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R Scott BraithwaiteSection of Value and Comparative Effectiveness, Division of General Internal Medicine, New York University School of Medicine, New York, NY, USAAbstract: Many consumers and clinicians incorrectly believe that the Food and Drug Administration (FDA) approval of a new therapeutic implies that its benefits have been proven to exceed its harms. While the FDA could require proof that benefits exceed harms prior to approval, it has been argued that this approach would be infeasible because of prohibitively large sample sizes. One possible alternative would be for the FDA to supplement its standard “label” denoting “safe and effective” with a secondary “label” denoting benefits have been demonstrated to exceed harms, which would be granted only after sufficient post-marketing data had accumulated to prove that its benefits exceeded its harms. This secondary label would not necessarily be linked to marketing restrictions or other commercial prohibitions but, rather, would be only information for consumers and clinicians. Strengths, weaknesses, and feasibility challenges of this approach are discussed.Keywords: drug label, Food and Drug Administration, safety, efficacy, benefit–risk assessment

OBJECTIVES:Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. METHODS:We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. RESULTS:The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. CONCLUSIONS:The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

OBJECTIVES:Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. METHODS:We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. RESULTS:The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. CONCLUSIONS:The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

Antiretroviral therapy (ART) has substantially altered the fate of HIV-infected people, transforming the infection from an invariably fatal disease to a chronic condition manageable by pharmacotherapy. However, in order for ART to be effective, patients must adhere strictly to an often-demanding treatment regimen. Alcohol consumption may impact survival of HIV-infected patients through a variety of pathways. Some of these are not related to the effectiveness of ART (e.g., alcohol-induced immunosuppression that exacerbates the HIV-related immunosuppression, increased hepatotoxicity, and increased mortality from non-HIV-related causes). However, some pathways mediating alcohol's negative effect on survival are related to ART effectiveness. In particular, alcohol consumption may reduce adherence to ART, leading to decreased ART effectiveness and, ultimately, increased HIV-related mortality. Both clinical data and computer simulations have yielded information about the impact of alcohol consumption on medication adherence in both HIV-infected and noninfected patients. The findings suggest that alcohol-related nonadherence may account for a substantial amount of preventable mortality among HIV-infected patients. These findings may have clinical implications with respect to optimal treatment for HIV-infected patients who also consume alcohol. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intentional exposures to aerosolized Bacillus anthracis spores have caused fatalities. OBJECTIVE: To evaluate the cost-effectiveness of strategies to reduce mortality from future inhalational anthrax exposures. METHODS: Computer cohort simulation of a 100,000-person single-site exposure (worst-case scenario) and a 100-person multiplesite exposure (resembling the recent US attack). For each scenario, universal vaccination and an emergency surveillance and response (ESR) system were compared with a default strategy that assumed eventual discovery of the exposure. RESULTS: If an exposure was unlikely to occur or was small in scale, neither vaccination nor an ESR system was cost-effective. If an exposure was certain and large in scale, an ESR system was more cost-effective than vaccination ($73 v. $29,600 per life-year saved), and a rapid response saved more lives than improved surveillance. CONCLUSIONS: Strategies to reduce deaths from anthrax attacks are cost-effective only if large exposures are certain. A faster response is more beneficial than enhanced surveillance. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies have shown that alcohol consumption is associated with decreased medication adherence, but this association may be confounded by characteristics common among those who drink heavily and those who fail to adhere (e.g., illicit drug use). Our objective was to determine whether there are temporal and dose-response relationships between alcohol consumption and poor adherence. METHODS: We administered telephone interview surveys to participants in the Veterans Aging Cohort Study, an eight-site observational study of HIV+ and matched HIV- veterans in care, to determine whether alcohol consumption on a particular day was associated with nonadherence to prescribed medications on that same day. We used the Time Line Follow Back to measure alcohol consumption and the Time Line Follow Back Modified for Adherence to measure adherence. Individuals were categorized as abstainers (no alcohol in past 30 days), nonbinge drinkers (alcohol in past 30 days but < or =four standard drinks on each day), or binge drinkers (> or =five standard drinks on at least one day). RESULTS: Among 2702 respondents, 1582 (56.6%) were abstainers, 931 (34.5%) were nonbinge drinkers, and 239 (8.9%) were binge drinkers. Abstainers missed medication doses on 2.4% of surveyed days. Nonbinge drinkers missed doses on 3.5% of drinking days, 3.1% of postdrinking days, and 2.1% of nondrinking days (p < 0.001 for trend), and this trend was more pronounced among HIV+ individuals than HIV- individuals. Binge drinkers missed doses on 11.0% of drinking days, 7.0% of postdrinking days, and 4.1% of nondrinking days (p < 0.001 for trend), and this trend was comparably strong for HIV+ and HIV- individuals. CONCLUSIONS: Among veterans in care, self-reported alcohol consumption demonstrates a temporal and dose-response relationship to poor adherence. HIV+ individuals may be particularly sensitive to alcohol consumption. [ABSTRACT FROM AUTHOR]

BACKGROUND: Male veterans represent a large population at risk for acquiring or transmitting human immunodeficiency virus (HIV) infection. We sought to determine the prevalence of risky sexual behavior among veterans with and without HIV infection and to assess the relationship of intoxication before intercourse and other measures of drug and alcohol use to risky sexual behavior in this population. METHODS: We analyzed baseline data on 1009 HIV-positive (mean age 49 years) and 710 HIV-negative male veterans (mean age 55 years) who were participating in the Veterans Aging Cohort 5-Site Study (VACS 5). Participants completed a written questionnaire that included measures of alcohol and drug use and risky sexual behavior. RESULTS: Compared with HIV-negative veterans, HIV-positive veterans were more likely to report 5 or more sexual partners in the past year (14% vs. 4%, P < 0.01), less likely to report not using a condom at last intercourse (25% vs. 75%, P < 0.01), and similarly likely to report having 2 or more partners and inconsistent condom use (10% vs. 10%). Among sexually active HIV-positive veterans, intoxication before intercourse was significantly associated with having 5 or more sexual partners in the past year (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1-2.8), inconsistent condom use (OR 1.8, 95% CI 1.2-2.7), and the combined measure of 2 or more partners and inconsistent condom use (OR 1.8, 95% CI 1.1-3.0). Intoxication before intercourse was not significantly associated with these behaviors in HIV-negative veterans, although similar trends were noted. CONCLUSION: Risky sexual behavior was common among male veterans attending outpatient clinics and is more common among HIV-positive veterans who use alcohol and drugs in sexual situations. Asking HIV-positive men a single question about intoxication before intercourse could help to identify men at increased risk of engaging in risky sexual behavior, and specific advice to avoid intoxication in sexual situations could help to reduce risky sexual behavior. [ABSTRACT FROM AUTHOR]

Many people at risk for or already infected with HIV abuse alcohol, contributing to the difficulties in preventing the spread of the infection and treating infected patients. Thus, alcohol-abusing patients may delay testing for HIV, accessing appropriate medical care, and initiating antiretroviral therapy (ART), which may hasten disease progression to full-blown AIDS. Alcohol abuse also increases the risk of HIV infection by promoting risky behaviors and counteracting efforts to minimize the risk of infection, prevent transmission of the virus to others once exposure has occurred, and reduce the risk of progression and organ or tissue injury after infection. In HIV-infected people undergoing treatment, concurrent alcohol abuse often renders treatment ineffective because patients frequently fail to adhere to the strict treatment regimens necessary to achieve control of the infection. Moreover, alcohol may interact with ART medications and exacerbate adverse effects of these medications. Future research needs to better integrate behavioral and biological research to identify strategies to prevent the spread of HIV infection in alcohol-abusing populations as well as focus on translational research to effectively implement promising approaches on a large scale. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) and major depressive disorder (MDD) drive HIV transmission in many sub-Saharan African settings. The impact of screening and treating AUD and MDD on HIV outcomes is unknown. We aimed to identify the cost-effectiveness of AUD and MDD interventions in Zimbabwe, and their potential contribution to reaching Zimbabwe's Ending the HIV Epidemic 2030 goal., Methods: Using a validated HIV compartmental transmission model in Zimbabwe, we compared four policy scenarios: prevention as usual (baseline); implement AUD screening (using AUDIT) and treatment (motivational interviewing and cognitive-behavioral therapy); implement MDD screening (using PHQ-9) and treatment (cognitive-behavioral therapy); and implement screening and treatment for both. Outcomes were HIV incidence projections, infections averted through 2030, quality-adjusted life-years gained, cost per infection averted, and cost per QALY gained. Analyses considered "spillover," when treatment for AUD also results in an improvement in MDD and the converse. Sensitivity analyses identified cost reductions necessary for AUD and MDD interventions to be as cost-effective as other HIV interventions, particularly the scale-up of long-acting PrEP., Results: AUD and MDD combined will be responsible for 21.1% of new HIV infections in Zimbabwe by 2030. Without considering spillover, compared to the baseline, MDD intervention can reduce new infections by 5.4% at $2039/infection averted and $3186/QALY. AUD intervention can reduce new infections by 5.8%, but at $2,968/infection averted and $4753/QALY, compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.1% at $2810/infection averted and $4229/QALY, compared to baseline. Considering spillover, compared to the baseline, MDD intervention can reduce new infections by 6.4% at $1714/infection averted and $2630/QALY. AUD intervention can reduce new infections by 7.4%, but at $2299/infection averted and $3560/QALY compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.9% at $2247/infection averted and $3382/QALY compared to baseline. For MDD intervention to match the cost-effectiveness of scaling long-acting PrEP, the cost of MDD intervention would need to be reduced from $16.64 to $12.88 per person., Conclusions: Implementing AUD and MDD interventions can play an important role in HIV reduction in Zimbabwe, particularly if intervention cost can be decreased while preserving effectiveness., (© 2024. The Author(s).)

Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic premalignant lesions frequently detected incidentally. Choosing between surgery and surveillance for IPMNs is rooted in uncertainty. We characterized patient preferences in IPMN management, and examined associations with patients' uncertainty profiles (risk perception, risk attitude, and uncertainty tolerance)., Methods: We conducted a cross-sectional survey drawn from a national opt-in panel. We simulated an encounter following an incidental computed tomography scan finding of an IPMN with a 5% cancer risk. We elicited participants' preferred treatment (surgery versus surveillance). Participant cancer risk perception, risk attitude (risk seeking versus risk averse), and uncertainty tolerance (comfort with the unknown) were determined using validated measures. Multivariate regression models assessed for independent predictors of treatment preference and risk perception., Results: The sample included 520 participants, ages 40-70, racially representative of the US population. Participants preferred surveillance (n = 331, 64%) over surgery (n = 189, 36%). Patients were significantly more likely to prefer surgery as their cancer risk perception increased (absolute difference = 12% from 1.0 standard deviation below to 1.0 standard deviation above the mean, 95% CI 3.5-20.2). Treatment preference was not significantly associated with risk attitude (P = 0.068) or uncertainty tolerance (P = 0.755). However, initial cancer risk perception was significantly associated with both uncertainty tolerance (P = 0.013) and baseline cancer anxiety (risk perception 16.4% versus 65%, not worried at all versus extremely worried, P < 0.001)., Conclusions: Patient preference varies widely for IPMN and is significantly associated with cancer risk perception, which is, in turn, significantly associated with uncertainty tolerance and cancer anxiety. These findings argue for the preference-sensitive nature of IPMN treatment decisions., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In mid-2022, New York City (NYC) became the epicenter of the US mpox outbreak. We provided real-time mpox case forecasts to the NYC Department of Health and Mental Hygiene to aid in outbreak response. Forecasting methodologies evolved as the epidemic progressed. Initially, lacking knowledge of at-risk population size, we used exponential growth models to forecast cases. Once exponential growth slowed, we used a Susceptible-Exposed-Infectious-Recovered (SEIR) model. Retrospectively, we explored if forecasts could have been improved using an SEIR model in place of our early exponential growth model, with or without knowing the case detection rate. Early forecasts from exponential growth models performed poorly, as 2-week mean absolute error (MAE) grew from 53 cases/week (July 1-14) to 457 cases/week (July 15-28). However, when exponential growth slowed, providing insight into susceptible population size, an SEIR model was able to accurately predict the remainder of the outbreak (7-week MAE: 13.4 cases/week). Retrospectively, we found there was not enough known about the epidemiological characteristics of the outbreak to parameterize an SEIR model early on. However, if the at-risk population and case detection rate were known, an SEIR model could have improved accuracy over exponential growth models early in the outbreak., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Quitting smoking may lead to improvement in substance use, psychiatric symptoms, and pain, especially among high-risk populations who are more likely to experience comorbid conditions. However, causal inferences regarding smoking cessation and its subsequent benefits have been limited., Methods: We emulated a hypothetical open-label randomized control trial of smoking cessation using longitudinal observational data of HIV-positive and HIV-negative US veterans from 2003-2015 in the Veterans Aging Cohort Study. We followed individuals from the first time they self-reported current cigarette smoking (baseline). We categorized participants as quitters or non-quitters at the first follow-up visit (approximately 1 year after baseline). Using inverse probability weighting to adjust for confounding and selection bias, we estimated odds ratios for improvement of co-occurring conditions (unhealthy alcohol use, cannabis use, illicit opioid use, cocaine use, depressive symptoms, anxiety symptoms, and pain symptoms) at second follow-up (approximately 2 years after baseline) for those who quit smoking compared to those who did not, among individuals who had the condition at baseline., Results: Of 4,165 eligible individuals (i.e., current smokers at baseline), 419 reported no current smoking and 2,330 reported current smoking at the first follow-up. Adjusted odds ratios (95% confidence intervals) for associations between quitting smoking and improvement of each condition at second follow-up were: 2.10 (1.01, 4.35) for unhealthy alcohol use, 1.75 (1.00, 3.06) for cannabis use, 1.10 (0.58, 2.08) for illicit opioid use, and 2.25 (1.20, 4.24) for cocaine use, 0.78 (0.44, 1.38) for depressive symptoms, 0.93 (0.58, 1.49) for anxiety symptoms, and 1.31 (0.84, 2.06) for pain symptoms., Conclusions: While a causal interpretation of our findings may not be warranted, we found evidence for decreased substance use among veterans who quit cigarette smoking but none for the resolution of psychiatric conditions or pain symptoms. Findings suggest the need for additional resources combined with smoking cessation to reduce psychiatric and pain symptoms for high-risk populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ban et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We used results from an optimization randomized controlled trial which tested five behavioral intervention components to support HIV antiretroviral adherence/HIV viral suppression, grounded in the multiphase optimization strategy and using a fractional factorial design to identify intervention components with cost-effectiveness sufficiently favorable for scalability. Results were incorporated into a validated HIV computer simulation to simulate longer-term effects of combinations of components on health and costs. We simulated the 32 corresponding long-term trajectories for viral load suppression, health related quality of life (HRQoL), and costs. The components were designed to be culturally and structurally salient. They were: motivational interviewing counseling sessions (MI), pre-adherence skill building (SB), peer mentorship (PM), focused support groups (SG), and patient navigation (short version [NS], long version [NL]. All participants also received health education on HIV treatment. We examined four scenarios: one-time intervention with and without discounting and continuous interventions with and without discounting. In all four scenarios, interventions that comprise or include SB and NL (and including health education) were cost effective (< $100,000/quality-adjusted life year). Further, with consideration of HRQoL impact, maximal intervention became cost-effective enough to be scalable. Thus, a fractional factorial experiment coupled with cost-effectiveness analysis is a promising approach to optimize multi-component interventions for scalability. The present study can guide service planning efforts for HIV care settings and health departments., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary., Methods: We developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons., Results: Maximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime., Conclusions: Maximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money., (© 2024. The Author(s).)

HIV infections disproportionately impact Latinx populations in the United States, yet oral pre-exposure prophylaxis (PrEP) uptake is low. This study was a secondary gendered analysis of interviews with Latina cisgender women ( n = 20) recruited from an urban safety net hospital inNew York City between August 2019 and October 2022. All women were indicated for PrEP by the provider. In-depth interviews were conducted with participants in English and Spanish and asked about social determinants of health, sexual partnerships and behaviors, and PrEP-specific enablers and barriers. Secondary thematic content analysis was conducted to identify gender-related factors influencing PrEP uptake. The following themes emerged from the data:structural factors (e.g., employment), partner-related factors, low sexual health knowledge, and resilience and empowerment. Partner-related factors were the most salient; partner infidelity served as reasons for initiating PrEP. Despite being constrained by low power in relationships, women made empowered choices to initiate PrEP and protect themselves. Findings indicated that the impact of gender inequity was an important factor in Latina women's PrEP decision making, pointing to a need to address partner-driven HIV risk, imbalance of power in relationships, and gender norms.

Objectives: We aimed to determine whether surgeon variation in management of intraductal papillary mucinous neoplasm (IPMN) is driven by differences in risk perception and quantify surgeons' risk threshold for changing their recommendations., Background: Surgeons vary widely in management of IPMN., Methods: We conducted a survey of members of the Americas HepatoPancreatoBiliary Association, presented participants with 2 detailed clinical vignettes and asked them to choose between surgical resection and surveillance. We also asked them to judge the likelihood that the IPMN harbors cancer and that the patient would have a serious complication if surgery was performed. Finally, we asked surgeons to rate the level of cancer risk at which they would change their treatment recommendation. We examined the association between surgeons' treatment recommendations and their risk perception and risk threshold., Results: One hundred fifty surgeons participated in the study. Surgeons varied in their recommendations for surgery [19% for vignette 1 (V1) and 12% for V2] and in their perception of the cancer risk (interquartile range: 2%-10% for V1 and V2) and risk of surgical complications (V1 interquartile range: 10%-20%, V2 20-30%). After adjusting for surgeon characteristics, surgeons who were above the median in cancer risk perception were 22 percentage points (27% vs 5%) more likely to recommend resection than those who were below the median (95% CI: 11%-4%; P <0.001). The median risk threshold at which surgeons would change their recommendation was 15% (V1 and V2). Surgeons who recommended surgery had a lower risk threshold for changing their recommendation than those who recommended surveillance (V1: 10.0 vs 15.0, P =0.06; V2: 7.0 vs 15.0, P =0.05)., Conclusions: The treatment that patients receive for IPMNs depends greatly on how their surgeons perceive the risk of cancer in the lesion. Efforts to improve cancer risk prediction for IPMNs may lead to decreased variations in care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We aimed to determine whether surgeon variation in management of intraductal papillary mucinous neoplasms (IPMN) is driven by differences in risk perception and quantify surgeons' risk threshold for changing their recommendations., Background: Surgeons vary widely in management of IPMN., Methods: We conducted a survey of members of the Americas HepatoPancreatoBiliary Association, presented participants with 2 detailed clinical vignettes and asked them to choose between surgical resection and surveillance. We also asked them to judge the likelihood that the IPMN harbors cancer and that the patient would have a serious complication if surgery was performed. Finally, we asked surgeons to rate the level of cancer risk at which they would change their treatment recommendation. We examined the association between surgeons' treatment recommendations and their risk perception and risk threshold., Results: One hundred and fifty surgeons participated in the study. Surgeons varied in their recommendations for surgery [19% for vignette 1 (V1) and 12% for V2] and in their perception of the cancer risk (interquartile range: 2%-10% for V1 and V2) and risk of surgical complications (V1 interquartile range: 10%-20%, V2 20%-30%). After adjusting for surgeon characteristics, surgeons who were above the median in cancer risk perception were 22 percentage points (27% vs. 5%) more likely to recommend resection than those who were below the median (95% CI: 11.34%; P <0.001). The median risk threshold at which surgeons would change their recommendation was 15% (V1 and V2). Surgeons who recommended surgery had a lower risk threshold for changing their recommendation than those who recommended surveillance (V1: 10.0 vs. 15.0, P =0.06; V2: 7.0 vs. 15.0, P =0.05)., Conclusions: The treatment that patients receive for IPMNs depends greatly on how their surgeons perceive the risk of cancer in the lesion. Efforts to improve cancer risk prediction for IPMNs may lead to decreased variations in care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

There is strong evidence linking stimulant use, namely methamphetamine use, to sexual risk behavior among sexual minority men (SMM); we do not, however, have a good understanding of this relationship among other at-risk populations. In this study, we systematically reviewed associations between stimulant use (i.e., methamphetamine, crack cocaine, cocaine) and sexual risk behaviors among populations facing elevated risk of HIV transmission and acquisition (i.e., SMM, people who inject drugs (PWID), and people living with HIV/AIDS (PLWH)). Random-effects meta-analyses and sensitivity analyses that included crude and adjusted estimates separately were conducted to evaluate the impact of potential confounding variables. The results showed strong relationships between stimulant use and condomless sex, transactional sex, and multiple sexual partners. Results were broadly consistent when analyses were stratified by type of stimulant (methamphetamine, crack cocaine, and other stimulants) and risk group. Sensitivity analyses with confounding variables did not greatly impact results. The results indicate that stimulant use is associated with numerous sexual risk behaviors regardless of risk group, suggesting prevention efforts focused on reducing methamphetamine-related HIV risk should target a range of at-risk populations., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To understand the impact of COVID-19-related disruptions on PrEP services, we reviewed PrEP prescriptions at NYC Health + Hospitals/Bellevue from July 2019 through July 2021. PrEP prescriptions were examined as PrEP person-equivalents (PrEP PE) in order to account for the variable time of refill duration (i.e., 1-3 months). To assess "PrEP coverage", we calculated PrEP medication possession ratios (MPR) while patients were under study observation. Pre-clinic closure, mean PrEP PE = 244.2 (IQR 189.2, 287.5; median = 252.5) were observed. Across levels of clinic closures, mean PrEP PE = 247.3, (IQR 215.5, 265.4; median = 219.9) during 100% clinic closure, 255.4 (IQR 224, 284.3; median = 249.0) during 80% closure, and 274.6 (IQR 273.0, 281.0; median = 277.2) during 50% closure were observed. Among patients continuously prescribed PrEP pre-COVID-19, the mean MPR mean declined from 83% (IQR 72-100%; median = 100%) to 63% (IQR 35-97%; median = 66%) after the onset of COVID-19. For patients newly initiated on PrEP after the onset of COVID-19, the mean MPR was 73% (IQR 41-100%; median = 100%). Our ability to sustain PrEP provisions, as measured by both PrEP PE and MPR, can likely be attributed to our pre-COVID-19 system for PrEP delivery, which emphasizes navigation, same-day initiation, and primary care integration. In the era of COVID-19 as well as future unforeseen healthcare disruptions, PrEP programs must be robust and flexible in order to sustain PrEP delivery., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Alcohol use, tobacco use, and other substance use often co-occur with depression, anxiety, and chronic pain, forming a constellation of alcohol, substance, and mood-related (CASM) conditions that disproportionately affects people with HIV in the USA. We used a microsimulation model to evaluate how alternative screening strategies accounting for CASM interdependence could affect life expectancy in people with HIV in the USA., Methods: We augmented a microsimulation model previously validated to predict US adult life expectancy, including in people with HIV. Using data from the Veterans Aging Cohort Study, we incorporated CASM co-occurrence, inferred causal relationships between CASM conditions, and assessed the effects of CASM on HIV treatment and preventive care. We simulated an in-care HIV cohort exposed to alternative CASM screening and diagnostic assessment strategies, ranging from currently recommended screenings (alcohol, tobacco, and depression, with diagnostic assessments for conditions screening positive) to a series of integrated strategies (screening for alcohol, tobacco, or depression with additional diagnostic assessments if any screened positive) to a maximal saturation strategy (diagnostic assessments for all CASM conditions)., Findings: The saturation strategy increased life expectancy by 0·95 years (95% CI 0·93-0·98) compared with no screening. Recommended screenings provided much less benefit: 0·06 years (0·03-0·09) gained from alcohol screening, 0·08 years (0·06-0·11) from tobacco screening, 0·10 years (0·08-0·11) from depression screening, and 0·25 years (0·22-0·27) from all three screenings together. One integrated strategy (screening alcohol, tobacco, and depression with diagnostic assessment for all CASM conditions if any screened positive) produced near-maximal benefit (0·82 years [0·80-0·84]) without adding substantial screening burden, albeit requiring additional diagnostic assessments., Interpretation: Primary care providers for people with HIV should consider comprehensive diagnostic assessment of CASM conditions if one or more conditions screen positive., Funding: US National Institute on Alcohol Abuse and Alcoholism., Competing Interests: Declaration of interests KJB declares advisory board participation as a representative of the US National Institute on Alcohol Abuse and Alcoholism. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Prioritization of higher-risk people for COVID-19 vaccination could prevent more deaths, but could slow vaccination speed. We used mathematical modeling to examine the trade-off between vaccination speed and prioritization for individuals age 65+ and essential workers., Methods: We used a stochastic, discrete-time susceptible-exposed-infected-recovered (SEIR) model with age- and comorbidity-adjusted COVID-19 outcomes (infections, hospitalizations, and deaths). The model was calibrated to COVID-19 hospitalizations, ICU census, and deaths in NYC. We assumed 10,000 vaccinations per day, initially restricted to healthcare workers and nursing home populations, and subsequently expanded to other populations at alternative times (4, 5, or 6 weeks after vaccine launch) and speeds (20,000, 50,000, 100,000, or 150,000 vaccinations per day), as well as prioritization options (+/- prioritization of people age 65+ and essential workers). In sensitivity analyses, we examined the effect of a SARS-COV-2 variant with greater transmissibility., Results: To be beneficial, prioritization must not create a bottleneck that decreases vaccination speed by > 50% without a more transmissible variant, or by > 33% with the emergence of the more transmissible variant. More specifically, prioritizing people age 65+ and essential workers increased the number of lives saved per vaccine dose delivered: 3000 deaths could be averted by delivering 83,000 vaccinations per day without prioritization or 50,000 vaccinations per day with prioritization. Other tradeoffs involve vaccination speed and timing. Compared to the slowest-examined vaccination speed of 20,000 vaccinations per day, achieving the fastest-examined vaccination speed of 150,000 vaccinations per day would avert additional 313,700 (28.6%) infections and 1693 (24.1%) deaths. Emergence of a more transmissible variant would double COVID-19 infections, hospitalizations, and deaths over the first 6 months of vaccination. The fastest-examined vaccination speed could only offset the harm of the more transmissible variant if achieved within 5 weeks of vaccine launch., Conclusions: Faster vaccination speed with sooner vaccination expansion would save more lives. Prioritization of COVID-19 vaccines to higher-risk populations would be more beneficial only if it does not create an excessive vaccine delivery bottleneck., (© 2023. The Author(s).)

Background: Among veterans in care reporting opioid use, we investigated the association between ceasing opioid use on subsequent reduction in report of other substance use and improvements in pain, anxiety, and depression., Methods: Using Veterans Aging Cohort Study survey data collected between 2003 and 2012, we emulated a hypothetical randomized trial (target trial) of ceasing self-reported use of prescription opioids and/or heroin, and outcomes including unhealthy alcohol use, smoking, cannabis use, cocaine use, pain, and anxiety and depressive symptoms. Among those with baseline opioid use, we compared participants who stopped reporting opioid use at the first follow-up (approximately 1 year after baseline) with those who did not. We fit logistic regression models to estimate associations with change in each outcome at the second follow-up (approximately 2 years after baseline) among participants with that condition at baseline. We examined two sets of adjusted models that varied temporality assumptions., Results: Among 2473 participants reporting opioid use, 872 did not report use, 606 reported use, and 995 were missing data on use at the first follow-up. Ceasing opioid use was associated with no longer reporting cannabis (adjusted odds ratio [AOR]=1.82, 95% confidence interval [CI] 1.10, 3.03) and cocaine use (AOR=1.93, 95% CI 1.16, 3.20), and improvements in pain (AOR=1.53, 95% CI 1.05, 2.24) and anxiety (AOR=1.56, 95% CI 1.01, 2.41) symptoms., Conclusion: Cessation of opioid misuse may be associated with subsequent cessation of other substances and reduction in pain and anxiety symptoms, which supports efforts to screen and provide evidence-based intervention where appropriate., Competing Interests: Conflict of Interest None to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Public health experts often assume that any policy promoting healthful behavior change is inherently and self-evidently ethical. This assumption is incorrect. This Viewpoint describes why evaluating the ethics of a policy to promote healthful behavior change should require (1) valuing consequences for wellbeing proportionately to consequences for health, (2) valuing changes to the distributional equity of health and wellbeing together with their aggregate improvement, and (3) anticipating and surveilling for unintended consequences sufficiently important to offset benefits. I illustrate these three requirements through a hypothetical salt restriction policy, which is unethical if it evokes strong preferences that detract from wellbeing, disproportionately confers health benefits to those who are already healthy, or elicits unintended consequences that offset health benefits. I discuss why analogies of salt restriction mandates are inappropriate. In summary, public health decision-makers should employ more structured, explicit and comprehensive criteria when considering the ethical consequences of policies., (© 2022. The Author(s).)

Socioeconomic status-related (SES-related) health disparities are worsening across resource-rich environments, despite increased knowledge about health determinants and inducements for healthful behavior change. We ask whether insights from addiction science and evolutionary biology may assist understanding and counteracting SES-related health disparities. It is known that a mismatch between evolved traits and behaviors that conserve energy drives many health deficits. We posit that this energy mismatch is one manifestation of a more expansive mismatch in levels of reward activation, between environments more versus less manipulated by human activity. This larger mismatch explains why SES-related health disparities arise not only from overeating and excessive sedentism, but also from alcohol, nicotine, other substances, and mood disorders. Lower SES persons are more likely to have lower baseline reward activation, which leads to higher prioritization of reward elevating activities, and at the same time are less likely to act on knowledge about unhealthfulness of behaviors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Braithwaite and Schwartz.)

Objective: To develop and pilot test a patient decision aid (DA) describing small kidney masses and risks and benefits of treatment for the masses., Methods: An expert committee iteratively designed a small kidney mass DA, incorporating evidence-based risk communication and informational needs for treatment options and shared decision-making. After literature review and drafting content with the feedback of urologists, radiologists, and an internist, a rapid qualitative assessment was conducted using two patient focus groups to inform user-centered design. In a pilot study, 30 patients were randomized at the initial urologic consultation to receive the DA or existing institutional patient educational material (PEM). Preconsultation questionnaires captured patient knowledge and shared decision-making preferences. After review of the DA and subsequent clinician consultation, patients completed questionnaires on discussion content and satisfaction. Proportions between arms were compared using Fisher exact tests, and decision measures were compared using Mann-Whitney tests., Results: Patient informational needs included risk of tumor growth during active surveillance and ablation, significance of comorbidities, and posttreatment recovery. For the DA, 84% of patients viewed all content, and mean viewing time was 20 min. Significant improvements in knowledge about small mass risks and treatments were observed (mean total scores: 52.6% DA versus 22.3% PEM, P < .001). DA use also increased the proportion of patients discussing ablation (66.7% DA versus 18.2% PEM, P = .02). Decision satisfaction measures were similar in both arms., Discussion: Patients receiving a small kidney mass DA are likely to gain knowledge and preparedness to discuss all treatment options over standard educational materials., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Stay-at-home restrictions such as closure of non-essential businesses were effective at reducing SARS-CoV-2 transmission in New York City (NYC) in the spring of 2020. Relaxation of these restrictions was desirable for resuming economic and social activities, but could only occur in conjunction with measures to mitigate the expected resurgence of new infections, in particular social distancing and mask-wearing. We projected the impact of individuals' adherence to social distancing and mask-wearing on the duration, frequency, and recurrence of stay-at-home restrictions in NYC. We applied a stochastic discrete time-series model to simulate community transmission and household secondary transmission in NYC. The model was calibrated to hospitalizations, ICU admissions, and COVID-attributable deaths over March-July 2020 after accounting for the distribution of age and chronic health conditions in NYC. We projected daily new infections and hospitalizations up to May 31, 2021 under the different levels of adherence to social distancing and mask-wearing after relaxation of stay-at-home restrictions. We assumed that the relaxation of stay-at-home policies would occur in the context of adaptive reopening, where a new hospitalization rate of ≥ 2 per 100,000 residents would trigger reinstatement of stay-at-home restrictions while a new hospitalization rate of ≤ 0.8 per 100,000 residents would trigger relaxation of stay-at-home restrictions. Without social distancing and mask-wearing, simulated relaxation of stay-at-home restrictions led to epidemic resurgence and necessary reinstatement of stay-at-home restrictions within 42 days. NYC would have stayed fully open for 26% of the time until May 31, 2021, alternating reinstatement and relaxation of stay-at-home restrictions in four cycles. At a low (50%) level of adherence to mask-wearing, NYC would have needed to implement stay-at-home restrictions between 8% and 32% of the time depending on individual adherence to social distancing. At moderate to high levels of adherence to mask-wearing without social distancing, NYC would have needed to implement stay-at-home restrictions. In threshold analyses, avoiding reinstatement of stay-at-home restrictions required a minimum of 60% adherence to mask-wearing at 50% adherence to social distancing. With low adherence to mask-wearing and social distancing, reinstatement of stay-at-home restrictions in NYC was inevitable. High levels of adherence to social distancing and mask-wearing could have attributed to avoiding recurrent surges without reinstatement of stay-at-home restrictions., (© 2022. The Author(s).)

Infectious disease transmission is a nonlinear process with complex, sometimes unintuitive dynamics. Modeling can transform information about a disease process and its parameters into quantitative projections that help decision makers compare public health response options. However, modelers face methodologic challenges, data challenges, and communication challenges, which are exacerbated under the time constraints of a public health emergency. We review methods, applications, challenges and opportunities for real-time infectious disease modeling during public health emergencies, with examples drawn from the two deadliest pandemics in recent history: HIV/AIDS and coronavirus disease 2019 (COVID-19).

We review and synthesize results from a series of analyses estimating the benefit of screening for unhealthy alcohol use, depression, and tobacco to detect individuals at heightened risk for co-occurring anxiety, pain, depression, unhealthy alcohol use, and other substance use among people with HIV and HIV-uninfected individuals in the Veterans Aging Cohort Study. We also examine the potential impact of reducing unhealthy alcohol use and depressive symptoms on the incidence of co-occurring conditions. We found that screening for alcohol and depression may help identify co-occurring symptoms of anxiety, depression, and pain interference, treating unhealthy alcohol use may improve co-occurring pain interference and substance use, and improving depressive symptoms may improve co-occurring anxiety, pain interference, and smoking. We propose that an integrated approach to screening and treatment for unhealthy alcohol use, depression, anxiety, pain, and other substance use may facilitate diagnostic assessment and treatment of these conditions, improving morbidity and mortality., (© 2021. The Author(s).)

Background: Almost half of Veterans with localized prostate cancer receive inappropriate, wasteful staging imaging. Our team has explored the barriers and facilitators of guideline-concordant prostate cancer imaging and found that (1) patients with newly diagnosed prostate cancer have little concern for radiographic staging but rather focus on treatment and (2) physicians trust imaging guidelines but are apt to follow their own intuition, fear medico-legal consequences, and succumb to influence from imaging-avid colleagues. We used a theory-based approach to design a multi-level intervention strategy to promote guideline-concordant imaging to stage incident prostate cancer., Methods: We designed the Prostate Cancer Imaging Stewardship (PCIS) intervention: a multi-site, stepped wedge, cluster-randomized trial to determine the effect of a physician-focused behavioral intervention on Veterans Health Administration (VHA) prostate cancer imaging use. The multi-level intervention, developed according to the Theoretical Domains Framework (TDF) and Behavior Change Wheel, combines traditional physician behavior change methods with novel methods of communication and data collection. The intervention consists of three components: (1) a system of audit and feedback to clinicians informing individual clinicians and their sites about how their behavior compares to their peers' and to published guidelines, (2) a program of academic detailing with the goal to educate providers about prostate cancer imaging, and (3) a CPRS Clinical Order Check for potentially guideline-discordant imaging orders. The intervention will be introduced to 10 participating geographically distributed study sites., Discussion: This study is a significant contribution to implementation science, providing VHA an opportunity to ensure delivery of high-quality care at the lowest cost using a theory-based approach. The study is ongoing. Preliminary data collection and recruitment have started; analysis has yet to be performed., Trial Registration: CliniclTrials.gov NCT03445559. Prospectively registered on February 26, 2018., (© 2021. The Author(s).)

The body of knowledge on alcohol use and communicable diseases has been growing in recent years. Using a narrative review approach, this paper discusses alcohol's role in the acquisition of and treatment outcomes from four different communicable diseases: these include three conditions included in comparative risk assessments to date-Human Immunodeficiency Virus (HIV)/AIDS, tuberculosis (TB), and lower respiratory infections/pneumonia-as well as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) because of its recent and rapid ascension as a global health concern. Alcohol-attributable TB, HIV, and pneumonia combined were responsible for approximately 360,000 deaths and 13 million disability-adjusted life years lost (DALYs) in 2016, with alcohol-attributable TB deaths and DALYs predominating. There is strong evidence that alcohol is associated with increased incidence of and poorer treatment outcomes from HIV, TB, and pneumonia, via both behavioral and biological mechanisms. Preliminary studies suggest that heavy drinkers and those with alcohol use disorders are at increased risk of COVID-19 infection and severe illness. Aside from HIV research, limited research exists that can guide interventions for addressing alcohol-attributable TB and pneumonia or COVID-19. Implementation of effective individual-level interventions and alcohol control policies as a means of reducing the burden of communicable diseases is recommended.

Unhealthy alcohol use, smoking, and depressive symptoms are risk factors for cardiovascular disease (CVD). Little is known about their co-occurrence - termed a syndemic, defined as the synergistic effect of two or more conditions-on CVD risk in people with HIV (PWH). We used data from 5621 CVD-free participants (51% PWH) in the Veteran's Aging Cohort Study-8, a prospective, observational study of veterans followed from 2002 to 2014 to assess the association between this syndemic and incident CVD by HIV status. Diagnostic codes identified cases of CVD (acute myocardial infarction, stroke, heart failure, peripheral artery disease, and coronary revascularization). Validated measures of alcohol use, smoking, and depressive symptoms were used. Baseline number of syndemic conditions was categorized (0, 1, ≥ 2 conditions). Multivariable Cox Proportional Hazards regressions estimated risk of the syndemic (≥ 2 conditions) on incident CVD by HIV-status. There were 1149 cases of incident CVD (52% PWH) during the follow-up (median 10.1 years). Of the total sample, 64% met our syndemic definition. The syndemic was associated with greater risk for incident CVD among PWH (Hazard Ratio [HR] 1.87 [1.47-2.38], p < 0.001) and HIV-negative veterans (HR 1.70 [1.35-2.13], p < 0.001), compared to HIV-negative with zero conditions. Among those with the syndemic, CVD risk was not statistically significantly higher among PWH vs. HIV-negative (HR 1.10 [0.89, 1.37], p = .38). Given the high prevalence of this syndemic combined with excess risk of CVD, these findings support linked-screening and treatment efforts., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We assessed whether tobacco screening provides clinically meaningful information about other substance use, including alcohol and other drug use, potentially facilitating targeting of screening for substance use. Using data from the Veterans Aging Cohort Study survey sample (VACS; N = 7510), we calculated test performance characteristics of tobacco use screening results for identification of other substance use including sensitivity, specificity, positive-likelihood-ratio (+LR = [sensitivity/(1-specificity)]: increase in odds of substance use informed by a positive tobacco screen), and negative-likelihood-ratio (-LR: [(1-sensitivity)/specificity]: reduction in odds of substance use informed by a negative tobacco screen). The sample was 95% male, 75% minority, and 43% were current and 33% were former smokers. Never smoking, versus any history, indicated an approximate four-fold decrease in the odds of injection drug use (-LR = 0.26), an approximate 2.5-fold decrease in crack/cocaine (-LR = 0.35) and unhealthy alcohol use (-LR = 0.40), an approximate two-fold decrease in marijuana (-LR = 0.51) and illicit opioid use (-LR = 0.48), and an approximate 30% decrease in non-crack/cocaine stimulant use (-LR = 0.75). Never smoking yielded more information than current non-smoking (never/former smoking). Positive results on tobacco screening were less informative than negative results; current smoking, versus former/never smoking, provided more information than lifetime smoking and was associated with a 40% increase in the odds of non-crack/cocaine stimulant use (+LR = 1.40) and opioid use (+LR = 1.44), 50% increase in marijuana use (+LR = 1.52) and injection drug use (+LR = 1.55), and an 80-90% increase in crack/cocaine use (+LR = 1.93) and unhealthy alcohol use (+LR = 1.75). When comprehensive screening for substance use is not possible, tobacco screening may inform decisions about targeting substance use screening., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Inc.)

Patient-centered care, defined as "providing care that is respectful of, and responsive to, individual patient preferences, needs and values, and ensuring that patient values guide all clinical decisions," is advocated by clinicians and professional organizations and is part of a composite criterion for augmented reimbursement for various health care settings, including patient-centered medical homes. Despite general agreement that patient-centered care is a good idea and worthy of incentivization, patient-centered care is difficult to assess accurately, scalably, and feasibly. In this commentary, we suggest that assessment of patient-centered care may be improved by identifying circumstances that indicate its probable absence-in particular, by flagging probable discordance between a patient's preferences and their treatment care plan. One potential marker of this discordance is persistent lack of control of a comorbid condition that is easily controllable by existing therapies and where existing therapies are sufficiently diverse to be compatible with a wide range of patient preferences (eg, stage 1 hypertension, type 2 diabetes with glycated hemoglobin < 8.5%). We outline how this approach may be tested, validated, and harmonized with existing quality improvement activities.