Smoking and All-cause Mortality in Older Adults: Results From the CHANCES Consortium

INTRODUCTION: Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited. Therefore, we aimed to estimate the influence of smoking and smoking cessation on all-cause mortality in people aged ≥60 years.

METHODS: Relative mortality and mortality rate advancement periods (RAPs) were estimated by Cox proportional hazards models for the population-based prospective cohort studies from Europe and the U.S. (CHANCES [Consortium on Health and Ageing: Network of Cohorts in Europe and the U.S.]), and subsequently pooled by individual participant meta-analysis. Statistical analyses were performed from June 2013 to March 2014.

RESULTS: A total of 489,056 participants aged ≥60 years at baseline from 22 population-based cohort studies were included. Overall, 99,298 deaths were recorded. Current smokers had 2-fold and former smokers had 1.3-fold increased mortality compared with never smokers. These increases in mortality translated to RAPs of 6.4 (95% CI=4.8, 7.9) and 2.4 (95% CI=1.5, 3.4) years, respectively. A clear positive dose-response relationship was observed between number of currently smoked cigarettes and mortality. For former smokers, excess mortality and RAPs decreased with time since cessation, with RAPs of 3.9 (95% CI=3.0, 4.7), 2.7 (95% CI=1.8, 3.6), and 0.7 (95% CI=0.2, 1.1) for those who had quit <10, 10 to 19, and ≥20 years ago, respectively.

CONCLUSIONS: Smoking remains as a strong risk factor for premature mortality in older individuals and cessation remains beneficial even at advanced ages. Efforts to support smoking abstinence at all ages should be a public health priority.

Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk

Background: Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus. 

Methods: We examined the associations between risks of EA and Barrett's esophagus and 387 SNPs that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 Barrett's esophagus) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn. 

Results: After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or Barrett's esophagus. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed. 

Conclusions: Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or Barrett's esophagus. 

Impact: To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and Barrett's esophagus.

Six-year follow-up of the SPHERE RCT: secondary prevention of heart disease in general practice.

Objective: To determine the long-term effectiveness of a complex intervention in primary care aimed at improving outcomes for patients with coronary heart disease.

Design: A 6-year follow-up of a cluster randomised controlled trial, which found after 18 months that both total and cardiovascular hospital admissions were significantly reduced in intervention practices (8% absolute reduction).

Setting: 48 general practices in the Republic of Ireland and Northern Ireland.

Participants: 903 patients with established coronary heart disease at baseline in the original trial.

Intervention: The original intervention consisted of tailored practice and patient plans; training sessions for practitioners in medication prescribing and behavioural change; and regular patient recall system. Control practices provided usual care. Following the intervention period, all supports from the research team to intervention practices ceased.

Outcome measures: Primary outcome: hospital admissions, all cause and cardiovascular; secondary outcomes: mortality; blood pressure and cholesterol control.

Results: At 6-year follow-up, data were collected from practice records of 696 patients (77%). For those who had died, we censored their data at the point of death and cause of death was established. There were no significant differences between the intervention and control practices in either total (OR 0.83 (95% CI 0.54 to 1.28)) or cardiovascular hospital admissions (OR 0.91 (95% CI 0.49 to 1.65)). We confirmed mortality status of 886 of the original 903 patients (98%). There were no significant differences in mortality (15% in intervention and 16% in control) or in the proportions of patients above target control for systolic blood pressure or total cholesterol.

Conclusions: Initial significant differences in the numbers of total and cardiovascular hospital admissions were not maintained at 6 years and no differences were found in mortality or blood pressure and cholesterol control. Policymakers need to continue to assess the effectiveness of previously efficacious programmes.

Trial registration number: Current Controlled Trials ISRCTN24081411.

Effect of major lifestyle risk factors, independent and jointly, on life expectancy with and without cardiovascular disease: results from the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES)

Seldom have studies taken account of changes in lifestyle habits in the elderly, or investigated their impact on disease-free life expectancy (LE) and LE with cardiovascular disease (CVD). Using data on subjects aged 50+ years from three European cohorts (RCPH, ESTHER and Tromsø), we used multi-state Markov models to calculate the independent and joint effects of smoking, physical activity, obesity and alcohol consumption on LE with and without CVD. Men and women aged 50 years who have a favourable lifestyle (overweight but not obese, light/moderate drinker, non-smoker and participates in vigorous physical activity) lived between 7.4 (in Tromsø men) and 15.7 (in ESTHER women) years longer than those with an unfavourable lifestyle (overweight but not obese, light/moderate drinker, smoker and does not participate in physical activity). The greater part of the extra life years was in terms of "disease-free" years, though a healthy lifestyle was also associated with extra years lived after a CVD event. There are sizeable benefits to LE without CVD and also for survival after CVD onset when people favour a lifestyle characterized by salutary behaviours. Remaining a non-smoker yielded the greatest extra years in overall LE, when compared to the effects of routinely taking physical activity, being overweight but not obese, and drinking in moderation. The majority of the overall LE benefit is in disease free years. Therefore, it is important for policy makers and the public to know that prevention through maintaining a favourable lifestyle is "never too late".

Visual symptoms and retinal straylight after laser peripheral iridotomy: the Zhongshan Angle-Closure Prevention Trial.

OBJECTIVE: To assess the impact of laser peripheral iridotomy (LPI) on forward-scatter of light and subjective visual symptoms and to identify LPI parameters influencing these phenomena. DESIGN: Cohort study derived from a randomized trial, using an external control group. PARTICIPANTS: Chinese subjects initially aged 50 or older and 70 years or younger with bilateral narrow angles undergoing LPI in 1 eye selected at random, and age- and gender-matched controls. METHODS: Eighteen months after laser, LPI-treated subjects underwent digital iris photography and photogrammetry to characterize the size and location of the LPI, Lens Opacity Classification System III cataract grading, and measurement of retinal straylight (C-Quant; OCULUS, Wetzlar, Germany) in the treated and untreated eyes and completed a visual symptoms questionnaire. Controls answered the questionnaire and underwent straylight measurement and (in a random one-sixth sample) cataract grading. MAIN OUTCOME MEASURES: Retinal straylight levels and subjective visual symptoms. RESULTS: Among 230 LPI-treated subjects (121 [58.8%] with LPI totally covered by the lid, 43 [19.8%] with LPI partly covered by the lid, 53 [24.4%] with LPI uncovered by the lid), 217 (94.3%) completed all testing, as did 250 (93.3%) of 268 controls. Age, gender, and prevalence of visual symptoms did not differ between treated subjects and controls, although nuclear (P<0.01) and cortical (P = 0.03) cataract were less common among controls. Neither presenting visual acuity nor straylight score differed between the treated and untreated eyes among all treated persons, nor among those (n = 96) with LPI partially or totally uncovered. Prevalence of subjective glare did not differ significantly between participants with totally covered LPI (6.61%; 95% confidence interval [CI], 3.39%-12.5%), partially covered LPI (11.6%; 95% CI, 5.07%-24.5%), or totally uncovered LPI (9.43%; 95% CI, 4.10%-10.3%). In regression models, only worse cortical cataract grade (P = 0.01) was associated significantly with straylight score, and no predictors were associated with subjective glare. None of the LPI size or location parameters were associated with straylight or subjective symptoms. CONCLUSIONS: These results suggests that LPI is safe regarding measures of straylight and visual symptoms. This randomized design provides strong evidence that treatment programs for narrow angles would be unlikely to result in important medium-term visual disability.

Prevention of Cataract Blindness in Rural China.

China has undergone dramatic economic and social reforms during last 30 years, leading to a notably higher level of living standards and health care access for Chinese citizens. However, China's cataract surgical rate of 780 cases/y per million population trails Asian neighbors with lower income levels such as India and Vietnam. Eye care providers and patients encounter many barriers in gaining access to one another.Hands-on training programs conducted by international nongovernmental organizations and the government have helped to increase the number of qualified cataract surgeons in rural area, but establishing a residency training system that produces ophthalmologists capable of performing independent surgery is the only sustainable way to meet the increasing demand for surgery from an aging population. The New Rural Cooperative Medical System has successfully reduced the financial burden of cataract surgery for the rural population; however, reimbursement for outpatient treatment of leading eye diseases is needed.Community outreach screening combined with education is essential in rural areas' increased demand for surgery. Methods to optimize the yield from such screening must still be devised and proven, however. Improvements in the hospital administration and management structure are also needed to improve the efficiency of China's rural hospitals in delivering high-quality, low-cost cataract surgical services.

A Reappraisal of the Safety and Cost-Effectiveness of Statin Therapy in Primary Prevention

Statins are among the most investigated drugs of all time. There is now a wealth of evidence supporting their use in the primary and secondary prevention arenas. The reduction in event recurrence has since been demonstrated across all levels of risk and in elderly patients. As a result, it is now accepted practice for statins to be prescribed universally in secondary prevention unless contraindicated. The extension of this policy into the primary prevention setting is more problematic, with moral and financial issues arising from the long-term treatment of many young apparently healthy individuals. For these reasons it is necessary to prove not only the financial sustainability of such a strategy but also the long-term safety of statins and the degree of benefit that might be expected.

Impact of non-pharmacological interventions on prevention and treatment of delirium in critically ill patients: protocol for a systematic review of quantitative and qualitative research

Background: Critically ill patients have an increased risk of developing delirium during their intensive care stay.To date, pharmacological interventions have not been shown to be effective for delirium management but non-pharmacological interventions have shown some promise. The aim of this systematic review is to identify effective non-pharmacological interventions for reducing the incidence or the duration of delirium in critically ill patients.

Methods: We will search MEDLINE, EMBASE, CINAHL, Web of Science, AMED, psycINFO and the Cochrane Library.We will include studies of critically ill adults and children. We will include randomised trials and controlled trials which measure the effectiveness of one or more non-pharmacological interventions in reducing incidence or duration ofdelirium in critically ill patients. We will also include qualitative studies that provide an insight into patients and their families’ experiences of delirium and non-pharmacological interventions. Two independent reviewers will assess studies for eligibility, extract data and appraise quality. We will conduct meta-analyses if possible or present results narratively.Qualitative studies will also be reviewed by two independent reviewers, and a specially designed quality assessment tool incorporating the CASP framework and the POPAY framework will be used to assess quality.

Discussion: Although non-pharmacological interventions have been studied in populations outside of intensive care units and multicomponent interventions have successfully reduced incidence and duration of delirium, no systematic review of non-pharmacological interventions specifically targeting delirium in critically ill patients have been undertaken to date. This systematic review will provide evidence for the development of a multicomponent intervention for delirium management of critically ill patients that can be tested in a subsequent multicentre randomised trial.

Root caries development in older adults- a prospective cohort study

Objectives: To identify factors associated with root caries development during a two year period in a population of independently living older adults. Methods: A prospective cohort study was carried out with 334 independently living volunteers aged 65 and older. At baseline (t0), each participant completed a questionnaire which recorded age, gender, medical history, fluoride exposure, oral and denture hygiene practices, smoking and alcohol consumption, diet information, and socio economic information. Clinical examinations were performed and stimulated saliva samples were collected. Patients were reviewed 12(t1) and 24(t2) months later to determine the root caries increment. Results: 307 adults were assessed at t1 and 280 were assessed at t2 with 83.8% of participants examined at 24 months. Incidence of root caries in this cohort was 17.4% at t1 and 21.6% at t2. The mean root caries increment was 0.43 (SD 1.45) surfaces at t1 and 0.70 (SD 1.86) surfaces at t2. Age >70 years, completing education at primary level, poor oral hygiene, xerostomia, coronal decay at baseline, higher root caries index at baseline and number of exposed root surfaces showed a statistically significant association (P < 0.05) with root caries development. Conclusion: Root caries is a substantive dental health problem for our older population. Root caries prevention strategies should be targeted at older adults who have poor plaque control and high levels of caries experience. In particular patients with xerostomia should be targeted with preventive measures.

Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium

BACKGROUND: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.

METHODS: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.

RESULTS: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.

CONCLUSIONS: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.

Retinopathy of prematurity: Causes, prevention and treatment

Advances in neonatal intensive care have improved survival rates in extremely premature an infant, which has led to an increase of Retinopathy of Prematurity (ROP) in the developed world. Left untreated, infants are at risk of developing strabismus, myopia, vitreous haemorrhage, vitreo-retinal fibrosis, retinal detachment, secondary angle closure glaucoma and ultimately complete loss of vision. The improvements in the understanding and treatment of ROP have been supported by seminal research, and its complexity is still being explored. However the importance of early screening and treatment is essential in the prevention and treatment of this disease. The following paper will examine the causes and treatments of ROP, as well as implications for future neonatal practice.