Differences in Drug Shortages in the US and Canada.

Importance: Drug shortages are a persistent public health issue that increased during the COVID-19 pandemic. Both the US and Canada follow similar regulatory standards and require reporting of drug-related supply chain issues that may result in shortages. However, it is unknown what proportion are associated with meaningful shortages (defined by a significant decrease in drug supply) and whether differences exist between Canada and the US. Objective: To compare how frequently reports of drug-related supply chain issues in the US vs Canada were associated with drug shortages. Design, Setting, and Participants: Longitudinal cross-sectional study conducted from January 2023 to March 2024 using drug-related reports of supply chain issues from 2017 to 2021 that were less than 180 days apart in Canada and the US. Shortages were assessed using data from the IQVIA Multinational Integrated Data Analysis database, comprising 89% of US and 100% of Canadian drug purchases. Exposure: Country (Canada vs US), timing of report issuance (before vs after the COVID-19 pandemic), and characteristics of the supply chain prior to the reports of drug-related supply chain issues (including World Health Organization essential medicine status, Health Canada tier 3 medicine [moderate risk classification], whether there was sole-source manufacturing of the drug, the formulation, the price per unit, ≥20 years since drug approval, and the number of therapeutic alternatives). Main Outcomes and Measures: A drug shortage (a decrease of ≥33% in monthly purchased standardized drug units) within 12 months, relative to the average units purchased during the 6 months prior to the report of supply chain issues to a US or Canadian reporting system. Results: Among the 104 drug-related reports of supply chain issues in both countries, 49.0% (95% CI, 39.3%-59.7%) were associated with drug shortages in the US vs 34.0% (95% CI, 25.0%-45.0%) in Canada (adjusted hazard ratio [HR], 0.53 [95% CI, 0.36-0.79]). The lower risk of drug shortages in Canada vs the US was consistent before the COVID-19 pandemic (adjusted HR, 0.47 [95% CI, 0.30-0.75]) and after the pandemic (adjusted HR, 0.31 [95% CI, 0.15-0.66]). After combining reports of supply chain issues in both countries, the shortage risk was double for sole-sourced drugs (adjusted HR, 2.58 [95% CI, 1.57-4.24]) and nearly half for Canadian tier 3 medicines (moderate risk) (adjusted HR, 0.56 [95% CI, 0.32-0.98]). Conclusions and Relevance: Drug-related reports of supply chain issues were 40% less likely to result in meaningful drug shortages in Canada compared with the US. These findings highlight the need for international cooperation between countries to curb the effects of drug shortages and improve resiliency of the supply chain for drugs.

CALMER Conflict: A Novel Curriculum for Graduating Medical Students to Manage and Defuse Patient-Provider Conflict.

BACKGROUND: Workplace violence disproportionately affects healthcare workers and verbal aggression from patients frequently occurs. While verbal de-escalation is the first-line approach to defusing anger, there is a lack of consistent curricula or robust evaluation in undergraduate medical education. AIM: To develop a medical school curriculum focused on de-escalation skills for adult patients and evaluate effectiveness with surveys and an objective structured clinical examination (OSCE). SETTING: We implemented this curriculum in the "Get Ready for Residency Bootcamp" of a single large academic institution in 2023. PARTICIPANTS: Forty-four fourth-year medical students PROGRAM DESCRIPTION: The curriculum consisted of an interactive didactic focused on our novel CALMER framework that prioritized six evidence-based de-escalation skills and a separate standardized patient practice session. PROGRAM EVALUATION: The post-curriculum survey (82% response rate) found a significant increase from 2.79 to 4.11 out of 5 (p ≤ 0.001) in confidence using verbal de-escalation. Preparedness improved with every skill and curriculum satisfaction averaged 4.79 out of 5. The OSCE found no differences in skill level between students who received the curriculum and those who did not. DISCUSSION: This evidence-based and replicable de-escalation skill curriculum improves medical student confidence and preparedness in managing agitated patients.

Some Perceptions Differ, Match Outcomes Do Not: A Multisite Retrospective Cross-Sectional Comparison of Virtual vs. In-Person Recruitment.

BACKGROUND: Virtual interviewing for residency provides considerable savings. Its impact on match outcomes remains unclear. OBJECTIVE: Evaluate the impact of virtual residency recruitment on program and applicant assessment and match outcomes. DESIGN: Cross-sectional survey, September 2020-July 2021 PARTICIPANTS: Faculty interviewers and 2019 and 2020 PGY-1 classes at three academic internal medicine residencies. MAIN MEASURES: Survey items rating effectiveness of interview format, preference for future interview format, and perceived impact on diversity. KEY RESULTS: A total of 247/436 faculty (57%) interviewers responded. Faculty perceived that in-person interviews enhanced applicant assessment (3.23 ± 0.38, p < 0.01) and recruitment of the most qualified applicants (p < 0.01) but did not impact recruitment of a racially or gender diverse class (3.03 ± 0.99, p = 0.95 and 3.09 ± 0.76, p = 0.14 respectively). They also did not demonstrate a preference for future interview formats. A total of 259/364 matched applicants responded, corresponding to a 76% response rate in the in-person cohort and a 66% response rate for virtual. Trainees were equally likely to match at their top choice when interviewing virtually vs. in-person (p = 0.56), and racial/ethnic and gender composition of the incoming class also did not differ (p = 0.81 and p = 0.19 respectively). Trainees perceived many aspects of the institution were better assessed in-person, though the impact varied according to assessment domain. Trainees who interviewed in-person preferred in-person formats. Of those who interviewed virtually, 47% preferred virtual and 54% preferred in-person. There were no predictors of virtual preference for future interview formats. CONCLUSIONS: Faculty and applicants who experienced virtual recruitment had no preference for future recruitment format. Virtual recruitment had no impact on the racial/gender diversity of matched classes or on applicants matching at their top-ranked institution. Institutions should consider the potential non-inferiority of virtual interviews with financial and other benefits when making decisions about future interview formats.

Psychosocial predictors of health behavior adherence in heart-failure patients with comorbid depression: a secondary analysis of the Hopeful Heart trial.

BACKGROUND: Depression affects 20-30% of individuals with heart failure (HF), and it is associated with worse health outcomes independent of disease severity. One potential explanation is the adverse impact of depression on HF patients' adherence to the health behaviors needed to self-manage their condition. The aim of this study is to identify characteristics associated with lower adherence in this population, which could help to recognize individuals at higher risk and eventually tailor health behavior interventions to their needs. METHODS: Using data from a randomized, controlled, collaborative care treatment trial in 629 patients with HF and comorbid depression, we performed mixed effects logistic regression analyses to examine the cross-sectional and prospective relationships between medical and psychosocial variables and health behavior adherence, including adherence to medications, a low-sodium diet, and physician appointments. RESULTS: In cross-sectional analyses, married marital status and higher physical health-related quality of life (HRQoL) were associated with greater overall adherence (compared to married, single Odds Ratio [OR] = 0.46, 95% Confidence Interval [CI] = 0.26-0.80; other OR = 0.60, CI = 0.38-0.94; p = .012. Physical HRQoL OR = 1.02, CI = 1.00-1.04, p = .047). Prospectively, greater levels of social support were associated with improved overall adherence one year later (OR = 1.04, 95% CI = 1.00-1.08, p = .037). Social support, HF symptom severity, race and ethnicity, and age were predictors of specific types of adherence. Neither depression nor optimism was significantly associated with adherence outcomes. CONCLUSIONS: These results provide important preliminary information about risk factors for poor adherence in patients with both HF and depression, which could, in turn, contribute to the development of interventions to promote adherence in this high-risk population. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02044211 ; registered 1/21/2014.

Active surveillance pharmacovigilance for Clostridioides difficile infection and gastrointestinal bleeding: an analytic framework based on case-control studies.

BACKGROUND: Active surveillance pharmacovigilance is an emerging approach to identify medications with unanticipated effects. We previously developed a framework called pharmacopeia-wide association studies (PharmWAS) that limits false positive medication associations through high-dimensional confounding adjustment and set enrichment. We aimed to assess the transportability and generalizability of the PharmWAS framework by using medical claims data to reproduce known medication associations with Clostridioides difficile infection (CDI) or gastrointestinal bleeding (GIB). METHODS: We conducted case-control studies using Optum's de-identified Clinformatics Data Mart Database of individuals enrolled in large commercial and Medicare Advantage health plans in the United States. Individuals with CDI (from 2010 to 2015) or GIB (from 2010 to 2021) were matched to controls by age and sex. We identified all medications utilized prior to diagnosis and analysed the association of each with CDI or GIB using conditional logistic regression adjusted for risk factors for the outcome and a high-dimensional propensity score. FINDINGS: For the CDI study, we identified 55,137 cases, 220,543 controls, and 290 medications to analyse. Antibiotics with Gram-negative spectrum, including ciprofloxacin (aOR 2.83), ceftriaxone (aOR 2.65), and levofloxacin (aOR 1.60), were strongly associated. For the GIB study, we identified 450,315 cases, 1,801,260 controls, and 354 medications to analyse. Antiplatelets, anticoagulants, and non-steroidal anti-inflammatory drugs, including ticagrelor (aOR 2.81), naproxen (aOR 1.87), and rivaroxaban (aOR 1.31), were strongly associated. INTERPRETATION: These studies demonstrate the generalizability and transportability of the PharmWAS pharmacovigilance framework. With additional validation, PharmWAS could complement traditional passive surveillance systems to identify medications that unexpectedly provoke or prevent high-impact conditions. FUNDING: U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

Drug Shortages Prior to and During the COVID-19 Pandemic.

Importance: Drug shortages are a chronic and worsening issue that compromises patient safety. Despite the destabilizing impact of the COVID-19 pandemic on pharmaceutical production, it remains unclear whether issues affecting the drug supply chain were more likely to result in meaningful shortages during the pandemic. Objective: To estimate the proportion of supply chain issue reports associated with drug shortages overall and with the COVID-19 pandemic. Design, Setting, and Participants: This longitudinal cross-sectional study used data from the IQVIA Multinational Integrated Data Analysis database, comprising more than 85% of drug purchases by US pharmacies from wholesalers and manufacturers, from 2017 to 2021. Data were analyzed from January to May 2023. Exposure: Presence of a supply chain issue report to the US Food and Drug Administration or the American Society of Health-Systems Pharmacists (ASHP). Main Outcomes and Measures: The main outcome was drug shortage, defined as at least 33% decrease in units purchased within 6 months of a supply chain issue report. Random-effects logistic regression models compared the marginal odds of shortages for drugs with vs without reports. Interaction terms assessed heterogeneity prior to vs during the COVID-19 pandemic and by drug characteristics (formulation, age, essential medicine status, clinician- vs self-administered, sales volume, and number of manufacturers). Results: A total of 571 drugs exposed to 731 supply chain issue reports were matched to 7296 comparison medications with no reports. After adjusting for drug characteristics, 13.7% (95% CI, 10.4%-17.8%) of supply chain issue reports were associated with subsequent drug shortages vs 4.1% (95% CI, 3.6%-4.8%) of comparators (marginal odds ratio [mOR], 3.7 [95% CI, 2.6-5.1]). Shortages increased among both drugs with and without reports in February to April 2020 (34.2% of drugs with supply chain issue reports and 9.5% of comparison drugs; mOR, 4.9 [95% CI, 2.1-11.6]), and then decreased after May 2020 (9.8% of drugs with reports and 3.6% of comparison drugs; mOR, 2.9 [95% CI, 1.6-5.3]). Significant associations were identified by formulation (parenteral mOR, 1.9 [95% CI, 1.1-3.2] vs oral mOR, 5.4 [95% CI, 3.3-8.8]; P for interaction = .008), WHO essential medicine status (essential mOR, 2.2 [95% CI, 1.3-5.2] vs nonessential mOR, 4.6 [95% CI, 3.2-6.7]; P = .02), and for brand-name vs generic status (brand-name mOR, 8.1 [95% CI, 4.0-16.0] vs generic mOR, 2.4 [95% CI, 1.7-3.6]; P = .002). Conclusions and Relevance: In this national cross-sectional study, supply chain issues associated with drug shortages increased at the beginning of the COVID-19 pandemic. Ongoing policy work is needed to protect US drug supplies from future shocks and to prioritize clinically valuable drugs at greatest shortage risk.

Characteristics differentiating problem representation synthesis between novices and experts.

BACKGROUND: Formulating a thoughtful problem representation (PR) is fundamental to sound clinical reasoning and an essential component of medical education. Aside from basic structural recommendations, little consensus exists on what characterizes high-quality PRs. OBJECTIVES: To elucidate characteristics that distinguish PRs created by experts and novices. METHODS: Early internal medicine residents (novices) and inpatient teaching faculty (experts) from two academic medical centers were given two written clinical vignettes and were instructed to write a PR and three-item differential diagnosis for each. Deductive content analysis described the characteristics comprising PRs. An initial codebook of characteristics was refined iteratively. The primary outcome was differences in characteristic frequencies between groups. The secondary outcome was characteristics correlating with diagnostic accuracy. Mixed-effects regression with random effects modeling compared case-level outcomes by group. RESULTS: Overall, 167 PRs were analyzed from 30 novices and 54 experts. Experts included 0.8 fewer comorbidities (p < .01) and 0.6 more examination findings (p = .01) than novices on average. Experts were less likely to include irrelevant comorbidities (odds ratio [OR] = 0.4, 95% confidence interval [CI] = 0.2-0.8) or a diagnosis (OR = 0.3, 95% CI = 0.1-0.8) compared with novices. Experts encapsulated clinical data into higher-order terms (e.g., sepsis) than novices (p < .01) while including similar numbers of semantic qualifiers (SQs). Regardless of expertise level, PRs following a three-part structure (e.g., demographics, temporal course, and clinical syndrome) and including temporal SQs were associated with diagnostic accuracy (p < .01). CONCLUSIONS: Compared with novices, expert PRs include less irrelevant data and synthesize information into higher-order concepts. Future studies should determine whether targeted educational interventions for PRs improve diagnostic accuracy.

Internal Medicine Residents' Perceptions of Their Continuity Clinic Training.

OBJECTIVES: Internal Medicine (IM) residents have reported dissatisfaction with continuity clinic (CC) training, which may contribute to the increasing shortage of primary care physicians. Studies show balancing inpatient and outpatient duties as a driver of dissatisfaction, but few studies have compared CC with inpatient (IP) training, following transition to an X + Y model, or assessed the impact of show rates, continuity, and telemedicine use on resident perceptions. The aim of this study was to adapt a validated survey to compare residents' perceptions of their CC with their inpatient medicine training and examine the impact of objective clinic measures on training. METHODS: This quantitative cross-sectional study included a survey that was sent to 152 residents at an academic IM program in May-June 2021. Clinic measures such as show versus no-show rates, continuity with the residents' own patients, and visit modality were obtained through the electronic health records at Veterans Affairs and non-Veterans Affairs CCs. RESULTS: The survey response rate was 78% (118/152). Residents were more satisfied with inpatient general medicine rotations than their CC experience (4.5 vs 3.3 on a 5-point scale, P < 0.001). Residents were more likely to pursue a profession in inpatient IM than in primary care (3.7 vs 2.3, P < 0.001). No correlation was found between higher show rates, continuity with patients, or proportion of visits conducted through telemedicine and resident satisfaction with CC. CONCLUSIONS: This study aligns with previous findings of IM resident dissatisfaction with CC training while adding a side-by-side comparison to inpatient training and including objective CC data. We identified new areas for improvement of CC training, including residents' medical knowledge through review of quality metrics, making CC representative of real-world practice, and mentorship from faculty.

Effects of the valsartan recall on heart failure patients: A nationwide analysis.

BACKGROUND: Valsartan is commonly used for cardiac conditions. In 2018, the Food and Drug Administration recalled generic valsartan due to the detection of impurities. Our objective was to determine if heart failure patients receiving valsartan at the recall date had a greater likelihood of unfavorable outcomes than patients using comparable antihypertensives. METHODS: We conducted a cohort study of Optum's de-identified Clinformatics® Datamart (July 2017-January 2019). Heart failure patients with commercial or Medicare Advantage insurance who received valsartan were compared to persons who received non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is) for 1 year prior and including the recall date. Outcomes included a composite for all-cause hospitalization, emergency department (ED), and urgent care (UC) use and a measure of cardiac events which included hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension at 6-months post-recall. Cox proportional hazard models with propensity score weighting compared the risk of outcomes between groups. RESULTS: Of the 87 130 adherent patients, 15% were valsartan users and 85% were users of non-recalled ARBs/ACE-Is. Valsartan use was not associated with an increased risk of all-cause hospitalization/ED/UC use six-months post-recall (HR 1.00; 95% CI 0.96-1.03), compared with individuals taking non-recalled ARBs/ACE-Is. Similarly, cardiac events 6-months post-recall did not differ between individuals on valsartan and non-recalled ARBs/ACE-Is (HR 1.04; 95% CI 0.97-1.12). CONCLUSIONS: The valsartan recall did not affect short-term outcomes of heart failure patients. However, the recall potentially disrupted the medication regimens of patients, possibly straining the healthcare system.

Team Functioning and Performance in Child Advocacy Center Multidisciplinary Teams.

The quality of teamwork in Child Advocacy Center (CAC) multidisciplinary teams is likely to affect the extent to which the CAC model improves outcomes for children and families. This study examines associations between team functioning and performance in a statewide sample of CAC teams. Multidisciplinary team members (N = 433) from 21 CACs completed measures of affective, behavioral, and cognitive team functioning. Team performance was assessed with three measures: team member ratings of overall performance, ratings of mental health screening/referral frequency, and caregiver satisfaction surveys. Linear mixed models and regression analyses tested associations between team functioning and performance. Affective team functioning (i.e., liking, trust, and respect; psychological safety) and cognitive team functioning (i.e., clear direction) were significantly associated with team members' ratings of overall performance. Behavioral team functioning (i.e., coordination) and cognitive team functioning were significantly associated with mental health screening/referral frequency. Team functioning was not associated with caregiver satisfaction with CAC services. Aspects of team functioning were associated with team members' perceptions of overall performance and mental health screening/referral frequency, but not caregiver satisfaction. Understanding associations between team functioning and performance in multidisciplinary teams can inform efforts to improve service quality in CACs and other team-based service settings.

A Retrospective Cohort Study of the 2018 Angiotensin Receptor Blocker Recalls and Subsequent Drug Shortages in Patients With Hypertension.

BACKGROUND: Valsartan was recalled by the US Food and Drug Administration in July 2018 for carcinogenic impurities, resulting in a drug shortage and management challenges for valsartan users. The influence of the valsartan recall on clinical outcomes is unknown. We compared the risk of adverse events between hypertensive patients using valsartan and a propensity score-matched group using nonrecalled angiotensin receptor blockers and angiotensin-converting enzyme inhibitors. METHODS AND RESULTS: We used Optum's deidentified Clinformatics Datamart (July 2017-January 2019). Hypertensive patients who received valsartan or nonrecalled angiotensin receptor blockers/angiotensin-converting enzyme inhibitors for 1 year before and on the recall date were compared. Primary outcomes were measured in the 6 months following the recall and included: (1) a composite measure of all-cause hospitalization, all-cause emergency department visit, and all-cause urgent care visit, and (2) a composite cardiac event measure of hospitalizations for acute myocardial infarction and hospitalizations/emergency department visits/urgent care visits for stroke/transient ischemic attack, heart failure, or hypertension. We compared the risk of outcomes between treatment groups using Cox proportional hazard models. Of the hypertensive patients, 76 934 received valsartan, and 509 472 received a nonrecalled angiotensin receptor blocker/angiotensin-converting enzyme inhibitor. Valsartan use at the time of recall was associated with a higher risk of all-cause hospitalization, emergency department use, or urgent care use (hazard ratio [HR], 1.02 [95% CI, 1.00-1.04]) and the composite of cardiac events (HR, 1.22 [95% CI, 1.15-1.29]) within 6 months after the recall. CONCLUSIONS: The valsartan recall and shortage affected hypertensive patients. Local- and national-level systems need to be enhanced to protect patients from drug shortages by providing safe and reliable medication alternatives.

Patterns of Telemedicine Use and Glycemic Outcomes of Endocrinology Care for Patients With Type 2 Diabetes.

Importance: Telemedicine can increase access to endocrinology care for people with type 2 diabetes (T2D), but patterns of use and outcomes of telemedicine specialty care for adults with T2D beyond initial uptake in 2020 are not known. Objective: To evaluate patterns of telemedicine use and their association with glycemic control among adults with varying clinical complexity receiving endocrinology care for T2D. Design, Setting, and Participants: Retrospective cohort study in a single large integrated US health system. Participants were adults who had a telemedicine endocrinology visit for T2D from May to October 2020. Data were analyzed from June 2022 to October 2023. Exposure: Patients were followed up through May 2022 and assigned to telemedicine-only, in-person, or mixed care (both telemedicine and in-person) cohorts according to visit modality. Main Outcomes and Measures: Multivariable regression models were used to estimate hemoglobin A1c (HbA1c) change at 12 months within each cohort and the association of factors indicating clinical complexity (insulin regimen and cardiovascular and psychological comorbidities) with HbA1c change across cohorts. Subgroup analysis was performed for patients with baseline HbA1c of 8% or higher. Results: Of 11 498 potentially eligible patients, 3778 were included in the final cohort (81 Asian participants [2%], 300 Black participants [8%], and 3332 White participants [88%]); 1182 used telemedicine only (mean [SD] age 57.4 [12.9] years; 743 female participants [63%]), 1049 used in-person care (mean [SD] age 63.0 [12.2] years; 577 female participants [55%]), and 1547 used mixed care (mean [SD] age 60.7 [12.5] years; 881 female participants [57%]). Among telemedicine-only patients, there was no significant change in adjusted HbA1c at 12 months (-0.06%; 95% CI, -0.26% to 0.14%; P = .55) while in-person and mixed cohorts had improvements of 0.37% (95% CI, 0.15% to 0.59%; P < .001) and 0.22% (95% CI, 0.07% to 0.38%; P = .004), respectively. Patients with a baseline HbA1c of 8% or higher had a similar pattern of glycemic outcomes. For patients prescribed multiple daily injections vs no insulin, the 12-month estimated change in HbA1c was 0.25% higher (95% CI, 0.02% to 0.47%; P = .03) for telemedicine vs in-person care. Comorbidities were not associated with HbA1c change in any cohort. Conclusions and Relevance: In this cohort study of adults with T2D receiving endocrinology care, patients using telemedicine alone had inferior glycemic outcomes compared with patients who used in-person or mixed care. Additional strategies may be needed to support adults with T2D who rely on telemedicine alone to access endocrinology care, especially for those with complex treatment or elevated HbA1c.

Predictors of 1-year enteral autonomy in children with intestinal failure: A descriptive retrospective cohort study.

INTRODUCTION: The International Intestinal Failure Registry (IIFR) is an international consortium to study intestinal failure (IF) outcomes in a large contemporary pediatric cohort. We aimed to identify predictors of early (1-year) enteral autonomy. METHODS: We included IIFR pilot phase patients. IF was defined by a parenteral nutrition need for at least 60 days due to a primary gastrointestinal etiology. The primary outcome was time to enteral autonomy achievement. We built a mixed-effects Weibull accelerated failure time model with random effects by center to analyze variables associated with enteral autonomy achievement with a primary outcome of time ratio (TR). RESULTS: We included 189 patients (82% with short bowel syndrome) representing 11 international centers. Cumulative incidence of early enteral autonomy was 51.6%, and death was 6.5%. In multivariable analysis, ostomy presence (TR, 2.63; 95% CI, 1.41-4.90) was associated with increased time to enteral autonomy achievement, and Asian/Indian (TR, 0.28; 95% CI, 0.10-0.81) and Pacific Islander race (TR, 0.34; 95% CI, 0.13-0.90) were associated with decreased time to enteral autonomy achievement. In a second model in the subset with measured percentage of bowel length remaining, ostomy presence (TR, 4.21; 95% CI, 1.90-9.33) was associated with increased time to enteral autonomy achievement, whereas greater percentage of bowel remaining (TR, 0.96; 95% CI, 0.94-0.98) was associated with decreased time to enteral autonomy achievement. CONCLUSIONS: Minimizing bowel resection at initial surgery and establishing bowel continuity by ostomy reversal can effectively decrease the time to early enteral autonomy achievement in children with IF.

Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial.

BACKGROUND: Heavy menstrual bleeding occurs in 80% of women with von Willebrand disease and is associated with iron deficiency and poor response to current therapies. International guidelines indicate low certainty regarding effectiveness of hormonal therapy and tranexamic acid. Although von Willebrand factor (VWF) concentrate is approved for bleeds, no prospective trials guide its use in heavy menstrual bleeding. We aimed to compare recombinant VWF with tranexamic acid for reducing heavy menstrual bleeding in patients with von Willebrand disease. METHODS: VWDMin, a phase 3, open-label, randomised crossover trial, was done in 13 haemophilia treatment centres in the USA. Female patients aged 13-45 years with mild or moderate von Willebrand disease, defined as VWF ristocetin cofactor less than 0·50 IU/mL, and heavy menstrual bleeding, defined as a pictorial blood assessment chart (PBAC) score more than 100 in one of the past two cycles were eligible for enrolment. Participants were randomly assigned (1:1) to two consecutive cycles each of intravenous recombinant VWF, 40 IU/kg over 5-10 min on day 1, and oral tranexamic acid 1300 mg three times daily on days 1-5, the order determined by randomisation. The primary outcome was a 40-point reduction in PBAC score by day 5 after two cycles of treatment. Efficacy and safety were analysed in all patients with any post-baseline PBAC scores. The trial was stopped early due to slow recruitment on Feb 15, 2022, by a data safety monitoring board request, and was registered at ClinicalTrials.gov, NCT02606045. FINDINGS: Between Feb 12, 2019, and Nov 16, 2021, 39 patients were enrolled, 36 of whom completed the trial (17 received recombinant VWF then tranexamic acid and 19 received tranexamic acid then recombinant VWF). At the time of this unplanned interim analysis (data cutoff Jan 27, 2022), median follow-up was 23·97 weeks (IQR 21·81-28·14). The primary endpoint was not met, neither treatment corrected PBAC score to the normal range. Median PBAC score was significantly lower after two cycles with tranexamic acid than with recombinant VWF (146 [95% CI 117-199] vs 213 [152-298]; adjusted mean treatment difference 46 [95% CI 2-90]; p=0·039). There were no serious adverse events or treatment-related deaths and no grade 3-4 adverse events. The most common grade 1-2 adverse events were mucosal bleeding (four [6%] patients during tranexamic acid treatment vs zero during recombinant VWF treatment) and other bleeding (four [6%] vs two [3%]). INTERPRETATION: These interim data suggest that recombinant VWF is not superior to tranexamic acid in reducing heavy menstrual bleeding in patients with mild or moderate von Willebrand disease. These findings support discussion of treatment options for heavy menstrual bleeding with patients based on their preferences and lived experience. FUNDING: National Heart Lung Blood Institute (National Institutes of Health).

Enrollee characteristics and receipt of colorectal cancer testing in Pennsylvania after adoption of the Affordable Care Act Medicaid expansion.

BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of cancer-related death in the U.S. Despite increased CRC screening rates, they remain low among low-income non-older adults, including Medicaid enrollees who are more likely to be diagnosed at advanced stages. OBJECTIVES: Given limited evidence regarding CRC screening service use among Medicaid enrollees, we examined multilevel factors associated with CRC testing among Medicaid enrollees in Pennsylvania after Medicaid expansion in 2015. RESEARCH DESIGN: Using the 2014-2019 Medicaid administrative data, we performed multivariable logistic regression models to assess factors associated with CRC testing, adjusting for enrollment length and primary care services use. SUBJECTS: We identified 15,439 adults aged 50-64 years newly enrolled through Medicaid expansion. MEASURES: Outcome measures include receiving any CRC testing and by modality. RESULTS: About 32% of our study population received any CRC testing. Significant predictors for any CRC testing include being male, being Hispanic, having any chronic conditions, using primary care services ≤4 times annually, and having a higher county-level median household income. Being 60-64 years at enrollment, using primary care services >4 times annually, and having higher county-level unemployment rates were significantly associated with a decreased likelihood of receiving any CRC tests. CONCLUSIONS: CRC testing rates were low among adults newly enrolled in Medicaid under the Medicaid expansion in Pennsylvania relative to adults with high income. We observed different sets of significant factors associated with CRC testing by modality. Our findings underscore the urgency to tailor strategies by patients' racial, geographic, and clinical conditions for CRC screening.

Sex-related differences in the prevalence of substance use disorders, treatment, and overdose among parents with young children.

Introduction: Risk factors and treatment rates for substance use disorders (SUDs) differ by sex. Females often have greater childcare and household responsibilities than males, which may inhibit SUD treatment. We examined how SUD, medication for opioid use disorder (MOUD) receipt, and overdose rates differ by sex among parents with young children (<5 years). Methods: Using deidentified national administrative healthcare data from Optum's Clinformatics® Data Mart Database version 8.1 (2007-2021), we identified parents aged 26-64 continuously enrolled in commercial insurance for ≥ 30 days and linked to ≥ 1 dependent child < 5 years from January 1, 2016-February 29, 2020. We used generalized estimating equations to estimate the average predicted prevalence of SUD diagnosis, MOUD receipt after opioid use disorder (OUD) diagnosis, and overdose by parent sex in any month, adjusting for age, race/ethnicity, state of residence, enrollment month, and mental health conditions. Results: From 2016 to 2020, there were 2,241,795 parents with a dependent child < 5 years, including 1,155,252 (51.5%) females and 1,086,543 (48.5%) males. Male parents had a higher average predicted prevalence of an SUD diagnosis (11.1% [11, 11.16]) than female parents (5.5% [5.48, 5.58]). Among parents with OUD, the average predicted prevalence of receiving MOUD was 27.4% [26.1, 28.63] among male and 19.7% [18.34, 21.04] among female parents, with no difference in overdose rates by sex. Conclusion: Female parents are less likely to be diagnosed with an SUD or receive MOUD than male parents. Removing policies that criminalize parental SUD and addressing childcare-related barriers may improve SUD identification and treatment.

Team-focused implementation strategies to improve implementation of mental health screening and referral in rural Children's Advocacy Centers: study protocol for a pilot cluster randomized hybrid type 2 trial.

BACKGROUND: Children's Advocacy Centers (CACs) use multidisciplinary teams to investigate and respond to maltreatment allegations. CACs play a critical role in connecting children with mental health needs to evidence-based mental health treatment, especially in low-resourced rural areas. Standardized mental health screening and referral protocols can improve CACs' capacity to identify children with mental health needs and encourage treatment engagement. In the team-based context of CACs, teamwork quality is likely to influence implementation processes and outcomes. Implementation strategies that target teams and apply the science of team effectiveness may enhance implementation outcomes in team-based settings. METHODS: We will use Implementation Mapping to develop team-focused implementation strategies to support the implementation of the Care Process Model for Pediatric Traumatic Stress (CPM-PTS), a standardized screening and referral protocol. Team-focused strategies will integrate activities from effective team development interventions. We will pilot team-focused implementation in a cluster-randomized hybrid type 2 effectiveness-implementation trial. Four rural CACs will implement the CPM-PTS after being randomized to either team-focused implementation (n = 2 CACs) or standard implementation (n = 2 CACs). We will assess the feasibility of team-focused implementation and explore between-group differences in hypothesized team-level mechanisms of change and implementation outcomes (implementation aim). We will use a within-group pre-post design to test the effectiveness of the CPM-PTS in increasing caregivers' understanding of their child's mental health needs and caregivers' intentions to initiate mental health services (effectiveness aim). CONCLUSIONS: Targeting multidisciplinary teams is an innovative approach to improving implementation outcomes. This study will be one of the first to test team-focused implementation strategies that integrate effective team development interventions. Results will inform efforts to implement evidence-based practices in team-based service settings. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05679154 . Registered on January 10, 2023.

Assessing Candidacy for Conversation Training Therapy: The Role of Patient Perception.

OBJECTIVE: Voice therapy is the primary treatment modality for voice rehabilitation. Specific patient-ability factors beyond patient-characteristic factors (eg, disorder diagnosis, age, etc.), that influence individual patient responses to voice treatment remain largely unknown. The goal of the current study was to determine the relationship between patient-perceived improvements in both the sound and feel of voice during stimulability assessment and voice therapy outcomes. STUDY DESIGN: Prospective Cohort study. METHODS: This study was a single-arm, single-center, prospective study. Fifty patients with primary muscle tension dysphonia and benign vocal fold lesions were enrolled. Patients read the first four sentences of the Rainbow Passage and were asked if they experienced a change in the feel or sound of their voice following the stimulability prompt. Patients then completed four sessions of conversation training therapy (CTT) voice therapy and followed up one-week and three-months after their last therapy session, for a total of six time-points. Demographic data were collected at baseline, and voice handicap index 10 (VHI-10) scores were collected at each follow-up time-point. The primary exposure variables were CTT intervention and patient perception of voice change to stimulability probes. The primary outcome was change in VHI-10 score. RESULTS: On average, VHI-10 scores improved for all participants following CTT treatment. All participants heard a change in the sound of voice with stimulability prompts. Descriptively, patients who reported a positive change in the feel of their voice after stimulability testing recovered faster (ie, experienced a sharper decline in VHI-10) compared to those who did not note a change in feel of voice during stimulability testing. However, the rate of change over time was not significantly different between groups. CONCLUSION: Patient self-perception of a change in the sound and feel of voice in response to stimulability probes during initial evaluation is an important factor in treatment outcomes. Patients who perceive an improved feel of their voice production after stimulability probes may respond to voice therapy more quickly.

Pediatric intestine transplant cost: Analysis of the Pediatric Health Information System database.

BACKGROUND: We aimed to evaluate costs from transplant to discharge in children who had undergone intestine transplant. METHODS: We performed a cross-sectional observational study of pediatric intestine transplant recipients from 2004 through 2020, utilizing the Pediatric Health Information System database. Standardized costs were applied to all charges and converted to 2021 US dollars. We analyzed the association of cost from transplant to discharge with age, sex, race and ethnicity, length of stay, insurance type, transplant year, short bowel syndrome diagnosis, liver-containing graft, hospitalization status, and immunosuppressive regimen. Predictors with a P value <0.20 in univariable analysis were included in a multivariable model, which was reduced using backwards selection with a P value of 0.05. RESULTS: We identified 376 intestinal transplant recipients across nine centers (median age, 2 years; 44% female). Most patients had short bowel syndrome (294; 78%). The liver was included in 218 transplants (58%). Median posttransplant cost was $263,724 (interquartile range [IQR], $179,564-$384,147), and length of stay was 51.5 days (IQR, 34-77). In the final model, increased cost from transplant to hospital discharge was associated with liver-containing graft (+$31,805; P = 0.028), T-cell-depleting antibody use (+$77,004; P < 0.001), and mycophenolate mofetil use (+$50,514; P = 0.012) while controlling for insurance type and length of stay. A 60-day posttransplant hospital stay would cost an estimated $272,533. CONCLUSIONS: Intestine transplant has high immediate cost and long length of stay that varies by center, graft type, and immunosuppression regimen. Future work will examine the cost-effectiveness of various management strategies before and after transplant.

Associations between teamwork and implementation outcomes in multidisciplinary cross-sector teams implementing a mental health screening and referral protocol.

PURPOSE: Teams play a central role in the implementation of new practices in settings providing team-based care. However, the implementation science literature has paid little attention to potentially important team-level constructs. Aspects of teamwork, including team interdependence, team functioning, and team performance, may affect implementation processes and outcomes. This cross-sectional study tests associations between teamwork and implementation antecedents and outcomes in a statewide initiative to implement a standardized mental health screening/referral protocol in Child Advocacy Centers (CACs). METHODS: Multidisciplinary team members (N = 433) from 21 CACs completed measures of team interdependence; affective, behavioral, and cognitive team functioning; and team performance. Team members also rated the acceptability, appropriateness, and feasibility of the screening/referral protocol and implementation climate. The implementation outcomes of days to adoption and reach were independently assessed with administrative data. Associations between team constructs and implementation antecedents and outcomes were tested with linear mixed models and regression analyses. RESULTS: Team task interdependence was positively associated with implementation climate and reach, and outcome interdependence was negatively correlated with days to adoption. Task and outcome interdependence were not associated with acceptability, appropriateness, or feasibility of the screening/referral protocol. Affective team functioning (i.e., greater liking, trust, and respect) was associated with greater acceptability, appropriateness, and feasibility. Behavioral and cognitive team functioning were not associated with any implementation outcomes in multivariable models. Team performance was positively associated with acceptability, appropriateness, feasibility, and implementation climate; performance was not associated with days to adoption or reach. CONCLUSIONS: We found associations of team interdependence, functioning, and performance with both individual- and center-level implementation outcomes. Implementation strategies targeting teamwork, especially task interdependence, affective functioning, and performance, may contribute to improving implementation outcomes in team-based service settings.