Predisposing, Precipitating, and Perpetuating Factors of Insomnia in Cancer Survivors.

OBJECTIVES: To explore and characterize predisposing, precipitating, and perpetuating factors of subthreshold, moderate, and severe insomnia in cancer survivors. SAMPLE & SETTING: 135 cancer survivors who self-reported symptom severity on the Insomnia Severity Index during the baseline phase of a randomized clinical trial on insomnia treatment. METHODS & VARIABLES: Participants completed measures assessing predisposing factors (age, sex, race and ethnicity, body mass index), precipitating factors (number of years since cancer diagnosis, depression and anxiety symptoms, health-related quality of life), and perpetuating factors (frequency of consuming alcoholic and caffeinated beverages, napping behavior, dysfunctional beliefs about sleep). RESULTS: In the multivariate model, being female was protective against insomnia, and being a person of color, having higher anxiety, having more depression symptoms, and having stronger dysfunctional beliefs about sleep were significantly associated with greater insomnia severity. IMPLICATIONS FOR NURSING: By fostering interprofessional collaboration and implementing evidence-based interventions, nurses can contribute to the well-being of cancer survivors and address their sleep-related challenges. This study underscores the importance of regular insomnia screenings for cancer survivors, with nurses as essential facilitators.

CHRFAM7A diversifies human immune adaption through Ca2+ signalling and actin cytoskeleton reorganization.

BACKGROUND: Human restricted genes contribute to human specific traits in the immune system. CHRFAM7A, a uniquely human fusion gene, is a negative regulator of the α7 nicotinic acetylcholine receptor (α7 nAChR), the highest Ca2+ conductor of the ACh receptors implicated in innate immunity. Understanding the mechanism of how CHRFAM7A affects the immune system remains unexplored. METHODS: Two model systems are used, human induced pluripotent stem cells (iPSC) and human primary monocytes, to characterize α7 nAChR function, Ca2+ dynamics and decoders to elucidate the pathway from receptor to phenotype. FINDINGS: CHRFAM7A/α7 nAChR is identified as a hypomorphic receptor with mitigated Ca2+ influx and prolonged channel closed state. This shifts the Ca2+ reservoir from the extracellular space to the endoplasmic reticulum (ER) leading to Ca2+ dynamic changes. Ca2+ decoder small GTPase Rac1 is then activated, reorganizing the actin cytoskeleton. Observed actin mediated phenotypes include cellular adhesion, motility, phagocytosis and tissue mechanosensation. INTERPRETATION: CHRFAM7A introduces an additional, human specific, layer to Ca2+ regulation leading to an innate immune gain of function. Through the actin cytoskeleton it drives adaptation to the mechanical properties of the tissue environment leading to an ability to invade previously immune restricted niches. Human genetic diversity predicts profound translational significance as its understanding builds the foundation for successful treatments for infectious diseases, sepsis, and cancer metastasis. FUNDING: This work is supported in part by the Community Foundation for Greater Buffalo (Kinga Szigeti) and in part by NIH grant R01HL163168 (Yongho Bae).

Insomnia and risk of mortality in older adults.

Existing evidence linking insomnia to all-cause mortality in older individuals remains inconclusive. We conducted a retrospective study of a large cohort of veterans aged 65-80 years old identified from the Corporate Data Warehouse, a large data repository derived from the Veterans Health Administration integrated medical records. Veterans' enrollees with and without International Classification of Diseases, Ninth and Tenth Revision, codes corresponding to insomnia diagnosis between 1 January 2010 and 30 March 2019 were assessed for eligibility. The primary outcome was all-cause mortality. A total of 36,269 veterans, 9584 with insomnia and 26,685 without insomnia, were included in the analysis. Baseline mean (SD) age was 72.6 (4.2) years. During a mean follow-up of 6.0 (2.9) years of the propensity score matched sample, the mortality rate was 34.8 [95% confidence interval: 33.2-36.6] deaths per 1000 person-years among patients with insomnia compared with 27.8 [95% confidence interval: 26.6-29.1] among patients without insomnia. In a Cox proportional hazards model, insomnia was significantly associated with higher mortality (hazard ratio: 1.39; [95% confidence interval: 1.27-1.52]). Patients with insomnia also had a higher risk of non-fatal cardiovascular events (hazard ratio: 1.21; [95% confidence interval: 1.06-1.37]). Secondary stratified analyses by sex, race, ethnicity and hypertension showed no evidence of effect modification. A higher risk of mortality (hazard ratio: 1.51; [95% confidence interval: 1.33-1.71]) was observed when depression was present compared with absent (hazard ratio: 1.26; [95% confidence interval: 1.12-1.44]; p = 0.02). In this cohort study, insomnia was associated with increased risk-adjusted mortality and non-fatal cardiovascular events in older individuals.

Emotion differentiation among individuals in a randomized clinical trial for alcohol use disorder: Within- and between-person associations with affect, craving, and alcohol use in daily life.

Emotion differentiation refers to cognitively distinguishing among discrete, same-valenced emotions. Negative emotion differentiation (NED) is a transdiagnostic indicator of emotional functioning. The role of positive emotion differentiation (PED) in clinical disorders, including alcohol use disorder (AUD), is less understood. Further, despite consensus that emotions are highly variable, little is known about within-person fluctuations in NED/PED. The current study leveraged 84 consecutive daily smartphone surveys from participants (N = 181) in a clinical trial of cognitive behavioral therapy for AUD to investigate whether between-person differences in overall NED/PED, or within-person variability in daily NED/PED, were associated with affect intensity, craving, drinking, and heavy drinking in daily life. Subsequent analyses explored whether associations were moderated by baseline alexithymia. At the between-persons level, greater average PED, but not NED, was associated with lower heavy drinking odds. At the within-persons level, higher-than-usual PED was associated with lower negative affect and odds of any drinking. Individuals with baseline alexithymia had stronger negative within-person associations between daily NED and both any and heavy drinking. PED is a skill linked to less alcohol use between- and within-persons irrespective of baseline alexithymia, whereas greater daily NED appears especially important for reduced alcohol use among individuals with co-morbid AUD and alexithymia.

Mechanisms of behavior change during alcohol treatment among negative affect drinkers: A time-varying effect model analysis using 84 consecutive days of ecological momentary assessment.

OBJECTIVE: To better understand the timing and unique contribution of four potential mechanisms of behavior change (MOBC) during alcohol use disorder (AUD) treatment (negative affect, positive affect, alcohol craving, and adaptive alcohol coping), we used a time-varying effect modeling analytic approach to examine the change trajectories of alcohol abstinence, heavy drinking, the hypothesized MOBCs, and the time-varying associations between the MOBCs and alcohol outcomes. METHOD: Participants (N = 181; Mage = 50.8 years, SD = 10.6; 51% women; 93.5% Caucasian) were enrolled in a 12-week randomized clinical trial of cognitive behavioral outpatient treatment program for AUD. For 84 consecutive days, participants provided self-reports of positive and negative affect, craving, alcohol use, and adaptive alcohol coping strategies employed. RESULTS: Throughout the 84-day treatment window, higher daily average craving levels were associated with both decreased likelihood of alcohol abstinence and increased odds of heavy drinking, whereas higher adaptive alcohol coping was associated with increased odds of abstinence and decreased odds of heavy drinking. Higher negative affect was associated with decreased odds of abstinence in the first 10 days of treatment and increased odds of heavy drinking before Day 4 or Day 5. Higher positive affect was associated with decreased odds of heavy drinking during the first 4 or 5 days. CONCLUSIONS: The differential time-varying associations between negative affect, positive affect, alcohol craving, adaptive alcohol coping, and alcohol use provide insights into how and when each of the MOBCs is active during AUD treatment. These findings can help optimize the efficacy of future AUD treatments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Association between sleep health and rates of self-reported medical errors in intern physicians: an ancillary analysis of the Intern Health Study.

STUDY OBJECTIVES: Reduced sleep duration and work hour variability contribute to medical error and physician burnout. This study assesses the relationships between physician performance, burnout, and the dimensions of sleep beyond hours slept. METHODS: This was an ancillary analysis of 3 years of data from an international prospective cohort study: the Intern Health Study. Actigraphy data from 3,654 intern physicians capturing sleep timing, regularity, efficiency, and duration were used individually and combined as a composite sleep health index to measure the association of multidimensional sleep patterns on self-reported medical errors and burnout. RESULTS: From 2017-2019, interns' work hours decreased by 4 hours per week and total sleep time also decreased (6.7 to 5.99 hours), and sleep efficiency, timing, and regularity all worsened (all P < .05). In the 21.2% of participants who committed an error, there was no difference in sleep duration, timing, or regularity. Lower sleep efficiency was associated with higher odds of committing an error (P = .003) and higher burnout scores (P < .001). Although overall sleep quality was poor in the entire cohort, interns in the lowest quintile of sleep duration, regularity, and efficiency had higher burnout scores than those in the best quintile. CONCLUSIONS: Sleep efficiency, not duration, was associated with increased self-reported medical errors and burnout in intern physicians. Overall sleep quality and duration worsened despite fewer hours worked. Future studies on physician burnout should measure all aspects of sleep health. CITATION: Hassinger AB, Velez C, Wang J, Mador MJ, Wilding GE, Mishra A. Association between sleep health and rates of self-reported medical errors in intern physicians: an ancillary analysis of the Intern Health Study. J Clin Sleep Med. 2024;20(2):221-227.

Sleep-wake state discrepancy among cancer survivors with insomnia symptoms.

PURPOSE: To evaluate the discrepancy and correlation between sleep-wake measures (i.e., time in bed (TIB), total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE%)) reported on sleep diary and measured by actigraphy among cancer survivors with insomnia symptoms; and examine the influences of sociodemographic and clinical variables on these measurement differences. METHODS: A heterogenous sample of cancer survivors with insomnia symptoms (n = 120; M age = 63.7 ± 10.1; female = 58.3%) was included. Seven consecutive days of sleep diary and actigraphic data were obtained along with information on demographic, sleep, and mental health symptoms. Bland-Altman plot, Pearson correlation coefficient, concordance correlation coefficient, and mixed linear model approach were used to conduct the analysis. RESULTS: Self-reported TIB, SOL, and WASO were longer than measured by actigraphy (TIB: 8.6 min. (95% CI, 3.7, 13.5; p < .001); SOL: 14.8 min. (95% CI, 9.4, 20.2; p < .0001); and WASO: 20.7 min. (95% CI, 9.4, 20.2; p < .0001), respectively); and self-reported TST and SE% were shorter than measured by actigraphy (TST: 6.8 min. (95% CI, -18.7, 5.13); and SE%: 0.7% (95%CI, -3.0, 2.0), respectively), but were not statistically significant. Sex, higher insomnia severity, and poor sleep quality were associated with discrepancy between several sleep-wake measures. CONCLUSION: Subjective and objective sleep-wake measures may present discrepant finding among cancer survivors with symptoms of insomnia. Future research is needed to validate appropriate sleep-wake assessment, and better understand factors that influence the discrepancy that exists between measures among this population. CLINICAL TRIAL REGISTRATION: Clinical trials identifier: NCT03810365. Date of registration: January 14, 2019.

Association Between Hypnotic Use and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease and Insomnia.

Purpose: Hypnotics are commonly prescribed in patients with COPD to manage insomnia. Given the considerable risks associated with these drugs, the aim of the study was to evaluate the risk of all-cause mortality associated with hypnotics in a cohort of veterans with COPD presenting with insomnia. Methods: We conducted a retrospective cohort study that used Veterans Health Administration Corporate Data Warehouse with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2010 through 2019. The primary outcome was all-cause mortality. Analyses were conducted using propensity score 1:1 matching to balance baseline characteristics. Results: Of the 5759 veterans with COPD (mean [SD] age, 71.7 [11.2]; 92% men), 3585 newly initiated hypnotic agents during the study period. During a mean follow-up of 7.4 (SD, 2.7) years, a total of 2301 deaths occurred, with 65.2 and 48.7 total deaths per 1000 person-years among hypnotic users and nonusers, respectively. After propensity matching, hypnotic use was associated with a 22% increased risk of mortality compared with hypnotic nonusers (hazard ratio [HR] 1.22; 95% confidence interval [CI],1.11-1.35). The benzodiazepine receptor agonists (BZRAs) group experienced a higher incidence rate of all-cause mortality compared to hypnotic nonusers (Incidence rate ratio [IRR] 1.27; 95% CI, 1.14-1.43). Conversely, the mortality rate of non-BZRA hypnotics decreased after the first 2 years and was not significantly different for hypnotic nonusers (IRR 1.04; 95% CI, 0.82-1.11). Conclusion: Among patients with COPD and insomnia, treatment with hypnotics was associated with a higher risk of all-cause mortality. The association was observed in patients prescribed BZRAs. The risk of mortality for non-BZRAs moderated after the first 2 years, indicating a class effect.

Clinical and economic effectiveness of a pharmacy and primary care collaborative transition of care program.

BACKGROUND: Primary care pharmacists are uniquely positioned to improve care quality by intervening within care transitions in the postdischarge period. However, additional evidence is required to demonstrate that pharmacist-led interventions can reduce health care utilization in a cost-effective manner. The study's objective was to evaluate the clinical and economic effectiveness of a pharmacy-led transition of care (TOC) program within a primary care setting. METHODS: This cluster randomized trial was conducted between 2019 and 2021 and included three primary care practices. Eligible patients were ≥18 years of age and at high risk of readmission. The multifaceted pharmacy intervention included medication reconciliation, comprehensive medication review, and patient and provider follow-up. The primary composite endpoint included hospital readmissions and emergency department (ED) visits within 30 days of discharge. Differences in outcomes were modeled using a generalized estimated equations approach and outcomes were assumed to be distributed as a Poisson random variable. A cost-benefit analysis was embedded within the study and estimated economic outcomes from a provider group/health system perspective. Cost measures included: net benefit, benefit to cost ratio (BCR), and return on investment (ROI). RESULTS: Of 300 eligible patients, 36 were in the intervention group and 264 in the control group. The intervention significantly reduced the primary composite outcome of all-cause readmissions and ED visits within 30 days (adjusted incidence rate ratio [aIRR], 0.54; 95% CI, 0.44-0.66; P < 0.001). There were significant reductions in both 30-day all-cause readmissions (aIRR, 0.64; 95% CI, 0.60-0.67; P < 0.001) and ED visits (aIRR, 0.25; 95% CI, 0.20, 0.31; P < 0.001) between groups. The net benefit of the intervention was $9,078, with a BCR of 2.11 and a ROI of 111%. Sensitivity analyses were robust to changes in economic inputs. CONCLUSION: This care transition program had positive clinical and economic benefits, providing further support for the essential role pharmacists demonstrate in providing TOC services.

Predictors of successful treatment of respiratory distress with aerosolized calfactant.

INTRODUCTION: Predictors for successful aerosolized surfactant treatment are not well defined. OBJECTIVE: To identify predictors for successful treatment in the AERO-02 trial and the AERO-03 expanded access program. METHODS: Neonates receiving nasal continuous positive airway pressure (NCPAP) at the time of first aerosolized calfactant administration were included in this analysis. Associations between demographic and clinical predictors to need for intubation were examined using univariate testing and multivariate logistic regression analyses. RESULTS: Three hundred and eighty infants were included in the study. Overall, 24% required rescue by intubation. Multivariate modeling revealed that the predictors of successful treatment were a gestational age ≥31 weeks, a respiratory severity score (RSS) of <1.9, and <2 previous aerosol treatments. CONCLUSION: Gestational age, number of aerosols, and RSS are predictive of successful treatment. These criteria will help select patients most likely to benefit from aerosolized surfactant.

The risk of major adverse cardiovascular events associated with the use of hypnotics in patients with insomnia.

OBJECTIVES: To examine whether hypnotic use in patients with insomnia reduces major adverse cardiovascular events, including all-cause mortality and nonfatal major adverse cardiovascular events. METHODS: Using the Veterans Affairs Corporate Data Warehouse, we conducted a retrospective cohort study of 16,064 patients who were newly diagnosed with insomnia between January 1, 2010, and December 31, 2019. A pair of 3912 hypnotic users and nonusers were selected based on a 1:1 propensity score methodology. The primary outcome was extended major adverse cardiovascular events, a composite of the first occurrence of all-cause mortality or nonfatal major adverse cardiovascular events. RESULTS: During the median follow-up of 4.8 years, a total of 2791 composite events occurred, including 2033 deaths and 762 nonfatal major adverse cardiovascular events. Although the incidence rates of major adverse cardiovascular events were comparable between hypnotic users and nonusers in the propensity-matched cohort, users of benzodiazepines and Z-drugs had a higher risk of all-cause mortality (hazard ratio 1.47 [95% CI, 1.17-1.88] and 1.20 [95% CI, 1.03-1.39], respectively), while serotonin antagonist and reuptake inhibitors users had a survival advantage (hazard ratio 0.79 [95% CI, 0.69-0.91]) compared with nonusers. There were no differences in the risk of nonfatal major adverse cardiovascular events between all classes of hypnotics. Male patients and those aged 60 years or younger who were using benzodiazepines or Z-drugs experienced higher major adverse cardiovascular events than their counterparts. CONCLUSIONS: In patients with newly diagnosed insomnia, treatment with hypnotics resulted in higher extended major adverse cardiovascular events but not nonfatal major adverse cardiovascular events with benzodiazepine and Z-drug users compared with nonusers. The use of serotonin antagonist and reuptake inhibitors agents had a protective effect against major adverse cardiovascular events warranting further investigation.

Development and psychometric properties of the Multidimensional Inventory of Recovery Capital (MIRC).

BACKGROUND: Researchers have developed several instruments to measure recovery capital-the social, physical, human, and cultural resources that help people resolve alcohol and other drug problems. However, existing measures are hampered by theoretical and psychometric weaknesses. The current study reports on process and psychometric outcomes for the Multidimensional Inventory of Recovery Capital (MIRC), a novel measure of recovery capital. METHODS: We used a three-phase, mixed methods approach to develop the MIRC. Individuals who identified as having resolved alcohol problems were recruited in each phase. Phase one focused on item development, with participants providing qualitative feedback on potential items. In phase two (pilot testing) and phase three (final psychometric evaluation), participants completed revised versions of the MIRC to assess its psychometric strength and item performance. RESULTS: Phase one (n=44) resulted in significant item alteration, culminating in a 48-item pilot measure. Pilot testing analyses (n=497) resulted in the deletion or replacement of 17 items. In the final psychometric evaluation (n=482), four additional items were deleted, resulting in a 28-item MIRC comprising four subscales measuring social, physical, human, and cultural capital. The psychometric properties of the final MIRC and its subscales ranged from sound to strong, with high response variability suggesting appropriate item discrimination. CONCLUSION: Results confirm the psychometric strength of the MIRC and underscore the importance of incorporating the insights of diverse samples of people in recovery. The MIRC holds promise as an assessment tool in future research and is available for use at no cost in treatment and community-based settings.

Lexical Characteristics of the Speech Intelligibility Test: Effects on Transcription Intelligibility for Speakers With Multiple Sclerosis and Parkinson's Disease.

PURPOSE: Lexical characteristics of speech stimuli can significantly impact intelligibility. However, lexical characteristics of the widely used Speech Intelligibility Test (SIT) are unknown. We aimed to (a) define variation in neighborhood density, word frequency, grammatical word class, and type-token ratio across a large corpus of SIT sentences and tests and (b) determine the relationship of lexical characteristics to speech intelligibility in speakers with multiple sclerosis (MS), Parkinson's disease (PD), and neurologically healthy controls. METHOD: Using an extant database of 92 speakers (32 controls, 30 speakers with MS, and 30 speakers with PD), percent correct intelligibility scores were obtained for the SIT. Neighborhood density, word frequency, word class, and type-token ratio were calculated and summed for each of the 11 sentences of each SIT test. The distribution of each characteristic across SIT sentences and tests was examined. Linear mixed-effects models were performed to assess the relationship between intelligibility and the lexical characteristics. RESULTS: There was large variability in the distribution of lexical characteristics across this large corpus of SIT sentences and tests. Modeling revealed a relationship between intelligibility and the lexical characteristics, with word frequency and word class significantly contributing to the model. CONCLUSIONS: Three primary findings emerged: (a) There was considerable variability in lexical characteristics both within and across the large corpus of SIT tests; (b) there was not a robust association between intelligibility and the lexical characteristics; and (c) findings from a study demonstrating an effect of neighborhood density and word frequency on intelligibility were replicated. Clinical and research implications of the findings are discussed, and three exemplar SIT tests systematically controlling for neighborhood density and word frequency are provided.

Repeated forms, testing intervals, and SDMT performance in a large multiple sclerosis dataset.

BACKGROUND: The Symbol Digit Modalities Test (SDMT), the most reliable and sensitive measure of cognition in people with multiple sclerosis (PwMS), is increasingly used in clinical trials and care. OBJECTIVES: We aimed to establish how SDMT performance is influenced by repeating forms and frequency of use in PwMS. METHODS: A retrospective analysis was completed on a large database of PwMS (n = 740) with multiple SDMT administrations. Change in SDMT performance was analyzed, accounting for frequency of tests and utilization of alternate- versus same-form conditions. RESULTS: SDMT administrations ranged from 2 to 14 per subject over a mean (SD) of 5.9 (4.5) years. Accounting for demographics, the mixed effects model revealed a significant main effect of SDMT exposures (1.8 point improvement per repetition, p = 0.001) and an interaction between time since previous SDMT and whether the same test form was administered in the previous administration (estimate=-1.1, p = 0.037). As well, SDMT decline is observed when testing intervals exceed two years (F = 9.69, p<0.001). CONCLUSION: Improvements in SDMT performance with repeated exposure, likely reflecting practice effects, were greatest when repeating the same SDMT form over briefer intervals. We recommend the use of alternate forms or analogous versions of timed symbol-digit coding particularly where samples are saturated with many administrations.

Clear Speech Variants: An Investigation of Intelligibility and Speaker Effort in Speakers With Parkinson's Disease.

PURPOSE: This study investigated the effects of three clear speech variants on sentence intelligibility and speaking effort for speakers with Parkinson's disease (PD) and age- and sex-matched neurologically healthy controls. METHOD: Fourteen speakers with PD and 14 neurologically healthy speakers participated. Each speaker was recorded reading 18 sentences from the Speech Intelligibility Test in their habitual speaking style and for three clear speech variants: clear (SC; given instructions to speak clearly), hearing impaired (HI; given instructions to speak with someone with a hearing impairment), and overenunciate (OE; given instructions to overenunciate each word). Speakers rated the amount of physical and mental effort exerted during each speaking condition using visual analog scales (averaged to yield a metric of overall speaking effort). Sentence productions were orthographically transcribed by 50 naive listeners. Linear mixed-effects models were used to compare intelligibility and speaking effort across the clear speech variants. RESULTS: Intelligibility was reduced for the PD group in comparison to the control group only in the habitual condition. All clear speech variants significantly improved intelligibility above habitual levels for the PD group, with OE maximizing intelligibility, followed by the SC and HI conditions. Both groups rated speaking effort to be significantly higher for both the OE and HI conditions versus the SC and habitual conditions. DISCUSSION: For speakers with PD, all clear speech variants increased intelligibility to a level comparable to that of healthy controls. All clear speech variants were also associated with higher levels of speaking effort than habitual speech for the speakers with PD. Clinically, findings suggest that clear speech training programs consider using the instruction "overenunciate" for maximizing intelligibility. Future research is needed to identify if high levels of speaking effort elicited by the clear speech variants affect long-term sustainability of the intelligibility benefit.

Adjuvant radiation therapy improves survival in stage IIIA (N2) non-small cell lung cancer with persistent N2 disease after neoadjuvant chemotherapy.

OBJECTIVES: Role of adjuvant radiation therapy in stage III (N2) non-small cell lung cancer has been controversial over the decades. Recent large, randomized trials have demonstrated that adjuvant radiation did not improve overall survival or disease-free survival; however, the trials either excluded or enrolled very few cases that have undergone neoadjuvant chemotherapy. Role of adjuvant radiation after neoadjuvant chemotherapy remains unclear. Whether the use of adjuvant radiation is associated with improved overall survival in those who have received neoadjuvant chemotherapy, especially in a subgroup of patients with persistent N2, is unknown. MATERIALS AND METHODS: Patients with clinical stage III (N2) non-small cell lung cancer diagnosed from 2004 through 2017 were queried to National Cancer Database. Eligibility criteria included completely resected (R0), pathological diagnosis, neoadjuvant multi-agent chemotherapy, information regarding post-surgical N2 status (persistent versus downstaged to pN0-1), adjuvant radiation (45 Gy+ versus none), and American Joint Commission on Cancer staging version (6th versus 7th). Those who have received neoadjuvant radiation with any dose or adjuvant radiation with less than 45 Gy total dose were excluded. Kaplan-Meier and log-rank tests were used for survival analyses. Propensity-score matching analysis was used for validation. All statistical analyses were two-sided, and p < 0.05 was required for statistical significance. RESULTS: A total of 1,855 patients met the eligibility criteria for analysis. In the overall cohort, there was a significant difference in overall survival between persistent N2 (Cohort P: N = 854, median survival 50.7 months) and downstaged N (Cohort D: N = 1,001, median survival 82.7 months). The use of adjuvant radiation showed a non-significant detrimental effect in overall survival in the overall and Cohort D (univariate p-values 0.27 and 0.077, respectively); however, both univariate and multivariate analyses demonstrated a significant improvement in overall survival in Cohort P (p = 0.004 and 0.028, respectively). These findings are also verified by propensity-score matching analysis (p = 0.0347). CONCLUSIONS: This large-scale retrospective analysis suggests that adjuvant radiation may still have a role in persistent N2 disease after neoadjuvant chemotherapy. Further investigations are warranted.

A nurse-delivered intervention to reduce insomnia in cancer survivors: Study protocol for a randomized-controlled trial.

Insomnia has been frequently reported as one of the most burdensome symptoms among cancer survivors. To date, little research exists on strategies to effectively reduce insomnia in cancer survivors, especially in the application of cognitive behavioral therapy for insomnia (CBTI) at the bedside by nurses. The current objective is to determine efficacy and durability of a streamlined, individually delivered version of CBTI, specifically Brief Behavioral Therapy for Insomnia (BBTI) versus a healthy eating attention control, using a large heterogeneous sample of 158 cancer survivors. Study participants will be adults ≥18 years of age; ≥1 month from treatment (except hormones and targeted therapies are acceptable) for stages I through III breast, colorectal, lung or prostate cancers; meet criteria for insomnia defined by Insomnia Severity Index (ISI) >7; screen negative for obstructive sleep apnea <15 events/h; and ability to complete data collection instruments in English. Baseline, and then 1-, 3-, and 12-month objective (i.e., actigraphy) and subjective sleep, mood, and quality of life assessments after the interventions are planned. The primary outcome will be measured with the ISI, a psychometrically-sound instrument used to measure perceived insomnia severity. The results of this trial will demonstrate the application of BBTI in a larger heterogenous sample of cancer survivors for the first time and may lead to implementation strategies that will promote the dissemination and sustainability of this intervention. Clinical trials identifier: http://ClinicalTrials.gov, NCT03810365.

Implementation of Surfactant Administration through Laryngeal or Supraglottic Airways (SALSA): A Jordanian NICU's Journey to Improve Surfactant Administration.

Administration of liquid surfactant through an endotracheal tube for the treatment of respiratory distress syndrome has been the standard of care for decades. Surfactant administration through laryngeal or supraglottic airways (SALSA) is a simplified procedure for delivery of surfactant that is less invasive and better tolerated. The Al Bashir Maternity and Children's Hospital NICU in Amman, Jordan, implemented SALSA as a potentially better practice in 2019 with the objective to effectively and efficiently deliver surfactant in a minimally invasive way and to decrease the adverse events associated with intubation−surfactant−extubation (InSurE) and laryngoscopy. The quality improvement initiative was conducted from March 2019 to December 2019. All infants who weighed 750 g or more who required surfactant were eligible. As physicians were trained in the technique and use expanded, we were able to use plan−do−study−act cycles to observe differences between SALSA and InSurE. The primary aim was the optimization of non-invasive ventilation by the effective and efficient delivery of surfactant. Balancing measures included episodes of bradycardia while receiving surfactant or the need for a second dose of surfactant. We evaluated 220 infants who received surfactant by SALSA or InSurE with a mean gestational age of 32 weeks and a mean birth weight of 1.8 kg. The Respiratory Severity Score (RSS) prior to surfactant administration was 2.7 in the SALSA group compared to 2.9 in the InSurE group (p = 0.024). Those in the InSurE group had a lower mean heart rate during the procedure (p =< 0.0001) and were more likely to need a second dose of surfactant (p = 0.026) or require intubation for mechanical ventilation (p = 0.022). Both groups were effectively delivered surfactant as evidenced by improvement in their RSS over an 8 h period. SALSA was a more time efficient surfactant delivery method (93 vs. 111 secs, p =< 0.0001). Implementation of SALSA into the Al Bashir NICU was successful. We found that it was equally effective to InSurE, but was a more efficient method of delivery. Infants who received surfactant by this method tolerated it well.

Susceptibility networks reveal independent patterns of brain iron abnormalities in multiple sclerosis.

Brain iron homeostasis is necessary for healthy brain function. MRI and histological studies have shown altered brain iron levels in the brains of patients with multiple sclerosis (MS), particularly in the deep gray matter (DGM). Previous studies were able to only partially separate iron-modifying effects because of incomplete knowledge of iron-modifying processes and influencing factors. It is therefore unclear to what extent and at which stages of the disease different processes contribute to brain iron changes. We postulate that spatially covarying magnetic susceptibility networks determined with Independent Component Analysis (ICA) reflect, and allow for the study of, independent processes regulating iron levels. We applied ICA to quantitative susceptibility maps for 170 individuals aged 9-81 years without neurological disease ("Healthy Aging" (HA) cohort), and for a cohort of 120 patients with MS and 120 age- and sex-matched healthy controls (HC; together the "MS/HC" cohort). Two DGM-associated "susceptibility networks" identified in the HA cohort (the Dorsal Striatum and Globus Pallidus Interna Networks) were highly internally reproducible (i.e. "robust") across multiple ICA repetitions on cohort subsets. DGM areas overlapping both robust networks had higher susceptibility levels than DGM areas overlapping only a single robust network, suggesting that these networks were caused by independent processes of increasing iron concentration. Because MS is thought to accelerate brain aging, we hypothesized that associations between age and the two robust DGM-associated networks would be enhanced in patients with MS. However, only one of these networks was altered in patients with MS, and it had a null age association in patients with MS rather than a stronger association. Further analysis of the MS/HC cohort revealed three additional disease-related networks (the Pulvinar, Mesencephalon, and Caudate Networks) that were differentially altered between patients with MS and HCs and between MS subtypes. Exploratory regression analyses of the disease-related networks revealed differential associations with disease duration and T2 lesion volume. Finally, analysis of ROI-based disease effects in the MS/HC cohort revealed an effect of disease status only in the putamen ROI and exploratory regression analysis did not show associations between the caudate and pulvinar ROIs and disease duration or T2 lesion volume, showing the ICA-based approach was more sensitive to disease effects. These results suggest that the ICA network framework increases sensitivity for studying patterns of brain iron change, opening a new avenue for understanding brain iron physiology under normal and disease conditions.