Protocol for a pragmatic trial of Cannabidiol (CBD) to improve chronic pain symptoms among United States Veterans.

BACKGROUND: Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD's analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD's effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC). METHODS: We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance). DISCUSSION: Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD's analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans. TRIAL REGISTRATION: This protocol is registered at clinicaltrials.gov under study number NCT06213233.

Comparative Effectiveness of Three Digital Interventions for Adults Seeking Psychiatric Services: A Randomized Clinical Trial.

Importance: There is a substantial gap between demand for and availability of mental health services. Digital mental health interventions (DMHIs) are promising tools for bridging this gap, yet little is known about their comparative effectiveness. Objective: To assess whether patients randomized to a cognitive behavioral therapy (CBT)-based or mindfulness-based DMHI had greater improvements in mental health symptoms than patients randomized to the enhanced personalized feedback (EPF)-only DMHI. DESIGN,: SETTING, AND PARTICIPANTS This randomized clinical trial was conducted between May 13, 2020, and December 12, 2022, with follow-up at 6 weeks. Adult patients of outpatient psychiatry services across various clinics within the University of Michigan Health System with a scheduled or recent outpatient psychiatry appointment were recruited. Eligible patients were randomized to an intervention arm. All analyses followed the intent-to-treat principle. Interventions: Participants were randomized to 1 of 5 intervention arms: (1) EPF only; (2) Silvercloud only, a mobile application designed to deliver CBT strategies; (3) Silvercloud plus EPF; (4) Headspace only, a mobile application designed to train users in mindfulness practices; and (5) Headspace plus EPF. Main Outcomes and Measures: The primary outcome was change in depressive symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9; score range: 0-27, with higher scores indicating greater depression symptoms). Secondary outcomes included changes in anxiety, suicidality, and substance use symptoms. Results: A total of 2079 participants (mean [SD] age, 36.8 [14.3] years; 1423 self-identified as women [68.4%]) completed the baseline survey. The baseline mean (SD) PHQ-9 score was 12.7 (6.4) and significantly decreased for all 5 intervention arms at 6 weeks (from -2.1 [95% CI, -2.6 to -1.7] to -2.9 [95% CI, -3.4 to -2.4]; n = 1885). The magnitude of change was not significantly different across the 5 arms (F4,1879 = 1.19; P = .31). Additionally, the groups did not differ in decrease in anxiety or substance use symptoms. However, the Headspace arms reported significantly greater improvements on a suicidality measure subscale compared with the Silvercloud arms (mean difference in mean change = 0.63; 95% CI, 0.20-1.06; P = .004). Conclusions and Relevance: This randomized clinical trial found decreases in depression and anxiety symptoms across all DMHIs and minimal evidence that specific applications were better than others. The findings suggest that DMHIs may provide support for patients during waiting list-related delays in care. Trial Registration: ClinicalTrials.gov Identifier: NCT04342494.

Duration of New-Onset Depressive Symptoms During Medical Residency.

Importance: The implications of new-onset depressive symptoms during residency, particularly for first-year physicians (ie, interns), on the long-term mental health of physicians are unknown. Objective: To examine the association between and persistence of new-onset and long-term depressive symptoms among interns. Design, Setting, and Participants: The ongoing Intern Health Study (IHS) is a prospective annual cohort study that assesses the mental health of incoming US-based resident physicians. The IHS began in 2007, and a total of 105 residency programs have been represented in this national study. Interns enrolled sequentially in annual cohorts and completed follow-up surveys to screen for depression using the 9-item Patient Health Questionnaire-9 (PHQ-9) throughout and after medical training. The data were analyzed from May 2023 to March 2024. Exposure: A positive screening result for depression, defined as an elevated PHQ-9 score of 10 or greater (indicating moderate to severe depression) at 1 or more time points during the first postgraduate year of medical training (ie, the intern year). Main Outcomes and Measures: The main outcomes assessed were mean PHQ-9 scores (continuous) and proportions of physicians with an elevated PHQ-9 score (≥10; categorical or binary) at the time of the annual follow-up survey. To account for repeated measures over time, a linear mixed model was used to analyze mean PHQ-9 scores and a generalized estimating equation (GEE) was used to analyze the binary indicator for a PHQ-9 score of 10 or greater. Results: This study included 858 physicians with a PHQ-9 score of less than 10 before the start of their internship. Their mean (SD) age was 27.4 (9.0) years, and more than half (53.0% [95% CI, 48.5%-57.5%]) were women. Over the follow-up period, mean PHQ-9 scores did not return to the baseline level assessed before the start of the internship in either group (those with a positive depression screen as interns and those without). Among interns who screened positive for depression (PHQ-9 score ≥10) during their internship, mean PHQ-9 scores were significantly higher at both 5 years (4.7 [95% CI, 4.4-5.0] vs 2.8 [95% CI, 2.5-3.0]; P < .001) and 10 years (5.1 [95% CI, 4.5-5.7] vs 3.5 [95% CI, 3.0-4.0]; P < .001) of follow-up. Furthermore, interns with an elevated PHQ-9 score (≥10) demonstrated a higher likelihood of meeting this threshold during each year of follow-up. Conclusions and Relevance: In this cohort study of IHS participants, a positive depression screening result during the intern year had long-term implications for physicians, including having persistently higher mean PHQ-9 scores and a higher likelihood of meeting this threshold again. These findings underscore the pressing need to address the mental health of physicians who experience depressive symptoms during their training and to emphasize the importance of interventions to sustain the health of physicians throughout their careers.

Association Between Cost Sharing and Naloxone Prescription Dispensing.

Importance: Increasing access to naloxone (an opioid antagonist that can reverse overdose) could slow the US opioid epidemic. Prior studies suggest cost sharing may be a barrier to dispensing of naloxone prescriptions, but these studies were limited by their cross-sectional designs and use of databases that do not capture prescriptions that are not filled (abandoned). Objective: To evaluate the association between cost sharing and naloxone prescription abandonment (nondispensing of naloxone prescriptions). Design, Setting, and Participants: This cross-sectional, regression discontinuity analysis exploited the fact that deductibles typically reset at the beginning of the year in commercial and Medicare plans. The included data were derived from the 2020-2021 IQVIA Formulary Impact Analyzer (a pharmacy transactions database that represents 63% of prescriptions at US pharmacies). The analysis included claims for naloxone nasal spray among commercially insured patients and Medicare patients that occurred during the 60 days before January 1, 2021, through 59 days after January 1, 2021. Exposure: Cost sharing, which is defined as the amount patients would have to pay to fill prescriptions. Main Outcomes and Measures: Local linear regression models were used to assess for abrupt changes in cost sharing and the probability of prescription abandonment on January 1, 2021. To estimate the association between cost sharing and prescription abandonment, a fuzzy regression discontinuity analysis was conducted. Results: These analyses included naloxone claims for 71 306 commercially insured patients and 101 706 Medicare patients (40 019 [56.1%] and 61 410 [60.4%], respectively, were female). The commercially insured patients and Medicare patients accounted for 73 311 and 106 076 naloxone claims, respectively. On January 1, 2021, the mean cost sharing per claim increased by $15.0 (95% CI, $13.8-$16.2) for commercially insured patients and increased by $12.3 (95% CI, $10.9-$13.6) for Medicare patients and the probability of abandonment increased by 4.7 (95% CI, 3.2-6.2) percentage points and 2.8 (95% CI, 1.6-4.1) percentage points, respectively. The results from the fuzzy regression discontinuity analysis suggest a decision by commercial and Medicare plans to increase naloxone cost sharing by $10 would be associated with percentage-point increases of 3.1 (95% CI, 2.2-4.1) and 2.3 (95% CI, 1.4-3.2), respectively, in the probability of abandonment. Conclusions: The elimination of cost sharing might be associated with increased naloxone dispensing to commercially insured and Medicare patients.

Regional variation in financial hardship among US veterans during the COVID-19 pandemic.

Geographic variation in hardship, especially health-related hardship, was identified prior to and during the pandemic, but we do not know whether this variation is consistent among Veterans Health Administration (VHA)-enrolled veterans, who reported markedly high rates of financial hardship during the pandemic, despite general and veteran-specific federal policy efforts aimed at reducing hardship. In a nationwide, regionally stratified sample of VHA-enrolled veterans, we examined whether the prevalence of financial hardship during the pandemic varied by US Census region. We found veterans in the South, compared with those in other census regions, reported higher rates of severe-to-extreme financial strain, using up all or most of their savings, being unable to pay for necessities, being contacted by collections, and changing their employment due to the kind of work they could perform. Regional variation in veteran financial hardship demonstrates a need for further research about the role and interaction of federal and state financial-assistance policies in shaping risks for financial hardship as well as potential opportunities to mitigate risks among veterans and reduce variation across regions.

Impact of Perceived Access and Treatment Knowledge on Medication Preferences for Opioid Use Disorder.

BACKGROUND: Medications for opioid use disorders (MOUDs) are effective, but most people with opioid use disorder (OUD) do not receive treatment. Prior research has explored patients' structural barriers to access and perceptions of MOUD. Little research has considered treatment knowledge and perceptions outside of the patient population. Members of the public without OUD themselves (eg, family, friends) can significantly influence treatment decisions of persons with OUD. Considering these gaps, we conducted an original survey with a diverse sample of US adults to explore knowledge and preferences toward OUD treatments. METHODS: We conducted an online survey with 1505 White, Black, and Latino/a Americans including a small percentage (8.5%) with self-reported lifetime OUD. The survey used vignettes to describe hypothetical patients with OUD, provide basic treatment information (ie, methadone, buprenorphine, naltrexone, nonmedication treatment), and then assessed treatment preferences. Using multivariable logistic regression, we examined associations between covariates of interest (eg, perceived access, knowledge, demographics) and preference for MOUD versus nonmedication treatment. RESULTS: There were 523 White, 502 Black, and 480 Latino/a respondents. Across racial/ethnic subsamples, respondents had the greatest knowledge of nonmedication treatments, with Black (72.7%) and Latino/a (70.2%) respondents having significantly greater knowledge compared to White respondents (61.8%). However, after viewing the vignette, a greater proportion of respondents chose methadone (35.8%) or buprenorphine (34.8%) as their first-choice treatment for hypothetical patients. Multivariable logistic regression suggested that among Black respondents, those with knowledge of nonmedication treatment were more likely to choose MOUD than those without knowledge (odds ratio = 2.41, 95% confidence interval = 1.34-4.34). Perceived treatment access did not affect treatment choice. CONCLUSIONS: Across racial groups, knowledge and perceived access to nonmedication treatment was greater than for MOUD, but many still selected MOUD as a first-choice treatment. Significant findings emphasized the importance of treatment knowledge around decision-making, highlighting opportunities for tailored education efforts to improve uptake of evidence-based treatment.

Association Between Cost-Sharing and Buprenorphine Prescription Abandonment.

BACKGROUND: Prior studies suggest cost-sharing decreases buprenorphine dispensing. However, these studies used databases that only report prescriptions filled by patients, not those that were "abandoned." Consequently, the studies could not calculate the probability of buprenorphine prescription abandonment or evaluate whether cost-sharing is associated with abandonment. OBJECTIVE: To evaluate the association between cost-sharing and buprenorphine prescription abandonment. DESIGN: Cross-sectional analysis of the IQVIA Formulary Impact Analyzer, a pharmacy transaction database representing 63% of U.S. retail pharmacies. The database includes transaction records ("claims") for prescriptions even if they are not filled. PARTICIPANTS: Buprenorphine claims in 2022 among commercially insured and Medicare patients. MAIN MEASURES: We evaluated the association between cost-sharing per 30-day supply and abandonment using logistic regression, controlling for patient characteristics, product type, and buprenorphine use in the prior 180 days. We assessed for effect modification by prior buprenorphine use. KEY RESULTS: Analyses included 2,346,994 and 1,242,596 buprenorphine prescription claims for commercially insured and Medicare patients, respectively. Among these claims, mean (SD) cost-sharing per 30-day supply was $28.1 (46.4) and $8.4 (20.2), and 1.5% and 1.2% were abandoned. Each $10 increase in cost-sharing per 30-day supply was associated with a 0.09 (95% CI: 0.09, 0.10) and 0.09 (95% CI: 0.08, 0.10) percentage-point increase in abandonment among commercially insured and Medicare patients. Among commercially insured and Medicare patients without prior buprenorphine use, respectively, a $10 increase in cost-sharing per 30-day supply was associated with a 0.12 (95% CI: 0.11, 0.14) and 0.13 (95% CI: 0.07, 0.18) percentage-point higher increase in the probability of abandonment compared with patients with > 90 days of prior buprenorphine use. CONCLUSIONS: Among commercially insured and Medicare patients, buprenorphine prescription abandonment is rare and only minimally associated with cost-sharing. Findings suggest elimination of buprenorphine cost-sharing should only be one component of a larger, multi-faceted campaign to increase buprenorphine dispensing.

Perceptions around medications for opioid use disorder among a diverse sample of U.S. adults.

INTRODUCTION: Medications for opioid use disorder (MOUD) including methadone (MMT), buprenorphine (BUP), and naltrexone (NTX) are safe and effective. However, there are significant negative perceptions surrounding MOUD, creating barriers to uptake. While research on MOUD stigma has largely focused on provider and patient experiences, fewer studies have explored MOUD perceptions among the general public. Given that MOUD stigma expressed by social ties surrounding individuals with OUD can influence treatment choices, we assessed MOUD perceptions among U.S. adults to determine how beliefs impacted treatment preference. We further explored how MOUD perceptions may be amplified among racialized groups with histories of experiencing drug-related discrimination. METHODS: The study collected survey data from a diverse sample of U.S. adults (n = 1508) between October 2020 and January 2021. The survey measured knowledge of MOUD and non-medication treatments, relative agreement with common MOUD perceptions, and treatment preferences. Multinomial logistic regression analysis tested associations with treatment preference, stratified by race/ethnicity. RESULTS: Descriptive results indicated that across groups, many respondents (66.8 %) had knowledge of MOUD, but believed MOUD was a "substitute" for opioids and had some degree of concern about misuse. Multivariable results showed knowledge of non-medication treatments was positively associated with MOUD preference among White (MMT OR = 3.16, 95 % CI = 1.35-7.39; BUP OR = 2.69, CI = 1.11-6.47), Black (MMT OR = 3.91, CI = 1.58-9.69), and Latino/a (MMT OR = 5.12, CI = 1.99-13.2; BUP OR = 3.85, CI = 1.5-9.87; NTX OR = 4.51, CI = 1.44-14.06) respondents. Among White respondents, we identified positive associations between MOUD experience and buprenorphine preference (OR = 4.33, CI = 1.17-16.06); non-medication treatment experience and preference for buprenorphine (OR = 2.86, CI = 1.03-7.94) and naltrexone (OR = 3.17, CI = 1.08-9.28). Concerns around misuse of methadone were negatively associated with methadone preference among White (OR = 0.65, CI = 0.43-0.98) and Latino/a (OR = 0.49, CI = 0.34-0.7), and concerns around misuse of buprenorphine was negatively associated with preference for MOUD among White (MMT OR = 0.62, CI = 0.39-0.99; BUP OR = 0.48, CI = 0.3-0.77; NTX OR = 0.6, CI = 0.36-0.99) and Latino/a (BUP OR = 0.59, CI = 0.39-0.89) respondents. CONCLUSIONS: This analysis offers critical insights into treatment perceptions beyond the patient population, finding that negative beliefs around MOUD are common and negatively associated with preferences for medication-based treatment. These findings highlight implications for public support of evidence-based treatment and lay the groundwork for future interventions addressing public stigma toward MOUD.

Responding to the ripple effects of sexual harassment: an emergency management framework.

Sexual harassment in academia is endemic driven by gender-based inequalities and sustained through organizational tolerance, and its impact extends beyond the primary victim(s). Applying principles of emergency management provides a framework for institutions to balance their obligations to the primary victim(s) while also acknowledging the need to restore the well-being and culture of secondary victims.

Association Between Prescription Drug Monitoring Program Use Mandate and Opioid Prescribing and Patient-Reported Outcomes After Surgery.

OBJECTIVE: To evaluate changes in opioid prescribing and patient-reported outcomes after surgery following implementation of Michigan's prescription drug monitoring program (PDMP) use mandate in June 2018. BACKGROUND: Most states mandate clinicians to query prescription drug monitoring program (PDMP) databases before prescribing controlled substances. Whether these PDMP use mandates affect opioid prescribing and patient-reported outcomes after surgery is unclear, especially among patients with elevated "Narx" scores, a risk score for overdose death used in most PDMPs. METHODS: We conducted an interrupted time series analysis of a statewide surgical registry linked to Michigan's PDMP database. Analyses included adults undergoing general surgical procedures during January 2017-October 2019. Outcomes included monthly mean days supplied in dispensed opioid prescriptions (those filled within 3 days of discharge) and monthly mean scores for 3 patient-reported outcomes (pain in the week after surgery, care satisfaction, regret undergoing surgery). Segmented regression models were used to assess for level and slope changes in outcomes in June 2018. Analyses were repeated among patients with Narx scores ≥200, a threshold that defines the top quartile. RESULTS: Analyses included 21,897 patients. The mandate was associated with a -0.5 (95% CI: -0.8, -0.2) level decrease in mean days supplied in dispensed opioid prescriptions, but not with worsened patient-reported outcomes. Findings were similar among patients with Narx scores ≥200. CONCLUSIONS: Following implementation of Michigan's PDMP use mandate, the duration of opioid prescriptions decreased, but patient-reported outcomes did not worsen. Findings suggest PDMP use mandates may not be associated with worsened experience among general surgical patients.

The effect of a pilot brief educational intervention on preferences regarding treatments for opioid use disorder.

Purpose: Negative perceptions around medications for opioid use disorder (MOUD) amongst the public could deter patients with opioid use disorder (OUD) from engaging with MOUD. Thus, we evaluated whether a brief intervention could improve preferences for MOUD in people who may or may not use opioids. Methods: We employed a pre-post design to assess the effect of a brief educational intervention on preferences for methadone, buprenorphine, naltrexone, and non-medication treatment in an online sample of US adults stratified by race, who may or may not use opioids. Respondents ranked their preferences in OUD treatment before and after watching four one-minute educational videos about treatment options. Changes in treatment preferences were analyzed using Bhapkar's test and post hoc McNemar's tests. A binary logistic generalized estimating equation (GEE) assessed factors associated with preference between treatments. Results: The sample had 530 responses. 194 identified as White, 173 Black, 163 Latinx. Treatment preferences changed significantly towards MOUD (p<.001). This effect was driven by changes toward buprenorphine (OR=2.38; p<.001) and away from non-medication treatment (OR=0.20; p<.001). There was no significant difference in effect by race/ethnicity. People with lower opioid familiarity were significantly more likely to change their preferences towards MOUD following the intervention. Conclusion: Respondent preferences for MOUD increased following the intervention suggesting that brief educational interventions can change treatment preferences towards MOUD. These findings offer insights into perceptions of OUD treatment in a racially stratified sample and serve as a foundation for future educational materials that target MOUD preferences in the general public.

Risk of Potentially Preventable Hospitalizations After SARS-CoV-2 Infection.

Importance: Research demonstrates that SARS-CoV-2 infection is associated with increased risk of all-cause hospitalization. However, no prior studies have assessed the association between SARS-CoV-2 and potentially preventable hospitalizations-that is, hospitalizations for conditions that can usually be effectively managed in ambulatory care settings. Objective: To examine whether SARS-CoV-2 is associated with potentially preventable hospitalization in a nationwide cohort of US veterans. Design, Setting, and Participants: This cohort study used an emulated target randomized trial design with monthly sequential trials to compare risk of a potentially preventable hospitalization among veterans with SARS-CoV-2 and matched comparators without SARS-CoV-2. A total of 189 136 US veterans enrolled in the Veterans Health Administration (VHA) who were diagnosed with SARS-CoV-2 between March 1, 2020, and April 30, 2021, and 943 084 matched comparators were included in the analysis. Data were analyzed from May 10, 2023, to January 26, 2024. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was a first potentially preventable hospitalization in VHA facilities, VHA-purchased community care, or Medicare fee-for-service care. Extended Cox models were used to examine adjusted hazard ratios (AHRs) of potentially preventable hospitalization among veterans with SARS-CoV-2 and comparators during follow-up periods of 0 to 30, 0 to 90, 0 to 180, and 0 to 365 days. The start of follow-up was defined as the date of each veteran's first positive SARS-CoV-2 diagnosis, with the same index date applied to their matched comparators. Results: The 1 132 220 participants were predominantly men (89.06%), with a mean (SD) age of 60.3 (16.4) years. Most veterans were of Black (23.44%) or White (69.37%) race. Veterans with SARS-CoV-2 and comparators were well-balanced (standardized mean differences, all <0.100) on observable baseline clinical and sociodemographic characteristics. Overall, 3.10% of veterans (3.81% of those with SARS-CoV-2 and 2.96% of comparators) had a potentially preventable hospitalization during 1-year follow-up. Risk of a potentially preventable hospitalization was greater among veterans with SARS-CoV-2 than comparators in 4 follow-up periods: 0- to 30-day AHR of 3.26 (95% CI, 3.06-3.46); 0- to 90-day AHR of 2.12 (95% CI, 2.03-2.21); 0- to 180-day AHR of 1.69 (95% CI, 1.63-1.75); and 0- to 365-day AHR of 1.44 (95% CI, 1.40-1.48). Conclusions and Relevance: In this cohort study, an increased risk of preventable hospitalization in veterans with SARS-CoV-2, which persisted for at least 1 year after initial infection, highlights the need for research on ways in which SARS-CoV-2 shapes postinfection care needs and engagement with the health system. Solutions are needed to mitigate preventable hospitalization after SARS-CoV-2.

Impact of SARS-CoV-2 Infection on Long-Term Depression Symptoms among Veterans.

BACKGROUND: Prior research demonstrates that SARS-COV-2 infection can be associated with a broad range of mental health outcomes including depression symptoms. Veterans, in particular, may be at elevated risk of increased depression following SARS-COV-2 infection given their high rates of pre-existing mental and physical health comorbidities. However, few studies have tried to isolate SARS-COV-2 infection associations with long term, patient-reported depression symptoms from other factors (e.g., physical health comorbidities, pandemic-related stress). OBJECTIVE: To evaluate the association between SARS-COV-2 infection and subsequent depression symptoms among United States Military Veterans. DESIGN: Survey-based non-randomized cohort study with matched comparators. PARTICIPANTS: A matched-dyadic sample from a larger, stratified random sample of participants with and without known to SARS-COV-2 infection were invited to participate in a survey evaluating mental health and wellness 18-months after their index infection date. Sampled participants were stratified by infection severity of the participant infected with SARS-COV-2 (hospitalized or not) and by month of index date. A total of 186 participants in each group agreed to participate in the survey and had sufficient data for inclusion in analyses. Those in the uninfected group who were later infected were excluded from analyses. MAIN MEASURES: Participants were administered the Patient Health Questionnaire-9 as part of a phone interview survey. Demographics, physical and mental health comorbidities were extracted from VHA administrative data. KEY RESULTS: Veterans infected with SARS-COV-2 had significantly higher depression symptoms scores compared with those uninfected. In particular, psychological symptoms (e.g., low mood, suicidal ideation) scores were elevated relative to the comparator group (MInfected = 3.16, 95%CI: 2.5, 3.8; MUninfected = 1.96, 95%CI: 1.4, 2.5). Findings were similar regardless of history of depression. CONCLUSION: SARS-COV-2 infection was associated with more depression symptoms among Veterans at 18-months post-infection. Routine evaluation of depression symptoms over time following SARS-COV-2 infection is important to facilitate adequate assessment and treatment.

Self-Reported Everyday Functioning After COVID-19 Infection.

Importance: Changes in everyday functioning are crucial to assessing the long-term impact of COVID-19 infection. Objective: To examine the impact of COVID-19 infection on everyday functioning 18 months after infection among veterans with and without histories of COVID-19 infection. Design, Setting, and Participants: This cohort study used data from the US Veterans Affairs (VA) and included 186 veterans who had COVID-19 between October 2020 and April 2021 (ie, COVID-19 cohort) and 186 matched comparators who did not have documented COVID-19 infections (ie, control cohort). This match balanced the risk of COVID-19 based on 39 variables measured in the 24 months before infection or match, using principles of target trial emulation. Data were analyzed from December 2022 to December 2023. Exposure: First documented COVID-19. Main Outcome and Measures: The differences in self-reported everyday functioning 18 months after COVID-19 infection were estimated and compared with their matched comparators. Within-matched pair logistic and linear regressions assessed differences in outcomes and were weighted to account for sampling and nonresponse. Results: Among the 186 matched pairs of participants, their weighted mean age was 60.4 (95% CI, 57.5 to 63.2) years among veterans in the COVID-19 cohort (weighted sample, 91 459 of 101 133 [90.4%] male; 30 611 [30.3%] Black or African American veterans; 65 196 [64.4%] White veterans) and 61.1 (95% CI, 57.8 to 64.4) years among their comparators in the control cohort (91 459 [90.4%] male; 24 576 [24.3%] Black or African American veterans; 70 157 [69.4%] White veterans). A high proportion of veterans in the COVID-19 cohort (weighted percentage, 44.9% [95% CI, 34.2% to 56.2%]) reported that they could do less than what they felt they could do at the beginning of 2020 compared with the control cohort (weighted percentage, 35.3%; [95% CI, 25.6% to 46.4%]; within-matched pair adjusted odds ratio [OR], 1.52 [95% CI, 0.79 to 2.91]). There was no association of documented COVID-19 infection with fatigue, substantial pain, limitations in either activities of daily living and instrumental activities of daily living, severely curtailed life-space mobility, employment, or mean health-related quality of life on a utility scale. Conclusions and Relevance: In this cohort study of veterans with and without documented COVID-19, many reported a substantial loss of everyday functioning during the pandemic regardless of whether or not they had a documented infection with COVID-19. Future work with larger samples is needed to validate the estimated associations.

Lifetime non-fatal overdose experiences among at-risk adolescents and young adults in the emergency department with past-year opioid use in the USA.

BACKGROUND: Adolescents and young adults with risk factors for opioid misuse and opioid use disorder are at elevated risk for overdose. We examined prior non-fatal overdose experiences among at-risk adolescents/young adults to inform prevention efforts. METHODS: Adolescents/young adults (ages 16-30) in two US emergency departments self-reporting past year opioid misuse or opioid use plus a misuse risk factor completed a baseline survey as part of an ongoing randomised controlled trial. We describe baseline factors associated with (a) overall non-fatal overdose experiences and (b) groups based on substance(s) used during the worst overdose experience. RESULTS: Among 771 participants (27.9% male), 40.7% reported a non-fatal overdose experience. Compared with those without a prior overdose experience, those with prior overdose experience(s) were less likely to be heterosexual, and more likely to report a prior suicide attempt and greater peer substance misuse. Regarding the worst overdose experience, substance(s) included: 36.6% alcohol only, 28.0% alcohol and cannabis, 22.6% alcohol with other substance(s) and 12.7% other substance(s) only (eg, opioids). Compared with the alcohol only group, the alcohol and cannabis group were younger and less likely to be heterosexual; the alcohol with other substance(s) group were older and had greater peer substance misuse; and the other substance(s) only group were more likely to be male, receive public assistance, screen positive for anxiety and less likely to be heterosexual. CONCLUSIONS: Among at-risk adolescents/young adults, findings support the need for tailored overdose prevention efforts based on substance(s) used, with consideration of sexuality, mental health and peer substance use. TRIAL REGISTRATION NUMBER: NCT04550715.

Changes in Outpatient Health Care Use After COVID-19 Infection Among Veterans.

Importance: The association of COVID-19 infection with outpatient care utilization is unclear. Many studies reported population surveillance studies rather than comparing outpatient health care use between COVID-19-infected and uninfected cohorts. Objective: To compare outpatient health care use across 6 categories of care (primary care, specialty care, surgery care, mental health, emergency care, and diagnostic and/or other care) between veterans with or without COVID-19 infection. Design, Setting, and Participants: In a retrospective cohort study of Veterans Affairs primary care patients, veterans with COVID-19 infection were matched to a cohort of uninfected veterans. Data were obtained from the Veterans Affairs Corporate Data Warehouse and the Centers for Medicare & Medicaid Services Fee-for-Service Carrier/Physician Supplier file from January 2019 through December 2022. Data analysis was performed from September 2022 to April 2023. Exposure: COVID-19 infection. Main Outcomes and Measures: The primary outcome was the count of outpatient visits after COVID-19 infection. Negative binomial regression models compared outpatient use over a 1-year preinfection period, and peri-infection (0-30 days), intermediate (31-183 days), and long-term (184-365 days) postinfection periods. Results: The infected (202 803 veterans; mean [SD] age, 60.5 [16.2] years; 178 624 men [88.1%]) and uninfected (202 803 veterans; mean [SD] age, 60.4 [16.5] years; 178 624 men [88.1%]) cohorts were well matched across all covariates. Outpatient use in all categories (except surgical care) was significantly elevated during the peri-infection period for veterans with COVID-19 infection compared with the uninfected cohort, with an increase in all visits of 5.12 visits per 30 days (95% CI, 5.09-5.16 visits per 30 days), predominantly owing to primary care visits (increase of 1.86 visits per 30 days; 95% CI, 1.85-1.87 visits per 30 days). Differences in outpatient use attenuated over time but remained statistically significantly higher at 184 to 365 days after infection (increase of 0.25 visit per 30 days; 95% CI, 0.23-0.27 visit per 30 days). One-half of the increased outpatient visits were delivered via telehealth. The utilization increase was greatest for veterans aged 85 years and older (6.1 visits, 95% CI, 5.9-6.3 visits) vs those aged 20 to 44 years (4.8 visits, 95% CI, 4.7-4.8 visits) and unvaccinated veterans (4.5 visits, 95% CI, 4.3-4.6 visits) vs vaccinated veterans (3.2 visits; 95% CI, 3.4-4.8 visits). Conclusions and Relevance: This study found that outpatient use increased significantly in the month after infection, then attenuated but remained greater than the uninfected cohorts' use through 12 months, which suggests that there are sustained impacts of COVID-19 infection.

A multidimensional appraisal of early menstrual pain experience.

BACKGROUND: Symptomatic dysmenorrhea is a global problem, affecting more than 40% of menstruating persons. Cross-sectional studies have implicated psychosocial, biological, and sensory factors in dysmenorrhea but the mechanisms are not fully understood. Only a few prospective longitudinal studies have evaluated such factors in relation to the emergence and course of dysmenorrhea at menarche. OBJECTIVE: This study aimed to describe the initial menstruation experience and to evaluate the association of premenarchal psychosocial and sensory factors with the intensity of dysmenorrhea during the period in the fourth month. STUDY DESIGN: This was a prospective cohort study of adolescents who completed premenarchal assessments and postmenarchal daily menstrual diaries for their first (n=149) and fourth month periods (n=114). They were recruited shortly before menarche and completed baseline assessments, including psychosocial questionnaires and experimental pain sensitivity (pressure testing, bladder provocation), and their parents completed related pain questionnaires. The relation between the hypothesized premenarchal factors and month 4 dysmenorrhea intensity was evaluated using Kruskal-Wallis and chi-square tests for low (<3 on a 0-10 scale) vs higher (≥3) menstrual pain groups based on maximal pain ratings recorded in a daily diary. RESULTS: Low levels of dysmenorrhea characterized the first (median, 1; interquartile range, 0-2) and fourth month periods (1; 0-3). Maximal pain ratings increased from the first to the fourth period (3; 1-5 vs 4; 1-6; P=.007). The distribution of dysmenorrhea was multimodal at month 4 with 31.6% of the participants having low levels of maximal pain (1; 0-1) and 68.4% having higher levels (5; 4-6; Hartigan's dip test P<.001). The baseline demographic, psychosocial, and parental pain characteristics were not associated with the development of worse dysmenorrhea. The baseline experimental pain sensitivity, based on pressure pain thresholds, did not differ between the low (15.7 N; 12.5-22.3) and higher (15.0 N; 10.9-21.4]) level dysmenorrhea groups. Baseline bladder pain at first urge also did not differ (low, 6; 0-20 vs higher, 7; 0-19). CONCLUSION: By their fourth month period, two-thirds of adolescents fell into the higher group for maximal dysmenorrhea, half reported some related impairments in physical activity, and one-seventh reported some related school absence. Premenarchal factors (experimental pain sensitivity, psychosocial profile, parental pain experience) linked to chronic pain emergence in the adult literature did not predict dysmenorrhea intensity, suggesting the dominant factor at menarche may be peripheral afferent activation. Further research is needed to understand the evolution of psychosocial and sensory mechanisms in the development and course of dysmenorrhea.

Risk of Suicide-Related Outcomes After SARS-COV-2 Infection: Results from a Nationwide Observational Matched Cohort of US Veterans.

BACKGROUND: Negative mental health-related effects of SARS-COV-2 infection are increasingly evident. However, the impact on suicide-related outcomes is poorly understood, especially among populations at elevated risk. OBJECTIVE: To determine risk of suicide attempts and other self-directed violence (SDV) after SARS-COV-2 infection in a high-risk population. DESIGN: We employed an observational design supported by comprehensive electronic health records from the Veterans Health Administration (VHA) to examine the association of SARS-COV-2 infection with suicide attempts and other SDV within one year of infection. Veterans with SARS-COV-2 infections were matched 1:5 with non-infected comparators each month. Three periods after index were evaluated: days 1-30, days 31-365, and days 1-365. PARTICIPANTS: VHA patients infected with SARS-COV-2 between March 1, 2020 and March 31, 2021 and matched non-infected Veteran comparators. MAIN MEASURES: Suicide attempt and other SDV events for the COVID-19 and non-infected comparator groups were analyzed using incidence rates per 100,000 person years and hazard ratios from Cox regressions modeling time from matched index date to first event. Subgroups were also examined. KEY RESULTS: 198,938 veterans with SARS-COV-2 (COVID-19 group) and 992,036 comparators were included. Unadjusted one-year incidence per 100,000 for suicide attempt and other SDV was higher among the COVID-19 group: 355 vs 250 and 327 vs 235, respectively. The COVID-19 group had higher risk than comparators for suicide attempts: days 1-30 hazard ratio (HR) = 2.54 (CI:2.05, 3.15), days 31-365 HR = 1.30 (CI:1.19, 1.43) and days 1-365 HR = 1.41 (CI:1.30, 1.54), and for other SDV: days 1-30 HR = 1.94 (CI:1.51, 2.49), days 31-365 HR = 1.32 (CI:1.20, 1.45) and days 1-365 HR = 1.38 (CI:1.26, 1.51). CONCLUSIONS: COVID-19 patients had higher risks of both suicide attempts and other forms of SDV compared to uninfected comparators, which persisted for at least one year after infection. Results support suicide risk screening of those infected with SARS-COV-2 to identify opportunities to prevent self-harm.