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1. Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib

Author

Hamood Alqahtani, Alexey V. Danilov, Sheila Hoff, Daniel O. Persky, Adam Kittai, Sudhir Manda, Michael Y. Choi, Stephen M. Amrock, Xavier Rivera, Max J. Gordon, Spencer L. James, Michael C. Churnetski, Stephen E. Spurgeon, and Jonathon B. Cohen

Subjects
Oncology, Male, Cancer Research, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Chronic lymphocytic leukemia, Comorbidity, Kaplan-Meier Estimate, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Chemoimmunotherapy, Internal medicine, medicine, Electronic Health Records, Humans, Prospective cohort study, Aged, Aged, 80 and over, Proportional hazards model, business.industry, Adenine, Cancer, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Progression-Free Survival, Discontinuation, Pyrimidines, Treatment Outcome, Geriatric oncology, chemistry, 030220 oncology & carcinogenesis, Ibrutinib, Pyrazoles, Female, Immunotherapy, Neoplasm Recurrence, Local, business, 030215 immunology
Abstract

Background Most patients with chronic lymphocytic leukemia (CLL) present with multiple comorbidities. Although comorbidities negatively affect outcomes for patients treated with chemoimmunotherapy, their impact on patients who receive targeted therapies is unknown. Methods This multicenter, retrospective analysis evaluated the significance of comorbidities, as assessed by the Cumulative Illness Rating Scale (CIRS), among patients with CLL treated with ibrutinib. Results One hundred forty-five patients received ibrutinib (80% in a relapsed/refractory setting). A high burden of comorbidities (CIRS score ≥ 7) was associated with inferior median event-free survival (EFS; 24 vs 37 months; P = .003) and 2-year overall survival (OS; 79% vs 100%; P = .005). In an adjusted Cox model, both EFS and OS worsened with an incremental increase in the CIRS score. Furthermore, comorbidities were associated with an increased risk of ibrutinib dose reduction and therapy discontinuation. CIRS was predictive in both frontline and relapsed CLL, regardless of patient age. Conclusions Comorbidities portend a poor prognosis among patients with CLL treated with ibrutinib. Prospective studies are needed to optimize the treatment of patients with CLL who have comorbidities. Cancer 2018. © 2018 American Cancer Society.

Published
2018

2. Multiple biomarkers for mortality prediction in peripheral arterial disease

Author

Stephen M. Amrock and Michael Weitzman

Subjects
Male, Time Factors, Homocysteine, Arterial disease, Neutrophils, 030232 urology & nephrology, Kaplan-Meier Estimate, Disease, 030204 cardiovascular system & hematology, Bioinformatics, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Cause of Death, Lymphocytes, 030212 general & internal medicine, Aged, 80 and over, Hazard ratio, Middle Aged, Nutrition Surveys, Prognosis, Peripheral, C-Reactive Protein, Creatinine, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, National Health and Nutrition Examination Survey, Urinary system, 030209 endocrinology & metabolism, Risk Assessment, Decision Support Techniques, Peripheral Arterial Disease, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Linear regression, medicine, Albuminuria, Humans, Ankle Brachial Index, Lymphocyte Count, Aged, Proportional Hazards Models, business.industry, United States, Cross-Sectional Studies, chemistry, Surgery, business, Biomarkers
Abstract

Few studies have assessed which biomarkers influence mortality risk among those with peripheral arterial disease (PAD). We analyzed data from 556 individuals identified to have PAD (i.e. ankle–brachial index ⩽0.9) with available measurements of C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR), homocysteine, and the urinary albumin-to-creatinine ratio (UACR) in the 1999–2004 National Health and Nutrition Examination Survey. We investigated whether a combination of these biomarkers improved the prediction of all-cause and cardiovascular mortality beyond conventional risk factors. During follow-up (median, 8.1 years), 277 of 556 participants died; 63 deaths were attributed to cardiovascular disease. After adjusting for conventional risk factors, Cox proportional-hazards models showed the following to be most strongly associated with all-cause mortality (each is followed by the adjusted hazard ratio [HR] per 1 standard deviation increment in the log values): homocysteine (1.31), UACR (1.21), and NLR (1.20). UACR alone significantly predicted cardiovascular mortality (1.53). Persons in the highest quintile of multimarker scores derived from regression coefficients of significant biomarkers had elevated risks of all-cause mortality (adjusted HR, 2.45; 95% CI, 1.66–3.62; p for trend

Published
2016
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3. The State of US Health, 1990-2016 Burden of Diseases, Injuries, and Risk Factors Among US States

Author

Christopher Troeger, Scott D Glenn, Nancy Fullman, Michael H. Criqui, Benn Sartorius, Derrick Tsoi, Stein Emil Vollset, Andrea Werdecker, Danny V. Colombara, Eun-Kee Park, Harvey Whiteford, Mitch T Wallin, Ben Zipkin, Gregory R. Wagner, Jasvinder A. Singh, Amir Kasaeian, Talha Farid, Yohannes Kinfu, Tejas V. Patel, Janni Leung, George C Patton, Samir Soneji, Ben Anderson, Roman Topor-Madry, Maryam S. Farvid, Louisa Degenhardt, Jürgen Unützer, Paul S Briant, Stephen M. Amrock, Michelle Echko, Fiona J Charlson, Simon I. Hay, Janet L Leasher, Alexis J. Handal, Rasmus Havmoller, Mojde Mirarefin, Yuichiro Yano, Philimon Gona, Spencer L. James, Abdur Rahman Khan, Jacob E. Sunshine, Leslie T. Cooper, Patrick Liu, Brian J. Biroscak, Honglei Chen, H. Dean Hosgood, Peter J. Hotez, Sudha Jayaraman, Damian Santomauro, Leah E. Cahill, Hsiang Huang, Jean B. Nachega, Guoqing Hu, Bryan L. Sykes, Kaja Abbas, Michelle L. Bell, E. Ray Dorsey, Michael Brauer, Jagdish Khubchandani, Hmwe H Kyu, Kanyin Ong, Juan Sanabria, Mark Moses, Simon Yadgir, David C. Schwebel, Tahiya Alam, Jost B. Jonas, Holly E. Erskine, Zulfiqar A Bhutta, Christopher J L Murray, Amit Kandel, Max Griswold, Alexander Lee, Kristopher J. Krohn, Alireza Ahmadi, Theo Vos, Mustafa Z. Younis, Eyal Oren, Ricky Leung, Tahvi Frank, Elaine O. Nsoesie, Leslie Cornaby, Dariush Mozaffarian, Mostafa Qorbani, Vegard Skirbekk, Saverio Stranges, Erin C Mullany, Minh Nguyen, Helen E Olsen, Austin Carter, Tsegaye Telwelde Gebrehiwot, Ali H. Mokdad, Colin D. Rehm, Stan Biryukov, Daniel Kim, Ziyad Al-Aly, Ruth W Kimokoti, Eric L. Ding, Ira Martopullo, Dhaval Kolte, Alem Mehari, Alize J. Ferrari, Masako Horino, Joshua A. Salomon, Nicholas J K Breitborde, Gregory A. Roth, Emma Nichols, Berrin Serdar, Karen M. Tabb, Till Bärnighausen, Katherine Ballestros, Christina Fitzmaurice, Ted R. Miller, Shahrzad Bazargan-Hejazi, and Tomi Akinyemiju

Subjects
Adult, Male, medicine.medical_specialty, Poison control, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Cost of Illness, Risk Factors, Injury prevention, Epidemiology, Disability-adjusted life year, Medicine, Humans, Disabled Persons, 030212 general & internal medicine, Mortality, business.industry, Mortality, Premature, Mortality rate, General Medicine, Health Status Disparities, Middle Aged, United States, Quality-adjusted life year, Years of potential life lost, Life expectancy, Wounds and Injuries, Female, Quality-Adjusted Life Years, Morbidity, business, Demography
Abstract

Introduction Several studies have measured health outcomes in the United States, but none have provided a comprehensive assessment of patterns of health by state. Objective To use the results of the Global Burden of Disease Study (GBD) to report trends in the burden of diseases, injuries, and risk factors at the state level from 1990 to 2016. Design and Setting A systematic analysis of published studies and available data sources estimates the burden of disease by age, sex, geography, and year. Main Outcomes and Measures Prevalence, incidence, mortality, life expectancy, healthy life expectancy (HALE), years of life lost (YLLs) due to premature mortality, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 333 causes and 84 risk factors with 95% uncertainty intervals (UIs) were computed. Results Between 1990 and 2016, overall death rates in the United States declined from 745.2 (95%UI, 740.6 to 749.8) per 100 000 persons to 578.0 (95%UI, 569.4 to 587.1) per 100 000 persons. The probability of death among adults aged 20 to 55 years declined in 31 states and Washington, DC from 1990 to 2016. In 2016, Hawaii had the highest life expectancy at birth (81.3 years) and Mississippi had the lowest (74.7 years), a 6.6-year difference. Minnesota had the highest HALE at birth (70.3 years), andWest Virginia had the lowest (63.8 years), a 6.5-year difference. The leading causes of DALYs in the United States for 1990 and 2016 were ischemic heart disease and lung cancer, while the third leading cause in 1990 was low back pain, and the third leading cause in 2016 was chronic obstructive pulmonary disease. Opioid use disorders moved from the 11th leading cause of DALYs in 1990 to the 7th leading cause in 2016, representing a 74.5%(95%UI, 42.8%to 93.9%) change. In 2016, each of the following 6 risks individually accounted for more than 5%of risk-attributable DALYs: tobacco consumption, high body mass index (BMI), poor diet, alcohol and drug use, high fasting plasma glucose, and high blood pressure. Across all US states, the top risk factors in terms of attributable DALYs were due to 1 of the 3 following causes: tobacco consumption (32 states), high BMI (10 states), or alcohol and drug use (8 states). Conclusions and Relevance There are wide differences in the burden of disease at the state level. Specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention. These data can be used to inform national health priorities for research, clinical care, and policy.

Published
2018

4. Health disparities among adult patients with a phenotypic diagnosis of familial hypercholesterolemia in the CASCADE-FH™ patient registry

Author

Michael D. Shapiro, Catherine D. Ahmed, Rolf Andersen, Dannielle Duffy, Daniel J. Rader, James A. Underberg, Thomas Knickelbine, Robert Fishberg, John Larry, Linda C. Hemphill, Seth S. Martin, Zahid Ahmad, Paul D. Thompson, Matthew T. Roe, Iris Kindt, Katherine Wilemon, Michael F. Murray, Karol E. Watson, Joanna Mitri, Stephen M. Amrock, MacRae F. Linton, Christie M. Ballantyne, Patrick M. Moriarty, Peter Shrader, P. Barton Duell, Iftikhar J. Kullo, John R. Guyton, Seth J. Baum, Joshua W. Knowles, Emily C. O'Brien, and Dervilla McCann

Subjects
Adult, Male, medicine.medical_specialty, Statin, medicine.drug_class, Population, Ethnic group, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Logistic regression, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Risk Factors, Internal medicine, parasitic diseases, medicine, Ethnicity, Odds Ratio, Humans, Multicenter Studies as Topic, 030212 general & internal medicine, Prospective Studies, Registries, Healthcare Disparities, education, Aged, Retrospective Studies, education.field_of_study, Patient registry, Asian, business.industry, PCSK9, Cholesterol, HDL, Cholesterol, LDL, Health Status Disparities, Middle Aged, medicine.disease, Health equity, Black or African American, Phenotype, Cardiovascular Diseases, Physical therapy, lipids (amino acids, peptides, and proteins), Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business
Abstract

Most familial hypercholesterolemia (FH) patients remain undertreated, and it is unclear what role health disparities may play for FH patients in the US. We sought to describe sex and racial/ethnic disparities in a national registry of US FH patients.We analyzed data from 3167 adults enrolled in the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE-FH) registry. Logistic regression was used to evaluate for disparities in LDL-C goals and statin use, with adjustments for covariates including age, cardiovascular risk factors, and statin intolerance.In adjusted analyses, women were less likely than men to achieve treated LDL-C of100 mg/dL (OR 0.68, 95% CI, 0.57-0.82) or ≥50% reduction from pretreatment LDL-C (OR 0.79, 95% CI, 0.65-0.96). Women were less likely than men to receive statin therapy (OR, 0.60, 95% CI, 0.50-0.73) and less likely to receive a high-intensity statin (OR, 0.60, 95% CI, 0.49-0.72). LDL-C goal achievement also varied by race/ethnicity: compared with whites, Asians and blacks were less likely to achieve LDL-C levels100 mg/dL (Asians, OR, 0.47, 95% CI, 0.24-0.94; blacks, OR, 0.49, 95% CI, 0.32-0.74) or ≥50% reduction from pretreatment LDL-C (Asians, OR 0.56, 95% CI, 0.32-0.98; blacks, OR 0.62, 95% CI, 0.43-0.90).In a contemporary US population of FH patients, we identified differences in LDL-C goal attainment and statin usage after stratifying the population by either sex or race/ethnicity. Our findings suggest that health disparities contribute to the undertreatment of US FH patients. Increased efforts are warranted to raise awareness of these disparities.

Published
2017

5. Risk Factors for Mortality Among Individuals With Peripheral Arterial Disease

Author

Cherrie Z. Abraham, Stephen M. Amrock, Pamela B. Morris, Michael D. Shapiro, and Enjae Jung

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, National Health and Nutrition Examination Survey, Cross-sectional study, Arterial disease, Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, Peripheral Arterial Disease, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Internal medicine, Cause of Death, medicine, Humans, Ankle Brachial Index, 030212 general & internal medicine, Aged, Proportional hazards model, business.industry, Mortality rate, Hazard ratio, Ultrasonography, Doppler, Middle Aged, Nutrition Surveys, Prognosis, Confidence interval, United States, Peripheral, Survival Rate, Cross-Sectional Studies, Predictive value of tests, Cardiology, Surgery, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Morbidity and mortality from peripheral arterial disease (PAD) continues to increase. Traditional cardiovascular risk factors are implicated in the development of PAD, yet the extent to which those risk factors correlate with mortality in such patients remains insufficiently assessed. Using data from the 1999 to 2004 National Health and Nutrition Examination Survey, Cox proportional hazards models were used to examine the association of cardiovascular risk factors and all-cause and cardiovascular mortality. A total of 647 individuals ≥40 years old with PAD (i.e., ankle-brachial index [ABI] ≤ 0.9) were followed for a median of 7.8 years. There were 336 deaths, of which 98 were attributable to cardiovascular disease. Compared with never smokers, current (hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.62 to 3.71) and former (HR 1.62, 95% CI 1.14 to 2.29) smokers with PAD had higher rates of death. Moderate or vigorous physical activity of ≥10 minutes monthly was associated with lower death rates (HR 0.63, 95% CI 0.44 to 0.91). Also associated with increased rates of cardiovascular death were an ABI of0.5 (HR 2.56, 95% CI 1.28 to 5.15, compared with those with an ABI of 0.7 to 0.9) and diabetes mellitus (HR 2.50, 95% CI 1.33 to 4.73). Neither C-reactive protein nor body mass index was associated with mortality. In conclusion, tobacco use increased the risk of all-cause and cardiovascular death, whereas physical activity was associated with a decreased mortality risk. A low ABI and diabetes were also predictive of cardiovascular death.

Published
2017

6. Health effects of overweight and obesity in 195 countries over 25 years

Author

Yun Jin Kim, Kalkidan Hassen Abate, Hirbos Shore Roba, Rafael Lozano, Lalit Dandona, Xiaofeng Liang, Azeem Majeed, Stephen M. Amrock, Yousef Khader, Derrick A Bennett, Theo Vos, Stephen T. McGarvey, Carla Makhlouf Obermeyer, Johan Ärnlöv, Liliana G Ciobanu, Diego Augusto Santos Silva, Rajaa Al-Raddadi, Tommi Vasankari, Tsegaye Tewelde Gebrehiwot, Samath D Dharmaratne, Sibhatu Biadgilign, Azmeraw T. Amare, Erkin M. Mirrakhimov, Rakhi Dandona, Philimon Gona, Jonathan I. Silverberg, Andre Pascal Kengne, Amir Kasaeian, Sadaf G. Sepanlou, Colm McAlinden, Stefanos Tyrovolas, Ivy Shiue, Saverio Stranges, Moretza Shamsizadeh, Kelly Cercy, Nima Hafezi-Nejad, Alireza Esteghamati, Patrick Liu, Maziar Moradi-Lakeh, Zerihun Menlkalew Zenebe, Saeid Safiri, Marissa B Reitsma, Abdullah Sulieman Terkawi, Jean Jacques Noubiap, Mall Leinsalu, Mohammad H. Forouzanfar, Jarnail Singh Thakur, Kingsley N. Ukwaja, Ismael R. Campos-Nonato, Barthelemy Kuate Defo, Rajesh Kumar Rai, Ala'a Alkerwi, Nikolas Reinig, Joshua Wesana, Christopher J L Murray, Benn Sartorius, Adeladza Kofi Amegah, Alan D. Lopez, João C. Fernandes, Elisabete Weiderpass, Kokeb T. Hadush, Aleksandra Barac, Amitava Banerjee, Juan Sanabria, Leslie Cornaby, Ritul Kamal, Felix Akpojene Ogbo, Joseph Salama, Yuichiro Yano, Gerald Yonga, Maria Inês Schmidt, Simon I. Hay, Solomon Abrha Damtew, Deborah Carvalho Malta, Haftay Berhane Mezgebe, Addisu Shunu Beyene, Gert B. M. Mensink, Audra L Gold, Dube Jara Boneya, George C Patton, Mayowa O. Owolabi, Mohsen Naghavi, Estifanos Baye, Chhabi Lal Ranabhat, Laurie B. Marczak, Patrick J Sur, Zoubida Zaidi, Stein Emil Vollset, Andrea Werdecker, Olalekan A. Uthman, Reza Malekzadeh, Kara Estep, Alexander Lee, Jasvinder A. Singh, Masako Horino, Chandrasekharan Nair Kesavachandran, Cristiana Abbafati, Vasiliy Victorovich Vlassov, Balewgizie Sileshi Tegegne, Ulrich O Mueller, Min Jeong Shin, Farhad Islami, Ben Zipkin, Srinivasa Vittal Katikireddi, Ali H. Mokdad, Soumya Swaminathan, Monika Sawhney, Mostafa Qorbani, Marcello Tonelli, Juan Jesus Carrero, Jagdish Khubchandani, Pedro Cecilio, Valery L. Feigin, Thomas Fürst, Bruce Bartholow Duncan, Joshua A. Salomon, Mohsen Mazidi, Tiffany Ku, Ziad Al-Aly, Alemayehu Amberbir, Itamar S. Santos, Soewarta Kosen, Atsushi Goto, Ronny Westerman, Anwar Rafay, Desalegn Tadese Mengistu, Stephen S Lim, Espen Bjertness, Tesfa Dejenie Habtewold, Muktar Beshir Ahmed, Naohiro Yonemoto, Hamid Asayesh, Young-Ho Khang, Rafael Tabarés-Seisdedos, Ashkan Afshin, Heidi J. Larson, Farshad Pourmalek, Sara Sheikhbahaei, Josef Schmidhuber, Yohannes Kinfu, Roman Topor-Madry, Babak Eshrati, Aletta E. Schutte, Rahman Shiri, Masoud Vaezghasemi, Ranjit Mohan Anjana, Erfan Amini, Stan Biryukov, Fentaw Tadese, George A. Mensah, Anil Kumar, Daniel Kim, Bemnet Amare Tedla, Afshin, Ashkan, Forouzanfar, Mohammad H, Reitsma, Marissa B, Sur, Patrick, Ciobanu, Liliana G, Murray, Christopher JL, and Veritati - Repositório Institucional da Universidade Católica Portuguesa

Subjects
Male, Gerontology, Pediatric Obesity, obesity, VDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, global health, Disease, Overweight, Global Health, VDP::Social science: 200::Demography: 300, DISEASE, VDP::Medical disciplines: 700::Health sciences: 800::Nutrition: 811, Body Mass Index, 0302 clinical medicine, RA0421, Pandemic, Prevalence, adults, Global health, 030212 general & internal medicine, Child, humans, ALL-CAUSE MORTALITY, child, adult, 1. No poverty, pediatric obesity/epidemiology, 11 Medical And Health Sciences, General Medicine, CANCER, 3. Good health, female, VDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803, Cardiovascular Diseases, Cohort, Female, medicine.symptom, Life Sciences & Biomedicine, obesitat, Research Article, Adult, prevalence, overweight/complications/epidemiology, WEIGHT-LOSS, 030209 endocrinology & metabolism, KNEE OSTEOARTHRITIS, VDP::Samfunnsvitenskap: 200::Demografi: 300, VDP::Medisinske Fag: 700::Helsefag: 800::Ernæring: 811, 03 medical and health sciences, cardiovascular diseases/complications/mortality, Medicine, General & Internal, children, male, General & Internal Medicine, Environmental health, medicine, Humans, overweight, COHORT, Obesity, Disease burden, METAANALYSIS, Science & Technology, GBD 2015 Obesity Collaborators, business.industry, ADULTS, medicine.disease, PREVENTION, BODY-MASS INDEX, Cross-Sectional Studies, business, Body mass index, obesity/complications/*epidemiology
Abstract

Source at: http://doi.org/10.1056/NEJMoa1614362 Background: Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain. Methods: We analyzed data from 68.5 million persons to assess the trends in the prevalence of overweight and obesity among children and adults between 1980 and 2015. Using the Global Burden of Disease study data and methods, we also quantified the burden of disease related to high body-mass index (BMI), according to age, sex, cause, and BMI in 195 countries between 1990 and 2015. Restults: In 2015, a total of 107.7 million children and 603.7 million adults were obese. Since 1980, the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most other countries. Although the prevalence of obesity among children has been lower than that among adults, the rate of increase in childhood obesity in many countries has been greater than the rate of increase in adult obesity. High BMI accounted for 4.0 million deaths globally, nearly 40% of which occurred in persons who were not obese. More than two thirds of deaths related to high BMI were due to cardiovascular disease. The disease burden related to high BMI has increased since 1990; however, the rate of this increase has been attenuated owing to decreases in underlying rates of death from cardiovascular disease. Conclusions: The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence-based interventions to address this problem.

Published
2017

7. Perceptions of e-Cigarettes and Noncigarette Tobacco Products Among US Youth

Author

Lily Lee, Michael Weitzman, and Stephen M. Amrock

Subjects
Male, Adolescent, media_common.quotation_subject, Electronic Nicotine Delivery Systems, Article, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, 030225 pediatrics, Environmental health, Perception, Medicine, Humans, 030212 general & internal medicine, media_common, Perceived safety, Tobacco harm reduction, business.industry, Addiction, Racial Groups, Tobacco Products, Health Surveys, United States, Harm, Smokeless tobacco, Pediatrics, Perinatology and Child Health, Female, business, Attitude to Health, Tobacco product
Abstract

BACKGROUND: Electronic cigarettes (e-cigarettes) are now the most commonly used tobacco product among US youth. The extent to which perceptions of e-cigarettes’ harm and addictiveness differ from those of other products remains unknown, as does whether these perceptions have changed over time. METHODS: Data from the 2012 and 2014 National Youth Tobacco Survey, a repeated cross-sectional survey of grade 6 to 12 students, were used. Cross-tabulations and logistic regression models were used to describe correlates of perceptions of harm and addictiveness of e-cigarettes, cigars, and smokeless tobacco compared with cigarettes. Trends in perceptions of e-cigarettes’ harm among different demographic groups were also assessed. RESULTS: In 2014, 73.0% believed that e-cigarettes were less harmful than cigarettes, compared with 20.2% for smokeless tobacco and 25.8% for cigars. By comparison, 47.1% believed that e-cigarettes were less addictive than cigarettes, compared with only 14.0% for smokeless tobacco and 31.5% for cigars. Use of each product was associated with a perception of decreased harm and addictiveness in adjusted analyses, as was being male, being a non-Hispanic white, and residing with a household member who used that product. Between 2012 and 2014, increasing numbers of US youth thought they were able to assess the relative harm of e-cigarettes and increasingly believed that e-cigarettes are less harmful than cigarettes. CONCLUSIONS: Most US youth view e-cigarettes as less harmful and addictive than cigarettes. Far fewer think similarly about cigars and smokeless tobacco. Increases in e-cigarettes’ perceived safety mirrors rapid increases observed in their use. Perceived safety correlates with use of each tobacco product.

Published
2016

8. Passive and Active Tobacco Exposure and Children’s Lipid Profiles

Author

Stephen M. Amrock, Joseph Zakhar, and Michael Weitzman

Subjects
Adult, Male, medicine.medical_specialty, Passive smoking, National Health and Nutrition Examination Survey, Adolescent, Physiology, Blood lipids, medicine.disease_cause, Systemic inflammation, Tobacco smoke, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, 030225 pediatrics, Internal medicine, medicine, Humans, 030212 general & internal medicine, Young adult, Child, Smoke, business.industry, Brief Report, Smoking, Public Health, Environmental and Occupational Health, Nutrition Surveys, Lipids, United States, Endocrinology, chemistry, Female, Tobacco Smoke Pollution, medicine.symptom, business, Cotinine
Abstract

INTRODUCTION: Despite reductions in smoking rates, exposure to cigarette smoke remains common among US children and adolescents. In adults, active smoking and secondhand smoke (SHS) exposure have been linked to adverse changes in lipid profiles and increases in inflammatory markers. Evidence that such changes are present before adulthood remains limited, and the extent to which active smoking and SHS exposure affect these cardiovascular measures in children has not been thoroughly assessed. METHODS: We employed data from 2008 individuals aged 12-19 years from the 2005-2010 National Health and Nutrition Examination Survey. Comparisons of the lipid and inflammatory marker levels among active smokers, those exposed to SHS (as determined by serum cotinine levels), and those unexposed to tobacco smoke were made using linear regression with multiple propensity score adjustment. RESULTS: Compared to unexposed children, lipid and inflammatory marker profiles did not differ among those exposed to SHS exposure. Among active smokers, differences compared to unexposed children were observed in triglyceride levels ( β=8.5 mg/dL, P = .01), the ratio of triglycerides to high-density lipoprotein ( β=0.2, P = .045), and low-density lipoprotein cholesterol ( β-4.1 mg/dL , P = .03), though these did not reach levels of confirmatory statistical significance. CONCLUSIONS: After accounting for sociodemographic characteristics and medical comorbidities, serum lipids and markers of systemic inflammation were not associated with SHS exposure. Tobacco smoke exposure in children may require longer durations of compounded effect before serum lipid abnormalities are detected. IMPLICATIONS: This paper adds detail to the study of secondhand smoke's effects on lipid profiles of children and adolescents. Prior research on this topic for these age groups has been limited, and this study provides national, cross-sectional data to show that both secondhand smoke and active smoking in childhood and adolescence is not associated with changes in lipid profiles or markers of inflammation. Tobacco smoke exposure may require longer durations of compounded effect before abnormalities are detected.

Published
2016
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9. Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Author

Vasiliki Stathopoulou, Kiran Thapa, Vesper Hichilombwe Chisumpa, Azeem Majeed, Hjalte Holm Andersen, Devasahayam J. Christopher, Alireza Mohammadi, John J. McGrath, Konstantin Kazanjan, Naohiro Yonemoto, Guoqing Hu, Yousef Khader, Suzanne Barker-Collo, Frida Namnyak Ngalesoni, Jennifer O Lam, Laetitia Huiart, Xiaofeng Liang, Amanuel Tesfay Gebremedhin, Lalit Dandona, Felix Masiye, Joseph R Fitchett, Derrick A Bennett, Rosana E. Norman, Theo Vos, Tuomo J. Meretoja, Rahman Shiri, Melvin Barrientos Marzan, Charles R. Newton, Kelly Cercy, Masoud Vaezghasemi, Elena Alvarez Martin, Christopher Troeger, Ismael R. Campos-Nonato, Amany H Refaat, Ruben Castro, Amiran Gamkrelidze, Michael R. Phillips, Samath D Dharmaratne, Reed J D Sorensen, Roderick J. Hay, Johan Ärnlöv, Ivo Rakovac, Alexandra Brazinova, Nancy Fullman, Sara Sheikhbahaei, Liliana G Ciobanu, Nader Jahanmehr, Yuming Guo, Luigi Naldi, Rana Jawad Asghar, Tsegaye Tewelde Gebrehiwot, Corine Karema, Biju Abraham, Rynaz H S Rabiee, Emerito Jose A. Faraon, Philimon Gona, Jonathan I. Silverberg, Alexandria Brown, Kovin Naidoo, Suleman Atique, Yun Jin Kim, Benn Sartorius, Hwashin Hyun Shin, George Mugambage Ruhago, Adugnaw Berhane, Tesfaye Tekle, Abdur Rahman Khan, Vipin Gupta, Nima Hafezi-Nejad, Héctor Gómez-Dantés, Jun She, Ted R. Miller, Tolesa Bekele, Yohannes Kinfu, Srinivas Murthy, Alaa Badawi, Mahfuzar Rahman, Raghib Ali, Robert G. Weintraub, Nicholas Steel, Khalid A Altirkawi, Muhammad Imran Nisar, Man Mohan Mehndiratta, Thomas N. 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Devina, Nangia, Vinay, Neupane, Suba, Newton, Charles R, Newton, John N, Ng, Marie, Ngalesoni, Frida Namnyak, Nguhiu, Peter, Nguyen, Quyen Le, Nisar, Muhammad Imran, Pete, Patrick Martial Nkamedjie, Norheim, Ole F, Norman, Rosana E, Ogbo, Felix Akpojene, Oh, In-Hwan, Ojelabi, Foluke Adetola, Olivares, Pedro R, Olusanya, Bolajoko Olubukunola, Olusanya, Jacob Olusegun, Oren, Eyal, Ota, Erika, Pa, Mahesh, Park, Eun-Kee, Park, Hye-Youn, Parsaeian, Mahboubeh, Caicedo, Angel J Paternina, Patten, Scott B, Pedro, João Mário, Pereira, David M, Perico, Norberto, Pesudovs, Konrad, Petzold, Max, Phillips, Michael Robert, Pillay, Julian David, Pishgar, Farhad, Polinder, Suzanne, Pope, Daniel, Popova, Svetlana, Pourmalek, Farshad, Qorbani, Mostafa, Rabiee, Rynaz H S, Rafay, Anwar, Rahimi-Movaghar, Vafa, Rahman, Mahfuzar, Rahman, Mohammad Hifz Ur, Rahman, Sajjad Ur, Rai, Rajesh Kumar, Raju, Murugesan, Ram, Usha, Rana, Saleem M, Ranabhat, Chhabi Lal, Rao, Puja, Refaat, Amany H, Remuzzi, Giuseppe, 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Chandrashekhar T, Stathopoulou, Vasiliki, Steel, Nichola, Stroumpoulis, Konstantino, Sturua, Lela, Sunguya, Bruno F, Swaminathan, Soumya, Sykes, Bryan L, Szoeke, Cassandra E I, Tabarés-Seisdedos, Rafael, Tavakkoli, Mohammad, Taye, Bineyam, Tedla, Bemnet Amare, Tefera, Worku Mekonnen, Tekle, Tesfaye, Shifa, Girma Temam, Terkawi, Abdullah Sulieman, Tesfay, Fisaha Haile, Tessema, Gizachew Assefa, Thapa, Kiran, Thomson, Alan J, Thorne-Lyman, Andrew L, Tobe-Gai, Ruoyan, Tonelli, Marcello, Topor-Madry, Roman, Topouzis, Foti, Tran, Bach Xuan, Troeger, Christopher, Truelsen, Thoma, Dimbuene, Zacharie Tsala, Tura, Abera Kenay, Tyrovolas, Stefano, Ukwaja, Kingsley N, Uneke, Chigozie Jesse, Uthman, Olalekan A, Vaezghasemi, Masoud, Vasankari, Tommi, Vasconcelos, Ana Maria Nogale, Venketasubramanian, Narayanaswamy, Verma, Raj Kumar, Violante, Francesco S, Vladimirov, Sergey K, Vlassov, Vasiliy Victorovich, Vollset, Stein Emil, Wang, Linhong, Wang, Yanping, Weichenthal, Scott, Weiderpass, Elisabete, 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Subjects
Pediatrics, Nutrition and Disease, Global Health, Communicable Disease, 0302 clinical medicine, Voeding en Ziekte, Infant Mortality, Compensation law of mortality, Global health, Medicine, LIFE EXPECTANCY, 030212 general & internal medicine, DEVELOPING-COUNTRIES, 10. No inequality, Medicine(all), NEWBORN BABIES, Medicine (all), Mortality rate, 1. No poverty, DEATH, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, 11 Medical And Health Sciences, Stillbirth, 3. Good health, Child Mortality, SURVIVAL, CHILD-MORTALITY, HEALTH, Life Sciences & Biomedicine, DEVELOPMENT GOAL 4, Human, INTERVENTIONS, medicine.medical_specialty, RJ, INTEGRATED APPROACH, Developing country, Communicable Diseases, neonatal, 03 medical and health sciences, Medicine, General & Internal, 030225 pediatrics, General & Internal Medicine, Life Science, Humans, Global Burden of Disease Study, VLAG, Estimation, Science & Technology, business.industry, Klinisk medicin, Infant, GBD 2015 Child Mortality Collaborators, Infant mortality, Malaria, Child mortality, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Life expectancy, Clinical Medicine, RG, business, Demography
Abstract

BACKGROUND: Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, financial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time. METHODS: Drawing from analytical approaches developed and refined in previous iterations of the GBD study, we generated updated estimates of child mortality by age group (neonatal, post-neonatal, ages 1-4 years, and under 5) for 195 countries and territories and selected subnational geographies, from 1980-2015. We also estimated numbers and rates of stillbirths for these geographies and years. Gaussian process regression with data source adjustments for sampling and non-sampling bias was applied to synthesise input data for under-5 mortality for each geography. Age-specific mortality estimates were generated through a two-stage age-sex splitting process, and stillbirth estimates were produced with a mixed-effects model, which accounted for variable stillbirth definitions and data source-specific biases. For GBD 2015, we did a series of novel analyses to systematically quantify the drivers of trends in child mortality across geographies. First, we assessed observed and expected levels and annualised rates of decrease for under-5 mortality and stillbirths as they related to the Soci-demographic Index (SDI). Second, we examined the ratio of recorded and expected levels of child mortality, on the basis of SDI, across geographies, as well as differences in recorded and expected annualised rates of change for under-5 mortality. Third, we analysed levels and cause compositions of under-5 mortality, across time and geographies, as they related to rising SDI. Finally, we decomposed the changes in under-5 mortality to changes in SDI at the global level, as well as changes in leading causes of under-5 deaths for countries and territories. We documented each step of the GBD 2015 child mortality estimation process, as well as data sources, in accordance with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). FINDINGS: Globally, 5·8 million (95% uncertainty interval [UI] 5·7-6·0) children younger than 5 years died in 2015, representing a 52·0% (95% UI 50·7-53·3) decrease in the number of under-5 deaths since 1990. Neonatal deaths and stillbirths fell at a slower pace since 1990, decreasing by 42·4% (41·3-43·6) to 2·6 million (2·6-2·7) neonatal deaths and 47·0% (35·1-57·0) to 2·1 million (1·8-2·5) stillbirths in 2015. Between 1990 and 2015, global under-5 mortality decreased at an annualised rate of decrease of 3·0% (2·6-3·3), falling short of the 4·4% annualised rate of decrease required to achieve MDG4. During this time, 58 countries met or exceeded the pace of progress required to meet MDG4. Between 2000, the year MDG4 was formally enacted, and 2015, 28 additional countries that did not achieve the 4·4% rate of decrease from 1990 met the MDG4 pace of decrease. However, absolute levels of under-5 mortality remained high in many countries, with 11 countries still recording rates exceeding 100 per 1000 livebirths in 2015. Marked decreases in under-5 deaths due to a number of communicable diseases, including lower respiratory infections, diarrhoeal diseases, measles, and malaria, accounted for much of the progress in lowering overall under-5 mortality in low-income countries. Compared with gains achieved for infectious diseases and nutritional deficiencies, the persisting toll of neonatal conditions and congenital anomalies on child survival became evident, especially in low-income and low-middle-income countries. We found sizeable heterogeneities in comparing observed and expected rates of under-5 mortality, as well as differences in observed and expected rates of change for under-5 mortality. At the global level, we recorded a divergence in observed and expected levels of under-5 mortality starting in 2000, with the observed trend falling much faster than what was expected based on SDI through 2015. Between 2000 and 2015, the world recorded 10·3 million fewer under-5 deaths than expected on the basis of improving SDI alone. INTERPRETATION: Gains in child survival have been large, widespread, and in many places in the world, faster than what was anticipated based on improving levels of development. Yet some countries, particularly in sub-Saharan Africa, still had high rates of under-5 mortality in 2015. Unless these countries are able to accelerate reductions in child deaths at an extraordinary pace, their achievement of proposed SDG targets is unlikely. Improving the evidence base on drivers that might hasten the pace of progress for child survival, ranging from cost-effective intervention packages to innovative financing mechanisms, is vital to charting the pathways for ultimately ending preventable child deaths by 2030. FUNDING: Bill & Melinda Gates Foundation. Erratum: Department of Error, The Lancet,Volume 389, Issue 10064, 2017, Page e1. DOI: 10.1016/S0140-6736(16)32608-3

Published
2016
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10. Medical Comorbidities Assessed By CIRS Negatively Impact Survival in the Era of Targeted Therapies in CLL: A Multicenter Retrospective Analysis

Author

Daniel O. Persky, Sudhir Manda, Alexey V. Danilov, Stephen M. Amrock, Xavier Rivera, Max J. Gordon, Spencer L. James, and Stephen E. Spurgeon

Subjects
Univariate analysis, medicine.medical_specialty, Performance status, business.industry, Proportional hazards model, Immunology, Organ dysfunction, Cell Biology, Hematology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, 030220 oncology & carcinogenesis, Ibrutinib, Internal medicine, medicine, Progression-free survival, medicine.symptom, Prospective cohort study, business, Survival analysis
Abstract

Introduction: The majority of patients with chronic lymphocytic leukemia (CLL) present with comorbidities, commensurate with the median age at diagnosis of 71 years. The Cumulative Illness Rating Scale (CIRS) is a widely used index which has been incorporated into clinical research in CLL. CIRS consists of 14 categories related to different body systems and scores the severity of each condition from 0-4. We have previously reported in a single-center study that CIRS predicted outcomes in patients with CLL treated with chemo-immunotherapy (CIT). However, to date it is not yet known how comorbidities impact outcomes in the era of novel agents. We tested a hypothesis that CIRS and severe organ dysfunction would retain prognostic significance. Methods: We conducted a retrospective analysis of patients with CLL who underwent treatment at three academic medical centers between 2000 and 2016. CIRS score was calculated as in Salvi et al, 2008. Overall survival (OS) and progression-free survival (PFS) were assessed by Cox proportional hazards models adjusting for performance status (PS), age group, and chemotherapy regimen. Survival analysis in patients treated with ibrutinib was adjusted for age, PS, Rai stage, del17p and prior treatment. In addition, the impact of severe organ dysfunction (CIRS-3+, i.e. CIRS score ≥3 in single organ system) was assessed. Results: Median age in patients receiving CIT was 65 years (N=233). The most common comorbidities were hypertension, endocrine (e.g. diabetes mellitus) and vascular (e.g. deep vein thrombosis). Fludarabine-Rituximab (N=61), Fludarabine-Cyclophosphamide-Rituximab (N=67), Rituximab-Cyclophosphamide-Vincristine-Prednisone (N=35), Bendamustine-Rituximab (N=38) and chlorambucil (N=47) were the most commonly used regimens. 79.5% of treatments were administered in a frontline setting. Average total CIRS was 6.6 and 47% had CIRS-3+. Median OS among all patients receiving CIT was 112 months (95% CI: 105 - 128 months). CIRS≥7 and CIRS3+ were associated with inferior OS compared to patients without significant comorbidities (87, 92 and 129 months, respectively, p In patients treated with ibrutinib the median age was 71 years (N=83), which was significantly older than in the CIT cohort (p Conclusion: In this multicenter retrospective analysis we show that CIRS has prognostic significance in patients with CLL treated with either CIT or ibrutinib, where increased comorbidities correlate with shortened progression-free and overall survival. CIRS appears to carry prognostic value in both upfront and relapsed settings, including patients whose disease can be salvaged with ibrutinib. Larger prospective studies of patients with lymphoid malignancies who have comorbidities are necessary to better define the prognostic value of CIRS in the era of targeted agents and determine the optimal approach to therapy of such patients. Figure 1 Figure 1. Disclosures Persky: Genentech: Consultancy; MorphoSys: Other: Independent Data Monitoring Committee member ; Verastem: Consultancy; Spectrum Pharmaceuticals: Research Funding.

Published
2017
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