Sex differences in the association between major risk factors and the risk of stroke in the UK Biobank cohort study.

OBJECTIVE: To determine whether there are sex differences in the association between risk factors and incident stroke, including stroke subtypes. METHODS: A total of 471,971 (56% women) UK Biobank participants without a history of cardiovascular disease were included. During 9 years of follow-up, 4,662 (44% women) cases of stroke were recorded. Cox models yielded adjusted hazard ratios (HRs) and women-to-men ratios of HRs (RHRs) for stroke associated with 7 risk factors. RESULTS: The incidence rate per 10,000 person-years was 8.66 (8.29-9.04) in women and 13.96 (13.44-14.50) in men for any stroke, 6.06 (5.75-6.38) in women and 11.35 (10.88; 11.84) in men for ischemic stroke, and 1.56 (1.41-1.73) in women and 2.23 (2.02-2.45) in men for hemorrhagic stroke. The association between increases in blood pressure, body anthropometry, and lipids, diabetes, and atrial fibrillation and any stroke was similar between men and women. Hypertension, smoking, and a low socioeconomic status were associated with a greater HR of any stroke in women than men; the RHRs were 1.36 (1.26-1.47), 1.18 (1.02-1.36), and 1.17 (1.03-1.33), respectively. Diabetes was associated with a higher HR of ischemic stroke in women than men (RHR 1.25 [1.00-1.56]). Atrial fibrillation was associated with a higher HR of hemorrhagic stroke in women than men (RHR 2.80 [1.07-7.36]). CONCLUSION: Several risk factors are more strongly associated with the risk of any stroke or stroke subtypes in women compared with men. Despite this, the incidence of stroke remains higher among men than women.

Sex Differences in Cardiovascular Medication Prescription in Primary Care: A Systematic Review and Meta-Analysis.

Background Sex differences in the management of cardiovascular disease have been reported in secondary care. We conducted a systematic review with meta-analysis of systematically investigated sex differences in cardiovascular medication prescription among patients at high risk or with established cardiovascular disease in primary care. Methods and Results PubMed and Embase were searched between 2000 and 2019 for observational studies reporting on the sex-specific prevalence of aspirin, statins, and antihypertensive medication prescription, including beta blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and diuretics, in primary care. Random effects meta-analysis was used to obtain pooled women-to-men prevalence ratios for each cardiovascular medication prescription. Metaregression models assessed the impact of age and year on the findings. A total of 43 studies were included, involving 2 264 600 participants (28% women) worldwide. Participants' mean age ranged from 51 to 76 years. The pooled prevalence of cardiovascular medication prescription for women was 41% for aspirin, 60% for statins, and 68% for any antihypertensive medications. Corresponding rates for men were 56%, 63%, and 69% respectively. The pooled women-to-men prevalence ratios were 0.81 (95% CI, 0.72-0.92) for aspirin, 0.90 (95% CI, 0.85-0.95) for statins, and 1.01 (95% CI, 0.95-1.08) for any antihypertensive medications. Women were less likely to be prescribed angiotensin-converting enzyme inhibitors (0.85; 95% CI, 0.81-0.89) but more likely with diuretics (1.27; 95% CI, 1.17-1.37). Mean age, mean age difference between the sexes, and year of study had no significant impact on findings. Conclusions Sex differences in the prescription of cardiovascular medication exist among patients at high risk or with established cardiovascular disease in primary care, with a lower prevalence of aspirin, statins, and angiotensin-converting enzyme inhibitors prescription in women and a lower prevalence of diuretics prescription in men.

Temporal Trends and Patterns in Mortality After Incident Heart Failure: A Longitudinal Analysis of 86 000 Individuals.

Importance: Despite considerable improvements in heart failure care, mortality rates among patients in high-income countries have changed little since the early 2000s. Understanding the reasons underlying these trends may provide valuable clues for developing more targeted therapies and public health strategies. Objective: To investigate mortality rates following a new diagnosis of heart failure and examine changes over time and by cause of death and important patient features. Design, Setting, and Participants: This population-based retrospective cohort study analyzed anonymized electronic health records of individuals who received a new diagnosis of heart failure between January 2002 and December 2013 who were followed up until December 2014 from the Clinical Practice Research Datalink, which links information from primary care, secondary care, and the national death registry from a subset of the UK population. The data were analyzed from January 2018 to February 2019. Main Outcomes and Measures: All-cause and cause-specific mortality rates at 1 year following diagnosis. Poisson regression models were used to calculate rate ratios (RRs) and 95% confidence intervals comparing 2013 with 2002, adjusting for age, sex, region, socioeconomic status, and 17 major comorbidities. Results: Of 86 833 participants, 42 581 (49%) were women, 51 215 (88%) were white, and the mean (SD) age was 76.6 (12.6) years. While all-cause mortality rates declined only modestly over time (RR comparing 2013 with 2002, 0.94; 95% CI, 0.88-1.00), underlying patterns presented explicit trends. A decline in cardiovascular mortality (RR, 0.73; 95% CI, 0.67-0.80) was offset by an increase in noncardiovascular deaths (RR, 1.22; 95% CI, 1.11-1.33). Subgroup analyses further showed that overall mortality rates declined among patients younger than 80 years (RR, 0.79; 95% CI, 0.71-0.88) but not among those older than 80 years (RR, 0.97; 95% CI, 0.90-1.06). After cardiovascular causes (898 [43%]), the major causes of death in 2013 were neoplasms (311 [15%]), respiratory conditions (243 [12%]), and infections (13%), the latter 2 explaining most of the observed increase in noncardiovascular mortality. Conclusions and Relevance: Among patients with a new heart failure diagnosis, considerable progress has been achieved in reducing mortality in young and middle-aged patients and cardiovascular mortality across all age groups. Improvements to overall mortality are hindered by high and increasing rates of noncardiovascular events. These findings challenge current research priorities and management strategies and call for a greater emphasis on associated comorbidities. Specifically, infection prevention presents as a major opportunity to improve prognosis.

Sex Differences in the Assessment of Cardiovascular Risk in Primary Health Care: A Systematic Review.

OBJECTIVE: To determine whether sex differences exist in the assessment of cardiovascular disease (CVD) risk scores/risk factors in primary health care. DESIGN/METHODS: PubMed and EMBASE were systematically searched on 31 January 2017. Clinical trials and observational studies were included if they reported on the assessment of CVD risk score, blood pressure (BP), cholesterol or smoking status in primary health care, stratified by sex. Meta-analyses were performed, using random effects models, to determine differences between sexes, separately for adjusted and unadjusted data. RESULTS: Of 14,928 studies found in the search, 22 studies (including 4,754,782 patients) were included in the systematic review with the meta-analysis for quantitative assessment. Overall, the assessment rates of CVD risk score and risk factors were similar in women and men (CVD risk score: 30.7% vs. 35.2% [difference (95% CI): -4.5 (-5.1, -3.9)]; BP: 91.3% vs. 88.5% [2.8 (2.5, 3.0)]; cholesterol: 69.9% vs. 71.0% [-1.1 (-1.5, -0.8)]; and smoking: 85.9% vs. 86.7% [-0.8 (-1.1, -0.5)]). The pooled, adjusted likelihood of having the risk score, BP and cholesterol assessments were comparable between women and men: OR (95% CI): 0.87 (0.70, 1.07); 1.41 (0.89, 2.25); and 1.15 (0.82, 1.60), respectively. However, women were 32% less likely to be assessed for smoking (0.68 [0.47, 1.00]). There was substantial heterogeneity between studies and the risk of publication bias was moderate. CONCLUSION: Despite the guideline recommendations, assessment of CVD risk score in primary health care was low in both sexes. Further, women were less likely to be assessed for their smoking status than men, whereas no sex discrepancies were found for BP and cholesterol assessments.

Sex differences in risk factors for myocardial infarction: cohort study of UK Biobank participants.

OBJECTIVES: To investigate sex differences in risk factors for incident myocardial infarction (MI) and whether they vary with age. DESIGN: Prospective population based study. SETTING: UK Biobank. PARTICIPANTS: 471 998 participants (56% women; mean age 56.2) with no history of cardiovascular disease. MAIN OUTCOME MEASURE: Incident (fatal and non-fatal) MI. RESULTS: 5081 participants (1463 (28.8%) of whom were women) had MI over seven years' mean follow-up, resulting in an incidence per 10 000 person years of 7.76 (95% confidence interval 7.37 to 8.16) for women and 24.35 (23.57 to 25.16) for men. Higher blood pressure indices, smoking intensity, body mass index, and the presence of diabetes were associated with an increased risk of MI in men and women, but associations were attenuated with age. In women, systolic blood pressure and hypertension, smoking status and intensity, and diabetes were associated with higher hazard ratios for MI compared with men: ratio of hazard ratios 1.09 (95% confidence interval 1.02 to 1.16) for systolic blood pressure, 1.55 (1.32 to 1.83) for current smoking, 2.91 (1.56 to 5.45) for type 1 diabetes, and 1.47 (1.16 to 1.87) for type 2 diabetes. There was no evidence that any of these ratios of hazard ratios decreased with age (P>0.2). With the exception of type 1 diabetes, the incidence of MI was higher in men than in women for all risk factors. CONCLUSIONS: Although the incidence of MI was higher in men than in women, several risk factors were more strongly associated with MI in women compared with men. Sex specific associations between risk factors and MI declined with age, but, where it occurred, the higher relative risk in women remained. As the population ages and the prevalence of lifestyle associated risk factors increase, the incidence of MI in women will likely become more similar to that in men.

Do influenza and pneumococcal vaccines prevent community-acquired respiratory infections among older people with diabetes and does this vary by chronic kidney disease? A cohort study using electronic health records.

OBJECTIVE: We aimed to estimate the effectiveness of influenza and 23-valent pneumococcal polysaccharide vaccination on reducing the burden of community-acquired lower respiratory tract infection (LRTI) among older people with diabetes, and whether this varied by chronic kidney disease (CKD) status. RESEARCH DESIGN AND METHODS: We used linked UK electronic health records for a retrospective cohort study of 190 492 patients ≥65 years with diabetes mellitus and no history of renal replacement therapy, 1997-2011. We included community-acquired LRTIs managed in primary or secondary care. Infection incidence rate ratios were estimated using the Poisson regression. Pneumococcal vaccine effectiveness (VE) was calculated as (1-effect measure). To estimate influenza VE, a ratio-of-ratios analysis (winter effectiveness/summer effectiveness) was used to address confounding by indication. Final VE estimates were stratified according to estimated glomerular filtration rate and proteinuria status. RESULTS: Neither influenza nor pneumococcal vaccine uptake varied according to CKD status. Pneumococcal VE was 22% (95% CI 11% to 31%) against community-acquired pneumonia for the first year after vaccination, but was negligible after 5 years. In the ratio-of-ratios analysis, current influenza vaccination had 7% effectiveness for preventing community-acquired LRTI (95% CI 3 to 12). Pneumococcal VE was lower among patients with a history of proteinuria than among patients without proteinuria (p=0.04), but otherwise this study did not identify variation in pneumococcal or influenza VE by markers of CKD. CONCLUSIONS: The public health benefits of influenza vaccine may be modest among older people with diabetes. Pneumococcal vaccination protection against community-acquired pneumonia declines swiftly: alternative vaccination schedules should be investigated.

Bronchiectasis and the risk of cardiovascular disease: a population-based study.

BACKGROUND: There are limited data on the burden of cardiovascular comorbidities in people with bronchiectasis. Our cross-sectional study estimates the burden of pre-existing diagnoses of coronary heart disease (CHD) and stroke in people with bronchiectasis compared with the general population. The historical cohort study investigates if individuals with bronchiectasis are at increased risk of incident CHD and stroke events. METHODS: We used primary care electronic records from the Clinical Practice Research Datalink. The cross-sectional study used logistic regression to quantify the association between bronchiectasis and recorded diagnoses of CHD or stroke. Cox regression was used to investigate if people with bronchiectasis experienced increased incident CHD and strokes compared with the general population, adjusting for age, sex, smoking habit and other risk factors for cardiovascular disease. RESULTS: Pre-existing diagnoses of CHD (OR 1.33, 95% CI 1.25 to 1.41) and stroke (OR 1.92, 95% CI 1.85 to 2.01) were higher in people with bronchiectasis compared with those without bronchiectasis, after adjusting for age, sex, smoking and risk factors for cardiovascular disease. The rate of first CHD and stroke were also higher in people with bronchiectasis (HR for CHD 1.44 (95% CI 1.27 to 1.63) and HR for stroke 1.71 (95% CI 1.54 to 1.90)). CONCLUSION: The risk of CHD and stroke are higher among people with bronchiectasis compared with the general population. An increased awareness of these cardiovascular comorbidities in this population is needed to provide a more integrated approach to the care of these patients.

Improved incidence estimates from linked vs. stand-alone electronic health records.

OBJECTIVE: Electronic health records are widely used for public health research, and linked data sources are increasingly available. The added value of using linked records over stand-alone data has not been quantified for common conditions such as community-acquired pneumonia (CAP). STUDY DESIGN AND SETTING: Our cohort comprised English patients aged ≥65 years from the Clinical Practice Research Datalink, eligible for record linkage to Hospital Episode Statistics. Stand-alone general practice (GP) records were used to calculate CAP incidence over time using population-averaged Poisson regression. Incidence was then recalculated for the same patients using their linked GP-hospital admission data. Results of the two analyses were compared. RESULTS: Over 900,000 patients were included in each analysis. Population-averaged CAP incidence was 39% higher using the linked data than stand-alone data. This difference grew over time from 7% in 1997 to 83% by 2010. An increasingly larger number of pneumonia events were recorded in the hospital admission data compared to the GP data over time. CONCLUSION: Use of primary or secondary care data in isolation may not give accurate incidence estimates for important infections in older populations. Further work is needed to establish the extent of this finding in other diseases, age groups, and populations.

Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study.

There is a paucity of data on incidence, prevalence and mortality associated with non-cystic fibrosis bronchiectasis.Using the Clinical Practice Research Datalink for participants registered between January 1, 2004 and December 31, 2013, we determined incidence, prevalence and mortality associated with bronchiectasis in the UK and investigated changes over time.The incidence and point prevalence of bronchiectasis increased yearly during the study period. Across all age groups, the incidence in women increased from 21.2 per 100 000 person-years in 2004 to 35.2 per 100 000 person-years in 2013 and in men from 18.2 per 100 000 person-years in 2004 to 26.9 per 100 000 person-years in 2013. The point prevalence in women increased from 350.5 per 100 000 in 2004 to 566.1 per 100 000 in 2013 and in men from 301.2 per 100 000 in 2004 to 485.5 per 100 000 in 2013. Comparing morality rates in women and men with bronchiectasis in England and Wales (n=11 862) with mortality rates in the general population from Office of National Statistics data showed that in women the age-adjusted mortality rate for the bronchiectasis population was 1437.7 per 100 000 and for the general population 635.9 per 100 000 (comparative mortality figure of 2.26). In men, the age-adjusted mortality rate for the bronchiectasis population was 1914.6 per 100 000 and for the general population 895.2 per 100 000 (comparative mortality figure of 2.14).Bronchiectasis is surprisingly common and is increasing in incidence and prevalence in the UK, particularly in older age groups. Bronchiectasis is associated with a markedly increased mortality.

Risk factors for hospital admission in the 28 days following a community-acquired pneumonia diagnosis in older adults, and their contribution to increasing hospitalisation rates over time: a cohort study.

OBJECTIVES: To determine factors associated with hospitalisation after community-acquired pneumonia (CAP) among older adults in England, and to investigate how these factors have contributed to increasing hospitalisations over time. DESIGN: Cohort study. SETTING: Primary and secondary care in England. POPULATION: 39,211 individuals from the Clinical Practice Research Datalink, who were eligible for linkage to Hospital Episode Statistics and mortality data, were aged ≥ 65 and had at least 1 CAP episode between April 1998 and March 2011. MAIN OUTCOME MEASURES: The association between hospitalisation within 28 days of CAP diagnosis (a 'post-CAP' hospitalisation) and a wide range of comorbidities, frailty factors, medications and vaccinations. We examined the role of these factors in post-CAP hospitalisation trends. We also looked at trends in post-CAP mortality and length of hospitalisation over the study period. RESULTS: 14 comorbidities, 5 frailty factors and 4 medications/vaccinations were associated with hospitalisation (of 18, 12 and 7 considered, respectively). Factors such as chronic lung disease, severe renal disease and diabetes were associated with increased likelihood of hospitalisation, whereas factors such as recent influenza vaccination and a recent antibiotic prescription decreased the odds of hospitalisation. Despite adjusting for these and other factors, the average predicted probability of hospitalisation after CAP rose markedly from 57% (1998-2000) to 86% (2009-2010). Duration of hospitalisation and 28-day mortality decreased over the study period. CONCLUSIONS: The risk factors we describe enable identification of patients at increased likelihood of post-CAP hospitalisation and thus in need of proactive case management. Our analyses also provide evidence that while comorbidities and frailty factors contributed to increasing post-CAP hospitalisations in recent years, the trend appears to be largely driven by changes in service provision and patient behaviour.

Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study.

RATIONALE: A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. OBJECTIVES: To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. METHODS: We quantified influenza A(H3N2) virus-specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. MEASUREMENTS AND MAIN RESULTS: A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. CONCLUSIONS: Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity.

CKD and the risk of acute, community-acquired infections among older people with diabetes mellitus: a retrospective cohort study using electronic health records.

BACKGROUND: Hospital admissions for community-acquired infection are increasing rapidly in the United Kingdom, particularly among older individuals, possibly reflecting an increasing prevalence of comorbid conditions such as chronic kidney disease (CKD). This study describes associations between CKD (excluding patients treated by dialysis or transplantation) and community-acquired infection incidence among older people with diabetes mellitus. STUDY DESIGN: Retrospective cohort study using primary care records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics admissions data. SETTING & PARTICIPANTS: 191,709 patients 65 years or older with diabetes mellitus and no history of renal replacement therapy, United Kingdom, 1997 to 2011. PREDICTOR: Estimated glomerular filtration rate (eGFR) and history of proteinuria. OUTCOMES: Incidence of community-acquired lower respiratory tract infections (LRTIs, with pneumonia as a subset) and sepsis, diagnosed in primary or secondary care, excluding hospital admissions from time at risk. MEASUREMENTS: Poisson regression was used to calculate incidence rate ratios (IRRs) adjusted for age, sex, smoking status, comorbid conditions, and characteristics of diabetes. Estimates for associations of eGFR with infection were adjusted for proteinuria, and vice versa. RESULTS: Strong graded associations between lower eGFRs and infection were observed. Compared with patients with eGFRs≥60mL/min/1.73m(2), fully adjusted IRRs for pneumonia among those with eGFRs<15, 15 to 29, 30 to 44, and 45 to 59mL/min/1.73m(2) were 3.04 (95% CI, 2.42-3.83), 1.73 (95% CI, 1.57-1.92), 1.19 (95% CI, 1.11-1.28), and 0.95 (95% CI, 0.89-1.01), respectively. Associations between lower eGFRs and sepsis were stronger, with fully adjusted IRRs up to 5.56 (95% CI, 3.90-7.94). Those associations with LRTI were weaker but still clinically relevant at up to 1.47 (95% CI, 1.34-1.62). In fully adjusted models, a history of proteinuria remained an independent marker of increased infection risk for LRTI, pneumonia, and sepsis (IRRs of 1.07 [95% CI, 1.05-1.09], 1.26 [95% CI, 1.19-1.33], and 1.33 [95% CI, 1.20-1.47]). LIMITATIONS: Patients without creatinine results were excluded. CONCLUSIONS: Strategies to prevent infection among people with CKD are needed.

Cardiotoxicity during invasive pneumococcal disease.

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and sepsis, with adult hospitalization linked to approximately 19% incidence of an adverse cardiac event (e.g., heart failure, arrhythmia, infarction). Herein, we review the specific host-pathogen interactions that contribute to cardiac dysfunction during invasive pneumococcal disease: (1) cell wall-mediated inhibition of cardiomyocyte contractility; (2) the new observation that S. pneumoniae is capable of translocation into the myocardium and within the heart, forming discrete, nonpurulent, microscopic lesions that are filled with pneumococci; and (3) the bacterial virulence determinants, pneumolysin and hydrogen peroxide, that are most likely responsible for cardiomyocyte cell death. Pneumococcal invasion of heart tissue is dependent on the bacterial adhesin choline-binding protein A that binds to laminin receptor on vascular endothelial cells and binding of phosphorylcholine residues on pneumococcal cell wall to platelet-activating factor receptor. These are the same interactions responsible for pneumococcal translocation across the blood-brain barrier during the development of meningitis. We discuss these interactions and how their neutralization, either with antibody or therapeutic agents that modulate platelet-activating factor receptor expression, may confer protection against cardiac damage and meningitis. Considerable collagen deposition was observed in hearts of mice that had recovered from invasive pneumococcal disease. We discuss the possibility that cardiac scar formation after severe pneumococcal infection may explain why individuals who are hospitalized for pneumonia are at greater risk for sudden death up to 1 year after infection.

Are pre-existing markers of chronic kidney disease associated with short-term mortality following acute community-acquired pneumonia and sepsis? A cohort study among older people with diabetes using electronic health records.

BACKGROUND: We aimed to examine whether pre-existing impaired estimated glomerular filtration rate (eGFR) and proteinuria were associated with mortality following community-acquired pneumonia or sepsis among people aged ≥ 65 years with diabetes mellitus, without end-stage renal disease. METHODS: Patients were followed up from onset of first community-acquired pneumonia or sepsis episode in a cohort study using large, linked electronic health databases. Follow-up was for up to 90 days, unlimited by hospital discharge. We used generalized linear models with log link, normal distribution and robust standard errors to calculate risk ratios (RRs) for all-cause 28- and 90-day mortality according to two markers of chronic kidney disease: eGFR and proteinuria. RESULTS: All-cause mortality among the 4743 patients with pneumonia was 29.6% after 28 days and 37.4% after 90 days. Among the 1058 patients with sepsis, all-cause 28- and 90-day mortality were 35.6 and 44.2%, respectively. eGFR <30 mL/min/1.73 m(2) was a risk marker of higher 28-day mortality for pneumonia (RR 1.27: 95% CI 1.12-1.43) and sepsis (RR 1.32: 95% CI 1.07-1.64), adjusted for age, sex, socio-economic status, smoking status and co-morbidities. Neither moderately impaired eGFR nor proteinuria were associated with short-term mortality following either infection. CONCLUSIONS: People with pre-existing low eGFR but not on dialysis are at higher risk of death following pneumonia and sepsis. This association was not explained by existing co-morbidities. These patients need to be carefully monitored to prevent modifiable causes of death.

Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study.

BACKGROUND: Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden. METHODS: Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006-11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable. FINDINGS: Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16-22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13-34), suggesting most influenza infections are asymptomatic. 25% (18-35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10-26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2. INTERPRETATION: Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2. FUNDING: Medical Research Council and the Wellcome Trust.

Incidence of community-acquired lower respiratory tract infections and pneumonia among older adults in the United Kingdom: a population-based study.

Community-acquired lower respiratory tract infections (LRTI) and pneumonia (CAP) are common causes of morbidity and mortality among those aged ≥65 years; a growing population in many countries. Detailed incidence estimates for these infections among older adults in the United Kingdom (UK) are lacking. We used electronic general practice records from the Clinical Practice Research Data link, linked to Hospital Episode Statistics inpatient data, to estimate incidence of community-acquired LRTI and CAP among UK older adults between April 1997-March 2011, by age, sex, region and deprivation quintile. Levels of antibiotic prescribing were also assessed. LRTI incidence increased with fluctuations over time, was higher in men than women aged ≥70 and increased with age from 92.21 episodes/1000 person-years (65-69 years) to 187.91/1000 (85-89 years). CAP incidence increased more markedly with age, from 2.81 to 21.81 episodes/1000 person-years respectively, and was higher among men. For both infection groups, increases over time were attenuated after age-standardisation, indicating that these rises were largely due to population aging. Rates among those in the most deprived quintile were around 70% higher than the least deprived and were generally higher in the North of England. GP antibiotic prescribing rates were high for LRTI but lower for CAP (mostly due to immediate hospitalisation). This is the first study to provide long-term detailed incidence estimates of community-acquired LRTI and CAP in UK older individuals, taking person-time at risk into account. The summary incidence commonly presented for the ≥65 age group considerably underestimates LRTI/CAP rates, particularly among older individuals within this group. Our methodology and findings are likely to be highly relevant to health planners and researchers in other countries with aging populations.