Lithium Aspartate for Long COVID Fatigue and Cognitive Dysfunction: A Randomized Clinical Trial.

Importance: Neurologic post-COVID-19 condition (PCC), or long COVID, symptoms of fatigue and cognitive dysfunction continue to affect millions of people who have been infected with SARS-CoV-2. There currently are no effective evidence-based therapies available for treating neurologic PCC. Objective: To assess the effects of lithium aspartate therapy on PCC fatigue and cognitive dysfunction. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled trial (RCT) enrolling participants in a neurology clinic from November 28, 2022, to June 29, 2023, with 3 weeks of follow-up, was conducted. Subsequently, an open-label lithium dose-finding study with 6 weeks of follow-up was performed among the same participants enrolled in the RCT. Eligible individuals needed to report new, bothersome fatigue or cognitive dysfunction persisting for more than 4 weeks after a self-reported positive test for COVID-19, Fatigue Severity Scale-7 (FSS-7) or Brain Fog Severity Scale (BFSS) score of 28 or greater, Beck Depression Inventory-II score less than 24, and no history of a condition known to cause fatigue or cognitive dysfunction. All participants in the RCT were eligible for the dose-finding study, except for those who responded to the placebo. Intention-to-treat analysis was used. Intervention: Lithium aspartate, 10 to 15 mg/d, or identically appearing placebo for 3 weeks followed by open-label lithium aspartate, 10 to 15 mg/d, for 2 weeks. In the subsequent dose-finding study, open-label lithium aspartate dosages up to 45 mg/d for 6 weeks were given. Main Outcomes and Measures: Change in sum of FSS-7 and BFSS scores. The scores for each measure range from 7 to 49, with higher scores indicating more severe symptoms. Secondary outcomes included changes from baseline in the scores of additional questionnaires. Results: Fifty-two participants were enrolled (30 [58%] males; mean [SD] age, 58.54 [14.34] years) and 26 were randomized to treatment with lithium aspartate (10 females) and 26 to placebo (12 female). Two participants assigned to lithium aspartate were lost to follow-up and none withdrew. No adverse events were attributable to lithium therapy. There were no significant intergroup differences for the primary outcome (-3.6; 95% CI, -16.6 to 9.5; P = .59) or any secondary outcomes. Among 3 patients completing a subsequent dose-finding study, open-label lithium aspartate, 40 to 45 mg/d, was associated with numerically greater reductions in fatigue and cognitive dysfunction scores than 15 mg/d, particularly in 2 patients with serum lithium levels of 0.18 and 0.49 mEq/L compared with 1 patient with a level of 0.10 mEq/L. Conclusions and Relevance: In this RCT, therapy with lithium aspartate, 10 to 15 mg/d, was ineffective for neurologic PCC fatigue and cognitive dysfunction. Another RCT is required to assess the potential benefits of higher lithium dosages for treating neurologic PCC. Trial Registration: ClinicalTrials.gov Identifier: NCT05618587 and NCT06108297.

Predictors of National Institute on Alcohol Abuse and Alcoholism (NIAAA) Alcohol Recovery among Individuals in Alcohol Treatment: Implications for Social Work.

The National Institute on Alcohol Abuse and Alcoholism's (NIAAA) definition of alcohol use disorder (AUD) recovery stipulates two criteria: remission from DSM-5 AUD and cessation of heavy drinking. Importantly, these criteria allow for consideration of nonabstinent alcohol treatment outcomes. However, researchers have yet to assess potential predictors of the NIAAA recovery outcome. The current study examined associations between mental health and coping predictors of NIAAA recovery status in an AUD treatment sample. At baseline (BL) and end-of-treatment (EOT) research interviews in a clinical trial, participants (N = 118) completed questionnaires assessing alcohol dependence, mental health, and confidence levels in reducing heavy drinking, as well as alcohol use and DSM-5 AUD symptom endorsement. Logistic regression models tested the associations between chosen predictors and the odds of achieving NIAAA recovery. Twenty-four percent of individuals (n = 28) met both criteria for NIAAA recovery at EOT. Higher levels of BL state anxiety and anxiety sensitivity predicted lower odds of achieving NIAAA recovery, while greater confidence to reduce heavy drinking predicted increased odds of NIAAA recovery. Social workers are encouraged to continue assessing and addressing mental health in AUD treatment to help individuals with alcohol problems achieve their AUD recovery goals.

Negative affect variability as a potential mechanism of behavior change in alcohol use disorder treatment.

OBJECTIVE: Negative affect and affect variability figure prominently in models of addictive behaviors but are not without controversy. Negative affect variability may better capture a mechanism of behavior change in alcohol use disorder (AUD) treatment because it contains information about affect regulation, a common clinical target. The aims of this study are to examine the change in: (a) trajectory of negative affect variability, (b) association of negative affect variability and abstinence, and (c) association of negative affect variability and heavy drinking during AUD treatment. METHOD: This article is a secondary analysis of data drawn from a randomized clinical trial. N = 181 participants diagnosed with Diagnostic and Statistical Manual of Mental Disorders, fifth edition AUD (Mage = 50.8, SDage = 10.6; 51.4% female) received 12 sessions of Cognitive Behavioral Coping Skills Therapy for AUD. Participants completed one daily diary prompt per day for 84 consecutive days. Each day, participants reported on negative affect and number of alcoholic drinks consumed the previous day. Time-varying effect models examined changes in negative affect variability and its associations with abstinence and heavy drinking. RESULTS: Negative affect variability decreased throughout treatment. The positive association between negative affect variability and heavy drinking became nonsignificant (decoupled) midway through treatment. The inverse association between negative affect variability and daily abstinence became nonsignificant (decoupled) at approximately day 75 of 84. When mean levels of NA were added as a covariate, the effects were in the same direction but no longer statistically significant. CONCLUSION: Reductions in negative affect variability may capture an important change mechanism of behavioral treatments for AUD because it contains information about affect regulation as compared with mean levels of negative affect. Negative affect variability warrants further consideration as a mechanism of behavior change. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Pilot study comparing sleep logs to a commercial wearable device in describing the sleep patterns of physicians-in-training.

With the increasing burden of professional burnout in physicians, attention is being paid to optimizing sleep health, starting in training. The multiple dimensions of physicians' sleep are not well described due to obstacles to easily and reliably measuring sleep. This pilot study tested the feasibility of using commercial wearable devices and completing manual sleep logs to describe sleep patterns of medical students and residents. Prospective pilot study of 50 resident physicians and medical students during a single year of training. Participants completed a manual sleep log while concurrently wearing the Fitbit Inspire device for 14-consecutive days over three clinical rotations of varying work schedules: light, medium, and heavy clinical rotations. Study completion was achieved in 24/50 (48%) participants. Overall correlation coefficients between the sleep log and Fitbit were statistically low; however, the discrepancies were acceptable, i.e., Fitbit underestimated time in bed and total sleep time by 4.3 and 2.7 minutes, respectively. Sleep onset time and waketime were within 8 minutes, with good agreement. Treatment of sleep episodes during the day led to variance in the data. Average missingness of collected data did not vary between medical students or residents or by rotation type. When comparing the light to heavy rotations, hours slept went from 7.7 (±0.64) to 6.7 (±0.88), quality-of-life and sleep health decreased and stress, burnout, and medical errors increased. Burnout was significantly associated with worse sleep health, hours worked, and quality-of-life. Prospective data collection of sleep patterns using both sleep logs and commercial wearable devices is burdensome for physicians-in-training. Using commercial wearable devices may increase study success as long as attention is paid to daytime sleep. In future studies investigating the sleep of physicians, the timing of data collection should account for rotation type.

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.

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.

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.

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).

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.

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.

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.

Exact unconditional inference for analyzing contingency tables in finite populations.

With recent developments in computer power the application of exact inferential methods has become more feasible which has resulted in increasing popularity of these approaches. However, there is a lack of such methodology for populations with more complex structure, such as finite populations. When a small sample is drawn from a finite population, the number of individuals with a specific characteristic of interest follows hypergeometric distribution. In order to test for the comparison of two proportions in finite populations we develop an exact unconditional test. We utilize the information gained from the sample to restrict our search for the maximum p-value. Our proposed test has power equal to its competitors while maintains the pre-specified nominal significance level.

A Multilevel Approach to Investigate Relationships Between Healthcare Resources and Lung Cancer.

BACKGROUND: Screening for lung cancer is an evidence-based but underutilized measure to reduce the burden of lung cancer mortality. Lack of adequate data on geographic availability of lung cancer screening inhibits the ability of healthcare providers to help patients with decision-making and impedes equity-focused implementation of screening-supportive services. OBJECTIVES: This analysis used data from the 2012-2016 Surveillance, Epidemiology, and End Results (SEER) Program, the Behavioral Risk Factor Surveillance System, and the county health ranking to examine (a) which cancer resources and county-level factors are associated with late-stage lung cancer at diagnosis and (b) associations between county rurality and lung cancer incidence/mortality rates. METHODS: Using the New York state SEER data, we identified 68,990 lung cancer patients aged 20-112 years; 48.3% had late-stage lung cancers, and the average lung cancer incidence and mortality rates were 70.7 and 46.2 per 100,000, respectively. There were 144 American College of Radiology-designated lung cancer screening centers and 376 Federally Qualified Health Centers identified in New York state. County rurality was associated with a higher proportion of late-stage lung cancers and higher lung cancer mortality rates. DISCUSSION: Visual geomapping showed the scarcity of rural counties' healthcare resources. County rurality is a significant factor in differences in lung cancer screening resources and patient outcomes. Use of publicly available data with geospatial methods provides ways to identify areas for improvement, populations at risk, and additional infrastructure needs.