Smokeless tobacco use: a meta-analysis of risk and attributable mortality estimates for India

Background: Use of smokeless tobacco (SLT) is widely prevalent in India and Indian subcontinent. Cohort and case-control studies in India and elsewhere report excess mortality due to its use. Objective: The aim was to estimate the SLT use-attributable deaths in males and females, aged 35 years and older, in India. Materials And Methods: Prevalence of SLT use in persons aged 35 years and older was obtained from the Global Adult Tobacco Survey in India and population size and deaths in the relevant age-sex groups were obtained from UN estimates (2010 revision) for 2008. A meta-relative risk (RR) based population attributable fraction was used to estimate attributable deaths in persons aged 35 years and older. A random effects model was used in the meta-analysis on all-cause mortality from SLT use in India including four cohort and one case-control study. The studies included in the meta-analysis were adjusted for smoking, age and education. Results: The prevalence of SLT use in India was 25.2% for men and 24.5% for women aged 35 years and older. RRs for females and males were 1.34 (1.27-1.42) and 1.17 (1.05-1.42), respectively. The number of deaths attributable to SLT use in India is estimated to be 368127 (217,076 women and 151,051 men), with nearly three-fifth (60%) of these deaths occurring among women. Conclusion: SLT use caused over 350,000 deaths in India in 2010, and nearly three-fifth of SLT use-attributable deaths were among women in India. This calls for targeted public health intervention focusing on SLT products especially among women

Household, community, sub-national and country-level predictors of primary cooking fuel switching in nine countries from the PURE study

Introduction. Switchingfrom polluting (e.g. wood, crop waste, coal)to clean (e.g. gas, electricity) cooking fuels can reduce household air pollution exposures and climate-forcing emissions.While studies have evaluated specific interventions and assessed fuel-switching in repeated cross-sectional surveys, the role of different multilevel factors in household fuel switching, outside of interventions and across diverse community settings, is not well understood. Methods.We examined longitudinal survey data from 24 172 households in 177 rural communities across nine countries within the Prospective Urban and Rural Epidemiology study.We assessed household-level primary cooking fuel switching during a median of 10 years offollow up (∼2005–2015).We used hierarchical logistic regression models to examine the relative importance of household, community, sub-national and national-level factors contributing to primary fuel switching. Results. One-half of study households(12 369)reported changing their primary cookingfuels between baseline andfollow up surveys. Of these, 61% (7582) switchedfrom polluting (wood, dung, agricultural waste, charcoal, coal, kerosene)to clean (gas, electricity)fuels, 26% (3109)switched between different polluting fuels, 10% (1164)switched from clean to polluting fuels and 3% (522)switched between different clean fuels

Cancer mortality in India: a nationally representative survey.

BACKGROUND: The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001-03 in homes in small areas that were chosen to be representative of all the parts of India. METHODS: At least 130 trained physicians independently assigned causes to 122,429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. FINDINGS: 7137 of 122,429 study deaths were due to cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400 (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300 women). At 30-69 years, the three most common fatal cancers were oral (including lip and pharynx, 45,800 [22·9%]), stomach (25,200 [12·6%]), and lung (including trachea and larynx, 22,900 [11·4%]) in men, and cervical (33,400 [17·1%]), stomach (27,500 [14·1%]), and breast (19,900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84,000) of male and 18·3% (35,700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100,000 were similar in rural (men 95·6 [99% CI 89·6-101·7] and women 96·6 [90·7-102·6]) and urban areas (men 102·4 [92·7-112·1] and women 91·2 [81·9-100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4-115·7] vs most educated 45·7 [37·8-53·6]; women, illiterate 106·7 [99·9-113·6] vs most educated 43·4 [30·7-56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64-0·71] vs 340, 1·06 [1·05-1·08]). INTERPRETATION: Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. FUNDING: Bill & Melinda Gates Foundation and US National Institutes of Health

Wormwood Review Project

BACKGROUND: Extrapolation from studies in the 1980s suggests that smoking causes 25% of deaths among women and men 35 to 69 years of age in the United States. Nationally representative measurements of the current risks of smoking and the benefits of cessation at various ages are unavailable. METHODS: We obtained smoking and smoking-cessation histories from 113,752 women and 88,496 men 25 years of age or older who were interviewed between 1997 and 2004 in the U.S. National Health Interview Survey and related these data to the causes of deaths that occurred by December 31, 2006 (8236 deaths in women and 7479 in men). Hazard ratios for death among current smokers, as compared with those who had never smoked, were adjusted for age, educational level, adiposity, and alcohol consumption. RESULTS: For participants who were 25 to 79 years of age, the rate of death from any cause among current smokers was about three times that among those who had never smoked (hazard ratio for women, 3.0; 99% confidence interval [CI], 2.7 to 3.3; hazard ratio for men, 2.8; 99% CI, 2.4 to 3.1). Most of the excess mortality among smokers was due to neoplastic, vascular, respiratory, and other diseases that can be caused by smoking. The probability of surviving from 25 to 79 years of age was about twice as great in those who had never smoked as in current smokers (70% vs. 38% among women and 61% vs. 26% among men). Life expectancy was shortened by more than 10 years among the current smokers, as compared with those who had never smoked. Adults who had quit smoking at 25 to 34, 35 to 44, or 45 to 54 years of age gained about 10, 9, and 6 years of life, respectively, as compared with those who continued to smoke. CONCLUSIONS: Smokers lose at least one decade of life expectancy, as compared with those who have never smoked. Cessation before the age of 40 years reduces the risk of death associated with continued smoking by about 90%

Comparative effectiveness of transitional care services in patients discharged from the hospital with heart failure: a systematic review and network meta-analysis

Aims To compare the effectiveness of transitional care services in decreasing all-cause death and all-cause readmissions following hospitalization for heart failure (HF). Methods and results We searched PubMed, Embase, CINAHL, and Cochrane Clinical Trials Register for randomized controlled trials (RCTs) published in 2000-2015 that tested the efficacy of transitional care services in patients hospitalized for HF, provided >= 1month of follow-up, and reported all-cause mortality or all-cause readmissions. Our network meta-analysis included 53 RCTs (12 356 patients). Among services that significantly decreased all-cause mortality compared with usual care, nurse home visits were most effective [ranking P-score 0.6794; relative risk (RR) 0.78, 95% confidence intervals (CI) 0.62-0.98], followed by disease management clinics (DMCs) (ranking P-score 0.6368; RR 0.80, 95% CI 0.67-0.97). Among services that significantly decreased all-cause readmission, nurse home visits were most effective [ranking P-score 0.8365; incident rate ratio (IRR) 0.65, 95% CI 0.49-0.86], followed by nurse case management (NCM) (ranking P-score 0.6168; IRR 0.77, 95% CI 0.63-0.95), and DMCs (ranking P-score 0.5691; IRR 0.80, 95% CI 0.66-0.97). There was no significant difference in the comparative effectiveness of services that improved each outcome. Nurse home visits had the greatest pooled cost-savings (3810 USD, 95% CI 3682-3937), followed by NCM (3435 USD, 95% CI 3224-3645), and DMCs (245 USD, 95% CI -70 to 559). Telephone, telemonitoring, pharmacist, and education interventions did not significantly improve clinical outcomes. Conclusion Nurse home visits and DMCs decrease all-cause mortality after hospitalization for HF. Along with NCM, they also reduce all-cause readmissions, with no significant difference in comparative effectiveness. These services reduce healthcare system costs to varying degree

Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes

BACKGROUND Four glucagon-like peptide-1 (GLP-1) receptor agonists that are structurally similar to human GLP-1 have been shown to reduce the risk of adverse cardiovascular events among persons with type 2 diabetes. The effect of an exendin-based GLP-1 receptor agonist, efpeglenatide, on cardiovascular and renal outcomes in patients with type 2 diabetes who are also at high risk for adverse cardiovascular events is uncertain. METHODS In this randomized, placebo-controlled trial conducted at 344 sites across 28 countries, we evaluated efpeglenatide in participants with type 2 diabetes and either a history of cardiovascular disease or current kidney disease (defined as an estimated glomerular filtration rate of 25.0 to 59.9 ml per minute per 1.73 m2 of body-surface area) plus at least one other cardiovascular risk factor. Participants were randomly assigned in a 1:1:1 ratio to receive weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg or placebo. Randomization was stratified according to use of sodium-glucose cotransporter 2 inhibitors. The primary outcome was the first major adverse cardiovascular event (MACE; a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or undetermined causes). RESULTS A total of 4076 participants were enrolled; 2717 were assigned to receive efpeglenatide and 1359 to receive placebo. During a median follow-up of 1.81 years, an incident MACE occurred in 189 participants (7.0%) assigned to receive efpeglenatide (3.9 events per 100 person-years) and 125 participants (9.2%) assigned to receive placebo (5.3 events per 100 person-years) (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P<0.001 for noninferiority; P=0.007 for superiority). A composite renal outcome event (a decrease in kidney function or macroalbuminuria) occurred in 353 participants (13.0%) assigned to receive efpeglenatide and in 250 participants (18.4%) assigned to receive placebo (hazard ratio, 0.68; 95% CI, 0.57 to 0.79; P<0.001). Diarrhea, constipation, nausea, vomiting, or bloating occurred more frequently with efpeglenatide than with placebo. CONCLUSIONS In this trial involving participants with type 2 diabetes who had either a history of cardiovascular disease or current kidney disease plus at least one other cardiovascular risk factor, the risk of cardiovascular events was lower among those who received weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg than among those who received placebo

Exploring the relationship between efpeglenatide dose and cardiovascular outcomes in type 2 diabetes: insights from the AMPLITUDE-O trial

Background: In the AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes) cardiovascular outcomes trial, adding either 4 mg or 6 mg weekly of the glucagon-like peptide-1 receptor agonist efpeglenatide to usual care reduced major adverse cardiovascular events (MACE) in people with type 2 diabetes at high cardiovascular risk. Whether these benefits are dose related remains uncertain. Methods: Participants were randomly assigned in a 1:1:1 ratio to placebo, 4 mg or 6 mg of efpeglenatide. The effect of 6 mg versus placebo and of 4 mg versus placebo on MACE (a nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or unknown causes) and on all the secondary composite cardiovascular and kidney outcomes was assessed. A dose-response relationship was assessed using the χ2 statistic for trend. Results: During a median follow-up of 1.8 years, MACE occurred in 125 (9.2%) participants assigned to placebo, 84 (6.2%) participants assigned to 6 mg of efpeglenatide (hazard ratio [HR], 0.65 [95% CI, 0.5–0.86]; P=0.0027), and 105 (7.7%) assigned to 4 mg of efpeglenatide (HR, 0.82 [95% CI, 0.63–1.06]; P=0.14). Participants receiving high-dose efpeglenatide also experienced fewer secondary outcomes, including the composite of MACE, coronary revascularization, or hospitalization for unstable angina (HR, 0.73 for 6 mg, P=0.011; HR, 0.85 for 4 mg, P=0.17), a kidney composite outcome comprising sustained new macroalbuminuria, a ≥40% decline in estimated glomerular filtration rate or renal failure (HR, 0.63 for 6 mg, P<0.0001; HR, 0.73 for 4 mg, P=0.0009), MACE or any death (HR, 0.67 for 6 mg, P=0.0021; HR, 0.81 for 4 mg, P=0.08), a kidney function outcome comprising a sustained ≥40% decline in estimated glomerular filtration rate, renal failure, or death (HR, 0.61 for 6 mg, P=0.0072; HR, 0.97 for 4 mg, P=0.83), and the composite of MACE, any death, heart failure hospitalization, or the kidney function outcome (HR, 0.63 for 6 mg, P=0.0002; HR, 0.81 for 4 mg, P=0.067). A clear dose-response was noted for all primary and secondary outcomes (all P for trend <0.012). Conclusions: The graded salutary relationship between efpeglenatide dose and cardiovascular outcomes suggests that titrating efpeglenatide and potentially other glucagon-like peptide-1 receptor agonists to high doses may maximize their cardiovascular and renal benefits. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03496298

Efpeglenatide and clinical outcomes with and without concomitant sodium-glucose co-transporter-2 inhibition use in type 2 diabetes: exploratory analysis of the AMPLITUDE-O trial

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) both reduce cardiovascular (CV) events among patients with type 2 diabetes. However, no CV outcome trial has evaluated the long-term effects of their combined use. The AMPLITUDE-O trial reported that once weekly injections of the GLP-1 RA efpeglenatide (vs. placebo) reduced major adverse cardiovascular events (MACE); MACE, coronary revascularization or unstable angina hospitalization (expanded MACE); a renal composite outcome; and MACE or death in people with type 2 diabetes and CV and/or renal disease. The trial uniquely stratified randomization by baseline or anticipated use of SGLT2 inhibitors and included the highest prevalence at baseline (N=618, 15.2%) of SGLT2 inhibitor use among GLP-1 RA CV outcome trials to date. Its results were analyzed to estimate the combined effect of SGLT2 inhibitors and efpeglenatide on clinical outcomes. Methods: Cardiovascular and renal outcomes were analyzed using Cox proportional hazards models adjusted for region, SGLT2 inhibitor randomization strata, and the SGLT2 inhibitor-by-treatment interaction. Continuous variables were analyzed using a mixed-effects models for repeated measures that also included an interaction term. Results: The effect (hazard ratio [95% confidence interval]) of efpeglenatide versus placebo in the absence and presence of baseline SGLT2 inhibitors, respectively, on MACE (0.74 [0.58- 0.94] and 0.70 [0.37- 1.30]), expanded MACE (0.77 [0.62- 0.96] and 0.87 [0.51- 1.48]), renal composite (0.70 [0.59- 0.83] and 0.52 [0.33- 0.83]), and MACE or death (0.74 [0.59- 0.93] and 0.65 [0.36- 1.19]) did not differ by baseline SGLT2 inhibitor use (P for all interactions >0.2). Efpeglenatide's reduction of blood pressure, body weight, low density lipoprotein cholesterol and urinary albumin:creatinine ratio also appeared to be independent of concurrent SGLT2 inhibitor use (all interaction P ≥0.08). Finally, adverse events did not differ by baseline SGLT2 inhibitor use. Conclusions: The efficacy and safety of efpeglenatide appear independent of concurrent SGLT2 inhibitor use. These data support combined SGLT2 inhibitor and GLP-1 RA therapy in type 2 diabetes

Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes

Background: Four glucagon-like peptide-1 (GLP-1) receptor agonists that are structurally similar to human GLP-1 have been shown to reduce the risk of adverse cardiovascular events among persons with type 2 diabetes. The effect of an exendin-based GLP-1 receptor agonist, efpeglenatide, on cardiovascular and renal outcomes in patients with type 2 diabetes who are also at high risk for adverse cardiovascular events is uncertain. Methods: In this randomized, placebo-controlled trial conducted at 344 sites across 28 countries, we evaluated efpeglenatide in participants with type 2 diabetes and either a history of cardiovascular disease or current kidney disease (defined as an estimated glomerular filtration rate of 25.0 to 59.9 ml per minute per 1.73 m2 of body-surface area) plus at least one other cardiovascular risk factor. Participants were randomly assigned in a 1:1:1 ratio to receive weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg or placebo. Randomization was stratified according to use of sodium–glucose cotransporter 2 inhibitors. The primary outcome was the first major adverse cardiovascular event (MACE; a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or undetermined causes). Results: A total of 4076 participants were enrolled; 2717 were assigned to receive efpeglenatide and 1359 to receive placebo. During a median follow-up of 1.81 years, an incident MACE occurred in 189 participants (7.0%) assigned to receive efpeglenatide (3.9 events per 100 person-years) and 125 participants (9.2%) assigned to receive placebo (5.3 events per 100 person-years) (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P<0.001 for noninferiority; P=0.007 for superiority). A composite renal outcome event (a decrease in kidney function or macroalbuminuria) occurred in 353 participants (13.0%) assigned to receive efpeglenatide and in 250 participants (18.4%) assigned to receive placebo (hazard ratio, 0.68; 95% CI, 0.57 to 0.79; P<0.001). Diarrhea, constipation, nausea, vomiting, or bloating occurred more frequently with efpeglenatide than with placebo. Conclusions: In this trial involving participants with type 2 diabetes who had either a history of cardiovascular disease or current kidney disease plus at least one other cardiovascular risk factor, the risk of cardiovascular events was lower among those who received weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg than among those who received placebo. (Funded by Sanofi; AMPLITUDE-O ClinicalTrials.gov number, NCT03496298