minority of deaths occur in previously healthy people, there is a case for extending the vaccination programme and for continuing to make early antiviral treatment widely available.
PMCID: PMC2791802  PMID: 20007665
16.  Effect of 20 mph traffic speed zones on road injuries in London, 1986-2006: controlled interrupted time series analysis 
Objective To quantify the effect of the introduction of 20 mph (32 km an hour) traffic speed zones on road collisions, injuries, and fatalities in London.
Design Observational study based on analysis of geographically coded police data on road casualties, 1986-2006. Analyses were made of longitudinal changes in counts of road injuries within each of 119 029 road segments with at least one casualty with conditional fixed effects Poisson models. Estimates of the effect of introducing 20 mph zones on casualties within those zones and in adjacent areas were adjusted for the underlying downward trend in traffic casualties.
Setting London.
Main outcome measures All casualties from road collisions; those killed and seriously injured (KSI).
Results The introduction of 20 mph zones was associated with a 41.9% (95% confidence interval 36.0% to 47.8%) reduction in road casualties, after adjustment for underlying time trends. The percentage reduction was greatest in younger children and greater for the category of killed or seriously injured casualties than for minor injuries. There was no evidence of casualty migration to areas adjacent to 20 mph zones, where casualties also fell slightly by an average of 8.0% (4.4% to 11.5%).
Conclusions 20 mph zones are effective measures for reducing road injuries and deaths.
PMCID: PMC2791801  PMID: 20007666
17.  Retrospective analysis of attitudes to ageing in the Economist: apocalyptic demography for opinion formers 
Objective To investigate the description of older people and ageing in a major weekly newspaper, influential in political and financial circles, to see whether it reflected ageing in a balanced manner, and to what extent it indulged in apocalyptic demography—the portrayal of population ageing as a financial burden rather than a scientific advance.
Design Electronic search of the digital archive of the Economist of articles published between January 1997 and April 2008.
Main outcomes measures Categorisation of articles as portraying population ageing as a burden or a benefit or with a balanced view.
Results Of 6306 identified articles, 262 were relevant. Most featured pensions, demography, and politics. Of these 262, 64% portrayed population ageing as a burden and 12% as a benefit; 24% had a balanced view. Most articles therefore showed a predominantly ageist view of older people as a burden on society, often portraying them as frail non-contributors. Recurrent themes included pension and demographic “time bombs” and future unsustainable costs of health care for older people.
Conclusion This negative view of older people might be influential in shaping the attitudes of readers, who include opinion formers in political and economic circles. Gerontologists (including geriatricians) need to engage with influential media, as well as helping to promote a professional development of journalists that is informed and knowledgeable about the negative impact of ageism on the wellbeing of older people.
PMCID: PMC2790575  PMID: 19995819
18.  Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis 
Objectives To update a 2005 Cochrane review that assessed the effects of neuraminidase inhibitors in preventing or ameliorating the symptoms of influenza, the transmission of influenza, and complications from influenza in healthy adults, and to estimate the frequency of adverse effects.
Search strategy An updated search of the Cochrane central register of controlled trials (Cochrane Library 2009, issue 2), which contains the Acute Respiratory Infections Group’s specialised register, Medline (1950-Aug 2009), Embase (1980-Aug 2009), and post-marketing pharmacovigilance data and comparative safety cohorts.
Selection criteria Randomised placebo controlled studies of neuraminidase inhibitors in otherwise healthy adults exposed to naturally occurring influenza.
Main outcome measures Duration and incidence of symptoms; incidence of lower respiratory tract infections, or their proxies; and adverse events.
Data extraction Two reviewers applied inclusion criteria, assessed trial quality, and extracted data.
Data analysis Comparisons were structured into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose.
Results 20 trials were included: four on prophylaxis, 12 on treatment, and four on postexposure prophylaxis. For prophylaxis, neuraminidase inhibitors had no effect against influenza-like illness or asymptomatic influenza. The efficacy of oral oseltamivir against symptomatic laboratory confirmed influenza was 61% (risk ratio 0.39, 95% confidence interval 0.18 to 0.85) at 75 mg daily and 73% (0.27, 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily was 62% efficacious (0.38, 0.17 to 0.85). Oseltamivir for postexposure prophylaxis had an efficacy of 58% (95% confidence interval 15% to 79%) and 84% (49% to 95%) in two trials of households. Zanamivir performed similarly. The hazard ratios for time to alleviation of influenza-like illness symptoms were in favour of treatment: 1.20 (95% confidence interval 1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Eight unpublished studies on complications were ineligible and therefore excluded. The remaining evidence suggests oseltamivir did not reduce influenza related lower respiratory tract complications (risk ratio 0.55, 95% confidence interval 0.22 to 1.35). From trial evidence, oseltamivir induced nausea (odds ratio 1.79, 95% confidence interval 1.10 to 2.93). Evidence of rarer adverse events from pharmacovigilance was of poor quality or possibly under-reported.
Conclusion Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza. Independent randomised trials to resolve these uncertainties are needed.
PMCID: PMC2790574  PMID: 19995812
19.  Lead poisoning as possible cause of deaths at the Swedish House at Kapp Thordsen, Spitsbergen, winter 1872-3 
Objective To investigate cause of death in 17 sealers who died in the Swedish house in Kapp Thordsen, Spitsbergen, during the winter of 1872-3.
Design Analysis of skeletal samples from one sealer’s grave.
Setting Field trip to Spitsbergen to exhume skeletal remains.
Subjects One of 17 sailors who died in 1872-3.
Results No objective signs of scurvy were found. The concentration of lead in the bone samples was 102.05 µg/g.
Conclusions The high concentrations of lead indicate that this man died from lead poisoning, probably from food tins. The absence of macroscopic signs of scurvy supports this theory.
PMCID: PMC2789173  PMID: 19965937
20.  Ingested foreign bodies and societal wealth: three year observational study of swallowed coins 
Objective To examine the relation between coins ingested by children and the Dow Jones Industrial Average.
Design Observational study.
Main outcome measures Total value of coins ingested and number of incidents of coins versus other objects swallowed, measured before and after the stock market crash of October 2008.
Results Eighteen objects, including 11 coins, were ingested (NASDAQ (numismatic and sundry detritus acquired) composite of 18). The total value of the 11 coins swallowed was $1.03 (FTSE 100 (fraction of the US$ or 100 cents) index of 103). The pecuniary extraction ratio (PE ratio) was 0.57 (9/16). Comparing values for a period before and after October 2008, the mean monthly NASDAQ composite (0.41 (SD 0.67) v 0.5 (0.85), P=0.75), FTSE 100 index in cents (2.3 (6.8) v 3.1 (7.8), P=0.77), and PE ratio (0.54 (0.52) v 0.66 (0.29), P=0.50) did not change. The mean end-of-month closing value of the Dow Jones, however, decreased significantly (12 537 (841.4) v 8388 (699.8), P<0.001)
Conclusion There was no detectable difference in the total value of coins ingested, or ratio of coins to other objects swallowed, before or after a massive stock market crash.
PMCID: PMC2789172  PMID: 19965938
22.  Duration and magnitude of the postoperative risk of venous thromboembolism in middle aged women: prospective cohort study 
Objective To examine the duration and magnitude of increased risk of venous thromboembolism after different types of surgery.
Design Prospective cohort study (Million Women Study).
Setting Questionnaire data from the Million Women Study linked with hospital admission and death records.
Participants 947 454 middle aged women in the United Kingdom recruited in 1996-2001 and followed by record linkage to routinely collected NHS data on hospital admissions and deaths. During follow-up 239 614 admissions were for surgery; 5419 women were admitted, and a further 270 died, from venous thromboembolism.
Main outcome measures Adjusted relative risks and standardised incidence rates for hospital admission or death from venous thromboembolism (pulmonary embolism or deep vein thrombosis), by time since and type of surgery.
Results Compared with not having surgery, women were 70 times more likely to be admitted with venous thromboembolism in the first six weeks after an inpatient operation (relative risk 69.1, 95% confidence interval 63.1 to 75.6) and 10 times more likely after a day case operation (9.6, 8.0 to 11.5). The risks were lower but still substantially increased 7-12 weeks after surgery (19.6, 16.6 to 23.1 and 5.5, 4.3 to 7.0, respectively). This pattern of risk was similar for pulmonary embolism (n=2487) and deep venous thrombosis (n=3529). The postoperative risks of venous thromboembolism varied considerably by surgery type, with highest relative risks after inpatient surgery for hip or knee replacement and for cancer—1-6 weeks after surgery the relative risks were, respectively, 220.6 (187.8 to 259.2) and 91.6 (73.9 to 113.4).
Conclusion The risk of deep vein thrombosis and pulmonary embolism after surgery is substantially increased in the first 12 postoperative weeks, and varies considerably by type of surgery. An estimated 1 in 140 middle aged women undergoing inpatient surgery in the UK will be admitted with venous thromboembolism during the 12 weeks after surgery (1 in 45 after hip or knee replacement and 1 in 85 after surgery for cancer), compared with 1 in 815 after day case surgery and only 1 in 6200 women during a 12 week period without surgery.
PMCID: PMC2788913  PMID: 19959589
23.  Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database 
Objective To investigate the risk of incident myocardial infarction, congestive heart failure, and all cause mortality associated with prescription of oral antidiabetes drugs.
Design Retrospective cohort study.
Setting UK general practice research database, 1990-2005.
Participants 91 521 people with diabetes.
Main outcome measures Incident myocardial infarction, congestive heart failure, and all cause mortality. Person time intervals for drug treatment were categorised by drug class, excluding non-drug intervals and intervals for insulin.
Results 3588 incident cases of myocardial infarction, 6900 of congestive heart failure, and 18 548 deaths occurred. Compared with metformin, monotherapy with first or second generation sulphonylureas was associated with a significant 24% to 61% excess risk for all cause mortality (P<0.001) and second generation sulphonylureas with an 18% to 30% excess risk for congestive heart failure (P=0.01 and P<0.001). The thiazolidinediones were not associated with risk of myocardial infarction; pioglitazone was associated with a significant 31% to 39% lower risk of all cause mortality (P=0.02 to P<0.001) compared with metformin. Among the thiazolidinediones, rosiglitazone was associated with a 34% to 41% higher risk of all cause mortality (P=0.14 to P=0.01) compared with pioglitazone. A large number of potential confounders were accounted for in the study; however, the possibility of residual confounding or confounding by indication (differences in prognostic factors between drug groups) cannot be excluded.
Conclusions Our findings suggest a relatively unfavourable risk profile of sulphonylureas compared with metformin for all outcomes examined. Pioglitazone was associated with reduced all cause mortality compared with metformin. Pioglitazone also had a favourable risk profile compared with rosiglitazone; although this requires replication in other studies, it may have implications for prescribing within this class of drugs.
PMCID: PMC2788912  PMID: 19959591
24.  Effect of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomised controlled trial 
Objective To assess the effect of weight loss induced by a very low energy diet on moderate and severe obstructive sleep apnoea in obese men.
Design Single centre, two arm, parallel, randomised, controlled, open label trial. Blocked randomisation procedure used for treatment allocation.
Setting Outpatient obesity clinic in a university hospital in Stockholm, Sweden.
Participants 63 obese men (body mass index 30-40, age 30-65 years) with moderate to severe obstructive sleep apnoea (apnoea-hypopnoea index (AHI) ≥15), treated with continuous positive airway pressure.
Interventions The intervention group received a liquid very low energy diet (2.3 MJ/day) for seven weeks to promote weight loss, followed by two weeks of gradual introduction of normal food, reaching 6.3 MJ/day at week 9. The control group adhered to their usual diet during the nine weeks of follow-up.
Main outcome measure AHI, the major disease severity index for obstructive sleep apnoea. Data from all randomised patients were included in an intention to treat analysis (baseline carried forward for missing data).
Results Of the 63 eligible patients, 30 were randomised to intervention and 33 to control. Two patients in the control group were dissatisfied with allocation and immediately discontinued. All other patients completed the trial. Both groups had a mean AHI of 37 events/h (SD 15) at baseline. At week 9, the intervention group’s mean body weight was 20 kg (95% confidence interval 18 to 21) lower than that of the control group, while its mean AHI was 23 events/h (15 to 30) lower. In the intervention group, five of 30 (17%) were disease free after the energy restricted diet (AHI <5), with 15 of 30 (50%) having mild disease (AHI 5-14.9), whereas the AHI of all patients in the control group except one remained at 15 or higher. In a subgroup analysis of the intervention group, baseline AHI significantly modified the effectiveness of treatment, with a greater improvement in AHI in patients with severe obstructive sleep apnoea (AHI >30) at baseline compared with those with moderate (AHI 15-30) sleep apnoea (AHI −38 v −12, P<0.001), despite similar weight loss (−19.2 v −18.2 kg, P=0.55).
Conclusion Treatment with a low energy diet improved obstructive sleep apnoea in obese men, with the greatest effect in patients with severe disease. Long term treatment studies are needed to validate weight loss as a primary treatment strategy for obstructive sleep apnoea.
Trial registration Current Controlled Trials ISRCTN70090382.
PMCID: PMC2788899  PMID: 19959590
25.  Multiple sclerosis risk sharing scheme: two year results of clinical cohort study with historical comparator 
Objective To generate evidence on the longer term cost effectiveness of disease modifying treatments in patients with relapsing-remitting multiple sclerosis.
Design Prospective cohort study with historical comparator.
Setting Specialist multiple sclerosis clinics in 70 centres in the United Kingdom.
Participants Patients with relapsing-remitting multiple sclerosis who started treatment from May 2002 to April 2005 under the UK risk sharing scheme.
Interventions Treatment with interferon beta or glatiramer acetate in accordance with guidelines of the UK Association of British Neurologists.
Main outcome measures Observed utility weighted progression in disability at two years’ follow-up assessed on the expanded disability status scale (EDSS) compared with that expected by applying the progression rates in a comparator dataset, modified for patients receiving treatment by multiplying by the hazard ratio derived separately for each disease modifying treatment from the randomised trials.
Results In the primary per protocol analysis, progression in disability was worse than that predicted and worse than that in the untreated comparator dataset (“deviation score” of 113%; excess in mean disability status scale 0.28). In sensitivity analyses, however, the deviation score varied from −72% (using raw baseline disability status scale scores, rather than applying a “no improvement” algorithm) to 156% (imputing missing data for year two from progression rates for year one).
Conclusions It is too early to reach any conclusion about the cost effectiveness of disease modifying treatments from this first interim analysis. Important methodological issues, including the need for additional comparator datasets, the potential bias from missing data, and the impact of the “no improvement” rule, will need to be addressed and long term follow-up of all patients is essential to secure meaningful results. Future analyses of the cohort are likely to be more informative, not least because they will be less sensitive to short term fluctuations in disability.
PMCID: PMC2787922  PMID: 19955128

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