Pain, Substance Use Disorders, Mental Health, and Buprenorphine Treatment among Patients With and Without HIV.

Treatment of opioid use disorder (OUD) with buprenorphine improves outcomes and mortality among people with HIV (PWH). However, engagement is low and is influenced by comorbidities. We examined the impact of patterns of co-occurring pain, substance use disorders (SUDs), and mental health diagnoses on buprenorphine initiation and retention in PWH. The Veterans Aging Cohort Study contained 7,875 patients (2,702 PWH and 5,173 without HIV) with new OUD clinical encounters (2008-2017). Buprenorphine initiation and retention were derived from prescription data. We identified patterns of co-occurring diagnoses (via ICD codes) and assessed the effects of class membership on both outcomes using latent class analysis and regression analyses. The mean age of patients was 55, 98% were male, 58% Black, 8% Hispanic, and only 8% initiated buprenorphine within 12 months of OUD diagnosis. Four classes of co-occurring diagnoses were identified: "Few Co-occurring Diagnoses" (42.3%); "Multiple Pain Conditions" (21.3%); "Pain + SUD" (18.4%) and "Pain + SUD + Mental Health" (18.0%). Patients in the "Pain + SUD" class and "Pain + SUD + Mental Health" class were significantly less likely to initiate buprenorphine and had 59% and 45% lower odds, respectively, of initiating buprenorphine compared with patients in the "Few Co-occurring Diagnoses" class; this effect did not vary by HIV status. Buprenorphine retention was not significantly associated with HIV status or class membership. However, Black Veterans were less likely to initiate or be retained in buprenorphine treatment. Higher comorbidity burden was negatively associated with buprenorphine initiation but not with retention. More research is warranted to determine other factors that may influence treatment retention.

Cost minimization analysis of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants.

BACKGROUND: Trials describing 4-12 week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R-transplants), may be limited in application by costs and delayed access to expensive DAAs. A short prophylactic strategy may be safer and cost-effective. Here, we report a cost minimization analysis using the health system perspective to determine the least expensive DAA regimen, using available published strategies. OBJECTIVES: To conduct cost-minimization analyses (CMAs) from the health system perspective of four DAA regimens to prevent and/or treat HCV transmission from D+/R-kidney transplants. METHODS: CMAs comparing 4 strategies: 1) 7-day prophylaxis with generic sofosbuvir/velpatasvir (SOF/VEL), with 12-week branded glecaprevir/pibrentasvir (G/P) for those with transmission; 2) 8-day branded G/P prophylaxis, with 12-week branded SOF/VEL/voxilaprevir for those with transmission; 3) 4-week perioperative generic SOF/VEL prophylaxis, with 12-week branded G/P for those with transmission; and 4) 8-week branded G/P "transmit-and-treat." We included data from published literature to estimate the probability of viral transmission in patients who received DAA prophylaxis, and assumed a 100% transmission rate for those who received the "transmit-and-treat" approach. RESULTS: In base-case analyses, strategies 1 (expected cost [EC]: $2326) and 2 (expected cost: $2646) were less expensive than strategies 3 (EC: $4859) and 4 (EC: $18,525). Threshold analyses for 7-day SOF/VEL versus 8-day G/P suggested that there were reasonable input levels at which the 8-day strategy may be least costly. The threshold values for the SOF/VEL prophylaxis strategies (7-day vs. 4- week) indicated that the 4-week strategy is unlikely to be less costly under any reasonable value of the input variables. CONCLUSIONS: Short duration DAA prophylaxis using 7 days of SOF/VEL or 8 days of G/P has the potential to yield significant cost savings for D+/R- kidney transplants.

Qualitative Evaluation of University Students' Experience Delivering an Obesity Prevention Programme in Elementary Schools.

The Coordinated Approach to Child Health (CATCH) programme is an accredited obesity prevention programme in the United States, teaching children about nutrition, physical activity, and screen time limits. This study aimed to evaluate the perceptions of undergraduate and graduate student leaders' about their experience delivering the CATCH programme in elementary schools in Northern Illinois school districts during the 2019-2020 school year and its impact on their personal and professional skills and on programme participants. An email questionnaire was sent to eligible students. Grounded theory was used to analyze the students' responses. Two researchers assigned codes to the data and identified themes. Twenty-one students responded (50% response rate). Six identified themes include "purpose of CATCH programme," "school facilities and resources," "university students experience with CATCH lessons and activities," "benefits to university student," "benefits to children and teachers," and "identified weaknesses and suggested improvements to CATCH." University students delivering the CATCH programme appreciated the opportunity to practice in a real-world setting, gained transferable professional skills, increased programme content knowledge, identified CATCH programme benefits/strengths, and planned to apply lessons learned to future practice.

Coverage of the opioid crisis in national network television news from 2000-2020: A content analysis.

Background: News coverage has both negatively and positively influenced public awareness and perceptions surrounding the opioid crisis. This study aimed to describe and analyze national network television news framing of the scope and impact of the opioid crisis in the United States. Methods: We performed a retrospective content analysis on national network television evening news segments covering the opioid crisis from 1/2000 to 8/2020, which were obtained from the Vanderbilt Television News Archive. The database was queried for: opioid epidemic, oxycontin, heroin, fentanyl, and naloxone. Two independent reviewers quantitatively coded segment characteristics, including theme, geographic location, opioids mentioned, strategies for combatting the epidemic discussed, interviews conducted, and patient demographics. Changes in segment characteristics over time were analyzed using chi-square analyses and Fisher's exact tests. Results: News segments (N = 191) most commonly provided an overview of the epidemic (55.5%) and/or conveyed personal stories (40.3%). Prescription opioids (59.7%) and heroin (62.8%) were more often referenced than fentanyl (17.8%); the focus on heroin peaked in 2011-2015 (84.8%), while references to fentanyl significantly increased over time (p = 0.021). The most frequently interviewed people included patients with opioid use disorder (OUD) (47.1%), healthcare providers (36.7%), family members/friends (31.9%), and law enforcement (30.9%). Most of the featured patients with OUD were male (63.0%), white (88.4%), and young (< 40 years) adults (77.9%). Coverage of the crisis peaked in 2016. Conclusions: Evening news segments' emphasis on personal stories, while emotionally compelling, came at the cost of thematically-framed coverage that may improve public understanding of the complexities of the epidemic. The depiction of primarily white, young adult patients with OUD revealed a need for a greater emphasis in the news on underrepresented minorities and older adults, as these populations face additional stigma and disparities in OUD treatment initiation and retention.

Outcomes of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants.

Trials describing 4- to 12-week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R- transplants) may be limited in "real-world" application by costs and delayed access to DAAs. We previously reported HCV transmission of 13% among D+/R- transplants with 2- to 4-day pangenotypic sofosbuvir/velpatasvir (SOF/VEL) perioperative prophylaxis, where one patient with HCV transmission was a nonresponder to first-line full-course DAA. Here, we report new data with a 7-day prophylaxis protocol (N = 50), as well as cumulative treatment and outcome data on all HCV D+/R- transplants (N = 102). Overall, nine patients (9/102; 9%; 95% CI: 5%-16%) developed HCV transmission, with a significant decline noted in the 7-day group (2/50; 4%; 95% CI: 0%-13%) compared with 2- to 4-day prophylaxis (7/52; 13%; 95% CI: 5%-25%). All patients with HCV transmission achieved sustained virologic response post full-course therapy (including one nonresponder from initial trial). A 1:1 matched analysis (N = 102) with contemporary HCV D-/R- transplants (controls) showed that although the pretransplant wait time was significantly shorter for D+/R- compared with D-/R- (mean: 1.8 vs. 4.4 years; p < .001), there were no differences in infections, rejection, development of de novo donor-specific antibody, or transplant outcomes up to 6 months of transplant.

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients.

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R - transplants.

Hip Arthroscopy in Patients Aged 40 Years and Older: Greater Success With Labral Reconstruction Compared With Labral Repair.

PURPOSE: To assess the outcomes of complete, primary, arthroscopic hip labral reconstruction among patients aged 40 years and older compared with those who underwent primary labral repair and compared with patients aged 30 to 39 years who underwent complete, primary labral reconstruction. METHODS: We recruited all patients who underwent arthroscopic labral reconstruction between March 2010 and June 2015 and were aged 30 to 65 years or who underwent arthroscopic labral repair between June 2009 and June 2015 and were aged 40 to 65 years. The modified Harris Hip Score (mHHS), Lower Extremity Function Score, and visual analog scale score for average pain were collected preoperatively and at minimum 2-year follow-up. Failure was defined as the need for revision ipsilateral hip surgery. The rate of conversion to total hip arthroplasty (a subset of failure) was assessed separately. RESULTS: A total of 363 hips in 343 patients met the inclusion criteria. Follow-up was available for 312 hips (86.0%), and the average time to follow-up was 4.2 years (range, 2.0-8.5 years). After adjustment for differences in follow-up time between groups, failure was 3.29 times more likely for hips in the repair group aged 40 years and older than for hips in the reconstruction group aged 40 years and older (relative rate, 3.29; 95% confidence interval, 1.25-8.69; P = .02), and there was no difference in the failure rate for hips in the reconstruction group aged 40 years and older compared with hips in the reconstruction group aged 30 to 39 years (relative rate, 0.58; 95% confidence interval, 0.18-1.89; P = .37). The rate of conversion to total hip arthroplasty was not meaningfully different between the 3 groups. Among hips for which treatment did not fail, average improvement in the mHHS measured 35 points and both labral reconstruction groups saw a greater mHHS improvement than the labral repair group of patients aged 40 years and older (P = .01 and P < .01). CONCLUSIONS: Labral reconstruction led to a lower failure rate, greater average improvement in the mHHS, and equivalent postoperative patient-reported outcome scores compared with labral repair among patients aged 40 years and older in this study population, and the outcomes of labral reconstruction were similar between patients aged 40 years and older and those aged 30 to 39 years. Complete labral reconstruction may be particularly advantageous in patients aged 40 years and older. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Development and feasibility of a community pharmacy-driven 24-hour ambulatory blood pressure monitoring service.

BACKGROUND: Although 24-hour ambulatory blood pressure monitoring (ABPM) is recommended by practice guidelines, access to ABPM is poor in the United States. Other countries have increased ABPM access by making it available in community pharmacies. It is not known if a similar approach is feasible in the United States. OBJECTIVE: The objective of this study was to develop and evaluate the feasibility of a community pharmacy-driven ABPM service in the United States. SETTING: Two independent community pharmacies. PRACTICE DESCRIPTION: The ABPM service was developed through a collaboration between an academic partner and the clinical service leads of each pharmacy. Eligible patients were those referred by their provider or self-referred for white coat, masked, or sustained hypertension (HTN), symptoms of hypotension, or requiring confirmation of an initial diagnosis of HTN. The service was appointment-based, and the pharmacist sent the ABPM results and interpretation to the referring provider via facsimile. PRACTICE INNOVATION: This is the first description of a community pharmacy-driven ABPM service in the United States. EVALUATION: Descriptive statistics were used to summarize the data for the baseline demographics, ABPM findings, and a 9-question patient satisfaction survey. RESULTS: A total of 52 patients with a mean (SD) age of 56.6 (16.1) years, 50% women, 75% white, and 71.2% with a prior diagnosis of HTN were enrolled. Forty-six patients (88.5%) had successful ABPM readings with the most common blood pressure phenotypes being nocturnal HTN (91.3%), nondipper (52.1%), sustained HTN (41.3%), normotensive (23.9%), and white coat HTN (19.6%). Overall, 88% of the patients strongly agreed or agreed that they were very satisfied with their experience using the ABPM service. CONCLUSION: A community pharmacy-driven ABPM service is feasible in the United States and may be one approach to improve access to ABPM.

Pharmacy patronage and service utilization: Associations with patient sociodemographic and health characteristics.

OBJECTIVES: This study describes associations between patient sociodemographic and health characteristics, pharmacy patronage, and service utilization. DESIGN: Cross-sectional survey. SETTING: United States. PARTICIPANTS: A Qualtrics research panel was used to obtain a sample of American adults (N = 741) who had filled at least one prescription at a community pharmacy in the last 12 months. Surveys were completed electronically in January 2017. MAIN OUTCOME MEASURES: Primary pharmacy patronage (chain, independent, grocery, mass merchandiser, or mail order) and utilization of pharmacy services. RESULTS: Respondents most commonly patronized chain pharmacies (51.6%), followed by mass merchandiser (17.1%), grocery (14.4%), and independent (11.0%) pharmacies. In multivariable analysis, geographic factors and age were the primary predictors of pharmacy patronage. Approximately one third (35.1%) of patients stated that their pharmacist knew their name. Being known by their pharmacists was significantly associated with patronage of independent pharmacies, long-term medication use, caregiving activities, and use of medication synchronization or adherence packaging services. Automatic refill (57.9%), e-mail or text reminders (37.4%), and influenza immunizations (26.7%) were the most commonly used pharmacy services surveyed. Younger patients were significantly more likely to report the use of medication synchronization and smartphone apps, whereas use of pharmacist-administered vaccination increased with age. Use of medication synchronization, home delivery, and adherence packaging services was higher among independent pharmacy patrons compared with chain pharmacy patrons. CONCLUSION: This study identified several sociodemographic and health-related predictors of pharmacy patronage and service utilization. Independent pharmacy patronage, caregiving activities, and utilization of some pharmacy services were associated with having an established patient-pharmacist relationship, as indicated by having a pharmacist who knew the patient's name. Future research should explore how patient characteristics affect the use of pharmacy services and combinations thereof to facilitate targeted marketing of expanded pharmacy services to different populations.

The effect of maternity practices on exclusive breastfeeding rates in U.S. hospitals.

The Baby-friendly Hospital Initiative (BFHI) includes a set of 10 evidenced-based maternity practices that when used together have been shown to improve breastfeeding outcomes. In 2007, the Centers for Disease Control and Prevention launched the Maternity Practices in Infant Nutrition and Care (mPINC) survey to assess and monitor these and other evidenced-based maternity practices. The purpose of this study was to explore individual maternity practices measured in the 2013 mPINC survey, along with hospital demographic information, and their relationships with exclusive breastfeeding (EBF) rates, using a sample of United States (U.S.) hospitals. We obtained mPINC survey data from 69 BFHI hospitals and 654 non-BFHI hospitals in the U.S., and EBF rates from The Joint Commission, a leading hospital accreditation agency. On the basis of linear regression analysis, we found that most maternity practices studied were significantly associated with EBF rates (max adjusted R2  = 14.9%). We found a parsimonious model with an adjusted R2 of 47.3%. This study supports the need for a systematic approach in providing breastfeeding support as no one maternity care practice was able to explain the variability in EBF rates as well as a collection of maternity care practices.

Bilateral Hip Arthroscopy: Direct Comparison of Primary Acetabular Labral Repair and Primary Acetabular Labral Reconstruction.

PURPOSE: Directly compare primary acetabular labral repair versus primary acetabular labral reconstruction using a self-controlled cohort study design. METHODS: Patients who underwent primary labral repair in one hip and primary labral reconstruction using iliotibial band allograft in the other hip by a single surgeon between August 2009 and November 2014 were identified. One patient with inflammatory arthritis was excluded. Patient-reported outcome data included change in Modified Harris Hip Score (MHHS), Lower Extremity Functional Scale (LEFS), average pain using a 10-point visual analog scale (VAS), and patient satisfaction (1: very dissatisfied, 10: very satisfied). Failure was defined as subsequent intra-articular hip surgery. Data were analyzed using McNemar's and Wilcoxon Signed Rank tests. RESULTS: Overall, 29 patients (58 hips) were included in the analysis. There were 23 females and 6 males. The average age at time of surgery was 32.6 years (range: 14.9-51.6 years). Follow-up was obtained from all 29 patients (100%) at a mean of 56 months (range = 27-85 months) postoperative for repaired hips and 40 months (range = 22-61 months) postoperative for reconstructed hips. No labral reconstruction hips failed, and 9 (31%) labral repair hips failed (P < .01). Among those that did not fail treatment, there was no difference in MHHS change (32.2 ± 15.4 vs 29.6 ± 15.4; P = .63), LEFS change (26.6 ± 16.5 vs 23.9 ± 17.8; P = .61), VAS pain change (-3.2 ± 2.4 vs -3.6 ± 2.1; P = .47), or satisfaction (8.6 ± 2.0 vs 8.7 ± 2.4; P = .59) between the repair and reconstruction groups, respectively. CONCLUSIONS: In this cohort of patients, hips that underwent primary labral repair were more likely to fail treatment than hips that underwent labral reconstruction (31% vs 0%, respectively). Among hips that did not fail treatment, patient-reported outcome scores were similar between groups. Excellent clinical results can be obtained with both forms of labral-preserving treatment but were more predictably observed with primary labral reconstruction in this cohort. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

The effect of Baby-friendly status on exclusive breastfeeding in U.S. hospitals.

In 2014, a leading hospital accreditation agency, mandated hospitals publicly report their exclusive breastfeeding (EBF) rates. This new regulation provided an opportunity to explore differences in EBF outcomes using a standardized definition across a large hospital sample in the United States. The purpose of this study was to examine the relationships between population demographics and the Baby-friendly (BF) hospital designation on EBF rates in hospitals throughout the United States. We obtained EBF rates from 121 BF hospitals and 1,608 hospitals without the BF designation. Demographic variables were computed using census tract data for the population surrounding each hospital. Relationships were explored using linear regression. We found that EBF rates were positively correlated with a bachelor's degree, log income, and those who identified as White or Asian and negatively correlated with those without college attendance, individuals living below the poverty line, and those who identified as African American or Hispanic. For all models, the BF designation of a hospital was associated with higher EBF rates (p < 0.01; effect sizes, 0.11-0.49) with the exception of the model containing log income. Using a multiple linear regression model that was allowed to contain more than one independent variable, we were able to explain 22% of the variability in EBF rates. The BF hospital designation was associated with significantly higher EBF rates independent of demographic variables. Support for hospitals to attain the BF hospital designation is a meaningful public health goal.

Revision Arthroscopic Acetabular Labral Treatment: Repair or Reconstruct?

PURPOSE: To compare the outcome of labral repair versus labral reconstruction in patients presenting to a single surgeon for revision hip arthroscopy following previous labral treatment. METHODS: Patients who underwent revision labral repair or labral reconstruction using iliotibial band allograft, after previous labral debridement or repair, between 2009 and 2013 were identified. Hips that underwent revision labral reconstruction were further stratified into 2 graft groups (freeze-dried vs frozen allograft). Exclusion criteria were age <16 years, previous open hip surgery, or previous labral reconstruction. Failure was defined by subsequent intra-articular hip surgery. RESULTS: 113 hips (15 repair, 98 reconstruction) met the inclusion criteria. Patients who underwent revision labral repair were younger than patients who underwent revision labral reconstruction (27.8 years vs 34.6 years; P = .02). Follow-up was obtained from 14 (93%) labral repairs at an average of 4.7 years postoperation (range: 2.0-6.0 years) and 90 (92%) labral reconstructions at an average of 2.4 years postoperation (range: 2.0-4.0 years). Seven of 14 (50%) labral repair hips failed compared with 11/90 (12%) labral reconstruction hips (P < .01). Six of 61 (10%) frozen allografts failed compared with 5/29 (17%) freeze-dried allografts (P = .32). Patients who underwent revision labral repair were 4.1 (95% confidence interval 1.9, 8.8) times more likely to fail than patients who underwent revision labral reconstruction. CONCLUSIONS: Patients who underwent revision labral repair following previous repair or debridement were 2.6 times more likely to fail than patients who underwent revision labral reconstruction, controlling for calendar time. In addition, revision labral reconstruction with frozen allograft had lower propensity of failure than freeze-dried allograft. However, there was no statistically significant difference in patient-reported outcome scores between the 2 groups. Based on these results, complete labral reconstruction with longer, nonsegmental graft led to a lower failure rate in this study population and can be considered for treatment of patients presenting for revision labral treatment. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Unintended consequences of the Inflation Reduction Act: clinical development toward subsequent indications.

OBJECTIVES: To describe the clinical development landscape for high-spend Medicare Part D small molecule drugs and illustrate the potential impact of the Inflation Reduction Act of 2022 (IRA) on research and development investments toward subsequent indications. STUDY DESIGN: Descriptive analysis of research and development time lines of small molecule drugs in the top 50 of 2020 Medicare Part D spending using publicly available dates when pivotal clinical trials were first posted to ClinicalTrials.gov and FDA approval dates for initial and subsequent indications. METHODS: We summarize the drugs, indications, and time lines using descriptive statistics. RESULTS: Thirty of the 50 drugs with highest gross spending by Medicare Part D in 2020 were small molecule drugs with subsequent indications. Subsequent indications based on preapproval research (n = 34) were often approved within 2 years of initial approval (n = 15) and, on average, 2.9 years after a drug's first approval. Additional indications based on postapproval clinical trials or real-world evidence (n = 42) received FDA approval, on average, 7.5 years after a drug was first approved, with the majority (55.8%) receiving FDA approval more than 7 years after the initial approval. CONCLUSIONS: Our analysis of clinical development for new indications reveals aspects of innovation in small molecule drugs that are at risk under the IRA. Specifically, the time lines described in this research demonstrate how the IRA may reduce economic incentives to develop multiple indications, including single-indication launches and investments in postapproval research for additional indications.

The accelerated approval program for oncology drugs: celebrating more than 250,000 life-years gained and counting.

This commentary explores how 2 recently published studies evaluating the clinical benefit of the FDA's accelerated approval program for oncology drugs came to different conclusions.

An active-learning laboratory focused on critical care topics.

BACKGROUND AND PURPOSE: To describe an active-learning laboratory on critical care topics including advanced cardiac life support (ACLS), rapid sequence intubation (RSI), and toxicology and its effect on students' knowledge, skills, and confidence. EDUCATIONAL ACTIVITY AND SETTING: Third year pharmacy students (n = 88) participated in a critical care focused laboratory with four stations focused on ACLS review, ABBOJECTⓇ syringe assembly, ACLS simulations, RSI cases, and toxicology. Prior to the critical care focused skills laboratory, students completed an optional assessment composed of six confidence and eight knowledge questions. After the laboratory, students completed the same confidence and knowledge assessment. Descriptive statistics assessed pre/post-assessment responses. Paired pre/post-assessment Likert data were analyzed using the Wilcoxon signed-rank test and paired pre/post-test multiple choice responses were analyzed using the McNemar test. FINDINGS: Of the 88 students in the cohort, 76 students completed both the pre/post-assessments (response rate: 86.4%). Students demonstrated a significant increase in their overall knowledge and confidence scores on the post-assessment. All students successfully assembled an ABBOJECTⓇ syringe. The majority of respondents rated the critical care laboratory as excellent or good with regards to how enjoyable and effective the activity was to help understand critical care topics. SUMMARY: A hands-on, active-learning laboratory devoted to teaching and reinforcing common critical care concepts allowed students to gain knowledge and confidence regarding ACLS, RSI, and toxicology.

Subsequent Indications in Oncology Drugs: Pathways, Timelines, and the Inflation Reduction Act.

INTRODUCTION: Recent research has raised questions about potential unintended consequences of the Inflation Reduction Act's Drug Price Negotiation Program (DPNP), suggesting that the timelines introduced by the law may reduce manufacturer incentives to invest in post-approval research towards additional indications. Given the role of multiple indications in expanding treatment options in patients with cancer, IRA-related changes to development incentives are especially relevant in oncology. This study aimed to describe heterogeneous drug-level trajectories and timelines of subsequent indications in a cohort of recently approved, multi-indication oncology drugs, including overall, across subgroups of drugs characterized by the timing and pace of additional indications, and by drug type (i.e., small molecule vs. biologic). METHODS: This cross-sectional study evaluated oncology drugs first approved by the FDA from 2008 to 2018 and later approved for one or more additional indications. Numbers, types, and approval timelines of subsequent indications were recorded at the drug level, with drugs grouped by quartile based on the pacing of post-approval development (i.e., "rapid pace" to "measured pace"). RESULTS: Multi-indication oncology drugs (N = 56/86, 65.1%) had one or more subsequent indication approved in a new: cancer type (60.7%), line of treatment (50.0%), combination (41.1%), mutation (32.1%), or stage (28.6%). The median time between FDA approvals for indications increased from 0.6 years (IQR: 0.48, 0.74) in the "rapid pace" group to 1.6 years (IQR: 1.32, 1.66), 2.4 years (IQR: 2.29, 2.61), and 4.9 years (IQR: 3.43, 6.23) in the "moderate," "measured-moderate," and "measured" pace groups, respectively. Drugs in the "rapid pace" group often received their first subsequent indication approval within 9 months of initial approval (median: 0.7 years; IQR: 0.54, 1.59), whereas the "measured pace" group took a median of 5.7 years (IQR: 3.43, 6.98). Across all multi-indication drugs, the median time to the most recent approval for a subsequent indication was 5.5 years (IQR: 3.18, 7.95). One quarter (25%) of drugs were approved for their most recent subsequent indication after the time at which they would be DPNP-eligible. CONCLUSION: Approval histories of new oncology drugs demonstrate the role of post-approval indications in expanding treatment options towards new cancer types, stages, lines, combinations, and mutations. Heterogeneous clinical development pathways provide insights into potential unintended consequences of IRA-related changes surrounding post-approval research and development.

Longitudinal medication adherence group-based trajectories of aging adults in the US: A retrospective analysis using monthly proportion of days covered calculations.

BACKGROUND: It is thought that half of the patients with chronic conditions are not adherent to their medications, which contributes to significant health and economic burden. Many studies estimate medication non-adherence by implementing a threshold of ≥80% of Proportion of Days Covered (PDC), categorizing patients as either adherent or non-adherent. Healthcare quality metrics pertaining to medication use are based on this dichotomous approach of medication adherence, including the Medicare Part D Star Ratings. Among others, the Medicare Part D Star Ratings rewards part D plan sponsors with quality bonus payments based on this dichotomous categorization of beneficiaries' medication adherence. OBJECTIVES: Describe the longitudinal adherence trajectories of adults ≥65 years of age covered by Medicare for 3 classes of drugs in the Part D Star Ratings: diabetes medications, statins, and select antihypertensives. METHODS: This study used Medicare healthcare administrative claims data linked to participants from the Health Retirement Study between 2008 and 2016. Group-based trajectory models (GBTM) elicited the number and shape of adherence trajectories from a sample of N = 11,068 participants for the three pharmacotherapeutic classes considered in this study. Medication adherence was estimated using monthly PDC. RESULTS: GBTM were estimated for the sample population taking antihypertensives (n = 7,272), statins (n = 8,221), and diabetes medications (n = 3,214). The hypertension model found three trajectories: high to very high adherence (47.55%), slow decline (32.99%), and rapid decline (19.47%) trajectories. The statins model found 5 trajectories: high to very high adherence (35.49%), slow decline (17.12%), low then increasing adherence (23.58%), moderate decline (12.62%), and rapid decline (11.20%). The diabetes medications model displayed 6 trajectories: high to very high adherence (24.15%), slow decline (16.84%), high then increasing adherence (25.56%), low then increasing (13.58%), moderate decline (10.60%), and rapid decline (9.27%). CONCLUSIONS: This study showed the fluid nature of long-term medication adherence to the medications considered in the Medicare Part D Star Ratings and how it varies by pharmacotherapeutic class. These challenge previous assumptions about which patients were considered adherent to chronic medications. Policy and methodological implications about medication adherence are discussed.

Immune correlates of herpes zoster in HIV-infected children and youth.

To identify immunologic factors that modulate the risk of herpes zoster (HZ), we compared varicella-zoster virus (VZV)-specific and nonspecific T-cell subpopulations of 47 HIV-infected children before they developed HZ with those of 141 VZV-positive HZ-negative matched controls. Compared with controls, HZ cases had lower VZV-specific CD8(+) CD107a(+) cell percentages independently of CD4(+) percentages or HIV loads, suggesting that VZV-specific cytotoxic T cells are protective against HZ. In contrast, high nonspecific regulatory and activated T cells were associated with an increased risk of HZ.

Gating of a novel brain potential is associated with perceptual anomalies in bipolar disorder.

OBJECTIVES: Our laboratory recently identified the P85 gating ratio as a candidate biomarker for bipolar disorder. In order to evaluate the phenomenological significance of P85 gating, the current study examined reports of perceptual anomalies and their relationship to the P50 and P85 physiological measures of sensory gating. METHODS: Reports of perceptual anomalies on the Structured Clinical Interview to Assess Perceptual Anomalies were compared in patients meeting DSM-IV criteria for paranoid schizophrenia (n = 66), schizoaffective disorder (n = 45), or bipolar I disorder (n = 42), and controls (n = 56), as well as their relationship with P85 and P50 gating. RESULTS: The bipolar disorder group reported significantly more auditory, visual, and total anomalies than both the schizophrenia and control groups. The schizophrenia group also had more anomalies than the control group. Comparison of psychiatric subgroups revealed that the bipolar depressed, bipolar disorder with psychosis, and schizoaffective bipolar type groups reported the most anomalies compared to the other patient groups (bipolar disorder without psychosis, schizoaffective, bipolar manic). The total perceptual anomalies score and the P85 ratio significantly differentiated the bipolar disorder, schizoaffective, and paranoid schizophrenia groups from each other. CONCLUSIONS: These findings provide evidence of the phenomenological significance of P85. The results also yield further support not only for the P85 ratio, but also for increased reports of perceptual anomalies as possible markers for bipolar disorder.