Citations

Abstract Rationale Adherence to center-based pulmonary rehabilitation after a COPD-related hospitalization—which improves all outcomes, including survival—is only 3%. Home-based programs have been proposed as a more feasible option, but they are not systematically offered, and patient preference is unknown. Objectives and Methods This pragmatic randomized trial involving patients with COPD recently hospitalized for a COPD exacerbation, originally aimed to investigate the comparative effect two arms: The choice of a facilitated referral to a center-based outpatient pulmonary rehabilitation program or a home-based program versus a home-based program on adherence to post-hospitalization rehabilitation and disease-specific QoL measured by the Chronic Respiratory Questionnaire. The trial aimed to investigate the patient’s preference of home vs center-based rehabilitation in individuals randomized to the choice arm. Daily steps were measured by Actigraph ®. The asynchronous home-based program included weekly health coaching and daily monitoring of daily steps, symptoms, and a 20-minute daily flexibility-balance exercise routine. Results Of 1,906 patients approached, 294 (15%) were randomized and agreed to the rehabilitation options offered by the study arms (uptake); of those, 56% completed the 12-week intervention (adherence). Of the 145 randomized to the choice arm, only one patient chose center-based PR; therefore, both groups received the same intervention, and results are presented as a one-group (before–after) analysis. Compared with baseline, the home intervention significantly improved (p < 0.01) physical and emotional QoL (Chronic Respiratory Questionnaire) and increased daily steps beyond the minimal clinically important difference. Trajectory models adjusted for age, FEV1%, and mMRC (breathlessness) confirmed sustained improvements in QoL at 6 and 12 months from baseline. Conclusions When offered a choice of rehabilitation setting after a COPD-related hospital admission for an exacerbation, home-based rehabilitation is patients’ preferred option. Sustained quality-of-life improvements in 1 year may represent an opportunity to regain well-being and/or deliver primary palliative care. Our results may have important implications for clinical practice.

Abstract A novel stationary tomographic Ultra-Fast Molecular Breast Imaging (UFMBI) technology was developed to reduce acquisition time and radiation dose of Molecular Breast Imaging (MBI), enabling its wider acceptance for supplemental dense breast screening. The system combines a stationary dual-head gamma camera made of CZT detectors with densely packed multi-pinhole collimators and novel de-multiplexing reconstruction methods, exploiting the ultra-high 3D position resolution of CZT detectors and their excellent energy resolution. A small field-of-view prototype (132 mm × 88 mm) was designed, built and calibrated. Raw detector data were processed using a machine-learning model providing 10×10 subpixelisation of 2 mm pixels in 5 mm thick CZT detectors and depth-of-interaction (DOI) estimation from anode signals alone. Tomographic images were reconstructed using an OSEM algorithm, including de-multiplexing and corrections for attenuation and collimator response. The prototype was evaluated using a 99mTc-filled phantom with lesions of different sizes and uniform background acquired separately. Prototype performance was compared with a clinical planar MBI system by imaging 99mTc-infused gel phantoms, with lesion detectability assessed via contrast-to-noise ratio (CNR). The results from the spheres’ phantom indicated that 5-7 mm diameter lesions with tumour-to-background ratios of 10-20:1 were detectable even with a dose/time reduction factor (DRF) of 8 relative to current MBI clinical practice. The gel phantom experiments showed that, with equal activity concentration and scanning time (DRF=1), the UFMBI prototype provided 2.5 to 3.9-fold CNR of the clinical planar system depending on the lesion activity and position within the field-of-view; with DRF of 6, UFMBI provided 1.6 to 2.4-fold CNR of the clinical system, improving to 2.5 to 3.4-fold with application of non-local means noise filtering. These results demonstrate the feasibility of UFMBI as a low-dose, high throughput approach and support its further development toward cancer screening of dense breasts and image-guided biopsy applications.

Abstract Background: Peripartum cardiomyopathy (PPCM) is an important cause of maternal heart failure associated with variable recovery and significant morbidity and mortality. Outcomes significantly differ from region to region with lower in high-income settings and very high in Africa and Asia. However, data from Ethiopia remain limited, particularly regarding one-year clinical and echocardiographic outcomes. Objective: To assess the one-year clinical and echocardiographic outcomes of patients diagnosed with peripartum cardiomyopathy and to identify factors associated with poor outcomes. Methods: A multicenter retrospective cohort study was conducted across selected tertiary and private hospitals in Addis Ababa, Ethiopia. All women diagnosed with PPCM between January 2020 and December 2024 were included using a census sampling approach. Data were extracted from electronic medical records and supplemented by phone follow-up when necessary. The primary outcomes were one-year mortality, heart failure–related hospital admission, and one-year ejection fraction recovery. A composite poor outcome was defined as death, hospital admission, or non-recovery of left ventricular function. Results: A total of 61 patients were included in the analysis. Five patients (8.2%) died within one year of diagnosis. Among patients with available one-year echocardiographic data, 50.8% achieved recovery of left ventricular systolic function. The remaining patients demonstrated either partial recovery or persistent systolic dysfunction. Higher baseline New York Heart Association (NYHA) functional class (III–IV) was associated with poorer outcomes, including lower rates of ejection fraction recovery and increased likelihood of adverse clinical outcomes. Conclusion: PPCM in this Ethiopia’s associated with measurable mortality, significant morbidity and heterogeneous recovery of left ventricular function at one year. Only about half of patients achieved full recovery, with worse outcomes observed among those presenting with advanced heart failure and severely reduced ejection fraction. Outcomes appear more favorable than those reported in some African settings but remain inferior to those observed in high-income countries.

ABSTRACT Among 9457 aquaporin‐4 (AQP4) immunoglobulin G‐positive patients, 2071 underwent autoimmune encephalitis antibody testing and 85 (4%) had coexisting antibodies, most commonly cerebrospinal fluid glial fibrillary acidic protein‐IgG and N‐methyl‐D‐aspartate receptor‐IgG, or serum high‐titer GAD65‐IgG. Compared with AQP4‐IgG positive neuromyelitis optica spectrum disorder controls, dual‐positive patients were younger and more frequently exhibited encephalopathy, psychiatric symptoms, seizures, ovarian teratomas, and deep gray matter, temporal lobe, or diencephalic MRI abnormalities. GAD65‐IgG‐positive patients developed stiff‐person syndrome. These findings define a distinct mixed glial‐neuronal autoimmune phenotype and support additional neural antibody testing in atypical AQP4‐IgG‐positive presentations.

BACKGROUND AND OBJECTIVES: Surgery for cervical spondylotic myelopathy improves quality of life but remains expensive. We conducted a cost-effectiveness analysis of patients treated with anterior cervical diskectomy/fusion (ACDF), posterior cervical decompression/fusion (PCDF), and laminoplasty (LP) in the Cervical Spondylotic Myelopathy Surgical (CSM-S) Trial, a randomized trial comparing surgical approaches for cervical spondylotic myelopathy. METHODS: In the trial, patients were randomized (2:3) to anterior (ACDF) or posterior surgery (LP or PCDF, at surgeon's discretion). A cost-effectiveness analysis was performed from a societal perspective with a 1-year time horizon, including only US patients as-treated. Cumulative costs were estimated using patient data on utilization and lost productivity using a human capital approach. Direct costs were calculated using 2022 Medicare rates for professional fees and cost-to-charge ratios for hospital services. Quality-adjusted life-years (QALYs) were calculated from patient responses to the EuroQol-5-Dimensions instrument at baseline and 3, 6, and 12 months postoperatively. Incremental cost-effectiveness ratio analysis was performed with bootstrapping to address uncertainty. RESULTS: Of 163 total patients enrolled in the CSM-S Trial, 153 from the United States (mean age, 62 years; 80 (52%) female) were included as-treated (ACDF = 61, PCDF = 64, LP = 28) in a cost-effectiveness analysis. Economic data were not available for 9 patients. The remaining 144 patients treated (ACDF = 55, PCDF = 61, LP = 28) had cost data through a 1-year follow-up. Mean hospitalization costs were higher after PCDF than ACDF and LP ($33 410 vs $26 468 vs $25 550; P < .001). Mean total costs were higher after PCDF than ACDF and LP ($62 383 vs $53 074 vs $47 426; P = .017). LP yielded greater QALY gains than ACDF (0.792 vs 0.732; P = .08) and PCDF (0.792 vs 0.698; P = .01). At a willingness-to-pay threshold of $150 000/QALY-gained, the probability that LP was cost-effective compared with PCDF was 99.7% and the probability compared with ACDF was 96%. CONCLUSION: In the CSM-S Trial, LP yielded greater 1-year quality-of-life improvements at lower costs than PCDF and ACDF.

Background & Aims: To evaluate safety and efficacy of FGFR1–3 kinase inhibitor derazantinib, in advanced intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions or rearrangements ( FGFR2 F ), mutations ( FGFR2 M ), or amplifications ( FGFR2 A ), previously treated with chemotherapy. Approach & Results: Open-label, non-controlled Phase 2 trial. Patients with advanced iCCA, ≥1 prior chemotherapy, and FGFR2 F (Substudy 1) or FGFR2 M /FGFR A (Substudy 2), received once-daily oral derazantinib 300 mg until disease progression, unacceptable toxicity, consent withdrawal or investigator decision to stop. Efficacy was assessed by central radiology review using RECIST v1.1. Primary endpoints were objective response rate (ORR; Substudy 1) and 3-month progression-free survival (PFS3; Substudy 2). Other endpoints were PFS, ORR (Substudy 2), disease control rate (DCR), duration of response (DOR), and overall survival (OS). In Substudy 1, ORR and DCR were 22.3% (23/103 partial responses) and 75.7%, respectively; median (95% CI) PFS was 8.1 (5.5,8.3) months, DOR was 6.5 (4.6,9.2) months, and OS was 17.2 (12.5,22.4) months. In Substudy 2, PFS3 was 63% (27/43), ORR was 9.3% (3 partial, 1 complete response), DCR was 69.8%, and OS was 11.9 (8.4,15.9) months. There were no Grade 4 or 5 drug-related events. FGFR inhibitor class-specific toxicities included drug-related hyperphosphataemia (38%, Grade 3: 3%) and dry eye (36%). Nail disorders (10%, any grade or causality), stomatitis (5%), retinal events (5%), and palmar-plantar erythrodysesthesia (1%) were infrequent. Conclusions: In previously chemotherapy treated, FGFR-inhibitor-naïve patients with iCCA harboring FGFR2 fusions, mutations, or amplifications, derazantinib showed clinically meaningful efficacy with durable objective responses, and a manageable safety profile.

Objective Assess if velopharyngeal gap size during speech is associated with consonant accuracy and whether hypernasality severity and compensatory misarticulation errors (CMAs) mediate this relationship. Design Cross-sectional. Setting Metropolitan hospital. Participants Eighty-one patients undergoing assessment for velopharyngeal insufficiency (VPI). Assessment(s) Each patient completed a preoperative magnetic resonance imaging protocol during sustained /i/ production and a perceptual speech evaluation. Velopharyngeal gap size was measured in millimeters. Hypernasality was rated using the Cleft Audit Protocol for Speech-Augmented-Americleft Modification. Percent consonants correct (PCC) and percent of CMAs used were derived from transcriptions of the American English sentence or phrase sample. Main Outcome Measure(s) A generalized structural equation model was used to examine whether velopharyngeal gap size is associated with PCC indirectly through hypernasality severity and CMA use. Results Larger velopharyngeal gap sizes were associated with more severe hypernasality ( P < .001), greater hypernasality severity was associated with increased CMA use ( P < .001), and greater CMA use was associated with lower PCC ( P < .001). Velopharyngeal gap size was not directly associated with PCC ( P = .400). However, the full indirect pathway from gap size to PCC through hypernasality severity and CMA use was significant ( P = .001); gap size was significantly associated with PCC when accounting for both direct and indirect pathways combined ( P = .005). Conclusions These findings suggest hypernasality severity is the key mediator between gap size and speech accuracy. Patients with more severe hypernasality may benefit from timely surgical remediation of VPI to increase overall consonant accuracy.

Objective To identify barriers and facilitators to changing provider's current approaches to evaluation and treatment decision-making for velopharyngeal insufficiency (VPI). Design Cross-sectional qualitative study. Setting Medium and large multidisciplinary cleft teams in the USA and Canada engaged in clinical research. Participants Twenty-eight surgeons and 16 speech-language pathologists from 12 cleft teams. Interventions Semi-structured interviews were conducted exploring perceived barriers and facilitators to changing VPI evaluation and treatment decision-making. Interviews were analyzed using a thematic approach guided by the Consolidated Framework for Implementation Research. Results Providers indicated that adoption of new approaches to VPI evaluation and decision-making would require evidence demonstrating improved speech outcomes or reduced risk of obstructive sleep apnea. Characteristics of persuasive evidence included prospective study design, comparable patient groups, standardized speech evaluations, and long-term follow-up. Providers favored applying new approaches to complex cases or defined subgroups, rather than broad adoption. Providers raised concerns about additional preoperative testing, perceiving it could increase treatment burden. When reflecting on prior changes in care delivery, providers indicated they started by discussing the potential change informally with team members to share information, gather input, and build consensus; in larger teams, discussions also occurred in formal meetings or through administrative hierarchies. Implementation decisions were consensus-based, although the pace of implementation varied among providers. Conclusions Providers have processes for implementing changes in their VPI evaluation and treatment decision-making, and criteria by which they make the decision to implement. These findings can inform the design of implementation strategies to accelerate clinical uptake of research findings.