Outcomes of a hydroxyapatite ceramic-coated femoral stem in primary total hip arthroplasty: a report of excellent survivorship from a single United Kingdom centre.

BACKGROUND: Hydroxyapatite (HA) coated femoral stems were introduced to enhance the biological fixation at the implant-bone interface, aiming to increase the longevity and survival of the prostheses. We aimed to assess the long-term outcomes of an HA ceramic (HAC) coated stem in primary total hip arthroplasty (THA), assess the stem survival, and clinically evaluate the patients using patient-reported outcome measures (PROMs) and radiological evaluation of stem osseointegration. PATIENTS AND METHODS: This was a prospective evaluation of a retrospective cohort of 385 patients (442 hips) who underwent primary THA between June 2008 and December 2018. The mean age was 63.83 years (range, 30-82 years). During the follow-up duration, 23 patients died, and 36 patients (38 hips) were lost to follow-up. Prospective data collected for 326 patients (381 hips) was used to evaluate stem survival with the Kaplan-Meier method using aseptic loosening or any revision as the endpoint. Clinical evaluation was done using the EuroQol five-dimension (EQ-5D) scoring system and PROMs using the Oxford Hip Score (OHS) and Merle D'Aubigne Postel (MDP) score. Radiological assessments were performed using the Engh radiological criteria for stem osteointegration. RESULTS: The mean follow-up duration was 9.39 years (range, 4-14.5 years). The survival of the HAC-coated femoral stem was 100% (95% confidence interval [CI], 96.7-100%) at 14 years with aseptic loosening as the endpoint, and 98.9% (CI, 96.7-100%) at 14 years with stem revision for any reason as the endpoint. The mean OHS was 44.5 (range, 30-48), and the mean MDP score was 15.87 (range, 10-18). Radiological evaluations showed full osseointegration of all stems. CONCLUSION: This HAC-coated femoral stem has shown excellent survivorship, functional outcomes, and full osseointegration at the final follow-up.

Knowledge, skills, and confidence gaps impacting treatment decision making in relapsed/refractory chronic lymphocytic leukemia and mantle cell lymphoma: a quantitative survey study in France, Germany, and the United States.

BACKGROUND: With recent advancements in the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), healthcare specialists may face challenges making treatment and management decisions based on latest evidence for the optimal care of patients with these conditions. This study aimed to identify specific knowledge, skills, and confidence gaps impacting the treatment of CLL and MCL, to inform future educational activities. METHODS: Hematologists and hemato-oncologists (HCPs, n = 224) from France (academic settings), Germany, and the United States (academic and community settings) responded to a 15-minute quantitative needs assessment survey that measured perceived knowledge, skills, and confidence levels regarding different aspects of treatment and management of CLL and MCL patients, as well as clinical case questions. Descriptive statistics (cross tabulations) and Chi-square tests were conducted. RESULTS: Four areas of educational need were identified: (1) sub-optimal knowledge of treatment guidelines; (2) sub-optimal knowledge of molecular testing to inform CLL/MCL treatment decisions; (3) sub-optimal skills when making treatment decisions according to patient profile (co-morbidities, molecular testing results); and (4) challenges balancing the risk of toxicities with benefits of treatment. Over one-third of the respondents reported skill gaps when selecting suitable treatment options and prescribing therapies and reported a lack in confidence to initiate and manage treatment. Larger gaps in knowledge of guidelines and skills in patient assessment were identified in MCL, compared to CLL. CONCLUSIONS: This study suggests the need for continuing medical education specifically to improve knowledge of treatment guidelines, and to assist clinicians in developing skills and confidence when faced with clinical decision-making scenarios of patients with specific comorbidities and/or molecular test results, for example, through case-based learning activities.

Intraoperative hypoglycemia among adults with intraoperative glucose measurements: a cross-sectional multicentre retrospective cohort study.

PURPOSE: Intraoperative hypoglycemia is presumed to be rare, but generalizable multicentre incidence and risk factor data for adult patients are lacking. We used a multicentre registry to characterize adults with intraoperative hypoglycemia and hypothesized that intraoperative insulin administration would be associated with hypoglycemia. METHODS: We conducted a cross-sectional retrospective multicentre cohort study. We searched the Multicenter Perioperative Outcomes Group registry to identify adult patients with intraoperative hypoglycemia (glucose < 3.3 mmol·L-1 [< 60 mg·dL-1]) from 1 January 2015 to 31 December 2019. We evaluated characteristics of patients with intraoperative glucose measurements and with intraoperative hypoglycemia. RESULTS: Of 516,045 patients with intraoperative glucose measurements, 3,900 (0.76%) had intraoperative hypoglycemia. Diabetes mellitus and chronic kidney disease were more common in the cohort with intraoperative hypoglycemia. The odds of intraoperative hypoglycemia were higher for the youngest age category (18-30 yr) compared with the odds for every age category above 40 yr (odds ratio [OR], 1.57-3.18; P < 0.001), and were higher for underweight or normal weight patients compared with patients with obesity (OR, 1.48-2.53; P < 0.001). Parenteral nutrition was associated with lower odds of hypoglycemia (OR, 0.23; 95% confidence interval [CI], 0.11 to 0.47; P < 0.001). Intraoperative insulin use was not associated with hypoglycemia (OR, 0.996; 95% CI, 0.91 to 1.09; P = 0.93). CONCLUSION: In this large cross-sectional retrospective multicentre cohort study, intraoperative hypoglycemia was a rare event. Intraoperative insulin use was not associated with hypoglycemia.

RéSUMé: OBJECTIF: L'hypoglycémie peropératoire est présumée rare, mais il n'existe pas de données généralisables sur l'incidence multicentrique et les facteurs de risque chez la patientèle adulte. Nous avons utilisé un registre multicentrique pour caractériser les personnes adultes atteintes d'hypoglycémie peropératoire et émis l'hypothèse que l'administration peropératoire d'insuline serait associée à l'hypoglycémie. MéTHODE: Nous avons réalisé une étude de cohorte multicentrique rétrospective transversale. Nous avons effectué des recherches dans le registre du Multicenter Perioperative Outcomes Group afin d'identifier les patient·es adultes atteint·es d'hypoglycémie peropératoire (glucose < 3,3 mmol· L−1 [< 60 mg·dL−1]) du 1er janvier 2015 au 31 décembre 2019. Nous avons évalué les caractéristiques des patient·es présentant des mesures de glucose et une hypoglycémie peropératoires. RéSULTATS: Sur 516 045 patient·es ayant des mesures de glucose peropératoires, 3900 (0,76 %) ont présenté une hypoglycémie peropératoire. Le diabète sucré et l'insuffisance rénale chronique étaient plus fréquents dans la cohorte présentant une hypoglycémie peropératoire. Les risques d'hypoglycémie peropératoire étaient plus élevés pour la catégorie d'âge la plus jeune (18-30 ans) par rapport aux catégories d'âge au-dessus de 40 ans (rapport des cotes [RC], 1,57-3,18; P < 0,001), et étaient plus élevés chez les patient·es de poids insuffisant ou de poids normal par rapport aux patient·es obèses (RC, 1,48-2,53; P < 0,001). La nutrition parentérale était associée à une probabilité plus faible d'hypoglycémie (RC, 0,23; intervalle de confiance [IC] à 95 %, 0,11 à 0,47; P < 0,001). L'utilisation peropératoire d'insuline n'était pas associée à l'hypoglycémie (RC, 0,996; IC 95 %, 0,91 à 1,09; P = 0,93). CONCLUSION: Dans cette vaste étude de cohorte multicentrique rétrospective transversale, l'hypoglycémie peropératoire était un événement rare. L'utilisation peropératoire d'insuline n'était pas associée à l'hypoglycémie.

Development and Validation of a Machine Learning COVID-19 Veteran (COVet) Deterioration Risk Score.

BACKGROUND AND OBJECTIVE: To develop the COVid Veteran (COVet) score for clinical deterioration in Veterans hospitalized with COVID-19 and further validate this model in both Veteran and non-Veteran samples. No such score has been derived and validated while incorporating a Veteran sample. DERIVATION COHORT: Adults (age ≥ 18 yr) hospitalized outside the ICU with a diagnosis of COVID-19 for model development to the Veterans Health Administration (VHA) (n = 80 hospitals). VALIDATION COHORT: External validation occurred in a VHA cohort of 34 hospitals, as well as six non-Veteran health systems for further external validation (n = 21 hospitals) between 2020 and 2023. PREDICTION MODEL: eXtreme Gradient Boosting machine learning methods were used, and performance was assessed using the area under the receiver operating characteristic curve and compared with the National Early Warning Score (NEWS). The primary outcome was transfer to the ICU or death within 24 hours of each new variable observation. Model predictor variables included demographics, vital signs, structured flowsheet data, and laboratory values. RESULTS: A total of 96,908 admissions occurred during the study period, of which 59,897 were in the Veteran sample and 37,011 were in the non-Veteran sample. During external validation in the Veteran sample, the model demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.88. This was significantly higher than NEWS (0.79; p < 0.01). In the non-Veteran sample, the model also demonstrated excellent discrimination (0.86 vs. 0.79 for NEWS; p < 0.01). The top three variables of importance were eosinophil percentage, mean oxygen saturation in the prior 24-hour period, and worst mental status in the prior 24-hour period. CONCLUSIONS: We used machine learning methods to develop and validate a highly accurate early warning score in both Veterans and non-Veterans hospitalized with COVID-19. The model could lead to earlier identification and therapy, which may improve outcomes.

Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in patients with B-cell malignancies: analysis of the Richter transformation subgroup from the multicentre, open-label, phase 1/2 BRUIN study.

BACKGROUND: Richter transformation usually presents as an aggressive diffuse large B-cell lymphoma, occurs in up to 10% of patients with chronic lymphocytic leukaemia, has no approved therapies, and is associated with a poor prognosis. Pirtobrutinib has shown promising efficacy and tolerability in patients with relapsed or refractory B-cell malignancies, including those who progress on covalent Bruton tyrosine kinase (BTK) inhibitors. This study aims to report the safety and activity of pirtobrutinib monotherapy in a subgroup of patients with Richter transformation from the multicentre, open-label, phase 1/2 BRUIN study. METHODS: This analysis included adult patients (aged ≥18 years) with histologically confirmed Richter transformation, an Eastern Cooperative Oncology Group performance status score of 0-2, and no limit of previous therapies, with patients receiving first-line treatment added in a protocol amendment (version 9.0, Dec 15, 2021). Pirtobrutinib 200 mg was administered orally once a day in 28-day cycles. The primary endpoint of phase 1 of the BRUIN trial as a whole, which has been previously reported, was to establish the recommended phase 2 dose for pirtobrutinib monotherapy and the phase 2 primary endpoint was overall response rate. Safety and activity were measured in all patients who received at least one dose of pirtobrutinib monotherapy. This BRUIN phase 1/2 trial was registered with ClinicalTrials.gov and is closed to enrolment (NCT03740529). FINDINGS: Between Dec 26, 2019, and July 22, 2022, 82 patients were enrolled, of whom five were enrolled during phase 1 and 77 during phase 2. All but one patient received a starting dose of 200 mg pirtobrutinib once a day as the recommended phase 2 dose. The remaining patient received 150 mg pirtobrutinib once a day, which was not escalated to 200 mg. The median age of patients was 67 years (IQR 59-72). 55 (67%) of 82 patients were male and 27 (33%) were female. Most patients were White (65 [79%] of 82). 74 (90%) of 82 patients received at least one previous Richter transformation-directed therapy. Most patients (61 [74%] of 82) had received previous covalent BTK inhibitor therapy for chronic lymphocytic leukaemia or Richter transformation. The overall response rate was 50·0% (95% CI 38·7-61·3). 11 (13%) of 82 patients had a complete response and 30 (37%) of 82 patients had a partial response. Eight patients with ongoing response electively discontinued pirtobrutinib to undergo stem-cell transplantation. The most common grade 3 or worse adverse event was neutropenia (n=19). There were no treatment-related deaths. INTERPRETATION: Pirtobrutinib shows promising safety and activity among patients with Richter transformation, most of whom received previous Richter transformation-directed therapy, including covalent BTK inhibitors. These data suggest that further investigation is warranted of pirtobrutinib as a treatment option for patients with relapsed or refractory Richter transformation after treatment with a covalent BTK inhibitor. FUNDING: Loxo Oncology.

Microneurosurgery for Ruptured Aneurysm of Distal Intracranial Vertebral Artery: A Case Report.

The International Subarachnoid Aneurysm Trial led to a shift from clipping to endovascular coiling as the primary therapy for cerebral aneurysm particularly in the management of posterior circulation aneurysm. However, endovascular therapy is often unavailable in low-resource settings, emphasizing the importance of maintaining surgical skill sets in resource-poor countries. This article presents a detailed case report on the successful microneurosurgical management of a 65-year-old female with a history of headache and weakness with past history of hypertension and a right posterior cerebral artery territory infarct who was diagnosed with a ruptured aneurysm situated within the intracranial vertebral artery. Patient was operated with the far lateral approach and clipping of the aneurysm. This case report elucidates the intricate surgical techniques employed, and the challenges neurosurgeons encountered in treating posterior circulation intracranial aneurysms, particularly those with ruptured complications. The aneurysms' intricate anatomy and increased rupture risk necessitate a meticulous microneurosurgical approach. The severity of subarachnoid hemorrhage from ruptured aneurysms increases morbidity and mortality rates.

Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission.

In patients with relapsed DLBCL in complete remission (CR), autologous hematopoietic cell transplantation (auto-HCT) and CAR-T therapy are both effective, but it is unknown which modality provides superior outcomes. We compared the efficacy of auto-HCT vs. CAR-T in patients with DLBCL in a CR. A retrospective observational study comparing auto-HCT (2015-2021) vs. CAR-T (2018-2021) using the Center for International Blood & Marrow Transplant Research registry. Median follow-up was 49.7 months for the auto-HCT and 24.7 months for the CAR-T cohort. Patients ages 18 and 75 with a diagnosis of DLBCL were included if they received auto-HCT (n = 281) or commercial CAR-T (n = 79) while in a CR. Patients undergoing auto-HCT with only one prior therapy line and CAR-T patients with a previous history of auto-HCT treatment were excluded. Endpoints included Progression-free survival (PFS), relapse rate, non-relapse mortality (NRM) and overall survival (OS). In univariate analysis, treatment with auto-HCT was associated with a higher rate of 2-year PFS (66.2% vs. 47.8%; p < 0.001), a lower 2-year cumulative incidence of relapse (27.8% vs. 48% ; p < 0.001), and a superior 2-year OS (78.9% vs. 65.6%; p = 0.037). In patients with early (within 12 months) treatment failure, auto-HCT was associated with a superior 2-year PFS (70.9% vs. 48.3% ; p < 0.001), lower 2-year cumulative incidence of relapse (22.8% vs. 45.9% ; p < 0.001) and trend for higher 2-year OS (82.4% vs. 66.1% ; p = 0.076). In the multivariable analysis, treatment with auto-HCT was associated with a superior PFS (hazard ratio 1.83; p = 0.0011) and lower incidence of relapse (hazard ratio 2.18; p < 0.0001) compared to CAR-T. In patients with relapsed LBCL who achieve a CR, treatment with auto-HCT is associated with improved clinical outcomes compared to CAR-T. These data support the consideration of auto-HCT in select patients with LBCL achieving a CR in the relapsed setting.

Fixed-Duration Pirtobrutinib plus Venetoclax with or without Rituximab in Relapsed/Refractory CLL: Phase 1b BRUIN Trial.

Pirtobrutinib is a highly selective, non-covalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) were treated with fixed-duration pirtobrutinib plus venetoclax (PV) or pirtobrutinib plus venetoclax and rituximab (PVR) in this phase 1b trial (NCT03740529). Prior covalent BTKi therapy was allowed, but not prior venetoclax. Patients were assigned to receive PV (n=15) or PVR (n=10) for 25 cycles. Median age was 66 years (range, 39-78). Median prior lines of therapy was 2 (range, 1-4), and 17 (68%) patients had received prior covalent BTKi. At the data-cutoff date (May 5, 2023), median time on study was 27.0 months for PV and 23.3 months for PVR. Overall response rates were 93.3% (95% CI:68.1-99.8%) for PV and 100% (95% CI:69.2-100.0%) for PVR, with 10 complete responses (PV:7; PVR:3). After 12 cycles of treatment, 85.7% (95% CI:57.2-98.2%) of PV and 90.0% (95% CI:55.5-99.7%) of PVR patients achieved undetectable minimal residual disease assessed in peripheral blood by clonoSEQ® assay at a sensitivity of <1x10-4. Progression-free survival at 18 months was 92.9% (95% CI: 59.1-99.0) for PV patients and 80.0% (95% CI: 40.9-94.6) for PVR patients. No DLTs were observed in either treatment combination during the 5-week assessment period. The most common grade ≥3 adverse events for all patients included neutropenia (52%) and anemia (16%). Adverse events led to dose reduction in 3 patients and discontinuation in 2. In conclusion, fixed-duration PV or PVR was well tolerated and had promising efficacy in patients with R/R CLL, including patients previously treated with a covalent BTKi.

Outpatient administration of CAR T-cell therapies using a strategy of no remote monitoring and early CRS intervention.

ABSTRACT: Recent studies demonstrating the feasibility of outpatient chimeric antigen receptor (CAR)-modified T-cell therapy administration are either restricted to CARs with 41BB costimulatory domains or use intensive at-home monitoring. We report outcomes of outpatient administration of all commercially available CD19- and B-cell maturation antigen (BCMA)-directed CAR T-cell therapy using a strategy of no remote at-home monitoring and an early cytokine release syndrome (CRS) intervention strategy. Patients with hematologic malignancies who received CAR T-cell therapy in the outpatient setting during 2022 to 2023 were included. Patients were seen daily in the cancer center day hospital for the first 7 to 10 days and then twice weekly through day 30. The primary end point was to determine 3-, 7-, and 30-day post-CAR T-cell infusion hospitalizations. Early CRS intervention involved administering tocilizumab as an outpatient for grade ≥1 CRS. Fifty-eight patients received outpatient CAR T-cell infusion (33 myeloma, 24 lymphoma, and 1 acute lymphoblastic leukemia). Of these, 17 (41%), 16 (38%), and 9 patients (21%) were admitted between days 0 to 3, 4 to 7, and 8 to 30 after CAR T-cell infusion, respectively. The most common reason for admission was CAR T-cell-related toxicities (33/42). Hospitalization was prevented in 15 of 35 patients who received tocilizumab for CRS as an outpatient. The nonrelapse mortality rates were 1.7% at 1 month and 3.4% at 6 months. In conclusion, we demonstrate that the administration of commercial CAR T-cell therapies in an outpatient setting is safe and feasible without intensive remote monitoring using an early CRS intervention strategy.

Comparison of Patch Testing Results of White and Black Patients.

Patch testing is the standard diagnostic test used for patients presenting with symptoms of allergic contact dermatitis. The grading of patch test results classically varies from 1 to 3. The assessment of these results begins with a visual inspection of the presence of erythema, vesiculation, and induration. This leads to a subjectivity in visual evaluation of a patch test. Positive patch testing results can present differently in patients with darker skin tones. A greater variety of images of allergic contact dermatitis in patients with darker skin phototypes can better guide the diagnosis of this condition in skin of color. People with darker phototypes are historically underrepresented in dermatologic images and texts; thus, identifying erythema in darker phototypes may be more difficult for dermatologists, whether or not they were trained in areas of decreased phototype diversity. In this article, we present positive patch testing findings on several different phototypes, with the intention of contributing to images of phototypes underrepresented in dermatology literature.

Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.

INTRODUCTION: Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment. METHODS: Here we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs). RESULTS: Of 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy. CONCLUSIONS: Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.

Beyond Brick and Mortar: The Rise of Street Medicine.

In 2023, approximately 650,000 people experienced homelessness (PEH) nightly in the United States, the highest number recorded in the country's history. This alarming statistic has made homelessness a key issue in the 2024 elections, especially with the White House's goal to reduce homelessness by 25% by 2025. Despite efforts and investments, homelessness remains a persistent public health challenge. The recent inclusion of street medicine services in Center for Medicare and Medicaid Services (CMS) billing codes represents a significant step forward. Street medicine, defined by CMS as healthcare provided in non-permanent locations to unsheltered individuals, now qualifies for Medicare reimbursement. This policy change, alongside state-level initiatives, aims to improve healthcare access for the unhoused, particularly older adults. However, challenges remain in establishing adequate fee schedules and integrating care management. Despite these obstacles, the integration of healthcare and housing services is crucial for addressing homelessness effectively, promoting stability, and improving health outcomes for PEH. This manuscript explores the history, practical guidance, and potential impacts of these developments on homelessness and public health.

Exploring Anesthesia Provider Preferences for Precision Feedback: Preference Elicitation Study.

Background: Health care professionals must learn continuously as a core part of their work. As the rate of knowledge production in biomedicine increases, better support for health care professionals' continuous learning is needed. In health systems, feedback is pervasive and is widely considered to be essential for learning that drives improvement. Clinical quality dashboards are one widely deployed approach to delivering feedback, but engagement with these systems is commonly low, reflecting a limited understanding of how to improve the effectiveness of feedback about health care. When coaches and facilitators deliver feedback for improving performance, they aim to be responsive to the recipient's motivations, information needs, and preferences. However, such functionality is largely missing from dashboards and feedback reports. Precision feedback is the delivery of high-value, motivating performance information that is prioritized based on its motivational potential for a specific recipient, including their needs and preferences. Anesthesia care offers a clinical domain with high-quality performance data and an abundance of evidence-based quality metrics. Objective: The objective of this study is to explore anesthesia provider preferences for precision feedback. Methods: We developed a test set of precision feedback messages with balanced characteristics across 4 performance scenarios. We created an experimental design to expose participants to contrasting message versions. We recruited anesthesia providers and elicited their preferences through analysis of the content of preferred messages. Participants additionally rated their perceived benefit of preferred messages to clinical practice on a 5-point Likert scale. Results: We elicited preferences and feedback message benefit ratings from 35 participants. Preferences were diverse across participants but largely consistent within participants. Participants' preferences were consistent for message temporality (α=.85) and display format (α=.80). Ratings of participants' perceived benefit to clinical practice of preferred messages were high (mean rating 4.27, SD 0.77). Conclusions: Health care professionals exhibited diverse yet internally consistent preferences for precision feedback across a set of performance scenarios, while also giving messages high ratings of perceived benefit. A "one-size-fits-most approach" to performance feedback delivery would not appear to satisfy these preferences. Precision feedback systems may hold potential to improve support for health care professionals' continuous learning by accommodating feedback preferences.

Randomized Placebo-Controlled Trial of 60-Day Percutaneous Peripheral Nerve Stimulation Treatment Indicates Relief of Persistent Postoperative Pain, and Improved Function After Knee Replacement.

OBJECTIVES: Total knee arthroplasty (TKA) is an effective surgery for end-stage knee osteoarthritis, but chronic postoperative pain and reduced function affect up to 20% of patients who undergo such surgery. There are limited treatment options, but percutaneous peripheral nerve stimulation (PNS) is a promising nonopioid treatment option for chronic, persistent postoperative pain. The objective of the present study was to evaluate the effect of a 60-day percutaneous PNS treatment in a multicenter, randomized, double-blind, placebo-controlled trial for treating persistent postoperative pain after TKA. MATERIALS AND METHODS: Patients with postoperative pain after knee replacement were screened for this postmarket, institutional review board-approved, prospectively registered (NCT04341948) trial. Subjects were randomized to receive either active PNS or placebo (sham) stimulation. Subjects and a designated evaluator were blinded to group assignments. Subjects in both groups underwent ultrasound-guided placement of percutaneous fine-wire coiled leads targeting the femoral and sciatic nerves on the leg with postoperative pain. Leads were indwelling for eight weeks, and the primary efficacy outcome compared the proportion of subjects in each group reporting ≥50% reduction in average pain relative to baseline during weeks five to eight. Functional outcomes (6-minute walk test; 6MWT and Western Ontario and McMaster Universities Osteoarthritis Index) and quality of life (Patient Global Impression of Change) also were evaluated at end of treatment (EOT). RESULTS: A greater proportion of subjects in the PNS groups (60%; 12/20) than in the placebo (sham) group (24%; 5/21) responded with ≥50% pain relief relative to baseline (p = 0.028) during the primary endpoint (weeks 5-8). Subjects in the PNS group also walked a significantly greater distance at EOT than did those in the placebo (sham) group (6MWT; +47% vs -9% change from baseline; p = 0.048, n = 18 vs n = 20 completed the test, respectively). Prospective follow-up to 12 months is ongoing. CONCLUSIONS: This study provides evidence that percutaneous PNS decreases persistent pain, which leads to improved functional outcomes after TKA at EOT.

Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.

Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) is uncertain. Objective: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. Design Setting and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate the effectiveness of repurposed medications in treating mild to moderate COVID-19. Between January 27, 2023, and June 23, 2023, 1250 participants ≥30 years of age with confirmed SARS-CoV-2 infection and ≥2 acute COVID-19 symptoms for ≤7 days, were included across 104 US sites to evaluate the use of montelukast. Interventions: Participants were randomized to receive montelukast 10 mg once daily or matched placebo for 14 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID clinical progression scale; and difference in mean time unwell. Results: Among participants who were randomized and received study drug, the median age was 53 years (IQR 42-62), 60.2% were female, 64.6% identified as Hispanic/Latino, and 56.3% reported ≥2 doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR] 1.02; 95% credible interval [CrI] 0.92-1.12; P(efficacy) = 0.63]). Unadjusted median time to sustained recovery was 10 days (95% confidence interval 10-11) in both groups. No deaths were reported and 2 hospitalizations were reported in each group; 36 participants reported healthcare utilization events (a priori defined as death, hospitalization, emergency department/urgent care visit); 18 in the montelukast group compared with 18 in the placebo group (HR 1.01; 95% CrI 0.45-1.84; P(efficacy)=0.48). Five participants experienced serious adverse events (3 with montelukast and 2 with placebo). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with montelukast does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov ( NCT04885530 ).

Multicenter Development and Prospective Validation of eCARTv5: A Gradient Boosted Machine Learning Early Warning Score.

Rationale: Early detection of clinical deterioration using early warning scores may improve outcomes. However, most implemented scores were developed using logistic regression, only underwent retrospective internal validation, and were not tested in important patient subgroups. Objectives: To develop a gradient boosted machine model (eCARTv5) for identifying clinical deterioration and then validate externally, test prospectively, and evaluate across patient subgroups. Methods: All adult patients hospitalized on the wards in seven hospitals from 2008- 2022 were used to develop eCARTv5, with demographics, vital signs, clinician documentation, and laboratory values utilized to predict intensive care unit transfer or death in the next 24 hours. The model was externally validated retrospectively in 21 hospitals from 2009-2023 and prospectively in 10 hospitals from February to May 2023. eCARTv5 was compared to the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS) using the area under the receiver operating characteristic curve (AUROC). Measurements and Main Results: The development cohort included 901,491 admissions, the retrospective validation cohort included 1,769,461 admissions, and the prospective validation cohort included 46,330 admissions. In retrospective validation, eCART had the highest AUROC (0.835; 95%CI 0.834, 0.835), followed by NEWS (0.766 (95%CI 0.766, 0.767)), and MEWS (0.704 (95%CI 0.703, 0.704)). eCART's performance remained high (AUROC ≥0.80) across a range of patient demographics, clinical conditions, and during prospective validation. Conclusions: We developed eCARTv5, which accurately identifies early clinical deterioration in hospitalized ward patients. Our model performed better than the NEWS and MEWS retrospectively, prospectively, and across a range of subgroups.

Sprint-inspired One-on-One Post-Go-Live Training Session (Mini-Sprint) Improves Provider Electronic Health Record Efficiency and Satisfaction.

BACKGROUND: Inefficient electronic health record (EHR) usage increases the documentation burden on physicians and other providers, which increases cognitive load and contributes to provider burnout. Studies show that EHR efficiency sessions, optimization sprints, reduce burnout using a resource-intense five-person team. We implemented sprint-inspired one-on-one post-go-live efficiency training sessions (mini-sprints) as a more economical training option directed at providers. OBJECTIVES: We evaluated a post-go-live mini-sprint intervention to assess provider satisfaction and efficiency. METHODS: NorthShore University HealthSystem implemented one-on-one provider-to-provider mini-sprint sessions to optimize provider workflow within the EHR platform. The physician informaticist completed a 9-point checklist of efficiency tips with physician trainees covering schedule organization, chart review, speed buttons, billing, note personalization/optimization, preference lists, quick actions, and quick tips. We collected postsession survey data assessing for net promoter score (NPS) and open-ended feedback. We conducted financial analysis of pre- and post-mini-sprint efficiency levels and financial data. RESULTS: Seventy-six sessions were conducted with 32 primary care physicians, 28 specialty physicians, and 16 nonphysician providers within primary care and other areas. Thirty-seven physicians completed the postsession survey. The average NPS for the completed mini-sprint sessions was 97. The proficiency score had a median of 6.12 (Interquartile range (IQR): 4.71-7.64) before training, and a median of 7.10 (IQR: 6.25-8.49) after training. Financial data analysis indicates that higher level billing codes were used at a greater frequency post-mini-sprint. The revenue increase 12 months post-mini-sprint was $213,234, leading to a return of $75,559.50 for 40 providers, or $1,888.98 per provider in a 12-month period. CONCLUSION: Our data show that mini-sprint sessions were effective in optimizing efficiency within the EHR platform. Financial analysis demonstrates that this type of training program is sustainable and pays for itself. There was high satisfaction with the mini-sprint training modality, and feedback indicated an interest in further mini-sprint training sessions for physicians and nonphysician staff.