Publications

2021
Cross SH, Warraich HJ. Rural-Urban Disparities in Mortality from Alzheimer's and Related Dementias in the United States, 1999-2018. J Am Geriatr Soc. 2021;69 :1095-1096.
Cross SH, Califf RM, Warraich HJ. Rural-Urban Disparity in Mortality in the US From 1999 to 2019. JAMA. 2021;325 :2312-2314.
Schlogl M, Pak ES, Bansal AD, Schell JO, Ganai S, Kamal AH, Swetz KM, Maguire JM, Perrakis A, Warraich HJ, et al. Top Ten Tips Palliative Care Clinicians Should Know About Prognostication in Critical Illness and Heart, Kidney, and Liver Diseases. J Palliat Med. 2021.Abstract
Specialty palliative care (PC) clinicians are frequently asked to discuss prognosis with patients and their families. When conveying information about prognosis, PC clinicians need also to discuss the likelihood of prolonged hospitalization, cognitive and functional disabilities, and death. As PC moves further and further upstream, it is crucial that PC providers have a broad understanding of curative and palliative treatments for serious diseases and can collaborate in prognostication with specialists. In this article, we present 10 tips for PC clinicians to consider when caring and discussing prognosis for the seriously ill patients along with their caregivers and care teams. This is the second in a three-part series around prognostication in adult and pediatric PC.
Cross SH, Lakin JR, Mendu M, Mandel EI, Warraich HJ. Trends in Place of Death for Individuals With Deaths Attributed to Advanced Chronic or End-Stage Kidney Disease in the United States. J Pain Symptom Manage. 2021;61 :112-120 e1.Abstract
CONTEXT: An important aspect of end-of-life care, place of death is understudied in advanced chronic (CKD) and end-stage kidney disease (ESKD). OBJECTIVE: We sought to examine trends and factors associated with where advanced CKD/ESKD patients die. METHODS: We conducted a retrospective cross-sectional study using mortality data from 2003 to 2017 for deaths attributed primarily to advanced CKD/ESKD in the United States. RESULTS: Between 2003 and 2017, 222,247 deaths were attributed to advanced CKD/ESKD. From 2003 to 2017, deaths occurring in hospitals declined from 56.0% (n = 5356) to 35.6% (n = 7764), whereas increases occurred in deaths at home (13.5% [n = 1292] to 24.3% [n = 5306]), nursing facilities (18.6% [n = 1776] to 19.3% [n = 4221]), and hospice facilities (0.3% [n = 29] to 13.4% [n = 2917]). Nonwhite race was associated with increased odds of hospital death (Black [OR = 1.59; 95% CI = 1.55, 1.62]; Native American [OR = 1.47; 95% CI = 1.32, 1.63]; Asian [OR = 1.43; 95% CI = 1.32, 1.55] and reduced odds of nursing facility (Black [OR = 0.622; 95% CI = 0.600, 0.645]; Native American [OR = 0.638; 95% CI = 0.572, 0.712]; Asian [OR = 0.574; 95% CI = 0.533, 0.619], or hospice facility death (Black [OR = 0.843; 95% CI = 0.773, 0.918]; Native American [OR = 0.380; 95% CI = 0.289, 0.500]; Asian [OR = 0.609; 95% CI = 0.502, 0.739]). Older age was associated with reduced odds of hospital death (>/=85 [OR = 0.334; 95% CI = 0.312, 0.358]) and increased odds of home (>/=85 [OR = 1.55; 95% CI = 1.43, 1.68]), nursing facility (>/=85 [OR = 3.09; 95% CI = 2.76, 3.45]) or hospice facility death (>/=85 [OR = 1.60; 95% CI = 1.49, 1.72]). CONCLUSIONS: Hospitals remain the most common place of death from advanced CKD/ESKD; however, the proportion of home, nursing facility, and hospice facility deaths have increased.
Iyer AS, Cross SH, Dransfield MT, Warraich HJ. Urban-Rural Disparities in Deaths from Chronic Lower Respiratory Disease in the United States. Am J Respir Crit Care Med. 2021;203 :769-772.
2020
Warraich HJ, Ali HJR, Nasir K. Financial Toxicity With Cardiovascular Disease Management: A Balancing Act for Patients. Circ Cardiovasc Qual Outcomes. 2020;13 :e007449.
Sumarsono A, Buckley LF, Machado SR, Wadhera RK, Warraich HJ, Desai RJ, Everett BM, McGuire DK, Fonarow GC, Butler J, et al. Medicaid Expansion and Utilization of Antihyperglycemic Therapies. Diabetes Care. 2020;43 :2684-2690.Abstract
OBJECTIVE: Certain antihyperglycemic therapies modify cardiovascular and kidney outcomes among patients with type 2 diabetes, but early uptake in practice appears restricted to particular demographics. We examine the association of Medicaid expansion with use of and expenditures related to antihyperglycemic therapies among Medicaid beneficiaries. RESEARCH DESIGN AND METHODS: We employed a difference-in-difference design to analyze the association of Medicaid expansion on prescription of noninsulin antihyperglycemic therapies. We used 2012-2017 national and state Medicaid data to compare prescription claims and costs between states that did (n = 25) and did not expand (n = 26) Medicaid by January 2014. RESULTS: Following Medicaid expansion in 2014, average noninsulin antihyperglycemic therapies per state/1,000 enrollees increased by 4.2%/quarter in expansion states and 1.6%/quarter in nonexpansion states. For sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA), quarterly growth rates per 1,000 enrollees were 125.3% and 20.7% for expansion states and 87.6% and 16.0% for nonexpansion states, respectively. Expansion states had faster utilization of SGLT2i and GLP-1RA than nonexpansion states. Difference-in-difference estimates for change in volume of prescriptions after Medicaid expansion between expansion versus nonexpansion states was 1.68 (95% CI 1.09-2.26; P < 0.001) for all noninsulin therapies, 0.125 (-0.003 to 0.25; P = 0.056) for SGLT2i, and 0.12 (0.055-0.18; P < 0.001) for GLP-1RA. CONCLUSIONS: Use of noninsulin antihyperglycemic therapies, including SGLT2i and GLP-1RA, increased among low-income adults in both Medicaid expansion and nonexpansion states, with a significantly greater increase in overall use and in GLP-1RA use in expansion states. Future evaluation of the population-level health impact of expanded access to these therapies is needed.
Khan S, Khan MZ, Khan MS, Greene S, Khan MU, Krasuski RA, Warraich HJ, Michos ED. Deaths in pulmonary hypertension: US location trends. BMJ Support Palliat Care. 2020.
Khan SU, Kalra A, Kapadia SR, Khan MU, Zia Khan M, Khan MS, Mamas MA, Warraich HJ, Nasir K, Michos ED, et al. Demographic, Regional, and State-Level Trends of Mortality in Patients With Aortic Stenosis in United States, 2008 to 2018. J Am Heart Assoc. 2020;9 :e017433.Abstract
Background Aortic stenosis-related mortality might vary across demographic subsets, regions, and states in the United States. Methods and Results We reviewed the death certificate data from the Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research database to examine aortic stenosis-related mortality trends from 2008 to 2018. Crude and age-adjusted mortality rates (AAMRs) per 100 000 people and annual percentage change with 95% CIs were calculated. Between 2008 and 2018, AAMR reduced from 12.7 to 11.5 (average annual percentage change, -1.0 [95% CI, -1.5 to -0.5]), because of an accelerated decline between 2015 and 2018 (annual percentage change, -4.4 [95% CI, -6.0 to -2.7]). Older (aged >85 years), male, and White patients had higher death rates than younger, female, and non-White patients, respectively. Although mortality reduction was similar across sexes, significant mortality reduction was limited to White patients only. The AAMRs were higher in rural than urban areas. States with AAMRs >90th percentile were distributed in the West and the Northeast, and <10th percentile in the South. The AAMRs for sex and race were highest in the West and lowest in the South. None of the states located in the Midwest showed a significant reduction in mortality. Mortality remained stable for hospital setting and nursing home/long-term care facility, except that the number of deaths increased at home and hospice facility since 2014. Conclusions The reduction in mortality in patients with aortic stenosis was not consistent among demographic subsets and states. The substantial public health and economic implications call for determination of underlying clinical and socioeconomic factors to narrow the gap.
Warraich HJ, Ali HJR, Nasir K. Financial Toxicity With Cardiovascular Disease Management: A Balancing Act for Patients. Circ Cardiovasc Qual Outcomes. 2020;13 :e007449.
Slavin SD, Allen LA, McIlvennan CK, Desai AS, Schaefer KG, Warraich HJ. Left Ventricular Assist Device Withdrawal: Ethical, Psychological, and Logistical Challenges. J Palliat Med. 2020;23 :456-458.
Warraich HJ, Manly D. A Man in His 20s With New-Onset Severe Heart Failure and Ventricular Tachycardia. JAMA Cardiol. 2020;5 :841.
Sumarsono A, Buckley LF, Machado SR, Wadhera RK, Warraich HJ, Desai RJ, Everett BM, McGuire DK, Fonarow GC, Butler J, et al. Medicaid Expansion and Utilization of Antihyperglycemic Therapies. Diabetes Care. 2020;43 :2684-2690.Abstract
OBJECTIVE: Certain antihyperglycemic therapies modify cardiovascular and kidney outcomes among patients with type 2 diabetes, but early uptake in practice appears restricted to particular demographics. We examine the association of Medicaid expansion with use of and expenditures related to antihyperglycemic therapies among Medicaid beneficiaries. RESEARCH DESIGN AND METHODS: We employed a difference-in-difference design to analyze the association of Medicaid expansion on prescription of noninsulin antihyperglycemic therapies. We used 2012-2017 national and state Medicaid data to compare prescription claims and costs between states that did (n = 25) and did not expand (n = 26) Medicaid by January 2014. RESULTS: Following Medicaid expansion in 2014, average noninsulin antihyperglycemic therapies per state/1,000 enrollees increased by 4.2%/quarter in expansion states and 1.6%/quarter in nonexpansion states. For sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA), quarterly growth rates per 1,000 enrollees were 125.3% and 20.7% for expansion states and 87.6% and 16.0% for nonexpansion states, respectively. Expansion states had faster utilization of SGLT2i and GLP-1RA than nonexpansion states. Difference-in-difference estimates for change in volume of prescriptions after Medicaid expansion between expansion versus nonexpansion states was 1.68 (95% CI 1.09-2.26; P < 0.001) for all noninsulin therapies, 0.125 (-0.003 to 0.25; P = 0.056) for SGLT2i, and 0.12 (0.055-0.18; P < 0.001) for GLP-1RA. CONCLUSIONS: Use of noninsulin antihyperglycemic therapies, including SGLT2i and GLP-1RA, increased among low-income adults in both Medicaid expansion and nonexpansion states, with a significantly greater increase in overall use and in GLP-1RA use in expansion states. Future evaluation of the population-level health impact of expanded access to these therapies is needed.
Cross SH, Ely EW, Kavalieratos D, Tulsky JA, Warraich HJ. Place of Death for Individuals With Chronic Lung Disease: Trends and Associated Factors From 2003 to 2017 in the United States. Chest. 2020;158 :670-680.Abstract
BACKGROUND: Although chronic lung disease is a common cause of mortality, little is known about where individuals with chronic lung disease die. RESEARCH QUESTION: The aim of this study was to determine the trends and factors associated with place of death among individuals with chronic lung disease. STUDY DESIGN AND METHODS: This cross-sectional analysis of natural deaths was conducted by using the Centers for Disease Control and Prevention Wide-ranging OnLine Data for Epidemiologic Research from 2003 to 2017 for which COPD, interstitial lung disease (ILD), or cystic fibrosis (CF) was the underlying cause. Place of death was categorized as hospital, home, nursing facility, hospice facility, and other. RESULTS: From 2003 to 2017, more than 2.2. million deaths were primarily attributed to chronic lung disease (51.6% female, 92.4% white). Most were attributed to COPD (88.9%), followed by ILD (10.8.%), and CF (0.3%). Hospital and nursing facility deaths declined from 44.4% (n = 59,470) and 22.6% (n = 30,285) to 28.3% (n = 49,655) and 19.7% (n = 34,495), while home and hospice facility deaths increased from 23.3% (n = 31,296) and 0.1% (n = 192) to 34.7% (n = 60,851) and 9.0% (n = 15,861), respectively. Male sex, being married, and having some college education were associated with increased odds of home death, whereas non-white race and Hispanic ethnicity were associated with increased odds of hospital death. Compared with individuals with COPD, individuals with ILD and CF had increased odds of hospital death and reduced odds of home, nursing facility, or hospice facility death. INTERPRETATION: Home deaths are rising among decedents from chronic lung disease, increasing the need for quality end-of-life care in this setting. Further research should explore the end-of-life needs and preferences of these patients and their caregivers, with particular attention paid to patients with ILD and CF who continue to have high rates of hospital death.
Vaduganathan M, Van Meijgaard J, Mehra MR, Joseph J, O'Donnell CJ, Warraich HJ. Prescription Fill Patterns for Commonly Used Drugs During the COVID-19 Pandemic in the United States. JAMA. 2020;323 :2524-2526.
Khan MS, Khan MS, Ansari ZN, Siddiqi TJ, Khan SU, Riaz IB, Asad ZUA, Mandrola J, Wason J, Warraich HJ, et al. Prevalence of Multiplicity and Appropriate Adjustments Among Cardiovascular Randomized Clinical Trials Published in Major Medical Journals. JAMA Netw Open. 2020;3 :e203082.Abstract
Importance: Multiple analyses in a clinical trial can increase the probability of inaccurately concluding that there is a statistically significant treatment effect. However, to date, it is unknown how many randomized clinical trials (RCTs) perform adjustments for multiple comparisons, the lack of which could lead to erroneous findings. Objectives: To assess the prevalence of multiplicity and whether appropriate multiplicity adjustments were performed among cardiovascular RCTs published in 6 medical journals with a high impact factor. Design, Setting, and Participants: In this cross-sectional study, cardiovascular RCTs were selected from all over the world, characterized as North America, Western Europe, multiregional, and rest of the world. Data were collected from past issues of 3 cardiovascular journals (Circulation, European Heart Journal, and Journal of the American College of Cardiology) and 3 general medicine journals (JAMA, The Lancet, and The New England Journal of Medicine) with high impact factors published between August 1, 2015, and July 31, 2018. Supplements and trial protocols of each of the included RCTs were also searched for multiplicity. Data were analyzed December 20 to 27, 2018. Exposures: Data from the selected RCTs were extracted and verified independently by 2 researchers using a structured data instrument. In case of disagreement, a third reviewer helped to achieve consensus. An RCT was considered to have multiple treatment groups if it had more than 2 arms; multiple outcomes were defined as having more than 1 primary outcome, and multiple analyses were defined as analysis of the same outcome variable in multiple ways. Multiplicity was examined only for the analysis of the primary end point. Main Outcomes and Measures: Outcomes of interest were percentages of primary analyses that performed multiplicity adjustment of primary end points. Results: Of 511 cardiovascular RCTs included in this analysis, 300 (58.7%) had some form of multiplicity; of these 300, only 85 (28.3%) adjusted for multiplicity. Intervention type and funding source had no statistically significant association with the reporting of multiplicity risk adjustment. Trials that assessed mortality vs nonmortality outcomes were more likely to contain a multiplicity risk in their primary analysis (66.3% [177 of 267] vs 50.4% [123 of 244]; P < .001), and larger trials vs smaller trials were less likely to make any adjustments for multiplicity (35.6% [52 of 146] vs 21.4% [33 of 154]; P = .001). Conclusions and Relevance: Findings from this study suggest that cardiovascular RCTs published in medical journals with high impact factors demonstrate infrequent adjustments to correct for multiple comparisons in the primary end point. These parameters may be improved by more standardized reporting.
Slavin SD, Warraich HJ. The right time for palliative care in heart failure: a review of critical moments for palliative care intervention. Rev Esp Cardiol (Engl Ed). 2020;73 :78-83.Abstract
Heart failure (HF) is a progressive condition with high mortality and heavy symptom burden. Despite guideline recommendations, cardiologists refer to palliative care at rates much lower than other specialties and very late in the course of the disease, often in the final 3 days of life. One reason for delayed referral is that prognostication is challenging in patients with HF, making it unclear when and how the limited resources of specialist palliative care will be most beneficial. It might be more prudent to consider palliative care referrals at critical moments in the trajectory of patients with HF. These include: a) the development of poor prognostic signs in the outpatient setting; b) hospitalization or intensive care unit admission, and c) at the time of evaluation for certain procedures, such as left ventricular assist device placement and ablation for refractory ventricular arrhythmias, among others. In this review, we also summarize the results of clinical trials evaluating palliative interventions in these settings.
Cross SH, Mehra MR, Bhatt DL, Nasir K, O'Donnell CJ, Califf RM, Warraich HJ. Rural-Urban Differences in Cardiovascular Mortality in the US, 1999-2017. JAMA. 2020;323 :1852-1854.
Khan MS, Shahid I, Siddiqi TJ, Khan SU, Warraich HJ, Greene SJ, Butler J, Michos ED. Ten-Year Trends in Enrollment of Women and Minorities in Pivotal Trials Supporting Recent US Food and Drug Administration Approval of Novel Cardiometabolic Drugs. J Am Heart Assoc. 2020;9 :e015594.Abstract
Background In 1993, the US Food and Drug Administration established guidelines to increase diversity by sex and race/ethnicity of participants in clinical trials supporting novel drug approvals. In this study we investigated the 10-year trends of participation of women and minorities in pivotal trials supporting approval of new molecular entities in cardiometabolic drugs from January 2008 to December 2017. Methods and Results A list of new molecular entities was abstracted from publicly available data at Drugs@Fda. Sex and race/ethnicity data were collected from trial publications. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled. Thirty-five novel cardiovascular (n=24) and diabetes mellitus (n=11) drugs were approved by the US Food and Drug Administration during the study period. The median number of participants supporting each drug was 5930 (interquartile range, 3175-10 942). Women represented 36% (n=108 052) of trial participants (n=296 163). Women were underrepresented compared with their proportion of the disease population in trials of coronary heart disease (participation-to-prevalence ratio, 0.52), heart failure (participation-to-prevalence ratio, 0.58), and acute coronary syndrome (participation-to-prevalence ratio, 0.68). Among trial participants, 81% were white, 4% black, 12% Asian, and 11% Hispanic/Latino. There was no significant association between enrollment of women (P=0.29) or underrepresented minorities (P=0.45) with the drug approval year. Conclusions Over the past decade (2008-2017), women and minorities, particularly blacks, have continued to be inadequately represented in pivotal cardiometabolic clinical trials that support US Food and Drug Administration approval of new molecular entities. This may have major implications in determining efficacy of such therapies in these groups, and may impair generalizability of trial results to routine clinical practice.
Bhatia V, Huang Y, Tulsky JA, Cross SH, Kamal AH, Warraich HJ. Trends and Characteristics of Medicare Hospice Beneficiaries in the USA. J Gen Intern Med. 2020.

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