Patients on Antithrombotic Agents with Small Bowel Bleeding -Yield of Small Bowel Capsule Endoscopy and Subsequent Management.

BACKGROUND AND AIMS: Small bowel gastrointestinal bleeding (GIB) is associated with multiple blood transfusions, prolonged and/or multiple hospital admissions, utilization of significant healthcare resources, and negative effects on patient quality of life. There is a well-recognized association between antithrombotic medications and small bowel GIB. We aimed to identify the diagnostic yield of small bowel capsule endoscopy (SBCE) in patients on antithrombotic medications and the impact of SBCE on treatment course. METHODS: The electronic medical records of nineteen hundred eighty-six patients undergoing SBCE were retrospectively reviewed. RESULTS: The diagnostic yield for detecting stigmata of recent bleeding and/or actively bleeding lesions in SBCE was higher in patients that were on antiplatelet agents (21.6%), patients on anticoagulation (22.5%), and in patients that had their SBCE performed while they were inpatient (21.8%), when compared to the patients not on antiplatelet agents (12.1%), patients not on anticoagulation (13.5%), and with patients that had their SBCE performed in the outpatient setting (12%). Of 318 patients who had stigmata of recent bleeding and/or actively bleeding lesion(s) identified on SBCE, SBCE findings prompted endoscopic evaluation (small bowel enteroscopy, esophagogastroduodenoscopy (EGD), and/or colonoscopy) in 25.2%, with endoscopic hemostasis attempted in 52.5%. CONCLUSIONS: Our study, the largest conducted to date, emphasizes the importance of performing SBCE as part of the evaluation for suspected small bowel bleeding, particularly in patients taking antithrombotic therapy, and especially during their inpatient hospital stay.

Exposure to Non-Steady-State Oxygen Is Reflected in Changes to Arterial Blood Gas Values, Prefrontal Cortical Activity, and Systemic Cytokine Levels.

Onboard oxygen-generating systems (OBOGSs) provide increased inspired oxygen (FiO2) to mitigate the risk of neurologic injury in high altitude aviators. OBOGSs can deliver highly variable oxygen concentrations oscillating around a predetermined FiO2 set point, even when the aircraft cabin altitude is relatively stable. Steady-state exposure to 100% FiO2 evokes neurovascular vasoconstriction, diminished cerebral perfusion, and altered electroencephalographic activity. Whether non-steady-state FiO2 exposure leads to similar outcomes is unknown. This study characterized the physiologic responses to steady-state and non-steady-state FiO2 during normobaric and hypobaric environmental pressures emulating cockpit pressures within tactical aircraft. The participants received an indwelling radial arterial catheter while exposed to steady-state or non-steady-state FiO2 levels oscillating ± 15% of prescribed set points in a hypobaric chamber. Steady-state exposure to 21% FiO2 during normobaria produced arterial blood gas values within the anticipated ranges. Exposure to non-steady-state FiO2 led to PaO2 levels higher upon cessation of non-steady-state FiO2 than when measured during steady-state exposure. This pattern was consistent across all FiO2 ranges, at each barometric condition. Prefrontal cortical activation during cognitive testing was lower following exposure to non-steady-state FiO2 >50% and <100% during both normobaria and hypobaria of 494 mmHg. The serum analyte levels (IL-6, IP-10, MCP-1, MDC, IL-15, and VEGF-D) increased 48 h following the exposures. We found non-steady-state FiO2 levels >50% reduced prefrontal cortical brain activation during the cognitive challenge, consistent with an evoked pattern of neurovascular constriction and dilation.

Circulating Monocytes Are Predictive and Responsive in Moderate-to-Severe Plaque Psoriasis Subjects Treated with Apremilast.

Monocytes play a critical role in the inflammation associated with psoriasis, and their abnormalities have been reported as biomarkers of cardiovascular event risk, a psoriasis comorbidity. Monocytic cells in chronic inflammatory disorders express elevated levels of cAMP phosphodiesterase. Restoring cAMP levels using the oral cAMP phosphodiesterase-4 inhibitor, apremilast, improves clinical outcomes for a subset of patients with psoriasis. We asked whether aberrant monocyte subsets or transcriptomic pathways can function as biomarkers of psoriasis endotypes that can predict enhanced clinical responses to cAMP phosphodiesterase inhibition. A 16-week open-label study of 22 patients with monocyte flow cytometric and transcriptomic analysis was performed. Subjects with elevated hyperadhesive monocyte doublets at baseline were more likely to be responders to apremilast (P < .0001); 82% of subjects with elevated hyperadhesive monocyte doublets achieved 50% reduction in PASI compared with 46% in those without elevated doublets. We observed a significant reduction in hyperadhesive monocyte-containing doublets and monocyte-platelet aggregates, suggesting an effect of apremilast on the adhesiveness of blood monocytes during chronic inflammation. Monocyte differentially expressed gene transcripts predictive of clinical response uncovered pharmacoendotypes with distinct patterns of nucleotide metabolism, energetics, and differentiation. Further study to understand the basis of drug responsiveness and to develop an apremilast psoriasis treatment algorithm using monocyte-refined gene expression is required to validate and become practical in clinical use, offering patients a test that personalizes their likelihood of clinical response.

A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia.

ABSTRACT: The curative potential of allogeneic hematopoietic transplantation (allo-HCT) in patients with acute lymphoblastic leukemia (ALL) is hampered by relapse. Inotuzumab ozogamicin (INO) is an anti-CD22 monoclonal antibody bound to calicheamicin, which has significant activity against ALL. We hypothesized that low-dose INO would be safe and feasible after allo-HCT. Therefore, we conducted a phase 1 study to determine the dose and safety in this setting. Patients were eligible if they were aged 16 to 75 years, had undergone allo-HCT for CD22+ ALL, were in complete remission (CR) after allo-HCT, had high risk of recurrence, were between day 40 and 100 after allo-HCT with adequate graft function, and did not have a history of sinusoidal obstruction syndrome (SOS). The objectives of this trial were to define INO maximum tolerated dose (MTD), to determine post-allo-HCT INO safety, and to measure 1-year progression-free survival (PFS). The trial design followed a "3+3" model. The treatment consisted of INO given on day 1 of 28-day cycles. Dose levels were 0.3 mg/m2, 0.4 mg/m2, 0.5 mg/m2, and 0.6 mg/m2. Median age was 44 years (range, 17-66 years; n = 18). Disease status at transplantation was first CR (n = 14) or second CR or beyond (n = 4). Preparative regimen was of reduced intensity in 72% of patients who received transplantation. Most common toxicity was thrombocytopenia. There were no instances of SOS; the MTD was 0.6 mg/m2. One-year nonrelapse mortality was 5.6%. With a median follow-up of 18.1 months (range, 8.6-59 months) 1-year post-allo-HCT PFS and overall survival is 89% and 94%, respectively. Low-dose INO has a favorable safety profile and was associated with high rates of 1-year PFS. This trial was registered at www.clinicaltrials.gov as #NCT03104491.

The Impact of Prophylactic Cranial Irradiation and Consolidative Thoracic Radiation Therapy for Extensive Stage Small-Cell Lung Cancer in the Transition to the Chemo-Immunotherapy Era: A Single Institution Series.

INTRODUCTION: Extensive-stage small-cell lung cancer (ES-SCLC) continues to have poor survival due to its aggressive behavior, despite improvements with incorporation of immunotherapy with standard chemotherapy. Controversy exists regarding the role of consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) in ES-SCLC due to high recurrence rates. We report our institutional result of the benefit of PCI and TRT in ES-SCLC. METHODS: Patients with ES-SCLC without intracranial metastasis at diagnosis (N = 163) were included. All patients completed systemic therapy with or without immunotherapy based on time of standard of care. Cohorts were divided by systemic therapy use and further subdivided by treatment with PCI and TRT. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method with log-rank test for comparison. The effects of TRT and PCI were estimated by multivariable (MVA) Cox regression. RESULTS: Seventy-four patients (45.4%) received TRT, and 33.1% (n = 54) received PCI. The median follow-up was 11 months (3-85 months). PCI improved median OS to 15 months from 10 months, P = .02) and median PFS to 8.5 months from 5 months (P = .02) which remained significant on MVA, P = .02 and P = .02, respectively. TRT improved OS on UVA (P = 0.002) but was not significant on MVA. TRT did not improve PFS. CONCLUSION: This study including chemotherapy and chemo-immunotherapy suggests improved outcomes with addition of PCI in patients with ES-SCLC while TRT did not show benefit to either OS or PFS. A future trial is needed to evaluate the role of TRT and PCI in the era of chemo-immunotherapy.

Outcomes of Antineoplastic Immunotherapy at a Large Healthcare Organization: Impact of Provider, Race and Socioeconomic Status.

Purpose: Disparities in cancer care delivery remain a pressing health-care crisis within the United States (US). The use of immune checkpoint inhibitors (ICIs) and their management may be a disparity generator that impacts survival. This retrospective study assessed disparities in a cohort of patients with a variety of solid tumors treated with ICIs within a single health-care organization focusing on the impact of race, socioeconomic status (SES) and site of care delivery on survival and the development of severe immune-related adverse events (irAEs). Patients and Methods: Manual chart review was performed on all patients with solid tumors treated with ICIs within a health-care organization from 2012 to 2018. Care delivery was dichotomized as DOP (disease-oriented provider at academic center) and COP (community oncology provider). Primary and secondary outcomes were overall survival (OS) and rates of grade 3-4 irAEs, respectively. Relationships with covariates of interest, including race, socioeconomic status and type of care delivery, were assessed among both outcomes. Results: A total of 1070 eligible patients were identified. Of those, 11.4% were of Black race, 59.7% had either non-small cell lung cancer (NSCLC) or melanoma and 82.8% had stage IV disease. Patients of Black race and lower SES were more likely to be treated by DOPs (p<0.0001). A superior OS was associated with care delivered by DOPs when compared to COPs (HR 0.68; 95% CI 0.56-0.84; p=0.0002), which was durable after accounting for race, SES, histopathologic diagnosis and disease stage. Melanoma patients experienced higher rates of severe irAEs (HR 2.37; 95% CI 1.42-3.97; p=0.001). Race, SES and site of care delivery were not related to rates of severe irAEs. Conclusion: In a large health-care organization, patients treated with checkpoint inhibitors by DOPs benefited from a significant OS advantage that was durable after controlling for racial and socioeconomic factors, providing evidence that disease-oriented care has the potential to mitigate racial and socioeconomic disparities.

Sleep health dimensions are associated with next-day symptoms in young adults with type 1 diabetes.

OBJECTIVE: We investigated intra-individual reciprocal associations between sleep health dimensions (individual and composite) and symptoms among young adults with type 1 diabetes (T1D). DESIGN AND MEASUREMENTS: Cross-lagged multilevel models were used to analyze electronic diary-reported sleep and symptom patterns over 7 days at waketime in 42 young adults with T1D. Sleep health dimensions included regularity, satisfaction, alertness, timing, efficiency (percentage of time spent asleep), and duration (total sleep time) and symptoms included mood, fatigue, and pain. Covariates included biological sex and age. SETTING AND PARTICIPANTS: We recruited young adults (mean age 21.5 ± 2.1 years, HbA1c 6.8%, 85% female, 10% gender minority) with T1D for at least 6 months and no other major medical or psychiatric comorbidity from social media platforms, the College Diabetes Network, and ResearchMatch. RESULTS: On days with a better sleep health composite, participants reported lower next-day symptoms (higher mood, lower fatigue, and lower pain) and on days when participants reported lower symptoms, participants reported better sleep health (as a composite). Several individual sleep health dimensions led to lower next-day symptoms (eg, higher satisfaction, alertness, and efficiency and higher mood); however, symptoms were no longer predictive of next-day sleep when controlling for prior day sleep. CONCLUSIONS: Optimal sleep health is an antecedent of fewer next day symptoms. Sleep health dimensions likely have positive additive effects on lower symptoms as some of the individual sleep health dimensions were not significantly associated with some symptoms among young adults with T1D.

Examining how congruence in and satisfaction with dyadic care type appraisal contribute to quality of life in heart failure care dyads.

AIMS: Given the complexity of heart failure (HF) management, persons with HF and their informal caregivers often engage in dyadic illness management. It is unknown how congruent appraisal of dyadic HF care type is associated with dyadic health. Our aim was to examine how congruence in and satisfaction with appraisal of dyadic HF care type contribute to quality of life (QOL) for dyads. METHODS AND RESULTS: This is a secondary analysis of cross-sectional data on 275 HF care dyads (patients 45.1% female, caregivers 70.5% female). Congruent appraisal and satisfaction were assessed using the Dyadic Symptom Management Type instrument. Quality of life was measured using the Short Form-12. Multilevel dyadic models were estimated to examine the contribution of congruence and satisfaction with dyadic care type to physical and mental QOL. Congruent appraisal of dyadic care type was positively associated with caregivers' mental QOL (B = 2.69, P = 0.026). Satisfaction with dyadic care type was positively associated with physical and mental QOL for persons with HF (B = 1.58, P = 0.011 and B = 2.09, P = 0.002, respectively) and informal caregivers (B = 1.70, P = 0.004 and B = 2.90, P < 0.001, respectively), while controlling for age, New York Heart Association class, daily hours spent together, relationship type, and congruence with dyadic care type. CONCLUSION: Satisfaction with dyadic care type appraisal was a stronger contributor to QOL for HF care dyads, compared with congruent appraisals. It is important to understand reasons for dissatisfaction within the dyad to assist dyad members in reaching shared appraisals while managing HF.

Racial and Ethnic Cardiometabolic Risk Disparities in the Type 1 Diabetes Exchange Clinic Registry Cohort.

OBJECTIVE: To determine whether individuals from a historically underrepresented racial group have a higher cardiometabolic risk than historically represented individuals with type 1 diabetes (T1D) considering socioeconomic deprivation. METHODS: We used the multivariable logistic and linear regression models to examine socioeconomic deprivation (upper 10th percentile) by race/ethnicity interaction for each cardiometabolic risk factor and cardiometabolic risk burden score, respectively, across 6320 zip code tabulation areas. We also determined the age-adjusted prevalence of low, moderate, and high cardiometabolic risks defined as 0, 1 to 2, and 3 or more risk factors for hypertension, obesity, dyslipidemia, and off-target glycemia for non-Hispanic White (n = 15 746), non-Hispanic Black (n = 1019), Hispanic (n = 1115), and other (n = 887), respectively. RESULTS: The sample comprised 18 767 adolescents and adults with T1D. Those identifying as non-Hispanic Black were more likely to have a high cardiometabolic risk profile, including a 4.5-fold increase in the odds of off-target glycemia, a twofold increase in the odds of systolic hypertension, and 0.29 (unadjusted) and 0.46 (adjusted) increases in a higher cardiometabolic risk burden compared with non-Hispanic White individuals (P < .01). Those identifying as Hispanic had a 3.4-fold increase in the odds of off-target glycemia but were less likely to be overweight/obese or have systolic hypertension compared with non-Hispanic White. However, the lower likelihood of overweight/obesity and hypertension did not persist after considering covariates. CONCLUSION: There is a need to investigate additional determinants of racially/ethnically underrepresented cardiometabolic health, including structural racism and implicit bias in cardiometabolic care for individuals with T1D.

Characterizing the Dose Response of Hyperoxia with Brain Perfusion.

BACKGROUND: Tactical aviators require administration of enhanced inspired oxygen concentrations (hyperoxia) to reduce risk of hypobaric hypoxia and decompression injuries. Hyperoxia is not without consequence; it reduces cerebral perfusion (CBF). Characterizing the relationship between FIO2 and CBF is necessary to establish FIO2 levels that do not reduce CBF yet are sufficient to mitigate risk of in-flight physiological stressors. To achieve that goal, this study's objective was to determine whether a dose-response relationship exists between FIO2 and CBF and, if so, the FIO2 at which CBF significantly declines.METHODS: Healthy male and female subjects (N = 26) were randomized to receive either low dose FIO2 of 30%, 40%, 50%, and 100% (Arm 1) or high dose FIO2 of 60%, 70%, 80%, and 100% (Arm 2), followed by a return to 21% for both groups. Subjects were placed within a 3-Tesla MRI scanner equipped with pseudocontinuous arterial spin labeling software (pCASL) to measure CBF. Baseline CBF measurements were obtained during exposure to 21% FIO2, with subsequent CBF measurements obtained at each predetermined FIO2 level.RESULTS: Baseline CBF did not differ between subjects in Arm 1 and Arm 2. Low dose FIO2 ≤ 50% did not affect CBF. In contrast, high dose FIO2 ≥ 60% significantly reduced CBF. Exposure to 100% FIO2 led to similar reductions of CBF for subjects in both Arm 1 and Arm 2.DISCUSSION: The neurovascular system appears to respond to increasing FIO2 levels in a dose dependent manner, with significant reductions in CBF with FIO2 exposures ≥ 60%.Damato EG, Fillioe SJ, Vannix IS, Norton LK, Margevicius SP, Beebe JL, Decker MJ. Characterizing the dose response of hyperoxia with brain perfusion. Aerosp Med Hum Perform. 2022; 93(6):493-498.

Increased Serum Levels of Proinflammatory Cytokines Are Accompanied by Fatigue in Military T-6A Texan II Instructor Pilots.

Tactical aviation imposes unprecedented physical challenges including repetitive exposure to hypergravity, hyperoxia, increased work of breathing, and profound cognitive workloads. Each stressor evokes outcomes ranging from musculoskeletal duress and atelectasis to physical and cognitive fatigue, the latter among the foremost threats to aviators. Whereas sleep loss is traditionally considered the primary cause of fatigue in aviators, converging experimental, observational, and medical studies have identified biochemical mechanisms promoting onset of fatigue. Those mechanisms, which fundamentally differ from sleep loss, revolve around increased proinflammatory cytokines, produced and released in response to tissue injury, chronic inflammatory disorders, allergens, or physical duress. This study's objective was to inform our understanding of potential relationships between serum levels of proinflammatory cytokines and onset of fatigue within a cohort of aviators who experience multiple high-performance sorties on a daily basis. Methods: Active duty and reservist T-6A Texan II instructor pilots were studied on three separate days across their week-long flying schedule. Data collected included a physical assessment, subjective fatigue levels, venous blood samples for measures of chemistry and serum analytes, and urine samples for specific gravity. Results: Twenty-three persons were studied, of which 22 fulfilled minimum study requirements of completing two sorties. The study cohort was comprised of primarily males, age 37.95 ± 4.73 years with a BMI of 26.63 ± 3.15 kg/m2. Of 37 measurable serum analytes, 20 differed significantly (p < 0.05) between baseline values with those measured at the study endpoint. Thirteen of the aviators reported increased fatigue scores across their flying schedule whereas nine did not. Eleven blood serum analytes were associated with increasing levels of fatigue. Discussion: Fatigue in aviators has been attributed almost solely to sleep loss, nocturnal sorties, or disrupted circadian rhythmicity. In contrast, our study findings suggest an alternative mechanism that can promote onset of fatigue: increased blood levels of proinflammatory cytokines. Specific mechanisms triggering synthesis and release of those cytokines and other analytes are yet to be determined. However, their expression patterns suggest responses to both chronic and acute inflammation, hyperoxia, or bronchopulmonary responses to inspiration of dry gas, positive airway pressure, or perhaps atelectasis.

Glucose and unstructured physical activity coupling during sleep and wake in young adults with type 1 diabetes.

Glucose variations have a bidirectional relationship with the sleep/wake and circadian systems in type 1 diabetes (T1D); however, the mechanisms remain unclear. The aim of this study was to describe the coupling between glucose and unstructured physical activity over 168 h in young adults with T1D. We hypothesized that there would be differences in sleep and wake characteristics and circadian variations. Glucose was measured with a continuous glucose monitoring device every 5 min and activity with a non-dominant wrist-worn actigraph in 30-s epochs over 6-14 days. There was substantial glucose and unstructured physical activity coupling during sleep and wake, along with circadian variation based on the wavelet coherence analysis. The extent to which glucose fluctuations result in disrupted sleep over longer than one week should be examined considering the harmful effects on achieving glycemic targets. Further studies are needed to delineate the respective roles of glucose production and utilization and the potential for improved meal and insulin timing to optimize glucose and sleep in this population reliant on exogenous insulin.

A randomized controlled trial of the effect of supervised exercise on functional outcomes in older African American and non-Hispanic White breast cancer survivors: Are there racial differences in the effects of exercise on functional outcomes?

BACKGROUND: The objective of this study was to test the hypothesis that exercise would be more effective than a support group plus Fitbit (SG+Fitbit) program in improving functional outcomes in older breast cancer survivors (BCSs) and that race would moderate the exercise effect on outcomes. METHODS: Older African American (AA) and non-Hispanic White (NHW) BCSs were purposively recruited and enrolled into the 52-week randomized controlled trial. The interventions included 20 weeks of supervised moderate-intensity aerobic and resistance training followed by 32 weeks of unsupervised exercise called IMPROVE (n = 108) and a 20-week SG+Fitbit program followed by 32 weeks of unsupervised activity (n = 105). Study outcomes were assessed at 20 and 52 weeks. The primary outcome was the change in Short Physical Performance Battery (SPPB) scores 20 weeks from the baseline between arms. Secondary outcomes included change in the 6-Minute Walk Test (6MWT) in meters 20 weeks from the baseline between arms. General linear regression and multivariable logistic regression analyses were used. RESULTS: The mean age was 71.9 years (SD, 5.9 years), and 44% were AA. SPPB scores did not differ between arms (adjusted difference in mean change, 0.13; 95% CI, -0.28 to 0.55; P = .53). However, the exercise arm (vs the SG+Fitbit arm) improved on the 6MWT (21.6 m; 95% CI, 2.5-40.6 m; P = .03). Race moderated the exercise effect on the 6MWT (adjusted interaction effect, 43.3 m; 95% CI, 6.3-80.2 m; P = .02); this implied that the change in the adjusted mean for the 6MWT at 20 weeks from the baseline was 43.3 m higher in AA exercise participants versus NHW exercise participants. CONCLUSIONS: Combined aerobic and resistance exercise appears to improve physical performance in older BCSs, and the exercise effect might be moderated by race, with AAs appearing to derive larger benefits in comparison with NHWs. Larger studies are warranted to confirm the study findings.

Sex modifies the association between HIV and coronary artery disease among older adults in Uganda.

INTRODUCTION: Little is known about the epidemiology of coronary artery disease (CAD) in sub-Saharan Africa, where the majority of people living with HIV (PLHIV) live. We assessed the association of HIV with CAD and explored relationships with monocyte activation in sex-stratified analyses of older PLHIV and people without HIV (PWOH) in Uganda. METHODS: The Ugandan Study of HIV effects on the Myocardium and Atherosclerosis (mUTIMA) follows 100 PLHIV on antiretroviral therapy (ART) and 100 age- and sex-matched PWOH controls in Kampala, Uganda; all >45 years of age with >1 cardiovascular disease risk factor. At the year 2 exam (2017-2019), 189 participants had available coronary calcium score and 165 had coronary CT angiography (CCTA) for this analysis. A subset of participants (n = 107) had both CCTA and fresh whole blood flow cytometry for monocyte phenotyping. RESULTS: Median age was 57.8 years and 63% were females. Overall, 88% had hypertension, 37% had diabetes and 4% were smokers. Atherosclerotic cardiovascular disease (ASCVD) risk was modestly higher for PWOH, but not statistically significant (median 10-year ASCVD risk 7.2% for PLHIV vs. 8.6% for PWOH, p = 0.09). Median duration of ART was 12.7 years and 86% had suppressed viral load. Despite a high prevalence of risk factors, only 34/165 (21%, 95% CI 15-28%) had any coronary plaque. After adjustment for ASCVD risk score, HIV status was not associated with CAD (OR 0.55, 95% CI 0.23-1.30) but was associated with more severe CAD (segment severity score>3) among those with disease (OR 10.9, 95% CI 1.67-70.45). Females had a trend towards higher odds of CAD among PLHIV (OR 4.1, 95% CI 0.4-44.9), but a trend towards lower odds of CAD among PWOH (OR 0.30; 95% CI 0.07-1.3; HIV*sex interaction p = 0.019). CAD was positively correlated with classical monocytes (r = 0.3, p = 0.012) and negatively correlated with CX3CR1 expression (r = -0.31, p = 0.011) in PLHIV and negatively correlated with patrolling monocytes (r = -0.36, p = 0.031) and tissue factor expression (r = -0.39, p = 0.017) in PWOH. CONCLUSIONS: Our results suggest that HIV may be associated more with severity rather than the presence of CAD in Uganda. Sex differences in the HIV effect suggest that tailored CAD prevention strategies may be required in this setting.

Variations in Sleep Characteristics and Glucose Regulation in Young Adults With Type 1 Diabetes.

CONTEXT: Short sleep duration and sleep disruptions are associated with impaired glucoregulation in type 1 diabetes (T1D). However, the mechanistic pathways between sleep and glucose variability remain unclear. OBJECTIVE: To determine within- and between-person associations between objective sleep-wake characteristics and glucose variability indices. METHODS: Multilevel models were used to analyze concurrent sleep and glucose patterns over 7 days in 42 young adults with T1D in their natural home environment. Young adults with T1D (mean age 22.2 ± 3.0 years, HbA1c 7.2%, 32.6% male) for at least 6 months with no other medical or major psychiatric comorbidity were included. Sleep-wake characteristics were measured via wrist actigraphy and glucose variability indices via a continuous glucose monitor (CGM). RESULTS: Lower sleep efficiency predicted higher glucose variability (less time in range ß = 0.011 and more time in hyperglycemia ß = -0.011) within-person. A longer wake after sleep onset and more sleep disruptions were associated with higher glucose variability between persons (ß = 0.28 and 0.31). Higher glucose variability predicted poorer sleep within-person (delayed bedtime, waketime, mid-sleep time, and lower sleep efficiency), while higher glucose variability was associated with poorer sleep and more sleep disruptions between persons (lower sleep efficiency, longer wake after sleep onset, and a higher sleep fragmentation index). CONCLUSION: Clinicians can address the reciprocal nature of the sleep-glucose relationship by optimizing sleep and targeting efforts toward a euglycemic range overnight. Sleep habits are a modifiable personal target in diabetes care.

Receipt of Serial Endoscopy Procedures Prior to Esophageal Adenocarcinoma Diagnosis Is Associated with Better Survival.

BACKGROUND: The poor prognosis of esophageal adenocarcinoma (EAC) has focused efforts on early detection by serial endoscopic surveillance of Barrett's esophagus (BE). Previously, we reported that receipt of endoscopy before EAC diagnosis was associated with improved survival. AIM: We aimed to refine our previous analysis, assessing surveillance as measured by performance of serial endoscopy before EAC diagnosis and evaluating its association with stage and survival. METHODS: A retrospective cohort study was performed using the Surveillance, Epidemiology and End Results-Medicare database. Patients aged ≥ 70 years with EAC diagnosed during 1998-2009 were identified. Diagnosis with BE and receipt of ≥ 2 upper endoscopic procedures within 5 years before cancer diagnosis were identified. We compared a reference group not receiving serial endoscopy to 3 patterns based on ≥ 2 endoscopy dates relative to a timepoint 2 years before cancer diagnosis: "remote," "recent," and "sustained." RESULTS: Among 5532 patients, 28% (n = 1,575) had localized stage. Thirteen percent (n = 703) received ≥ 2 endoscopic procedures before cancer diagnosis: 224, 298, and 181 in the "recent," "remote," and "sustained" groups. Serial endoscopy and prior BE were associated with localized stage ("sustained" group OR 2.95, 95% confidence interval [CI] 2.07, 4.19; prior BE OR 2.68, 95% CI 2.03, 3.56). Serial endoscopy was associated with improved survival even with adjustment for lead time bias ("sustained" group HR 0.45, 95% CI 0.37, 0.55) and length time bias. CONCLUSIONS: Sustained endoscopy was associated with earlier stage and improved survival. These results support the role of sustained surveillance in early detection of EAC.

A Pilot Study Evaluating the Effects of a Technology-Based and Positive Psychological Training Intervention on Blood Pressure in African Americans With Hypertension.

Behavioral interventions consolidating technology are underutilized and do not reach diverse populations such as African Americans with hypertension. This pilot study aimed to evaluate the effects of a theoretically derived, technology-based intervention in African Americans with hypertension. African Americans with hypertension (N = 18; age range 25-85; 72.22% females) were randomized to the technology-based plus positive psychological training (PPT) experimental group (n = 10) or the comparison group (n = 8) for 12 weeks. The technology-based intervention included analytic components (web-based education, self-monitoring of blood pressure [BP], and medication management using a commercially free app-Medisafe) and an emotional component (comprised of skills and behaviors directed at engaging 1 in positive activities to help build increasing healthy behaviors). The comparison group received the technology-based intervention alone. Demographic information, self-management cognitive processes, self-management behaviors, and health status outcomes were assessed. After completing the 12-week intervention, the groups did not significantly differ in health outcomes, health behavior outcomes, and technology utilization outcomes. Mean systolic BP decrease 6.02 mmHg (standard deviation [SD] = 22.75) in the comparison group and 1.1 mmHg (SD = 20.64; P = .439) in the experimental group. Diastolic BP decreased 0.1 mmHg (SD = 11.78) in the comparison group and 1.5 mmHg (SD = 12.7; P = .757) in the experimental group. Our findings suggest that behavioral interventions using technology have the potential to improve self-management outcomes among African American populations. Further research is warranted in a larger sample size and a longer time frame to identify the intervention's effectiveness.

Airway Thiol-NO Adducts as Determinants of Exhaled NO.

Thiol-NO adducts such as S-nitrosoglutathione (GSNO) are endogenous bronchodilators in human airways. Decreased airway S-nitrosothiol concentrations are associated with asthma. Nitric oxide (NO), a breakdown product of GSNO, is measured in exhaled breath as a biomarker in asthma; an elevated fraction of expired NO (FENO) is associated with asthmatic airway inflammation. We hypothesized that FENO could reflect airway S-nitrosothiol concentrations. To test this hypothesis, we first studied the relationship between mixed expired NO and airway S-nitrosothiols in patients endotracheally intubated for respiratory failure. The inverse (Lineweaver-Burke type) relationship suggested that expired NO could reflect the rate of pulmonary S-nitrosothiol breakdown. We thus studied NO evolution from the lungs of mice (GSNO reductase -/-) unable reductively to catabolize GSNO. More NO was produced from GSNO in the -/- compared to wild type lungs. Finally, we formally tested the hypothesis that airway GSNO increases FENO using an inhalational challenge model in normal human subjects. FENO increased in all subjects tested, with a median t1/2 of 32.0 min. Taken together, these data demonstrate that FENO reports, at least in part, GSNO breakdown in the lungs. Unlike GSNO, NO is not present in the lungs in physiologically relevant concentrations. However, FENO following a GSNO challenge could be a non-invasive test for airway GSNO catabolism.

Circadian characteristics of the rest-activity rhythm, executive function, and glucose fluctuations in young adults with type 1 diabetes.

Circadian alignment is an important element in individual health, and one behavioral marker, rest-activity rhythm, could influence self-management in young adults with type 1 diabetes (T1D). Little is known about the rest-activity rhythms, executive function, and glycemia among young adults with type 1 diabetes (T1D). The purpose of this study was to evaluate parametric and nonparametric circadian characteristics of the rest-activity rhythm and the associations between these variables, sleep-wake behavior, executive function, and glycemia among young adults with T1D. Young adults with T1D, recruited from diabetes clinics, wore wrist actigraphs and a continuous glucose monitor (CGM) concurrently for 6-14 days. Participants completed a 3-minute Trail Making Test on paper and electronic questionnaires - 8-item PROMIS v1.0 Emotional Distress Scale, 17-item Diabetes Distress Scale, including twice-daily Pittsburgh sleep diaries. Cosinor and nonparametric analyses were used to compute the rest-activity rhythm parameters, and linear regression modeling procedures were performed to determine the associations among the study variables. The sample included 46 young adults (mean age 22.3 ± 3.2; 32.6% male; 84.8% non-Hispanic White, HbA1c mean 7.2 ± 1.1%, BMI mean 27.0 ± 4.4 kg/m2). A number of parametric associations were observed between a stronger rhythm, better objective sleep-wake characteristics, and less daytime sleepiness. Nonparametric circadian parameters were significantly associated with several outcomes: a stronger rhythm adherence (higher inter-daily stability) with better objective sleep-wake characteristics, better executive function, lower diabetes distress, less hyperglycemia risk, and more time spent in hypoglycemia/hypoglycemia risk; and a more robust rhythm (higher relative amplitude) with better objective sleep-wake characteristics and more time spent in hypoglycemia/higher hypoglycemia risk. Future work should be directed at designs that test causality, such as interventions directed at the strength and stability of rest-activity rhythms, for the potential to improve glucoregulation and other diabetes outcomes.

Randomized trial of a web-based nurse education intervention to increase discussion of clinical trials.

BACKGROUND: Clinical trials are a critical source of evidence for oncology care, yet very few patients participate. Among healthcare providers, nurses spend the most time with cancer patients and are the most highly trusted professionals. We developed and evaluated an educational program for oncology nurses targeting knowledge, attitudes, self-efficacy and perceived norms to facilitate discussion about clinical trials and support patient decision making. METHODS: A nationwide sample of oncology nurses were randomly assigned to receive general clinical trials education delivered as text (attention control) vs. tailored video vignettes (intervention) in a web-based continuing education program. Participants completed a baseline assessment and follow up assessments immediately after the educational program and three months later. The primary outcome was intention to discuss clinical trials with patients. Secondary outcomes were knowledge and attitudes about clinical trials, self-efficacy, and perceived norms. RESULTS: 1393 nurses enrolled and completed the educational program and post-intervention assessment (720 control, 673 video). Both text education and tailored video education increased intention to discuss clinical trials with patients, with a greater effect in the video group (p < .0001). Likewise, knowledge, attitudes, perceived behavioral control, and perceived norms were all improved with education in both groups, and the magnitude of benefit was greater (p < .001) for the video group in all outcomes except knowledge. CONCLUSION: A one-time online educational program for oncology nurses improves knowledge, attitudes, self-efficacy and intention to engage patients in discussions about clinical trials. A tailored video format was associated with a greater effect than standard text only material.