Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Exclusive Photoproduction of the Cascade (Xi) Hyperons

We report on the first measurement of exclusive Xi-(1321) hyperon photoproduction in gamma p --> K+ K+ Xi- for 3.2 < E(gamma) < 3.9 GeV. The final state is identified by the missing mass in p(gamma,K+ K+)X measured with the CLAS detector at Jefferson Laboratory. We have detected a significant number of the ground-state Xi-(1321)1/2+, and have estimated the total cross section for its production. We have also observed the first excited state Xi-(1530)3/2+. Photoproduction provides a copious source of Xi's. We discuss the possibilities of a search for the recently proposed Xi5-- and Xi5+ pentaquarks.Comment: submitted to Phys. Rev.

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Protocol for serious fall injury adjudication in the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study.

BackgroundThis paper describes a protocol for determining the incidence of serious fall injuries for Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE), a large, multicenter pragmatic clinical trial with limited resources for event adjudication. We describe how administrative data (from participating health systems and Medicare claims) can be used to confirm participant-reported events, with more time- and resource-intensive full-text medical record data used only on an "as-needed" basis.MethodsSTRIDE is a pragmatic cluster-randomized controlled trial involving 5451 participants age ≥ 70 and at increased risk for falls, served by 86 primary care practices in 10 US health systems. The STRIDE intervention involves a nurse falls care manager who assesses a participant's underlying risks for falls, suggests interventions using motivational interviewing, and then creates, implements and longitudinally follows up on an individualized care plan with the participant (and caregiver when appropriate), in partnership with the participant's primary care provider. STRIDE's primary outcome is serious fall injuries, defined as a fall resulting in: (1) medical attention billable according to Medicare guidelines with a) fracture (excluding isolated thoracic vertebral and/or lumbar vertebral fracture), b) joint dislocation, or c) cut requiring closure; OR (2) overnight hospitalization with a) head injury, b) sprain or strain, c) bruising or swelling, or d) other injury determined to be "serious" (i.e., burn, rhabdomyolysis, or internal injury). Two sources of data are required to confirm a serious fall injury. The primary data source is the participant's self-report of a fall leading to medical attention, identified during telephone interview every 4 months, with the confirmatory source being (1) administrative data capturing encounters at the participating health systems or Medicare claims and/or (2) the full text of medical records requested only as needed.DiscussionAdjudication is ongoing, with over 1000 potentially qualifying events adjudicated to date. Administrative data can be successfully used for adjudication, as part of a hybrid approach that retrieves full-text medical records only when needed. With the continued refinement and availability of administrative data sources, future studies may be able to use administrative data completely in lieu of medical record review to maximize the quality of adjudication with finite resources.Trial registrationClinicalTrials.gov (NCT02475850)

Protocol for serious fall injury adjudication in the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study

Abstract Background This paper describes a protocol for determining the incidence of serious fall injuries for Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE), a large, multicenter pragmatic clinical trial with limited resources for event adjudication. We describe how administrative data (from participating health systems and Medicare claims) can be used to confirm participant-reported events, with more time- and resource-intensive full-text medical record data used only on an “as-needed” basis. Methods STRIDE is a pragmatic cluster-randomized controlled trial involving 5451 participants age ≥ 70 and at increased risk for falls, served by 86 primary care practices in 10 US health systems. The STRIDE intervention involves a nurse falls care manager who assesses a participant’s underlying risks for falls, suggests interventions using motivational interviewing, and then creates, implements and longitudinally follows up on an individualized care plan with the participant (and caregiver when appropriate), in partnership with the participant’s primary care provider. STRIDE’s primary outcome is serious fall injuries, defined as a fall resulting in: (1) medical attention billable according to Medicare guidelines with a) fracture (excluding isolated thoracic vertebral and/or lumbar vertebral fracture), b) joint dislocation, or c) cut requiring closure; OR (2) overnight hospitalization with a) head injury, b) sprain or strain, c) bruising or swelling, or d) other injury determined to be “serious” (i.e., burn, rhabdomyolysis, or internal injury). Two sources of data are required to confirm a serious fall injury. The primary data source is the participant’s self-report of a fall leading to medical attention, identified during telephone interview every 4 months, with the confirmatory source being (1) administrative data capturing encounters at the participating health systems or Medicare claims and/or (2) the full text of medical records requested only as needed. Discussion Adjudication is ongoing, with over 1000 potentially qualifying events adjudicated to date. Administrative data can be successfully used for adjudication, as part of a hybrid approach that retrieves full-text medical records only when needed. With the continued refinement and availability of administrative data sources, future studies may be able to use administrative data completely in lieu of medical record review to maximize the quality of adjudication with finite resources. Trial registration ClinicalTrials.gov (NCT02475850)

Study Design, Rationale, and Methodology for Promote Weight Loss in Patients With Peripheral Artery Disease Who Also Have Obesity: The PROVE Trial

Background Overweight and obesity are associated with adverse functional outcomes in people with peripheral artery disease (PAD). The effects of weight loss in people with overweight/obesity and PAD are unknown. Methods The PROVE (Promote Weight Loss in Obese PAD Patients to Prevent Mobility Loss) Trial is a multicentered randomized clinical trial with the primary aim of testing whether a behavioral intervention designed to help participants with PAD lose weight and walk for exercise improves 6‐minute walk distance at 12‐month follow‐up, compared with walking exercise alone. A total of 212 participants with PAD and body mass index ≥25 kg/m2 will be randomized. Interventions are delivered using a Group Mediated Cognitive Behavioral intervention model, a smartphone application, and individual telephone coaching. The primary outcome is 12‐month change in 6‐minute walk distance. Secondary outcomes include total minutes of walking exercise/wk at 12‐month follow‐up and 12‐month change in accelerometer‐measured physical activity, the Walking Impairment Questionnaire distance score, and the Patient‐Reported Outcomes Measurement Information System mobility questionnaire. Tertiary outcomes include 12‐month changes in perceived exertional effort at the end of the 6‐minute walk, diet quality, and the Short Physical Performance Battery. Exploratory outcomes include changes in gastrocnemius muscle biopsy measures of mitochondrial cytochrome C oxidase activity, mitochondrial biogenesis, capillary density, and inflammatory markers. Conclusions The PROVE randomized clinical trial will evaluate the effects of exercise with an intervention of coaching and a smartphone application designed to achieve weight loss, compared with exercise alone, on walking performance in people with PAD and overweight/obesity. Results will inform optimal treatment for the growing number of patients with PAD who have overweight/obesity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04228978

Factores psicosociales asociados a un alto, medio y bajo riesgo de síntomas depresivos en el posparto inmediato Psychosocial factors associated to low, medium and high risk of depressive symptoms in the immediate postpartum period

OBJETIVOS: evaluar factores psicosociales asociados a síntomas depresivos en el posparto inmediato. MÉTODOS: 45 mujeres puérperas de un hospital público de Buenos Aires, Argentina, fueron entrevistadas entre el 1er y el 3er día posparto, de marzo-diciembre 2010. La Escala de Depresión Posnatal de Edimburgo (EPDS) fue administrada para evaluar síntomas depresivos. La entrevista psicológica perinatal (EPP) fue administrada para detectar variables psicosociales. A partir de los resultados obtenidos en la EPDS, se separó la muestra en tres grupos con diferentes grados de riesgo de sintomatología depresiva: "negativas o de bajo riesgo", "positivas de riesgo medio" y "positivas de alto riesgo". Los puntajes de corte utilizados fueron 9 y 19. RESULTADOS: se encontraron diferencias significativas entre los tres grupos con violencia familiar, migración, historia previa de depresión, presencia de síntomas depresivos durante el embarazo y mayor cantidad de estresores. CONCLUSIONES: el establecimiento de los dos puntajes de corte en la EPDS permite una detección temprana de las mujeres que presentan síntomas depresivos. Se sugiere la utilidad del puntaje de corte de 19 para la detección temprana de mujeres con mayor riesgo de desarrollar depresión posparto.<br>OBJECTIVES: evaluate psychosocial factors associated to depressive symptoms during the immediate postpartum period. METHODS: a total of 45 argentine puerperal women hospitalized in a public maternal hospital of Buenos Aires, Argentina, were interviewed on the 1st and 3rd day postpartum from March to December 2010. Aiming to assess the presence of depressive symptoms, the Edinburgh Postnatal Depression Scale (EPDS) was administrated. The Perinatal Psychological Interview was administrated to explore psychosocial variables. Based on the scores obtained in the EPDS, the sample was separated in three different groups with increasing risk of depressive symptomatology: "negative or low risk", "positive medium risk" and "positive high risk". Cut-off scores were 9 and 19 points. RESULTS: out of the total psychosocial variables analyzed, statistically significant differences were found among the three groups regarding family violence, migration, previous history of depression, depressive symptoms during pregnancy and increasing number of life events. CONCLUSIONS: the setting of two cut-off scores in EPDS allows the early detection of women with depressive symptoms. It is suggested the usefulness of cut-off value of 19 for early detection of women at high risk to developing postpartum depression