Long-Term Survival in HIV Positive Patients with up to 15 Years of Antiretroviral Therapy

Background

Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models.

Methods

Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models.

Results

The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2–10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5–2.9) for CD4 = 350–499 cells/µl; and 1.5 (95% CI: 1.1–2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment.

Conclusion

Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.     

SNP rs10248565 in HDAC9 as a novel genomic aberration biomarker of lung adenocarcinoma in non-smoking women

Background

Numerous efforts have been made to elucidate the etiology and improve the treatment of lung cancer, but the overall five-year survival rate is still only 15%. Although cigarette smoking is the primary risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of smoking. Since cancer results from progressive accumulation of genetic aberrations, genomic rearrangements may be early events in carcinogenesis.

Results

In order to identify biomarkers of early-stage adenocarcinoma, the genome-wide DNA aberrations of 60 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined using Affymetrix Genome-Wide Human SNP 6.0 arrays. Common copy number variation (CNV) regions were identified by ≥30% of patients with copy number beyond 2 ± 0.5 of copy numbers for each single nucleotide polymorphism (SNP) and at least 100 continuous SNP variant loci. SNPs associated with lung adenocarcinoma were identified by McNemar’s test. Loss of heterozygosity (LOH) SNPs were identified in ≥18% of patients with LOH in the locus. Aberration of SNP rs10248565 at HDAC9 in chromosome 7p21.1 was identified from concurrent analyses of CNVs, SNPs, and LOH.

Conclusion

The results elucidate the genetic etiology of lung adenocarcinoma by demonstrating that SNP rs10248565 may be a potential biomarker of cancer susceptibility.     

The Value of Serum Prealbumin in the Diagnosis and Therapeutic Response of Tuberculosis: A Retrospective Study

Objective

The aim of this study was to examine serum prealbumin (PA) levels in patients with tuberculosis and lung cancer, and to evaluate the correlations of serum PA levels with clinicopathological characteristics.

Method

Total 760 patients were included in the study: 320 patients with tuberculosis, 320 patients with lung cancer, and 120 healthy subjects. Serum PA was detected using a biochemical analyzer to determine the value of serum PA in the diagnosis and therapeutic response of tuberculosis.

Results

Compared to lung cancer and healthy individuals, TB patients were more frequent in suffering from low serum PA (75.0% vs.30.9% vs.6.7%,P<0.01), and the serum PA levels of TB patients were significantly reduced (137.5±42.4 mg/L vs. 183.5±49.1 mg/L vs. 240.0±43.9 mg/L, P<0.01). Among various clinical characteristics, type (with pleuritis), age (≥60), ESR (>20 mm/h) and smoking status (≥20 pack×years) were associated with low serum PA levels of TB patients, while ECOG performance status (≥2) was associated with low serum PA levels of lung cancer patients. The change of serum PA levels was in accordance with the therapeutic effects of anti-TB drugs, which might present a valuable and objective indicator for monitoring the therapeutic effects of TB drugs on TB patients.

Conclusion

Low serum prealbumin levels are very common in TB patients and can be served as a potential indicator for differential diagnosis of lung cancer and monitoring the therapeutic effects of TB drugs.     

Combined Effects of Smoking and Bilirubin Levels on the Risk of Lung Cancer in Korea: The Severance Cohort Study

Background

Smoking is a major risk factor for lung cancer. Bilirubin, an antioxidant, is inversely associated with the risk of diseases related to oxidative stress. This study was conducted to determine the influence of smoking and bilirubin levels on the risk of lung cancer in the Severance cohort study.

Methods

This study included 68,676 Korean who received a health examination at Severance Health Promotion Center from 1994 to 2004. Serum bilirubin measurements within normal range were divided into tertiles whereas smoking states were divided as never-smokers, former smokers and current smokers. A diagnosis of lung cancer was coded as occurring based on the report from the National Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards model.

Results

At the end of the study period, 240 patients (men: 181, women: 59) developed lung cancer. Compared to those with bilirubin levels ≥1.0 mg/dL, HRs (95% CI) for lung cancer were 2.8 (1.8–4.2) for subjects having bilirubin levels from 0.2 to 0.7 mg/dL in men. When we stratified our analysis by smoking status, bilirubin consistently showed a protective effect on the risk of lung cancer on both never- and current smokers. Current smokers having bilirubin levels from 0.2 to 0.7 mg/dL had a risk of lung cancer by 6.0-fold higher than never-smokers with bilirubin levels ≥1.0 mg/dL in men.

Conclusion

In this large prospective study, higher baseline bilirubin level in the normal range was associated with low risk of lung cancer. Smoking and low bilirubin levels were cumulatively associated with a higher risk of lung cancer.     

Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA2LEN Study

Background

Women who smoke have higher risk of lung function impairment, COPD and lung cancer than smoking men. An influence of sex hormones has been demonstrated, but the mechanisms are unclear and the associations often subject to confounding. This was a study of wheeze in relation to smoking and sex with adjustment for important confounders.

Methods

In 2008 the Global Allergy and Asthma European Network (GA²LEN) questionnaire was mailed to 45.000 Swedes (age 16–75 years), and 26.851 (60%) participated. “Any wheeze”: any wheeze during the last 12 months. “Asthmatic wheeze”: wheeze with breathlessness apart from colds.

Results

Any wheeze and asthmatic wheeze was reported by 17.3% and 7.1% of women, vs. 15.8% and 6.1% of men (both p<0.001). Although smoking prevalence was similar in both sexes, men had greater cumulative exposure, 16.2 pack-years vs. 12.8 in women (p<0.001). Most other exposures and characteristics associated with wheeze were significantly overrepresented in men. Adjusted for these potential confounders and pack-years, current smoking was a stronger risk factor for any wheeze in women aged <53 years, adjusted odds ratio (aOR) 1.85 (1.56–2.19) vs. 1.60 (1.30–1.96) in men. Cumulative smoke exposure and current smoking each interacted significantly with female sex, aOR 1.02 per pack-year (p<0.01) and aOR 1.28 (p = 0.04) respectively. Female compared to male current smokers also had greater risk of asthmatic wheeze, aOR 1.53 vs. 1.03, interaction aOR 1.52 (p = 0.02). These interactions were not seen in age ≥53 years.

Discussion

In addition to the increased risk of COPD and lung cancer female, compared to male, smokers are at greater risk of significant wheezing symptoms in younger age. This became clearer after adjustment for important confounders including cumulative smoke exposure. Estrogen has previously been shown to increase the bioactivation of several compounds in tobacco smoke, which may enhance smoke-induced airway inflammation in fertile women.     

Burden of Total and Cause-Specific Mortality Related to Tobacco Smoking among Adults Aged ≥45 Years in Asia: A Pooled Analysis of 21 Cohorts

Background

Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men''s smoking prevalence is among the world''s highest.

Methods and Findings

We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan—accounting for ∼71% of Asia''s total population. An approximately 1.44-fold (95% CI = 1.37–1.51) and 1.48-fold (1.38–1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%–17.2%) and 3.3% (2.6%–4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000–1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y.

Conclusions

Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented. Please see later in the article for the Editors'' Summary     

Reductions in Cardiovascular,Cerebrovascular, and Respiratory Mortality following the National Irish Smoking Ban: Interrupted Time-Series Analysis

Background

Previous studies have shown decreases in cardiovascular mortality following the implementation of comprehensive smoking bans. It is not known whether cerebrovascular or respiratory mortality decreases post-ban. On March 29, 2004, the Republic of Ireland became the first country in the world to implement a national workplace smoking ban. The aim of this study was to assess the effect of this policy on all-cause and cause-specific, non-trauma mortality.

Methods

A time-series epidemiologic assessment was conducted, utilizing Poisson regression to examine weekly age and gender-standardized rates for 215,878 non-trauma deaths in the Irish population, ages ≥35 years. The study period was from January 1, 2000, to December 31, 2007, with a post-ban follow-up of 3.75 years. All models were adjusted for time trend, season, influenza, and smoking prevalence.

Results

Following ban implementation, an immediate 13% decrease in all-cause mortality (RR: 0.87; 95% CI: 0.76–0.99), a 26% reduction in ischemic heart disease (IHD) (RR: 0.74; 95% CI: 0.63–0.88), a 32% reduction in stroke (RR: 0.68; 95% CI: 0.54–0.85), and a 38% reduction in chronic obstructive pulmonary disease (COPD) (RR: 0.62; 95% CI: 0.46–0.83) mortality was observed. Post-ban reductions in IHD, stroke, and COPD mortalities were seen in ages ≥65 years, but not in ages 35–64 years. COPD mortality reductions were found only in females (RR: 0.47; 95% CI: 0.32–0.70). Post-ban annual trend reductions were not detected for any smoking-related causes of death. Unadjusted estimates indicate that 3,726 (95% CI: 2,305–4,629) smoking-related deaths were likely prevented post-ban. Mortality decreases were primarily due to reductions in passive smoking.

Conclusions

The national Irish smoking ban was associated with immediate reductions in early mortality. Importantly, post-ban risk differences did not change with a longer follow-up period. This study corroborates previous evidence for cardiovascular causes, and is the first to demonstrate reductions in cerebrovascular and respiratory causes.     

Health Behaviours and Potentially Preventable Hospitalisation: A Prospective Study of Older Australian Adults

Objective

Several studies have demonstrated the effects of health behaviours on risk of chronic diseases and mortality, but none have investigated their contribution to potentially preventable hospitalisation (PPH). We aimed to quantify the effects on risk of PPH of six health behaviours: smoking; alcohol consumption; physical activity; fruit and vegetables consumption; sitting time; and sleeping time.

Design/Setting

Prospective observational study in New South Wales, Australia.

Subjects

267,006 men and women aged 45 years and over.

Outcome Measures

PPH admissions and mortality during follow-up according to individual positive health behaviours (non-smoking, <14 alcoholic drinks per week, ≥2.5 hours of physical activity per week, ≥2 servings of fruit and 5 servings of vegetables per day, <8 hours sitting and ≥7 hours sleeping per day) and the total number of these behaviours.

Results

During an average of 3 years follow-up, 20971 (8%) participants had at least one PPH admission. After adjusting for potential confounders, participants who reported all six positive health behaviours at baseline had 46% lower risk of PPH admission (95% CI 0.48–0.61), compared to those who reported having only one of these behaviours. Based on these risk estimates, approximately 29% of PPH admissions in Australians aged 45 years and over were attributable to not adhering to the six health behaviours. Estimates were similar for acute, chronic and vaccine-preventable categories of PPH admissions.

Conclusions

Individual and combined positive health behaviours were associated with lower risk of PPH admission. These findings suggest that there is a significant opportunity to reduce PPH by promoting healthy behaviours.     

Rate of progression of CT-quantified emphysema in male current and ex-smokers: a follow-up study

Background

Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV₁-decline in male heavy smokers.

Methods

3,670 male smokers with mean (SD) 40.8 (17.9) packyears underwent chest CT scans and pulmonary function tests at baseline and after 1 and 3 years follow-up. Smoking status (quitted ≥5, ≥1-<5, <1 years or current smoker) was noted. Rate of progression of emphysema and FEV₁-decline after follow-up were assessed by analysis of variance adjusting for age, height, baseline pulmonary function and emphysema severity, packyears, years in study and respiratory symptoms. The quitted ≥5 group was used as reference.

Results

Median (Q1-Q3) emphysema severity,<-950 HU, was 8.8 (5.1 – 14.1) and mean (SD) FEV₁ was 3.4 (0.73) L or 98.5 (18.5) % of predicted. The group quitted ‘>5 years’ showed significantly lower rates of progression of emphysema compared to current smokers, 1.07% and 1.12% per year, respectively (p<0.001). Current smokers had a yearly FEV₁-decline of 69 ml, while subjects quit smoking >5 years had a yearly decline of 57.5 ml (p<0.001).

Conclusion

Quit smoking >5 years significantly slows the rate of emphysema progression and lung function decline.

Trial registration

Registered at http://www.trialregister.nl with trial number ISRCTN63545820.     

Relationships among Smoking Habits,Airflow Limitations,and Metabolic Abnormalities in School Workers

Background

Chronic obstructive pulmonary disease is caused mainly by habitual smoking and is common among elderly individuals. It involves not only airflow limitation but also metabolic disorders, leading to increased cardiovascular morbidity and mortality.

Objective

We evaluated relationships among smoking habits, airflow limitation, and metabolic abnormalities.

Methods

Between 2001 and 2008, 15,324 school workers (9700 males, 5624 females; age: ≥30 years) underwent medical checkups, including blood tests and spirometry. They also responded to a questionnaire on smoking habits and medical history.

Results

Airflow limitation was more prevalent in current smokers than in ex-smokers and never-smokers in men and women. The frequency of hypertriglyceridemia was higher in current smokers in all age groups, and those of low high-density-lipoprotein cholesterolemia and diabetes mellitus were higher in current smokers in age groups ≥ 40 s in men, but not in women. There were significant differences in the frequencies of metabolic abnormalities between subjects with airflow limitations and those without in women, but not in men. Smoking index was an independent factor associated with increased frequencies of hypertriglyceridemia (OR 1.015; 95% CI: 1.012–1.018; p<0.0001) and low high-density-lipoprotein cholesterolemia (1.013; 1.010–1.016; p<0.0001) in men. Length of smoking cessation was an independent factor associated with a decreased frequency of hypertriglyceridemia (0.984; 0.975–0.994; p = 0.007).

Conclusions

Habitual smoking causes high incidences of airflow limitation and metabolic abnormalities. Women, but not men, with airflow limitation had higher frequencies of metabolic abnormalities.     

A Cost-Utility Analysis of Lung Cancer Screening and the Additional Benefits of Incorporating Smoking Cessation Interventions

Background

A 2011 report from the National Lung Screening Trial indicates that three annual low-dose computed tomography (LDCT) screenings for lung cancer reduced lung cancer mortality by 20% compared to chest X-ray among older individuals at high risk for lung cancer. Discussion has shifted from clinical proof to financial feasibility. The goal of this study was to determine whether LDCT screening for lung cancer in a commercially-insured population (aged 50–64) at high risk for lung cancer is cost-effective and to quantify the additional benefits of incorporating smoking cessation interventions in a lung cancer screening program.

Methods and Findings

The current study builds upon a previous simulation model to estimate the cost-utility of annual, repeated LDCT screenings over 15 years in a high risk hypothetical cohort of 18 million adults between age 50 and 64 with 30+ pack-years of smoking history. In the base case, the lung cancer screening intervention cost $27.8 billion over 15 years and yielded 985,284 quality-adjusted life years (QALYs) gained for a cost-utility ratio of $28,240 per QALY gained. Adding smoking cessation to these annual screenings resulted in increases in both the costs and QALYs saved, reflected in cost-utility ratios ranging from $16,198 per QALY gained to $23,185 per QALY gained. Annual LDCT lung cancer screening in this high risk population remained cost-effective across all sensitivity analyses.

Conclusions

The findings of this study indicate that repeat annual lung cancer screening in a high risk cohort of adults aged 50–64 is highly cost-effective. Offering smoking cessation interventions with the annual screening program improved the cost-effectiveness of lung cancer screening between 20% and 45%. The cost-utility ratios estimated in this study were in line with other accepted cancer screening interventions and support inclusion of annual LDCT screening for lung cancer in a high risk population in clinical recommendations.     

An Assessment of Health Risks and Mortality from Exposure to Secondhand Smoke in Chinese Restaurants and Bars

Introduction

Smoking is generally not regulated in restaurants or bars in China, or the restrictions are not fully implemented if there are any, while the related hazard health effects are not recognized by the majority of the Chinese population.

Objectives

This study aims to assess the excess health risks and mortality attributed to secondhand smoke (SHS) exposure in restaurants and bars for both servers and patrons to provide necessary evidence for advancing tobacco control in this microenvironment.

Methods

Two approaches were used for the assessment. One is a continuous approach based on existing field measurements and Repace and Lowrey’s dose-response model, and the other is a categorical approach based on exposure or not and epidemiological studies.

Results

Based on the continuous approach, servers were estimated to have a lifetime excess risk (LER) of lung cancer death (LCD) of 730 to 1,831×10⁻⁶ for working five days a week for 45 years in smoking restaurants and 1,862 to 8,136×10⁻⁶ in smoking bars, and patrons could have a LER of LCD of 47 to 117×10⁻⁶ due to visiting smoking restaurants for an average of 13 minutes a day for 60 years, and 119 to 522×10⁻⁶ due to visiting smoking bars. The categorical approach estimated that SHS exposure in restaurants and bars alone caused 84 LCD and 57 ischemic heart disease (IHD) deaths among nonsmoking servers and 1,2419 LCDs and 1,689 IHD deaths among the nonsmoking patron population.

Conclusions

SHS exposure in restaurants and bars alone can impose high lifetime excess risks of lung cancer death and ischemic heart disease deaths to both servers and patrons, and can cause a significant number of deaths each year in China. These health risks and deaths can be prevented by banning smoking in restaurants and bars and effectively implementing these smoking bans.     

Association of Body Mass Index with All-Cause and Cardiovascular Disease Mortality in the Elderly

Objectives

To evaluate the associations of body mass index (BMI) with all-cause, cardiovascular disease (CVD), and expanded CVD mortality in the elderly.

Design

Observational cohort study.

Setting

Annual physical examination program for the elderly from 2006 to 2010.

Participants

We included 77,541 Taipei residents aged ≥65 years (39,365 men and 38,176 women).

Measurements

BMI was categorized as underweight (BMI<18.5), normal weight (18.5≤BMI<25), overweight (25≤BMI<30), grade 1 obesity (30≤BMI<35), or grade 2–3 obesity (BMI≥35). Mortality was ascertained by national death files.

Results

Underweight (hazard ratios [HRs] of all-cause, CVD, and expanded CVD mortality: 1.92, 1.74, and 1.77, respectively), grade 2–3 obesity (HRs: 1.59, 2.36, and 2.22, respectively), older age, male sex, smoking, and high fasting blood sugar were significant predictors of mortality. Meanwhile, being married/cohabitating, higher education, alcohol consumption, more regular exercise, and high total cholesterol were inversely associated with mortality. Multivariate stratified subgroup analyses verified smokers (HRs of all-cause, CVD, and expanded CVD mortality: 3.25, 10.71, and 7.86, respectively, for grade 2–3 obesity), the high triglyceride group (HRs: 5.82, 10.99, and 14.22, respectively for underweight), and patients with 3–4 factors related to metabolic syndrome (HRs: 4.86, 12.72, and 11.42, respectively, for underweight) were associated with mortality.

Conclusion

The associations of BMI with all-cause, CVD, expanded CVD mortality in the elderly are represented by U-shaped curves, suggesting unilateral promotions or interventions in weight reduction in the elderly may be inappropriate. Heterogeneous effects of grades 1 and 2–3 obesity on mortality were observed and should be treated as different levels of obesity.     

Molecular Alterations Associated with Breast Cancer Mortality

Background

Breast cancer is a heterogeneous disease and patients with similar pathologies and treatments may have different clinical outcomes. Identification of molecular alterations associated with disease outcome may improve risk assessment and treatments for aggressive breast cancer.

Methods

Allelic imbalance (AI) data was generated for 122 invasive breast tumors with known clinical outcome. Levels and patterns of AI were compared between patients who died of disease (DOD) and those with ≥5 years disease-free survival (DFS) using Student t-test and chi-square analysis with a significance value of P<0.05.

Results

Levels of AI were significantly higher in tumors from the 31 DOD patients (28.6%) compared to the 91 DFS patients (20.1%). AI at chromosomes 7q31, 8p22, 13q14, 17p13.3, 17p13.1 and 22q12.3 was associated with DOD while AI at 16q22–q24 was associated with DFS. After multivariate analysis, AI at chromosome 8p22 remained an independent predictor of breast cancer mortality. The frequency of AI at chromosome 13q14 was significantly higher in patients who died ≥5 years compared to those who died <5 years from diagnosis.

Conclusion

Tumors from DOD compared to DFS patients are marked by increased genomic instability and AI at chromosome 8p22 is significantly associated with breast cancer morality, independent of other clinicopathological factors. AI at chromosome 13q14 was associated with late (>5-years post-diagnosis) mortality but not with death from disease within five years, suggesting that patients with short- and long-term mortality may have distinct genetic diseases.     

Association between Smoking and Latent Tuberculosis in the U.S. Population: An Analysis of the National Health and Nutrition Examination Survey

Background

Evidence of an association between cigarette smoking and latent tuberculosis infection (LTBI) is based on studies in special populations and/or from high prevalence settings. We sought to evaluate the association between LTBI and smoking in a low prevalence TB setting using population-based data from the National Health and Nutrition Examination Survey (NHANES).

Methods

In 1999–2000, NHANES assessed LTBI (defined as a tuberculin skin test measurement ≥10 mm) in participants, and those ≥20 years of age were queried regarding their tobacco use and serum cotinine was measured. We evaluated the association of LTBI with self-reported smoking history and smoking intensity in multivariable logistic regression models that adjusted for known confounders (gender, age, birthplace, race/ethnicity, poverty, education, history of BCG vaccination, and history of household exposure to tuberculosis disease).

Results

Estimated LTBI prevalence was 5.3% among those ≥20 years of age. The LTBI prevalence among never smokers, current smokers, and former smokers was 4.1%, 6.6%, and 6.2%, respectively. In a multivariable model, current smoking was associated with LTBI (OR 1.8; 95% CI, 1.1–2.9). The association between smoking and LTBI was strongest for Mexican-American and black individuals. In multivariate analysis stratified by race/ethnicity, cigarette packs per day among Mexican-American smokers and cotinine levels among black smokers, were significantly associated with LTBI.

Conclusions

In the large, representative, population-based NHANES sample, smoking was independently associated with significantly increased risks of LTBI. In certain populations, a greater risk of LTBI corresponded with increased smoking exposure.     

Long-term ischaemic and bleeding outcomes after primary percutaneous coronary intervention for ST-elevation myocardial infarction in the elderly

Background

The population is ageing rapidly and the proportion of patients aged ≥ 80 years undergoing primary percutaneous coronary intervention (PCI) is rising, but clinical trials have primarily been performed in younger patients.

Methods

Patients undergoing primary PCI between 2003 and 2008 were subdivided into 3 groups: < 60, 60-79, and ≥ 80 years. Endpoints at 3-year follow-up included all-cause mortality, recurrent myocardial infarction (reMI), stent thrombosis, target lesion revascularisation (TLR), bleeding (BARC bleeding ≥ 3), stroke, and major adverse cardiovascular events (MACE, a composite of cardiac mortality, reMI, stroke and TLR).

Results

2002 patients with ST-segment elevation myocardial infarction (STEMI) were included, 885 (44.2 %) aged < 60, 921 (46.0 %) 60–79, and 196 (9.7 %) ≥ 80 years. Comorbidities such as diabetes mellitus, prior stroke, malignant disease, anaemia, and chronic kidney disease were more prevalent in patients ≥ 80 years. The incidence of both ischaemic and bleeding events strongly increased with age. Age ≥ 80 years was an independent predictor of mortality (HR 2.56, 95 % CI1.69–3.87, p < 0.001), a borderline non-significant predictor of overall bleeding (HR 1.38, 95 %CI 0.95–2.00, p = 0.088), and a significant predictor of non-access site bleeding (HR 2.26, 95 %CI 1.46–3.51, p < 0.001).

Conclusion

Patients ≥ 80 years experienced high rates of ischaemic and bleeding complications; especially in this high-risk patient group individualised therapy is needed to optimise clinical outcomes.

Electronic Supplementary Material

The online version of this article (doi:10.1007/s12471-015-0733-2 contains supplementary material, which is available to authorized users.     

Mortality Rates Across 25-Hydroxyvitamin D (25[OH]D) Levels among Adults with and without Estimated Glomerular Filtration Rate <60 ml/min/1.73 m2: The Third National Health and Nutrition Examination Survey

Background

Previous studies exploring the association between 25[OH]D levels and mortality in adults with and without kidney disease utilized 25[OH]D thresholds that have recently been scrutinized by the Institute of Medicine Committee to Review Dietary References Intakes for Vitamin D and Calcium.

Objective

We explored all-cause mortality rates across the spectrum of 25[OH]D levels over an eighteen-year follow-up among adults with and without an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m².

Design

The study included 1,097 U.S. adults with eGFR <60 ml/min/1.73 m² and 14, 002 adults with eGFR ≥60 ml/min/1.73 m². Mortality rates and rate ratios (RR) across 25[OH]D groups were calculated with Poisson regression and restricted cubic splines while adjusting for covariates.

Results

Prevalence of 25[OH]D levels <30 and <20 ng/ml among adults with eGFR <60 ml/min/1.73 m² was 76.5% (population estimate 6.2 million) and 35.4% (population estimate 2.9 million), respectively. Among adults with eGFR ≥60 ml/min/1.73 m², 70.5% had 25[OH]D levels <30 ng/ml (population estimate 132.2 million) while 30.3% had 25[OH]D levels <20 ng/ml (population estimate 56.8 million). Significantly higher mortality rates were noted among individuals with 25[OH]D levels <12 ng/ml compared to referent group (24 to <30 ng/ml): RR1.41 (95% CI 1.17, 1.71) among individuals with eGFR <60 ml/min/1.73 m² and RR 1.32 (95% CI 1.13, 1.56) among individuals with eGFR ≥60 ml/min/1.73 m² after adjustment for covariates including co-morbid conditions. Mortality rates were fairly similar across all 25[OH]D groups with levels >20 ng/ml after adjustment for all covariates.

Conclusions

Regardless of presence of eGFR <60 ml/min/1.73 m², mortality rates across groups with 25[OH]D levels 20–40 ng/ml are similar.     

Longitudinal association of body mass index with lung function: The CARDIA Study

Background

Lung function at the end of life depends on its peak and subsequent decline. Because obesity is epidemic in young adulthood, we quantified age-related changes in lung function relative to body mass index (BMI).

Methods

The Coronary Artery Risk Development in Young Adults (CARDIA) study in 1985–86 (year 0) recruited 5,115 black and white men and women, aged 18–30. Spirometry testing was conducted at years 0, 2, 5 and 10. We estimated 10 year change in FVC, FEV₁ and FEV₁/FVC according to baseline BMI and change in BMI within birth cohorts with initial average ages 20, 24, and 28 years, controlling for race, sex, smoking, asthma, physical activity, and alcohol consumption.

Measurements and Main Results

Participants with baseline BMI < 21.3 kg/m² experienced 10 year increases of 71 ml in FVC and 60 ml in FEV₁ and neither measure declined through age 38. In contrast, participants with baseline BMI ≥ 26.4 kg/m² experienced 10 year decreases of 185 ml in FVC and 64 ml in FEV₁. FEV₁/FVC increased with increasing BMI. Weight gain was also associated with lung function. Those who gained the most weight over 10 years had the largest decrease in FVC, but FVC increased with weight gain in those initially thinnest. In contrast, FEV₁ decreased with increasing weight gain in all participants, with maximum decline in obese individuals who gained the most weight during the study.

Conclusion

Among healthy young adults, increasing BMI in the initially thin participants was associated with increasing then stable lung function through age 38, but there were substantial lung function losses with higher and increasing fatness. These results suggest that the obesity epidemic threatens the lung health of the general population.     

A Higher Dosage of Oral Alendronate Will Increase the Subsequent Cancer Risk of Osteoporosis Patients in Taiwan: A Population-Based Cohort Study

Background

Controversy still exists regarding whether alendronate (ALN) use increases the risk of esophageal cancer or breast cancer.

Methods

This paper explores the possible association between the use of oral ALN in osteoporosis patients and subsequent cancer risk using the National Health Insurance (NHI) system database of Taiwan with a Cox proportional-hazard regression analysis. The exposure cohort contained 5,624 osteoporosis patients used ALN and randomly frequency-matched by age and gender of 3 osteoporosis patients without any kind of anti-osteoporosis drugs in the same period.

Results

For a dose ≥1.0 g/year, the risk of developing overall cancer was significantly higher (hazard ratio: 1.69, 95% confidence ratio: 1.39–2.04) than in osteoporosis patients without any anti-osteoporosis drugs. The risks for developing liver, lung, and prostate cancers and lymphoma were also significantly higher than in the control group.

Conclusions

This population-based retrospective cohort study did not find a relationship between ALN use and either esophageal or breast cancer, but unexpectedly discovered that use of ALN with dose ≥1.0 g/year significantly increased risks of overall cancer incidence, as well as liver, lung, and prostate cancers and lymphoma. Further large population-based unbiased studies to enforce our findings are required before any confirmatory conclusion can be made.     

Impact of statins and ACE inhibitors on mortality after COPD exacerbations

Background

The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.

Methods

We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation. Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.

Results

We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation. In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB). After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40–0.64) and ACE inhibitor/ARB use (0.55, 0.46–0.66) were significantly associated with decreased 90-day mortality.

Conclusion

Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation. Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations.