A Longitudinal Multivariable Analysis: State Policies and Opioid Dispensing in Medicare Beneficiaries Undergoing Surgery.

BACKGROUND: States have implemented policies to decrease clinically unnecessary opioid prescribing, but few studies have examined how state policies affect opioid dispensing rate trends for surgical patients. OBJECTIVE: To examine trends in the perioperative opioid dispensing rates for fee-for-service Medicare beneficiaries and the effects of select state policies. DESIGN AND PARTICIPANTS: A retrospective cohort study using 2006 to 2018 Medicare claims data for individuals undergoing surgical procedures for which opioid analgesic treatment is common. EXPOSURES: State policies mandating prescription drug monitoring program (PDMP; PDMP policies) use, initial opioid prescription duration limit (duration limit policies), and mandated continuing medical education (CME; CME pain policies) on pain management. MAIN MEASURES: Opioid dispensing rates, days' supply, and the daily morphine milligram equivalent dose (MMED). KEY RESULTS: The percentage of Medicare beneficiaries dispensed opioids in the perioperative period increased from 2007 to 2018; MMED and days' supply decreased over the same period, with significant variation by age, sex, and race. None of the three state policies affected the likelihood of Medicare beneficiaries being dispensed perioperative opioids. However, CME pain policies and duration limit policies were associated with decreased days' supply and decreased MMED in the several years following implementation, respectively. CONCLUSION: While we observed a slight increase in the rate of Medicare beneficiaries dispensed opioids perioperatively and a substantial decrease in MMED and days' supply for those receiving opioids, state policies examined had relatively modest effects on the main measures. Our findings suggest that these state policies may have a limited impact on opioid dispensing for a patient population that is commonly dispensed opioid analgesics to help control surgical pain, and as a result may have little direct effect on clinical outcomes for this population. Changes in opioid dispensing for this population may be the result of broader societal trends than such state policies.

Bilateral Implant-based Breast Reconstruction with Unilateral Radiotherapy: A Matched Cohort Study Comparing Nipple-sparing Mastectomy and Skin-sparing Mastectomy.

Background: Nipple-sparing mastectomy (NSM) preserves the natural nipple-areola complex and entire native breast skin, with the goal of better cosmetic outcomes in breast reconstruction. In bilateral TE/implant-based reconstruction requiring unilateral postmastectomy radiotherapy (PMRT), progressive radiation-induced fibrosis can lead to increasing nipple asymmetry with cosmetic dissatisfaction. Thus, PMRT may ultimately negate the intended positive cosmetic value of NSM compared with skin-sparing mastectomy (SSM). This study compares (1) surgical complications, (2) patient satisfaction, and (3) aesthetic outcomes between NSM versus SSM in bilateral implant-based reconstruction with unilateral PMRT. Methods: This retrospective matched cohort study included consecutive NSM patients with bilateral TE/implant breast reconstruction + unilateral PMRT matched 1:2 to SSM group. Patients completed PMRT and TE exchange to implants. Demographics, oncologic stage, comorbidities, and complications were collected. Patient satisfaction was evaluated by BREAST-Q. Aesthetic outcomes were assessed by blinded reviewers with a five-point Likert scale. Results: Among 58 patients who underwent bilateral TE/implant reconstruction with unilateral PMRT, 17 NSM patients were matched to 41 SSM patients by age, body mass index, and comorbidities. No significant differences existed in overall surgical complications and individual BREAST-Q questionnaire scores between cohorts. However, aesthetic outcomes scores were higher in SSM compared with NSM. Conclusions: Although NSM is generally associated with superior cosmetic outcomes compared with SSM, it has far less impact in bilateral implant-based breast reconstruction with unilateral PMRT due to the negative postradiotherapy effect on nipple symmetry.

Cerebral and Peripheral Immune Cell Changes following Rodent Juvenile Traumatic Brain Injury.

Traumatic brain injury (TBI) is one of the leading causes of death and disability. TBI is associated with neuroinflammation, but temporal changes in immune and inflammatory signaling following TBI have not been fully elucidated. Furthermore, there have been no previous studies on changes in immune cell populations following TBI via the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA). The current study aimed to determine the time course changes to inflammatory marker mRNA expression in the acute period following TBI in juvenile rats and to determine acute changes to brain and circulating immune cell populations. For this study, post-natal day (PND)-30 male Long Evans rats sustained a TBI or Sham TBI and were euthanized at 0, 3, 6, 12, 24, or 96 h post-injury. Prefrontal cortex and hippocampus samples were used to determine mRNA expression changes of inflammatory factors. The mRNA expression of the pro-inflammatory cytokine TNF-α was significantly elevated at 6 h post-injury in both regions evaluated. To evaluate immune cell populations, male Long Evans rats were euthanized at 48 h post-injury, and brain and blood samples were used for cell sorting by marker-specific antibodies. In the peripheral blood, there was an elevation in CD3+ total T cells, CD45R+ total B cells, and CD3+CD4+ helper T cells in the TBI subjects. However, there were no changes to natural killer cells or CD3+CD8+ cytotoxic T cell populations. In the brain, there was a reduction in CD11b/c+ monocytes/macrophages, but no changes in other immune cell populations. At 48 h post-injury, the TBI subjects also demonstrated expansion of the thymic medulla. These changes in the cerebral and blood immune cell populations and thymic medulla expansion may implicate the subacute recovery timeframe as a vulnerable window for the immune system in the pediatric population.

TCF1-LEF1 co-expression identifies a multipotent progenitor cell (TH2-MPP) across human allergic diseases.

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (TH2) cells with co-expression of TCF7 and LEF1, and features of chronic activation. These cells, which we termed TH2-multipotent progenitors (TH2-MPP) could self-renew and differentiate into cytokine-producing effector cells, regulatory T (Treg) cells and follicular helper T (TFH) cells. Single-cell T-cell-receptor lineage tracing confirmed lineage relationships between TH2-MPP, TH2 effectors, Treg cells and TFH cells. TH2-MPP persisted despite in vivo IL-4 receptor blockade, while thymic stromal lymphopoietin (TSLP) drove selective expansion of progenitor cells and rendered them insensitive to glucocorticoid-induced apoptosis in vitro. Together, our data identify TH2-MPP as an aberrant T cell population with the potential to sustain type 2 inflammation and support the paradigm that chronic T cell responses can be coordinated over time by progenitor cells.

Sir2 and Fun30 regulate ribosomal DNA replication timing via Mcm helicase positioning and nucleosome occupancy.

The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well-known, yet the specific mechanisms underlying this link remain uncertain. In Saccharomyces cerevisiae, the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA arrays (rDNA). We have previously reported that in the absence of SIR2, a derepressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy. By developing a method that can distinguish activation of closely spaced MCM complexes, here we show that the displaced MCMs at rDNA origins have increased firing propensity compared to the non-displaced MCMs. Furthermore, we found that both, activation of the repositioned MCMs and low occupancy of the adjacent nucleosomes critically depend on the chromatin remodeling activity of FUN30. Our study elucidates the mechanism by which Sir2 delays replication timing, and it demonstrates, for the first time, that activation of a specific replication origin in vivo relies on the nucleosome context shaped by a single chromatin remodeler.

Performance and reliability assessment of a lower dose, task-based scoliosis radiography protocol in pediatric patients.

BACKGROUND: Follow-up scoliosis radiographs are performed to assess the degree of spinal curvature and skeletal maturity, which can be done at lower radiation exposures than those in standard-dose radiography. OBJECTIVE: Describe and evaluate a protocol that reduced the radiation in follow-up frontal-view scoliosis radiographs. MATERIALS AND METHODS: We implemented a postero-anterior lower dose modified-technique for scoliosis radiography with task-based definition of adequate image quality and use of technique charts based on target exposure index and patient's height and weight. We subsequently retrospectively evaluated 40 consecutive patients who underwent a follow-up radiograph using the modified-technique after an initial standard-technique radiograph. We evaluated comparisons of proportions for subjective assessment with chi-squared tests, and agreements of reader's scores with intraclass correlation coefficients and Bland-Altman plots. We determined incident air kerma, exposure index, deviation index/standard deviation, dose-area product (DAP), and effective dose for each radiograph. We set statistical significance at P<0.05. RESULTS: Forty patients (65% female), aged 4-17 years. Median effective dose was reduced from 39 to 10 µSv (P<0.001), incident air kerma from 139 to 29 µSv (P<0.001), and DAP from 266 to 55 mGy*cm2 (P<0.001). All modified-technique parameters were rated with a mean score of acceptable or above. All modified-technique measurements obtained inter- and intra-observer correlation coefficient agreements of 0.86 ("Good") or greater. CONCLUSION: Substantial dose reduction on follow-up scoliosis imaging with existing radiography units is achievable through task-based definition of adequate image quality and tailoring of radiation to each patient's height and weight, while still allowing for reliable assessment and reproducible measurements.

Prominent Structural Dependence of Quantum Capacitance Unraveled by Nitrogen-Doped Graphene Mesosponge.

Porous carbons are important electrode materials for supercapacitors. One of the challenges associated with supercapacitors is improving their energy density without relying on pseudocapacitance, which is based on fast redox reactions that often shorten device lifetimes. A possible solution involves achieving high total capacitance (Ctot ), which comprises Helmholtz capacitance (CH ) and possibly quantum capacitance (CQ ), in high-surface carbon materials comprising minimally stacked graphene walls. In this work, a templating method is used to synthesize 3D mesoporous graphenes with largely identical pore structures (≈2100 m2 g-1 with an average pore size of ≈7 nm) but different concentrations of oxygen-containing functional groups (0.3-6.7 wt.%) and nitrogen dopants (0.1-4.5 wt.%). Thus, the impact of the heteroatom functionalities on Ctot is systematically investigated in an organic electrolyte excluding the effect of pore structures. It is found that heteroatom functionalities determine Ctot , resulting in the cyclic voltammetry curves being rectangular or butterfly-shaped. The nitrogen functionalities are found to significantly enhance Ctot owing to increased CQ .

Leptin antagonism attenuates hypertension and renal injury in an experimental model of autoimmune disease.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by B- and T-lymphocyte dysfunction and altered cytokine production, including elevated levels of the adipocytokine leptin. Leptin has various immunomodulatory properties, including promoting the expansion of proinflammatory T lymphocytes and the proliferation and survival of B cells. In the present study, we hypothesized that leptin antagonism would improve B- and T-cell dysfunction and attenuate hypertension in an experimental model of SLE, the NZBWF1 mouse. To test this hypothesis, 28-week-old female control and SLE mice were administered 5 mg/kg of murine leptin superantagonist (LA) or vehicle via ip injection every other day for four weeks. Analysis of peripheral blood immune cell populations showed no changes in total CD45R+ B and CD3+ T cell percentages after treatment with LA. However, SLE mice treated with LA had an improved CD4/CD8 ratio and decreased CD3+CD4-CD8- double negative (DN) T cells. Blood pressure was higher in SLE than in control, and treatment with LA decreased blood pressure in SLE mice. Treatment with LA also delayed the onset of albuminuria and decreased glomerulosclerosis in SLE mice. Renal immune cell infiltration was significantly higher in SLE mice as compared with control, but LA treatment was associated with decreased levels of renal CD4+ T cells. In conclusion, these data suggest that leptin plays a pathogenic role in the development of hypertension in SLE, in part, by promoting the expansion of inflammatory DN T cells and the infiltration of T cells into the kidneys.

How are state telehealth policies associated with services offered by substance use disorder treatment facilities? Evidence from 2019 to 2022.

BACKGROUND: The COVID-19 pandemic led several states to adopt policies permitting the delivery of substance use disorder treatment (SUDT) by telehealth. We assess the impact of state-level telehealth policies in 2020 that specifically permitted audio or audiovisual forms of telehealth offerings among SUDT facilities. PROCEDURE: Cross-sectional analysis of secondary data from between 2019 and 2022. Pre-pandemic, federal law permitted states to allow audiovisual telehealth modes for SUDT to a limited extent. 2020 laws permitted states to allow audio-only modes for the first time and strengthened ability to offer audiovisual modes. We compared national SUDT facility self-reported telehealth offerings in 2020 and beyond to 2019, in states that in 2020 had policies permitting audiovisual and audio only, compared to other states. MAIN FINDINGS: Among outpatient SUDT facilities (n = 5227) present in all four years of our data, the proportion offering telehealth increased from 18% (n = 921) in 2019-26% in 2020, 60% in 2021, and 79% in 2022. We estimate an audiovisual and audio only policy in 2020 was associated with an increase in telehealth offering rates in 2022 of +16.5% points (pp) (95% CI [+10.4,+22.6]) compared to the rates in states with no such listed policy. There was little evidence of an influence on telehealth offering in 2020 (-2.9 pp, CI [-9.0,+3.2]) and 2021 (+0.6 pp, CI [-5.5,+6.7]). CONCLUSIONS: The enactment of state-level telehealth policies that allow audio and audiovisual modalities may have increased SUDT facilities' likelihood of offering telehealth services two years after enactment.

Impressions of child advocacy center leaders: How problematic sexual behavior in children and adolescents is perceived by community professionals.

BACKGROUND: Consistent with the goals of National Children's Alliance, Children's Advocacy Centers (CACs) are optimal for addressing needs related to problematic sexual behavior (PSB) of youth due to their multidisciplinary approach and emphasis on community-level evidence-based interventions (Kelley et al., 2019). To promote child well-being and safety, decisions of the CAC's multidisciplinary team must be based on an accurate understanding of youth with PSB, child sexual development, and best-practice responses. However, misperceptions about youth who have engaged in PSB appear to broadly persist (Hackett, Masson, et al., 2013), leading to obstacles for CACs in addressing PSB. OBJECTIVE: To better understand and address the training and service needs of CACs across the country, the goal of this study was to assess CAC community professionals' (e.g., MDT members) perceptions of children and adolescents with PSB, as reported by CAC leaders. PARTICIPANTS AND SETTING: Participants were 351 CACs from 47 US states, a representative sample based on regional and community distributions. METHOD: A designated point-of-contact (e.g., the Director) for each CAC completed an online survey reflecting on their CAC's professional community's perceptions of youth with PSB. RESULTS: Findings suggested that a number of misperceptions about youth with PSB, particularly adolescents, are commonly reported for CAC professional communities. Prevalent misperceptions surrounded the etiology of PSB, treatment-related needs, and differences between youth with PSB and adults. CONCLUSIONS: Results can be used to inform policy, practice, training, and resource utilization to address youth with PSB in CACs, with specific recommendations provided to enhance an evidence-based approach.

Urine drug testing in the context of opioid analgesic prescribing for chronic pain: a content analysis of U.S. state laws in 2022.

BACKGROUND: In response to the opioid crisis, U.S. states have passed laws requiring urine drug testing (UDT) when opioid analgesics are prescribed for chronic pain. We sought to identify state law UDT requirements. METHODS: We searched NexisUni legal database using terms related to UDT, chronic pain, and opioids. We included laws effective during spring 2022 that required UDT when opioids were prescribed for chronic pain. We performed deductive content analysis, coding laws for mandated UDT frequency, type of clinician and type of payer to whom the law applied, and circumstances under which UDT was mandated. RESULTS: We found 32 laws across 13 states that met our inclusion criteria. UDT requirements varied substantially by state, including with regard to the type of clinician to whom the law applied, the mandated frequency of UDT (eg, at initiation/assessment, at least annually, more than once per year), and the circumstances in which UDT was mandated (eg, patient had substance use disorder; dosage/day threshold). DISCUSSION: Relatively few states have UDT mandates associated with prescribing opioids as chronic pain treatment. When developing policy indicators for empirical studies, researchers evaluating how UDT policy affects health outcomes must consider the complexity and lack of uniformity of UDT requirements. In addition, even if states mandate UDT, it is unclear whether clinicians understand the best way to use the test results.

Trends in Methadone Dispensing for Opioid Use Disorder After Medicare Payment Policy Changes.

Importance: A significant proportion of Medicare beneficiaries have a diagnosed opioid use disorder (OUD). Methadone and buprenorphine are both effective medications for the treatment of OUD (MOUDs); however, Medicare did not cover methadone until 2020. Objective: To examine trends in methadone and buprenorphine dispensing among Medicare Advantage (MA) enrollees after 2 policy changes in 2020 related to methadone access. Design, Setting, and Participants: This cross-sectional analysis of temporal trends in methadone and buprenorphine treatment dispensing assessed MA beneficiary claims from January 1, 2019, through March 31, 2022, captured by Optum's Clinformatics Data Mart. Of 9 870 791 MA enrollees included in the database, 39 252 had at least 1 claim for methadone, buprenorphine, or both during the study period. All available MA enrollees were included. Subanalyses by age and dual eligibility for Medicare and Medicaid status were conducted. Exposures: Study exposures were (1) the Centers for Medicare & Medicaid Services (CMS) Medicare bundled payment reimbursement policy for OUD treatment and (2) the Substance Abuse and Mental Health Administration and CMS Medicare policies designed to facilitate access to treatment for OUD, specifically during the COVID-19 pandemic. Main Outcomes and Measures: Study outcomes were trends in methadone and buprenorphine dispensing by beneficiary characteristics. National methadone and buprenorphine dispensing rates were calculated as claims-based dispensing rates per 1000 MA enrollees. Results: Among the 39 252 MA enrollees with at least 1 MOUD dispensing claim (mean age, 58.6 [95% CI, 58.57-58.62] years; 45.9% female), 195 196 methadone claims and 540 564 buprenorphine pharmacy claims were identified, for a total of 735 760 dispensing claims. The methadone dispensing rate for MA enrollees was 0 in 2019 because the policy did not allow any payment until 2020. Claims rates per 1000 MA enrollees were low initially, increasing from 0.98 in the first quarter of 2020 to 4.71 in the first quarter of 2022. Increases were primarily associated with dually eligible beneficiaries and beneficiaries younger than 65 years. National buprenorphine dispensing rates were 4.64 per 1000 enrollees in quarter 1 of 2019, increasing to 7.45 per 1000 enrollees in quarter 1 of 2022. Conclusions and Relevance: This cross-sectional study found that methadone dispensing increased among Medicare beneficiaries after the policy changes. Rates of buprenorphine dispensing did not provide evidence that beneficiaries substituted buprenorphine for methadone. The 2 new CMS policies represent an important first step in increasing access to MOUD treatment for Medicare beneficiaries.

The APE2 nuclease is essential for DNA double-strand break repair by microhomology-mediated end joining.

Microhomology-mediated end joining (MMEJ) is an intrinsically mutagenic pathway of DNA double-strand break (DSB) repair essential for proliferation of homologous recombination (HR)-deficient tumors. Although targeting MMEJ has emerged as a powerful strategy to eliminate HR-deficient (HRD) cancers, this is limited by an incomplete understanding of the mechanism and factors required for MMEJ repair. Here, we identify the APE2 nuclease as an MMEJ effector. We show that loss of APE2 inhibits MMEJ at deprotected telomeres and at intra-chromosomal DSBs and is epistatic with Pol Theta for MMEJ activity. Mechanistically, we demonstrate that APE2 possesses intrinsic flap-cleaving activity, that its MMEJ function in cells depends on its nuclease activity, and further identify an uncharacterized domain required for its recruitment to DSBs. We conclude that this previously unappreciated role of APE2 in MMEJ contributes to the addiction of HRD cells to APE2, which could be exploited in the treatment of cancer.

CRISPR/dCas9-KRAB-Mediated Suppression of S100b Restores p53-Mediated Apoptosis in Melanoma Cells.

Overexpression of S100B is routinely used for disease-staging and for determining prognostic outcomes in patients with malignant melanoma. Intracellular interactions between S100B and wild-type (WT)-p53 have been demonstrated to limit the availability of free WT-p53 in tumor cells, inhibiting the apoptotic signaling cascade. Herein, we demonstrate that, while oncogenic overexpression of S100B is poorly correlated (R < 0.3; p > 0.05) to alterations in S100B copy number or DNA methylation in primary patient samples, the transcriptional start site and upstream promoter of the gene are epigenetically primed in melanoma cells with predicted enrichment of activating transcription factors. Considering the regulatory role of activating transcription factors in S100B upregulation in melanoma, we stably suppressed S100b (murine ortholog) by using a catalytically inactive Cas9 (dCas9) fused to a transcriptional repressor, Krüppel-associated box (KRAB). Selective combination of S100b-specific single-guide RNAs and the dCas9-KRAB fusion significantly suppressed expression of S100b in murine B16 melanoma cells without noticeable off-target effects. S100b suppression resulted in recovery of intracellular WT-p53 and p21 levels and concomitant induction of apoptotic signaling. Expression levels of apoptogenic factors (i.e., apoptosis-inducing factor, caspase-3, and poly-ADP ribose polymerase) were altered in response to S100b suppression. S100b-suppressed cells also showed reduced cell viability and increased susceptibility to the chemotherapeutic agents, cisplatin and tunicamycin. Targeted suppression of S100b therefore offers a therapeutic vulnerability to overcome drug resistance in melanoma.

Making the Case for Virtual Surgical Planning: Bilateral Sequential Fibula Flaps with Immediate Dental Implants for Maxillectomy.

SUMMARY: Oncologic maxillectomy defects requiring bony reconstruction are among the most challenging head and neck cases because of the complex three-dimensional geometry of the midface. Virtual surgical planning technology is advantageous in these cases because it provides superior positional precision and accuracy compared with traditional techniques and facilitates prosthodontic rehabilitation. Maxillary cancer recurrence after an initial fibula flap reconstruction presents a unique challenge. The authors report the first two cases of sequential fibula flaps after second or recurrent cancer of the maxilla. Virtual surgical planning facilitated resection with adequate tumor margins, optimized anatomic positioning of the fibula construct with three-dimensional printed plates, and enabled immediate functional dental implant placement.

Paravertebral Blocks in Tissue Expander Breast Reconstruction: Propensity-Matched Analysis of Opioid Consumption and Patient Outcomes.

BACKGROUND: The paravertebral block (PVB) is an adjunctive perioperative pain control method for patients undergoing breast reconstruction that may improve perioperative pain control and reduce narcotic use. This study determined the efficacy of preoperative PVBs for perioperative pain management in patients undergoing tissue expander breast reconstruction. METHODS: A retrospective review was performed of patients who underwent tissue expander breast reconstruction from December of 2017 to September of 2019. Two patients with PVBs were matched using propensity scoring to one no-block patient. Perioperative analgesic use, pain severity scores on days 2 to 10 after discharge, and BREAST-Q Physical Well-Being scores before surgery and at 2 weeks, 6 weeks, and 3 months after surgery were compared between the two groups. RESULTS: The propensity-matched cohort consisted of 471 patients (314 PVB and 157 no block). The PVB group used significantly fewer morphine milligram equivalents than the no-block group (53.7 versus 69.8; P < 0.001). Average daily postoperative pain severity scores were comparable, with a maximum difference of 0.3 points on a 0-point to 4-point scale. BREAST-Q Physical Well-Being scores were significantly higher for the PVB group than the no-block group at 6 weeks after surgery (60.6 versus 51.0; P = 0.015) but did not differ significantly at 2 weeks or 3 months after surgery. CONCLUSIONS: PVBs may help reduce perioperative opioid requirements but did not reduce pain scores after discharge when used as part of an expander-based reconstruction perioperative pain management protocol. Continued research should examine additional or alternative regional block procedures as well as financial cost and potential long-term impact of PVBs. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Sex and molecular differences in cardiovascular parameters at peak influenza disease in mice.

There is a growing interest in the detection of subtle changes in cardiovascular physiology in response to viral infection to develop better disease surveillance strategies. This is not only important for earlier diagnosis and better prognosis of symptomatic carriers but also useful to diagnose asymptomatic carriers of the virus. Previous studies provide strong evidence of an association between inflammatory biomarker levels and both blood pressure (BP) and heart rate (HR) during infection. The identification of novel biomarkers during an inflammatory event could significantly improve predictions for cardiovascular events. Thus, we evaluated changes in cardiovascular physiology induced in A/Puerto Rico/8/34 (PR8) influenza infections in female and male C57BL/6J mice and compared them with the traditional method of influenza disease detection using body weight (BW). Using radiotelemetry, changes in BP, HR, and activity were studied. Change in BW of infected females was significantly decreased from 5 to 13 days postinfection (dpi), yet alterations in normal physiology including loss of diurnal rhythm and reduced activity was observed starting at about 3 dpi for HR and 4 dpi for activity and BP; continuing until about 13 dpi. In contrast, males had significantly decreased BW 8 to 12 dpi and demonstrated altered physiological measurements for a shorter period compared with females with a reduction starting at 5 dpi for activity, 6 dpi for BP, and 7 dpi for HR until about 12 dpi, 10 dpi, and 9 dpi, respectively. Finally, females and males exhibited different patterns of inflammatory maker expression in lungs at peak disease by analyzing bulk RNA-sequencing data for lungs and Bio-plex cytokine assay for blood collected from influenza-infected and naïve C57BL/6J female and male mice at 7 dpi. In total, this study provides insight into cardiovascular changes and molecular markers to distinguish sex differences in peak disease caused by influenza virus infection.NEW & NOTEWORTHY This study performed longitudinal cardiovascular measurements of influenza viral infection and identified sex difference in both physiological and molecular markers at peak disease.

Prazosin for nightmares in serious illness.

Nightmares can be a distressing symptom in patients living with serious illness. Prazosin, a selective alpha-1 adrenergic antagonist, has been suggested to treat nightmares, with most data supporting its use in post-traumatic stress disorder (PTSD). We present the case of a 60-year-old woman with metastatic breast cancer who experienced healthcare-associated nightmares following hospitalisation. She did not meet diagnostic criteria for PTSD. Atypical antipsychotics and benzodiazepines were ineffective in controlling her nightmares, resulting in referral to our outpatient palliative medicine clinic. Prazosin was initiated alongside interdisciplinary psychosocial support, resulting in rapid resolution of her nightmares. To our knowledge, this is the first case to report on use of prazosin to manage nightmares in the outpatient palliative medicine setting.

Antihypertensive effects of immunosuppressive therapy in autoimmune disease.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder that primarily affects women of childbearing age. While immune system dysfunction has been implicated in the development of hypertension (HTN) in SLE, the effect of immunomodulatory drugs on blood pressure (BP) control in SLE patients is unknown. In the present study, we hypothesized that first-line immunomodulatory therapies prescribed to SLE patients would have a beneficial impact on BP. We retrospectively analyzed the Research Data Warehouse containing de-identified patient data (n = 1,075,406) from the University of Mississippi Medical Center for all patients with a clinical diagnosis of SLE. BP responses were analyzed in SLE patients that were initially prescribed a single therapy (methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil (MMF), or prednisone). Of the 811 SLE patients who met criteria, most were hypertensive (56%), female (94%), and black (65%). Individuals prescribed MMF or hydroxychloroquine had significantly decreased BP and improved BP control at follow-up (>7 days and <3 months after initial visit). Our results suggest that MMF and hydroxychloroquine have beneficial effects on BP, independent of adjunctive antihypertensive therapies and existing renal disease.

Systematic Identification and Categorization of Opioid Prescribing and Dispensing Policies in 16 States and Washington, DC.

OBJECTIVES: State policies can impact opioid prescribing or dispensing. Some state opioid policies have been widely examined in empirical studies, including prescription drug monitoring programs and pain clinic licensure requirements. Other relevant policies might exist that have received limited attention. Our objective was to identify and categorize a wide range of state policies that could affect opioid prescribing/dispensing. METHODS: We used stratified random sampling to select 16 states and Washington, DC, for our sample. We collected state regulations and statutes effective during 2020 from each jurisdiction, using search terms related to opioids, pain management, and prescribing/dispensing. We then conducted qualitative template analysis of the data to identify and categorize policy categories. RESULTS: We identified three dimensions of opioid prescribing/dispensing laws: the prescribing/dispensing rule, its applicability, and its disciplinary consequences. Policy categories of prescribing/dispensing rules included clinic licensure, staff credentials, evaluating the appropriateness of opioids, limiting the initiation of opioids, preventing the diversion or misuse of opioids, and enhancing patient safety. Policy categories related to applicability of the law included the pain type, substance type, practitioner, setting, payer, and prescribing situation. The disciplinary consequences dimension included specific consequences and inspection processes. DISCUSSION: Policy categories within each dimension of opioid prescribing/dispensing laws could become a foundation for creating variables to support empirical analyses of policy effects, improving operationalization of policies in empirical studies, and helping to disentangle the effects of multiple state laws enacted at similar times to address the opioid crisis. Several of the policy categories we identified have been underexplored in previous empirical studies.