Citations

Research has shown a consistent positive association between patient and provider experience and improved patient outcomes and safety. There is a belief that patient satisfaction and physician productivity are competing interests. The relationship for primary care physicians, in a Midwest Health system was evaluated as part of this project. Data from Press Ganey patient satisfaction surveys on likelihood of recommending the practice and the physician were compared between primary care physicians in the top quartile of average monthly patient visits and those that were in the three lower quartiles. A secondary analysis of patient satisfaction scores related to continuous years of service was also performed. Results of a multi-level logistic regression analysis showed a statistically significant difference between quartiles on average monthly visits and the likelihood of receiving a top box score on recommendation of the practice, but not the provider. The odds ratio was 0.7 for lower quartiles compared to highest quartile of visits. There was not a statistically significant difference for the categories of continuous years of service. On the question of recommending the physician, the odds ratios were not different, although there was a significant difference for the categories of years of service, with those between 0-5 years having a 0.62 odds ratio of a top box score compared to greater than 10 years. The results would tend to refute the belief that patient satisfaction must be sacrificed for physician productivity.

Objectives Describe a single institution's cochlear implant outcomes for patients with inner ear schwannomas (IES) in the setting of various tumor management strategies (observation, surgical resection, or stereotactic radiosurgery [SRS]). Study Design Single-institution retrospective review. Patients Patients diagnosed with isolated, sporadic IES who underwent cochlear implantation (CI). Interventions CI with or without IES treatment. Main Outcome Measures Speech perception outcomes, tumor status. Results Twelve patients with IES underwent CI with a median audiologic and radiologic follow-up of 12 months. Six patients underwent complete resection of the tumor at the time of CI, four underwent tumor observation, and two underwent SRS before CI. At 1 year after CI for all patients, the median consonant–nucleus–consonant (CNC) word score was 55% (interquartile range, 44–73%), and the median AzBio sentence in quiet score was 77% (interquartile range, 68–93%). Overall, those with surgical resection performed similarly to those with tumor observation (CNC 58 versus 61%; AzBio in quiet 74 versus 91%, respectively). Patients who underwent tumor resection before implantation had a wider range of speech performance outcomes compared with patients who underwent tumor observation. Two patients had SRS treatment before CI (10 months previous and same-day as CI) with CNC word scores of 6 and 40%, respectively. Conclusions Patients with IES who underwent CI demonstrated similar speech performance outcomes (CNC 56% and AzBio 82%), when compared with the general cochlear implant population. Patients who underwent either tumor observation or surgical resection performed well after CI.

Background Sealing of the aneurysm neck with a Woven EndoBridge (WEB) device is recommended for disrupting the blood flow inside the aneurysm. This study investigates the relationship between WEB neck apposition and aneurysm occlusion rates. Methods Aneurysms treated with a WEB from March 2017 to May 2022 at a single center were included. WEB neck apposition (poor/good) and WEB protrusion (yes/no) were evaluated on post-detachment high resolution cone beam CT images. Angiographic occlusion was assessed with the Bicêtre Occlusion Scale score (BOSS). Univariate and multivariable analysis tested the association between neck apposition and occlusion rates. Results The study included 159 aneurysms in 141 patients (mean age 55.8±11.2 years; 64.2% women). Good neck apposition and protrusion were noted in 123 (77.4%) and 30 (18.9%) cases, respectively. Inter-rater agreements were good for neck apposition (κ=0.75) and protrusion (κ=0.78). Complete and adequate occlusion was achieved in 104 (65%) and 130 (82%) cases, respectively (median follow-up 18 months). Good neck apposition was a strong independent predictor for both adequate (adjusted OR (aOR)=5.9, 95% CI 2.4 to 14.9; P<0.001) and complete occlusion (aOR=7.1, 95% CI 3.0 to 18.1; P<0.001). Protrusion was more frequent in the adequate occlusion group versus the aneurysm recurrence group without reaching statistical significance (P=0.06), but was associated with more thromboembolic complications (9/30 (30%) vs 12/129 (9%); P<0.01). WEB shape modification was significantly greater in poor apposition cases (P=0.03). Conclusions Achieving good neck apposition of the WEB strongly predicts aneurysm occlusion during follow-up. WEB protrusion should be minimized due to the increase in thromboembolic risk with limited impact on aneurysm occlusion.

Abstract Background and Aims Type 1 long QT syndrome (LQT1) is caused by pathogenic variants in the KCNQ1-encoded Kv7.1 potassium channels, which pathologically prolong ventricular action potential duration (APD). Herein, the pathologic phenotype in transgenic LQT1 rabbits is rescued using a novel KCNQ1 suppression-replacement (SupRep) gene therapy. Methods KCNQ1-SupRep gene therapy was developed by combining into a single construct a KCNQ1 shRNA (suppression) and an shRNA-immune KCNQ1 cDNA (replacement), packaged into adeno-associated virus serotype 9, and delivered in vivo via an intra-aortic root injection (1E10 vg/kg). To ascertain the efficacy of SupRep, 12-lead electrocardiograms were assessed in adult LQT1 and wild-type (WT) rabbits and patch-clamp experiments were performed on isolated ventricular cardiomyocytes. Results KCNQ1-SupRep treatment of LQT1 rabbits resulted in significant shortening of the pathologically prolonged QT index (QTi) towards WT levels. Ventricular cardiomyocytes isolated from treated LQT1 rabbits demonstrated pronounced shortening of APD compared to LQT1 controls, leading to levels similar to WT (LQT1-UT vs. LQT1-SupRep, P &lt; .0001, LQT1-SupRep vs. WT, P = ns). Under β-adrenergic stimulation with isoproterenol, SupRep-treated rabbits demonstrated a WT-like physiological QTi and APD90 behaviour. Conclusions This study provides the first animal-model, proof-of-concept gene therapy for correction of LQT1. In LQT1 rabbits, treatment with KCNQ1-SupRep gene therapy normalized the clinical QTi and cellular APD90 to near WT levels both at baseline and after isoproterenol. If similar QT/APD correction can be achieved with intravenous administration of KCNQ1-SupRep gene therapy in LQT1 rabbits, these encouraging data should compel continued development of this gene therapy for patients with LQT1.

Abstract With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate interstudy comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group–European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to (1) account for gender-specific differences in determining hemoglobin levels for eligibility criteria; (2) revise the definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices; and (3) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks before study enrollment) and hemoglobin thresholds for eligibility criteria (&lt;10 g/dL for women and &lt;11 g/dL for men). The revised document also provides separate (TDA vs non-TDA) and graded (major vs minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment.

AbstractIntroductionRelapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) remains a therapeutic challenge. Preclinical data in both B‐ and T‐ALL suggests synergy of venetoclax (VEN) with vincristine (VCR). We designed a phase I/II trial (EA9152) of the combination of L‐VCR and VEN for patients with r/r B‐or T‐cell ALL or LL. Here, we report the safety and efficacy outcomes of the phase I portion of this trial (NCT03504644).MethodsIn a 3+3 dose escalation design, r/r ALL subjects were given single‐agent VEN doses reaching 400, 600, or 800 mg for the three respective dose levels. Weekly L‐VCR at 2.25 mg/m2 IV was started on D15 of cycle 1. The primary phase I objective was to determine the maximum tolerated dose (MTD) of the combination.ResultsAmong the 18 patients in phase I, grade ≥ 3 treatment‐related adverse events were reported in 89% of treated patients. Two patients (two of three) at dose level 3 experienced dose‐limiting toxicities. Therefore, the MTD of the combination was determined to be dose level 2 (VEN 600 mg). Twenty‐two percent of evaluable patients (N = 4) achieved a complete response, with two of them showing no evidence of measurable residual disease (MRD).ConclusionThe combination of VEN and L‐VCR was found to be safe for patients with r/r ALL and encouraging preliminary efficacy, including MRD negative responses. With the removal of L‐VCR from the US market, the phase 2 portion of this trial is actively enrolling with vincristine sulfate.

Background Postoperative urinary retention (POUR) is a common and distressing surgical complication that may be associated with the pharmacological reversal technique of neuromuscular blockade (NMB). Objective This study aimed to investigate the impact that POUR has on medical charges. Methods This was a retrospective observational study of adult patients undergoing select surgeries who were administered neuromuscular blockade agent (NMBA), which was pharmacologically reversed between February 2017 and November 2021 using data from the PINC-AI™ Healthcare Database. Patients were divided into 2 groups: those experiencing POUR (composite of retention of urine, insertion of temporary indwelling bladder catheter, insertion of non-indwelling bladder catheter) during index hospitalization following surgery and those without POUR. Surgeries in inpatient and outpatient settings were analyzed separately. A cross-sectional comparison was performed to report total hospital charges for the 2 groups. Furthermore, patients experiencing subsequent POUR events within three days after discharge from index hospitalization were studied. Results A total of 330 838 inpatients and 437 063 outpatients were included. POUR developed in 13 020 inpatients and 2756 outpatients. Unadjusted results showed that POUR was associated with greater charges in both inpatient ($92 529 with POUR vs $78 556 without POUR, p < .001) and outpatient ($48 996 with POUR vs $35 433 without POUR, p < .001) settings. After adjusting for confounders, POUR was found to be associated with greater charges with an overall mean adjusted difference of $10 668 (95% confidence interval [CI] $95 760-$11 760, p < .001) in inpatient and $13 160 (95% CI $11 750-$14 571, p < .001) in outpatient settings. Charges associated with subsequent POUR events following discharge ranged from $9418 inpatient charges to $1694 outpatient charges. Conclusions Surgical patients who were pharmacologically reversed for NMB and developed a POUR event incurred greater charges than patients without POUR. These findings support the use of NMB reversal agents associated with a lower incidence of POUR.

AbstractPhase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI4) magnetic resonance imaging (MRI) protocols aim to maintain longitudinal consistency across two decades of data acquisition, while adopting new technologies. Here we describe and justify the study's design and targeted biomarkers. The ADNI4 MRI protocol includes nine MRI sequences. Some sequences require the latest hardware and software system upgrades and are continuously rolled out as they become available at each site. The main sequence additions/changes in ADNI4 are: (1) compressed sensing (CS) T1‐weighting, (2) pseudo‐continuous arterial spin labeling (ASL) on all three vendors (GE, Siemens, Philips), (3) multiple‐post‐labeling‐delay ASL, (4) 1 mm3 isotropic 3D fluid‐attenuated inversion recovery, and (5) CS 3D T2‐weighted. ADNI4 aims to help the neuroimaging community extract valuable imaging biomarkers and provide a database to test the impact of advanced imaging strategies on diagnostic accuracy and disease sensitivity among individuals lying on the cognitively normal to impaired spectrum.Highlights A summary of MRI protocols for phase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI 4). The design and justification for the ADNI 4 MRI protocols. Compressed sensing and multi‐band advances have been applied to improve scan time. ADNI4 protocols aim to streamline safety screening and therapy monitoring. The ADNI4 database will be a valuable test bed for academic research.