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The health economic analysis of surgery versus rehabilitation in non-traumatic musculoskeletal shoulder disorders: A systematic review of trial-based studies.
OBJECTIVE: Non-traumatic musculoskeletal shoulder disorders are common. Their treatment, surgical or non-surgical, is associated with a considerable financial burden to health systems. The aim of this study was therefore to investigate the cost-effectiveness of surgical or rehabilitative treatments in this population. DATA SOURCES: PubMed, Embase, NHS Economic Evaluation Database, Cost-Effectiveness Analysis registry, PEDro Database, Cochrane Library, and Google Scholar. REVIEW METHODS: Trial-based economic evaluations assessing nonoperative and/or operative interventions for the management of non-traumatic shoulder disorders, published from January 2000 to October 2024, were searched. The selection process, data extraction and quality assessment (carried out with the Quality of Health Economic Studies instrument) were independently conducted by two reviewers. RESULTS: Four studies (883 patients) were included in the review. Subacromial decompression for rotator cuff-related shoulder pain was found not to be cost-effective when compared with physiotherapy. Although it was not as cost-effective, Physiotherapy could be a socially beneficial alternative to mobilisation under anaesthesia in the early management of a frozen shoulder, due to lower costs and the delays in accessing surgical management in the pain-predominant phase. Productivity loss was the main driver of costs. It was not possible to determine the cost-effectiveness of other shoulder-related disorders due to sparsity of evidence. CONCLUSION: Priority should be given to interventions that reduce productivity loss and facilitate patients' return to work as soon as possible. There is a definite need for multiplication and standardization of high-quality economic studies (and the trials they are based on) regarding the management of non-traumatic musculoskeletal shoulder disorders.
Impact of public release of performance data on the behaviour of healthcare consumers and providers.
BACKGROUND: It is becoming increasingly common to publish information about the quality and performance of healthcare organisations and individual professionals. However, we do not know how this information is used, or the extent to which such reporting leads to quality improvement by changing the behaviour of healthcare consumers, providers, and purchasers. OBJECTIVES: To estimate the effects of public release of performance data, from any source, on changing the healthcare utilisation behaviour of healthcare consumers, providers (professionals and organisations), and purchasers of care. In addition, we sought to estimate the effects on healthcare provider performance, patient outcomes, and staff morale. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers on 26 June 2017. We checked reference lists of all included studies to identify additional studies. SELECTION CRITERIA: We searched for randomised or non-randomised trials, interrupted time series, and controlled before-after studies of the effects of publicly releasing data regarding any aspect of the performance of healthcare organisations or professionals. Each study had to report at least one main outcome related to selecting or changing care. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for eligibility and extracted data. For each study, we extracted data about the target groups (healthcare consumers, healthcare providers, and healthcare purchasers), performance data, main outcomes (choice of healthcare provider, and improvement by means of changes in care), and other outcomes (awareness, attitude, knowledge of performance data, and costs). Given the substantial degree of clinical and methodological heterogeneity between the studies, we presented the findings for each policy in a structured format, but did not undertake a meta-analysis. MAIN RESULTS: We included 12 studies that analysed data from more than 7570 providers (e.g. professionals and organisations), and a further 3,333,386 clinical encounters (e.g. patient referrals, prescriptions). We included four cluster-randomised trials, one cluster-non-randomised trial, six interrupted time series studies, and one controlled before-after study. Eight studies were undertaken in the USA, and one each in Canada, Korea, China, and The Netherlands. Four studies examined the effect of public release of performance data on consumer healthcare choices, and four on improving quality.There was low-certainty evidence that public release of performance data may make little or no difference to long-term healthcare utilisation by healthcare consumers (3 studies; 18,294 insurance plan beneficiaries), or providers (4 studies; 3,000,000 births, and 67 healthcare providers), or to provider performance (1 study; 82 providers). However, there was also low-certainty evidence to suggest that public release of performance data may slightly improve some patient outcomes (5 studies, 315,092 hospitalisations, and 7502 providers). There was low-certainty evidence from a single study to suggest that public release of performance data may have differential effects on disadvantaged populations. There was no evidence about effects on healthcare utilisation decisions by purchasers, or adverse effects. AUTHORS' CONCLUSIONS: The existing evidence base is inadequate to directly inform policy and practice. Further studies should consider whether public release of performance data can improve patient outcomes, as well as healthcare processes.
Algebraic representation of Gaussian Markov combinations
Markov combinations for structural meta-analysis problems provide a way of constructing a statistical model that takes into account two or more marginal distributions by imposing conditional independence constraints between the variables that are not jointly observed. This paper considers Gaussian distributions and discusses how the covariance and concentration matrices of the different combinations can be found via matrix operations. In essence all these Markov combinations correspond to finding a positive definite completion of the covariance matrix over the set of random variables of interest and respecting the constraints imposed by each Markov combination. The paper further shows the potential of investigating the properties of the combinations via algebraic statistics tools. An illustrative application will motivate the importance of solving problems of this type.
On the importance of cognitive profiling: A graphical modelling analysis of domain-specific and domain-general deficits after stroke.
Cognitive problems following stroke are typically analysed using either short but relatively uninformative general tests or through detailed but time consuming tests of domain specific deficits (e.g., in language, memory, praxis). Here we present an analysis of neuropsychological deficits detected using a screen designed to fall between other screens by being 'broad' (testing multiple cognitive abilities) but 'shallow' (sampling the abilities briefly, to be time efficient) - the BCoS. Assessment using the Birmingham Cognitive Screen (BCoS) enables the relations between 'domain specific' and 'domain general' cognitive deficits to be evaluated as the test generates an overall cognitive profile for individual patients. We analysed data from 287 patients tested at a sub-acute stage of stroke (<3 months). Graphical modelling techniques were used to investigate the associative structure and conditional independence between deficits within and across the domains sampled by BCoS (attention and executive functions, language, memory, praxis and number processing). The patterns of deficit within each domain conformed to existing cognitive models. However, these within-domain patterns underwent substantial change when the whole dataset was modelled, indicating that domain-specific deficits can only be understood in relation to linked changes in domain-general processes. The data point to the importance of using over-arching cognitive screens, measuring domain-general as well as domain-specific processes, in order to account for neuropsychological deficits after stroke. The paper also highlights the utility of using graphical modelling to understand the relations between cognitive components in complex datasets.
Graphical modeling for gene set analysis: A critical appraisal.
Current demand for understanding the behavior of groups of related genes, combined with the greater availability of data, has led to an increased focus on statistical methods in gene set analysis. In this paper, we aim to perform a critical appraisal of the methodology based on graphical models developed in Massa et al. (2010) that uses pathway signaling networks as a starting point to develop statistically sound procedures for gene set analysis. We pay attention to the potential of the methodology with respect to the organizational aspects of dealing with such complex but highly informative starting structures, that is pathways. We focus on three themes: the translation of a biological pathway into a graph suitable for modeling, the role of shrinkage when more genes than samples are obtained, the evaluation of respondence of the statistical models to the biological expectations. To study the impact of shrinkage, two simulation studies will be run. To evaluate the biological expectation we will use data from a network with known behavior that offer the possibility of carrying out a realistic check of respondence of the model to changes in the experimental conditions.
Alcohol consumption and cause-specific mortality in Cuba: prospective study of 120 623 adults.
BACKGROUND: The associations of cause-specific mortality with alcohol consumption have been studied mainly in higher-income countries. We relate alcohol consumption to mortality in Cuba. METHODS: In 1996-2002, 146 556 adults were recruited into a prospective study from the general population in five areas of Cuba. Participants were interviewed, measured and followed up by electronic linkage to national death registries until January 1, 2017. After excluding all with missing data or chronic disease at recruitment, Cox regression (adjusted for age, sex, province, education, and smoking) was used to relate mortality rate ratios (RRs) at ages 35-79 years to alcohol consumption. RRs were corrected for long-term variability in alcohol consumption using repeat measures among 20 593 participants resurveyed in 2006-08. FINDINGS: After exclusions, there were 120 623 participants aged 35-79 years (mean age 52 [SD 12]; 67 694 [56%] women). At recruitment, 22 670 (43%) men and 9490 (14%) women were current alcohol drinkers, with 15 433 (29%) men and 3054 (5%) women drinking at least weekly; most alcohol consumption was from rum. All-cause mortality was positively and continuously associated with weekly alcohol consumption: each additional 35cl bottle of rum per week (110g of pure alcohol) was associated with ∼10% higher risk of all-cause mortality (RR 1.08 [95%CI 1.05-1.11]). The major causes of excess mortality in weekly drinkers were cancer, vascular disease, and external causes. Non-drinkers had ∼10% higher risk (RR 1.11 [1.09-1.14]) of all-cause mortality than those in the lowest category of weekly alcohol consumption (<1 bottle/week), but this association was almost completely attenuated on exclusion of early follow-up. INTERPRETATION: In this large prospective study in Cuba, weekly alcohol consumption was continuously related to premature mortality. Reverse causality is likely to account for much of the apparent excess risk among non-drinkers. The findings support limits to alcohol consumption that are lower than present recommendations in Cuba. FUNDING: Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen).
Development and Internal Validation of a Risk Score to Detect Asymptomatic Carotid Stenosis.
OBJECTIVE: Asymptomatic carotid stenosis (ACS) is associated with an increased risk of ischaemic stroke and myocardial infarction. Risk scores have been developed to detect individuals at high risk of ACS, thereby enabling targeted screening, but previous external validation showed scope for refinement of prediction by adding additional predictors. The aim of this study was to develop a novel risk score in a large contemporary screened population. METHODS: A prediction model was developed for moderate (≥50%) and severe (≥70%) ACS using data from 596 469 individuals who attended screening clinics. Variables that predicted the presence of ≥50% and ≥70% ACS independently were determined using multivariable logistic regression. Internal validation was performed using bootstrapping techniques. Discrimination was assessed using area under the receiver operating characteristic curves (AUROCs) and agreement between predicted and observed cases using calibration plots. RESULTS: Predictors of ≥50% and ≥70% ACS were age, sex, current smoking, diabetes mellitus, prior stroke/transient ischaemic attack, coronary artery disease, peripheral arterial disease, blood pressure, and blood lipids. Models discriminated between participants with and without ACS reliably, with an AUROC of 0.78 (95% confidence interval [CI] 0.77-0.78) for ≥ 50% ACS and 0.82 (95% CI 0.81-0.82) for ≥ 70% ACS. The number needed to screen in the highest decile of predicted risk to detect one case with ≥50% ACS was 13 and that of ≥70% ACS was 58. Targeted screening of the highest decile identified 41% of cases with ≥50% ACS and 51% with ≥70% ACS. CONCLUSION: The novel risk model predicted the prevalence of ACS reliably and performed better than previous models. Targeted screening among the highest decile of predicted risk identified around 40% of all cases with ≥50% ACS. Initiation or intensification of cardiovascular risk management in detected cases might help to reduce both carotid related ischaemic strokes and myocardial infarctions.
Body-mass index, blood pressure, diabetes and cardiovascular mortality in Cuba: prospective study of 146,556 participants.
BACKGROUND: Cardiovascular disease accounts for about one-third of all premature deaths (ie, age =120 mmHg), diabetes, and BMI (>=22.5 kg/m2): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88-2.18]), as did diabetes (2.15, 1.95-2.37), and 10 kg/m2 higher usual BMI (1.92, 1.64-2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m2) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively. CONCLUSIONS: This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.
Variability and agreement of frailty measures and risk of falls, hospital admissions and mortality in TILDA.
Little is known about the within-person variability of different frailty instruments, their agreement over time, and whether use of repeat assessments could improve the strength of associations with adverse health outcomes. Repeat measurements recorded in 2010-2011 (Wave 1) and 2012 (Wave 2) from The Irish Longitudinal Study on Ageing (TILDA) were used to classify individuals with frailty using the frailty phenotype (FP) and frailty index (FI). Within-person variability and agreement of frailty classifications were assessed using ANOVA and kappa (K) statistics, respectively. Associations of each frailty measure (wave 1, wave 2, or mean of both waves) with risk of falls, hospitalisations and all-cause mortality were assessed using logistic regression. Among 7455 individuals (mean age 64.7 [SD 9.9] years), within-person SD was 0.664 units (95% CI 0.654-0.671) for FP and 2 health deficits (SD 0.050 [0.048-0.051]) for FI. Agreement of frailty was modest for both measures, but higher for FI (K 0.600 [0.584-0.615]) than FP (K 0.370 [0.348-0.401]). The odds ratios (ORs) for all-cause mortality were higher for frailty assessed using the mean of two versus single measurements for FI (ORs for mortality 3.5 [2.6-4.9] vs. 2.7 [1.9-3.4], respectively) and FP (ORs for mortality 6.9 [4.6-10.3] vs. 4.0 [2.8-5.635], respectively). Frailty scores based on single measurements had substantial within-person variability, but the agreement in classification of frailty was higher for FI than FP. Frailty assessed using the mean of two or more measurements recorded at separate visits was more strongly associated with adverse health outcomes than those recorded at a single visit.
Validation of Risk Prediction Models to Detect Asymptomatic Carotid Stenosis.
Background Significant asymptomatic carotid stenosis (ACS) is associated with higher risk of strokes. While the prevalence of moderate and severe ACS is low in the general population, prediction models may allow identification of individuals at increased risk, thereby enabling targeted screening. We identified established prediction models for ACS and externally validated them in a large screening population. Methods and Results Prediction models for prevalent cases with ≥50% ACS were identified in a systematic review (975 studies reviewed and 6 prediction models identified [3 for moderate and 3 for severe ACS]) and then validated using data from 596 469 individuals who attended commercial vascular screening clinics in the United States and United Kingdom. We assessed discrimination and calibration. In the validation cohort, 11 178 (1.87%) participants had ≥50% ACS and 2033 (0.34%) had ≥70% ACS. The best model included age, sex, smoking, hypertension, hypercholesterolemia, diabetes mellitus, vascular and cerebrovascular disease, measured blood pressure, and blood lipids. The area under the receiver operating characteristic curve for this model was 0.75 (95% CI, 0.74-0.75) for ≥50% ACS and 0.78 (95% CI, 0.77-0.79) for ≥70% ACS. The prevalence of ≥50% ACS in the highest decile of risk was 6.51%, and 1.42% for ≥70% ACS. Targeted screening of the 10% highest risk identified 35% of cases with ≥50% ACS and 42% of cases with ≥70% ACS. Conclusions Individuals at high risk of significant ACS can be selected reliably using a prediction model. The best-performing prediction models identified over one third of all cases by targeted screening of individuals in the highest decile of risk only.
Independent effects of adiposity measures on risk of atrial fibrillation in men and women: a study of 0.5 million individuals.
BACKGROUND: Atrial fibrillation (AF) has a higher prevalence in men than in women and is associated with measures of adiposity and lean mass (LM). However, it remains uncertain whether the risks of AF associated with these measures vary by sex. METHODS: Among 477 904 UK Biobank participants aged 40-69 without prior AF, 23 134 incident AF cases were identified (14 400 men, 8734 women; median follow-up 11.1 years). Cox proportional hazards models were used to estimate the covariate adjusted hazard ratios (HRs) describing the association of AF with weight, measures of adiposity [fat mass (FM), waist circumference (WC)] and LM, and their independent relevance, by sex. RESULTS: Weight and WC were independently associated with risk of AF [HR: 1.25 (1.23-1.27) per 10 kg, HR: 1.11 (1.09-1.14) per 10 cm, respectively], with comparable effects in both sexes. The association with weight was principally driven by LM, which, per 5 kg, conferred double the risk of AF compared with FM when mutually adjusted [HR: 1.20 (1.19-1.21), HR: 1.10 (1.09-1.11), respectively]; however, the effect of LM was weaker in men than in women (p-interaction = 4.3 x 10-9). Comparing the relative effects of LM, FM and WC identified different patterns within each sex; LM was the strongest predictor for both, whereas WC was stronger than FM in men but not in women. CONCLUSIONS: LM and FM (as constituents of weight) and WC are risk factors for AF. However, the independent relevance of general adiposity for AF was more limited in men than in women. The relevance of both WC and LM suggests a potentially important role for visceral adiposity and muscle mass in AF development.
Development of a Model to Predict 10-Year Risk of Ischemic and Hemorrhagic Stroke and Ischemic Heart Disease Using the China Kadoorie Biobank.
BACKGROUND AND OBJECTIVES: Contemporary cardiovascular disease (CVD) risk prediction models are rarely applied in routine clinical practice in China due to substantial regional differences in absolute risks of major CVD types within China. Moreover, the inclusion of blood lipids in most risk prediction models also limits their use in the Chinese population. We developed 10-year CVD risk prediction models excluding blood lipids that may be applicable to diverse regions of China. METHODS: We derived sex-specific models separately for ischemic heart disease (IHD), ischemic stroke (IS), and hemorrhagic stroke (HS) in addition to total CVD in the China Kadoorie Biobank. Participants were age 30-79 years without CVD at baseline. Predictors included age, systolic and diastolic blood pressure, use of blood pressure-lowering treatment, current daily smoking, diabetes, and waist circumference. Total CVD risks were combined in terms of conditional probability using the predicted risks of 3 submodels. Risk models were recalibrated in each region by 2 methods (practical and ideal) and risk prediction was estimated before and after recalibration. RESULTS: Model derivation involved 489,596 individuals, including 45,947 IHD, 43,647 IS, and 11,168 HS cases during 11 years of follow-up. In women, the Harrell C was 0.732 (95% CI 0.706-0.758), 0.759 (0.738-0.779), and 0.803 (0.778-0.827) for IHD, IS, and HS, respectively. The Harrell C for total CVD was 0.734 (0.732-0.736), 0.754 (0.752-0.756), and 0.774 (0.772-0.776) for models before recalibration, after practical recalibration, and after ideal recalibration. The calibration performances improved after recalibration, with models after ideal recalibration showing the best model performances. The results for men were comparable to those for women. DISCUSSION: Our CVD risk prediction models yielded good discrimination of IHD and stroke subtypes in addition to total CVD without including blood lipids. Flexible recalibration of our models for different regions could enable more widespread use using resident health records covering the overall Chinese population. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that a prediction model incorporating accessible clinical variables predicts 10-year risk of IHD, IS, and HS in the Chinese population age 30-79 years.
Systematic review of the utility of the frailty index and frailty phenotype to predict all-cause mortality in older people.
BACKGROUND: Current guidelines for healthcare of community-dwelling older people advocate screening for frailty to predict adverse health outcomes, but there is no consensus on the optimum instrument to use in such settings. The objective of this systematic review of population studies was to compare the ability of the frailty index (FI) and frailty phenotype (FP) instruments to predict all-cause mortality in older people. METHODS: Studies published before 27 July 2022 were identified using Ovid MEDLINE, Embase, Scopus, Web of Science and CINAHL databases. The eligibility criteria were population-based prospective studies of community-dwelling older adults (aged 65 years or older) and evaluation of both the FI and FP for prediction of all-cause mortality. The Scottish Intercollegiate Guidelines Network's Methodology checklist was used to assess study quality. The areas under the receiver operator characteristic curves (AUC) were compared, and the proportions of included studies that achieved acceptable discriminatory power (AUC>0.7) were calculated for each frailty instrument. The results were stratified by the use of continuous or categorical formats of each instrument. The review was reported in accordance with the PRISMA and SWiM guidelines. RESULTS: Among 8 studies (range: 909 to 7713 participants), both FI and FP had comparable predictive power for all-cause mortality. The AUC values ranged from 0.66 to 0.84 for FI continuous, 0.60 to 0.80 for FI categorical, 0.63 to 0.80 for FP continuous and 0.57 to 0.79 for FP categorical. The proportion of studies achieving acceptable discriminatory power were 75%, 50%, 63%, and 50%, respectively. The predictive ability of each frailty instrument was unaltered by the number of included items. CONCLUSIONS: Despite differences in their content, both the FI and FP instruments had modest but comparable ability to predict all-cause mortality. The use of continuous rather than categorical formats in either instrument enhanced their ability to predict all-cause mortality.
Cardiovascular risk factors and frailty in a cross-sectional study of older people: implications for prevention.
OBJECTIVE: to examine the associations of cardiovascular disease (CVD) and cardiovascular risk factors with frailty. DESIGN: a cross-sectional study. SETTING: the Irish Longitudinal Study on Ageing (TILDA). PARTICIPANTS: frailty measures were obtained on 5,618 participants and a subset of 4,330 participants with no prior history of CVD. EXPOSURES FOR OBSERVATIONAL STUDY: cardiovascular risk factors were combined in three composite CVD risk scores (Systematic Coronary Risk Evaluation [SCORE], Ideal Cardiovascular Health [ICH] and Cardiovascular Health Metrics [CHM]). MAIN OUTCOME MEASURES: a frailty index (40-items) was used to screen for frailty. METHODS: the associations of CVD risk factors with frailty were examined using logistic regression. RESULTS: overall, 16.4% of participants had frailty (7.6% at 50-59 years to 42.5% at 80+ years), and the prevalence was higher in those with versus those without prior CVD (43.0% vs. 10.7%). Among those without prior CVD, mean levels of CVD risk factors were closely correlated with higher frailty index scores. Combined CVD risk factors, assessed using SCORE, were linearly and positively associated with frailty. Compared to low-to-moderate SCOREs, the odds ratio (OR) (95% confidence interval, CI) of frailty for those with very high risk was 3.18 (2.38-4.25). Conversely, ICH was linearly and inversely associated with frailty, with an OR for optimal health of 0.29 (0.21-0.40) compared with inadequate health. CONCLUSIONS: the concordant positive associations of SCORE and inverse associations of ICH and CHM with frailty highlight the potential importance of optimum levels of CVD risk factors for prevention of disability in frail older people.
Five-year outcomes for patients sustaining severe fractures of the lower limb from the Wound Healing in Surgery for Trauma (WHIST) trial.
AIMS: The aims of this study were to report the outcomes of patients with a complex fracture of the lower limb in the five years after they took part in the Wound Healing in Surgery for Trauma (WHIST) trial. METHODS: The WHIST trial compared negative pressure wound therapy (NPWT) dressings with standard dressings applied at the end of the first operation for patients undergoing internal fixation of a complex fracture of the lower limb. Complex fractures included periarticular fractures and open fractures when the wound could be closed primarily at the end of the first debridement. A total of 1,548 patients aged ≥ 16 years completed the initial follow-up, six months after injury. In this study we report the pre-planned analysis of outcome data up to five years. Patients reported their Disability Rating Index (DRI) (0 to 100, in which 100 = total disability), and health-related quality of life, chronic pain scores and neuropathic pain scores annually, using a self-reported questionnaire. Complications, including further surgery related to the fracture, were also recorded. RESULTS: A total of 1,015 of the original patients (66%) provided at least one set of outcome data during the five years of follow-up. There was no evidence of a difference in patient-reported disability between the two groups at five years (NPWT group mean DRI 30.0 (SD 26.5), standard dressing group mean DRI 31.5 (SD 28.8), adjusted difference -0.86 (95% CI -4.14 to 2.40; p = 0.609). There was also no evidence of a difference in the complication rates at this time. CONCLUSION: We found no evidence of a difference in disability ratings between NPWT compared with standard wound dressings in the five years following the surgical treatment of a complex fracture of the lower limb. Patients in both groups reported high levels of persistent disability and reduced quality of life, with little evidence of improvement during this time.
Cigarette smoking and risk of severe infectious respiratory diseases in UK adults: 12-year follow-up of UK biobank.
BACKGROUND: The relevance of tobacco smoking for infectious respiratory diseases (IRD) is uncertain. We investigated the associations of cigarette smoking with severe IRD resulting in hospitalization or death in UK adults. METHODS: We conducted a prospective study of cigarette smoking and risk of severe IRD in UK Biobank. The outcomes included pneumonia, other acute lower respiratory tract infections (OA-LRTI) and influenza. Multivariable Cox regression analyses were used to estimate hazard ratios (HRs) of severe IRD associated with smoking habits after adjusting for confounding factors. RESULTS: Among 341 352 participants with no prior history of major chronic diseases, there were 12 384 incident cases with pneumonia, 7054 with OA-LRTI and 795 with influenza during a 12-year follow-up. Compared with non-smokers, current smoking was associated with ⁓2-fold higher rates of severe IRD (HR 2.40 [2.27-2.53] for pneumonia, 1.99 [1.84-2.14] for OA-LRTI and 1.82 [95% confidence interval: 1.47-2.24] for influenza). Incidence of all severe IRDs were positively associated with amount of cigarettes smoked. The HRs for each IRD (except influenza) also declined with increasing duration since quitting. CONCLUSIONS: Current cigarette smoking was positively associated with higher rates of IRD and the findings extend indications for tobacco control measures and vaccination of current smokers for prevention of severe IRD.