Citations

Abstract A041202 (NCT01886872) is a phase 3 study comparing bendamustine plus rituximab (BR) with ibrutinib and the combination of ibrutinib plus rituximab (IR) in previously untreated older patients with chronic lymphocytic leukemia (CLL). The initial results showed that ibrutinib-containing regimens had superior progression-free survival (PFS) and rituximab did not add additional benefits. Here we present an updated analysis. With a median follow-up of 55 months, the median PFS was 44 months (95% confidence interval [CI], 38-54) for BR and not yet reached in either ibrutinib-containing arm. The 48-month PFS estimates were 47%, 76%, and 76% for BR, ibrutinib, and IR, respectively. The benefit of ibrutinib regimens over chemoimmunotherapy was consistent across subgroups of patients defined by TP53 abnormalities, del(11q), complex karyotype, and immunoglobulin heavy chain variable region (IGHV). No significant interaction effects were observed between the treatment arm and del(11q), the complex karyotype, or IGHV. However, a greater difference in PFS was observed among the patients with TP53 abnormalities. There was no difference in the overall survival. Notable adverse events with ibrutinib included atrial fibrillation (afib) and hypertension. Afib was observed in 11 patients (pts) on BR (3%) and 67 pts on ibrutinib (18%). All-grade hypertension was observed in 95 pts on BR (27%) and 263 pts on ibrutinib (55%). These data show that ibrutinib regimens prolong PFS compared with BR for older patients with treatment-naïve CLL. These benefits were observed across subgroups, including high-risk groups. Strikingly, within the ibrutinib arms, there was no inferior PFS for patients with abnormalities in TP53, the highest risk feature observed in CLL. These data continue to demonstrate the efficacy of ibrutinib in treatment-naïve CLL.

Introduction: Postoperative pain management and postoperative nausea and vomiting are a persistent challenge for both health care providers and patients. Acupuncture is an effective and safe modality for the management of pain and nausea, and has the potential to play a key role in postoperative pain management. This study explores the utility and feasibility of acupuncture in the immediate postoperative setting. Methods: In a retrospective case–control study, 22 patients who underwent elective surgeries and received acupuncture in the post-anesthesia care unit (PACU) were compared with 88 case controls. Indications for acupuncture therapy included persistent pain, nausea, or anxiety. Patient satisfaction and symptom improvement after acupuncture were assessed. PACU nurses and patients were queried on their perspectives on using this therapy. Demographic data, perioperative opioid consumption, pain score in the PACU, incidence of postoperative nausea, PACU length of stay, and unintended hospital admission were assessed. The groups with/without acupuncture were compared using Wilcoxon rank sum test or Fisher's exact test as appropriate. Results: A total of 78.9% of patients receiving acupuncture felt improvement in their symptoms. 94.7% of recovery nurses who cared for patients who received acupuncture felt that it was helpful and 78.9% did not believe it was disruptive. Patients who opted for acupuncture had a statistically significant higher overall median (interquartile range) pain score in the PACU (7.0 [5.2, 9.5] vs. 5.0 [3.0, 7.0], p = 0.009) and higher postoperative opioid consumption (22.5 [9.8, 44.8] vs. 15.0 [0.0, 30.0], p = 0. 03). There was no difference between total perioperative opioid consumption between groups ( p = 0.94). Conclusions: Most patients who received acupuncture therapy in the PACU were satisfied with their therapy and would recommend it to future patients undergoing surgery. Most recovery nurses felt it was helpful, was not disruptive, and would like to see it utilized in the PACU.

Background: The COVID-19 pandemic led to a dramatic increase in Medicare reimbursed telehealth utilization in the United States, but significant racial disparities persist. Methods: This research analyzed trends and disparities in Medicare reimbursed telehealth usage and claims from 2020 through 2022 using data from the Centers for Medicare & Medicaid Services. Results: Medicare telehealth user claims were 10.1 million in 2020, 52.7 million in 2021, and 85.3 million in 2023. The adjusted odds of telehealth use were significantly lower in 2021 (adjusted odds ratios [aORs]: 0.746; 95% confidence intervals [CI]: 0.683–0.815) and 2022 (aOR: 0.529; 95% CI: 0.484–0.578) compared with 2020. Large racial differences were observed in 2020–2022, with lower telehealth usage among African Americans (aOR: 0.068; 95% CI: 0.054–0.087), Hispanics (aOR: 0.036; 95% CI: 0.027–0.047), American Indians/Alaska Natives (aOR: 0.012; 95% CI: 0.009–0.017), and Asian Pacific Americans (aOR: 0.001; 95% CI: 0.001–0.002) versus Non-Hispanic Whites. Rural residents, older adults, and beneficiaries with disabilities also had reduced telehealth utilization. However, women were more likely to use telehealth versus men (aOR: 1.689; 95% CI: 1.363–2.094). Conclusion: Despite telehealth expansion during the pandemic, significant disparities remain, highlighting the need for targeted efforts to increase access and reduce barriers among underserved populations. Addressing disparities is critical to ensuring equitable access to health care through telehealth.

ABSTRACT The growing threat of antibiotic-resistant bacterial pathogens necessitates the development of alternative antimicrobial approaches. This is particularly true for chronic wound infections, which commonly harbor biofilm-dwelling bacteria. A novel electrochemical bandage (e-bandage) delivering low-levels of hypochlorous acid (HOCl) was evaluated against Pseudomonas aeruginosa murine wound biofilms. 5 mm skin wounds were created on the dorsum of mice and infected with 10 6 colony-forming units (CFU) of P. aeruginosa . Biofilms were formed over 2 days, after which e-bandages were placed on the wound beds and covered with Tegaderm. Mice were administered Tegaderm-only (control), non-polarized e-bandage (no HOCl production), or polarized e-bandage (using an HOCl-producing potentiostat), with or without systemic amikacin. Purulence and wound areas were measured before and after treatment. After 48 hours, wounds were harvested for bacterial quantification. Forty-eight hours of polarized e-bandage treatment resulted in mean biofilm reductions of 1.4 log 10 CFUs/g ( P = 0.0107) vs non-polarized controls and 2.2 log 10 CFU/g ( P = 0.004) vs Tegaderm-only controls. Amikacin improved CFU reduction in Tegaderm-only ( P = 0.0045) and non-polarized control groups ( P = 0.0312) but not in the polarized group ( P = 0.3876). Compared to the Tegaderm-only group, there was less purulence in the polarized group ( P = 0.009). Wound closure was neither impeded nor improved by either polarized or non-polarized e-bandage treatment. Concurrent amikacin did not impact wound closure or purulence. In conclusion, an HOCl-producing e-bandage reduced P. aeruginosa in wound biofilms with no impairment in wound healing, representing a promising antibiotic-free approach for addressing wound infection.

ABSTRACT Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that primarily causes the growth of tumors along nerves. Additionally, the germline mutations involved in NF1 predispose patients to develop further malignancies. The mainstay initial treatment for these malignancies is surgical removal at diagnosis, although targeted therapies are under evaluation in the relapsed setting. We report a case of malignant peripheral nerve sheath tumor (MPNST), gastrointestinal stromal tumor (GIST), and pheochromocytoma in a patient with NF1 who presented with an infected right shoulder lesion that was confirmed to be spindle cell sarcoma via biopsy. She was treated with antibiotics; however, she rapidly deteriorated and opted for hospice care. NF1 germline mutations increase the risk of patients developing various types of cancer. Recent studies have shown that there is a role for using MEK inhibitors such as selumetinib for treating patients with NF1.

ImportanceVacation has been shown to be an important restorative activity in the general population; less is known about physicians’ vacation behaviors and their association with burnout and professional fulfillment.ObjectiveTo examine the number of vacation days taken per year and the magnitude of physician work while on vacation and their association with physician burnout and professional fulfillment, by individual and organizational characteristics.Design, Setting, and ParticipantsThis cross-sectional survey of US physicians was conducted between November 20, 2020, and March 23, 2021. Data analysis was performed from March to July 2023.Main Outcomes and MeasuresBurnout was measured using the Maslach Burnout Index, and professional fulfillment was measured using the Stanford Professional Fulfillment Index. Number of vacation days taken in the last year, time spent working on patient care and other professional tasks per typical vacation day (ie, work on vacation), electronic health record (EHR) inbox coverage while on vacation, barriers to taking vacation, and standard demographics were collected.ResultsAmong 3024 respondents, 1790 of 3004 (59.6%), took 15 or fewer days of vacation in the last year, with 597 of 3004 (19.9%) taking 5 or fewer days. The majority, 2104 respondents (70.4%), performed patient care–related tasks on vacation, with 988 of 2988 (33.1%) working 30 minutes or more on a typical vacation day. Less than one-half of physicians (1468 of 2991 physicians [49.1%]) reported having full EHR inbox coverage while on vacation. On multivariable analysis adjusting for personal and professional factors, concern about finding someone to cover clinical responsibilities (odds ratio [OR], 0.48 [95% CI, 0.35-0.65] for quite a bit; OR, 0.30 [95% CI, 0.21-0.43] for very much) and financial concerns (OR, 0.49 [95% CI, 0.36-0.66] for quite a bit; OR, 0.38 [95% CI, 0.27-0.54] for very much) were associated with decreased likelihood of taking more than 3 weeks of vacation per year. Taking more than 3 weeks of vacation per year (OR, 0.66 [95% CI, 0.45-0.98] for 16-20 days; OR, 0.59 [95% CI, 0.40-0.86] for >20 days vs none) and having full EHR inbox coverage while on vacation (OR, 0.74; 95% CI, 0.63-0.88) were associated with lower rates of burnout on multivariable analysis, whereas spending 30 minutes or longer per vacation day on patient-related work (OR, 1.58; 95% CI, 1.22-2.04 for 30-60 minutes; OR, 1.97; 95% CI, 1.41-2.77 for 60-90 minutes; OR, 1.92; 95% CI, 1.36-2.73 for >90 minutes) was associated with higher rates of burnout.Conclusions and RelevanceIn this cross-sectional study of 3024 physicians, the number of vacation days taken and performing patient-related work while on vacation were associated with physician burnout. System-level efforts to ensure physicians take adequate vacation and have coverage for clinical responsibilities, including EHR inbox, may reduce physician burnout.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.

AbstractMetabolic pathways are known to generate byproducts—some of which have no clear metabolic function and some of which are toxic. Nicotinamide adenine dinucleotide phosphate hydrate (NAD(P)HX) is a toxic metabolite that is produced by stressors such as a fever, infection, or physical stress. Nicotinamide adenine dinucleotide phosphate hydrate dehydratase (NAXD) and nicotinamide adenine dinucleotide phosphate hydrate epimerase (NAXE) are part of the nicotinamide repair system that function to break down this toxic metabolite. Deficiency of NAXD and NAXE interrupts the critical intracellular repair of NAD(P)HX and allows for its accumulation. Clinically, deficiency of NAXE manifests as progressive, early onset encephalopathy with brain edema and/or leukoencephalopathy (PEBEL) 1, while deficiency of NAXD manifests as PEBEL2. In this report, we describe a case of probable PEBEL2 in a patient with a variant of unknown significance (c.362C>T, p.121L) in the NAXD gene who presented after routine immunizations with significant skin findings and in the absence of fevers.

The incidence and mortality of hepatocellular carcinoma (HCC) in Sub-Saharan Africa is projected to increase sharply by 2040 against a backdrop of limited diagnostic and therapeutic options. Two large South African-based case control studies have developed a serum-based miRNome for Hepatitis B-associated hepatocellular carcinoma (HBV-HCC), as well as identifying their gene targets and pathways. Using a combination of RNA sequencing, differential analysis and filters including a unique molecular index count (UMI) ≥ 10 and log fold change (LFC) range > 2: <−0.5 (p < 0.05), 91 dysregulated miRNAs were characterized including 30 that were upregulated and 61 were downregulated. KEGG analysis, a literature review and other bioinformatic tools identified the targeted genes and HBV-HCC pathways of the top 10 most dysregulated miRNAs. The results, which are based on differentiating miRNA expression of cases versus controls, also develop a serum-based miRNA diagnostic panel that indicates 95.9% sensitivity, 91.0% specificity and a Youden Index of 0.869. In conclusion, the results develop a comprehensive African HBV-HCC miRNome that potentially can contribute to RNA-based diagnostic and therapeutic options.

Background We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high‐sensitivity cardiac troponin T, N‐terminal pro‐B‐type natriuretic peptide, high‐sensitivity C‐reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long‐term mortality risk. Methods and Results BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high‐frequency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker‐based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all‐cause death were evaluated using accelerated failure time models (median follow‐up, 9.1 years; 141 deaths). Three biomarker‐based clusters were identified: cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long‐term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44–0.93; P =0.018) compared with cluster 1, and 0.71 (95% CI, 0.39–1.32; P =0.281) compared with patients with a repeat ACS. Conclusions Patients with subphenotypes of post‐ACS with different all‐cause mortality risks during long‐term follow‐up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.