Secondhand smoke exposure and risk of incident peripheral arterial disease and mortality: a Scotland-wide retrospective cohort study of 4045 non-smokers with cotinine measurement

Background: Active smoking is an important risk factor for all-cause mortality and peripheral arterial disease (PAD). In contrast, published studies on the associations with secondhand smoke (SHS) are limited. The aim of this study was to examine the associations between SHS exposure and incident PAD, as well as mortality, among middle-aged non-smokers. Methods: We undertook a retrospective, cohort study using record linkage of the Scottish Health Surveys between 1998 and 2010 to hospital admissions and death certificates. Inclusion was restricted to participants aged > 45 years. Cox proportional hazard models were used to examine the association between SHS exposure and incident PAD (hospital admission or death) and all-cause mortality, with adjustment for potential confounders. Results: Of the 4045 confirmed non-smokers (self-reported non-smokers with salivary cotinine concentrations < 15 ng/mL), 1163 (28.8%) had either moderate or high exposure to SHS at baseline. In men, high exposure to SHS (cotinine ≥2.7 ng/mL) was associated with increased risk of all-cause mortality (fully adjusted hazard ratio [HR] 1.54, 95% CI 1.07–2.22, p = 0.020) with evidence of a dose-relationship (p for trend = 0.004). In men, high exposure to SHS was associated with increased risk of incident PAD over the first five years of follow-up (fully adjusted HR 4.29, 95% CI 1.14–16.10, p = 0.031) but the association became non-significant over longer term follow-up. Conclusions: SHS exposure was independently associated with all-cause mortality and may be associated with PAD, but larger studies, or meta-analyses, are required to confirm the latter

Association between self-reported general and mental health and adverse outcomes: a retrospective cohort study of 19 625 Scottish adults

<b>Objective</b><p></p> Self-reported general health and mental health are independent predictors of all-cause mortality. This study examines whether they are also independent predictors of incident cancer, coronary heart disease and psychiatric hospitalisation. <b>Methods</b><p></p> We conducted a retrospective, population cohort study by linking the 19 625 Scottish adults who participated in the Scottish Health Surveys 1995–2003, to hospital admissions, cancer registration and death certificate records. We conducted Cox proportional hazard models adjusting for potential confounders including age, sex, socioeconomic status, alcohol, smoking status, body mass index, hypertension and diabetes. <b>Results</b><p></p> Poor general health was reported by 1215 (6.2%) participants and was associated with cancer registrations (adjusted Hazard Ratio [HR] 1.30, 95% CI 1.10, 1.55), coronary heart disease events (adjusted HR 2.30, 95% CI 1.86, 2.84) and psychiatric hospitalisations (adjusted HR 2.42, 95% CI 1.65, 3.56). There was evidence of dose relationships and the associations remained significant after adjustment for mental health. 3172 (16%) participants had poor mental health (GHQ ≥4). After adjustment for general health, the associations between poor mental health and coronary heart disease events (adjusted HR 1.36, 95% CI 1.13, 1.63) and all-cause death (adjusted HR 1.38, 95% CI 1.23, 1.55) became non-significant, but mental health remained associated with psychiatric hospitalisations (fully adjusted HR 2.02, 95% CI 1.48, 2.75). <b>Conclusion</b><p></p> Self-reported general health is a significant predictor of a range of clinical outcomes independent of mental health. The association between mental health and non-psychiatric outcomes is mediated by general health but it is an independent predictor of psychiatric outcome. Individuals with poor general health or mental health warrant close attention

Non-fatal self-harm in Scottish military veterans: a retrospective cohort study of 57,000 veterans and 173,000 matched non-veterans

Purpose: Although suicide risk in veterans has been widely studied, there is little information on the risk of non-fatal self-harm in this population. We used data from the Scottish Veterans Health Study to conduct an epidemiological analysis of self-harm in veterans, in comparison with people who have never served. Methods: We conducted a retrospective, 30-year cohort study of 56,205 veterans born 1945–1985, and 172,741 people with no record of military service, and used Cox proportional hazard models to examine the association between veteran status and cumulative risk of non-fatal self-harm, overall and stratified by birth cohort, sex and length of service. We also examined mental and physical comorbidities, and association of suicide with prior self-harm. Results: There were 1620 (2.90%) first episodes of self-harm in veterans, compared with 4212 (2.45%) in non-veterans. The difference was statistically significant overall (unadjusted HR 1.27, 95% CI 1.21–1.35, p < 0.001). The risk was highest in the oldest veterans, and in the early service leavers who failed to complete initial training (unadjusted HR 1.69, 95% CI 1.50–1.91, p < 0.001). The risk reduced with longer service and in the intermediate birth cohorts but has increased again in the youngest cohort. Conclusions: The highest risk of non-fatal self-harm was in veterans with the shortest service, especially those who did not complete training or minimum engagement, and in the oldest birth cohorts, whilst those who had served the longest were at reduced risk. The risk has increased again in the youngest veterans, and further study of this subgroup is indicated

Lymphohaematopoietic malignancies in Scottish military veterans: Retrospective cohort study of 57,000 veterans and 173,000 non-veterans

Background: Lymphohaematopoietic malignancies are common in the general population. There have been concerns that military service may be associated with increased risk as a result of occupational exposures. To date, few studies have demonstrated an increased risk, although a disability pension is payable to veterans who were present at nuclear tests and who develop leukaemia (other than chronic lymphocytic leukaemia). The aim of the study was to utilise data from the Scottish Veterans Health Study to examine the risk of lymphohaematopoietic malignancy following military service in a large national cohort of veterans. Methods: Retrospective cohort study of 57,000 veterans and 173,000 non-veterans born between 1945 and 1985 matched for age, sex and area of residence, adjusted for areal deprivation and followed up for up to 30 years, using Cox proportional hazard models to compare the risk of lymphohaematopoietic malignancy overall, by diagnosis and by sex and birth cohort. Results: We found no statistically significant difference in risk between veterans and non-veterans either for all leukaemias (Cox proportional hazard ratio 1.03, 95% confidence intervals 0.84–1.27, p = 0.773), Hodgkin lymphoma (hazard ratio 1.19, 95% confidence intervals 0.87–1.61, p = 0.272) or for non-Hodgkin lymphoma (hazard ratio 0.86, 95% confidence intervals 0.71–1.04, p = 0.110). Conclusion: Our findings provide reassurance that service in the UK Armed Forces is not associated with increased risk of lymphohaematopoietic malignancy

Cost-effectiveness analysis in R using a multi-state modelling survival analysis framework: a tutorial

This tutorial provides a step-by-step guide to performing cost-effectiveness analysis using a multi-state modelling approach. Alongside the tutorial we provide easy-to-use functions in the statistics package R. We argue this multi-state modelling approach using a package such as R has advantages over approaches where models are built in a spreadsheet package. In particular, using a syntax-based approach means there is a written record of what was done and the calculations are transparent. Reproducing the analysis is straightforward as the syntax just needs to be run again. The approach can be thought of as an alternative way to build a Markov decision analytic model, which also has the option to use a state-arrival extended approach if the Markov property does not hold. In the state-arrival extended multi-state model a covariate that represents patients’ history is included allowing the Markov property to be tested. We illustrate the building of multi-state survival models, making predictions from the models and assessing fits. We then proceed to perform a cost-effectiveness analysis including deterministic and probabilistic sensitivity analyses. Finally, we show how to create two common methods of visualising the results, namely cost-effectiveness planes and cost-effectiveness acceptability curves. The analysis is implemented entirely within R. It is based on adaptions to functions in the existing R package mstate, to accommodate parametric multi-state modelling which facilitates extrapolation of survival curves

Ten-year follow-up of the impact of Scottish smoke-free legislation on acute myocardial infarction

Worldwide, 181 countries have ratified the World Health Organization’s Framework Convention on Tobacco Control and become Parties to the convention,1 and 1.5 billion people in 55 countries are now protected by comprehensive smoke-free legislation.2 Smoke-free legislation has been associated with many health benefits, but the most extensively researched has been myocardial infarction. Thirty-one studies, covering legislation in 47 jurisdictions, produced a pooled relative risk reduction of 12%.3 Many used simple before and after comparisons and most had follow-up to only 1 to 2 years after legislation. In Scotland, the Smoking, Health and Social Care Act prohibited smoking in all enclosed public and workplaces from March 2006. There was a 17% reduction in myocardial infarctions in the year after implementation compared with a 4% decline in England where legislation had not been introduced.4 The primary aim was to protect nonsmokers from the harmful effects of secondhand smoke. However, the legislation was associated with a short-term increase in quit attempts and temporary reduction in smoking prevalence.5 Hence, in the year after legislation, myocardial infarctions fell among current, as well as nonsmokers,4 and it is not known whether the overall reduction in myocardial infarctions has been maintained long-term. This study uses interrupted time-series analysis to investigate whether myocardial infarction incidence over the 10 years after Scottish legislation differed from the underlying trend before legislation

Smoking-related cancer in military veterans: retrospective cohort study of 57,000 veterans and 173,000 matched non-veterans

Background: Serving military personnel are more likely to smoke, and to smoke more heavily, than civilians. The aim of our study was to examine whether veterans have an increased risk of a range of smoking-related cancers compared with non-veterans, using a large, national cohort of veterans. Methods: We conducted a retrospective cohort study of 57,000 veterans resident in Scotland and 173,000 age, sex and area of residence matched civilians. We used Cox proportional hazard models to compare the risk of any cancer, lung cancer and other smoking-related cancers overall, by sex and by birth cohort, adjusting for the potential confounding effect of socioeconomic deprivation. Results: Over a mean of 29 years follow-up, 445 (0.79 %) veterans developed lung cancer compared with 1106 (0.64 %) non-veterans (adjusted hazard ratio 1.16, 95 % confidence intervals 1.04–1.30, p = 0.008). Other smoking-related cancers occurred in 737 (1.31 %) veterans compared with 1883 (1.09 %) non-veterans (adjusted hazard ratio 1.18, 95 % confidence intervals 1.08–1.29, p < 0.001). A significantly increased risk was observed among veterans born 1950–1954 for lung cancer and 1945–1954 for other smoking-related cancers. The risk of lung cancer was decreased among veterans born 1960 onwards. In comparison, there was no difference in the risk of any cancer overall (adjusted hazard ratio 0.98, 95 % confidence intervals 0.94–1.01, p = 0.171), whilst younger veterans were at reduced risk of any cancer (adjusted hazard ratio 0.88, 95 % confidence intervals 0.81–0.97, p = 0.006). Conclusions: Military veterans living in Scotland who were born before 1955 are at increased risk of smoking-related cancer compared with non-veterans, but younger veterans are not. The differences may reflect changing patterns of smoking behaviour over time in military personnel which may, in turn, be linked to developments in military health promotion policy and a changing military operational environment, as well as to wider societal factors

Apgar score and the risk of cause specific infant mortality: a population based cohort study of 1,029,207 livebirths

Background<p></p> The Apgar score has been used worldwide as an index of early neonatal condition for more than 60 years. With advances in health-care service provision, neonatal resuscitation, and infant care, its present relevance is unclear. The aim of the study was to establish the strength of the relation between Apgar score at 5 min and the risk of neonatal and infant mortality, subdivided by specific causes.<p></p> Methods<p></p> We linked routine discharge and mortality data for all births in Scotland, UK between 1992 and 2010. We restricted our analyses to singleton livebirths, in women aged over 10 years, with a gestational age at delivery between 22 and 44 weeks, and excluded deaths due to congenital anomalies or isoimmunisation. We calculated the relative risks (RRs) of neonatal and infant death of neonates with low (0–3) and intermediate (4–6) Apgar scores at 5 min referent to neonates with normal Apgar score (7–10) using binomial log-linear modelling with adjustment for confounders. Analyses were stratified by gestational age at birth because it was a significant effect modifier. Missing covariate data were imputed.<p></p> Findings<p></p> Complete data were available for 1 029 207 eligible livebirths. Across all gestational strata, low Apgar score at 5 min was associated with an increased risk of neonatal and infant death. However, the strength of the association (adjusted RR, 95% CI referent to Apgar 7–10) was strongest at term (p<0·0001). A low Apgar (0–3) was associated with an adjusted RR of 359·4 (95% CI 277·3–465·9) for early neonatal death, 30·5 (18·0–51·6) for late neonatal death, and 50·2 (42·8–59·0) for infant death. We noted similar associations of a lower magnitude for intermediate Apgar (4–6). The strongest associations were for deaths attributed to anoxia and low Apgar (0–3) for term infants (RR 961·7, 95% CI 681·3–1357·5) and preterm infants (141·7, 90·1–222·8). No association between Apgar score at 5 min and the risk of sudden infant death syndrome was noted at any gestational age (RR 0·6, 95% CI 0·1–4·6 at term; 1·2, 0·3–4·8 at preterm).<p></p> Interpretation<p></p> Low Apgar score at 5 min was strongly associated with the risk of neonatal and infant death. Our findings support its continued usefulness in contemporary practice

Five-minute Apgar score and educational outcomes: retrospective cohort study of 751 369 children

Background: The Apgar score is used worldwide for assessing the clinical condition and short-term prognosis of newborn infants. Evidence for a relationship with long-term educational outcomes is conflicting. We investigated whether Apgar score at 5 min after birth was associated with additional support needs (ASN) and educational attainment. Methods: Data on pregnancy, delivery and later educational outcomes for children attending Scottish schools between 2006 and 2011 were collated by linking individual-level data from national educational and maternity databases. The relationship between Apgar score and overall ASN, type-specific ASN and educational attainment was assessed using binary, multinomial and generalised ordinal logistic regression models, respectively. Missing covariate data were imputed. Results: Of the 751 369 children eligible, 9741 (1.3%) had a low or intermediate Apgar score and 49 962 (6.6%) had ASN. Low Apgar score was independently associated with overall ASN status (adjusted OR for Apgar ≤3, OR 1.52 95% CI 1.35 to 1.70), as well as ASN due to cognitive (OR 1.26, 95% CI 1.09 to 1.47), sensory (OR 2.49 95% CI 1.66 to 3.73) and motor (OR 3.57, 95% CI 2.86 to 4.47) impairments. There was a dose-response relationship between Apgar score and overall ASN status: of those scoring 0–3, 10.1% had ASN, compared with 9.1% of those scoring 4–7 and 6.6% of those scoring 7–10. A low Apgar score was associated with lower educational attainment, but this was not robust to adjustment for confounders. Conclusions: Apgar scores are associated with long-term as well as short-term prognoses, and with educational as well as clinical outcomes at the population level

Association between exposure to second-hand smoke and telomere length: cross-sectional study of 1303 non-smokers

Background: Both active smoking and second-hand smoke (SHS) are important risk factors for many age-related diseases. Active smoking is associated with shortened telomere length. However, whether SHS accelerates telomere attrition with age is uncertain. The aim of this study was to examine the association between SHS exposure and shortening by age of leukocyte telomere length among adult non-smokers. Methods: We undertook a cross-sectional study of the association between self-reported levels of SHS exposure and telomere length shortening per annum on a subgroup of participants from the Scottish Family Health Study. Inclusion was restricted to non-smokers aged ≥ 18 years, who had provided self-reported overall usual SHS exposure (total hours per week) and blood samples for telomere analysis. Linear regression models were used to compare the ratio of telomere repeat copy number to single copy gene number (T/S)by age according to SHS exposure. Results: Of the 1303 eligible participants, 779 (59.8%) reported no SHS exposure, 495 (38.0%) low exposure (1–19 h per week) and 29 (2.2%) high exposure (≥20 h per week). In the univariate linear regression analyses, relative T/S ratio declined with increasing age in all exposure groups. Telomere length decreased more rapidly with increasing age among those with high exposure to SHS [adjusted coefficient −0.019, 95% confidence interval (CI) −0.031- −0.007) when compared with both those with no exposure to SHS (adjusted coefficient −0.006, 95% CI −0.008- −0.004) (high vs no SHS: P = 0.010) and those with low exposure to SHS (adjusted coefficient −0.005, 95% CI −0.007- −0.003) (high vs low SHS: P = 0.005). Conclusions: Our findings suggest that high SHS exposure may accelerate normal biological ageing, and support efforts to protect the public from SHS exposure. Further studies on relevant mechanisms should be conducted