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Irina Topchiy,1,2,* Anne M Fink,1,2 Katherine A Maki,2,3 Michael W Calik1,2,* 1Center for Sleep and Health Research, University of Illinois Chicago, Chicago, IL, USA; 2Department of Biobehavioral Nursing Science; University of Illinois Chicago, Chicago, IL, USA; 3Translational Biobehavioral and Health Disparities Branch, Clinical Center; National Institutes of Health, Bethesda, MD, USA*These authors contributed equally to this workCorrespondence: Michael W Calik, University of Illinois Chicago, 845 South Damen Avenue (M/C 802), College of Nursing, Room 740, Chicago, IL, 60612, USA, Tel +1 312 413 0581, Email mcalik@uic.eduIntroduction: Current methods of sleep research in rodents involve invasive surgical procedures of EEG and EMG electrodes implantation. Recently, a new method of measuring sleep, PiezoSleep, has been validated against implanted electrodes in mice and rats. PiezoSleep uses a piezoelectric film transducer to detect the rodent’s movements and respiration and employs an algorithm to automatically score sleep. Here, we validate PiezoSleep scoring versus EEG/EMG implanted electrodes sleep scoring in rats.Methods: Adult male Brown Norway and Wistar Kyoto rats were implanted with bilateral stainless-steel screws into the skull for EEG recording and bilateral wire electrodes into the nuchal muscles for EMG assessment. In Brown Norway rats, the EEG/EMG electrode leads were soldered to a miniature connector plug and fixed to the skull. In Wistar Kyoto rats, the EEG/EMG leads were tunneled subcutaneously to a telemetry transmitter implanted in the flank. Rats were allowed to recover from surgery for one week. Brown Norway rats were placed in PiezoSleep cages, and had their headsets connected to cable for recording EEG/EMG signals, which were then manually scored by a human scorer in 10-sec epochs. Wistar Kyoto rats were placed in PiezoSleep cages, and EEG/EMG signals were recorded using a telemetry system (DSI). Sleep was scored automatically in 4-sec epochs using NeuroScore software. PiezoSleep software recorded and scored sleep in the rats.Results: Rats implanted with corded EEG/EMG headsets had 85.6% concurrence of sleep-wake scoring with PiezoSleep. Rats implanted with EEG/EMG telemetry had 80.8% concurrence sleep-wake scoring with PiezoSleep. Sensitivity and specificity rates were similar between the EEG/EMG recording systems. Total sleep time and hourly sleep times did not differ in all three systems. However, automatic sleep detection by NeuroScore classified more sleep during the light period compared to the PiezoSleep.Conclusion: We showed that PiezoSleep system can be a reliable alternative to both automatic and visual EEG/EMG- based sleep-wake scoring in rat.Keywords: piezoelectric, noninvasive sleep scoring, telemetry, automated sleep scoring, EEG/EMG, rat

Terri E Weaver,1,2 Michael W Calik,1,2 Sarah S Farabi,1,2 Anne M Fink,1,2 Maria T Galang-Boquiren,2,3 Mary C Kapella,1,2 Bharati Prasad,2,4 David W Carley1,21Biobehavioral Health Science Department, College of Nursing, University of Illinois at Chicago; 2Center for Narcolepsy, Sleep and Health, University of Illinois at Chicago College of Nursing, 3Department of Orthodontics, University of Illinois at Chicago College of Dentistry, 4Sleep Center, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, USAAbstract: Obstructive sleep apnea (OSA) affects one in five adult males and is associated with significant comorbidity, cognitive impairment, excessive daytime sleepiness, and reduced quality of life. For over 25 years, the primary treatment has been continuous positive airway pressure, which introduces a column of air that serves as a pneumatic splint for the upper airway, preventing the airway collapse that is the physiologic definition of this syndrome. However, issues with patient tolerance and unacceptable levels of treatment adherence motivated the exploration of other potential treatments. With greater understanding of the physiologic mechanisms associated with OSA, novel interventions have emerged in the last 5 years. The purpose of this article is to describe new treatments for OSA and associated complex sleep apnea. New approaches to complex sleep apnea have included adaptive servoventilation. There is increased literature on the contribution of behavioral interventions to improve adherence with continuous positive airway pressure that have proven quite effective. New non-surgical treatments include oral pressure devices, improved mandibular advancement devices, nasal expiratory positive airway pressure, and newer approaches to positional therapy. Recent innovations in surgical interventions have included laser-assisted uvulopalatoplasty, radiofrequency ablation, palatal implants, and electrical stimulation of the upper airway muscles. No drugs have been approved to treat OSA, but potential drug therapies have centered on increasing ventilatory drive, altering the arousal threshold, modifying loop gain (a dimensionless value quantifying the stability of the ventilatory control system), or preventing airway collapse by affecting the surface tension. An emerging approach is the application of cannabinoids to increase upper airway tone.Keywords: obstructive sleep apnea, innovative treatment, continuous positive airway pressure, oral appliance, nerve stimulation

In this paper we use our advanced Hadamard Inequality together with Grüss's Inequality to get improved versions of Hadamard's Inequality and some quadrature formulas.

We derive Opial-type inequalities for a class of real functions satisfying nonhomogenous boundary conditions and determine the best constant and extremals. The results are then used to obtain generalized Lyapunov and De la Valée Poussin inequalities.

In response to federal requests for investigation into measures to eradicate health disparities, a concept analysis of the term health disparity was conducted. Health-related and multidisciplinary literature was reviewed. Multiple terms were explored alone and in combination with no limitations on search date parameters. Findings indicated several definitions of the concept, with the term health care disparity being used interchangeably with the term health disparity . New theoretical and operational definitions, antecedents, characteristics, and consequences of the concept are proffered. Model, borderline, and contrary cases are developed to illustrate the concept. Nursing implications and recommendations for future research are discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND AND RESEARCH OBJECTIVE: Fatigue is one of the most prevalent symptoms in persons with systolic heart failure (HF). There remains insufficient information about the physiological and psychosocial underpinnings of fatigue in HF. The specific aims of this study were to (1) determine the psychometric properties of 2 fatigue questionnaires in patients with HF, (2) compare fatigue in patients with HF to published scores of healthy adults and patients with cancer undergoing treatment, and (3) identify the physiological (eg, hemoglobin, B-type natriuretic peptide, body mass index, and ejection fraction) and psychosocial (eg, depressed mood) correlates of fatigue in HF. SUBJECTS AND METHODS: A convenience sample of 87 HF outpatients was recruited from 2 urban medical centers. Patients completed the Fatigue Symptom Inventory, Profile of Mood States, and Short Form-36 Health Survey. RESULTS AND CONCLUSIONS: Patients with HF and patients with cancer reported similar levels of fatigue, and both patient groups reported significantly more fatigue than did healthy adults. Physical functioning and hemoglobin categories explained 30% of the variance in Fatigue Symptom Inventory-Interference Scale scores, whereas depressed mood and physical functioning explained 47% of the variance in Profile of Mood States Fatigue subscale scores. Patients with HF experienced substantial fatigue that is comparable with cancer-related fatigue. Low physical functioning, depressed mood, and low hemoglobin level were associated with HF-related fatigue. [ABSTRACT FROM AUTHOR]

Although endocarditis is relatively rare--an estimated 15,000 to 20,000 new cases are diagnosed annually--people with prosthetic valves are among those at highest risk. [ABSTRACT FROM AUTHOR]

Abstract: Ingested foreign bodies may lead to perforation of the gastrointestinal tract. We present a case of a 14-month-old boy who presented with an unusual abdominal mass secondary to ingesting a foreign body 4 months previously. Abdominal computerized tomography scan was valuable in making this diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events. Patient reported outcomes of time until definitive deterioration (TUDD) in quality of life (QoL) were analyzed. At a median observation time of 76.4 months, PFS remained superior for Ven-Obi compared with Clb-Obi (median, 76.2 vs 36.4 months; hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.31-0.52; P < .0001). Likewise, TTNT was longer after Ven-Obi (6-year TTNT, 65.2% vs 37.1%; HR, 0.44; 95% CI, 0.33-0.58; P < .0001). In the Ven-Obi arm, presence of del(17p), unmutated immunoglobulin heavy-chain variable region, and lymph node size of ≥5 cm were independent prognostic factors for shorter PFS. The 6-year OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR, 0.69; 95% CI, 0.48-1.01; P = .052). A significantly longer TUDD in global health status/QoL was observed in the Ven-Obi than in the Clb-Obi arm (median, 82.1 vs 65.1 months; HR, 0.70; 95% CI, 0.51-0.97). Follow-up-adjusted second primary malignancies incidence rates were 2.3 and 1.4 per 1000 patient-months in the Ven-Obi and Clb-Obi arm, respectively. The sustained long-term survival and QoL benefits support the use of 1-year fixed-duration Ven-Obi in CLL. This trial was registered at www.ClinicalTrials.gov as #NCT02242942., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Aim: The aim is to delineate the concept of sleep disturbances in health professional students during the COVID-19 pandemic., Design: A concept analysis was conducted., Methods: A systematic search was conducted for relevant articles published and performed from inception to July 5, 2024. Electronic databases searched included PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase and Web of Science. Rodgers' method of evolutionary concept analysis was used., Results: A total of 50 pertinent articles were included in our analysis. Utilising inductive thematic analysis, this study identified attributes, antecedents and consequences of sleep disturbances. Important attributes included insomnia, disrupted sleep patterns, altered sleep duration/nocturnal sleep duration and poor sleep quality. Antecedents encompassed factors such as gender, age/grade levels, physical activity, screen time of digital production, mental health issues, COVID-19-related stressors, financial strain and academic stress. Consequences included both mental and physical health implications. By addressing sleep disturbances and promoting better sleep health among students, we can enhance their learning and performance, which could translate to improved patient care outcomes. Additionally, understanding and mitigating sleep disturbances can contribute to the development of a more resilient and effective health care workforce, capable of providing high-quality care even during crises like the COVID-19 pandemic., Patient or Public Contribution: No patient or public contribution., (© 2024 The Author(s). Nursing Open published by John Wiley & Sons Ltd.)

Background: This systematic review synthesized evidence from randomized controlled trials (RCTs) on the effects of integrated behavioral interventions for adults with alcohol use disorder (AUD)., Methods: A comprehensive search of three databases was conducted in 2022, utilizing terms related to alcohol/substance use disorders and integrated interventions. The sample included adults aged ≥18 years at low, moderate, or high risk for AUD, and had at least two other mental health conditions. Only RCTs were included and screened using Covidence. The quality of the study was evaluated using Cochrane risk of bias tool., Results: Across all 11 studies, the total AUD participants were 1543 aged 18 or older. Integrated intervention led to significant reductions in heavy drinking compared to usual care or other interventions. Measures included percent days of alcohol use, grams of alcohol consumed, and increased days of abstinence. Three studies compared integrated treatments with Twelve-Step Facilitation, indicating a better abstinence rate among participants in the integrated group at the end of treatment. Comparisons between delivery modes demonstrated more significant reductions in alcohol consumption with interventionists. Integrated interventions were also compared with various other treatments, including brief intervention, telephone and individual counseling, and psychological education. Participants in the integrated group showed greater improvement in alcohol consumption and depression compared to those in the standalone intervention group., Conclusions: Integrated behavioral interventions effectively reduce alcohol consumption, decrease heavy drinking and promote alcohol abstinence. However, there is limited evidence to determine whether these interventions are more effective than usual care for individuals with AUD., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Surrogate end points are commonly used to estimate treatment efficacy in clinical studies of chronic lymphocytic leukemia (CLL). This patient- and trial-level analysis describes the correlation between progression-free survival (PFS) and minimal residual disease (MRD) with overall survival (OS) in first-line trials for CLL., Patients and Methods: First, patient-level correlation was confirmed using source data from 12 frontline German CLL Study Group (GCLLSG)-trials. Additionally, a joint-frailty copula model was fitted to validate correlation in the setting of targeted therapies (TT). Second, a meta-analysis of first-line phase III trials in CLL from 2008 to 2024 was performed. Treatment effect correlation was quantified from seven GCLLSG and nine published trials, using hazard ratios (HRs) for time-to-event and odds ratios for binary end points., Results: The GCLLSG analysis set comprised 4,237 patients. Patient-level correlation for PFS/OS was strong with Spearman Rho >0.9. The joint-frailty copula indicated a weak correlation for chemotherapy/chemoimmunotherapy (C/CIT) with a tau of 0.52 (95% CI, 0.49 to 0.55) while the correlation was strong for TT (tau, 0.91 [95% CI, 0.89 to 0.93). The meta-analysis set contained a total of 8,065 patients including 5,198 (64%) patients treated with C/CIT and 2,867 (36%) treated with TT. Treatment-effect correlation of the HRs for PFS and OS was R = 0.75 (95% CI, 0.74 to 0.76, R 2 = 0.56) while correlation of end-of-treatment MRD with PFS and OS was R = 0.88 (95% CI, -0.87 to 0.89; R 2 = 0.78) and 0.71 (95% CI, 0.69 to 0.73; R 2 = 0.5), respectively., Conclusion: Patient-level correlation was confirmed in the setting of TTs while treatment-effect correlation between PFS and OS remains uncertain. MRD response status showed a high treatment-effect correlation with PFS but not OS, with the caveat of a limited number of randomized trials with available MRD data.

Long-term data of chronic lymphocytic leukemia (CLL) patients with favorable risk who were treated with fludarabine, cyclophosphamide, and rituximab (FCR) within clinical trials show good efficacy. We here report long-term data collected within the GCLLSG registry. Altogether, 417 CLL patients who received first-line treatment with FCR were analyzed, of which 293 (70.3%) were treated outside of clinical trials. The median observation time from first-line was 95.8 (interquartile range 58.7-126.8) months. Focusing on data of 194 (46.5%) patients who received FCR first-line treatment after 2013 (start of data collection within GCLLSG registry), responses were documented in 85% of the patients, non-responses in 15%, and for 3.6% the assessment was missing. Median event-free survival (EFS, time until disease progression, subsequent treatment, or death) was 60.2 months with a 5-year EFS-rate of 50.6%. Patients with higher-risk disease, characterized by unmutated IGHV (N = 78), had a median EFS of 45.4 months with a 5-year EFS rate of 36.3%, while the median EFS was 77.5 months with a 5-year EFS rate of 60.3% in patients with mutated IGHV (N = 40). Median overall survival was not reached with a 5-year survival rate of 92.7%. In summary, first-line FCR was associated with long EFS, especially in patients exhibiting a mutated IGHV status., (© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Abstract: The phase 2 CLL2-BAAG trial tested the measurable residual disease (MRD)-guided triple combination of acalabrutinib, venetoclax, and obinutuzumab after optional bendamustine debulking in 45 patients with relapsed/refractory chronic lymphocytic leukemia (CLL). MRD was measured by flow cytometry (FCM; undetectable MRD <10-4) in peripheral blood (PB) and circulating tumor DNA (ctDNA) using digital droplet polymerase chain reaction of variable-diversity-joining (VDJ) rearrangements and CLL-related mutations in plasma. The median number of previous treatments was 1 (range, 1-4); 18 patients (40%) had received a Bruton tyrosine kinase inhibitor (BTKi) and/or venetoclax before inclusion, 14 of 44 (31.8%) had TP53 aberrations, and 34 (75.6%) had unmutated immunoglobulin heavy-chain variable region genes. With a median observation time of 36.3 months and all patients off-treatment for a median of 21.9 months, uMRD <10-4 in PB was achieved in 42 of the 45 patients (93.3%) at any time point, including 17 of 18 (94.4%) previously exposed to venetoclax/BTKi and 13 of 14 (92.9%) with TP53 aberrations. The estimated 3-year progression-free and overall survival rates were 85.0% and 93.8%, respectively. Overall, 585 paired FCM/ctDNA samples were analyzed and 18 MRD recurrences (5 with and 13 without clinical progression) occurred after the end of treatment. Twelve samples were first detected by ctDNA, 3 by FCM, and 3 synchronously. In conclusion, time-limited MRD-guided acalabrutinib, venetoclax, and obinutuzumab achieved deep remissions in almost all patients with relapsed/refractory CLL. The addition of ctDNA-based analyses to FCM MRD assessment seems to improve early detection of relapses. This trial was registered at www.clinicaltrials.gov as #NCT03787264., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Abstract: We evaluated the chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) in patients with CLL treated first line with targeted drugs (n = 991) or chemoimmunotherapy (n = 1256). With a median observation time of 40.5 months, the 3-year progression-free survival (PFS) rates for targeted drug-treated patients varied by CLL-IPI risk group: 96.5% (low), 87.6% (intermediate), 82.4% (high), and 78.7% (very high). Differences between consecutive CLL-IPI risk groups were observed for intermediate vs low and high vs intermediate, but not very high vs high. CLL-IPI factors β2-microglobulin, immunoglobulin heavy variable (IGHV) status, and TP53 status each retained prognostic value for PFS. The 3-year overall survival (OS) rates by CLL-IPI risk groups were 100%, 96%, 93.9%, and 89.4%, respectively, with no differences between consecutive risk groups. Age, Binet stage, β2-microglobulin, and TP53 status each retained prognostic value for OS. In chemoimmunotherapy patients (median observation time, 66.9 months), 3-year PFS rates for CLL-IPI risk groups were 78.1%, 51.4%, 40.1%, and 16.5%, respectively; corresponding 3-year OS rates were 97.4%, 93.1%, 81.8%, and 57.3%. In a matched-pair analysis, PFS differences in targeted therapies (n = 812) vs chemoimmunotherapy (n = 812) across all risk groups and OS differences in all but patients at low risk were demonstrated. The CLL-IPI maintains its prognostic value in predicting PFS outcomes with targeted drugs, but its impact in predicting survival appears diminished. Targeted therapies showed enhanced outcomes over chemoimmunotherapy, highlighting their effectiveness across various risk groups. Our findings support ongoing assessment of prognostic tools in CLL treatment evolution. These trials were registered at www.ClinicalTrials.gov as #NCT02345863, #NCT02401503, #NCT02689141, #NCT02445131, #NCT02758665, #NCT02950051, #NCT02242942, #NCT00262782, #NCT00281918, and #NCT01010061., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Leadership development, career advancement, and collaboration among scholars are essential to nurturing nursing research excellence and sustainability. The Midwest Nursing Research Society (MNRS) has incorporated several strategies to advance nursing science and to increase the pool of future nurse leaders. In this article, we describe the process, activities, and outcomes of the Leadership Academy (LA), an innovative initiative from MNRS developed to identify, engage, and nurture future generations of leaders., Methods: For the LA 2022 to 2023 period, the MNRS leaders selected a cohort of 5 nurse scholars and engaged them in activities to develop, enhance, and advance their leadership skills. By following the LA purposes, the cohort participated in monthly meetings with MNRS leaders, received individual mentoring sessions, assessed strengths and areas for further development, attended seminars, participated in a book club, and implemented a cohort project that focused on the promotion and support of early career scholars., Results: Outcomes showed increased knowledge about organizational governance, direction, and resource development; leadership confidence culminating with leadership positions inside and outside MNRS; career development plans; engagement with board members, and enhanced networking. Moreover, the cohort members planned and executed a well-attended conference special session that engaged a large group of scholars to discuss challenges and opportunities for career development at the MNRS Annual Conference., Conclusion: The MNRS LA is a thriving organizational initiative that promotes engagement and leadership skills development thereby increasing the pool of candidates confidently prepared to lead the nursing profession., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In the primary analysis report of the GAIA/CLL13 trial, we found that venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib improved undetectable measurable residual disease (MRD) rates and progression-free survival compared with chemoimmunotherapy in patients with previously untreated chronic lymphocytic leukaemia. However, to our knowledge, no data on direct comparisons of different venetoclax-based combinations are available., Methods: GAIA/CLL13 is an open-label, randomised, phase 3 study conducted at 159 sites in ten countries in Europe and the Middle East. Eligible patients were aged 18 years or older, with a life expectancy of at least 6 months, an Eastern Cooperative Oncology group performance status of 0-2, a cumulative illness rating scale score of 6 or lower or a single score of 4 or lower, and no TP53 aberrations. Patients were randomly assigned (1:1:1:1), with a computer-generated list stratified by age, Binet stage, and regional study group, to either chemoimmunotherapy, venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. All treatments were administered in 28-day cycles. Patients in the chemoimmunotherapy group received six cycles of treatment, with patients older than 65 years receiving intravenous bendamustine (90 mg/m 2 , days 1-2), whereas patients aged 65 years or younger received intravenous fludarabine (25 mg/m 2 , days 1-3) and intravenous cyclophosphamide (250 mg/m 2 , days 1-3). Intravenous rituximab (375 mg/m 2 , day 1 of cycle 1; 500 mg/m 2 , day 1 of cycles 2-6) was added to chemotherapy. In the experimental groups, patients received daily venetoclax (400 mg orally) for ten cycles after a 5-week ramp-up phase starting on day 22 of cycle 1. In the venetoclax-rituximab group, intravenous rituximab (375 mg/m 2 , day 1 of cycle 1; 500 mg/m 2 , day 1 of cycles 2-6) was added. In the obinutuzumab-containing groups, obinutuzumab was added (cycle 1: 100 mg on day 1, 900 mg on day 2, and 1000 mg on days 8 and 15; cycles 2-6: 1000 mg on day 1). In the venetoclax-obinutuzumab-ibrutinib group, daily ibrutinib (420 mg orally, from day 1 of cycle 1) was added until undetectable MRD was reached in two consecutive measurements (3 months apart) or until cycle 36. The planned treatment duration was six cycles in the chemoimmunotherapy group, 12 cycles in the venetoclax-rituximab and the venetoclax-obinutuzumab group and between 12 and 36 cycles in the venetoclax-obinutuzumab-ibrutinib group. Coprimary endpoints were the undetectable MRD rate in peripheral blood at month 15 for the comparison of venetoclax-obinutuzumab versus standard chemoimmunotherapy and investigator-assessed progression-free survival for the comparison of venetoclax-obinutuzumab-ibrutinib versus standard chemoimmunotherapy, both analysed in the intention-to-treat population (ie, all patients randomly assigned to treatment) with a split α of 0·025 for each coprimary endpoint. Both coprimary endpoints have been reported elsewhere. Here we report a post-hoc exploratory analysis of updated progression-free survival results after a 4-year follow-up of our study population. Safety analyses included all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT02950051, recruitment is complete, and all patients are off study treatment., Findings: Between Dec 13, 2016, and Oct 13, 2019, 1080 patients were screened and 926 were randomly assigned to treatment (chemoimmunotherapy group n=229; venetoclax-rituximab group n=237; venetoclax-obinutuzumab group n=229; and venetoclax-obinutuzumab-ibrutinib group n=231); mean age 60·8 years (SD 10·2), 259 (28%) of 926 patients were female, and 667 (72%) were male (data on race and ethnicity are not reported). At data cutoff for this exploratory follow-up analysis (Jan 31, 2023; median follow-up 50·7 months [IQR 44·6-57·9]), patients in the venetoclax-obinutuzumab group had significantly longer progression-free survival than those in the chemoimmunotherapy group (hazard ratio [HR] 0·47 [97·5% CI 0·32-0·69], p<0·0001) and the venetoclax-rituximab group (0·57 [0·38-0·84], p=0·0011). The venetoclax-obinutuzumab-ibrutinib group also had a significantly longer progression-free survival than the chemoimmunotherapy group (0·30 [0·19-0·47]; p<0·0001) and the venetoclax-rituximab group (0·38 [0·24-0·59]; p<0·0001). There was no difference in progression-free survival between the venetoclax-obinutuzumab-ibrutinib and venetoclax-obinutuzumab groups (0·63 [0·39-1·02]; p=0·031), and the proportional hazards assumption was not met for the comparison between the venetoclax-rituximab group versus the chemoimmunotherapy group (log-rank p=0·10). The estimated 4-year progression-free survival rate was 85·5% (97·5% CI 79·9-91·1; 37 [16%] events) in the venetoclax-obinutuzumab-ibrutinib group, 81·8% (75·8-87·8; 55 [24%] events) in the venetoclax-obinutuzumab group, 70·1% (63·0-77·3; 84 [35%] events) in the venetoclax-rituximab group, and 62·0% (54·4-69·7; 90 [39%] events) in the chemoimmunotherapy group. The most common grade 3 or worse treatment-related adverse event was neutropenia (114 [53%] of 216 patients in the chemoimmunotherapy group, 109 [46%] of 237 in the venetoclax-rituximab group, 127 [56%] of 228 in the venetoclax-obinutuzumab group, and 112 [48%] of 231 in the venetoclax-obinutuzumab-ibrutinib group). Deaths determined to be associated with study treatment by the investigator occurred in three (1%) patients in the chemoimmunotherapy group (n=1 due to each of sepsis, metastatic squamous cell carcinoma, and Richter's syndrome), none in the venetoclax-rituximab and venetoclax-obinutuzumab groups, and four (2%) in the venetoclax-obinutuzumab-ibrutinib group (n=1 due to each of acute myeloid leukaemia, fungal encephalitis, small-cell lung cancer, and toxic leukoencephalopathy)., Interpretation: With more than 4 years of follow-up, venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib significantly extended progression-free survival compared with both chemoimmunotherapy and venetoclax-rituximab in previously untreated, fit patients with chronic lymphocytic leukaemia, thereby supporting their use and further evaluation in this patient group, while still considering the higher toxicities observed with the triple combination., Funding: AbbVie, Janssen, and F Hoffmann-La Roche., Competing Interests: Declaration of interests MF reports research funding from AbbVie, AstraZeneca, BeiGene, Janssen, and Roche, and honoraria from AbbVie. JvT reports honoraria from AbbVie, BeiGene, Amgen, AstraZeneca, Janssen, Lilly, and Roche; travel grants from AbbVie, AstraZeneca, BeiGene, Roche, Lilly, and Janssen; and has received consulting fees from and participated on advisory boards for AbbVe, BeiGene, Amgen, and AstraZeneca. MG has received honoraria for participation in symposia and advisory boards from AbbVie, Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb (BMS)/Celgene, GSK, Novartis, Incyte, Janssen-Cilag, Jazz, Roche, Pfizer, Sanofi, and Servier; travel support from AbbVie, BeiGene, Pfizer, and Roche; all fees went to their institution. GJ has received honoraria from Astellas and AbbVie and participated on advisory boards for AbbVie and Servier. M-DL reports travel grants from AbbVie and Janssen. CdC-B reports consulting fees from Janssen, honoraria for lectures from Octapharma, support for attending meetings from AbbVie and Octapharma, and participation on advisory boards for Janssen, BeiGene, and AstraZeneca. CSchn reports speakers fees from AstraZeneca and AbbVie, travel support from AbbVie, and participation on an advisory board for Janssen. RB reports travel support from BeiGene, Janssen, and AbbVie, and honoraria for participation on an advisory board from AbbVie. TN reports honoraria for lectures or presentations and has participated at advisory boards from AbbVie, Roche, AstraZeneca, Gilead, BeiGene, and Janssen. CBP is the chairman of the Danish CLL group. HF reports research funding from Sanofi, Novartis, and Alexion and honoraria for lectures from Sanofi. NK reports research funding from AstraZeneca; honoraria from AbbVie, AstraZeneca, Kite/Gilead, BMS, and Lilly; and travel support from AbbVie, AstraZeneca, BeiGene, Lilly, and Janssen; and participation on advisory boards for AstraZeneca and Janssen. JD reports consulting fees, honoraria, and travel support from AbbVie and Janssen. SB reports honoraria from and participation on speakers bureaus for Roche, Janssen, AbbVie, AstraZeneca, and Sanofi; travel support from Janssen, BeiGene, and Roche; and research funding from Janssen and Miltenyi. FS reports speakers fees from AstraZeneca, travel support from Lilly, and research funding from AstraZeneca. A-MF reports research funding and honoraria from AstraZeneca and travel support from AbbVie. KF reports research grants from AbbVie and Roche, honoraria for advisory boards from AstraZeneca, and travel support from Roche. K-AK reports consulting fees, participation on speakers bureaus, and research funding from Roche, AbbVie, and Janssen. MR reports honoraria from Janssen, Roche, and AstraZeneca; consulting fees from Roche, Janssen, AstraZeneca, and AbbVie; research funding from AbbVie and Roche, and travel support from AstraZeneca. MBr reports research funding and consulting fees from Amgen; honoraria for speakers bureaus from Amgen, Becton Dickinson, Janssen, and Pfizer; travel support from Janssen; and participation on advisory boards for Incyte and Amgen. ET reports participation on advisory boards and honoraria from AbbVie, Janssen-Cilag, and BeiGene, AstraZeneca, and Roche; and travel support from AstraZeneca, AbbVie, BeiGene, Janssen. SS reports honoraria from AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann-La Roche, Janssen, Novartis, and Sunesis; research funding from AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann-La Roche, Janssen, Novartis, and Sunesis; travel support from AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann-La Roche, Janssen, Novartis, Sunesis; and speaker fees from AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann-La Roche, Janssen, Novartis, and Sunesis. MH reports consulting fees from Roche, Gilead, Janssen, BMS, AbbVie, and AstraZeneca and honoraria from Roche, Gilead, Janssen, BMS, AbbVie, and AstraZeneca. APK reports honoraria from AbbVie, AstraZeneca, BMS, Janssen, LAVA, and Roche/Genentech; travel grants from AbbVie and Janssen; research funding from AstraZeneca, Janssen, Roche/Genentech, AbbVie, and BMS. CUN reports research funding from Octapharma and AstraZeneca; consultancy and speaker fees from AbbVie, AstraZeneca, Janssen, Genmab, BeiGene, Octapharma, CSL Behring, Takeda, Lilly, and MSD; and participation on advisory boards for AstraZeneca, MSD, Genmab, and Janssen. BE reports consulting fees fromJanssen, AbbVie, Gilead, AstraZeneca, MSD, BeiGene, and Lilly; participation on speakers bureau for Roche, AbbVie, BeiGene, AstraZeneca, and MSD; honoraria from Roche, AbbVie, AstraZeneca, BeiGene, and MSD; research funding from Janssen, Gilead, Roche, AbbVie, BeiGene, and AstraZeneca; and travel support from BeiGene. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Shift workers support critical 24-hr operations; their health can be impaired by disrupted circadian rhythms and dysfunctional sleep. Shift work sleep disorder (SWSD) is a prevalent condition with significant psychological consequences. Nurse leaders have not yet implemented effective policies to prevent SWSD and optimize shift workers' mental health. The purpose of this integrative review was to examine research about SWSD within the context of neurobiological, sociological, and psychological perspectives that can inform policy changes. The Centers for Disease Control and Prevention Policy Analytic Framework was used to determine the priority recommendations. A search of three databases provided 19 research articles about SWSD and mental health, which illustrated how SWSD is common around the world in many occupations. Backward-rotating schedules and quick returns were risk factors for SWSD. In addition, SWSD was associated with circadian languidity, sleep reactivity, depressive symptoms, and anxiety. Collectively, the studies lacked objective measures of sleep and circadian rhythms, which has hindered the ability to devise interventions that will target the neurobiological causes of SWSD. The research also lacked attention to important sociological factors, such as workers' pay and benefits. Using these findings, nurse leaders can contribute to public policy reforms that increase funding for more rigorous SWSD research. Lawmakers should be advised by nurse leaders to enforce new regulations that provide incentives for employers to create healthier workplaces, such as prohibiting the overuse of schedules that make employees vulnerable to SWSD and providing funds for interventions to prevent SWSD and support mental health.

Background: Heart surgery is an effective intervention for managing heart disease, the leading cause of death globally. After surgery, physical activity is key to improving patients' quality of life and decreasing mortality, but patients are frequently physically inactive after heart surgery., Objective: This cross-sectional pilot study aimed to examine how psychosocial and sleep factors influenced physical activity in patients after heart surgery. The mediating role of sleep factors between psychosocial factors and physical activity was also examined., Methods: Thirty-three patients who had undergone heart surgery were recruited. Psychosocial and sleep factors and physical activity were measured using an online survey and a wrist-worn ActiGraph for 7 days and nights., Results: The participants had heart surgery an average of about 7 years previously. They exceeded the recommended 150 minutes per week of moderate-intensity physical activity for Americans; however, 64% of them showed poor sleep quality (Pittsburgh Sleep Quality Index >5). Higher anxiety and depressive symptoms, lower self-efficacy, and greater sleep disturbances were associated with lower physical activity. Moreover, self-efficacy, sleep duration, sleep disturbance, sleep efficiency, and wake after sleep onset were predictors for physical activity. No mediating role of sleep factors was observed between psychosocial factors and physical activity., Conclusions: Psychosocial and sleep factors should be considered when developing and implementing physical activity strategies for patients after heart surgery. Researchers should examine the relationships among the study variables with larger samples of postsurgical cardiac patients during different periods after heart surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.R. received honoraria from Eli Lilly. Other authors declare that there is no conflict of interest.

Objective: Preventing severe COVID-19 remains a priority globally, particularly in the immunocompromised population. As shown in healthy individuals, immunity against SARS-CoV-2 can be yielded by previous infection, vaccination, or both (hybrid immunity). The objective of this observation study was to investigate hybrid immunity in patients with chronic lymphocytic leukemia (CLL)., Methods/results: Blood samples of six patients with CLL were collected 55 days after fourth COVID-19 vaccination. All patients had a SARS-CoV-2 infection within 12 months before the second booster (fourth vaccination). SARS-CoV-2 spike receptor binding domain (RBD)-specific IgG antibodies were detectable in 6/6 (100.0%) CLL patients after four compared to 4/6 (66.7%) after three vaccinations. The median number of SARS-CoV-2 spike-specific T cells after repeated booster vaccination plus infection was 166 spot-forming cells (SFC) per million peripheral blood mononuclear cells. Overall, 5/5 (100%) studied patients showed a detectable increase in T cell activity., Conclusion: Our data reveal an increase of cellular and humoral immune response in CLL patients after fourth COVID-19 vaccination combined with SARS-CoV-2 infection, even in those undergoing B cell-depleting treatment. Patients with prior vaccination failure now show a specific IgG response. Future research should explore the duration and effectiveness of hybrid immunity considering various factors like past infection and vaccination rates, types and numbers of doses, and emerging variants., (© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: Maintaining physical activity is challenging after cardiac surgery. Postsurgical cardiac patients often experience sleep problems showing a reciprocal interaction with physical activity. As sleep and physical activity show day-to-day variations, their daily relationships need to be assessed. However, no studies have examined daily sleep-physical activity relationships in postsurgical cardiac patients., Objectives: This study aimed to examine the effects of daily sleep factors on daily physical activity after cardiac surgery., Methods: Among 33 patients who underwent cardiac surgery at least 10 weeks earlier, 5 sleep and 4 physical activity variables were measured using a wrist-worn ActiGraph for 7 days. Mixed-effects models were applied for data analyses., Results: Most participants were male (57.6 %), non-Hispanic whites (63.6 %) who had coronary artery bypass graft surgery (54.6 %). Participants averaged 60.8 ± 10.1 years of age and 85.7 ± 91.2 months since surgery. They slept for an average of 385.6 ± 74.6 min (6.4 ± 1.2 h). Among sleep factors, greater number of awakenings (NOA) predicted lower next-day sedentary time. Higher sleep efficiency (SE) was associated with lower next-day sedentary time when not controlling for covariates. Among the psychosocial, demographic, and clinical covariates, higher comorbidity index was associated with fewer kcals expended, less daily moderate-to-vigorous physical activity, and more daily sedentary time., Conclusions: Daily SE and NOA and individual health status, including comorbidity, should be assessed over time to support improvement of daily physical activity after cardiac surgery. Researchers should examine the relationship between NOA and next-day sedentary time with larger samples. Such research should address multiple psychosocial, demographic, and clinical factors and the potential mediating role of sleep., Competing Interests: Declaration of competing interest S.R. received honoraria from Eli Lilly. Other authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Noncommunicable diseases (NCD), such as obesity, diabetes, and cardiovascular disease, are defining healthcare challenges of the 21st century. Medical infrastructure, which for decades sought to reduce the incidence and severity of communicable diseases, has proven insufficient in meeting the intensive, long-term monitoring needs of many NCD disease patient groups. In addition, existing portable devices with rigid electronics are still limited in clinical use due to unreliable data, limited functionality, and lack of continuous measurement ability. Here, a wearable system for at-home cardiovascular monitoring of postpartum women-a group with urgently unmet NCD needs in the United States-using a cloud-integrated soft sternal device with conformal nanomembrane sensors is introduced. A supporting mobile application provides device data to a custom cloud architecture for real-time waveform analytics, including medical device-grade blood pressure prediction via deep learning, and shares the results with both patient and clinician to complete a robust and highly scalable remote monitoring ecosystem. Validated in a month-long clinical study with 20 postpartum Black women, the system demonstrates its ability to remotely monitor existing disease progression, stratify patient risk, and augment clinical decision-making by informing interventions for groups whose healthcare needs otherwise remain unmet in standard clinical practice., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

We use Fawcett and DeSanto-Madeya's framework to critique Fisher and Fisher's information-motivation-behavioral skills model and determine its usefulness and applicability for nursing. Our analysis and evaluation show that the model is a parsimonious and useful situation-specific theory for guiding nursing research and practice because it shows good fit with the nursing context, has social and theoretical significance, and exhibits empirical and pragmatic adequacy. More consistency in using terms referring to each concept would help to improve the model's internal consistency. The model's testability could also be improved by measuring health outcomes (eg, viral load or CD4 count) in future research., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

In patients with chronic lymphocytic leukemia, Richter transformation (RT) reflects the development of an aggressive lymphoma that is associated with poor response to chemotherapy and short survival. We initiated an international, investigator-initiated, prospective, open-label phase 2 study in which patients with RT received a combination of the PD-1 inhibitor tislelizumab plus the BTK inhibitor zanubrutinib for 12 cycles. Patients responding to treatment underwent maintenance treatment with both agents. The primary end point was overall response rate after six cycles. Of 59 enrolled patients, 48 patients received at least two cycles of treatment and comprised the analysis population according to the study protocol. The median observation time was 13.9 months, the median age was 67 (range 45-82) years. Ten patients (20.8%) had received previous RT-directed therapy. In total, 28 out of 48 patients responded to induction therapy with an overall response rate of 58.3% (95% confidence interval (CI) 43.2-72.4), including 9 (18.8%) complete reponse and 19 (39.6%) partial response, meeting the study's primary end point by rejecting the predefined null hypothesis of 40% (P = 0.008). Secondary end points included duration of response, progression-free survival and overall survival. The median duration of response was not reached, the median progression-free survival was 10.0 months (95% CI 3.8-16.3). Median overall survival was not reached with a 12-month overall survival rate of 74.7% (95% CI 58.4-91.0). The most common adverse events were infections (18.0%), gastrointestinal disorders (13.0%) and hematological toxicities (11.4%). These data suggest that combined checkpoint and BTK inhibition by tislelizumab plus zanubrutinib is an effective and well-tolerated treatment strategy for patients with RT. ClinicalTrials.gov Identifier: NCT04271956 ., (© 2023. The Author(s).)

Sleep disturbances are serious issues in individuals with end stage kidney disease because they are associated with worsening kidney function and other negative health outcomes, especially in older adults. Our analysis aimed to provide clinicians with the conceptual clarity required for managing sleep disturbances in older patients who are receiving dialysis. A literature review revealed three attributes that define this population's sleep disturbances: sleep initiation and maintenance difficulties, restless sleep and short sleep, and abnormal breathing during sleep. Con sidering the serious consequences and correlates of sleep disturbances in older patients who are receiving dialysis, tailored interventions are needed to improve their sleep. Our literature review, concept analysis, and case studies provide key information for designing future mechanistic, clinical-translational, and interventional research., Competing Interests: The authors reported no actual or potential conflict of interest in relation to this nursing continuing professional development (NCPD) activity., (Copyright© by the American Nephrology Nurses Association.)

Idelalisib in combination with rituximab is an efficacious treatment for patients suffering from chronic lymphocytic leukemia (CLL) with known limitations due to toxicities. However, the benefit after prior Bruton tyrosine kinase inhibitor (BTKi) therapy remains unclear. For this analysis, 81 patients included in a non-interventional registry study of the German CLL study group (registered at www.clinicaltrials.gov as # NCT02863692) meeting the predefined criteria of a confirmed diagnosis of CLL and being treated with idelalisib containing regimens outside clinical trials were considered. 11 patients were treatment naïve (13.6%) and 70 patients (86.4%) pretreated. Patients had median of one prior therapy line (range 0-11). Median treatment duration with idelalisib was 5.1 months (range 0-55.0 months). Of 58 patients with documented treatment outcome, 39 responded to idelalisib containing therapy (67.2%). Patients treated with the BTKi ibrutinib as last prior treatment prior to idelalisib responded in 71.4% compared to a response rate of 61.9% in patients without prior ibrutinib. Median event free survival (EFS) was 15.9 months with a 16 versus 14 months EFS in patients with ibrutinib as last prior treatment or not, respectively. Median overall survival was 46.6 months. In conclusion, treatment with idelalisib appears to have a valuable impact in patients being refractory to prior ibrutinib therapy even though there are limitations in our analysis due to the low number of patients included., (© 2023. The Author(s).)

Asian family caregivers of older adults with dementia have stressful caregiving situations over long periods; they must become resilient to recover from adversity. A conceptual definition of resilience specific to Asian family caregivers is important for understanding their caregiving phenomena and the relationships with mental health and psychological well-being. The purpose of this concept analysis was to define resilience in family caregivers of Asian older adults with dementia using Walker and Avant's method. The findings of the analysis will guide future research about the modifiable factors that will prevent negative health outcomes in this population of caregivers., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The final analysis of the open-label, multicenter phase 2 CLL2-GIVe trial shows response and tolerability of the triple combination of obinutuzumab, ibrutinib, and venetoclax (GIVe regimen) in 41 previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) with del(17p) and/or TP53 mutation. Induction consisted of 6 cycles of GIVe; venetoclax and ibrutinib were continued up to cycle 12 as consolidation. Ibrutinib was given until cycle 15 or up to cycle 36 in patients not achieving a complete response and with detectable minimal residual disease. The primary end point was the complete remission rate at cycle 15, which was achieved at 58.5% (95% CI, 42.1-73.7; P < .001). The last patient reached the end of the study in January 2022. After a median observation time of 38.4 months (range, 3.7-44.9), the 36-month progression-free survival was 79.9%, and the 36-month overall survival was 92.6%. Only 6 patients continued ibrutinib maintenance. Adverse events of concern were neutropenia (48.8%, grade ≥3) and infections (19.5%, grade ≥3). Cardiovascular toxicity grade 3 occurred as atrial fibrillation at a rate of 2.4% between cycles 1 and 12, as well as hypertension (4.9%) between cycles 1 and 6. The incidence of adverse events of any grade and grade ≥3 was highest during induction and decreased over time. Progressive disease was observed in 7 patients between cycles 27 and 42. In conclusion, the CLL2-GIVe regimen is a promising fixed-duration, first-line treatment for patients with high-risk CLL with a manageable safety profile., (© 2023 by The American Society of Hematology.)

Complex karyotypes have been associated with inferior outcomes in chronic lymphocytic leukemia (CLL) treated with chemoimmunotherapy (CIT), whereas their prognostic impact in the context of venetoclax-based treatments is still debated. In this prospective analysis on karyotype complexity in CLL, we evaluated the impact of complex (≥3 chromosomal aberrations [CAs], CKTs) and highly complex karyotypes (≥5 CAs; hCKTs) as well as specific aberrations in previously untreated patients without TP53 aberrations undergoing either CIT or time-limited venetoclax-based therapies in the phase 3 GAIA/CLL13 trial. Karyotype analyses were available for 895 of 926 patients (96.7%), of whom 153 (17%) had a CKT and 43 (5%) hCKT. In the CIT arm, CKT was associated with shorter progression-free survival (PFS) (hazard ratio [HR] 2.58; 95% confidence interval [95% CI], 1.54-4.32; P < .001) and overall survival (HR, 3.25; 95% CI, 1.03-10.26; P = .044). In the pooled venetoclax arms, a multivariable analysis identified hCKTs (HR, 1.96; 95% CI, 1.03-3.72; P = .041), but not CKTs, as independent adverse prognosticators for PFS. The presence of translocations (unbalanced and/or balanced) was also independently associated with shorter PFSs in the venetoclax arms. CIT led to the acquisition of additional CAs (mean CAs, 2.0-3.4; from baseline to CLL progression), whereas karyotype complexity remained stable after venetoclax-based treatments (2.0, both time points). This analysis establishes highly complex karyotypes and translocations as adverse prognostic factors in the context of venetoclax-based combination treatments. The findings of this study support the incorporation of karyotyping into the standard diagnostic workup of CLL, because it identifies patients at high risk of poor treatment outcomes and thereby improves prognostication. This trial was registered at www.clinicaltrials.gov as #NCT02950051., (© 2023 by The American Society of Hematology.)

Background: Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking., Methods: In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, <10 -4 [i.e., <1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival., Results: A total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax-rituximab, 229 to venetoclax-obinutuzumab, and 231 to venetoclax-obinutuzumab-ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax-obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44.4 to 59.5; P<0.001 for both comparisons), but it was not significantly higher in the venetoclax-rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P = 0.32). Three-year progression-free survival was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P<0.001). Progression-free survival at 3 years was also higher with venetoclax-obinutuzumab (87.7%; hazard ratio for disease progression or death, 0.42; 97.5% CI, 0.26 to 0.68; P<0.001), but not with venetoclax-rituximab (80.8%; hazard ratio, 0.79; 97.5% CI, 0.53 to 1.18; P = 0.18). Grade 3 and grade 4 infections were more common with chemoimmunotherapy (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%)., Conclusions: Venetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL. (Funded by AbbVie and others; GAIA-CLL13 ClinicalTrials.gov number, NCT02950051; EudraCT number, 2015-004936-36.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Critical thinking is an essential nursing competency. Faculty can teach students how to think critically by emphasizing the connections between their philosophy and nursing curricula to ensure that students recognize the cognitive processes they use to make complex decisions., Purpose: The purpose of this article is to examine the definitions, history, and utility of philosophical perspectives that inform critical thinking. We explain several approaches: Socratic inquiry, syllogism, schematic cases, and symbolism., Methods: We conducted a narrative review about educational approaches and their associated philosophies., Results: Philosophical awareness can enhance students' abilities to examine data, communicate ideas, evaluate diverse opinions, understand theories, and apply innovative solutions to problems they will encounter in clinical practice., Conclusions: Clinical issue dialogues, dramatizations (that link philosophical and practical themes), self-reflection exercises, and case studies (that are less content-laden and more focused on nurses' theories and decision-making processes) represent important and innovative critical thinking skill-building exercises., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Data on long-term outcomes and biological drivers associated with depth of remission after BCL2 inhibition by venetoclax in the treatment of chronic lymphocytic leukemia (CLL) are limited. In this open-label parallel-group phase-3 study, 432 patients with previously untreated CLL were randomized (1:1) to receive either 1-year venetoclax-obinutuzumab (Ven-Obi, 216 patients) or chlorambucil-Obi (Clb-Obi, 216 patients) therapy (NCT02242942). The primary endpoint was investigator-assessed progression-free survival (PFS); secondary endpoints included minimal residual disease (MRD) and overall survival. RNA sequencing of CD19-enriched blood was conducted for exploratory post-hoc analyses. After a median follow-up of 65.4 months, PFS is significantly superior for Ven-Obi compared to Clb-Obi (Hazard ratio [HR] 0.35 [95% CI 0.26-0.46], p < 0.0001). At 5 years after randomization, the estimated PFS rate is 62.6% after Ven-Obi and 27.0% after Clb-Obi. In both arms, MRD status at the end of therapy is associated with longer PFS. MRD + ( ≥ 10 -4 ) status is associated with increased expression of multi-drug resistance gene ABCB1 (MDR1), whereas MRD6 (< 10 -6 ) is associated with BCL2L11 (BIM) expression. Inflammatory response pathways are enriched in MRD+ patient solely in the Ven-Obi arm. These data indicate sustained long-term efficacy of fixed-duration Ven-Obi in patients with previously untreated CLL. The distinct transcriptomic profile of MRD+ status suggests possible biological vulnerabilities., (© 2023. The Author(s).)

Aim: We analysed nurses' experiences during military conflicts since World War II., Background: Nurses have successfully reduced morbidity and mortality in populations affected by wars; despite centuries of nurses' global involvement in wars, there is limited knowledge about their experiences., Method: We used Rodger's evolutionary concept analysis methodology to understand the antecedents, attributes, consequences, context and implications of nurses' war-related experiences. We analysed data from quantitative and qualitative research, media reports, editorials, historical reviews and published accounts of nurses' experiences in many locations, including Afghanistan, Bosnia, Croatia, Korea, Kosovo, Iran, Iraq, Israel, Palestine, Russia, Somalia, Ukraine and Vietnam., Findings: Two antecedent conditions preceded nurses' war involvement: actively responding to human suffering and having resources for readiness. Nurses were defined by five attributes: sacrifice, resourcefulness, tunnel-vision, survival mindset and comradery. We also found evidence for seven consequences; nurses saved lives (reduced morbidity and mortality), however, some nurses faced professional burnout/disillusionment, restricted practice authority, isolation and post-traumatic stress after war. In addition, growth and pacifism were consequences for some nurses who were exposed to war., Conclusion: The findings of our concept analysis illustrate how nurses have fulfilled critical life-saving roles, but some nurses' post-war experiences were debilitating, stigmatized and unsupported. We conclude that research about the resourcefulness, innovations and resiliency nurses have developed during wars is essential, and professional support mechanisms must be developed to prevent post-traumatic stress, burnout and attrition from the profession. Governments can use utilize the knowledge nurses developed during wars to expand emergency preparedness skillsets and promote nurses as the leaders of international efforts to promote peace., No Patient or Public Contribution: Patients, service users, caregivers and members of the public were not involved in conducting this concept analysis or preparing the manuscript., Impact Statement: By understanding nurses' involvement with post-WWII conflicts, we have demonstrated the significant public health contributions, challenges and personal and professional growth experienced by nurses. Nurses' war-related knowledge should be utilized to innovate healthcare practices during disasters and to advise policymakers in developing, implementing and evaluating peace-promoting operations., (© 2022 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Background: South Asians comprise 20% of the world population. There is a high prevalence of cardiovascular diseases among South Asians, and sleep disorders may be a key risk factor., Objective: The review examined literature about cardiovascular and sleep disorders in South Asian countries and in the United States, United Kingdom, Canada, and the Netherlands., Methods: Methods from Arksey and O'Malley's framework and Peter et al. were used to synthesize findings from 23 research studies., Results: The studies addressed sleep disorders with hypertension, heart failure, diabetes, and obesity. Obstructive sleep apnea and short sleep duration were common and associated with cardiovascular morbidity and mortality at early ages in South Asians. Researchers analyzed polysomnography-derived sleep measures, vascular functions, polymorphisms, C-reactive protein levels, public knowledge about cardiovascular health, and sleep-related questionnaire scores. Most studies were conducted in major metropolitan areas; no data were available about people living in locations with limited health care resources. Among migrant South Asians, researchers did not explore the role of acculturation on sleep patterns and cardiovascular outcomes., Conclusions: The review highlights important considerations for researchers who plan to investigate cardiovascular conditions in South Asian communities. There is a need for more knowledge about sleep-related risk factors, and researchers should also examine cultural, political, and socioeconomic factors that affect health care access. This knowledge will be imperative for designing effective and tailored disease prevention strategies for South Asian populations., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)