Protocol for randomized personalized trial for stress management compared to standard of care.

Stress is a significant public health burden in the United States, with most Americans reporting unhealthy levels of stress. Stress management techniques include various evidence-based treatments shown to be effective but with heterogeneous treatment responses, indicating a lack of uniform benefits for all individuals. Designed to assess a participant's response to a specific intervention, personalized (N-of-1) trials provide guidance for which treatment (s) work (s) best for the individual. Prior studies examining the effects of mindfulness meditation, yoga, and walking for stress reduction found all three interventions to be associated with significant reductions in self-reported measures of stress. Delivering these treatments using a personalized trial approach has the potential to assist clinicians in identifying the best stress management techniques for individuals with persistently high stress while fostering treatment decisions that consider their personal condition/barriers. This trial will evaluate a personalized approach compared to standard of care for three interventions (guided mindfulness meditation; guided yoga; and guided brisk walking) to manage perceived stress. Participants will respond to daily surveys and wear a Fitbit device for 18 weeks. After a 2-week baseline period, participants in the personalized trial groups will receive 12 weeks of interventions in randomized order, while participants in the standard-of-care group will have access to all interventions for self-directed stress management. After intervention, all participants will undergo 2 weeks of observation, followed by two additional weeks of the stress management intervention of their choosing while continuing outcome measurement. At study completion, all participants will be sent a satisfaction survey. The primary analysis will compare perceived stress levels between the personalized and standard of care arms. The results of this trial will provide further support for the use of personalized designs for managing stress. Clinical Trial Registration: clinicaltrials.gov, NCT05408832. Protocol version: 9/14/2022, 21-0968-MRB.

A Series of Remote Melatonin Supplement Interventions for Poor Sleep: Protocol for a Feasibility Pilot Study for a Series of Personalized (N-of-1) Trials.

BACKGROUND: Poor sleep, defined as short-duration or poor-quality sleep, is a frequently reported condition with many deleterious effects including poorer cognitive functioning, increased accidents, and poorer health. Melatonin has been shown to be an efficacious treatment to manage symptoms of poor sleep. However, the treatment effects of melatonin on sleep can vary greatly between participants. Personalized, or N-of-1, trial designs represent a method for identifying the best treatment for individual participants. Although using N-of-1 trials of melatonin to treat poor sleep is possible, the feasibility, acceptability, and effectiveness of N-of-1 trials using melatonin are unknown. Using the National Institutes of Health Stage Model for Behavioral Intervention Development, a stage IB (intervention refinement, modification, and adaptation and pilot testing) design appeared to be needed to address these feasibility questions. OBJECTIVE: This trial series evaluates the feasibility, acceptability, and effectiveness of a series of personalized interventions for remote delivery of melatonin dose (3 and 0.5 mg) versus placebo supplements for self-reported poor sleep among 60 participants. The goal of this study is to provide valuable information about implementing remote N-of-1 randomized controlled trials to improve poor sleep. METHODS: Participants will complete a 2-week baseline followed by six 2-week alternating intervention periods of 3 mg of melatonin, 0.5 mg of melatonin, and placebo. Participants will be randomly assigned to 2 intervention orders. The feasibility and acceptability of the personalized trial approach will be determined with participants' ratings of usability and satisfaction with the remote, personalized intervention delivery system. The effectiveness of the intervention will be measured using participants' self-reported sleep quality and duration and Fitbit tracker-measured sleep duration and efficiency. Additional measures will include ecological momentary assessment measures of fatigue, stress, pain, mood, concentration, and confidence as well as measures of participant adherence to the intervention, use of the Fitbit tracker, and survey data collection. RESULTS: As of the submission of this protocol, recruitment for this National Institutes of Health stage IB personalized trial series is approximately 78.3% complete (47/60). We expect recruitment and data collection to be finalized by June 2023. CONCLUSIONS: Evaluating the feasibility, acceptability, and effectiveness of a series of personalized interventions of melatonin will address the longer term aim of this program of research-is integrating N-of-1 trials useful patient care? The personalized trial series results will be published in a peer-reviewed journal and will follow the CONSORT (Consolidated Standards of Reporting Trials) extension for N-of-1 trials (CENT 2015) reporting guidelines. This trial series was approved by the Northwell Health institutional review board. TRIAL REGISTRATION: ClinicalTrials.gov NCT05349188; https://www.clinicaltrials.gov/study/NCT05349188. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45313.

Mechanical ventilation for COVID-19: Outcomes following discharge from inpatient treatment.

Though mechanical ventilation (MV) is used to treat patients with severe coronavirus disease 2019 (COVID-19), little is known about the long-term health implications of this treatment. Our objective was to determine the association between MV for treatment of COVID-19 and likelihood of hospital readmission, all-cause mortality, and reason for readmission. This study was a longitudinal observational design with electronic health record (EHR) data collected between 3/1/2020 and 1/31/2021. Participants included 17,652 patients hospitalized for COVID-19 during this period who were followed through 6/30/2021. The primary outcome was readmission to inpatient care following discharge. Secondary outcomes included all-cause mortality and reason for readmission. Rates of readmission and mortality were compared between ventilated and non-ventilated patients using Cox proportional hazards regression models. Differences in reasons for readmission by MV status were compared using multinomial logistic regression. Patient characteristics and measures of illness severity were balanced between those who were mechanically ventilated and those who were not utilizing 1-to-1 propensity score matching. The sample had a median age of 63 and was 47.1% female. There were 1,131 (6.4%) patients who required MV during their initial hospitalization. Rates (32.1% versus 9.9%) and hazard of readmission were greater for patients requiring MV in the propensity score-matched samples [hazard ratio (95% confidence interval) = 3.34 (2.72-4.10)]. Rates (15.3% versus 3.4%) and hazard [hazard ratio (95% confidence interval) = 3.12 (2.32-4.20)] of all-cause mortality were also associated with MV status. Ventilated patients were more likely to be readmitted for reasons which were classified as COVID-19, infectious diseases, and respiratory diagnoses compared to non-ventilated patients. Mechanical ventilation is a necessary treatment for severely ill patients. However, it may be associated with adverse outcomes including hospital readmission and death. More intense post-discharge monitoring may be warranted to decrease this associational finding.

Differential response of positive valence systems to psychotherapy for late-life depression: A pilot study.

BACKGROUND: Depression is characterized by deficits in the positive valence systems (PVS), which also decline with age. However, few studies have examined changes in PVS as a mechanism of treatment for depression, and none have done so using reward-focused interventions in older adults. AIM: The aim of this proof-of-concept study was to investigate changes in two event-related potential measures of PVS function, the late positive potential and the reward positivity, during psychotherapy designed to treat late-life depression by increasing rewarding experiences. METHODS: Eighteen adults age ≥ 60 with major depressive disorder recruited for a larger randomized controlled trial received 9 weeks of Problem-Solving Therapy or Engage therapy. The late positive potential and the reward positivity were recorded at baseline and week 6 of treatment. RESULTS: The late positive potential was larger for rewarding compared to neutral stimuli and increased from baseline to week 6. Exploratory analyses found that this increase was specific to rewarding stimuli. There were no significant effects for the reward positivity. LIMITATIONS: The small sample size limited power to detect associations with clinical measures or evaluate moderating effects of treatment modality, age, or gender. CONCLUSIONS: This study provides preliminary evidence that distinct facets of the PVS respond differently to psychotherapy in older adults with major depression. The late positive potential may be a dynamic marker of depressive state, whereas the reward positivity may constitute a vulnerability index for late-life depression.

Transfusion in Root Replacement for Aortic Dissection: The STS Adult Cardiac Surgery Database Analysis.

BACKGROUND: Transfusion in acute aortic syndromes has been studied in a limited fashion. We sought to describe contemporary transfusion practice for root replacement in acute (Stanford) type A aortic dissection. METHODS: The Society of Thoracic Surgeons Adult Cardiac Surgery Database was interrogated to identify patients who underwent primary aortic root replacement for acute (Stanford) type A aortic dissection (July 2014 to June 2017). Patients (n = 1558) were stratified by type of root replacement. Multivariate regression was used to determine those variables associated with transfusion and postoperative morbidity. RESULTS: Transfusion was required in 90.5% of cases (n = 1410). Operative mortality for all patients was 17.3% (261 deaths). Intraoperative red blood cell transfusion portended reduced short-term survival (odds ratio [OR] 2.00, P = .025). Massive postoperative transfusion was associated with prolonged ventilation (OR 13.47, P < .001), sepsis (OR 4.13, P < .001), and new dialysis-dependent renal failure (OR 2.43, P < .001). Women were more likely to require transfusion (OR 3.03, P < .001), as were patients who had coronary artery bypass (OR 1.57, P = .009), and those in shock (OR 2.27, P < .001). Valve-sparing aortic root replacement was associated with reduced transfusion requirements vs composite roots. Institutional case volume was not appreciably correlated with transfusion. CONCLUSIONS: Most patients undergoing root replacement for aortic dissection require blood products. Composite root replacement is associated with a greater likelihood of transfusion than a valve-sparing operation. Transfusion independently foreshadows greater operative mortality.

Dimensions of Poststroke Depression and Neuropsychological Deficits in Older Adults.

OBJECTIVE: Poststroke depression (PSD) has a heterogeneous presentation and is often accompanied by cognitive impairment. This study aimed to identify distinct dimensions of depressive symptoms in older adults with PSD and to evaluate their relationship to cognitive functioning. DESIGN: Cross-sectional factor and correlational analyses of patients with poststroke depression. SETTING: Patients were recruited from the community and from acute inpatient stroke rehabilitation hospitals. PARTICIPANTS: Participants had suffered a stroke and met DSM-IV criteria for major depression (≥18 Montgomery Åsberg Depression Scale; MADRS). INTERVENTION: None. MEASUREMENTS: MADRS was used to quantify depression severity at study entry. Neuropsychological assessment at the time of study entry consisted of measures of Global Cognition, Attention, Executive Function, Processing Speed, Immediate Memory, Delayed Memory, and Language. RESULTS: There were 135 (age ≥50) older adult participants with PSD and varying degrees of cognitive impairment (MMSE Total ≥20). Factor analysis of the MADRS identified three factors, that is sadness, distress, and apathy. Items comprising each factor were totaled and correlated with neuropsychological domain z-score averages. Symptoms of the apathy factor (lassitude, inability to feel) were significantly associated with greater impairment in executive function, memory, and global cognition. Symptoms of the sadness and distress factors had no relationship to cognitive impairment. CONCLUSION: PSD consists of three correlated dimensions of depressive symptoms. Apathy symptoms are associated with cognitive impairment across several neuropsychological domains. PSD patients with prominent apathy may benefit from careful attention to cognitive functions and by interventions that address both psychopathology and behavioral deficits resulting from cognitive impairment.