Design of a multi-institutional neurocognitive discovery study in adult congenital heart disease (MINDS-ACHD).

BACKGROUND: Neurocognitive dysfunction (NCD) is a common comorbidity among children with congenital heart disease (CHD). However, it is unclear how underlying CHD and its sequelae combine with genetics and acquired cardiovascular and neurological disease to impact NCD and outcomes across the lifespan in adults with CHD. METHODS: The Multi-Institutional Neurocognitive Discovery Study in Adults with Congenital Heart Disease (MINDS-ACHD) is a partnership between the Pediatric Heart Network (PHN) and the Adult Alliance for Research in Congenital Cardiology (AARCC) that examines objective and subjective neurocognitive function and genetics in young ACHD. This multicenter cross-sectional pilot study is enrolling 500 young adults between 18 and 30 years with moderate or severe complexity CHD at 14 centers in North America. Enrollment includes 4 groups (125 participants each): (1) d-looped Transposition of the Great Arteries (d-TGA); (2) Tetralogy of Fallot (TOF); (3) single ventricle (SV) physiology; and (4) "other moderately or severely complex CHD." Participants complete the standardized tests from the NIH Toolbox Cognitive Battery, the NeuroQoL, the Hospital Anxiety and Depression Scale, and the PROMIS Global QoL measure. Clinical and demographic variables are collected by interview and medical record review, and an optional biospecimen is collected for genetic analysis. Due to the COVID-19 pandemic, participation may be done remotely. Tests are reviewed by a Neurocognitive Core Laboratory. CONCLUSIONS: MINDS-ACHD is the largest study to date characterizing NCD in young adults with moderate or severely complex CHD in North America. Its results will provide valuable data to inform screening and management strategies for NCD in ACHD and improve lifelong care.

The Use of Virtual Reality Learning on Transition Education in Adolescents with Congenital Heart Disease.

Improvement in congenital heart disease (CHD) outcomes has created a growing population of adolescents and young adults with unique health needs that require thoughtful transition planning and eventual transfer of care to an adult provider. Often, poor health literacy and limited resources can lead to interrupted care, which places them at risk for adverse health-related consequences. In 2019, the Wisconsin Adult Congenital Heart Disease transition program partnered with Stanford Virtual Heart (SVH), a virtual reality (VR) platform, to allow young adult patients to learn about their CHD in a clinic-based setting. We completed a single-center pilot study to evaluate these patients' experience and perceptions to using VR during their transition education. At an initial transition visit, we used an immediate post-VR experience survey, scored using Likert scales of 1-5 (1 = strongly disagree, 5 = strongly agree). Twenty-two patients (13 males) between the ages of 16 and 19 participated. Lesions included pulmonary stenosis, Tetralogy of Fallot, atrial and ventricular septal defect, coarctation, aortic stenosis, hypoplastic left heart syndrome, and patent ductus arteriosus. Likert averages were 4.7 for finding VR helped with understanding their heart lesion, 4.6 for finding VR helped with understanding their heart surgery, 4.7 for enjoying the VR heart simulation, and 4.6 for finding that it was a good use of time. This study demonstrates that adolescents enjoyed using SVH and found it helpful. Clinical implementation shows promise as a plausible adjunct tool for transition education.

Diagnostic Performance of High-Sensitivity Cardiac Troponin T Strategies and Clinical Variables in a Multisite US Cohort.

BACKGROUND: European data support the use of low high-sensitivity troponin (hs-cTn) measurements or a 0/1-hour (0/1-h) algorithm for myocardial infarction to exclude major adverse cardiac events (MACEs) among patients in the emergency department with possible acute coronary syndrome. However, modest US data exist to validate these strategies. This study evaluated the diagnostic performance of an initial hs-cTnT measure below the limit of quantification (LOQ: 6 ng/L), a 0/1-h algorithm, and their combination with history, ECG, age, risk factors, and initial troponin (HEART) scores for excluding MACE in a multisite US cohort. METHODS: A prospective cohort study was conducted at 8 US sites, enrolling adult patients in the emergency department with symptoms suggestive of acute coronary syndrome and without ST-elevation on ECG. Baseline and 1-hour blood samples were collected, and hs-cTnT (Roche; Basel, Switzerland) was measured. Treating providers blinded to hs-cTnT results prospectively calculated HEART scores. MACE (cardiac death, myocardial infarction, and coronary revascularization) at 30 days was adjudicated. The proportion of patients with initial hs-cTnT measures below the LOQ and risk according to a 0/1-h algorithm was determined. The negative predictive value (NPV) was calculated for both strategies when used alone or with a HEART score. RESULTS: Among 1462 participants with initial hs-cTnT measures, 46.4% (678 of 1462) were women and 37.1% (542 of 1462) were Black with an age of 57.6±12.9 (mean±SD) years. MACEs at 30 days occurred in 14.4% (210 of 1462) of participants. Initial hs-cTnT measures below the LOQ occurred in 32.8% (479 of 1462), yielding an NPV of 98.3% (95% CI, 96.7-99.3) for 30-day MACEs. A low-risk HEART score with an initial hs-cTnT below the LOQ occurred in 20.1% (294 of 1462), yielding an NPV of 99.0% (95% CI, 97.0-99.8) for 30-day MACEs. A 0/1-h algorithm was complete in 1430 patients, ruling out 57.8% (826 of 1430) with an NPV of 97.2% (95% CI, 95.9-98.2) for 30-day MACEs. Adding a low HEART score to the 0/1-h algorithm ruled out 30.8% (441 of 1430) with an NPV of 98.4% (95% CI, 96.8-99.4) for 30-day MACEs. CONCLUSIONS: In a prospective multisite US cohort, an initial hs-cTnT below the LOQ combined with a low-risk HEART score has a 99% NPV for 30-day MACEs. The 0/1-h hs-cTnT algorithm did not achieve an NPV >99% for 30-day MACEs when used alone or with a HEART score. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02984436.

Physical Activity and Exercise for Cardiorespiratory Health and Fitness in Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular disease (CVD), major adverse CVD events, and cardiovascular mortality. Low levels of physical activity and reduced cardiorespiratory fitness further compound the health consequences in this patient population. Aerobic exercise alone and the combination of aerobic and resistance exercise have beneficial effects for improving aerobic capacity while resistance exercise alone improves strength and skeletal muscle health. Given the prevalence of CVD in CKD patients and limited treatment options targeting traditional and non-traditional CVD risk factors in this population, the incoroporation of physical activity and exercise into the care of CKD seems critical for improving patient outcomes. Therefore, the purpose of this narrative review is to discuss the evidence of physical activity and exercise in CKD patients and the effects on cardiovascular outcomes and fitness.

Fatigability and the Role of Neuromuscular Impairments in Chronic Kidney Disease.

BACKGROUND: The combination of neuromuscular impairments plus psychosocial aspects of chronic kidney disease (CKD) may predispose these patients to greater risk for experiencing increased levels of fatigability. There has been extensive clinical and scientific interest in the problem of fatigue in CKD and end-stage kidney disease (ESKD) patients, whereas less attention has been directed to understanding fatigability. Accordingly, the primary purposes of this review are to (1) discuss fatigue and fatigability and their potential interactions in patients with CKD and ESKD, (2) provide evidence for increased fatigability in CKD and ESKD patients, (3) examine how commonly experienced neuromuscular impairments in CKD and ESKD patients may contribute to the severity of performance fatigability, and (4) highlight preliminary evidence on the effects of exercise as a potential clinical treatment for targeting fatigability in this population. SUMMARY: Fatigue is broadly defined as a multidimensional construct encompassing a subjective lack of physical and/or mental energy that is perceived by the individual to interfere with usual or desired activities. In contrast, fatigability is conceptualized within the context of physical activity and is quantified as the interactions between reductions in objective measures of performance (i.e., performance fatigability) and perceptual adjustments regulating activity performance (i.e., perceived fatigability). We propose herein a conceptual model to extend current understandings of fatigability by considering the interactions among fatigue, perceived fatigability, and performance fatigability. Neuromuscular impairments reported in patients with CKD and ESKD, including reductions in force capacity, skeletal muscle atrophy, mitochondrial dysfunction, abnormal skeletal muscle excitability, and neurological complications, may each contribute to the greater performance fatigability observed in these patients. KEY MESSAGES: Considering the interactions among fatigue, perceived fatigability, and performance fatigability provides a novel conceptual framework to advance the understanding of fatigability in CKD and ESKD patients. Measures of fatigability may provide valuable clinical insights into the overall health status of CKD and ESKD patients. Existing data suggest that CKD and ESKD patients are at greater risk of experiencing increased fatigability, partly due to neuromuscular impairments associated with reduced kidney function. Further investigations are warranted to determine the potential clinical role fatigability measures can play in monitoring the health of CKD and ESKD patients, and in identifying potential treatments targeting fatigability in this patient population.

Mineralocorticoid Receptor Antagonists in the Treatment of Diabetic Kidney Disease: Their Application in the Era of SGLT2 Inhibitors and GLP-1 Receptor Agonists.

PURPOSE OF REVIEW: This review focuses on new clinical data involving a novel class of drugs, nonsteroidal mineralocorticoid receptor antagonists (NS-MRAs), specifically, finerenone and its effects on cardiovascular and diabetic kidney disease outcomes. RECENT FINDINGS: NS-MRAs are a novel class of agents for treating diabetic kidney disease (DKD). While they are chemically and pharmacologically distinct from steroidal MRAs (spironolactone, eplerenone), they effectively inhibit the MR receptor differently. Inhibition of MR receptor activation reduces inflammatory and profibrotic pathways involving the cardiorenal/vascular systems. Small diabetic kidney disease (DKD) clinical studies demonstrate that steroidal MRAs reduce albuminuria relative to placebo, although hyperkalemia is a major adverse event that has precluded large outcome trials. The NS-MRA, finerenone, demonstrated slowed progression of DKD and reduction of cardiovascular death primarily driven by reduced heart failure incidence in two separate randomized controlled clinical trials (FIDELIO and FIGARO). Use of NS-MRAs, therefore, provides a third "pillar of therapy" to reduce cardiorenal events added to blockers of the renin-angiotensin system and SGLT2 inhibitors. If the pending outcome trial, FLOW, is positive, potentially, GLP1-RAs may also be part of this "pillar" structure.

Unrecognized cardiac arrests: A one-year review of audio from emergency medical dispatch calls.

OBJECTIVES: Immediate recognition of out-of-hospital cardiac arrest (OHCA) by Emergency Medical Dispatch (EMD) operators is crucial to facilitate timely initiation of telephone cardiopulmonary resuscitation (T-CPR) and to enable the appropriate level of Emergency Medical Services (EMS) response. The goal of this study was to identify patterns that can increase EMD-level recognition of cardiac arrests prior to EMS arrival. METHODS: The Combined Communications Center in Alachua County, Florida provided audio recordings of all emergency calls from January 1, 2018 to November 16, 2018 dispatched as a chief complaint other than OHCA, but later identified as cardiac arrest. A multi-disciplinary medical team transcribed and analyzed the calls to determine common themes and trends. RESULTS: Out of an initial 81 calls meeting inclusion criteria, 69 were immediately recognized as OHCA by EMDs, leaving 12 calls of unrecognized OHCA. In 11 of 12 calls respiratory issues were described to EMD. In 10 of 12 calls the subject was described as unconscious, and in the other 2 calls, the subject lost consciousness during the call. CONCLUSIONS: Lack of recognition of OHCA by EMD occurred in most calls due to difficulty communicating the subject's respiratory status. Further emphasis should be placed on identifying non-viable respirations in unconscious patients in EMD training and algorithms to increase recognition of OHCA and initiation of T-CPR. A multi-year review of a comparable dataset from geographically and socioeconomically diverse regions in the United States can validate and expand these preliminary trends.

Pregabalin for Recurrent Seizures in Critical Illness: A Promising Adjunctive Therapy, Especially for cyclic Seizures.

BACKGROUND: Pregabalin (PGB) is an effective adjunctive treatment for focal epilepsy and acts by binding to the alpha2-delta subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release. Limited data exist on its use in the neurocritical care setting, including cyclic seizures-a pattern of recurrent seizures occurring at nearly regular intervals. Although the mechanism underpinning cyclic seizures remains elusive, spreading excitation linked to spreading depolarizations may play a role in seizure recurrence and periodicity. PGB has been shown to increase spreading depolarization threshold; hence, we hypothesized that the magnitude of antiseizure effect from PGB is more pronounced in patients with cyclic versus noncyclic seizures in a critically ill cohort with recurrent seizures. METHODS: We conducted a retrospective case series of adults admitted to two academic neurointensive care units between January 2017 and March 2019 who received PGB for treatment of seizures. Data collected included demographics, etiology of brain injury, antiseizure medications, and outcome. Continuous electroencephalogram recordings 48 hours before and after PGB administration were reviewed by electroencephalographers blinded to the administration of antiseizure medications to obtain granular data on electrographic seizure burden. Cyclic seizures were determined quantitatively (i.e., < 50% variation of interseizure intervals for at least 50% of consecutive seizures). Coprimary outcomes were decrease in hourly seizure burden in minutes and decrease in seizure frequency in the 48 hours after PGB initiation. We used nonparametric tests for comparison of seizure frequency and burden and segmented linear regression to assess PGB effect. RESULTS: We included 16 patients; the median age was 69 years, 11 (68.7%) were women, three (18.8%) had undergone a neurosurgical procedure, and five (31%) had underlying epilepsy. All seizures had focal onset; ten patients (62.5%) had cyclic seizures. The median hourly seizure burden over the 48 hours prior to PGB initiation was 1.87 min/hour (interquartile range 1.49-8.53), and the median seizure frequency was 1.96 seizures/hour (interquartile range 1.06-3.41). In the 48 hours following PGB (median daily dose 300 mg, range 75-300 mg), the median number of seizures per hour was reduced by 0.80 seizures/hour (95% confidence interval 0.19-1.40), whereas the median hourly seizure burden decreased by 1.71 min/hour (95% confidence interval 0.38-3.04). When we compared patients with cyclic versus noncyclic seizures, there was a relative decrease in hourly seizure frequency (- 86.7% versus - 2%, p = 0.04) and hourly seizure burden (- 89% versus - 7.8%, p = 0.03) at 48 hours. CONCLUSIONS: PGB was associated with a relative reduction in seizure burden in neurocritically ill patients with recurrent seizures, especially those with cyclic seizures, and may be considered in the therapeutic arsenal for refractory seizures. Whether this effect is mediated via modulation of spreading depolarization requires further study.

Assessing Nephrology Fellows' Skills in Communicating About Kidney Replacement Therapy and Kidney Biopsy: A Multicenter Clinical Simulation Study on Breaking Bad News.

RATIONALE & OBJECTIVE: Interpersonal communication skills and professionalism competencies are difficult to assess among nephrology trainees. We developed a formative "Breaking Bad News" simulation and implemented a study in which nephrology fellows were assessed with regard to their skills in providing counseling to simulated patients confronting the need for kidney replacement therapy (KRT) or kidney biopsy. STUDY DESIGN: Observational study of communication competency in the setting of preparing for KRT for kidney failure, for KRT for acute kidney injury (AKI), or for kidney biopsy. SETTING & PARTICIPANTS: 58 first- and second-year nephrology fellows assessed during 71 clinical evaluation sessions at 8 training programs who participated in an objective structured clinical examination of simulated patients in 2017 and 2018. PREDICTORS: Fellowship training year and clinical scenario. OUTCOME: Primary outcome was the composite score for the "overall rating" item on the Essential Elements of Communication-Global Rating Scale 2005 (EEC-GRS), as assessed by simulated patients. Secondary outcomes were the score for EEC-GRS "overall rating" item for each scenario, score < 3 for any EEC-GRS item, Mini-Clinical Examination Exercise (Mini-CEX) score < 3 on at least 1 item (as assessed by faculty), and faculty and fellow satisfaction with simulation exercise (via a survey they completed). ANALYTICAL APPROACH: Nonparametric tests of hypothesis comparing performance by fellowship year (primary goal) and scenario. RESULTS: Composite scores for EEC-GRS overall rating item were not significantly different between fellowship years (P = 0.2). Only 4 of 71 fellow evaluations had an unsatisfactory score for the EEC-GRS overall rating item on any scenario. On Mini-CEX, 17% scored < 3 on at least 1 item in the kidney failure scenario; 37% and 53% scored < 3 on at least 1 item in the AKI and kidney biopsy scenarios, respectively. In the survey, 96% of fellows and 100% of faculty reported the learning objectives were met and rated the experience good or better in 3 survey rating questions. LIMITATIONS: Relatively brief time for interactions; limited familiarity with and training of simulated patients in use of EEC-GRS. CONCLUSIONS: The fellows scored highly on the EEC-GRS regardless of their training year, suggesting interpersonal communication competency is achieved early in training. The fellows did better with the kidney failure scenario than with the AKI and kidney biopsy scenarios. Structured simulated clinical examinations may be useful to inform curricular choices and may be a valuable assessment tool for communication and professionalism.

Differences in perceptions of transition readiness between parents and teens with congenital heart disease: do parents and teens agree?

BACKGROUND: Amongst patients with CHD, the time of transition to adulthood is associated with lapses in care leading to significant morbidity. The purpose of this study was to identify differences in perceptions between parents and teens in regard to transition readiness. METHODS: Responses were collected from 175 teen-parent pairs via the validated CHD Transition Readiness survey and an information request checklist. The survey was distributed via an electronic tablet at a routine clinic visit. RESULTS: Parents reported a perceived knowledge gap of 29.2% (the percentage of survey items in which a parent believes their teen does not know), compared to teens self-reporting an average of 25.9% of survey items in which they feel deficient (p = 0.01). Agreement was lowest for long-term medical needs, physical activities allowed, insurance, and education. In regard to self-management behaviours, agreement between parent and teen was slight to moderate (weighted κ statistic = 0.18 to 0.51). For self-efficacy, agreement ranged from slight to fair (weighted κ = 0.16 to 0.28). Teens were more likely to request information than their parents (79% versus 65% requesting at least one item) particularly in regard to pregnancy/contraception and insurance. CONCLUSION: Parents and teens differ in several key perceptions regarding knowledge, behaviours, and feelings related to the management of heart disease. Specifically, parents perceive a higher knowledge deficit, teens perceive higher self-efficacy, and parents and teens agree that self-management is low.

Transition Readiness in Teens and Young Adults with Congenital Heart Disease: Can We Make a Difference?

OBJECTIVES: To examine changes in transition readiness (knowledge, self-efficacy, self-management) over time and explore factors associated with transition readiness, including psychosocial quality of life (QOL) and health service utilization in teens/young adults with congenital heart disease. STUDY DESIGN: In a multicenter prospective cohort study, 356 patients, age 14-27 years, completed transition readiness and QOL assessments at routine cardiology visits at baseline and 1-year follow-up. RESULTS: Median patient age was 19.8 years at 1.03 years (IQR 0.98-1.24) following baseline transition readiness assessment. Average knowledge deficit scores decreased at follow-up (P < .0001) and self-efficacy scores increased (P < .0001). Self-management scores increased (P < .0001), but remained low (mean 57.7, 100-point scale). Information was requested by 73% of patients at baseline and was associated with greater increase in knowledge at follow-up (P = .005). Increased knowledge (P = .003) and perceived self-efficacy (P = .01) were associated with improved psychosocial QOL, but not health service utilization at follow-up. Patients who preferred face-to-face information from healthcare providers (47%) vs other information sources were more likely to request information (P < .0001). In patients <18 years old, greater agreement between teen and parental perception of teen's knowledge was associated with greater increase in patient knowledge (P = .02) and self-efficacy (P = .003). CONCLUSION: Transition readiness assessment demonstrated improved knowledge, self-efficacy, and self-management at 1-year follow-up in teens/young adults with congenital heart disease. Improved knowledge and self-efficacy were associated with improved psychosocial QOL. Self-management remained low. Supplemental media for conveying information and greater involvement of parents may be needed to optimize transition readiness.

Patient, Neighborhood, and Spatial Determinants of Out-of-Hospital Cardiac Arrest Outcomes Throughout the Chain of Survival: A Community-Oriented Multilevel Analysis.

Objective: Global and national trends of out-of-hospital cardiac arrest (OHCA) have been examined; however, geographic variation and socioeconomic disparities of OHCA outcomes in the community setting are less understood. We developed and tested a replicable, community-oriented assessment strategy aimed to identify spatial variations in OHCA outcomes using socioeconomic, prehospital, and in-hospital factors. Methods: Emergency medical service (EMS) records of adult, non-traumatic OHCA within Alachua County, FL (2012-2017) were retrospectively reviewed and matched to corresponding medical records at the University of Florida (UF). Incidence of cardiac arrest was geocoded to census tracts and connected to U.S. census socioeconomic attribute data. Primary outcomes include survival to emergency department (ED), hospital admission, discharge, and discharge to home. Multilevel mixed-effects logistic regression models were developed to assess sub-county geographic variance, probabilities of survival, and prehospital risk factors. Getis-Ord Gi statistic and Moran's I-test was applied to assess spatial clustering in outcome survival rates. Results: Of the 1562 OHCA cases extracted from EMS records, 1,335 (85.5%) were included with 372 transported to study site. Predicted probability of survival to ED was 57.0% (95CI: 51.3-62.3%). Of transported cases to study site ED, predicted probabilities of survival was to 41.7% (95CI: 36.1-47.6%) for hospital admission, 16.1% (95CI: 10.7-23.5%) for hospital discharge, and 7.1% (95CI: 3.7-13.3%) for home discharge. Census tracts accounted for significant variability in survival to ED (p < 0.001), discharge (p = 0.031), and home discharge outcomes (p = 0.036). There was no significant geographic variation in survival to admission outcome. Neighborhood-level factors significantly improved model fit for survival to ED, discharge, and discharge home outcomes. Multiple modifiable patient- and neighborhood-level variables of interest were identified, including rural-urban differences. Conclusion: We identified important geographic disparities that exist in OHCA outcomes at the community level. By using a replicable schematic, this variation can be explained through community-oriented modifiable socioeconomic and prehospital factors.

Human RTEL1 stabilizes long G-overhangs allowing telomerase-dependent over-extension.

Telomere maintenance protects the cell against genome instability and senescence. Accelerated telomere attrition is a characteristic of premature aging syndromes including Dyskeratosis congenita (DC). Mutations in hRTEL1 are associated with a severe form of DC called Hoyeraal-Hreidarsson syndrome (HHS). HHS patients carry short telomeres and HHS cells display telomere damage. Here we investigated how hRTEL1 contributes to telomere maintenance in human primary as well as tumor cells. Transient depletion of hRTEL1 resulted in rapid telomere shortening only in the context of telomerase-positive cells with very long telomeres and high levels of telomerase. The effect of hRTEL1 on telomere length is telomerase dependent without impacting telomerase biogenesis or targeting of the enzyme to telomeres. Instead, RTEL1 depletion led to a decrease in both G-overhang content and POT1 association with telomeres with limited telomere uncapping. Strikingly, overexpression of POT1 restored telomere length but not the overhang, demonstrating that G-overhang loss is the primary defect caused by RTEL1 depletion. We propose that hRTEL1 contributes to the maintenance of long telomeres by preserving long G-overhangs, thereby facilitating POT1 binding and elongation by telomerase.

Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial.

Background: Although depression is common among patients receiving maintenance hemodialysis, data on their acceptance of treatment and on the comparative efficacy of various therapies are limited. Objective: To determine the effect of an engagement interview on treatment acceptance (phase 1) and to compare the efficacy of cognitive behavioral therapy (CBT) versus sertraline (phase 2) for treating depression in patients receiving hemodialysis. Design: Multicenter, parallel-group, open-label, randomized controlled trial. (ClinicalTrials.gov: NCT02358343). Setting: 41 dialysis facilities in 3 U.S. metropolitan areas. Participants: Patients who had been receiving hemodialysis for at least 3 months and had a Beck Depression Inventory-II score of 15 or greater; 184 patients participated in phase 1, and 120 subsequently participated in phase 2. Intervention: Engagement interview versus control visit (phase 1) and 12 weeks of CBT delivered in the dialysis facility versus sertraline treatment (phase 2). Measurements: The primary outcome for phase 1 was the proportion of participants who started depression treatment within 28 days. For phase 2, the primary outcome was depressive symptoms measured by the Quick Inventory of Depressive Symptoms-Clinician-Rated (QIDS-C) at 12 weeks. Results: The proportion of participants who initiated treatment after the engagement or control visit did not differ (66% vs. 64%, respectively; P = 0.77; estimated risk difference, 2.1 [95% CI, -12.1 to 16.4]). Compared with CBT, sertraline treatment resulted in lower QIDS-C depression scores at 12 weeks (effect estimate, -1.84 [CI, -3.54 to -0.13]; P = 0.035). Adverse events were more frequent in the sertraline than the CBT group. Limitation: No randomized comparison was made with no treatment, and persistence of treatment effect was not assessed. Conclusion: An engagement interview with patients receiving maintenance hemodialysis had no effect on their acceptance of treatment for depression. After 12 weeks of treatment, depression scores were modestly better with sertraline treatment than with CBT. Primary Funding Source: Patient-Centered Outcomes Research Institute, Dialysis Clinic, Kidney Research Institute, and National Institute of Diabetes and Digestive and Kidney Diseases.

Prevalence, Risk Factors, and Impact of Obstructive Sleep Apnea in Adults with Congenital Heart Disease.

The objective of our study was to determine the prevalence, risk factors, and the impact of obstructive sleep apnea (OSA) in the adult with congenital heart disease (ACHD). One hundred forty-nine consecutive patients seen in our ACHD program were screened for OSA using the Berlin Questionnaire. Demographic and clinical details on subjects were collected through a chart review. Clinical variables were analyzed to determine risk factors for positive OSA screen, as well as associated outcomes. Seventy-seven (52%) of our cohort were females. The median age of the cohort was 33 years (range = 18-74) and median weight was 79 kg (range = 50-145 kg). Overall, 47 (31%) of our cohort were found to have a positive OSA screen using the Berlin questionnaire. Median age of the patients whom tested positive was 34 years. Compared to patients with a negative screen, patients with a positive OSA screen were more likely to be heavier with a median weight of 99 kg vs 71 kg (p < 0.01) and a larger BMI (31 vs 25 kg/m2, p < 0.01). Overall, 55% of patients whom screened positive were obese (defined as a BMI > 30) compared to 15% in the negative group (p < 0.02). Patients with a positive screen were more likely to have other co-morbidities including diabetes (p < 0.04), hypertension (p < 0.05), depression (p < 0.002), and were more likely to have decreased exercise capacity (p < 0.01) and a defibrillator (p < 0.007). Our data demonstrates that OSA is common in the ACHD patient and is associated with increasing weight and BMI. Patients with a positive screen are at increased risk for multiple co morbidities including diabetes, hypertension, and depression. We believe our data supports the use of screening protocols for OSA in the ACHD population in effort to identify early, treat, and potentially prevent late complications.

Health Impact of Hurricanes Irma and Maria on St Thomas and St John, US Virgin Islands, 2017-2018.

Objectives. To assess the health impact of Hurricane Irma and Hurricane Maria on St Thomas, US Virgin Islands.Methods. We collected data from interviews conducted 6 and 9 months after the hurricanes, a review of 597 randomly selected emergency department (ED) encounters, and administrative records from 10 716 ED visits 3 months before, between, and 3 months after the hurricanes.Results. Informants described damaged hospital infrastructure, including flooding, structural damage, and lost staff. The greatest public health impact was on the elderly and persons with chronic diseases. In the setting of loss of the electronic medical record system, ED chart reviews were limited by problems with missing data. ED administrative data demonstrated that posthurricane patients, compared with prehurricane patients, were older and had less severe complaints. There was a significant increase in patients being seen for diabetes-related and respiratory complaints, especially asthma. Suboptimal recordkeeping for medical evacuees limited the ability to assess outcomes for patients with severe illnesses.Conclusions. Hurricanes Irma and Maria caused major disruptions to health care on St Thomas. Emphasis should be given to building a resilient health care system that will optimally respond to future hurricanes.

Public perception towards bystander cardiopulmonary resuscitation.

OBJECTIVE: Bystander cardiopulmonary resuscitation (CPR) after out-of-hospital cardiac arrest (OHCA) improves survival and neurological outcomes. Nonetheless, many OHCA patients do not receive bystander CPR during a witnessed arrest. Our aim was to identify potential barriers to bystander CPR. METHODS: Participants at CPR training events conducted in the USA between February and May 2018 answered a 14-question survey prior to training. Respondents were asked about their overall comfort level performing CPR, and about potential concerns specific to performing CPR on a middle-aged female, a geriatric male, and male and female adolescent patients. Open-ended responses were analysed qualitatively by categorising responses into themes. RESULTS: Of the 677 participants, 582 (86.0%) completed the survey, with 509 (88.1%) between 18 and 29 years of age, 341 (58.6%) without prior CPR training and 556 (96.0%) without prior CPR experience. Across all four scenarios of patients in cardiac arrest, less than 65% of respondents reported that they would be 'Extremely Likely' (20.6%-29.1%) or 'Moderately Likely' (26.9%-34.8%) to initiate CPR. The leading concerns were 'causing injury to patient' for geriatric (n=193, 63.1%), female (n=51, 20.5%) and adolescent (n=148, 50.9%) patients. Lack of appropriate skills was the second leading concern when the victim was a geriatric (n=41, 13.4%) or adolescent (n=68, 23.4%) patient, whereas for female patients, 35 (14.1%) were concerned about exposing the patient or the patient's breasts interfering with performance of CPR and 15 (6.0%) were concerned about being accused of sexual assault. Significant differences were observed in race, ethnicity and age regarding the likelihood of starting to perform CPR on female and adolescent patients. CONCLUSIONS: Participants at CPR training events have multiple concerns and fears related to performing bystander CPR. Causing additional harm and lack of skills were among the leading reservations reported. These findings should be considered for improved CPR training and public education.

Quantitative assays for measuring human telomerase activity and DNA binding properties.

Telomerase is the ribonucleoprotein enzyme that catalyzes the processive addition of the telomeric DNA repeat 5'-TTAGGG-3' onto chromosome ends. In addition to its fascinating biochemical and enzymatic properties, clinical interest in telomerase stems from its dysregulated expression in ∼90% of human cancers, representing a broad spectrum of diseases. Exploiting telomerase as a therapeutic target and hence identifying and/or evaluating potential inhibitors requires quantitative measurement of its activity. This article presents procedures for measuring multiple aspects of telomerase enzymology that are relevant to both fundamental biochemistry and drug discovery: direct activity assays, DNA binding affinity, DNA dissociation, and cell-based over-expression of the active enzyme complex.