Sensory Neuron Diversity in the Inner Ear Is Shaped by Activity.

In the auditory system, type I spiral ganglion neurons (SGNs) convey complex acoustic information from inner hair cells (IHCs) to the brainstem. Although SGNs exhibit variation in physiological and anatomical properties, it is unclear which features are endogenous and which reflect input from synaptic partners. Using single-cell RNA sequencing, we derived a molecular classification of mouse type I SGNs comprising three subtypes that express unique combinations of Ca2+ binding proteins, ion channel regulators, guidance molecules, and transcription factors. Based on connectivity and susceptibility to age-related loss, these subtypes correspond to those defined physiologically. Additional intrinsic differences among subtypes and across the tonotopic axis highlight an unexpectedly active role for SGNs in auditory processing. SGN identities emerge postnatally and are disrupted in a mouse model of deafness that lacks IHC-driven activity. These results elucidate the range, nature, and origins of SGN diversity, with implications for treatment of congenital deafness.

Less extreme and earlier outbursts of ice-dammed lakes since 1900.

Episodic failures of ice-dammed lakes have produced some of the largest floods in history, with disastrous consequences for communities in high mountains1-7. Yet, estimating changes in the activity of ice-dam failures through time remains controversial because of inconsistent regional flood databases. Here, by collating 1,569 ice-dam failures in six major mountain regions, we systematically assess trends in peak discharge, volume, annual timing and source elevation between 1900 and 2021. We show that extreme peak flows and volumes (10 per cent highest) have declined by about an order of magnitude over this period in five of the six regions, whereas median flood discharges have fallen less or have remained unchanged. Ice-dam floods worldwide today originate at higher elevations and happen about six weeks earlier in the year than in 1900. Individual ice-dammed lakes with repeated outbursts show similar negative trends in magnitude and earlier occurrence, although with only moderate correlation to glacier thinning8. We anticipate that ice dams will continue to fail in the near future, even as glaciers thin and recede. Yet widespread deglaciation, projected for nearly all regions by the end of the twenty-first century9, may bring most outburst activity to a halt.

A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.

Anti-T-lymphocyte globulin exposure is associated with acute graft-versus-host disease and relapse in pediatric acute lymphoblastic leukemia patients undergoing hematopoietic stem cell transplantation: a multinational prospective study.

Anti-T-lymphocyte globulin (ATLG) is used in hematopoietic stem cell transplantation (HSCT) to prevent graft-versus-host disease (GVHD) and graft failure. To date, insight in ATLG pharmacokinetics and -dynamics (PK/PD) is limited, and population PK (POPPK) models are lacking. In this prospective study, we describe ATLG POPPK using NONMEM® and the impact of ATLG exposure on clinical outcome and immune reconstitution in a homogeneous cohort of pediatric acute lymphoblastic leukemia (ALL) patients transplanted with a matched unrelated donor and receiving uniform ATLG dosing. Based on 121 patients and 812 samples for POPPK analysis, a two-compartmental model with parallel linear and non-linear clearance and bodyweight as covariate, best described the ATLG concentration-time data. The level of ATLG exposure (day active ATLG <1 AU/mL, median 16 days post-HSCT) was strongly associated with aGVHD grade II-IV, with a lower incidence in patients with prolonged active ATLG exposure (≤day 16 50% vs. >day 16 8.2%; P<0.001). When stratified for remission state, patients transplanted in complete remission (CR) 2 or 3 with prolonged ATLG exposure had a higher relapse risk, while this effect was not seen in CR1 patients (P=0.010). High level ATLG exposure was associated with delayed CD4 T-cell recovery at 4 and 8 weeks post-HSCT, but not at 12 weeks, and overall and relapse-free survival were not influenced by CD4 recovery at 12 weeks post-HSCT. This study underlines the importance of individualized ATLG exposure with the use of model-informed precision dosing in order to optimize the HSCT outcome in pediatric ALL.

Impact of Evidence-Based Quality Improvement on Tailoring VA's Patient-Centered Medical Home Model to Women Veterans' Needs.

BACKGROUND: Women Veterans' numerical minority, high rates of military sexual trauma, and gender-specific healthcare needs have complicated implementation of comprehensive primary care (PC) under VA's patient-centered medical home model, Patient Aligned Care Teams (PACT). OBJECTIVE: We deployed an evidence-based quality improvement (EBQI) approach to tailor PACT to meet women Veterans' needs and studied its effects on women's health (WH) care readiness, team-based care, and burnout. DESIGN: We evaluated EBQI effectiveness in a cluster randomized trial with unbalanced random allocation of 12 VAMCs (8 EBQI vs. 4 control). Clinicians/staff completed web-based surveys at baseline (2014) and 24 months (2016). We adjusted for individual-level covariates (e.g., years at VA) and weighted for non-response in difference-in-difference analyses for readiness and team-based care overall and by teamlet type (mixed-gender PC-PACTs vs. women-only WH-PACTs), as well as post-only burnout comparisons. PARTICIPANTS: We surveyed all clinicians/staff in general PC and WH clinics. INTERVENTION: EBQI involved structured engagement of multilevel, multidisciplinary stakeholders at network, VAMC, and clinic levels toward network-specific QI roadmaps. The research team provided QI training, formative feedback, and external practice facilitation, and support for cross-site collaboration calls to VAMC-level QI teams, which developed roadmap-linked projects adapted to local contexts. MAIN MEASURES: WH care readiness (confidence providing WH care, self-efficacy implementing PACT for women, barriers to providing care for women, gender sensitivity); team-based care (change-readiness, communication, decision-making, PACT-related QI, functioning); burnout. KEY RESULTS: Overall, EBQI had mixed effects which varied substantively by type of PACT. In PC-PACTs, EBQI increased self-efficacy implementing PACT for women and gender sensitivity, even as it lowered confidence. In contrast, in WH-PACTs, EBQI improved change-readiness, team-based communication, and functioning, and was associated with lower burnout. CONCLUSIONS: EBQI effectiveness varied, with WH-PACTs experiencing broader benefits and PC-PACTs improving basic WH care readiness. Lower confidence delivering WH care by PC-PACT members warrants further study. TRIAL REGISTRATION: The data in this paper represent results from a cluster randomized controlled trial registered in ClinicalTrials.gov (NCT02039856).

Gender-affirming care in urology: emergency care of the gender-affirming surgical patient-what the primary urologist needs to know.

OBJECTIVE: To present a narrative review of fundamental information needed to manage postoperative complications in patients who have undergone genital gender-affirming surgery (GAS). METHODS: A narrative review was performed using the following keywords: 'gender-affirming surgery', 'complications', 'emergency', 'postoperative'. Articles were included after being reviewed by two primary authors for relevance. Four clinicians with significant experience providing both primary and ongoing urological care to patients after GAS were involved in article selection and analysis. RESULTS: The most common feminising genital GAS performed is a vaginoplasty. The main post-surgical complications seen by urologists include wound healing complications, voiding dysfunction, postoperative bleeding, vaginal stenosis, acute vaginal prolapse and graft loss, rectovaginal fistula, and urethrovaginal fistula. The most common masculinising genital GAS options include metoidioplasty and phalloplasty. Complications for these surgeries include urethral strictures, urethral fistulae, and urethral diverticula. Penile implants may also accompany phalloplasties and their complications include infection, erosion, migration, and mechanical failure. CONCLUSION: Genital GAS is increasing, yet there are still many barriers that individuals face not only in accessing the surgeries, but in receiving follow-up care critical for optimal outcomes. Improved education and training programmes would be helpful to identify and manage postoperative complications. Broader cultural level changes are also important to ensure a safe, gender-inclusive environment for all patients.

Assurance methods for designing a clinical trial with a delayed treatment effect.

An assurance calculation is a Bayesian alternative to a power calculation. One may be performed to aid the planning of a clinical trial, specifically setting the sample size or to support decisions about whether or not to perform a study. Immuno-oncology is a rapidly evolving area in the development of anticancer drugs. A common phenomenon that arises in trials of such drugs is one of delayed treatment effects, that is, there is a delay in the separation of the survival curves. To calculate assurance for a trial in which a delayed treatment effect is likely to be present, uncertainty about key parameters needs to be considered. If uncertainty is not considered, the number of patients recruited may not be enough to ensure we have adequate statistical power to detect a clinically relevant treatment effect and the risk of an unsuccessful trial is increased. We present a new elicitation technique for when a delayed treatment effect is likely and show how to compute assurance using these elicited prior distributions. We provide an example to illustrate how this can be used in practice and develop open-source software to implement our methods. Our methodology has the potential to improve the success rate and efficiency of Phase III trials in immuno-oncology and for other treatments where a delayed treatment effect is expected to occur.

Prevention of Post-Mastectomy Pain Syndrome: A Review of Recent Literature on Perioperative Interventions.

PURPOSE OF REVIEW: Up to 60% of breast cancer patients continue to experience pain three months or more after surgery, with 15 to 25% reporting moderate to severe pain. Post-mastectomy pain syndrome (PMPS) places a high burden on patients. We reviewed recent studies on perioperative interventions to prevent PMPS incidence and severity. RECENT FINDINGS: Recent studies on pharmacologic and regional anesthetic interventions were reviewed. Only nine of the twenty-three studies included reported a significant improvement in PMPS incidence and/or severity, sometimes with mixed results for similar interventions. Evidence for prevention of PMPS is mixed. Further investigation of impact of variations in dosing is warranted. In addition, promising newer interventions for prevention of PMPS such as cryoneurolysis of intercostal nerves and stellate ganglion block need confirmatory studies.

An Overview of Cannabidiol.

Cannabidiol (CBD) is one of the most interesting constituents of cannabis, garnering significant attention in the medical community in recent years due to its proven benefit for reducing refractory seizures in pediatric patients. Recent legislative changes in the United States have made CBD readily available to the general public, with up to 14% of adults in the United States having tried it in 2019. CBD is used to manage a myriad of symptoms, including anxiety, pain, and sleep disturbances, although rigorous evidence for these indications is lacking. A significant advantage of CBD over the other more well-known cannabinoid delta-9-tetrahydroncannabinol (THC) is that CBD does not produce a "high." As patients increasingly self-report its use to manage their medical conditions, and as the opioid epidemic continues to drive the quest for alternative pain management approaches, the aims of this narrative review are to provide a broad overview of the discovery, pharmacology, and molecular targets of CBD, its purported and approved neurologic indications, evidence for its analgesic potential, regulatory implications for patients and providers, and future research needs.

Functional Independence of Children With Arthrogryposis.

BACKGROUND: Arthrogryposis (AMC) is a descriptive term to characterize a child born with multiple joint contractures. Treatment aims to improve functional independence, yet the literature objectively describing functional independence in this population is scarce. This study aimed to describe the functional independence of children with AMC through the lens of the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) and observational activities of daily living (ADL) tasks. METHODS: Patients with AMC between the ages of 3 and 12 years participated in this prospective study. Parents completed the PEDI-CAT while a trained occupational therapist observed children as they completed a checklist of functional ADL tasks. Patients were grouped according to developmental age groups: "preschoolers" (3 to 5 y), "early school-age" (6 to 9 y), and "late school-age" (10 to 12 y). Patient's PEDI-CAT normative scores were described, comparing the study population to typically developing children, and differences in each domain were examined between developmental age groups. The observed ADL tasks completed were also described, and differences in scores were examined between developmental age groups. RESULTS: Forty-four patients (mean age of 7±2.86 y) were enrolled. The distribution between age groups was nearly even. Mean daily activities T -score for patients with AMC was 25.80±11.98 and the mean mobility T -score was 17.39±9.77. Late school-age children scored significantly lower than preschool-age children in both of these domains ( P <0.01). Observed ADL tasks demonstrated a high level of required assistance for patients (range: 27.3% to 61.4%), although older school-age children did show greater independence with tested activities than preschool-age children ( P =0.05). CONCLUSION: Children with AMC are significantly limited in functional independence, particularly regarding age-appropriate daily activities and mobility. Outcomes from this study provide a reference to help gauge the results of nonoperative and surgical treatment toward improving functional independence in this population. LEVEL OF EVIDENCE: Level III: prognostic study.

Understanding How Contingency Staffing Programs Can Support Mental Health Services in the Veterans Health Administration.

Introduction: Beginning in 2019, the Department of Veterans Affairs (VA) prioritized improving access to care nationally to deliver virtual care and implemented 18 regionally based Clinical Resource Hubs (CRHs) to meet this priority. This observational study describes the quantity and types of care delivered by CRH Mental Health teams, and the professions of those hired to deliver it. Methods: A retrospective cohort study, based on national VA CRH mental health care utilization data and CRH staffing data for CRH's first 3 years, was conducted. Results: CRH Mental Health teams primarily used Telemental Health (TMH) to provide care (98.1% of all CRH MH encounters). The most common disorders treated included depression, post-traumatic stress disorder, and anxiety disorders. The amount of care delivered overtime steadily increased as did the racial and ethnic diversity of Veterans served. Psychologists accounted for the largest share of CRH staffing, followed by psychiatrists. Conclusions: CRH TMH delivered from a regional hub appears to be a feasible and acceptable visit modality, based on the continuously increasing CRH TMH visit rates. Our results showed that CRH TMH was predominantly used to address common mental health diagnoses, rather than serious mental illnesses. Traditionally marginalized patient populations increased over the 3-year window, suggesting that CRH TMH resources were accessible to many of these patients. Future research should assess barriers and facilitators for accessing CRH TMH, especially for difficult-to-service patient populations, and should consider whether similar results to ours occur when regional TMH is delivered to non-VA patient populations.

Associations Between Primary Care Providers and Staff-Reported Access Management Challenges and Patient Perceptions of Access.

BACKGROUND/OBJECTIVE: Optimizing patients' access to primary care is critically important but challenging. In a national survey, we asked primary care providers and staff to rate specific care processes as access management challenges and assessed whether clinics with more of these challenges had worse access outcomes. METHODS: Study design: Cross sectional. National Primary Care Personnel Survey (NPCPS) (2018) participants included 6210 primary care providers (PCPs) and staff in 813 clinics (19% response rate) and 158,645 of their patients. We linked PCP and staff ratings of access management challenges to veterans' perceived access from 2018-2019 Survey of Healthcare Experiences of Patients-Patient Centered Medical Home (SHEP-PCMH) surveys (35.6% response rate). MAIN MEASURES: The NPCPS queried PCPs and staff about access management challenges. The mean overall access challenge score was 28.6, SD 6.0. The SHEP-PCMH access composite asked how often veterans reported always obtaining urgent appointments same/next day; routine appointments when desired and having medical questions answered during office hours. ANALYTIC APPROACH: We aggregated PCP and staff responses to clinic level, and use multi-level, multivariate logistic regressions to assess associations between clinic-level access management challenges and patient perceptions of access. We controlled for veteran-, facility-, and area-level characteristics. KEY RESULTS: Veterans at clinics with more access management challenges (> 75th percentile) had a lower likelihood of reporting always receiving timely urgent care appointments (AOR: .86, 95% CI: .78-.95); always receiving routine appointments (AOR: .74, 95% CI: .67-.82); and always reporting same- or next-day answers to telephone questions (AOR: .79, 95% CI: .70-.90) compared to veterans receiving care at clinics with fewer (< 25th percentile) challenges. DISCUSSION/CONCLUSION: Findings show a strong relationship between higher levels of access management challenges and worse patient perceptions of access. Addressing access management challenges, particularly those associated with call center communication, may be an actionable path for improved patient experience.

A scoping review of office-based prostatic stents: past, present, and future of true minimally invasive treatment of benign prostatic hyperplasia.

PURPOSE: To conduct a scoping review of the existing literature and recent developments on prostatic stents for the treatment of benign prostatic hyperplasia (BPH). METHODS: A comprehensive search was performed on Embase, MEDLINE, and Web of Science to identify English literature on prostatic stents for the treatment of BPH. Additional studies and upcoming devices were identified through grey literature search and expert consultation. Study characteristics and stent information were extracted and tabulated narratively. RESULTS: Of the 1171 search results, 64 studies were included in this review. iTiND was the prostatic stent with the most long-term evidence. iTiND is a safe and effective minimally invasive treatment for BPH that preserves sexual function. Adverse events are mild and transitory. Emerging stents (e.g. Zenflow, Butterfly, Urocross, and Exime) had 7/64 eligible studies, where no studies had long-term follow-up. These newer stents show promising results for quality of life and BPH symptom management; however, long-term monitoring and head-to-head comparisons are needed. CONCLUSION: Over the last 50 years, prostatic stents have evolved and demonstrated improved clinical efficacy. iTiND provides a safe and effective outpatient treatment of LUTS secondary to BPH preserving erectile and ejaculatory function. Emerging prostatic stents are a promising, effective, and safe intervention in well-selected patients interested in its benefits.

Safety and efficacy of GreenLight PVP in octogenarians: evaluation of the Global GreenLight Group database.

INTRODUCTION: The present study analyzes the largest international GreenLight database, the Global GreenLight Group (GGG), to evaluate the functional and safety profile of GreenLight photoselective vaporization of the prostate (PVP) in octogenarians. METHODS: The GGG is a database comprised of patients that underwent GreenLight PVP from 2011 to 2019 performed by 8 experienced urologists at 7 international hospitals. Patients 80 years or older at the time of surgery were categorized as octogenarians. They were compared to a similar group of PVP patients below the age of 80. RESULTS: Among 3,648 patients, 586 men were above the age of 80. Compared to patients under the age of 80, octogenarians had larger prostates (76.0 vs 71.9 ml, p = 0.02) and a lower BMI (25.6 vs 26.7, p = 0.045). Operative time was not significantly longer in octogenarians. The improvement in functional outcomes between 80-year-old patients and control patients was not significantly different at one-year follow-up, with the exception of maximum urinary flow (Qmax) that favoured younger patients (10.3 vs 12.6 ml/s, p = 0.02). The odds of transfusion were greater for older patients [OR 8.2 (95% CI 3.6-18.9, p < 0.01)], but they were not at increased risk of hematuria. Octogenarians had higher readmission rates (23.0 vs 11.9%, p < 0.01). CONCLUSIONS: GreenLight PVP is a safe option in well-selected octogenarians in a cohort of patients treated by surgeons experienced with the technology. The odds of transfusion were higher in patients over 80, but the absolute risk remains low. The 30-day hospital readmission rate was higher in octogenarians.

IL-7 and IL-15 Levels Reflect the Degree of T Cell Depletion during Lymphopenia and Are Associated with an Expansion of Effector Memory T Cells after Pediatric Hematopoietic Stem Cell Transplantation.

Differentially and functionally distinct T cell subsets are involved in the development of complications after allogeneic hematopoietic stem cell transplantation (HSCT), but little is known about factors regulating their recovery after HSCT. In this study, we investigated associations between immune-regulating cytokines, T cell differentiation, and clinical outcomes. We included 80 children undergoing allogeneic HSCT for acute leukemia using bone marrow or peripheral blood stem cells grafted from a matched sibling or unrelated donor. Cytokines (IL-7, IL-15, IL-18, SCF, IL-6, IL-2, and TNF-α) and active anti-thymocyte globulin (ATG) levels were longitudinally measured along with extended T cell phenotyping. The cytokine profiles showed a temporary rise in IL-7 and IL-15 during lymphopenia, which was strongly dependent on exposure to active ATG. High levels of IL-7 and IL-15 from graft infusion to day +30 were predictive of slower T cell recovery during the first 2 mo post-HSCT; however, because of a major expansion of memory T cell stages, only naive T cells remained decreased after 3 mo (p < 0.05). No differential effect was seen on polarization of CD4+ T cells into Th1, Th2, or Th17 cells or regulatory T cells. Low levels of IL-7 and IL-15 at day +14 were associated with acute graft-versus-host disease grades II-IV in ATG-treated patients (p = 0.0004 and p = 0.0002, respectively). Children with IL-7 levels comparable to healthy controls at day +14 post-HSCT were less likely to develop EBV reactivation posttransplant. These findings suggest that quantification of IL-7 and IL-15 may be useful as biomarkers in assessing the overall T cell depletion and suggest a potential for predicting complications after HSCT.

Evaluating chronic pain as a risk factor for COVID-19 complications among New York State Medicaid beneficiaries: a retrospective claims analysis.

OBJECTIVE: To assess whether chronic pain increases the risk of COVID-19 complications and whether opioid use disorder (OUD) differentiates this risk among New York State Medicaid beneficiaries. DESIGN, SETTING, AND SUBJECTS: This was a retrospective cohort study of New York State Medicaid claims data. We evaluated Medicaid claims from March 2019 through December 2020 to determine whether chronic pain increased the risk of COVID-19 emergency department (ED) visits, hospitalizations, and complications and whether this relationship differed by OUD status. We included beneficiaries 18-64 years of age with 10 months of prior enrollment. Patients with chronic pain were propensity score-matched to those without chronic pain on demographics, utilization, and comorbidities to control for confounders and were stratified by OUD. Complementary log-log regressions estimated hazard ratios (HRs) of COVID-19 ED visits and hospitalizations; logistic regressions estimated odds ratios (ORs) of hospital complications and readmissions within 0-30, 31-60, and 61-90 days. RESULTS: Among 773 880 adults, chronic pain was associated with greater hazards of COVID-related ED visits (HR = 1.22 [95% CI: 1.16-1.29]) and hospitalizations (HR = 1.19 [95% CI: 1.12-1.27]). Patients with chronic pain and OUD had even greater hazards of hospitalization (HR = 1.25 [95% CI: 1.07-1.47]) and increased odds of hepatic- and cardiac-related events (OR = 1.74 [95% CI: 1.10-2.74]). CONCLUSIONS: Chronic pain increased the risk of COVID-19 ED visits and hospitalizations. Presence of OUD further increased the risk of COVID-19 hospitalizations and the odds of hepatic- and cardiac-related events. Results highlight intersecting risks among a vulnerable population and can inform tailored COVID-19 management.

Diagnostic test accuracy for cessation of circulation during death determination: a systematic review.

PURPOSE: To synthesize the available evidence comparing noninvasive methods of measuring the cessation of circulation in patients who are potential organ donors undergoing death determination by circulatory criteria (DCC) with the current accepted standard of invasive arterial blood pressure (IAP) monitoring. SOURCE: We searched (from inception until 27 April 2021) MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. We screened citations and manuscripts independently and in duplicate for eligible studies that compared noninvasive methodologies assessing circulation in patients who were monitored around a period of cessation of circulation. We performed risk of bias assessment, data abstraction, and quality assessment using Grading of Recommendations, Assessment, Development, and Evaluation in duplicate and independently. We presented findings narratively. PRINCIPAL FINDINGS: We included 21 eligible studies (N = 1,177 patients). Meta-analysis was not possible because of study heterogeneity. We identified low quality evidence from four indirect studies (n = 89) showing pulse palpation is less sensitive and specific than IAP (reported sensitivity range, 0.76-0.90; specificity, 0.41-0.79). Isoelectric electrocardiogram (ECG) had excellent specificity for death (two studies; 0% [0/510]), but likely increases the average time to death determination (moderate quality evidence). We are uncertain whether point-of-care ultrasound (POCUS) pulse check, cerebral near-infrared spectroscopy (NIRS), or POCUS cardiac motion assessment are accurate tests for the determination of circulatory cessation (very low-quality evidence). CONCLUSION: There is insufficient evidence that ECG, POCUS pulse check, cerebral NIRS, or POCUS cardiac motion assessment are superior or equivalent to IAP for DCC in the setting of organ donation. Isoelectric ECG is specific but can increase the time needed to determine death. Point-of-care ultrasound techniques are emerging therapies with promising initial data but are limited by indirectness and imprecision. STUDY REGISTRATION: PROSPERO (CRD42021258936); first submitted 16 June 2021.

RéSUMé: OBJECTIF: Synthétiser les données probantes disponibles comparant les méthodes non invasives de mesure de l'arrêt de la circulation chez les patients qui sont des donneurs d'organes potentiels soumis à une détermination du décès selon des critères circulatoires (DCC) avec la norme actuellement acceptée de surveillance invasive de la tension artérielle (TA). SOURCES: Nous avons mené des recherches dans les bases de données MEDLINE, EMBASE, Web of Science et le registre Cochrane des essais contrôlés de leur création jusqu'au 27 avril 2021. Nous avons examiné les citations et les manuscrits de manière indépendante et en double pour en tirer les études éligibles qui comparaient des méthodologies non invasives d'évaluation de la circulation chez les patients qui étaient sous surveillance avant, pendant et après une période d'arrêt de la circulation. Nous avons réalisé l'évaluation du risque de biais, l'extraction des données et l'évaluation de la qualité en nous fondant sur la méthodologie GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) en double et de manière indépendante. Nous présentons les résultats de façon narrative. CONSTATATIONS PRINCIPALES: Nous avons inclus 21 études éligibles (N = 1177 patients). Une méta-analyse n'a pas été possible en raison de l'hétérogénéité des études. Nous avons identifié des données de faible qualité issues de quatre études indirectes (n = 89) montrant que la palpation du pouls est moins sensible et spécifique que la mesure invasive de la TA (plage de sensibilité rapportée, 0,76-0,90; spécificité, 0,41-0,79). L'électrocardiogramme (ECG) isoélectrique avait une excellente spécificité pour le décès (deux études; 0 % [0/510]), mais augmente probablement le délai moyen avant la détermination du décès (données probantes de qualité modérée). Nous ne savons pas si la vérification du pouls par échographie ciblée (POCUS), la spectroscopie proche infrarouge (SPIR) cérébrale ou l'évaluation ciblée (POCUS) des mouvements cardiaques sont des examens précis pour la détermination de l'arrêt circulatoire (données probantes de très faible qualité). CONCLUSION: Il n'y a pas suffisamment de données probantes pour affirmer que l'ECG, la vérification ciblée du pouls, la SPIR cérébrale ou l'évaluation ciblée des mouvements cardiaques sont supérieurs ou équivalents à la mesure invasive de la TA pour un DCC dans le cadre du don d'organes. L'ECG isoélectrique est spécifique, mais peut augmenter le délai nécessaire avant de déterminer le décès. Les techniques d'échographie ciblée sont des thérapies émergentes avec des données initiales prometteuses, mais elles sont limitées par leur caractère indirect et l'imprécision de l'examen. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021258936); soumis pour la première fois le 16 juin 2021.

Litigation associated with 5-alpha-reductase-inhibitor use: A Canadian legal database review.

INTRODUCTION: 5α-reductase inhibitors (5ARI) are commonly prescribed medications. There is ongoing controversy about the adverse events of these medications. The aim of this study is to characterize lawsuits in Canada involving medical complications of 5ARIs use. MATERIALS AND METHODS: Legal cases were queried from CanLII. Cases were included if they involved a party taking a 5ARI who alleged an adverse event. Relevant full cases were retained, and pertinent characteristics were extracted with the help of a legal expert. RESULTS: Our deduplicated search yielded 67 unique legal documents from December 2013 to February 2019. Twelve of these documents met the inclusion criteria (representing 3 cases, considering each case had several hearings). The medical complaints filed by the plaintiffs were all related to medication side effects (n = 3, 100%). The plaintiffs were commonly patients themselves. Defendants were exclusively pharmaceutical companies. Persistent erectile dysfunction after stopping the medication was cited as a side effect in all complaints. The prescriptions were made for male pattern hair loss (n = 3, 100%) in all cases. All cases represent class actions brought by the plaintiffs, and they have been certified by their respective court. However, the cases are still ongoing. CONCLUSION: While 5ARI use has been linked to undesired sexual side effects, there have been few litigations on this issue in Canada. Persisting sexual dysfunction after stopping the medication is the only complaint presented in legal action. To date, no judgment against a physician or pharmaceutical company was identified. Cases are still ongoing.

Learning from national implementation of the Veterans Affairs Clinical Resource Hub (CRH) program for improving access to care: protocol for a six year evaluation.

BACKGROUND: The Veterans Affairs (VA) Clinical Resource Hub (CRH) program aims to improve patient access to care by implementing time-limited, regionally based primary or mental health staffing support to cover local staffing vacancies. VA's Office of Primary Care (OPC) designed CRH to support more than 1000 geographically disparate VA outpatient sites, many of which are in rural areas, by providing virtual contingency clinical staffing for sites experiencing primary care and mental health staffing deficits. The subsequently funded CRH evaluation, carried out by the VA Primary Care Analytics Team (PCAT), partnered with CRH program leaders and evaluation stakeholders to develop a protocol for a six-year CRH evaluation. The objectives for developing the CRH evaluation protocol were to prospectively: 1) identify the outcomes CRH aimed to achieve, and the key program elements designed to achieve them; 2) specify evaluation designs and data collection approaches for assessing CRH progress and success; and 3) guide the activities of five geographically dispersed evaluation teams. METHODS: The protocol documents a multi-method CRH program evaluation design with qualitative and quantitative elements. The evaluation's overall goal is to assess CRH's return on investment to the VA and Veterans at six years through synthesis of findings on program effectiveness. The evaluation includes both observational and quasi-experimental elements reflecting impacts at the national, regional, outpatient site, and patient levels. The protocol is based on program evaluation theory, implementation science frameworks, literature on contingency staffing, and iterative review and revision by both research and clinical operations partners. DISCUSSION: Health systems increasingly seek to use data to guide management and decision-making for newly implemented clinical programs and policies. Approaches for planning evaluations to accomplish this goal, however, are not well-established. By publishing the protocol, we aim to increase the validity and usefulness of subsequent evaluation findings. We also aim to provide an example of a program evaluation protocol developed within a learning health systems partnership.

Therapeutic Relational Connection in Telehealth: Concept Analysis.

BACKGROUND: Therapeutic relational connection (TRC) in telehealth is a new concept that refers to the intentional use of relationship connection between health care providers and their patients as both parties work toward a therapeutic aim. It has been demonstrated that TRC positively affects patient-centered outcomes including adherence, self-management, and satisfaction with care. What is not known are best practices for establishing TRC during telehealth visits. The rapid emergence of telehealth during the COVID-19 pandemic has identified a number of challenges. These challenges include lack of human contact, distance creating mistrust, the inability to rely on nonverbal communication, and a sense of depersonalization. Training for health care providers in these interpersonal communication skills needed to establish TRC during telehealth visits is needed. OBJECTIVE: This paper aims to explore the evolutionary concept of TRC in telehealth. The purpose of this paper is to provide a concept analysis of TRC during telehealth interactions between providers and patients through a comprehensive review of the existing published literature. METHODS: Rodgers' evolutionary concept analysis method was used to guide this study. PubMed, Embase, PsycINFO, and CINAHL were used to search for relevant publications. An integrative review strategy aided by Rayyan software was used to identify a final sample of 13 papers for analysis. RESULTS: The proposed definition of TRC in telehealth is the experience of a mutually responsive patient-provider relationship that is built on mutual respect and understanding and informed by cultural humility, presence, empathy, and the ability to effectively evaluate patient concerns to work toward a therapeutic aim. The key attributes of TRC in telehealth are the provider's ability to evaluate patient concerns, interpersonal communication, cultural humility, mutual trust and respect, presence, empathy, and building relationships. Clinical presence, proper environment, knowledge about the use of technology (both patient and provider), use of verbal and nonverbal communication, and knowledge about community and culture are important antecedents of TRC. Consequences of TRC include improved communication resulting in mutual respect and caring, adherence to follow-up recommendations, increased coping, collaborative decision-making, and satisfaction with care. CONCLUSIONS: Telehealth visits necessitate alternative approaches to establishing TRC as compared to in-person clinic visits. With the rapid expansion of telehealth platforms and a heightened acceptance of the technology, there is a need to integrate knowledge and provide a clear conceptualization of TRC in telehealth as TRC has been demonstrated to result in positive patient-centered outcomes. Identifying the attributes and antecedents of TRC in telehealth allows us the opportunity to develop guidelines and educational interventions aimed at training health care providers in the skills needed to establish TRC during telehealth visits.