A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer ...(NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with a protocol-specified propensity-matched comparison with a prospectively registered, contemporary institutional cohort of patients who underwent video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND).
This single-arm prospective trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and enrolled patients aged 18 years or older with a Zubrod performance status of 0–2, newly diagnosed and histologically confirmed NSCLC with N0M0 disease (squamous cell, adenocarcinoma, large cell, or NSCLC not otherwise specified), and a tumour diameter of 3 cm or less. This trial did not include patients from the previous pooled analysis. SABR dosing was 54 Gy in three fractions (for peripheral lesions) or 50 Gy in four fractions (for central tumours; simultaneous integrated boost to gross tumour totalling 60 Gy). The primary endpoint was the 3-year overall survival. For the propensity-matching analysis, we used a surgical cohort from the MD Anderson Department of Thoracic and Cardiovascular Surgery's prospectively registered, institutional review board-approved database of all patients with clinical stage I NSCLC who underwent VATS L-MLND during the period of enrolment in this trial. Non-inferiority could be claimed if the 3-year overall survival rate after SABR was lower than that after VATS L-MLND by 12% or less and the upper bound of the 95% CI of the hazard ratio (HR) was less than 1·965. Propensity matching consisted of determining a propensity score using a multivariable logistic regression model including several covariates (age, tumour size, histology, performance status, and the interaction of age and sex); based on the propensity scores, one patient in the SABR group was randomly matched with one patient in the VATS L-MLND group using a 5:1 digit greedy match algorithm. This study is registered with ClinicalTrials.gov, NCT02357992.
Between Sept 1, 2015, and Jan 31, 2017, 80 patients were enrolled and included in efficacy and safety analyses. Median follow-up time was 5·1 years (IQR 3·9–5·8). Overall survival was 91% (95% CI 85–98) at 3 years and 87% (79–95) at 5 years. SABR was tolerated well, with no grade 4–5 toxicity and one (1%) case each of grade 3 dyspnoea, grade 2 pneumonitis, and grade 2 lung fibrosis. No serious adverse events were recorded. Overall survival in the propensity-matched VATS L-MLND cohort was 91% (95% CI 85–98) at 3 years and 84% (76–93) at 5 years. Non-inferiority was claimed since the 3-year overall survival after SABR was not lower than that observed in the VATS L-MLND group. There was no significant difference in overall survival between the two patient cohorts (hazard ratio 0·86 95% CI 0·45–1·65, p=0·65) from a multivariable analysis.
Long-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended.
Varian Medical Systems and US National Cancer Institute (National Institutes of Health).
Cigars are a growing public health concern, given the changes in cigar use patterns in the US and elsewhere since the 1960s. We conducted a systematic review of published studies on current cigar ...smoking and all-cause and cause-specific mortality risks to inform potential regulatory approaches and future research that would strengthen the body of evidence.
Using 3 different databases and handsearching, we identified epidemiological studies published prior to June 2014 that examined the association between cigar smoking and all-cause mortality and smoking-related mortality. Detailed study characteristics as well as association-level characteristics, including effect estimates and 95% confidence intervals, were abstracted or calculated from each selected study.
A total of 22 studies from 16 different prospective cohorts were identified. Primary cigar smoking (current, exclusive cigar smoking with no history of previous cigarette or pipe smoking) was associated with all cause-mortality, oral cancer, esophageal cancer, pancreatic cancer, laryngeal cancer, lung cancer, coronary heart disease (CHD), and aortic aneurysm. Strong dose trends by cigars per day and inhalation level for primary cigar smoking were observed for oral, esophageal, laryngeal, and lung cancers. Among primary cigar smokers reporting no inhalation, relative mortality risk was still highly elevated for oral, esophageal, and laryngeal cancers.
In summary, cigar smoking carries many of the same health risks as cigarette smoking. Mortality risks from cigar smoking vary by level of exposure as measured by cigars per day and inhalation level and can be as high as or exceed those of cigarette smoking. The body of evidence would be strengthened by future studies that focus on the health effects of primary cigar smoking and incorporate more contemporary and diverse study populations to better reflect the current patterns of cigar use in the US. Ideally, these studies would also collect detailed information on cigar type, exposure level, and biomarkers of exposure and potential harm.
We previously reported the effect of certain factors on cardiovascular disease (CVD) in 250 women with systemic lupus erythematosus (SLE) followed for 8 years. The aim of this study was to delineate ...their evolution after 15 years of followup.
There were 210 women with SLE and 138 age-matched healthy women available for analysis after 15 years. Cardiovascular events (CVE) included angina pectoris, myocardial infarction (fatal and nonfatal), transient ischemic attack, and stroke (fatal and nonfatal). Analysis was performed with SAS 9.3 software; p < 0.05 was considered significant.
CVE occurred in 41/210 patients (19.5%) and 9/138 controls (6.5%), most of them in the second part (2008-2015) of the study (24/210, 11.4% vs 17/241, 7.1% in SLE group). Coronary artery disease was more common in patients (32/210, 15.2% vs 5/138, 3.6%, p = 0.0041). There was no significant difference for cerebrovascular disease (10/210, 4.8% vs 3/138, 2.2%, p = 0.213). SLE was the most prominent CVE predictor in the first 8 years (HR 2.8, 95% CI 1.3-6.3). Hypertension and diabetes were more frequent in patients who developed CVE during the second half of the study. Thirty-one deaths occurred in patients with SLE (10 because of CVD) and 6 in controls (none because of CVD).
The relative importance of atherosclerotic risk factors is significantly differentiated over time in SLE. Disease-related factors seem to dominate CV risk during the early stages while traditional factors, partially related to corticosteroid treatment, play a significant role later in the disease course.
Aims/hypothesis
People with type 1 diabetes have reduced life expectancy (LE) compared with the general population. Our aim is to quantify mortality changes from 2002 to 2011 in people with type 1 ...diabetes in Sweden.
Methods
This study uses health records from the Swedish National Diabetes Register (NDR) linked with death records. Abridged period life tables for those with type 1 diabetes aged 20 years and older were derived for 2002–06 and 2007–11 using Chiang’s method. Cox proportional hazard models were used to assess trends in overall and cause-specific mortality.
Results
There were 27,841 persons aged 20 years and older identified in the NDR as living with type 1 diabetes between 2002 and 2011, contributing 194,685 person-years of follow-up and 2,018 deaths. For men with type 1 diabetes, the remaining LE at age 20 increased significantly from 47.7 (95% CI 46.6, 48.9) in 2002–06 to 49.7 years (95% CI 48.9, 50.6) in 2007–11. For women with type 1 diabetes there was no significant change, with an LE at age 20 of 51.7 years (95% CI 50.3, 53.2) in 2002–06 and 51.9 years (95% CI 50.9, 52.9) in 2007–11. Cardiovascular mortality significantly reduced, with a per year HR of 0.947 (95% CI 0.917, 0.978) for men and 0.952 (95% CI 0.916, 0.989) for women.
Conclusions/interpretation
From 2002–06 to 2007–11 the LE at age 20 of Swedes with type 1 diabetes increased by approximately 2 years for men but minimally for women. These recent gains have been driven by reduced cardiovascular mortality.
An increasing proportion of new cancers is registered in patients who have received a previous cancer diagnosis. As data are inconsistent across studies, we provided information for populations long ...covered by valid cancer registration. Data were derived from the Swiss cancer Registries of Vaud and Neuchâtel (885 000 inhabitants). Patients diagnosed with a new malignancy (except skin basal and squamous cell carcinomas) during the period 2005–2010 were included. Over the period 2005–2010, 24 859 patients were registered with incident cancer. Of these, 3127 (13%) had multiple primary cancers and 578 (2.3%) were synchronous. Breast, prostate, colorectum, skin, melanomas, and squamous cell carcinomas of the head and neck (SHN) and bladder/ureter were the most common sites of first neoplasms, whereas breast, lung, colorectum, prostate, melanoma, and SHN were the most common sites of second neoplasms. The most common pairing was breast with breast (31% synchronous), followed by the bladder/ureter with the prostate (72% synchronous), prostate with the colorectum, SHN with SHN, and SHN with lung. Five-year crude survival of patients with synchronous cancers (34%) was not significantly lower than that of patients with single neoplasms (39%). This population-based study indicates that about one in eight incident neoplasms in these mature registries are second neoplasms and almost 1/40 patients are diagnosed with synchronous primary cancers. These are related to shared genetic and environmental factors as well as diagnostic and therapeutic procedures. As cancer diagnosis and survival is likely to improve, the proportion of patients with multiple primary cancers will further increase in the future.
Taller populations are typically richer populations, and taller individuals live longer and earn more. In consequence, adult height has recently become a focus in understanding the relationship ...between health and wealth. We investigate the childhood determinants of population adult height, focusing on the respective roles of income and of disease. Across a range of European countries and the United States, we find a strong inverse relationship between postneonatal (ages 1 month to 1 year) mortality, interpreted as a measure of the disease and nutritional burden in childhood, and the mean height of those children as adults. Consistent with these findings, we develop a model of selection and stunting in which the early-life burden of undernutrition and disease not only is responsible for mortality in childhood but also leaves a residue of long-term health risks for survivors, risks that express themselves in adult height and in late-life disease. The model predicts that at sufficiently high mortality levels, selection can dominate scarring, leaving a taller population of survivors. We find evidence of this effect in the poorest and highest-mortality countries of the world, supplementing recent findings on the effects of the Great Chinese Famine.
Background The study of premature deaths in people with intellectual disability (ID) has become the focus of recent policy initiatives in England. This is the first UK population‐based study to ...explore cause‐specific mortality in adults with ID compared with the general population.
Methods Cause‐specific standardised mortality ratios (SMRs) and exact 95% confidence intervals were calculated by age and sex for adults with moderate to profound ID living in the unitary authorities of Leicester, Leicestershire and Rutland, UK, between 1993 and 2006. Causes of death were also studied to determine how often ID and associated conditions, such as Down syndrome, were mentioned.
Results A total of 503 (17% of population) adults with ID died during the 14‐year study period (30 144 person‐years). Relatively high cause‐specific mortality was seen for deaths caused by congenital abnormalities (SMR = 8560), diseases of the nervous system and sense organs (SMR = 1630), mental disorders (other than dementia) (SMR = 1141) and bronchopneumonia (SMR = 647). Excess deaths were also seen for diseases of the genitourinary system or digestive system, cerebrovascular disease, other respiratory infections, dementia (in men only), other circulatory system diseases (in women only) and accidental deaths (in women only). Two‐fifths (n = 204; 41%) of deaths recorded in adults with ID mentioned ID or an associated condition as a contributing cause of death.
Conclusions Strategies to reduce inequalities in people with ID need to focus on decreasing mortality from potentially preventable causes, such as respiratory infections, circulatory system diseases and accidental deaths. The lack of mention of ID on death certificates highlights the importance of effective record linkage and ID reporting in health and social care settings to facilitate the government's confidential inquiry into causes of death in this population.
Abstract Background Accelerated aging has been proposed as a mechanism explaining the increased prevalence of comorbid general medical illnesses in bipolar disorder. Aims To test the hypothesis that ...lost life years due to natural causes starts in early and mid-adulthood, supporting the hypothesis of accelerated aging. Methods Using individual data from nationwide registers of patient with a diagnosis of bipolar disorder we calculated remaining life expectancies before age 90 years for values of age 15, 25, 35…75 years among all individuals alive in year 2000. Further, we estimated the reduction in life expectancy due to natural causes (physical illnesses) and unnatural causes (suicide and accidents) in relation to age. Results A total of 22,635 patients with bipolar disorder were included in the study in addition to data from the entire Danish general population of 5.4 million people. At age 15 years, remaining life expectancy before age 90 years was decreased 12.7 and 8.9 life years, respectively, for men and women with bipolar disorder. For 15-year old boys with bipolar disorder, natural causes accounted for 58% of all lost life years and for 15-year old girls, natural causes accounted for 67% increasing to 74% and 80% for 45-year old men and women, respectively. Limitations Data concern patients who get contact to hospital psychiatry only. Conclusions Natural causes of death is the most prevalent reason for lost life years already from adolescence and increases substantially during early and mid-adulthood, in this way supporting the hypothesis of accelerated aging. Early intervention in bipolar disorder should not only focus on improving outcome of the bipolar disorder but also on decreasing the risk of comorbid general medical illnesses.
Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the ...leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups.
We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs.
Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.
PDF
