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INTRODUCTION: Patients experience high symptom burden during critical care hospitalization and mechanical ventilation. Medications are of limited effectiveness and are associated with increased morbidity such as delirium and long-term cognitive and psychological impairments. Music-based interventions have been used for pain and anxiety management in critical care but remain understudied in terms of music selection and range of symptoms. This study aimed to describe the ways in which a diverse sample of critically ill adults used personalized music listening and their perceptions of the effects of music listening on symptom experience after critical injury. METHODS: Semi-structured interviews (N = 14) of adult patients, families and friends who were provided with personalized music in an urban, academic, neurotrauma intensive care unit were collected and analyzed with grounded theory methodology. Open coding of transcripts, field notes and memos was performed using Atlas.ti.9.1. Recruitment and data collection were deemed complete once thematic saturation was achieved. RESULTS: We identified 6 uses of personalized music listening in critical care: 1) Restoring consciousness; 2) Maintaining cognition; 3) Humanizing the hospital experience; 4) Providing a source of connection; 5) Improving psychological wellbeing; and 6) Resolving the problems of silence. Patients used music to address psychological experiences of loneliness, fear, confusion, and loss of control. Personalized music helped patients maintain their identity and process their trauma. Additional benefits of music included experiencing pleasure, hope, resilience, and feelings of normalcy. Patients disliked being sedated and used music to wake up. Findings also highlighted the problem of the lack of meaningful stimulation in critical care. CONCLUSION: Critically injured adults used personalized music to achieve psychological and cognitive homeostasis during critical care hospitalization. These results can inform future studies designed to explore the use of music-based interventions to prevent and treat the cognitive and emotional morbidity of critical care.

BackgroundDisease prevalence and distribution by patient characteristics data are needed to guide "representative" patient enrollment in clinical trials and assess relevance of results to patient populations. Our objective was to describe disease prevalence, and age/sex distribution of patients with common chronic conditions from a large population sample.MethodsA cross-sectional study of all members of Clalit Health Services, alive on January 1, 2020. Included were 26 chronic diseases, and 21 types of malignancies regarded as active by being diagnosed between January 1, 2018- to January 1, 2020, or by prescription of oncologic treatment medications January 1, 2018 and January 1, 2020.ResultsData from 4,627,183 individuals, 2,274,349 males and 2,352,834 females from newborn to 110 years. Obesity (19%), hypertension (13%), diabetes mellitus (9%), esophagitis-gastritis (5.5%), thyroid disease (5.3%), asthma (5.1%), ischemic heart disease (4.5%), depression (4.5%), osteoporosis (3.8%), and atopic dermatitis (3.6%) were the ten most prevalent conditions. Proportions of age groups varied between conditions (67% of hypertensives were ≥65 years old, 24% ≥80 years; 73% with ischemic heart disease were ≥65 years, 29% ≥80 years; 59% of diabetics were ≥65 years, 17% ≥80 years; 42% of atrial fibrillation patients were ≥80 years; 40% of heart failure patients were ≥80 years). Proportions of males and females for most conditions paralleled prevalence except proportions of women increased after age 80 for cardiovascular diseases, and for diabetes after age 75. The five most frequent active cancers were breast, prostate, colon/rectal, lymphoma and melanoma. The prevalence of cancers increased with age beginning in the middle-aged groups and peaking at very old ages. Women had lower prevalence of lung cancers and accounted for lower percentages of patients with lung cancers (45 vs 55%) but similar percentages for women and men were seen in the patients with colon and rectal cancer (50.4 vs. 49.6% in women) and lymphoma (50.7 vs. 49.3% in women).ConclusionsPrevalence of medical conditions and distributions differ by age and sex. This information serves as an example and resource for data needed to describe a "representative" clinical population.

Dyadic conditions of patients with heart failure and their caregivers may affect both patient self-care and caregiver contribution to patient self-care (CCPS). The purpose of this study was to examine the relationships of patient-caregiver physical function and depressive symptoms to the patient self-care (maintenance and management) and CCPS. Data from 55 were analyzed using an Actor-Partner Interdependence Model to address the aim through AMOS. Patient self-care was very poor. Better patient physical function was related to better patient self-care management (actor effect) and poorer CCPS maintenance (partner effect). Better caregiver physical function was related to CCPS management (actor effect). Severer patient depressive symptoms were related to poorer patient self-care maintenance (actor effect) and poorer CCPS management (partner effect). Physical function and depressive symptoms in patient-caregiver dyads were related to patient self-care and CCPS. To improve patient self-care and CCPS, dyadic support for physical function and depressive symptoms is needed.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) represents an important but limited treatment for patients with severe COVID-19. We assessed the effects of an educational intervention on a persons ECMO care preference and examined whether patients and providers had similar ECMO preferences. METHODS: In the Video+Survey group, patients watched an educational video about ECMOs purpose, benefits, and risks followed by an assessment of ECMO knowledge and care preferences in seven scenarios varying by hypothetical patient age, function, and comorbidities. Patients in the Survey Only group and providers didnt watch the video. Logistic regression was used to estimate the probability of agreement for each ECMO scenario between the two patient groups and then between all patients and providers. RESULTS: Video+Survey patients were more likely (64% vs. 17%; p = 0.02) to correctly answer all ECMO knowledge questions than Survey Only patients. Patients in both groups agreed that ECMO should be considered across all hypothetical scenarios, with predicted agreement above 65%. In adjusted analyses, patients and providers had similar predicted agreement for ECMO consideration across six of the seven scenarios, but patients showed greater preference (84% vs. 41%, p = 0.003) for the scenario of a functionally dependent 65-year-old with comorbidities than providers. DISCUSSION AND CONCLUSIONS: An educational video increased a persons ECMO knowledge but did not change their ECMO preferences. Clinicians were less likely than patients to recommend ECMO for older adults, so advanced care planning discussion between patients and providers about treatment options in critically ill patients with COVID-19 is critical.

BACKGROUND: Disparities in colorectal cancer screening have been documented among people with intellectual and developmental disabilities (IDD). However, surgical outcomes in this population have yet to be studied. The present work aimed to evaluate the association of IDD with outcomes following colorectal cancer resection. METHODS: All adults undergoing resection for colorectal cancer in the 2011-2020 National Inpatient Sample were identified. Multivariable linear and logistic regression models were developed to examine the association of IDD with risk factors as well as outcomes including mortality, complications, costs, length of stay (LOS), and non-home discharge. The study is limited by its retrospective nature and did not capture disease staging or time of diagnosis. RESULTS: Among 722,736 patients undergoing colorectal cancer resection, 2,846 (0.39%) had IDD. Compared to patients without IDD, IDD patients were younger and had a higher burden of comorbidities. IDD status was associated with increased odds of non-elective admission (AOR 1.40 [95% CI 1.14-1.73]) and decreased odds of treatment at high-volume centers (AOR 0.64 [95% CI 0.51-0.81]). Furthermore, IDD patients experienced significantly greater LOS (9 vs 6 days, p

BackgroundNoninvasive respiratory support modalities are common alternatives to mechanical ventilation in acute hypoxemic respiratory failure. However, studies historically compare noninvasive respiratory support to conventional oxygen rather than mechanical ventilation. In this study, we compared outcomes in patients with acute hypoxemic respiratory failure treated initially with noninvasive respiratory support to patients treated initially with invasive mechanical ventilation.MethodsThis is a retrospective observational cohort study between January 1, 2018 and December 31, 2019 at a large healthcare network in the United States. We used a validated phenotyping algorithm to classify adult patients (≥18 years) with eligible International Classification of Diseases codes into two cohorts: those treated initially with noninvasive respiratory support or those treated invasive mechanical ventilation only. The primary outcome was time-to-in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders. Secondary outcomes included time-to-hospital discharge alive. A secondary analysis was conducted to examine potential differences between noninvasive positive pressure ventilation and nasal high flow.ResultsDuring the study period, 3177 patients met inclusion criteria (40% invasive mechanical ventilation, 60% noninvasive respiratory support). Initial noninvasive respiratory support was not associated with a decreased hazard of in-hospital death (HR: 0.65, 95% CI: 0.35-1.2), but was associated with an increased hazard of discharge alive (HR: 2.26, 95% CI: 1.92-2.67). In-hospital death varied between the nasal high flow (HR 3.27, 95% CI: 1.43-7.45) and noninvasive positive pressure ventilation (HR 0.52, 95% CI 0.25-1.07), but both were associated with increased likelihood of discharge alive (nasal high flow HR 2.12, 95 CI: 1.25-3.57; noninvasive positive pressure ventilation HR 2.29, 95% CI: 1.92-2.74).ConclusionsThese data show that noninvasive respiratory support is not associated with reduced hazards of in-hospital death but is associated with hospital discharge alive.

A hallmark of Parkinsons disease is the specific degeneration of dopaminergic neurons in the substantia nigra pars compacta. Interestingly, not all of these neurons are affected to the same extent. Studies revealed that neurons located more ventrally within the substantia nigra pars compacta have a higher prevalence to degenerate than those located in the dorsal tier. The underlying reasons for this selective neuronal vulnerability are still unknown. The aim of the present study was to gain a better understanding of molecular differences between these two neuronal subpopulations that may explain the selective neuronal vulnerability within the human substantia nigra. For this purpose, the neurons from the ventral as well as dorsal tier of the substantia nigra were specifically isolated out of neuropathologically unremarkable human substantia nigra sections with laser microdissection. Following, their proteome was analyzed by data independent acquisition mass spectrometry. The samples were analysed donor-specifically and not pooled for this purpose. A total of 5,391 proteins were identified in the substantia nigra. Of these, 2,453 proteins could be quantified in 100% of the dorsal tier samples. 1,629 could be quantified in 100% of the ventral tier samples. Nine proteins were differentially regulated with a log2 value ≥0.5 and a Qvalue ≤0.05. Of these 7 were higher abundant in the dorsal tier and 2 higher in the ventral tier. These proteins are associated with the cytoskeleton, neuronal plasticity, or calcium homeostasis. With these findings a deeper understanding can be gained of the selective neuronal vulnerability within the substantia nigra and of protective mechanisms against neurodegeneration in specific neuronal subpopulations.

BACKGROUND: Myelin and iron are major contributors to the cortical MR signal. The aim of this study was to investigate 1. Can MP2RAGE-derived contrasts at 7T in combination with k-means clustering be used to distinguish between heavily and sparsely myelinated layers in cortical gray matter (GM)? 2. Does this approach provide meaningful biological information? METHODS: The following contrasts were generated from the 7T MP2RAGE images from 45 healthy controls (age: 19-75, f/m = 23/22) from the ATAG data repository: 1. T1 weighted image (UNI). 2. T1 relaxation image (T1map). 3. INVC/T1map ratio (RATIO). K-means clustering identified 6 clusters/tissue maps (csf, csf/gm-transition, wm, wm/gm transition, heavily myelinated cortical GM (dGM), sparsely myelinated cortical GM (sGM)). These tissue maps were then processed with SPM/DARTEL (volume-based analyses) and Freesurfer (surface-based analyses) and dGM and sGM volume/thickness of young adults (n = 27, 19-27 years) compared to those of older adults (n = 18, 42-75 years) at p

INTRODUCTION: Sepsis is a major cause of morbidity and mortality worldwide. In the updated, 2016 Sepsis-3 criteria, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, where organ dysfunction can be represented by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. We sought to apply the Sepsis-3 criteria to characterise the septic cohort in the Amsterdam University Medical Centres database (Amsterdam UMCdb). METHODS: We examined adult intensive care unit (ICU) admissions in the Amsterdam UMCdb, which contains de-identified data for patients admitted to a mixed surgical-medical ICU at a tertiary academic medical centre in the Netherlands. We operationalised the Sepsis-3 criteria, defining organ dysfunction as an increase in the SOFA score of 2 points or more, while infection was defined as a new course of antibiotics or an escalation in antibiotic therapy, with at least one antibiotic given intravenously. Patients with sepsis were determined to be in septic shock if they additionally required the use of vasopressors and had a lactate level >2 mmol/L. RESULTS: We identified 18,221 ICU admissions from 16,408 patients in our cohort. There were 6,312 unique sepsis episodes, of which 30.2% met the criteria for septic shock. A total of 4,911/6,312 sepsis (77.8%) episodes occurred on ICU admission. Forty-seven percent of emergency medical admissions and 36.7% of emergency surgical admissions were for sepsis. Overall, there was a 12.5% ICU mortality rate; patients with septic shock had a higher ICU mortality rate (38.4%) than those without shock (11.4%). CONCLUSIONS: We successfully operationalised the Sepsis-3 criteria to the Amsterdam UMCdb, allowing the characterization and comparison of sepsis epidemiology across different centres.

Loss of lean muscle mass and accumulation of adipose tissue are changes associated with aging. Previous studies have documented various components of body composition as predictors for insulin resistance. The objective of this study was to investigate whether components of body composition-appendicular lean mass (ALM) and/or abdominal fat mass (AFM)-correlate with insulin resistance in older men and women. This was a cross-sectional study of 92 older men and women. Weight was classified according to body mass index (BMI)-normal (BMI 30). All body composition data was determined by dual energy x-ray absorptiometry (DEXA), and insulin resistance was assessed by the homeostatic model assessment of insulin resistance (HOMA-IR). Multivariable regression models with two-way interaction terms were employed to assess whether the associations between components of body composition and log HOMA varied by BMI categories. Adjusted regression showed that log HOMA was significantly associated with AFM (estimate ± standard error: 0.055 ± 0.026) and ALM (0.057 ± 0.029) for the overweight participants (p-values

INTRODUCTION: Literature regarding the impact of esophagectomy approach on hospitalizations costs and short-term outcomes is limited. Moreover, few have examined how institutional MIS experience affects costs. We thus examined utilization trends, costs, and short-term outcomes of open and minimally invasive (MIS) esophagectomy as well as assessing the relationship between institutional MIS volume and hospitalization costs. METHODS: All adults undergoing elective esophagectomy were identified from the 2016-2020 Nationwide Readmissions Database. Multiple regression models were used to assess approach with costs, in-hospital mortality, and major complications. Additionally, annual hospital MIS esophagectomy volume was modeled as a restricted cubic spline against costs. Institutions performing > 16 cases/year corresponding with the inflection point were categorized as high-volume hospitals (HVH). We subsequently examined the association of HVH status with costs, in-hospital mortality, and major complications in patients undergoing minimally invasive esophagectomy. RESULTS: Of an estimated 29,116 patients meeting inclusion, 10,876 (37.4%) underwent MIS esophagectomy. MIS approaches were associated with $10,600 in increased incremental costs (95% CI 8,800-12,500), but lower odds of in-hospital mortality (AOR 0.76; 95% CI 0.61-0.96) or major complications (AOR 0.68; 95% CI 0.60, 0.77). Moreover, HVH status was associated with decreased adjusted costs, as well as lower odds of postoperative complications for patients undergoing MIS operations. CONCLUSION: In this nationwide study, MIS esophagectomy was associated with increased hospitalization costs, but improved short-term outcomes. In MIS operations, cost differences were mitigated by volume, as HVH status was linked with decreased costs in the setting of decreased odds of complications. Centralization of care to HVH centers should be considered as MIS approaches are increasingly utilized.

PURPOSE: The population with serious mental illness has high risk for hospitalization or death due to unhealthy behaviors and inadequate medical care, though the level of risk varies substantially. Programs that integrate medical and psychiatric services improve outcomes but are challenging to implement and access is limited. It would be useful to know whether benefits are confined to patients with specific levels of risk. METHODS: In a population with serious mental illness and increased risk for hospitalization or death, a specialized medical home integrated services and improved treatment and outcomes. Treatment quality, chronic illness care, care experience, symptoms, and quality of life were assessed for a median of 385 days. Analyses examine whether improvements varied by baseline level of patient risk. RESULTS: Patients with greater risk were more likely to be older, more cognitively impaired, and have worse mental health. Integrated services increased appropriate screening for body mass index, lipids, and glucose, but increases did not differ significantly by level of risk. Integrated services also improved chronic illness care, care experience, mental health-related quality of life, and psychotic symptoms. There were also no significant differences by risk level. CONCLUSIONS: There were benefits from integration of primary care and psychiatric care at all levels of increased risk, including those with extremely high risk above the 95th percentile. When developing integrated care programs, patients should be considered at all levels of risk, not only those who are the healthiest.

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimers disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. OBJECTIVE: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. METHODS: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. CONCLUSION: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360.

OBJECTIVE: To describe the implementation of a test-negative design case-control study in California during the Coronavirus Disease 2019 (COVID-19) pandemic. STUDY DESIGN: Test-negative case-control study. METHODS: Between February 24, 2021 - February 24, 2022, a team of 34 interviewers called 38,470 Californians, enrolling 1,885 that tested positive for SARS-CoV-2 (cases) and 1,871 testing negative for SARS-CoV-2 (controls) for 20-minute telephone survey. We estimated adjusted odds ratios for answering the phone and consenting to participate using mixed effects logistic regression. We used a web-based anonymous survey to compile interviewer experiences. RESULTS: Cases had 1.29-fold (95% CI: 1.24-1.35) higher adjusted odds of answering the phone and 1.69-fold (1.56-1.83) higher adjusted odds of consenting to participate compared to controls. Calls placed from 4pm to 6pm had the highest adjusted odds of being answered. Some interviewers experienced mental wellness challenges interacting with participants with physical (e.g., food, shelter, etc.) and emotional (e.g., grief counseling) needs, and enduring verbal harassment from individuals called. CONCLUSIONS: Calls placed during afternoon hours may optimize response rate when enrolling controls to a case-control study during a public health emergency response. Proactive check-ins and continual collection of interviewer experience(s) and may help maintain mental wellbeing of investigation workforce. Remaining adaptive to the dynamic needs of the investigation team is critical to a successful study, especially in emergent public health crises, like that represented by the COVID-19 pandemic.

OBJECTIVE: To investigate the feasibility of pre- and post-encounter patient-reported outcome (PRO) measure collection within an outpatient integrative health and medicine (IHM) clinic and to characterize factors associated with successful completion. METHODS: We conducted a retrospective review of 27,464 outpatient IHM encounters including 9,520 chiropractic; 8,237 acupuncture; 5,847 massage; 2,345 IHM consultation; and 1,515 osteopathic manipulation treatment encounters at four clinics offering IHM over 18 months. Patients were asked to complete paper questionnaires rating pain, anxiety, and stress from 0-10 immediately pre- and post-encounter. Generalized linear mixed effect regression models were used to examine the relationship between demographic, clinical, and operational covariates and completing (1) pre-encounter and (2) paired (i.e., pre and post) PROs. RESULTS: Patients (N = 5587, mean age 49 years, 74% white, 77% female) generally presented for musculoskeletal conditions (81.7%), with a chief complaint of pain (55.1%). 21,852 (79.6%) encounters were among patients who completed pre-encounter PROs; 11,709/21,852 (53.6%) completed subsequent post-encounter PROs. Odds of PRO completion were more impacted by provider, operational, and clinical-level factors than patient factors. Covariates associated with increased odds of pre-encounter PRO completion included being female, having additional IHM encounters, and having a pain or anxiety complaint. Covariates associated with increased odds of paired PRO completion included being aged 31-40 vs. 51-60 years and having additional IHM encounters. CONCLUSION: Implementing a paper-based PRO collection system in outpatient IHM is feasible; however, collecting post-encounter PROs was challenging. Future endeavors should leverage the electronic health record and patient portals to optimize PRO collection and engage patients and clinical providers.

OBJECTIVE: To describe the protocol of a prospective study to test the validity of intermuscular coherence (IMC) as a diagnostic tool and biomarker of upper motor neuron degeneration in amyotrophic lateral sclerosis (ALS). METHODS: This is a multicenter, prospective study. IMC of muscle pairs in the upper and lower limbs is gathered in ∼650 subjects across three groups using surface electrodes and conventional electromyography (EMG) machines. The following subjects will be tested: 1) neurotypical controls; 2) patients with symptomatology suggestive for early ALS but not meeting probable or definite ALS by Awaji Criteria; 3) patients with a known ALS mimic. The recruitment period is between 3/31/2021 and 12/31/2025. Written consent will be sought from the subject or the subjects legally authorized representative during enrollment. RESULTS: The endpoints of this study include: 1) whether adding IMC to the Awaji ALS criteria improve its sensitivity in early ALS and can allow for diagnosis earlier; 2) constructing a database of IMC across different ages, genders, and ethnicities. SIGNIFICANCE: This study may validate a new inexpensive, painless, and widely available tool for the diagnosis of ALS.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) has garnered interest as a viable alternative to the traditional surgical mitral valve replacement (SMVR) for high-risk patients requiring redo operations. This study aims to evaluate the association of TMVR with selected clinical and financial outcomes. METHODS: Adults undergoing isolated redo mitral valve replacement were identified in the 2016-2020 Nationwide Readmissions Database and categorized into TMVR or SMVR cohorts. Various regression models were developed to assess the association between TMVR and in-hospital mortality, as well as additional secondary outcomes. Transseptal and transapical catheter-based approaches were also compared in relation to study endpoints. RESULTS: Of an estimated 7,725 patients, 2,941 (38.1%) underwent TMVR. During the study period, the proportion of TMVR for redo operations increased from 17.8% to 46.7% (nptrend

Strategies to prevent or delay Alzheimers disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.

BACKGROUND: Acupuncture and chiropractic care are evidence-based pain management alternatives to opioids. The Veterans Health Administration (VA) provides this care in some VA facilities, but also refers patients to community providers. We aimed to determine if patient-reported outcomes differ for acupuncture and chiropractic care from VA versus community providers. MATERIALS AND METHODS: We conducted an observational study using survey outcome data and electronic medical record utilization data for acupuncture and chiropractic care provided in 18 VA facilities or in community facilities reimbursed by VA. Study participants were users of VA primary care, mental health, pain clinic, complementary and integrative therapies, coaching or education services in 2018-2019. Patients received 1) 4+ acupuncture visits (N = 201) or 4+ chiropractic care visits (N = 178) from a VA or community provider from 60 days prior to baseline to six-months survey and 2) no acupuncture or chiropractic visits from 1 year to 60 days prior to baseline. Outcomes measured included patient-reported pain (PEG) and physical health (PROMIS) at baseline and six-month surveys. Multivariate analyses examined outcomes at six months, adjusting for baseline outcomes and demographics. RESULTS: In unadjusted analyses, pain and physical health improved for patients receiving community-based acupuncture, while VA-based acupuncture patients experienced no change. Unadjusted analyses also showed improvements in physical health, but not pain, for patients receiving VA-based chiropractic care, with no changes for community-based chiropractic care patients. Using multivariate models, VA-based acupuncture was no different from community-based acupuncture for pain (-0.258, p = 0.172) or physical health (0.539, p = 0.399). Similarly, there were no differences between VA- and community-based chiropractic care in pain (-0.273, p = 0.154) or physical health (0.793, p = 0.191). CONCLUSIONS: Acupuncture and chiropractic care were associated with modest improvements at six months, with no meaningful differences between VA and community providers. The choice to receive care from VA or community providers could be based on factors other than quality, like cost or convenience.

BACKGROUND: Studies suggest that distress is associated with various health conditions such as hypertension, asthma, diabetes, and coronary heart disease. However, only few studies focused on Asian Americans and little is known about the association with multiple comorbidity. METHODS: We conducted a cross-sectional analysis among 400 Chinese and Korean American participants (aged 50-75 years) of the STOP CRC randomized controlled trial. Perceived distress was assessed using the distress thermometer scale (range 0-10). Disease diagnosis was self-reported by the participants. Multimorbidity (MM) was defined as having ≥2 chronic conditions. Complex multimorbidity (CMM) was defined as having ≥3 of the following body system disorders: circulation disorder, endocrine-metabolic disorder, cancer, anxiety or depression, breathing problem, and other health problems. We performed logistic regression for CMM and Poisson regression with robust error variance for MM to estimate associations with distress, adjusting for potential confounders. RESULTS: The mean age was 58.4 years and mean distress score was 3.65. One-unit increase in distress score was associated with a 1.22-fold increase in the odds of having CMM (95% CI: 1.04-1.42). The magnitude of association slightly increased after additional adjustment for socioeconomic factors and health insurance status (OR: 1.29; 95% CI: 1.10-1.52). Higher distress score was positively associated with MM but the association was only marginally significant (PR: 1.04; 95% CI: 0.99-1.10), adjusting for socioeconomic factors and health insurance status. CONCLUSION: Our data suggest that higher perceived distress may be associated with simultaneous dysfunction of multiple distinct body systems among Chinese and Korean American older adults.

BackgroundAntibodies to citrullinated protein antigens have been linked to altered left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA). Serum reactivity to several citrullinated protein/peptide antigens has been identified in RA, which are detectable years before RA onset and in individuals who may never develop RA. Among community-living individuals without heart failure (HF) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated associations between serum reactivity to citrullinated protein/peptide antigens, LV mass, LV ejection fraction (LVEF), and incident HF.MethodsAmong 1232 MESA participants, we measured serum reactivity to 28 different citrullinated proteins/peptides using a multiplex bead-based array. Each antibody was defined as having extremely high reactivity (EHR) if >95th percentile cut-off in MESA. Number of EHR antibody responses to citrullinated protein/peptide antigens were summed for each participant (range 0-28). LV mass(g) and LVEF(%) were measured on cardiac MRI. Associations between EHR antibodies and LV mass and LVEF were evaluated using linear regression. Cox proportional hazards models were used to evaluate associations between EHR antibodies and incident HF during 11 years of follow-up, adjusting for age, gender, race/ethnicity, smoking status, systolic blood pressure, use of anti-hypertensive medications, self-reported arthritis, IL-6, body surface area, and estimated glomerular filtration rate.ResultsMean age was 65±10, 50% were female, 40% were White, 21% were Black, 26% were Hispanic/Latino, and 14% were Chinese. Twenty-seven percent of MESA participants had extremely high reactivity to ≥ 1 citrullinated protein/peptide antigen. In fully adjusted analysis, every additional EHR antibody was significantly associated with 0.1% lower LVEF (95% CI: -0.17%, -0.02%). No association was observed with LV mass (β per additional EHR antibody) = 0.13±0.15 (p = 0.37)). Neither the presence nor number of EHR antibodies was associated with incident HF during follow-up (HR per additional EHR antibody = 1.008 (95% CI: 0.97, 1.05)).ConclusionGreater number of extremely highly reactive antibodies was associated with lower LVEF, but not with LV mass or incident HF. Thus, serum reactivity to citrullinated protein/peptide antigens was associated with subtle subclinical changes in myocardial contractility, but the significance in relation to clinically apparent HF is uncertain.

INTRODUCTION: Latinos are the fastest growing aging population in the U.S. However, there has been limited attention to conceptualizing successful aging among Latinos, especially those residing in rural communities. Latinos are the largest racial or ethnic group residing in rural underserved communities and rural Latinos experience significant structural barriers to access the conditions they need to age well. The goal of this study is to make unique contributions to the successful aging literature by describing what successful aging means for middle-aged Latinas residing in a rural community. METHODS: This qualitative paper used inductive thematic content analysis to examine definitions of successful aging among Latina women (n = 40) residing in an underserved agricultural community and entering mid-life (mean = 49 years old; age range 40-64). RESULTS: With regards to definitions of successful aging, four themes emerged: 1) Having good health; 2) maintaining an active lifestyle; 3) the wellbeing of ones children; and 4) being independent. DISCUSSION: Participants definitions of successful aging aligned to some extent with existing frameworks, specifically related to health and independence. However, middle-aged Latina participants unique definitions of successful aging also diverged from existing frameworks, especially around the wellbeing of their children and the importance of work as a way of maintaining an active lifestyle. More research is needed to understand the unique social context and circumstances of middle-aged Latinos residing in rural communities and how they influence their aging journeys. This can provide important information for the development of culturally sensitive services, interventions, and policies to help Latinos age well.

Functional status, or the ability to perform activities of daily living, is central to older adults health and quality of life. However, health systems have been slow to incorporate routine measurement of function into patient care. We used multiple qualitative methods to develop a patient-centered, interprofessional intervention to improve measurement of functional status for older veterans in primary care settings. We conducted semi-structured interviews with patients, clinicians, and operations staff (n = 123) from 7 Veterans Health Administration (VHA) Medical Centers. Interviews focused on barriers and facilitators to measuring function. We used concepts from the Consolidated Framework for Implementation Science and sociotechnical analysis to inform rapid qualitative analyses and a hybrid deductive/inductive approach to thematic analysis. We mapped qualitative findings to intervention components. Barriers to measurement included time pressures, cumbersome electronic tools, and the perception that measurement would not be used to improve patient care. Facilitators included a strong interprofessional environment and flexible workflows. Findings informed the development of five intervention components, including (1) an interprofessional educational session; (2) routine, standardized functional status measurement among older patients; (3) annual screening by nurses using a standardized instrument and follow-up assessment by primary care providers; (4) electronic tools and templates to facilitate increased identification and improved management of functional impairment; and (5) tailored reports on functional status for clinicians and operations leaders. These findings show how qualitative methods can be used to develop interventions that are more responsive to real-world contexts, increasing the chances of successful implementation. Using a conceptually-grounded approach to intervention development has the potential to improve patient and clinician experience with measuring function in primary care.

BACKGROUND: High sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups. METHODS: Depressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-

PurposeIn young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population.MethodsA retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS.ResultsAmong the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%).ConclusionTrough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

BackgroundParkinson disease (PD) psychosis (PDP) is a disabling non-motor symptom. Pharmacologic treatment is limited to pimavanserin, quetiapine, and clozapine, which do not worsen parkinsonism. A Food and Drug Administration black box warning exists for antipsychotics, suggesting increased mortality in elderly patients with dementia. However, the reasons for higher mortality are unknown.AimExpanding on prior work exploring mortality in treated PDP patients, we conducted a retrospective comparison to understand the links between treatment regimen, clinical characteristics, and negative outcomes.MethodsElectronic medical record data extraction included clinically diagnosed PD patients between 4/29/16-4/29/19 and excluded patients with primary psychiatric diagnoses or atypical parkinsonism. Mortality and clinical characteristics during the study period were compared between untreated patients and those receiving pimavanserin, quetiapine, or both agents (combination). Mortality analyses were adjusted for age, sex, levodopa equivalent daily dose (LEDD), and dementia.ResultsThe pimavanserin group (n = 34) had lower mortality than the untreated group (n = 66) (odds ratio = 0.171, 95% confidence interval: 0.025-0.676, p = 0.026). The untreated group had similar mortality compared to the quetiapine (n = 147) and combination (n = 68) groups. All treated groups had a higher LEDD compared to the untreated group, but no other differences in demographics, hospitalizations, medical comorbidities, medications, or laboratory values were found between the untreated and treated groups.ConclusionsPDP patients receiving pimavanserin had lower mortality than untreated patients. We found no other clear differences in clinical characteristics to explain the mortality risk. Prospective randomized trials are needed to definitively identify the optimal PDP treatment regimen and associated risks.

OBJECTIVES: Despite documented benefits and physicians recommendations to participate in cardiac rehabilitation (CR) programs, the average dropout rate remains between 12-56%. This studys goal was to demonstrate that using personalized interventions can significantly increase patient adherence. METHOD: Ninety-five patients (ages 18-90) eligible for the CR program were randomly recruited and received personalized interventions using the Well-Beat system. Adherence levels were compared to those of a historical control group. The Well-Beat system provided Sheba CR Health Care Provider (HCP) guidelines for personalized patient-therapist dialogue. The system also generated ongoing personalized text messages for each patient sent twice a week and related each patients dynamic profile to their daily behavior, creating continuity, and reinforcing the desired behavior. RESULTS: A significant increase in patient adherence to the CR program: Three months after initiation, 76% remained active compared to the historical average of 24% in the matched control group (log-rank p-value = 0.001). CONCLUSIONS: Using an Artificial Intelligence (AI)-based engine that generated recommendations and messages made it possible to improve patient adherence without increasing HCP load, benefiting all. Presenting customized patient insights to the HCP and generating personalized communications along with action motivating text messages can also be useful for remote care.

BACKGROUND: Respiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States. METHODS: Population-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015-2017) from October 1-April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (

ObjectiveType 2 Diabetes Mellitus (henceforth diabetes) affects roughly 35 million individuals in the US and is a major risk factor for cardiovascular and kidney disease. Serum Cystatin-C is used to monitor renal function and detect kidney damage. Recent research has focused on linking Cystatin-C to cardiovascular risk and disease, but most findings focus on small sample sizes and generalize poorly to diverse populations, thus limiting epidemiological inferences. The aim of this manuscript is to study the association between Cystatin-C, diabetes, and mortality and test for possible sex or racial/ethnic background modifications in these relationships.MethodsWe analyzed 8-years of biennial panel data from Health and Retirement Study participants 50-years and older who self-identified as White (unweighted N (uN) = 5,595), Black (uN = 867), or Latino (uN = 565) for a total of uN = 7,027 individuals. We modeled diabetes and death over 8-years as function of baseline Cystatin-C (log transformed) adjusting for covariates and tested modifications in associations by race/ethnic background and sex.ResultsMean log Cystatin-C at visit 1 was 0.03±0.32 standard deviation. A 10% increase in Cystatin-C levels was associated with 13% increased relative risk of diabetes at baseline (11% and 9% by years 4 and 8). A 10% increase in Cystatin-C was highly associated with increased relative risk of death (28% and 31% by years 4 and 8). These associations were present even after adjusting for possible confounders and were not modified by sex or racial/ethnic background.ConclusionDespite differential risks for diabetes and mortality by racial/ethnic groups, Cystatin-C was equally predictive of these outcomes across groups. Cystatin-C dysregulations could be used as a risk indicator for diabetes and as a warning sign for accelerated risk of mortality.

BackgroundIdentifying Obstructive Sleep Apnea (OSA) phenotypes among middle-aged and older Hispanics/Latinos can facilitate personalized care, better inform treatment decisions, and could lead to improved clinical outcomes.MethodsWe focused on middle-aged and older adults (ages ≥45-74 years at baseline) with an apnea-hypopnea index (AHI) ≥5 from the HCHS/SOL (2008-2011) (unweighted n = 3,545). We used latent class analyses (LCA) to identify empirical and clinically meaningful OSA phenotypes. Sleep variables included AHI, percent sleep time SpO2

PURPOSE: To identify meanings of and challenges to enacting equitable diversification of genomics research, and specifically precision medicine research (PMR), teams. METHODS: We conducted in-depth interviews with 102 individuals involved in three U.S.-based precision medicine research consortia and conducted over 400 observation hours of their working group meetings, consortium-wide meetings, and conference presentations. We also reviewed published reports on genomic workforce diversity (WFD), particularly those relevant to the PMR community. RESULTS: Our study finds that many PMR teams encounter challenges as they strive to achieve equitable diversification on scientific teams. Interviewees articulated that underrepresented team members were often hired to increase the studys capacity to recruit diverse research participants, but are limited to on-the-ground staff positions with little influence over study design. We find existing hierarchies and power structures in the academic research ecosystem compound challenges for equitable diversification. CONCLUSION: Our results suggest that meaningful diversification of PMR teams will only be possible when team equity is prioritized as a core value in academic research communities.

BackgroundThe co-existence of undernutrition and overnutrition is a global public health threat. We aim to report the burden of both nutritional deficiency (Protein-Energy Malnutrition) and overweight (high Body Mass Index) in Nepal over a decade (2010-2019) and observe the changes through trend charts.MethodsWe did a secondary data analysis using the Institute for Health Metrics and Evaluation (IHME)'s Global Burden of Disease (GBD) database to download age-standardized data on Protein Energy Malnutrition (PEM) and high Body Mass Index (BMI). We presented the trend of death, Disability Adjusted Life Years (DALYs), Years of Life Lost (YLL), and Years Lost due to Disability (YLD) of PEM and high BMI in Nepal from 2010 to 2019 and also compared data for 2019 among South Asian countries.ResultsBetween 2010 and 2019, in Nepal, the Disability Adjusted Life Years (DALYs) due to PEM were declining while high BMI was in increasing trend. Sex-specific trends revealed that females had higher DALYs for PEM than males. In contrast, males had higher DALYs for high BMI than females. In 2019, Nepal had the highest death rate for PEM (5.22 per 100,000 populations) than any other South Asian country. The burden of PEM in terms of DALY was higher in under-five children (912 per 100,000 populations) and elderly above 80 years old (808.9 per 100,000 populations), while the population aged 65-69 years had the highest burden of high BMI (5893 per 100,000 populations). In the last decade, the DALYs for risk factors contributing to PEM such as child growth failure (stunting and wasting), unsafe water, sanitation and handwashing, and sub-optimal breastfeeding have declined in Nepal. On the contrary, the DALYs for risk factors contributing to high BMI, such as a diet high in sugar-sweetened beverages, a diet high in trans fatty acid, and low physical activity, have increased. This could be a possible explanation for the increasing trend of high BMI and decreasing trend of PEM.ConclusionRapidly growing prevalence of high BMI and the persistent existence of undernutrition indicate the double burden of malnutrition in Nepal. Public health initiatives should be planned to address this problem.

Renalase is a secreted flavoprotein with anti-inflammatory and pro-cell survival properties. COVID-19 is associated with disordered inflammation and apoptosis. We hypothesized that blood renalase levels would correspond to severe COVID-19 and survival. In this retrospective cohort study, clinicopathologic data and blood samples were collected from hospitalized COVID-19 subjects (March-June 2020) at a single institution tertiary hospital. Plasma renalase and cytokine levels were measured and clinical data abstracted from health records. Of 3,450 COVID-19 patients, 458 patients were enrolled. Patients were excluded if

PurposeTo investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women.DesignThis was a retrospective study using data from the Women's Health Initiative.MethodsPatients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics.ResultsFinal analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007).ConclusionsIndependent of the CDR GRS, women with large CDR had a lower cognitive function.

BackgroundRecently, tau PET tracers have shown strong associations with clinical outcomes in individuals with cognitive impairment and cognitively unremarkable elderly individuals. flortaucipir PET scans to measure tau deposition in multiple brain areas as the disease progresses. This information needs to be summarized to evaluate disease severity and predict disease progression. We, therefore, sought to develop a machine learning-derived index, SPARE-Tau, which successfully detects pathology in the earliest disease stages and accurately predicts progression compared to a priori-based region of interest approaches (ROI).Methods587 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort had flortaucipir scans, structural MRI scans, and an Aβ biomarker test (CSF or florbetapir PET) performed on the same visit. We derived the SPARE-Tau index in a subset of 367 participants. We evaluated associations with clinical measures for CSF p-tau, SPARE-MRI, and flortaucipir PET indices (SPARE-Tau, meta-temporal, and average Braak ROIs). Bootstrapped multivariate adaptive regression splines linear regression analyzed the association between the biomarkers and baseline ADAS-Cog13 scores. Bootstrapped multivariate linear regression models evaluated associations with clinical diagnosis. Cox-hazards and mixed-effects models investigated clinical progression and longitudinal ADAS-Cog13 changes. The Aβ positive cognitively unremarkable participants, not included in the SPARE-Tau training, served as an independent validation group.ResultsCompared to CSF p-tau, meta-temporal, and averaged Braak tau PET ROIs, SPARE-Tau showed the strongest association with baseline ADAS-cog13 scores and diagnosis. SPARE-Tau also presented the strongest association with clinical progression in cognitively unremarkable participants and longitudinal ADAS-Cog13 changes. Results were confirmed in the Aβ+ cognitively unremarkable hold-out sample participants. CSF p-tau showed the weakest cross-sectional associations and longitudinal prediction.DiscussionFlortaucipir indices showed the strongest clinical association among the studied biomarkers (flortaucipir, florbetapir, structural MRI, and CSF p-tau) and were predictive in the preclinical disease stages. Among the flortaucipir indices, the machine-learning derived SPARE-Tau index was the most sensitive clinical progression biomarker. The combination of different biomarker modalities better predicted cognitive performance.

BackgroundAs global populations age, cross-national comparisons of cognitive health and dementia risk are increasingly valuable. It remains unclear, however, whether country-level differences in cognitive function are attributable to population differences or bias due to incommensurate measurement. To demonstrate an effective method for cross-national comparison studies, we aimed to statistically harmonize measures of episodic memory and language function across two population-based cohorts of older adults in the United States (HRS HCAP) and India (LASI-DAD).MethodsData for 3,496 HRS HCAP (≥65 years) and 3,152 LASI-DAD (≥60 years) participants were statistically harmonized for episodic memory and language performance using confirmatory factor analysis (CFA) methods. Episodic memory and language factor variables were investigated for differential item functioning (DIF) and precision.ResultsCFA models estimating episodic memory and language domains based on a priori adjudication of comparable items fit the data well. DIF analyses revealed that four out of ten episodic memory items and five out of twelve language items measured the underlying construct comparably across samples. DIF-modified episodic memory and language factor scores showed comparable patterns of precision across the range of the latent trait for each sample.ConclusionsHarmonization of cognitive measures will facilitate future investigation of cross-national differences in cognitive performance and differential effects of risk factors, policies, and treatments, reducing study-level measurement and administrative influences. As international aging studies become more widely available, advanced statistical methods such as those described in this study will become increasingly central to making universal generalizations and drawing valid conclusions about cognitive aging of the global population.

Main objectiveThere is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic.Study design and methodsUniversity of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission.Results and significanceThe 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months.ConclusionsMortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes.Trial registrationClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

Los Angeles, California became a warzone of COVID-19 infections with up to one death every 10 minutes at the end of 2020. As resources thinned, and ICU beds and ventilators became scarce, physicians began agonizing over potentially rationing medical care. In this study, we conducted a retrospective cohort analysis of 7,429 confirmed COVID-19 positive patients from two community hospitals in Los Angeles, California between March 16, 2020 and June 9, 2021. We applied the Cox proportional hazards regression model to determine the risk factors most strongly associated with in-hospital mortality. Using the multivariable Cox proportional hazards model, there was a higher hazard ratio (HR) for mortality in patients who were older (age ≥60 years) [HR 2.189, 95% CI 1.991-2.407, p

BackgroundNeuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)-with its capability to improve neuronal function-may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC).MethodsEleven PWH (47-69 years old, 2 females, 100% African Americans, disease duration 16-36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2-3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1.ResultsCompared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test-Part B (TMT-B) to TMT-Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS.ConclusionsCingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted.

BackgroundEarly reports of increased thrombosis risk with SARS-CoV-2 infection led to changes in venous thromboembolism (VTE) management. Real-world data on the prevalence, efficacy and harms of these changes informs best practices.ObjectiveDefine practice patterns and clinical outcomes related to VTE diagnosis, prevention, and management in hospitalized patients with coronavirus disease-19 (COVID-19) using a multi-hospital US sample.MethodsIn this retrospective cross-sectional study of 1121 patients admitted to 33 hospitals, exposure was dose of anticoagulant prescribed for VTE prophylaxis (standard, intensified, therapeutic), and primary outcome was VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]); secondary outcomes were PE, DVT, arterial thromboembolism (ATE), and bleeding events. Multivariable logistic regression models accounting for clustering by site and adjusted for risk factors were used to estimate odds ratios (ORs). Inverse probability weighting was used to account for confounding by indication.Results1121 patients (mean age 60 ± 18, 47% female) admitted with COVID-19 between February 2, 2020 and December 31, 2020 to 33 US hospitals were included. Pharmacologic VTE prophylaxis was prescribed in 86%. Forty-seven patients (4.2%) had PE, 51 (4.6%) had DVT, and 23 (2.1%) had ATE. Forty-six patients (4.1%) had major bleeding and 46 (4.1%) had clinically relevant non-major bleeding. Compared to standard prophylaxis, adjusted odds of VTE were 0.67 (95% CI 0.21-2.1) with no prophylaxis, 1.0 (95% CI 0.06-17) with intensified, and 3.0 (95% CI 0.89-10) with therapeutic. Adjusted odds of bleeding with no prophylaxis were 5.6 (95% CI 3.0-11) and 5.3 (95% CI 3.0-10) with therapeutic (no events on intensified dosing).ConclusionsTherapeutic anticoagulation was associated with a 3-fold increased odds of VTE and 5-fold increased odds of bleeding. While higher bleeding rates with high-intensity prophylaxis were likely due to full-dose anticoagulation, we conclude that high thrombosis rates were due to clinical concern for thrombosis before formal diagnosis.

PurposeInadequacies in healthcare access and utilization substantially impact outcomes for diabetic patients. The All of Us database offers extensive survey data pertaining to social determinants that is not routinely available in electronic health records. This study assesses whether social determinants were associated with an increased risk of developing proliferative diabetic retinopathy or related complications (e.g. related diagnoses or procedures).MethodsWe identified 729 adult participants in the National Institutes of Health All of Us Research Program data repository with diabetic retinopathy (DR) who answered survey questions pertaining to healthcare access and utilization. Electronic health record data regarding co-morbidities, laboratory values, and procedures were extracted. Multivariable logistic regression with bi-directional stepwise variable selection was performed from a wide range of predictors. Statistical significance was defined as p

BackgroundOral anticoagulants (OACs) mitigate the risk of stroke in atrial fibrillation (AF) patients.ObjectiveElderly AF patients who were treated with OACs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) were compared against AF patients who were not treated with OACs with respect to their clinical and economic outcomes.MethodsNewly diagnosed AF patients were identified between January 2013 and December 2017 in the Medicare database. Evidence of an OAC treatment claim on or after the first AF diagnosis was used to classify patients into treatment-defined cohorts, and these cohorts were further stratified based on the initial OAC prescribed. The risks of stroke/systemic embolism (SE), major bleeding (MB), and death were analyzed using inverse probability treatment weighted time-dependent Cox regression models, and costs were compared with marginal structural models.ResultsThe two treatment groups were composed of 1,421,187 AF patients: OAC treated (N = 583,350, 41.0% [36.4% apixaban, 4.9% dabigatran, 0.1% edoxaban, 26.7% rivaroxaban, and 31.9% warfarin patients]) and untreated (N = 837,837, 59.0%). OAC-treated patients had a lower adjusted risk of stroke/SE compared to untreated patients (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.68-0.72). Additionally patients receiving OACs had a lower adjusted risk of death (HR: 0.56; 95% CI: 0.55-0.56) and a higher risk of MB (HR: 1.57; 95% CI: 1.54-1.59) and this trend was consistent across each OAC sub-group. The OAC-treated cohort had lower adjusted total healthcare costs per patient per month ($4,381 vs $7,172; p < .0001).ConclusionFor the OAC-treated cohort in this elderly US population, stroke/SE and all-cause death were lower, while risk of MB was higher. Among OAC treated patients, total healthcare costs were lower than those of the untreated cohort.

ObjectivesTo investigate the objective sleep influencers behind older adult responses to subjective sleep measures, in this case, the Pittsburgh Sleep Quality Index (PSQI). Based on previous literature, we hypothesized that SE would be associated with PSQI reported sleep disruption. Furthermore, because SOL increases progressively with age and it tends to be easily remembered by the patients, we also expected it to be one of the main predictors of the perceived sleep quality in the elderly.MethodsWe studied 32 cognitively healthy community-dwelling older adults (age 74 ± 0.3 years) who completed an at-home sleep assessment (Zeo, Inc.) and the PSQI. Linear mixed models were used to analyze the association of the objective sleep parameters (measured by the Zeo) with the PSQI total score and sub-scores, adjusting for age, gender, years of education and likelihood of sleep apnea.ResultsObjective sleep parameters did not show any association with the PSQI total score. We found that objective measures of Wake after sleep onset (WASO, % and min) were positively associated with the PSQI sleep disturbance component, while SE and Total Sleep Time (TST) were negatively associated with PSQI sleep disturbance. Lastly, objective SE was positively associated with PSQI SE.ConclusionsOur findings showed that WASO, SE and TST, are associated with PSQI sleep disturbance, where the greater WASO, overall lower SE and less TST, were associated with increased subjective report of sleep disturbance. As expected, subjective (PSQI) and objective measures of SE were related. However, PSQI total score did not relate to any of the objective measures. These results suggest that by focusing on the PSQI total score we may miss the insight this easily administered self-report tool can provide. If interpreted in the right way, the PSQI can provide further insight into cognitively healthy older adults that have the likelihood of objective sleep disturbance.

BackgroundReports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection.MethodsINSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses.ResultsParticipating sites obtained institutional review board approval. Enrollment and follow-up are ongoing.ConclusionsThis study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic continues to spread globally and as of February 4, 2021, there are more than 26 million confirmed cases and more than 440,000 deaths in the United States (US). A top priority of the Centers for Disease Control and Prevention (CDC) is to identify risk factors for severe COVID-19 illness. The objective of this study was to analyze the characteristics and outcomes of COVID-19 adults who were managed in an outpatient setting compared to patients who required hospitalization at US academic centers.MethodsUsing the Vizient clinical database, Discharge records of adults with a diagnosis of COVID-19 between March 1, 2020 and January 31, 2021 were reviewed. Outcome measures included demographics, characteristics, rate of hospitalization, and mortality, and data were analyzed based on inpatient versus outpatient management.ResultsAmong COVID-19 adults, 1,360,078 patients were managed in an outpatient setting while 545,635 patients required hospitalization. Compared to hospitalized COVID-19 adults, COVID-19 adults who were managed in an outpatient setting were more likely to be female (56.1% vs 47.5%, p 75 years. The rate of hospitalization was lowest for age group 18-30 years at 10.6% (35,607 of 330,719) and highest for age group >75 years at 56.1% (150,381 of 268,247).ConclusionThis analysis of US academic centers showed that 28.6% of COVID-19 adults who sought care at one of the hospitals reporting data to the Vizient clinical database required in-patient treatment. The rate of hospitalization in our study was lowest for the youngest age group of 18-30 years and highest for age group >75 years. Beside older age, other factors associated with outpatient management included female gender, white race, and having commercial insurance.

ContextMultimorbidity is highly prevalent among older adults and associated with a high mortality. Prediction of mortality in multimorbid people would be clinically useful but there is no mortality risk index designed for this population. Our objective was therefore to develop and internally validate a 1-year mortality prognostic index for older multimorbid adults.MethodsWe analysed data of the OPERAM cohort study in Bern, Switzerland, including 822 adults aged 70 years or more with multimorbidity (3 or more chronic medical conditions) and polypharmacy (use of 5 drugs or more for >30 days). Time to all-cause mortality was assessed up to 1 year of follow-up. We performed a parametric Weibull regression model with backward stepwise selection to identify mortality risk predictors. The model was internally validated and optimism corrected using bootstrapping techniques. We derived a point-based risk score from the regression coefficients. Calibration and discrimination were assessed by the calibration slope and C statistic.Results805 participants were included in the analysis. During 1-year of follow-up, 158 participants (20%) had died. Age, Charlson-Comorbidity-Index, number of drugs, body mass index, number of hospitalizations, Barthel-Index (functional impairment), and nursing home residency were predictors of 1-year mortality in a multivariable model. Using these variables, the 1-year probability of dying could be predicted with an optimism-corrected C statistic of 0.70. The optimism-corrected calibration slope was 0.93. Based on the derived point-based risk score to predict mortality risk, 7% of the patients classified at low-risk of mortality, 19% at moderate-risk, and 37% at high-risk died after one year of follow-up. A simpler mortality score, without the Charlson-Comorbidity-Index and Barthel-Index, showed reduced discriminative power (optimism-corrected C statistic: 0.59) compared to the full score.ConclusionWe developed and internally validated a mortality risk index including for the first-time specific predictors for multimorbid adults. This new 1-year mortality prediction point-based score allowed to classify multimorbid older patients into three categories of increasing risk of mortality. Further validation of the score among various populations of multimorbid patients is needed before its implementation into practice.

The traditional approach to biomarker discovery for any pathology has been through hypothesis-based research one candidate at a time. The objective of this study was to develop an agnostic approach for the simultaneous screening of plasma for consistent molecular differences between a group of individuals exhibiting a pathology and a group of healthy individuals. To achieve this, we focused on developing a predictive tool based on plasma for the amount of brain amyloid-β deposition as observed in PET scans. The accumulation of brain amyloid-β (Aβ) plaques is a key risk factor for the development of Alzheimer's disease. A contrast was established between cognitively normal individuals above the age of 70 that differed for the amount of brain amyloid-β observed in PET scans (INSIGHT study group). Positive selection was performed against a pool of plasma from individuals with high brain amyloid and negative selection against a pool of plasma from individuals with low brain amyloid This enriched, selected library was then applied to plasma samples from 11 individuals with high levels of brain amyloid and 11 individuals with low levels of brain Aβ accumulation. Each of these individually selected libraries was then characterized by next generation sequencing, and the relative frequency of 10,000 aptamer sequences that were observed in each selection was screened for ability to explain variation in brain amyloid using sparse partial least squares discriminant analysis. From this analysis a subset of 44 aptamers was defined, and the individual aptamers were synthesized. This subset was applied to plasma samples from 70 cognitively normal individuals all above the age of 70 that differed for brain amyloid deposition. 54 individuals were used as a training set, and 15 as a test set. Three of the 15 individuals in the test set were mis-classified resulting in an overall accuracy of 80% with 86% sensitivity and 75% specificity. The aptamers included in the subset serve directly as biomarkers, thus we have named them Aptamarkers. There are two potential applications of these results: extending the predictive capacity of these aptamers across a broader range of individuals, and/or using the individual aptamers to identify targets through covariance analysis and reverse omics approaches. We are currently expanding applications of the Aptamarker platform to other diseases and target matrices.

BackgroundCuba's life expectancy at 79 is third highest in Latin America. Many attribute this to social investments in health and education, but comparative research is sparse, thus we compare Cuba with neighboring Dominican Republic, Costa Rica due to its strong social protections, and the U.S. Given high cardiovascular mortality, we focus on cardiovascular risk factor levels. To assess the role of health care, we distinguish medically amenable biomarkers from behavioral risk factors. To assess the role of Cuba's focus on equity, we compare education gradients in risk factors.MethodsWe analyze Cuban data from the 10/66 Dementia Research Group baseline survey of urban adults ages 65 plus. Comparison samples are drawn from the Dominican Republic 10/66 survey, the Costa Rican CRELES, and U.S. NHANES. We analyze cross-country levels and education gradients of medically amenable (hypertension, diabetes, hypercholesterolemia, access to health care) and behavioral (smoking, obesity) risk factors,-using sex-stratified weighted means comparisons and age-adjusted logistic regression.ResultsNeither medically amenable nor behavioral risk factors are uniformly better in Cuba than comparison countries. Obesity is lower in Cuba, but male smoking is higher. Hypertension, diabetes, and hypercholesterolemia levels are high in all countries, though Cuba's are lower than Costa Rica. Hypertension awareness in Cuba is similar to Costa Rica. Cuba has a higher proportion of hypertensives on treatment than Costa Rica, though lower than the U.S. Comparative gradients by education are similarly mixed. For behavioral factors, Cuba shows the strongest gradients (primarily for men) among the countries compared: smoking improves, but obesity worsens with education. Hypertension awareness also improves with education in Cuba, but Cuba shows no significant differences by education in hypertension treatment.ConclusionSmoking is comparatively high in Cuba, but obesity is low, and the resulting biomarkers show comparatively mixed patterns. Cuba's social protections have not eliminated strong educational gradients in behavioral risk factors, but the healthcare system appears to have eliminated disparities such as in hypertension treatment.

BACKGROUND: Neuroendocrine neoplasms (NENs) comprise a rare and heterogenous group of cancers, for which the role of radiation therapy continues to evolve. The purpose of this study is to analyze oncologic outcomes after the use of high-dose radiation in management of NENs at a tertiary hospital. MATERIALS AND METHODS: We performed a retrospective review of patients who received high-dose radiation with intent to cure or provide durable local control (defined as biologically effective dose (BED) ≥40, α/β = 10) for a localized or metastatic NEN from 2006 to 2019. Evaluation of disease status after radiation was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria when possible. Patients were grouped by differentiation (well-differentiated (WD) or poorly-differentiated (PD)) and stage (localized/locally advanced disease (L) or metastatic (M)) in analysis of probabilities of progression after radiation. RESULTS: 45 patients completed a radiation course with BED ≥40 for a NEN (median BED 72). With a median follow-up of 24 months after radiation, the 2-year actuarial rates of local relapse-free survival, new metastasis-free survival, progression-free survival, and overall survival after radiation were 98%, 45%, 41%, and 69%, respectively. 25 patients (56%) developed new metastases after completion of radiation, including 33% (n = 3) of patients with WD-L disease, 44% (n = 8) of WD-M, 77% (n = 10) of PD-L, and 80% (n = 4) of PD-M, with progressively shorter median times to progression (26, 9, 8, and 3 months, respectively; p = 0.093). Of the 25 patients evaluable by RECIST, 68% (n = 17) achieved either a complete or partial best response in the irradiated lesion. CONCLUSIONS: These data suggest that focal, high-dose radiation has a role in the management of selected patients with NENs. Local failure is rare in patients with both well-differentiated and poorly-differentiated disease, although the predominant pattern of failure remains development of new metastases.

Cross-species transmission of pathogens is intimately linked to human and environmental health. With limited healthcare and challenging living conditions, people living in poverty may be particularly susceptible to endemic and emerging diseases. Similarly, wildlife is impacted by human influences, including pathogen sharing, especially for species in close contact with people and domesticated animals. Here we investigate human and animal contacts and human health in a community living around the Bwindi Impenetrable National Park (BINP), Uganda. We used contact and health survey data to identify opportunities for cross-species pathogen transmission, focusing mostly on people and the endangered mountain gorilla. We conducted a survey with background questions and self-reported diaries to investigate 100 participants health, such as symptoms and behaviours, and contact patterns, including direct contacts and sightings over a week. Contacts were revealed through networks, including humans, domestic, peri-domestic, and wild animal groups for 1) contacts seen in the week of background questionnaire completion, and 2) contacts seen during the diary week. Participants frequently felt unwell during the study, reporting from one to 10 disease symptoms at different intensity levels, with severe symptoms comprising 6.4% of the diary records and tiredness and headaches the most common symptoms. After human-human contacts, direct contact with livestock and peri-domestic animals were the most common. The contact networks were moderately connected and revealed a preference in contacts within the same taxon and within their taxa groups. Sightings of wildlife were much more common than touching. However, despite contact with wildlife being the rarest of all contact types, one direct contact with a gorilla with a timeline including concerning participant health symptoms was reported. When considering all interaction types, gorillas mostly exhibited intra-species contact, but were found to interact with five other species, including people and domestic animals. Our findings reveal a local human population with recurrent symptoms of illness in a location with intense exposure to factors that can increase pathogen transmission, such as direct contact with domestic and wild animals and proximity among animal species. Despite significant biases and study limitations, the information generated here can guide future studies, such as models for disease spread and One Health interventions.