Alkene Isomerization Using a Heterogeneous Nickel-Hydride Catalyst.

Transition metal-catalyzed alkene isomerization is an enabling technology used to install an alkene distal to its original site. Due to their well-defined structure, homogeneous catalysts can be fine-tuned to optimize reactivity, stereoselectivity, and positional selectivity, but they often suffer from instability and nonrecyclability. Heterogeneous catalysts are generally highly robust but continue to lack active-site specificity and are challenging to rationally improve through structural modification. Known single-site heterogeneous catalysts for alkene isomerization utilize precious metals and bespoke, expensive, and synthetically intense supports. Additionally, they generally have mediocre reactivity, inspiring us to develop a heterogeneous catalyst with an active site made from readily available compounds made of Earth-abundant elements. Previous work demonstrated that a very active homogeneous catalyst is formed upon protonation of Ni[P(OEt)3]4 by H2SO4, generating a [Ni-H]+ active site. This catalyst is incredibly active, but also decomposes readily, which severely limits its utility. Herein we show that by using a solid acid (sulfated zirconia, SZO300), not only is this decomposition prevented, but high activity is maintained, improved selectivity is achieved, and a broader scope of functional groups is tolerated. Preliminary mechanistic experiments suggest that the catalytic reaction likely goes through an intermolecular, two-electron pathway. A detailed kinetic study comparing the state-of-the-art Ni and Pd isomerization catalysts reveals that the highest activity and selectivity is seen with the Ni/SZO300 system. The reactivity of Ni/SZO300, is not limited to alkene isomerization; it is also a competent catalyst for hydroalkenylation, hydroboration, and hydrosilylation, demonstrating the broad application of this heterogeneous catalyst.

REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19.

BACKGROUND: Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads. METHODS: In this ongoing, double-blind, phase 1-3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive or serum antibody-negative). Key end points included the time-weighted average change in viral load from baseline (day 1) through day 7 and the percentage of patients with at least one Covid-19-related medically attended visit through day 29. Safety was assessed in all patients. RESULTS: Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was -0.56 log10 copies per milliliter (95% confidence interval [CI], -1.02 to -0.11) among patients who were serum antibody-negative at baseline and -0.41 log10 copies per milliliter (95% CI, -0.71 to -0.10) in the overall trial population. In the overall trial population, 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit; among patients who were serum antibody-negative at baseline, the corresponding percentages were 15% and 6% (difference, -9 percentage points; 95% CI, -29 to 11). The percentages of patients with hypersensitivity reactions, infusion-related reactions, and other adverse events were similar in the combined REGN-COV2 dose groups and the placebo group. CONCLUSIONS: In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.).

REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19.

BACKGROUND: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. METHODS: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated. RESULTS: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups. CONCLUSIONS: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).

Use of induction therapy post-heart transplantation: Clinical practice recommendations based on systematic review and network meta-analysis of evidence.

BACKGROUND: The use of induction therapy (IT) agents in the early post-heart transplant period remains controversial. The following recommendations aim to provide guidance on the use of IT agents, including Basiliximab and Thymoglobulin, as part of routine care in heart transplantation (HTx). METHODS: We recruited an international, multidisciplinary panel of 15 stakeholders, including patient partners, transplant cardiologists and surgeons, nurse practitioners, pharmacists, and methodologists. We commissioned a systematic review on benefits and harms of IT on patient-important outcomes, and another on patients' values and preferences to inform our recommendations. We used the GRADE framework to summarize our findings, rate certainty in the evidence, and develop recommendations. The panel considered the balance between benefits and harms, certainty in the evidence, and patient's values and preferences, to make recommendations for or against the routine post-operative use of Thymoglobulin or Basiliximab. RESULTS: The panel made recommendations on three major clinical problems in HTx: (1) We suggest against the routine post-operative use of Basiliximab compared to no IT, (2) we suggest against the routine use of Thymoglobulin compared to no IT, and (3) for those patients for whom IT is deemed desirable, we suggest for the use of Thymoglobulin as compared to Basiliximab. CONCLUSION: This report highlights gaps in current knowledge and provides directions for clinical research in the future to better understand the clinical utility of IT agents in the early post heart transplant period, leading to improved management and care.

Casirivimab and Imdevimab for the Treatment of Hospitalized Patients With COVID-19.

BACKGROUND: The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD). METHODS: In this phase 1/2/3, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4 g or 8.0 g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus. RESULTS: In total, 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was -0.28 log10 copies/mL (95% confidence interval [CI], -.51 to -.05; P = .0172). The primary clinical analysis of death or mechanical ventilation from day 6 to 29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2%-74.0%). No safety concerns were noted. CONCLUSIONS: In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients. CLINICAL TRIALS REGISTRATION: NCT04426695.

Lay Summary . Monoclonal antibody therapies that block the virus that causes COVID-19 (SARS-CoV-2) can prevent patients from being hospitalized. We hypothesized that these antibodies may also benefit patients who are already hospitalized with COVID-19. Therefore, we performed a study to determine if the monoclonal antibody combination of casirivimab and imdevimab (CAS + IMD) can decrease the amount of virus in the nose of hospitalized patients and prevent the disease from becoming more severe. The study, conducted from June 2020 to April 2021, found that CAS + IMD treatment reduced the amount of virus in these patients, and may reduce their chance of dying or needing a ventilator (a machine that helps patients breathe). Patients were examined in 2 groups: those whose immune systems, at the start of the study, had not produced their own antibodies to fight SARS-CoV-2 (seronegative patients); or those that had already produced their own antibodies (seropositive patients) at the start of the study. Seronegative patients benefited the most from CAS + IMD. No safety concerns related to CAS + IMD were observed. These results demonstrate that monoclonal antibody therapy can help hospitalized patients with COVID-19 and may decrease their chances of needing assistance to breathe or dying.

Implementation of INHERET, an Online Family History and Cancer Risk Interpretation Program for Primary Care and Specialty Clinics.

BACKGROUND: Individuals at increased risk for cancer are ascertained at low rates of 1% to 12% in primary care (PC). Underserved populations experience disparities of ascertainment, but data are lacking. INHERET is an online personal and family history tool to facilitate the identification of individuals who are eligible, according to guidelines, to be counseled on germline genetic testing and risk management. PATIENTS AND METHODS: INHERET data entry uses cancer genetics clinic questionnaires and algorithms that process patient data through NCCN Clinical Practice Guidelines in Oncology and best practice guidelines. The tool was tested in silico on simulated and retrospective patients and prospectively in a pilot implementation trial. Patients in cancer genetics and in PC clinics were invited to participate via email or a card. Informed consent was completed online. RESULTS: INHERET aimed to integrate patient data by algorithms based on professional and best practice guidelines to elicit succinct, actionable recommendations that providers can use without affecting clinic workflow or encounter length. INHERET requires a 4th-grade reading level, has simple navigation, and produces data lists and pedigree graphs. Prospective implementation testing revealed understandability of 90% to 100%, ease of use of 85%, and completion rates of 85% to 100%. Physicians using INHERET reported no added time to their encounters when patients were identified for counseling. In a specialty genetics clinic, INHERET's data were input, on average, within 72 hours compared with 4 to 6 weeks through standard care, and the queue for scheduling patients decreased from 400 to fewer than 15 in <6 months. CONCLUSIONS: INHERET was found to be accessible for all education and age levels, except patients aged >70 years, who encountered more technical difficulties. INHERET aided providers in conveying high-risk status to patients and eliciting appropriate referrals, and, in a specialty clinic, it produced improved workflows and shortened queues.

PSYCHOPATHY AND RISKY SEXUAL BEHAVIOR IN INCARCERATED WOMEN.

To date, very few studies have explored the association between psychopathic traits and risky sexual behavior (RSB) among women. Here, we investigated this relationship in a sample of 137 incarcerated women. Psychopathic traits were assessed via the Hare Psychopathy Checklist-Revised (PCL-R) and lifetime RSB measures, including number of lifetime sexual partners, frequency of engaging in sexual intercourse while intoxicated, and frequency of forgoing protection (e.g., condom usage) during sexual intercourse, were assessed through self-report. PCL-R Facet 3 scores (assessing lifestyle psychopathic traits) were associated with an increased frequency of engaging in sexual intercourse while intoxicated. In addition, women scoring high on the PCL-R were more likely to engage in sexual intercourse while intoxicated compared with a previously collected sample of men scoring high on the PCL-R. The results obtained in the current study help improve our understanding of the association between psychopathic traits and RSB among women.

Marijuana Decriminalization, Medical Marijuana Laws, and Fatal Traffic Crashes in US Cities, 2010-2017.

Objectives. To determine the impact of city-level cannabis decriminalization and medical marijuana laws (MMLs) on fatal traffic crashes in US cities.Methods. Using a census of fatal traffic crashes from the 2010 to 2017 Fatality Analysis Reporting System, we examined MMLs and cannabis decriminalization on fatal crashes by age and sex of driver. We used a Poisson difference-in-differences approach, exploiting temporal and geographic variation in marijuana decriminalization laws.Results. Cities experienced a 13% increase in fatal crashes involving 15- to 24-year-old male drivers following decriminalization (incidence rate ratio = 1.125; 95% confidence interval = 1.014, 1.249). This effect was immediate and strongest on weekend nights. We found no effect on female drivers or older males. Conversely, we found that MMLs were associated with fewer fatal crashes for both males and females, which was most pronounced in 15- to 24-year-old drivers.Conclusions. Unlike MMLs, which are associated with fewer fatal crashes, cities experienced a relative increase in fatal crashes involving young male drivers following marijuana decriminalization.Public Health Implications. MMLs stipulate consumption occurs at home, whereas decriminalization only lessens the penalty for marijuana possession. Therefore, travel incentives of such laws have heterogeneous effects on traffic safety.

The relationship between psychopathic traits and risky sexual behavior in incarcerated adult male offenders.

Individuals scoring high on psychopathic traits engage in various forms of risky behavior. However, the relationship between psychopathic traits and risky sexual behavior (RSB) is less understood, especially with participants recruited from incarcerated settings. Here, we investigated the relationship between RSB and psychopathic traits with n = 179 incarcerated adult male offenders who completed a self-report RSB questionnaire asking participants about their lifetime number of sexual partners and frequency of using a condom during sex. Psychopathic traits were assessed using the Hare Psychopathy Checklist - Revised (PCL-R). In independent-samples t-tests, participants scoring high on psychopathic traits (i.e., PCL-R total score ≥ 30) reported greater total number of sexual partners throughout their lifetime and were less likely to use a condom during sex compared to low-scorers (i.e., PCL-R total score ≤ 15). In multiple regression analyses, PCL-R total scores emerged as a significant predictor of reduced condom usage during sex, but covariate measures assessing general externalizing psychopathology, did not. Our results suggest that several public health concerns, including sexually transmitted infection transmittal and unwanted pregnancies, may arise due to individuals scoring higher on psychopathy engaging in risky sexual behavior to a greater extent compared to those scoring lower on psychopathy.

Understanding the Lewis Acidity of Co(II) Sites on a Silica Surface.

Heterogeneous catalysts consisting of isolated transition-metal sites dispersed on the surface of metal oxide supports are commonly used in the chemical industry. Often their reactivity relies on the Lewis acidity of the active sites on the surface of the catalyst. A recent report from our group showed that silica-supported Co(II) sites, prepared via surface organometallic chemistry, are active in both alkene hydrogenation and alkane dehydrogenation, possibly linked to the Lewis acidity of the Co(II) sites. Here we use molecular probes and analogues to both qualitatively and quantitatively model the Lewis acidity of the surface sites. Some sites do not bind probe molecules like carbon monoxide, tetrahydrofuran, and olefins, while others exhibit a continuum of Lewis acidities. This is consistent with variations in the coordination environment of Co. These results suggest that only the most Lewis acidic sites are involved in dehydrogenation and hydrogenation, consistent with catalyst poisoning studies.

Mechanism of the palladium-catalyzed arene C-H acetoxylation: a comparison of catalysts and ligand effects.

This article describes detailed mechanistic studies focused on elucidating the impact of pyridine ligands on the Pd-catalyzed C-H acetoxylation of benzene. Three different catalysts, Pd(OAc)2, Pd(OAc)2/pyridine (1:1), and Pd(OAc)2/pyridine (1:2), are compared using a combination of mechanistic tools, including rate and order studies, Hammett analysis, detailed characterization of catalyst resting states, and isotope effects. The data from these experiments implicate C-H activation as the rate-limiting step in all cases. The major difference between the three catalysts is proposed to be the resting state of Pd. Under the reaction conditions, Pd(OAc)2 rests as an acetate bridged dimer, while the Pd(OAc)2/pyridine (1:2) catalyst rests as the monomer (pyridine)2Pd(OAc)2. In contrast, a variety of experiments suggest that the highly active catalyst generated from the 1:1 combination of Pd(OAc)2 and pyridine rests as the dimeric structure [(pyridine)Pd(OAc)2]2.

Functional health status in children and adolescents after Fontan: comparison of generic and disease-specific assessments.

PURPOSE: The aim of this study was to compare associations between generic versus disease-specific functional health status assessments and patient and clinical characteristics for patients with severe congenital heart disease. METHODS: This was a cross-sectional observational study involving 325 single ventricle patients, aged 10-18 years, after Fontan procedure. Enrolled patients underwent a medical history review, laboratory testing, and assessment of the functional health status by completion of the generic Child Report Child Health Questionnaire and the disease-specific Congenital Heart Adolescent and Teenage questionnaire. Correlated conceptually equivalent domains from both questionnaires were identified and their associations with patient and clinical variables were compared. RESULTS: From the generic assessment, patients perceived marginally lower physical functioning (p = 0.05) but greater freedom from bodily pain compared with a normal population (p < 0.001). The equivalent physical functioning/limitations domain of the generic instrument, compared with the disease-specific instrument, had similar associations (higher multi-variable model R²) with medical history variables (R² = 0.14 versus R² = 0.12, respectively) and stronger associations with exercise testing variables (R² = 0.22 versus R² = 0.06). Similarly, the corresponding freedom from bodily pain/symptoms domains from both questionnaires showed a greater association for the generic instrument with medical history variables (R² = 0.15 versus R² = 0.09, respectively) and non-cardiac conditions (R² = 0.13 versus R² = 0.06). The associations of each questionnaire with echocardiographic results, cardiac magnetic resonance imaging results, and serum brain natriuretic peptide levels were uniformly weak (R² range <0.01 to 0.04). CONCLUSIONS: Assessment of the physical functional health status using generic and disease-specific instruments yields few differences with regard to associations between conceptually similar domains and patient and clinical characteristics for adolescents after Fontan procedure.

A Case-Based, Longitudinal Curriculum in Pediatric Behavioral and Mental Health.

Introduction: Pediatric behavioral and mental health (BMH) disorders are increasingly common, but most pediatricians feel inadequately trained to manage them. We implemented a case-based, longitudinal curriculum in BMH within a pediatric residency program to prepare trainees to diagnose and manage these conditions. Methods: The pediatric residency program at Wright State University/Wright-Patterson Medical Center implemented a new BMH curriculum in 2020-2021. The curriculum consisted of five simulated cases involving depression, anxiety, attention deficit disorder with hyperactivity (ADHD), developmental delays, behavioral concerns, and autism. To reflect follow-up within a continuity clinic, cases included initial encounters and multiple follow-up visits. Faculty facilitators led residents in monthly small-group meetings over the academic year, with each session consisting of two to three simulated patient encounters. Residents completed pre-post surveys regarding their confidence in diagnosing and managing BMH conditions and pre- and posttests to evaluate the impact of the curriculum on knowledge gains. Results: All 47 pediatric residents participated in the curriculum; 38 (81%) completed pre-post surveys. Upon completion of the curriculum, residents reported significantly increased confidence in managing ADHD, treating depression, creating safety plans for suicidality, recognizing autism, and counseling patients and families on special education services. Knowledge-based pre- and posttests completed by 25 residents (53%) also demonstrated significant improvement (M = 92.4, SD = 10.9, pre vs. M = 99.3, SD = 6.6, post, p = .009). Discussion: This case-based, longitudinal curriculum in pediatric BMH simulating patient continuity improved residents' confidence and knowledge in diagnosing and managing common BMH conditions.

S1 is associated with chronic low back pain: a functional and structural MRI study.

A fundamental characteristic of neural circuits is the capacity for plasticity in response to experience. Neural plasticity is associated with the development of chronic pain disorders. In this study, we investigated 1) brain resting state functional connectivity (FC) differences between patients with chronic low back pain (cLBP) and matched healthy controls (HC); 2) FC differences within the cLBP patients as they experienced different levels of endogenous low back pain evoked by exercise maneuvers, and 3) morphometric differences between cLBP patients and matched HC. We found the dynamic character of FC in the primary somatosensory cortex (S1) in cLBP patients, i.e., S1 FC decreased when the patients experienced low intensity LBP as compared with matched healthy controls, and FC at S1 increased when cLBP patients experienced high intensity LBP as compared with the low intensity condition. In addition, we also found increased cortical thickness in the bilateral S1 somatotopically associated with the lower back in cLBP patients as compared to healthy controls. Our results provide evidence of structural plasticity co-localized with areas exhibiting FC changes in S1 in cLBP patients.

Association of impaired linear growth and worse neurodevelopmental outcome in infants with single ventricle physiology: a report from the pediatric heart network infant single ventricle trial.

OBJECTIVES: To describe neurodevelopmental outcomes in infants with single ventricle (SV) physiology and determine factors associated with worse outcomes. STUDY DESIGN: Neurodevelopmental outcomes for infants with SV enrolled in a multicenter drug trial were assessed at 14 months of age using the Bayley Scales of Infant Development-II. Multivariable regression analysis was used to identify factors associated with worse outcomes. RESULTS: Neurodevelopmental testing was performed at 14 ± 1 months in 170/185 subjects in the trial. Hypoplastic left heart syndrome was present in 59% and 75% had undergone the Norwood operation. Mean Psychomotor Developmental Index (PDI) and mental developmental index (MDI) were 80 ± 18 and 96 ± 14, respectively, (normal 100 ± 15, P < .001 for each). Group-based trajectory analysis provided a 2-group model ("high" and "low") for height z-score trajectory and brain type natriuretic peptide (BNP) trajectory. The predicted PDI scores were 15 points higher in the "high" height z-score trajectory compared with the "low" cluster (P < .001). A higher number of serious adverse events during the trial was associated with lower PDI scores (P = .02). The predicted MDI scores were 13-17 points lower in "low height trajectory-high BNP trajectory" group compared with the other 3 groups (P < .001). MDI scores were also lower in subjects who required extracorporeal membrane oxygenation during the neonatal hospitalization (P = .01) or supplemental oxygen at discharge (P = .01). CONCLUSIONS: Neurodevelopmental outcome at 14 months of age is impaired in infants with SV physiology. Low height trajectory and high BNP trajectory were associated with worse neurodevelopmental outcomes. Efforts to improve nutritional status alone may not improve neurodevelopmental outcomes.

Fraternity and sorority membership and risky sexual behavior.

Objectives: To determine the impact of fraternity and sorority membership on condom use during sex. Methods: Utilizing data from The American College Health Association (ACHA) National College Health Assessment from 2016-2018, we estimated a linear probability, logistic, and instrumental variable model to determine the relationship between fraternity and sorority membership and the frequency of condom use during sex. Results: Compared to non-fraternity members, fraternity members experience an increase in sex without a condom for both oral sex (13.5%, 95% ci= 0.048, 0.221) and anal sex (28.5%, 95% ci= 0.174, 0.396). Compared to non-sorority members, sorority members are more likely to engage in oral sex without a condom. This result is not robust to single sorority members. Conclusions: Fraternity membership increases the probability of risky oral and anal sex. Policy Implications: The reduced use of condoms has implications on sexual health including an increased risk of contracting or spreading sexually transmitted infections.

Medical cannabis laws lower individual market health insurance premiums.

BACKGROUND: To evaluate the impact of medical cannabis laws (MCLs) on health insurance premiums. We study whether cannabis legalization significantly impacts aggregate health insurer premiums in the individual market. Increases in utilization could have spillover effects to patients in the form of higher health insurance premiums. METHODS: We use 2010-2021 state-level U.S. private health insurer financial data from the National Association of Insurance Commissioners. We examined changes to individual market health insurance premiums after the implementation of medical cannabis laws. We employed a robust difference-in-differences estimator that accounted for variation in policy timing to exploit temporal and geographic variation in state-level medical cannabis legalization. RESULTS: Seven years after the implementation of Medical Cannabis laws, we observe lower health insurer premiums in the individual market. Starting seven years post-MCL implementation, we find a reduction of $-1662.7 (95% confidence interval [CI -2650.1, -605.7]) for states which implemented MCLs compared to the control group, a reduction of -$1541.8 (95% confidence interval [CI 2602.1, -481.4]) in year 8, and a reduction of $-1625.8, (95% confidence interval [CI -2694.2, -557.5]) in year 9. Due to the nature of insurance pooling and community rating, these savings are appreciated by cannabis users and non-users alike in states that have implemented MCLs. CONCLUSIONS: The implementation of MCLs lowers individual-market health insurance premiums. Health insurance spending, including premiums, comprises between 16% and 34% of household budgets in the United States. As healthcare costs continue to rise, our findings suggest that households that obtain their health insurance on the individual (i.e., not employer sponsored) market in states with MCLs appreciate significantly lower premiums.

Changes in left ventricular systolic function after transcatheter patent ductus arteriosus closure in premature infants.

Background: Changes in left ventricular (LV) systolic function have not been well described in premature neonates after transcatheter patent ductus arteriosus (PDA) closure. Methods and Results: We retrospectively identified all premature neonates < 3 kg who underwent a transcatheter PDA closure at our center between January 1 2015 and January 31, 2021. LV indices before and after closure were extracted and an analysis was performed. Overall, 23 neonates were included with a mean procedural weight of 1894 ± 622 g. At 24 h after closure, the median left ventricular ejection fraction (LVEF) (66% interquartile range [IQR] 12% vs. 61% IQR 12, P< 0.001) and median LV end-diastolic dimension z-score (3.3 IQR 1.8 vs. 1.4 IQR 2.6, P < 0.001) both decreased and 5 (22%) neonates had an LVEF <55%. Patients who had an LVEF <55% at 24 h had a higher preprocedure LV end-diastolic dimension z-score (4.2 IQR 1.2 vs. 2.8 IQR 1.6, P = 0.01), a higher preprocedure LV end-diastolic volume (19 mL IQR 4 mL vs. 11 mL IQR 11, P = 0.03), a higher birth weight (940 g IQR 100 g vs. 760 g IQR 140, P = 0.04), and were more likely to receive intravenous calcium during the procedure (60% vs. 11%, P = 0.04) compared to those with an LVEF ≥55% at 24 h after closure. Of those with LVEF <55% at 24 h, all normalized before discharge. Conclusion: In preterm neonates who underwent successful transcatheter PDA closure, 23% developed abnormal LVEF after closure and those with significant LV dilation before the procedure were at increased risk for the development of LVEF <55% after closure.

Prophylactic Intraoperative Antibiotic Dosing in Head and Neck Surgery: Opportunities for Improvement and Future Study.

OBJECTIVES: To investigate rates of Surgical Care Improvement Project (SCIP) guideline adherence with regard to intraoperative antibiotic prophylaxis in head and neck surgery with free tissue transfer. STUDY DESIGN: Retrospective case series. SETTING: A single academic center. METHODS: All patients who underwent mucosa-violating head and neck oncologic surgery with free tissue transfer between March 2017 and June 2019 were reviewed. Intraoperative antibiotic data included type, dosage, frequency of administration, and duration. Any deviation from SCIP recommendations was defined as nonadherence. Antibiotic type was categorized as ampicillin-sulbactam, cefazolin/metronidazole, clindamycin, and others. As a secondary exploratory analysis, postoperative infections were analyzed and stratified by adherent vs nonadherent and by antibiotic type. RESULTS: A total of 129 surgical procedures were included. The mean ± SD number of antibiotic doses during surgery was 3.16 ± 1.2. The mean number of missed doses was 1.86 ± 1.65. Adherence rate with first dosing recommendation was 100%, as compared with 41.7% for dose 2, 23.1% for dose 3, 13.7% for dose 4, 5.26% for dose 5, 2.56% for dose 6, and 0% for dose 7 (P < .001). Ampicillin-sulbactam (6.4%) had a significantly lower rate of average redosing adherence when compared with cefazolin/metronidazole (73.2%) and clindamycin (63.3%; P < .001). CONCLUSION: Significant opportunities exist in SCIP guideline adherence rates for intraoperative antibiotic prophylaxis. Cefazolin/metronidazole had a significantly higher rate of appropriate redosing when compared with ampicillin-sulbactam, which should be considered when choosing a prophylactic antibiotic regimen and performing antibiotic-based outcomes studies. More attention should be given to intraoperative antibiotic prophylaxis in head and neck surgery with free tissue transfer, as this presents an opportunity for quality improvement and future study heretofore not explored.

Traumatic Brain Injury and Psychopathic Traits in Justice-Involved Adult Women.

Studies have documented associations between traumatic brain injury (TBI) and mental disorders. The relationship between psychopathic personality and TBI remains poorly understood, though both are associated with similar characteristics (e.g., low empathy, aggression, disturbances in social/moral behavior). Yet, it is not clear whether assessment of psychopathic features is influenced by presence versus absence of TBI, and which aspects of TBI may be associated with psychopathic traits. This study examined the psychopathy-TBI association in justice-involved women (N = 341) with structural equation modeling. We tested if measurement invariance of psychopathic traits was evident among those with versus without TBI and which TBI variables (number, severity, age at first TBI) predicted psychopathic features in conjunction with symptoms of psychopathology, IQ, and age. Results provided evidence of measurement invariance, and more women with TBI, compared to those without, met criteria for psychopathy. Younger age of TBI and TBI severity predicted interpersonal-affective psychopathic features.