Mortality among people who inject drugs: a prospective cohort followed over three decades in Baltimore, MD, USA.

BACKGROUND AND AIMS: During the past decades, people who inject drugs (PWID) have been impacted by the development of combination antiretroviral therapy (cART) to combat HIV/AIDS, the prescription opioid crisis and increased use of lethal synthetic opioids. We measured how these dynamics have impacted mortality among PWID in an urban US city. DESIGN: Prospective cohort study using data from the AIDS Linked to the Intravenous Experience (ALIVE). SETTING: Baltimore, MD, USA from 1988 to 2018. PARTICIPANTS: A total of 5506 adult PWIDs (median age at baseline 37 years). MEASUREMENTS: Mortality was identified by linkage to National Death Index-Plus (NDI-Plus) and categorized into HIV/infectious disease (HIV/ID) deaths, overdose and violence-related (drug-related) deaths and chronic disease deaths. Person-time at risk accrued from baseline and ended at the earliest of death or study period. All-cause and cause-specific mortality were calculated annually. The Fine & Gray method was used to estimate the subdistribution hazards of cause-specific deaths accounting for competing risks. FINDINGS: Among 5506 participants with 84 226 person-years of follow-up, 43.9% were deceased by 2018. Among all deaths, 30.5% were HIV/ID deaths, 24.4% drug-related deaths and 33.3% chronic disease deaths. Age-standardized all-cause mortality increased from 23 to 45 per 1000 person-years from 1988 to 1996, declined from 1996 to 2014, then trended upward to 2018. HIV/ID deaths peaked in 1996 coincident with the availability of cART, then continuously declined. Chronic disease deaths increased continuously as the cohort aged. Drug-related deaths declined until 2011, but increased more than fourfold by 2018. HIV/HCV infection and active injecting were independently associated with HIV/ID and drug-related deaths. Female and black participants had a higher risk of dying from HIV/ID deaths and a lower risk of dying from drug-related deaths than male and non-black participants. CONCLUSIONS: Deaths in Baltimore, MD, USA attributable to HIV/ID appear to have declined following the widespread use of combination antiretroviral therapy. Increases in the rates of drug-related deaths in Baltimore were observed prior to and continue in conjunction with national mortality rates associated with the opiate crisis.

The association of novel inflammatory marker GlycA and incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Emerging evidence has implicated that inflammation contributes to the pathogenesis of atrial fibrillation (AF). GlycA is a novel marker of systemic inflammation with low intra-individual variability and high analytic precision. GlycA has been associated with incident cardiovascular disease (CVD) independent of other inflammatory markers. However, whether GlycA is associated with AF, specifically, has yet to be established. We examined the association between GlycA and AF in a multi-ethnic cohort. METHODS: We studied 6,602 MESA participants aged 45-85, with no clinical CVD at baseline, with data on GlycA and incident AF. We used multivariable-adjusted Cox models to evaluate the association between GlycA and incident AF. We also examined other inflammatory markers [high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6) and fibrinogen] and incident AF for comparison. RESULTS: The mean (SD) age was 62 (10) years, 53% women. The mean plasma GlycA was 381 (62) µmol/L. Over median follow-up of 12.9 years, 869 participants experienced AF. There was no statistically significant association between GlycA and incident AF after adjusting for sociodemographics, CVD risk factors, and other inflammatory markers [Hazard Ratio (95% CI) per 1 SD increment in GlycA: 0.97 (0.88-1.06)]. Neither hsCRP nor fibrinogen was associated with incident AF in same model. In contrast, IL-6 was independently associated with incident AF [HR 1.12 per 1 SD increment (1.05-1.19)]. CONCLUSIONS: Although GlycA has been associated with other CVD types, we found that GlycA was not associated with AF. More research will be required to understand why IL-6 was associated with AF but not GlycA. CLINICAL TRIAL REGISTRATION: MESA is not a clinical trial. However, the cohort is registered at: URL: https://clinicaltrials.gov/ct2/show/NCT00005487 Unique identifier: NCT00005487.

Prevalence and Factors Associated With Liver Fibrosis Among Adult HIV-Infected Patients Attending Urban and Rural Care Clinics in Uganda.

BACKGROUND: Liver fibrosis is common among HIV-infected patients. Risk factors vary by location. Understanding this variation may inform prevention strategies. We compared the prevalence and correlates of liver fibrosis among HIV-infected patients attending care clinics in Uganda. METHODS: This was a cross-sectional study involving 2030 HIV-infected patients attending care clinics in urban and rural Uganda. Liver fibrosis was defined as liver stiffness measurement (LSM) >7.1 KPa. Proportions and correlates of liver fibrosis were assessed and compared using logistic regression stratified by gender and site. RESULTS: Prevalence of liver fibrosis was higher among participants in the rural clinic (15% vs 11%; P = .017). History of tobacco use (urban P = .022; rural P = .035) and serologic evidence of hepatitis C infection (HCV; urban P = .028; rural P = .03) was associated with liver fibrosis in all men. Elevated liver transaminases (urban P = .002; rural P = .028) and increasing age (urban P = .008; rural P = .052) were risk factors among all women. Tobacco use among women was only a risk factor in those attending the rural clinic (P = .003), and detectable HIV viral load (P = .002) for men in the urban clinic. CONCLUSIONS: Liver fibrosis is prevalent among HIV-infected persons in Uganda. HIV viral suppression and avoiding tobacco may be strategies to prevent liver fibrosis and cancer risk.

Association of the Novel Inflammatory Marker GlycA and Incident Heart Failure and Its Subtypes of Preserved and Reduced Ejection Fraction: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: GlycA, a nuclear magnetic resonance composite marker of systemic inflammation, reflects serum concentration and glycosylation state of main acute phase reactants. Prior studies have shown plasma GlycA levels were associated with cardiovascular disease even after adjusting for other inflammatory markers. However, little is known about the association of GlycA with the heart failure (HF) subtypes: heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction. We examined the association of GlycA with incident HF and its subtypes in a multiethnic cohort. METHODS: We studied 6507 Multi-Ethnic Study of Atherosclerosis participants aged 45 to 84 without baseline cardiovascular disease or HF who had data on GlycA and incident hospitalized HF. We used multivariable-adjusted Cox hazards models to evaluate the association of GlycA with incident total HF, HFpEF, and heart failure with reduced ejection fraction. Models were adjusted for sociodemographics, cardiovascular disease risk factors, and inflammatory biomarkers. RESULTS: The mean (SD) for age was 62 (10) years and for GlycA was 375 (82) µmol/L; 53% women. Over a median follow-up of 14.0 years, participants in the highest quartile of GlycA, compared with the lowest, experienced increased risk of developing any HF (hazard ratio, 1.48 [95% CI, 1.01-2.18]) in fully adjusted models. However, this increased risk was only seen for HFpEF (2.18 [1.15-4.13]) and not heart failure with reduced ejection fraction [1.06 (0.63-1.79)]. There was no significant interaction by sex, age, or race/ethnicity. CONCLUSIONS: GlycA was associated with an increased risk of any HF, and in particular, HFpEF. Future studies should examine mechanisms that might explain differential association of GlycA with HF subtypes, and whether therapeutic lowering of GlycA can prevent HFpEF development. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005487.

Participation of Women and Older Participants in Randomized Clinical Trials of Lipid-Lowering Therapies: A Systematic Review.

Importance: Randomized clinical trials (RCTs) of lipid-lowering therapies form the evidence base for national and international guidelines. However, concerns exist that women and older patients are underrepresented in RCTs. Objective: To determine the trends of representation of women and older patients (≥65 years) in RCTs of lipid-lowering therapies from 1990 to 2018. Data Sources: The electronic databases of MEDLINE and ClinicalTrials.gov were searched from January 1990 through December 2018. Study Selection: RCTs of lipid-lowering therapies with sample sizes of at least 1000 patients and follow-up periods of at least 1 year were included. Data Extraction and Synthesis: Two independent investigators abstracted the data on a standard data collection form. Main Outcomes and Measures: Patterns of representation of women and older adults were examined overall in lipid-lowering RCTs and according to RCT-level specific characteristics. The participation-to-prevalence ratio (PPR) metric was used to estimate the representation of women compared with their share of disease burden. Results: A total of 60 RCTs with 485 409 participants were included. The median (interquartile range) number of participants per trial was 5264 (1062-27 564). Overall, representation of women was 28.5% (95% CI, 24.4%-32.4%). There was an increase in the enrollment of women from the period 1990 to 1994 (19.5%; 95% CI, 18.4%-20.5%) to the period 2015 to 2018 (33.6%; 95% CI, 33.4%-33.8%) (P for trend = .01). Among common limiting factors were inclusion of only postmenopausal women or surgically sterile women (28.3%; 95% CI, 18.5%-40.7%) or exclusion of pregnant (23.3%; 95% CI, 14.4%-35.4%) and lactating (16.6%; 95% CI, 9.3%-28.1%) women. Women were underrepresented compared with their disease burden in lipid RCTs of diabetes (PPR, 0.74), heart failure (PPR, 0.27), stable coronary heart disease (PPR, 0.48), and acute coronary syndrome (PPR, 0.51). Only 23 RCTs with 263 628 participants reported the proportion of older participants. Overall representation of older participants was 46.7% (95% CI, 46.5%-46.9%), which numerically increased from 31.6% (95% CI, 30.8%-32.3%) in the period 1995 to 1998 to 46.2% (95% CI, 46.0%-46.5%) in the period 2015 to 2018 (P for trend = .43). A total of 53.0% (95% CI, 41.8%-65.3%) and 36.6% (95% CI, 25.6% to 49.3%) trials reported outcomes according to sex and older participants, respectively, which did not improve over time. Conclusions and Relevance: In this systematic review of RCTs of lipid-lowering therapies, the enrollment of women and older participants increased over time, but women and older participants remained consistently underrepresented. This limits the evidence base for efficacy and safety in these subgroups.

Age-specific differences in patient reported outcomes among adults with atherosclerotic cardiovascular disease: Medical expenditure panel survey 2006-2015.

OBJECTIVE: The prevalence of atherosclerotic cardiovascular disease (ASCVD) in younger adults has increased over the past decade. However, it is less well established whether patient reported outcomes differ between younger and older adults with ASCVD. We sought to evaluate age-specific differences in patient reported outcomes among adults with ASCVD. METHODS: This was a retrospective cross-sectional survey study. We used data from the 2006-2015 Medical Expenditure Panel Survey (MEPS), a nationally representative sample of the United States population. Adults ≥18 years with a diagnosis of ASCVD, ascertained by ICD9 codes or self-reported data, were included. Logistic regression was used to compare self-reported patient-clinician communication, patient satisfaction, perception of health, emergency department (ED) visits, and use of preventive medications (aspirin and statins) by age category [Young: 18-44, Middle: 45-64, Older: ≥65 years]. We used two-part econometric modeling to evaluate age-specific annual healthcare expenditure. RESULTS: There were 21,353 participants included. Over 9000 (42.6%-weighted) of the participants were young or middle aged, representing ~9.9 million adults aged <65 years with ASCVD nationwide. Compared with older adults, middle-aged and young adults with ASCVD were more likely to report poor patient-clinician communication [OR 1.73 (95% CI 1.28-2.33) and 2.49 (1.76-3.51), respectively], poor healthcare satisfaction, and poor perception of health status, have increased ED utilization and were also less likely to be using aspirin and statins. The mean annual healthcare expenditure was highest among middle-aged adults [$10,798 (95% CI, $10,012 to $11,583)]. CONCLUSION: Compared with older adults, younger adults with ASCVD were more likely to report poor patient experience and poor health status and less likely to be using preventive medications. More effort needs to be geared towards understanding the age-specific differences in healthcare quality and delivery to improve outcomes among high-risk young adults with ASCVD.

Sex differences in the association between ideal cardiovascular health and biomarkers of cardiovascular disease among adults in the United States: a cross-sectional analysis from the multiethnic study of atherosclerosis.

OBJECTIVES: This study investigated the sex differences in the associations between ideal cardiovascular health (CVH), measured by the American Heart Association's Life's Simple 7 metrics, and cardiovascular disease (CVD)-related biomarkers among an ethnically diverse cohort of women and men free of clinical CVD at baseline. SETTING: We analysed data from the Multi-Ethnic Study of Atherosclerosis conducted in six centres across the USA (Baltimore, Maryland; Chicago, Illinois; Forsyth County, North Carolina; Los Angeles, California; New York, New York; and St Paul, Minnesota). PARTICIPANTS: This is a cross-sectional study of 5379 women and men, aged 45-84 years old. Mean age (SD) was 62 (10), 52% were women, 38% White, 11% Chinese American, 28% Black and 23% Hispanic. PRIMARY MEASURES: The seven metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure and blood glucose) were each scored as 0 points (poor), 1 point (intermediate) or 2 points (ideal). The total CVH score ranged from 0 to 14. The CVD-related biomarkers studied were high-sensitivity C-reactive protein, D-dimer, fibrinogen, homocysteine, high-sensitivity cardiac troponin T, N-terminal pro B-type natriuretic peptide (NT-proBNP) and interleukin 6. We examined the association between the CVH score and each biomarker using multivariable linear regression, adjusting for age, race/ethnicity, education, income and health insurance status. RESULTS: Higher CVH scores were associated with lower concentrations of all biomarkers, except for NT-proBNP where we found a direct association. There were statistically significant interactions by sex for all biomarkers (p<0.001), but results were qualitatively similar between women and men. CONCLUSION: A more favourable CVH score was associated with lower levels of multiple CVD-related biomarkers for women and men, except for NT-proBNP. These data suggest that promotion of ideal CVH would have similarly favourable impact on the reduction of biomarkers of CVD risk for both women and men.

Association of Depression Risk with Patient Experience, Healthcare Expenditure, and Health Resource Utilization Among Adults with Atherosclerotic Cardiovascular Disease.

BACKGROUND: Approximately 20% of patients with atherosclerotic cardiovascular disease (ASCVD) suffer from depression. OBJECTIVE: To compare healthcare expenditures and utilization, healthcare-related quality of life, and patient-centered outcomes among ASCVD patients, based on their risk for depression (among those without depression), and those with depression (vs. risk-stratified non-depressed). DESIGN AND SETTING: The 2004-2015 Medical Expenditure Panel Survey (MEPS) was used for this study. PARTICIPANTS: Adults ≥ 18 years with a diagnosis of ASCVD, ascertained by ICD-9 codes and/or self-reported data. Individuals with a diagnosis of depression were identified by ICD-9 code 311. Participants were stratified by depression risk, based on the Patient Health Questionnaire-2. RESULTS: A total of 19,840 participants were included, translating into 18.3 million US adults, of which 8.6% (≈ 1.3 million US adults) had a high risk for depression and 18% had a clinical diagnosis of depression. Among ASCVD patients without depression, those with a high risk (compared with low risk) had increased overall and out-of-pocket expenditures (marginal differences of $2880 and $287, respectively, both p < 0.001), higher odds for resource utilization, and worse patient experience and healthcare quality of life (HQoL). Furthermore, compared with individuals who had depression, participants at high risk also reported worse HQoL and had higher odds of poor perception of their health status (OR 1.83, 95% CI [1.50, 2.23]) and poor patient-provider communication (OR 1.29 [1.18, 1.42]). LIMITATION: The sample population includes self-reported diagnosis of ASCVD; therefore, the risk of underestimation of the cohort size cannot be ruled out. CONCLUSION: Almost 1 in 10 individuals with ASCVD without diagnosis of depression is at high risk for it and has worse health outcomes compared with those who already have a diagnosis of depression. Early recognition and treatment of depression may increase healthcare efficiency, positive patient experience, and HQoL among this vulnerable population.

Trends and Costs Associated With Suboptimal Physical Activity Among US Women With Cardiovascular Disease.

Importance: Cardiovascular disease (CVD) is the leading cause of death and disability among women. Achievement of recommended physical activity (PA) levels is an essential component of CVD management. Objective: To describe trends, sociodemographic factors, and health care expenditures associated with suboptimal PA among a nationally representative sample of US women with CVD. Design, Setting, and Participants: This cross-sectional study used serial data from the Medical Expenditure Panel Survey from 2006 through 2015. The analyses were conducted in August 2018. Women who had self-reported and/or International Classification of Diseases, Ninth Revision, diagnosis of CVD were included. Main Outcomes and Measures: Recommended PA was defined as 30 minutes or more of moderate- to vigorous-intensity exercise, 5 or more days per week. Weighted logistic regression was used to examine the associations of various sociodemographic factors with suboptimal PA, adjusted for comorbidities. A 2-part econometric model was used to assess health care expenditures. Results: A total of 18 027 women were included in this study. The results were weighted to provide estimates for approximately 19.5 million adult women in the United States with CVD (mean [SD] age, 60.4 [16.9] years). More than half of the women with CVD reported suboptimal PA, a trend that increased during the 10-year period, with 58.2% (95% CI, 55.9%-60.5%) of participants reporting suboptimal PA in 2006-2007 vs 61.9% (95% CI, 59.7%-64.2%) in 2014-2015 (P = .004). The proportion of women with suboptimal PA differed by sociodemographic factors. In adjusted models, compared with non-Hispanic white women, African American women (odds ratio, 1.22; 95% CI, 1.08-1.38) and Hispanic women (odds ratio, 1.33; 95% CI, 1.13-1.58) were more likely to have suboptimal PA. Women from low- or very low-income strata (compared with high-income strata), enrolled in public insurance (compared with private insurance), and with less than high school education (compared with at least some college education) were more likely to have suboptimal PA. Health care costs among women with CVD with suboptimal PA were higher compared with those among women who met the recommended PA, and this increased through time, from a mean total health care expenditure of $12 724 (95% CI, $11 627-$13 821) in 2006-2007 to $14 820 (95% CI, $13 521-$16 119) in 2014-2015. Conclusions and Relevance: The proportion of women with CVD not meeting recommended PA is high and increasing, particularly among certain racial/ethnic and socioeconomic groups, and is associated with significant health care costs. More must be done to improve PA for secondary prevention and reduction of expenditures among women with CVD.

Associations of ideal cardiovascular health with GlycA, a novel inflammatory marker: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Unhealthy lifestyles and inflammation contribute to cardiovascular disease (CVD). GlycA is a novel biomarker of systemic inflammation representing post-translational glycosylation of acute phase reactants and associated with increased clinical CVD risk. HYPOTHESIS: We hypothesized that ideal cardiovascular health (CVH), as assessed by (higher) Life's Simple 7 (LS7) scores, would be associated with lower GlycA levels among individuals free of CVD in a multiethnic community-based population. METHODS: This was a cross-sectional study of 6479 Multi-Ethnic Study of Atherosclerosis participants [53% women; mean age 62 ± 10 years] with GlycA levels measured at baseline by nuclear magnetic resonance spectroscopy. The LS7 metrics (smoking, physical activity, diet, body mass index, blood pressure, cholesterol, and glucose) were each scored as ideal (2), moderate (1), or poor (0). Total scores were summed and categorized as optimal (12-14), average (8-11), and inadequate (0-7). Linear regression assessed percent difference in GlycA by LS7 scores, after adjusting for age, sex, ethnicity, education, income, family history of CVD, and other inflammatory biomarkers. RESULTS: GlycA levels were 403.4 ± 63.1, 374.4 ± 59.2, and 350.3 ± 56.2 micromoles per liter (µmol/L) for inadequate, average, and optimal CVH, respectively (P-trend <0.001). After multivariable adjustment, GlycA remained independently and inversely associated with CVH categories, with a lower mean GlycA level of 5 µmol/L (95% confidence interval 4.5-5.8) for each one unit increment in LS7 score. CONCLUSIONS: Among this group of ethnically diverse individuals without CVD, suboptimal CVH is associated with higher GlycA levels, independent of traditional inflammatory biomarkers. Strategies aimed at improving CVH might reduce GlycA, which could be a marker of reduced risk of future CVD events.

Incidence of medically attended influenza among residents of Shai-Osudoku and Ningo-Prampram Districts, Ghana, May 2013 - April 2015.

BACKGROUND: Influenza vaccination is recommended by the World Health Organization for high risk groups, yet few data exist on influenza disease burden in West Africa. METHODS: We estimated medically attended influenza-associated illness rates among residents of Shai-Osudoku and Ningo Pram-Pram Districts (SONPD), Ghana. From May 2013 to April 2015, we conducted prospective surveillance for severe acute respiratory illness (SARI) and influenza-like illness (ILI) in 17 health facilities. In 2015, we conducted a retrospective assessment at an additional 18 health facilities to capture all SONPD SARI and ILI patients during the study period. We applied positivity rates to those not tested to estimate total influenza cases. RESULTS: Of 612 SARI patients tested, 58 (9%) were positive for influenza. The estimated incidence of influenza-associated SARI was 30 per 100,000 persons (95% CI: 13-84). Children aged 0 to 4 years had the highest influenza-associated SARI incidence (135 per 100,000 persons, 95% CI: 120-152) and adults aged 25 to 44 years had the lowest (3 per 100,000 persons, 95% CI: 1-7) (p < 0.01). Of 2,322 ILI patients tested, 407 (18%) were positive for influenza. The estimated incidence of influenza-associated ILI was 844 per 100,000 persons (95% CI: 501-1,099). The highest incidence of influenza-associated ILI was also among children aged 0 to 4 years (3,448 per 100,000 persons, 95% CI: 3,727 - 3,898). The predominant circulating subtype during May to December 2013 and January to April 2015 was influenza A(H3N2) virus, and during 2014 influenza B virus was the predominant circulating type. CONCLUSIONS: Influenza accounted for 9% and 18% of medically attended SARI and ILI, respectively. Rates were substantive among young children and suggest the potential value of exploring the benefits of influenza vaccination in Ghana, particularly in this age group.