Search

Clinical practice guidelines support sustained use of renin-angiotensin-aldosterone-system (RAAS) inhibitors over time in heart failure with reduced ejection fraction, yet few data are available regarding the frequency, timing or predictors of early treatment discontinuation in clinical practice.Among prevalent or new users of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs) in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, we estimated the frequency and independent predictors of treatment discontinuation during follow-up. Among sites with5 users of a given RAAS inhibitor, we evaluated practice variation in the proportion of patients with treatment discontinuation.Over median follow-up of 18 months, frequency of drug discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.7% (444 of 3509 users), 10.4% (140 of 1352 users), and 20.4% (435 of 2129 users), respectively. An additional, 149 (11.0%) of ARNI users were switched to ACEis/ARBs, and 447 (12.7%) of ACEi/ARB users were switched to ARNIs during follow-up. Across sites, the median proportion of discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.5% (25th-75th percentiles 6.9%-18.9%), 18.8% (25th-75th percentiles 12.5%-28.6%), and 19.6% (25th-75th percentiles 10.7%-27.0%), respectively. Chronic kidney disease was the only independent predictor of increased risk of discontinuation of each of the RAAS inhibitor classes (P0.02 for all). Higher Kansas City Cardiomyopathy Questionnaire overall summary scores independently predicted lower risk of discontinuation of ACEis/ARBs and ARNIs (both P0.001) but not of MRAs. Investigator clinical experience was predictive of lower risks of discontinuation of ACEis/ARBs and MRAs (P0.02) but not of ARNIs. All other independent predictors of discontinuation were unique to individual therapeutic classes.One in 10 patients discontinue ACEis/ARBs or ARNIs, and 1 in 5 discontinue MRAs in routine clinical practice of heart failure with reduced ejection fraction. Unique patient-level and clinician/practice-level factors are associated with premature discontinuation of individual RAAS inhibitors, which may help to guide structured efforts to promote treatment persistence in clinical care.

Aims We aimed to develop a risk prediction tool that incorporated both clinical events and worsening health status for patients with heart failure (HF) with reduced ejection fraction (HFrEF). Identifying patients with HFrEF at increased risk of a poor outcome may enable proactive interventions that improve outcomes. Methods and results We used data from a longitudinal HF registry, CHAMP‐HF, to develop a risk prediction tool for poor outcomes over the next 6 months. A poor outcome was defined as death, an HF hospitalization, or a ≥20‐point decrease (or decrease below 25) in 12‐item Kansas City Cardiomyopathy Questionnaire (KCCQ‐12) overall summary score. Among 4546 patients in CHAMP‐HF, 1066 (23%) experienced a poor outcome within 6 months (1.3% death, 11% HF hospitalization, and 11% change in KCCQ‐12). The model demonstrated moderate discrimination (c‐index = 0.65) and excellent calibration with observed data. The following variables were associated with a poor outcome: age, race, education, New York Heart Association class, baseline KCCQ‐12, atrial fibrillation, coronary disease, diabetes, chronic kidney disease, smoking, prior HF hospitalization, and systolic blood pressure. We also created a simplified model with a 0–10 score using six variables (New York Heart Association class, KCCQ‐12, coronary disease, chronic kidney disease, prior HF hospitalization, and systolic blood pressure) with similar discrimination (c‐index = 0.63). Patients scoring 0–3 were considered low risk (event rate 40%). Conclusions The PROMPT‐HF risk model can identify outpatients with HFrEF at increased risk of poor outcomes, including clinical events and health status deterioration. With further validation, this model may help inform therapeutic decision making.

BACKGROUND: Fatigue has a major impact on health‐related quality of life (HR‐QOL) in Parkinson's disease (PD). OBJECTIVES: To determine whether demographic characteristics modify the relationship between fatigue and HR‐QOL. METHODS: Patients with PD in the Fox Insight study completed the Parkinson Fatigue Scale (PFS‐16) and Geriatric Depression Scale (GDS‐15). Linear regression examined the relationship between the PFS‐16 and Parkinson Disease Quality of Life, as modified by age, sex, and GDS‐15. RESULTS: A total of 1029 participants (44% female, mean age 67.4 years, and mean disease duration 4.6 years) were included in this analysis. Multivariable regression modeling demonstrated a negative effect modification for age (β = −0.07, P

Background A large proportion of all deaths are sudden cardiac deaths (SCDs). Reliable estimates of nationwide incidence of SCD, however, are missing. Objectives The goals of this study were to estimate SCD burden across all age groups in Denmark and to compare it with the estimates of other common causes of death. Methods All deaths in Denmark (population of 5.5 million) in 2010 were manually reviewed case by case. Autopsy reports, death certificates, and information from nationwide health registries were systematically examined to identify all SCD cases in 2010. According to the level of detail of the available information, all deaths were categorized as either non-SCD, definite SCD, probable SCD, or possible SCD. Results There were 54,028 deaths in Denmark in 2010, of which 6867 (13%) were categorized as SCD (591 (9%) definite SCD, 1568 (23%) probable SCD, and 4708 (68%) possible SCD). The incidence rate of definite SCD was 11 (95% confidence interval 10–12) per 100,000 person-years. Including definite, probable, and possible SCD cases, the highest possible overall SCD incidence rate was 124 (95% confidence interval 121–127) per 100,000 person-years. Estimated SCD burden was similar to or greater than the estimates of all other common causes of death. Of all SCD cases, 49% were not diagnosed with cardiovascular disease before death. Conclusion SCD accounted for up to 13% of all deaths. Almost half of all SCD cases occurred in persons without a history of cardiovascular disease. Consequently, the optimization of risk stratification and prevention of SCD in the general population should be given high priority.

Background The aim of this study was to describe outcomes of patients undergoing surgical ablation for atrial fibrillation (AF) as either stand-alone or concomitant cardiosurgical procedures in Germany. Methods Patients with AF undergoing concomitant or stand-alone surgical ablation were included in the registry. Cardiac surgery centers across Germany were invited to participate and sought to enroll 1,000 consecutive patients. Data was obtained through electronic case report forms. The protocol mandated follow-up interviews at 1 year. Results Between January 2017 and April 2020, 17 centers enrolled 1,000 consecutive patients. Among concomitant surgical patients (n = 899), paroxysmal AF was reported in 55.4% patients. Epicardial radio frequency (RF) bilateral pulmonary vein isolation (PVI) with excision of the left atrial appendage (LAA) was the most common operative strategy. In the stand-alone cohort (n = 101), persistent AF forms were reported in 84.1% of patients. Moderate-to-severe symptoms were reported in 85.1%. Sixty-seven patients had previously underwent at least two failed catheter ablative procedures. Thoracoscopic epicardial RF bilateral PVI and completion of a “box-lesion” with LAA closure were frequently preformed. Major cardiac and cerebrovascular complications occurred in 38 patients (4.3%) in the concomitant group. No deaths were reported in the stand-alone group. At discharge, sinus rhythm was achieved in 88.1% of stand-alone and 63.4% concomitant patients. Conclusion The CArdioSurgEry Atrial Fibrillation registry provides insights into surgical strategies for AF ablation in a considerable cohort across Germany. This in-hospital data demonstrates that concomitant and stand-alone ablation during cardiac surgery is safe and effective with low complication rates.

Background: Despite excellent data on lowering long-term stroke and all-cause mortality rates, currently, only 25–40% of atrial fibrillation (AF) patients undergo simultaneous surgical ablation therapy (SA) during cardiac surgery. Surgeon’s fear exposing their patients to an additional, unjustified, and disproportionate risk when performing SA in AF patients presenting with sinus rhythm (SR) before surgery. To clarify the influence of preoperative SR before SA for AF, we conducted a subgroup analysis of the German Cardiosurgical Atrial Fibrillation (CASE-AF) register. Methods: Between September 2016 and August 2020, 964 AF patients with an underlying cardiac disease were scheduled for surgery with SA and enrolled in the CASE-AF register. Data prospectively were collected and analyzed retrospectively. We divided the entire cohort into an SR-group (38.2%, N = 368) and an AF-group (61.8%, N = 596), based on preoperative heart rhythm. Results: Over half of the patients were moderately affected by their AF, with no difference between the groups (European Heart Rhythm Association class ≥IIb: SR-group 54.2% versus AF-group 58.5%, P = .238). The AF-group had a higher preoperative EuroSCORE II (4.8 ± 8.0% versus 4.2 ± 6.3%, P = .014). In-hospital mortality (SR-group 0.8% versus AF-group 1.7%, P = .261), major perioperative adverse cardiac and cerebrovascular events (SR-group 2.7% versus AF-group 3.5%, P = .500), and the new pacemaker implantation rate (SR-group 6.0% versus AF-group 5.9%, P = .939) were low and showed and no group difference. Logistic regression analysis showed a protective effect for preoperative SR to perioperative complications in AF patients undergoing SA (odds ratio (OR) 0.72 (95% CI 0.52 - 0.998); P = .0485). Conclusions: Concomitant SA in AF patients presenting in SR before cardiac surgery is safe, has a low perioperative risk profile, and should be carried out with almost no exceptions.

Purpose The aims of this study were to examine interrater agreement of delirium between clinical nurses and a clinical nurse specialist, determine delirium subtype prevalence, and examine associated patient, procedure, and hospital factors. Design A descriptive cross-sectional design and a convenience sample of nurses and patients on progressive care units were used in this study. Methods Clinical nurse specialist data were collected on a case report form, and clinician and patient data were obtained from electronic databases. Interrater agreement of delirium prevalence was assessed by κ statistic, and logistic regression models were used to determine patient factors associated with delirium. Results Of 216 patients, 23 had delirium; clinical nurses identified fewer cases than the clinical nurse specialist: 1.8% versus 10.7%; κ agreement, 0.27 (0.06, 0.49). By delirium subtype, hypoactive delirium was more frequent (n = 10). Factors associated with delirium were history of cerebrovascular disease (odds ratio [95% confidence interval], 2.8 [1.01-7.7]; P = .044), history of mitral valve disease (odds ratio [95% confidence interval], 0.31 [0.09-0.90]; P = .041), and longer perfusion time (odds ratio [95% confidence interval], 1.7 [1.1-2.7]; P = .016). One factor was associated with hypoactive delirium, longer perfusion time (odds ratio [95% confidence interval], 2.2 [1.3-4.2]; P = .008). Conclusions Because clinician-clinical nurse specialist delirium agreement was low and hypoactive delirium was common, clinical interventions are needed.

ObjectivesThis pilot study examines effectiveness of an innovative pharmacy design change on over-the-counter (OTC) medication misuse in older adults (ages ≥65). Few interventions have attempted to decrease older adult OTC misuse, and none have addressed system barriers. A structural redesign of the pharmacy (the Senior Section™) was conceptualized to increase awareness of higher-risk OTC medications. The Senior Section contains a curated selection of OTC medications (for pain, cough/cold, allergy, sleep) and is close to the prescription department to facilitate pharmacy staff/patient engagement to reduce misuse.MethodsA pre-/post-implementation design was used to recruit 87 older adults from three pharmacies. Using a hypothetical scenario, participants selected an OTC medication, which was compared to their medication list and health conditions, and their reported use was compared against the product labeling. Four misuse outcomes were determined: (1) Drug/Drug, (2) Drug/Disease, (3) Drug/Age, and (4) Drug/Label with five sub-types. Patient characteristics were collected and compiled into a propensity-score matching logistic regression model to estimate their effects on the Senior Section’s association with misuse outcomes at pre-/post-implementation.ResultsPatient characteristic were uniform between pre-/post-implementation and, once entered into a propensity-score matching model, Drug/Disease Misuse significantly lessened over time (z=-2.09, p=0.037). The Senior Section reduced Drug/Drug Misuse, but not significantly. Drug/Label Misuse varied according to the sub-type, with reduced Daily-Dosage (z=-2.42, p=0.016) and Single-Dosage misuse (z=-5.82, p=0.001); however, Timing/Frequency misuse increased (z=2.16, p=0.031).ConclusionsThese nascent outcomes support a well-conceived pharmacy-based OTC aisles redesign as valuable for reducing older adult OTC medication misuse. The Senior Section, when broadly implemented, would create new permanent structures and processes to assist older adults in accessing risk information for confidently selecting safer OTC medications.

This article presents an analytic approach to assessing the relationship between policy advocacy activities and outcomes for discrete episodes of advocacy, using a holistic array of factors that affect the relationship between advocacy and policy change. The factors pertain to not only advocacy organizational structure and strategies, but also the policy environment, the policy issue and available options to address it, and technical assistance that advocates receive. By focusing on the entire context in which advocates operate, this approach can be used to assess both advocacy campaign strategies and the broader contextual factors that contribute to advocacy outcomes. The array of factors also facilitates analytic generalizability across advocacy episodes, as evaluators can compare the role of similar factors across advocacy efforts. This analytic approach is illustrated by its application to a multiple case study evaluation of Voices for Healthy Kids.

Locoregional delivery of chimeric antigen receptor (CAR) T cells has resulted in objective responses in adults with glioblastoma, but the feasibility and tolerability of this approach is yet to be evaluated for pediatric central nervous system (CNS) tumors. Here we show that engineering of a medium-length CAR spacer enhances the therapeutic efficacy of human erb-b2 receptor tyrosine kinase 2 (HER2)-specific CAR T cells in an orthotopic xenograft medulloblastoma model. We translated these findings into BrainChild-01 ( NCT03500991 ), an ongoing phase 1 clinical trial at Seattle Children’s evaluating repetitive locoregional dosing of these HER2-specific CAR T cells to children and young adults with recurrent/refractory CNS tumors, including diffuse midline glioma. Primary objectives are assessing feasibility, safety and tolerability; secondary objectives include assessing CAR T cell distribution and disease response. In the outpatient setting, patients receive infusions via CNS catheter into either the tumor cavity or the ventricular system. The initial three patients experienced no dose-limiting toxicity and exhibited clinical, as well as correlative laboratory, evidence of local CNS immune activation, including high concentrations of CXCL10 and CCL2 in the cerebrospinal fluid. This interim report supports the feasibility of generating HER2-specific CAR T cells for repeated dosing regimens and suggests that their repeated intra-CNS delivery might be well tolerated and activate a localized immune response in pediatric and young adult patients. In an interim analysis of a phase 1 trial, repeated intracranial infusions of HER2-specific CAR T cells were well tolerated with no observed dose-limiting toxicities in three young adult patients with CNS tumors.

Potentially inappropriate prescription and polypharmacy are well‐known risk factors for morbidity and mortality among older adults. However, recent systematic reviews have failed to demonstrate the overall survival benefits of deprescribing. Thus, it is necessary to synthesize the current evidence to provide a practical direction for future research and clinical practice. This review summarizes the existing body of evidence regarding deprescribing to identify useful intervention elements. There is evidence that even simple interventions, such as direct deprescribing targeted at risky medications and explicit criteria‐based approaches, effectively reduce inappropriate prescribing. On the other hand, if the goal is to improve clinical outcomes such as hospitalization and emergency department visits, patient‐centered multimodal interventions such as a combination of medication review, multidisciplinary collaboration, and patient education are likely to be more effective. We also consider the opportunities and challenges for deprescribing within the Japanese healthcare system., This review summarizes the existing body of evidence regarding deprescribing to identify useful intervention elements. There is evidence that even simple interventions, such as direct deprescribing targeted at risky medications and explicit criteria‐based approaches, effectively reduce inappropriate prescribing. On the other hand, if the goal is to improve clinical outcomes such as hospitalization and emergency department visits, patient‐centered multimodal interventions such as a combination of medication review, multidisciplinary collaboration, and patient education are likely to be more effective.

Background and Objectives The high prevalence of overweight or obesity in older adults is a public health concern because obesity affects health, including the risk of mobility disability. Research Design and Methods The Mobility and Vitality Lifestyle Program, delivered by community health workers (CHWs), enrolled 303 community-dwelling adults to assess the impact of a 32-session behavioral weight management intervention. Participants completed the program at 26 sites led by 22 CHWs. Participation was limited to people aged 60–75 who had a body mass index (BMI) of 27–45 kg/m2. The primary outcome was the performance on the Short Physical Performance Battery (SPPB) over 12 months. Results Participants were aged 67.7 (SD 4.1) and mostly female (87%); 22.7% were racial minorities. The mean (SD) BMI at baseline was 34.7 (4.7). Participants attended a median of 24 of 32 sessions; 240 (80.3%) completed the 9- or 13-month outcome assessment. Median weight loss in the sample was 5% of baseline body weight. SPPB total scores improved by +0.31 units (p < .006), gait speed by +0.04 m/s (p < .0001), and time to complete chair stands by −0.95 s (p < .0001). Weight loss of at least 5% was associated with a gain of +0.73 in SPPB scores. Increases in activity (by self-report or device) were not independently associated with SPPB outcomes but did reduce the effect of weight loss. Discussion and Implications Promoting weight management in a community group setting may be an effective strategy for reducing the risk of disability in older adults.

This international multidisciplinary document intends to provide clinicians with evidence‐based practical patient‐centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.

Background Per national guidelines, early follow-up appointments should be scheduled before discharge, but in previous research, appointments scheduled before discharge were not associated with appointment adherence. Objectives The purpose of this study was to determine whether patient, heart failure (HF), and hospital factors were associated with predischarge appointment scheduling. Methods A secondary analysis of a medical record review included patients hospitalized for decompensated HF at 3 health system hospitals who had a scheduled office appointment post discharge at 14 days or less. Patient demographics, and social, HF, and hospital factors were studied for association with predischarge scheduling. Results In multivariable modeling, the odds of having an appointment scheduled predischarge were based on 3 factors: nonwhite race, history of chronic renal insufficiency, and no admission within 14 days before HF hospitalization. Conclusions Appointment scheduling may be based on provider perceptions of readmission risk. Follow-up appointment scheduling practices should be based on systematic processes.

Introduction Caregiver burden is high among caregivers of PD patients (CPD). Neuropsychiatric symptoms are leading contributors to CPD burden, but whether different symptoms differentially impact domains of caregiver burden is not known. Our objective was to examine which neuropsychiatric symptoms and demographic factors contribute to different domains of caregiver burden in PD. Methods This was a cross-sectional online survey study. Participants were recruited from the Fox Insight (FI) study and were eligible if they identified themselves as a CPD. The primary outcome was the Caregiver Burden Inventory (CBI) total score and its 5 sub-domain scores. The Neuropsychiatric Inventory Questionnaire (NPI-Q) assessed caregiver-reported neuropsychiatric symptoms in the care recipient. Multivariable linear regression models were used to characterize the associations between NPI-Q symptom severity scores and CBI scores. Covariates were caregiver age, sex, education, and caregiving duration. Results The sample consisted of 450 CPD, mean age 65.87 (SD 10.39) years, 74% females. After adjusting for covariates, CBI total score was predicted by NPI-Q total score (β = 1.96, p R2 = 39.2%. Anxiety severity had the largest effect size [standardized β (sβ) = 0.224] on the time-dependency domain, which was also associated with female sex (sβ = − 0.133) and age (sβ = 0.088). Severity of disinhibition (sβ = 0.218), agitation (sβ = 0.199), and female sex (sβ = 0.104) were associated with greater emotional burden. Conclusion Our findings indicate that demographic characteristics and specific neuropsychiatric symptoms contribute differentially to domains of caregiver burden. Tailored interventions to support CPD are needed.

Background: Digital health is transforming healthcare delivery. Objective: To compare the current digital health landscape in select groups of cardiac electrophysiology (EP) professionals prior to and during the COVID-19 era. Methods: Two online surveys were emailed to 4 Heart Rhythm Society communities and tweeted out to Twitter EP, 1 before and 1 during the pandemic. Categorical variables were analyzed using the χ2 test and reported as absolute numbers and percentages. Results: There were 253 pre-pandemic (S1) and 273 follow-up surveys (S2) completed. The majority of respondents to both surveys were male, aged

Background We aimed to identify trajectories of inflammation in older adults at elevated risk for syndromal depression and anxiety and to determine whether baseline physical, cognitive, and psychosocial factors could distinguish 15-month longitudinal trajectories. Methods Older adults (N = 195, mean age (±SD) = 74.4 years (9.0) participating in three depression and anxiety prevention protocols completed a comprehensive battery of psychosocial assessments and provided blood samples for analysis of interleukin-6 (IL-6) every 3 months over a maximum of 15 months. Group-based trajectory modeling identified trajectories. Adjusted logistic regression examined associations between baseline factors and trajectory groups. Results Two 15-month trajectories were identified: stable lower IL-6 levels (84%; mean (±SD) = 3.2 (2.1) pg/mL); and consistently higher IL-6 levels (16%; mean = 9.5 (7.4) pg/mL). Poor sleep quality predicted consistently higher levels of IL-6 (OR = 1.9, 95% CI = 1.03–3.55). Conclusion Poor sleep quality may represent a therapeutic target to reduce inflammation.

We examined features of everyday activities (capacity and frequency) between older adults with and without cognitive impairment over 12 months. Participants aged ≥60 years and at risk for depression were included (n = 260); 26% ( n = 69) had an acquired cognitive impairment at baseline. Cognitive impairment was defined as one standard deviation below norms on the Repeatable Battery for the Assessment of Neuropsychological Status. Features of everyday activities were measured by a computerized adaptive test version of Late-Life Function and Disability Instrument (LLFDI) at six time points (baseline, 6 weeks, 3, 6, 9, 12 months). There were significant between-group differences in activity frequency ( p = .04), but not activity capacity ( p = .05). The group difference in activity frequency exceeded minimal detectable changes (MDC90 = 3.7) and reached moderate clinical meaningfulness (∆ at six time points = 3.7–4.7). Generalized linear mixed models revealed no Group × Time interactions on activity capacity and frequency ( p = .65 and p = .98). Practitioners may assess changes in activity frequency to monitor cognitive status of clients even when there is no loss of activity capacity.

Objectives The authors sought to evaluate the association of heart failure hospitalization (HFH) with guideline-directed medical therapy (GDMT) prescribing patterns among patients with heart failure with reduced ejection fraction (HFrEF). Background HFH represents an important opportunity to titrate GDMT among patients with HFrEF. Methods The CHAMP-HF (Change the Management of Patients With Heart Failure) registry is a prospective registry of adults with HFrEF (ejection fraction ≤40%). Using data from the CHAMP-HF registry (N = 4,365), adjusted time-to-event models were created to study the association of HFH with GDMT prescribing patterns. Results HFH (compared with no HFH) was positively associated with initiation of angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA). HFH positively associated with dose escalation of ACE inhibitor/ARB (probability ratio: 1.71, 95% confidence interval [CI]: 1.36 to 2.16) and MRA (probability ratio: 8.71, 95% CI: 4.19 to 18.10). In those on prior therapy, HFH was associated with discontinuation and de-escalation of all classes of GDMT. ACE inhibitor/ARB, angiotensin receptor-neprilysin inhibitor, beta-blocker, and MRA de-escalation/discontinuation after HFH was associated with increased risk of all-cause mortality with hazard ratios of 3.82 (95% CI: 2.42 to 6.03), 4.76 (95% CI: 2.06 to 11.03), 2.94 (95% CI: 2.04 to 4.25), and 4.81 (95% CI: 2.61 to 8.87), respectively. Conclusions HFH positively associated with changes in GDMT, including initiation, dose escalation, discontinuation, and dose de-escalation. De-escalation/discontinuation of GDMT after HFH associated with increased risk of all-cause mortality. Educational endeavors are needed to ensure GDMT is not inappropriately held in the setting of HFH. For those in whom GDMT must be held/decreased, improvement tools at discharge and post-discharge titration clinics may help ensure lifesaving GDMT regimens remain optimized.

OBJECTIVES: To compare the characteristics of Medicare beneficiaries hospitalized for heart failure (HF) and discharged home who received home healthcare (HHC) to those who did not, and to examine associations between HHC and readmission and mortality rates. BACKGROUND: After hospitalization for HF, some patients receive HHC; however, utilization of HHC over time, factors associated with its use and post-discharge outcomes after receiving it are not well studied. METHODS: We used Get With The Guidelines-HF data, merged with Medicare fee-for-service claims. Propensity-score matching and Cox proportional hazards models were used to evaluate the associations between HHC and post-discharge outcomes. RESULTS: From 2005 to 2015, 95,531 patients were admitted for HF and 32,697 (34.2%) received HHC after discharge. The rate of HHC increased over time from 31.4% to 36.1% (p

Background Purposeful hourly rounding and information on whiteboards in patients' rooms have been known to reduce use of call lights. Problem Call light activation was higher than desired. Methods This continuous improvement initiative used retrospective data collection (pre-, early- and maintenance postintervention) to assess call light responsiveness. Intervention A bundled purposeful hourly rounding approach was used. Results Call light frequency was higher in the early postintervention period than in the preintervention; however, there was no change in the frequency of call lights that extended beyond 5 minutes. In the maintenance postintervention period, compared with the pre- and early postintervention periods, call lights per patient/unit day and call lights extending beyond 5 minutes per patient/unit day decreased (all P Conclusions Activation of a bundled purposeful hourly rounding approach was associated with a decrease in all call lights and call lights extending beyond 5 minutes per patient/unit day.

Heart failure (HF) is a growing health problem associated with high morbidity and mortality. Use of evidence-based therapies improves clinical outcomes in patients with HF with reduced ejection fraction (HFrEF). However, in real-world research studies, adults with HFrEF were often medically undermanaged, including failure to use the right medications and failure to up titrate core HF therapies to doses similar to those used in randomized controlled trials. Although guidelines provide best-practice statements about care management, nurse practitioners and physician assistants (NPs and PAs) and clinical nurses often have questions about how to implement guideline-directed therapies in patient care management. With emerging new medications for managing HFrEF, and the possibility of new medications for patients with HF with preserved ejection fraction, complexity of care management will continue to increase. The aims of this review are to provide a summary of the 2017 updates to the national chronic HF management guidelines and use a case-based approach to discuss treatment change considerations associated with optimal guideline-based clinical care.

Highlights Abstract Background: In pediatric patients, intravenous placement success may be related to predetermined vascular access difficulty. The study purpose was to examine validity and reliability of the 6-item Pediatric Intravenous Difficulty Score. Methods: We determined if a tool that assesses pediatric intravenous difficulty was associated with clinical outcomes of peripheral attempts (criterion validity), hypotheses regarding patients’ age, race, and medical diagnosis (construct validity), and reliability of difficulty levels. Results: In 596 episodes of peripheral intravenous attempts, first-attempt success, overall success, and number of staff attempting access were associated with level of intravenous access difficulty by tool score. The tool met hypothesized construct validity criteria, and in multivariable modeling, the tool was reliable based on difficulty levels of 2 user groups. Conclusions: The 6-item Pediatric Intravenous Difficulty Score has criterion and construct validity and is reliable over time among clinicians with different levels of expertise in peripheral vascular access.

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted healthcare delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for patients with arrhythmia. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serological testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.

Little is known about the impact of accountable care organizations (ACO) on hospitalized heart failure (HF) patients, a high-cost and high-risk population.We linked Medicare fee-for-service claims from 2013 to 2015 with data from American Heart Association Get With The Guidelines-HF registry to compare HF care, post-discharge outcomes, and total annual Medicare spending by ACO status at discharge.Using adjusted Cox models and accounting for competing risks of death, we compared all-cause mortality and readmission at 1 year by ACO status with reporting of hazard ratios (HR) and 99% confidence intervals (CI).The study included 45,259 HF patients from 300 hospitals, with 21.1% assigned to an ACO. Patient characteristics were similar between the two groups with a few exceptions. The ACO patients lived in geographic areas with higher median income ($54400 [IQR $48600-65900] vs $52300 [$45900-61200], P.0001). Compliance with four HF-specific quality measures was modestly higher in the ACO group (80% vs 76%, P.0001). In adjusted analysis, ACO status was associated with similar all-cause readmission (HR: 1.03; 99% CI: 0.99, 1.07) but lower risk of 1-year mortality (HR: 0.85; 99% CI: 0.85, 0.90) compared with non-ACO status. Median Medicare spending in the calendar year of hospitalization was similar (ACO $42,737 [IQR $23,011-72,667] vs non-ACO $42,586 [$22,896-72,518], P = 0.06).Among Medicare patients hospitalized for HF, participation in an ACO was associated with similar rates of all-cause readmission and no associated cost reductions compared with non-ACO status. There was a lower risk of 1-year mortality associated with ACO participation, which warrants further evaluation.

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.

Coronary angiography is often performed in patients with recurrent angina after successful coronary artery bypass grafting (CABG) in search of the progression of atherosclerosis. However, in many of these patients, no relevant stenosis can be detected. We speculate that coronary spasm may be associated with angina in these patients. From 2307 patients with unobstructed coronaries who underwent intracoronary acetylcholine spasm provocation testing (ACh-test) between 2012 and 2016, 54 consecutive patients who fulfilled the following inclusion criteria were included in this cohort study: previous left internal thoracic artery (LITA) bypass on the left anterior descending (LAD) coronary artery, ongoing/recurrent angina pectoris, no significant (

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF.

More than 50 individuals with activating variants in the receptor tyrosine kinase PDGFRB have been reported, separated based on clinical features into solitary myofibromas, infantile myofibromatosis, Penttinen syndrome with premature aging and osteopenia, Kosaki overgrowth syndrome, and fusiform aneurysms. Despite their descriptions as distinct clinical entities, review of previous reports demonstrates substantial phenotypic overlap. We present a case series of 12 patients with activating variants in PDGFRB and review of the literature. We describe five patients with PDGFRB activating variants whose clinical features overlap multiple diagnostic entities. Seven additional patients from a large family had variable expressivity and late-onset disease, including adult onset features and two individuals with sudden death. Three patients were treated with imatinib and had robust and rapid response, including the first two reported infants with multicentric myofibromas treated with imatinib monotherapy and one with a recurrent p.Val665Ala (Penttinen) variant. Along with previously reported individuals, our cohort suggests infants and young children had few abnormal features, while older individuals had multiple additional features, several of which appeared to worsen with advancing age. Our analysis supports a diagnostic entity of a spectrum disorders due to activating variants in PDGFRB. Differences in reported phenotypes can be dramatic and correlate with advancing age, genotype, and to mosaicism in some individuals.

Objectives The purpose of this study was to characterize the clinical profile, treatment patterns, and clinical outcomes of patients with comorbid diabetes mellitus (DM) and heart failure with reduced ejection fraction (HFrEF) in a contemporary, real-world U.S. outpatient registry in the context of evolving treatment strategies. Background Specific antihyperglycemic classes have differential risks and benefits with respect to HF. Limited data are available evaluating contemporary treatment patterns and outcomes of patients with comorbid DM and HFrEF. Methods Among 4,970 patients with chronic HFrEF (≤40%) across 152 U.S. sites in the CHAMP-HF prospective, observational registry (2015 to 2017), we examined therapies and clinical outcomes by DM status. Results Median age was 68 (58 to 75) years of age; 29% were women; 73.5% were white; and 64% had coronary artery disease. Overall, 42% (n = 2,085) had comorbid DM with a median hemoglobin A1c (HbA1c) level of 7.2% (interquartile range [IQR]: 6.4% to 8.3%). One-fourth of DM patients (24%) were not treated with an antihyperglycemic therapy. Most patients with DM were taking 1 (46%) or 2 (23%) antihyperglycemic therapies: metformin (40%), insulin (33%); sulfonylureas (24%); dipeptidyl peptidase-4 inhibitors (10%); glucagon-like peptide (GLP)-1 receptor agonists (4%); sodium-glucose cotransporter (SGLT)-2 inhibitors (2%); and thiazolidinediones (2%). Among patients with DM, 62%, 16%, 80%, and 33.5% were receiving any angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), β-blockers, or mineralocorticoid receptor antagonists (MRAs) at baseline, respectively. Among patients without DM, corresponding baseline rates were 65%, 15%, 80%, and 37%, respectively. Patients with or without DM were infrequently treated with guideline-directed HFrEF therapies at target doses (≤27% across classes). During median 15-month follow-up, patients with DM experienced higher rates of all-cause mortality or HF hospitalization (30% vs. 23%, respectively), independent of 11 pre-specified covariates (adjusted hazard ratio: 1.35 (95% confidence interval: 1.21 to 1.52); p Conclusions Despite higher risk-adjusted clinical event rates in patients with comorbid HFrEF and DM, guideline-directed medical therapies for both disease states are incomplete and represent an important target for quality improvement through multidisciplinary care pathways.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.

BACKGROUND Illness perceptions, patients' beliefs about their health condition, may affect medication adherence as well as self-efficacy for managing the condition in type 2 diabetes (T2DM). OBJECTIVES The aims of this study were to investigate the associations between illness perceptions, self-efficacy, and self-reported medication adherence among persons (≥50 years of age) with T2DM and explore whether the number of comorbid conditions moderates these associations. METHODS This secondary analysis of cross-sectional data used baseline data from persons with T2DM. Self-administered questionnaires, including the Brief Illness Perception Questionnaire, Self-efficacy for Managing Chronic Disease, and the 4-item Morisky-Green-Levine Medication Adherence Scale, were used. We performed hierarchical multiple linear regression analyses. RESULTS Participants (N = 146) were 57.5% female, 67.1% white, and on average 64 years old. Six dimensions of illness perceptions (ie, consequences, personal control, treatment control, identity, concerns, and emotional representations) were associated with self-efficacy for managing T2DM. Five dimensions (ie, timeline, personal control, treatment control, coherence, and emotional representations) were significant predictors of self-reported medication adherence. Whereas the number of comorbid conditions was significantly associated with self-efficacy for managing T2DM in all models (P values < .001), the number of comorbid conditions was not associated with self-reported medication adherence. CONCLUSIONS This study suggests that illness perceptions and comorbid conditions may play a critical role in either self-efficacy or self-reported medication adherence in persons (≥50 years of age) with T2DM. Future research should incorporate an individual's illness perceptions and comorbid conditions into the development of interventions that may improve both self-efficacy and medication adherence in T2DM.

BackgroundThe selective TRK inhibitor larotrectinib was approved for paediatric and adult patients with advanced TRK fusion-positive solid tumours based on a primary analysis set of 55 patients. The aim of our analysis was to explore the efficacy and long-term safety of larotrectinib in a larger population of patients with TRK fusion-positive solid tumours.MethodsPatients were enrolled and treated in a phase 1 adult, a phase 1/2 paediatric, or a phase 2 adolescent and adult trial. Some eligibility criteria differed between these studies. For this pooled analysis, eligible patients were aged 1 month or older, with a locally advanced or metastatic non-CNS primary, TRK fusion-positive solid tumour, who had received standard therapy previously if available. This analysis set includes the 55 patients on which approval of larotrectinib was based. Larotrectinib was administered orally (capsule or liquid formulation), on a continuous 28-day schedule, to adults mostly at a dose of 100 mg twice daily, and to paediatric patients mostly at a dose of 100 mg/m2 (maximum of 100 mg) twice daily. The primary endpoint was objective response as assessed by local investigators in an intention-to-treat analysis. Contributing trials are registered with ClinicalTrials.gov, NCT02122913 (active not recruiting), NCT02637687 (recruiting), and NCT02576431 (recruiting).FindingsBetween May 1, 2014, and Feb 19, 2019, 159 patients with TRK fusion-positive cancer were enrolled and treated with larotrectinib. Ages ranged from less than 1 month to 84 years. The proportion of patients with an objective response according to investigator assessment was 121 (79%, 95% CI 72-85) of 153 evaluable patients, with 24 (16%) having complete responses. In a safety population of 260 patients treated regardless of TRK fusion status, the most common grade 3 or 4 larotrectinib-related adverse events were increased alanine aminotransferase (eight [3%] of 260 patients), anaemia (six, 2%), and decreased neutrophil count (five [2%]). The most common larotrectinib-related serious adverse events were increased alanine aminotransferase (two [

Objective: To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial. Design: Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial. Participants: Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension. Methods: I brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis. Main Outcome Measures: Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation. Results: As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%–15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%–13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P 0.08). Conclusions: Local treatment failure and enucleation were relatively infrequent events after I brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe. Ophthalmology 2002;109:2197–2206 © 2002 by the American Academy of Ophthalmology.

Intravenous (IV) placement outcomes in pediatric patients need to be improved. The purpose of the study was to examine if a pediatric peripheral vascular access algorithm with a pediatric vascular access team (PPVAA-VAT) improved IV placement outcomes compared with Pediatric Peripheral Vascular Access Algorithm (PPVAA)-alone use.This study was a prospective, comparative, two-group design of hospitalized children. Multivariable logistic regression models were used to evaluate differences between cohort outcomes.The PPVAA-alone IV attempts (n = 302) were followed by PPVAA-VAT attempts (n = 294). First attempt and overall IV success were higher in the PPVAA-VAT group after adjusting for confounding patient characteristics (p .001 and p = .002, respectively). The IV attempts and staff required per encounter decreased in the PPVAA-VAT vs. PPVAA-alone group.The PPVAA-VAT group had greater first attempt and overall IV success, and was more likely to have fewer attempts and staff involved in IV access encounters.

Objectives This study evaluated whether plasma miRNAs were specifically associated with sudden cardiac and/or arrhythmic death (SCD) in a cohort of patients with coronary heart disease (CHD), most of whom were without primary prevention implantable cardioverter-defibrillators. Background Novel biomarkers for sudden death risk stratification are needed in patients with CHD to more precisely target preventive therapies, such as implantable cardioverter-defibrillators. miRNAs have been implicated in regulating inflammation and cardiac fibrosis in cells, and plasma miRNAs have been shown to predict cardiovascular death in patients with CHD. Methods We performed a nested case control study within a multicenter cohort of 5,956 patients with CHD followed prospectively for SCD. Plasma levels of 18 candidate miRNAs previously associated with cardiac remodeling were measured in 129 SCD cases and 258 control subjects matched on age, sex, race, and left ventricular ejection fraction. Results miR-150-5p, miR-29a-3p, and miR-30a-5p were associated with increased SCD risk (odds ratios and 95% confidence intervals: 2.03 [1.12 to 3.67]; p = 0.02; 1.93 [1.07 to 3.50]; p = 0.02; 0.55 [0.31 to 0.97]; p = 0.04, respectively, for third vs. first tertile miRNA level). Unfavorable levels of all 3 miRNAs was associated with a 4.8-fold increased SCD risk (1.59 to 14.51; p = 0.006). A bioinformatics-based approach predicted miR-150-5p, miR-29a-3p, and miR-30a-5p to be involved in apoptosis, fibrosis, and inflammation. Conclusions These findings suggest that plasma miRNAs may regulate pathways important for remodeling and may be useful in identifying patients with CHD at increased risk of SCD.

Healthcare-acquired infections are a tremendous challenge to the US medical system. Stethoscopes touch many patients, but current guidance from the Centers for Disease Control and Prevention does not support disinfection between each patient. Stethoscopes are rarely disinfected between patients by healthcare providers. When cultured, even after disinfection, stethoscopes have high rates of pathogen contamination, identical to that of unwashed hands. The consequence of these practices may bode poorly in the coronavirus 2019 disease (COVID-19) pandemic. Alternatively, the CDC recommends the use of disposable stethoscopes. However, these instruments have poor acoustic properties, and misdiagnoses have been documented. They may also serve as pathogen vectors among staff sharing them. Disposable aseptic stethoscope diaphragm barriers can provide increased safety without sacrificing stethoscope function. We recommend that the CDC consider the research regarding stethoscope hygiene and effective solutions to contemporize this guidance and elevate stethoscope hygiene to that of the hands, by requiring stethoscope disinfection or change of disposable barrier between every patient encounter.

Background: Diuretics are a mainstay therapy for the symptomatic treatment of heart failure. However, in contemporary US outpatient practice, the degree to which diuretic dosing changes over time and the associations with clinical outcomes and health care resource utilization are unknown. Methods: Among 3426 US outpatients with chronic heart failure with reduced ejection fraction in the Change the Management of Patients with Heart Failure registry with complete medication data and who were prescribed a loop diuretic, diuretic dose increase was defined as: (1) change to a total daily dose higher than their previous total daily dose, (2) addition of metolazone to the regimen, (3) change from furosemide to either bumetanide or torsemide, and the change persists for at least 7 days. Adjusted hazard ratios or rate ratios along with 95% CIs were reported for clinical outcomes among patients with an increase in oral diuretic dose versus no increase in diuretic dose. Results: Overall, 796 (23%) had a diuretic dose increase (18 episodes per 100 patient-years). The proportion of patients with dyspnea at rest (38% versus 26%), dyspnea at exertion (79% versus 67%), orthopnea (32% versus 21%), edema (60% versus 43%), and weight gain (40% versus 23%) were significantly (all P Conclusions: In this contemporary US registry, 1 in 4 patients with heart failure with reduced ejection fraction had outpatient escalation of diuretic therapy over longitudinal follow-up, and these patients were more likely to have sign/symptoms of congestion. Outpatient diuretic dose escalation of any magnitude was associated with heart failure hospitalizations and resource utilization, but not all-cause mortality.

Background: Health status outcomes are increasingly being promoted as measures of health care quality, given their importance to patients. In heart failure (HF), an American College of Cardiology/American Heart Association Task Force proposed using the proportion of patients with preserved health status as a quality measure but not as a performance measure because risk adjustment methods were not available. Methods: We built risk adjustment models for alive with preserved health status and for preserved health status alone in a prospective registry of outpatients with HF with reduced ejection fraction across 146 US centers between December 2015 and October 2017. Preserved health status was defined as not having a ≥5-point decrease in the Kansas City Cardiomyopathy Questionnaire Overall Summary score at 1 year. Using only patient-level characteristics, hierarchical multivariable logistic regression models were developed for 1-year outcomes and validated using data from 1 to 2 years. We examined model calibration, discrimination, and variability in sites’ unadjusted and adjusted rates. Results: Among 3932 participants (median age [interquartile range] 68 years [59–75], 29.7% female, 75.4% White), 2703 (68.7%) were alive with preserved health status, 902 (22.9%) were alive without preserved health status, and 327 (8.3%) had died by 1 year. The final risk adjustment model for alive with preserved health status included baseline Kansas City Cardiomyopathy Questionnaire Overall Summary, age, race, employment status, annual income, body mass index, depression, atrial fibrillation, renal function, number of hospitalizations in the past 1 year, and duration of HF (optimism-corrected C statistic=0.62 with excellent calibration). Similar results were observed when deaths were ignored. The risk standardized proportion of patients alive with preserved health status across the 146 sites ranged from 62% at the 10th percentile to 75% at the 90th percentile. Variability across sites was modest and changed minimally with risk adjustment. Conclusions: Through leveraging data from a large, outpatient, observational registry, we identified key factors to risk adjust sites’ proportions of patients with preserved health status. These data lay the foundation for building quality measures that quantify treatment outcomes from patients’ perspectives.

Background: Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine ɷ-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose-related. Methods: The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012, and December 31, 2020, in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine ɷ-3 fatty acids that reported results for AF, either as a prespecified outcome, an adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year were included. RCTs specifically examining shorter-term effects of ɷ-3 fatty acids on recurrent AF in patients with established AF or postoperative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was meta-analyzed using random effects model with Knapp-Hartung adjustment and evaluated a dose-response relationship with a meta-regression model. Results: Of 4049 screened records, 7 studies were included in the meta-analysis. Of those, 5 were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81 210 patients from 7 trials, 58 939 (72.6%) were enrolled in trials testing ≤1 g/d and 22 271 (27.4%) in trials testing >1 g/d of ɷ-3 fatty acids. The mean age was 65 years, and 31 842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine ɷ-3 fatty acid supplements was associated with an increased risk of AF (n=2905; HR, 1.25 [95% CI, 1.07–1.46]; P =0.013). In analyses stratified by dose, the HR was greater in the trials testing >1 g/d (HR, 1.49 [95% CI, 1.04–2.15]; P =0.042) compared with those testing ≤1 g/d (HR, 1.12 [95% CI, 1.03–1.22]; P =0.024; P for interaction P =0.001). Conclusions: In RCTs examining cardiovascular outcomes, marine ɷ-3 supplementation was associated with an increased risk of AF. The risk appeared to be greater in trials testing >1 g/d.

Objective. We examined heat stress symptoms and urine markers of chronic kidney disease (CKDu) in Sri Lanka to assess differences between endemic vs. non-endemic regions and by occupation. Sample and Methods. We assessed a total of 475 villagers. In the endemic region, 293 were agricultural workers and 67 were not working primarily in agriculture. In the non-endemic region, 76 were agricultural workers. Of the residents, 218 were assessed for neutrophil gelatinase-associated lipocalin (NGAL), an early predictor of acute kidney injury, along with urine markers of chronic kidney disease. Results. The mean (sd) age of the sample was 45.2 (12.6), with males comprising 52.7%, 7.2% reported kidney disease (n = 34), and 5.7% reported diabetes (n = 27). The heat stress index (mean (sd)) was highest among agricultural workers in the endemic region (8.05 (5.9)), intermediate in non-agricultural workers in the endemic region (4.61 (4.5)), and lowest among agricultural workers in the non-endemic region (3.85 (3.3)), p &lt, 0.0001. Correlations were higher between NGAL and serum microalbumin in the endemic agricultural worker sample than in the other two samples (Spearman’s r = 0.34 vs. 0.15 and 0.20). Conclusions. Both heat stress symptoms and NGAL values were higher among agricultural workers in endemic CKDu regions. Correlations between NGAL and microalbumin suggested a link between acute kidney injury and chronic kidney disease in the more-exposed sample.

Among the estimated 6.2 million Americans living with heart failure (HF), ≈5%/y may progress to advanced, or stage D, disease. Advanced HF has a high morbidity and mortality, such that early recognition of this condition is important to optimize care. Delayed referral or lack of referral in patients who are likely to derive benefit from an advanced HF evaluation can have important adverse consequences for patients and their families. A 2-step process can be used by practitioners when considering referral of a patient with advanced HF for consideration of advanced therapies, focused on recognizing the clinical clues associated with stage D HF and assessing potential benefits of referral to an advanced HF center. Although patients are often referred to an advanced HF center to undergo evaluation for advanced therapies such as heart transplantation or implantation of a left ventricular assist device, there are other reasons to refer, including access to the infrastructure and multidisciplinary team of the advanced HF center that offers a broad range of expertise. The intent of this statement is to provide a framework for practitioners and health systems to help identify and refer patients with HF who are most likely to derive benefit from referral to an advanced HF center.

Purpose To better understand the history and epidemiology of Bartonella henselae infections of the eye and adnexa, and their relationship to cat scratch disease (CSD). We also assess B. henselae infection as a public health threat. Methods We reviewed the available literature concerning B. henselae infections of the eye and CSD, and attempted calculation of the incidence and prevalence of both B. henselae eye infections and CSD from the database of the Rochester Epidemiology Project. Results It took nearly a century of determined effort to reveal that Henri Parinaud’s oculoglandular syndrome (POGS) (1889) and Leber’s stellate retinitis (1916) were the result of B. henselae infection and are subtypes of CSD. These ocular infections remain of clinical, epidemiologic, and public health concern to ophthalmologists with many unanswered questions. Their incidence and prevalence have yet to be accurately determined. Our attempt to achieve this through the Rochester Epidemiology Project database suggests a major obstacle is inconsistent with nonunanimous diagnostic terminology and coding. Conclusions Modern serologic testing and molecular diagnostic techniques offer ophthalmologists the opportunity to make B. henselae infection of the eyes an area of “precision medicine.” For this to happen, greater awareness and teaching about this disease, updated terminology, and a greater clinical and research effort are required.

Background: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. Short-term exposures to air pollution have been associated with AF triggering; less is known regarding associations between long-term air pollution exposures and AF incidence. Objectives: Our objective was to assess the association between long-term exposures to air pollution and distance to road on incidence of AF in a cohort of U.S. women. Methods: We assessed the association of high resolution spatiotemporal model predictions of long-term exposures to particulate matter (PM10 and PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and distance to major roads with incidence of AF diagnosis, identified through Medicare linkage, among 83,117 women in the prospective Women’s Health Initiative cohort, followed from enrollment in Medicare through December 2012, incidence of AF, or death. Using time-varying Cox proportional hazards models adjusted for age, race/ethnicity, study component, body mass index, physical activity, menopausal hormone therapy, smoking, diet quality, alcohol consumption, educational attainment, and neighborhood socioeconomic status, we estimated the relative risk of incident AF in association with each pollutant. Results: A total of 16,348 incident AF cases were observed over 660,236 person-years of follow-up. Most exposure–response associations were nonlinear. NO2 was associated with risk of AF in multivariable adjusted models [Hazard Ratio (HR)=1.18; 95% confidence interval (CI): 1.13, 1.24, comparing the top to bottom quartile, p-for-trend=