A multimorbidity model for estimating health outcomes from the syndemic of injection drug use and associated infections in the United States.

BACKGROUND: Fatal drug overdoses and serious injection-related infections are rising in the US. Multiple concurrent infections in people who inject drugs (PWID) exacerbate poor health outcomes, but little is known about how the synergy among infections compounds clinical outcomes and costs. Injection drug use (IDU) converges multiple epidemics into a syndemic in the US, including opioid use and HIV. Estimated rates of new injection-related infections in the US are limited due to widely varying estimates of the number of PWID in the US, and in the absence of clinical trials and nationally representative longitudinal observational studies of PWID, simulation models provide important insights to policymakers for informed decisions. METHODS: We developed and validated a MultimorbiditY model to Reduce Infections Associated with Drug use (MYRIAD). This microsimulation model of drug use and associated infections (HIV, hepatitis C virus [HCV], and severe bacterial infections) uses inputs derived from published data to estimate national level trends in the US. We used Latin hypercube sampling to calibrate model output against published data from 2015 to 2019 for fatal opioid overdose rates. We internally validated the model for HIV and HCV incidence and bacterial infection hospitalization rates among PWID. We identified best fitting parameter sets that met pre-established goodness-of-fit targets using the Pearson's chi-square test. We externally validated the model by comparing model output to published fatal opioid overdose rates from 2020. RESULTS: Out of 100 sample parameter sets for opioid use, the model produced 3 sets with well-fitting results to key calibration targets for fatal opioid overdose rates with Pearson's chi-square test ranging from 1.56E-5 to 2.65E-5, and 2 sets that met validation targets. The model produced well-fitting results within validation targets for HIV and HCV incidence and serious bacterial infection hospitalization rates. From 2015 to 2019, the model estimated 120,000 injection-related overdose deaths, 17,000 new HIV infections, and 144,000 new HCV infections among PWID. CONCLUSIONS: This multimorbidity microsimulation model, populated with data from national surveillance data and published literature, accurately replicated fatal opioid overdose, incidence of HIV and HCV, and serious bacterial infections hospitalization rates. The MYRIAD model of IDU could be an important tool to assess clinical and economic outcomes related to IDU behavior and infections with serious morbidity and mortality for PWID.

Warning about the harms of tobacco use in 22 countries: findings from a cross-sectional household survey.

BACKGROUND: Knowledge about the harms of tobacco use deters initiation and is associated with cessation. Most studies on this knowledge in the general population have been in high-income countries, but the tobacco use burden is increasing in low-income and middle-income countries. We sought to estimate levels of knowledge about tobacco-related diseases in 22 countries and determine the factors associated with differences in knowledge. METHODS: We used data from the Global Adult Tobacco Survey (GATS), a nationally representative survey of persons aged ≥15 years. GATSs were conducted from 2008 to 2013 in 22 low-income and middle-income countries. Information was gathered on tobacco-related knowledge and noticing of antismoking mass media messages and health warning labels on cigarette packages. We constructed a four-point knowledge scale and performed multivariate regression analyses. RESULTS: Median country values for the proportion of adults who believed smoking causes a specific illness were 95.9% for lung cancer, 82.5% for heart attack and 74.0% for stroke. Knowledge scores ranged from 2.1 to 3.8. In multivariate regressions, adults scored significantly higher on the knowledge scale if they noticed antismoking media messages (22 countries) or health warning labels (17 countries). Significantly higher knowledge scores occurred in all 9 countries with pictorial health warning labels compared with only 8 out of 13 countries with text-only warning labels. CONCLUSIONS: Antismoking media messages appear effective for warning the public about the harms from tobacco use in all 22 countries, while warning labels are effective in the majority of these countries. Our findings suggest opportunities to motivate smoking cessation globally.

Evaluation of Hepatitis C Treatment Outcomes Among Patients Enrolled in Outpatient Parenteral Antibiotic Therapy-Boston, Massachusetts, 2016-2021.

In our Boston-based outpatient parenteral antibiotic therapy (OPAT) program between 2016 and 2021, we found that a low proportion of patients with active hepatitis C virus (HCV) were prescribed HCV treatment by their OPAT provider and few achieved sustained virologic response. Clinicians should consider concurrent HCV treatment during OPAT.

Projected Life Expectancy Gains From Improvements in HIV Care in Black and White Men Who Have Sex With Men.

Importance: Substantial racial inequities exist across the HIV care continuum between non-Hispanic Black and White men who have sex with men (MSM) in the US. Objectives: To project years of life gained (YLG) with improving the HIV care continuum among Black MSM and White MSM in the US and to determine the outcomes of achieving health equity goals. Design, Setting, and Participants: The Cost-Effectiveness of Preventing AIDS Complications microsimulation model was used and populated with 2021 race-specific data to simulate HIV care among Black MSM and White MSM in the US who have acquired HIV. Analyses were completed from July 2021 to October 2023. Intervention: The study simulated status quo care using race-specific estimates: age at infection, time to diagnosis, receipt of care, and virologic suppression. The study next projected the outcomes of attaining equity-centered vs non-equity-centered goals by simulating 2 equal improvements in care goals: (10-point increased receipt of care and 5-point increased virologic suppression), 3 equity-centered goals (annual HIV testing, 95% receiving HIV care, and 95% virologic suppression) and lastly, an equitable care continuum that achieves annual HIV testing, 95% receiving care, and 95% virologic suppression in Black MSM and White MSM. One-way and multiway sensitivity and scenario analyses were conducted. Main Outcomes and Measures: Mean age at death and YLG. Results: In the simulated cohort, the mean (SD) age at HIV infection was 27.0 (10.8) years for Black MSM and 35.5 (13.6) years for White MSM. In status quo, mean age at death would be 68.8 years for Black MSM and 75.6 years for White MSM. The equal improvements in care goals would result in 0.5 YLG for Black MSM and 0.5 to 0.9 YLG for White MSM. Achieving any 1 equity-centered goal would result in 0.5 to 1.7 YLG for Black MSM and 0.4 to 1.3 YLG for White MSM. With an equitable care continuum compared with the nationally reported status quo, Black MSM and White MSM would gain 3.5 and 2.1 life-years, respectively. If the status quo HIV testing was every 6 years with 75% retained in care and 75% virologically suppressed, Black MSM would gain 4.2 life-years with an equitable care continuum. Conclusions and Relevance: In this simulation modeling study of HIV care goals, equal improvements in HIV care for Black and White MSM maintained or worsened inequities. These results suggest that equity-centered goals for the HIV care continuum are critical to mitigate long-standing inequities in HIV outcomes.

Evaluation of Three Clinical Prediction Tools to Predict Mortality in Hospitalized Patients with Lassa Fever.

Lassa fever is a viral hemorrhagic illness with a case fatality rate for hospitalized patients as high as 69%. Identifying cases before they progress to serious illness can lead to earlier treatment and improved clinical outcomes. Three existing clinical prediction tools were evaluated on their ability to predict the in-hospital mortality in Lassa fever: the quick Sequential Organ Failure Assessment (qSOFA), the Modified Early Warning System (MEWS), and the Universal Vital Assessment (UVA). This was a retrospective cohort study of patients admitted to the dedicated Lassa fever ward of the Kenema Government Hospital in Sierra Leone between May 2013 and December 2019. Data among three serology groups were analyzed: Lassa antigen-positive (Ag+) regardless of IgM status, Lassa Ag- and IgM+, and Lassa Ag- and IgM- cases. There were 123 cases of suspected Lassa fever included in this study. Abnormalities in respiratory rate, oxygenation status, mental status, and serum markers of kidney and liver dysfunction were more likely seen in the Ag+ group, which had an in-hospital mortality of 85.7%. For the Lassa Ag+ group, the sensitivity and positive predictive value of qSOFA ≥ 2 was 70.6% and 92.3%, MEWS ≥ 5 was 96.9% and 86.1%, and UVA ≥ 5 was 60.0% and 100.0%. The MEWS and UVA scores show potential for use in Lassa fever, but there is opportunity for future development of a tool that includes the clinical and laboratory markers specific to Lassa fever.

Projected survival gains from revising state laws requiring written opt-in consent for HIV testing.

BACKGROUND: Although the Centers for Disease Control and Prevention recommends HIV testing in all settings unless patients refuse (opt-out consent), many state laws require written opt-in consent. OBJECTIVE: To quantify potential survival gains from passing state laws streamlining HIV testing consent. DESIGN: We retrieved surveillance data to estimate the current annual HIV diagnosis rate in states with laws requiring written opt-in consent (19.3%). Published data informed the effect of removing that requirement on diagnosis rate (48.5% increase). These parameters then served as input for a model-driven projection of survival based on consent method. Other inputs included undiagnosed HIV prevalence (0.101%); and annual HIV incidence (0.023%). PATIENTS: Hypothetical cohort of adults (>13 years) living in written opt-in states. MEASUREMENTS: Life years gained (LYG). RESULTS: In the base-case, of the 53,036,383 adult persons living in written opt-in states, 0.66% (350,040) will be infected with HIV. Due to earlier diagnosis, revised consent laws yield 1.5 LYG per HIV-infected person, corresponding to 537,399 LYG among this population. Sensitivity analyses demonstrate that diagnosis rate increases of 24.8-72.3% result in 304,765-724,195 LYG. Net survival gains vanish if the proportion of HIV-infected persons refusing all testing in response to revised laws exceeds 18.2%. CONCLUSIONS: The potential survival gains of increased testing are substantial, suggesting that state laws requiring opt-in HIV testing should be revised.

Clinical, Laboratory, and Radiologic Characteristics of Patients With Initial False-Negative Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid Amplification Test Results.

BACKGROUND: Concerns about false-negative (FN) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) have prompted recommendations for repeat testing if suspicion for coronavirus disease 2019 (COVID-19) infection is moderate to high. However, the frequency of FNs and patient characteristics associated with FNs are poorly understood. METHODS: We retrospectively reviewed test results from 15 011 adults who underwent ≥1 SARS-CoV-2 NAATs; 2699 had an initial negative NAAT and repeat testing. We defined FNs as ≥1 negative NAATs followed by a positive NAAT within 14 days during the same episode of illness. We stratified subjects with FNs by duration of symptoms before the initial FN test (≤5 days versus >5 days) and examined their clinical, radiologic, and laboratory characteristics. RESULTS: Sixty of 2699 subjects (2.2%) had a FN result during the study period. The weekly frequency of FNs among subjects with repeat testing peaked at 4.4%, coinciding with peak NAAT positivity (38%). Most subjects with FNs had symptoms (52 of 60; 87%) and chest radiography (19 of 32; 59%) consistent with COVID-19. Of the FN NAATs, 18 of 60 (30%) were performed early (ie, ≤1 day of symptom onset), and 18 of 60 (30%) were performed late (ie, >7 days after symptom onset) in disease. Among 17 subjects with 2 consecutive FNs on NP NAATs, 9 (53%) provided lower respiratory tract (LRT) specimens for testing, all of which were positive. CONCLUSIONS: Our findings support repeated NAATs among symptomatic patients, particularly during periods of higher COVID-19 incidence. The LRT testing should be prioritized to increase yield among patients with high clinical suspicion for COVID-19.

Racial and sex disparities in life expectancy losses among HIV-infected persons in the united states: impact of risk behavior, late initiation, and early discontinuation of antiretroviral therapy.

BACKGROUND: Most persons with human immunodeficiency virus (HIV) infection in the United States present to care with advanced disease, and many patients discontinue therapy prematurely. We sought to evaluate sex and racial/ethnic disparities in life-years lost as a result of risk behavior, late presentation, and early discontinuation of HIV care, and we compared these survival losses for HIV-infected persons with losses attributable to high-risk behavior and HIV disease itself. METHODS: With use of a state-transition model of HIV disease, we simulated cohorts of HIV-infected persons and compared them with uninfected individuals who had similar demographic characteristics. We estimated non-HIV-related mortality with use of risk-adjusted standardized mortality ratios, as well as years of life lost because of late presentation and early discontinuation of antiretroviral therapy (ART) for HIV infection. Data from the national HIV Research Network, stratified by sex and race/ethnicity, were used for estimating CD4+ cell counts at ART initiation. RESULTS: For HIV-uninfected persons in the United States who have risk profiles similar to those of individuals with HIV infection, the projected life expectancy, starting at 33 years of age, was 34.58 years, compared with 42.91 years for the general US population. Those with HIV infection lost an additional 11.92 years of life if they received HIV care concordant with guidelines; late treatment initiation resulted in 2.60 additional years of life lost, whereas premature ART discontinuation led to 0.70 more years of life lost. Losses from late initiation and early discontinuation were greatest for Hispanic individuals (3.90 years). CONCLUSIONS: The high-risk profile of HIV-infected persons, HIV infection itself, as well as late initiation and early discontinuation of care, all lead to substantial decreases in life expectancy. Survival disparities resulting from late initiation and early discontinuation of therapy are most pronounced for Hispanic HIV-infected men and women. Interventions focused on risk behaviors, as well as on earlier linkage to and better retention in care, will lead to improved survival for HIV-infected persons in the United States.