Clinical predictors of hypoxic pneumonia in children from the Eastern Highlands Province, Papua New Guinea: secondary analysis of two prospective observational studies.

Background: Pneumonia is the leading cause of death in young children globally and is prevalent in the Papua New Guinea highlands. We investigated clinical predictors of hypoxic pneumonia to inform local treatment guidelines in this resource-limited setting. Methods: Between 2013 and 2020, two consecutive prospective observational studies were undertaken enrolling children 0-4 years presenting with pneumonia to health-care facilities in Goroka Town, Eastern Highlands Province. Logistic regression models were developed to identify clinical predictors of hypoxic pneumonia (oxygen saturation <90% on presentation). Model performance was compared against established criteria to identify severe pneumonia. Findings: There were 2067 cases of pneumonia; hypoxaemia was detected in 36.1%. The strongest independent predictors of hypoxic pneumonia were central cyanosis on examination (adjusted odds ratio [aOR] 5.14; 95% CI 3.47-7.60), reduced breath sounds (aOR 2.92; 95% CI 2.30-3.71), and nasal flaring or grunting (aOR 2.34; 95% CI 1.62-3.38). While the model developed to predict hypoxic pneumonia outperformed established pneumonia severity criteria, it was not sensitive enough to be clinically useful at this time. Interpretation: Given signs and symptoms are unable to accurately detect hypoxia, all health care facilities should be equipped with pulse oximeters. However, for the health care worker without access to pulse oximetry, consideration of central cyanosis, reduced breath sounds, nasal flaring or grunting, age-specific tachycardia, wheezing, parent-reported drowsiness, or bronchial breathing as suggestive of hypoxaemic pneumonia, and thus severe disease, may prove useful in guiding management, hospital referral and use of oxygen therapy. Funding: Funded by Pfizer Global and the Bill & Melinda Gates Foundation.

Pneumococcal carriage, serotype distribution, and antimicrobial susceptibility in Papua New Guinean children vaccinated with PCV10 or PCV13 in a head-to-head trial.

BACKGROUND: Children in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13). METHODS: Infants (N = 262) were randomized to receive 3 doses of PCV10 or PCV13 at 1-2-3 months of age, followed by pneumococcal polysaccharide vaccination (PPV) or no PPV at 9 months of age. Nasopharyngeal swabs (NPS) collected at ages 1, 4, 9, 10, 23 and 24 months were cultured using standard bacteriological procedures. Morphologically distinct Streptococcus pneumoniae colonies were serotyped by the Quellung reaction. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC). RESULTS: S. pneumoniae was isolated from 883/1063 NPS collected at 1-23 months of age, including 820 serotypeable (64 different serotypes) and 144 non-serotypeable isolates. At age 23 months, 93.6% (95%CI 86.6-97.6%) of PCV10 recipients and 88.6% (95%CI 80.1-94.4%) of PCV13 recipients were pneumococcal carriers, with higher carriage of PCV10 serotypes by PCV10 recipients (19.8%, 95%CI 12.2-29.5) than PCV13 recipients (9.3%, 95%CI 4.1-17.3) (p = 0.049). There were no other statistically significant differences between PCV10 and PCV13 recipients and children receiving PPV or no PPV. Nearly half (45.6%) of carried pneumococci were non-susceptible to penicillin based on the meningitis breakpoint (MIC ≥ 0.12 µg/mL), but resistance was rare (1.1%) using the non-meningitis cut-off (MIC ≥ 8 µg/mL). Non-susceptibility to trimethoprim-sulfamethoxazole (SXT) was common: 23.2% of isolates showed intermediate resistance (MIC 1/19-2/38 µg/mL) and 16.9% full resistance (MIC ≥ 4/76 µg/mL). PCV serotypes 14 and 19A were commonly non-susceptible to both penicillin (14, 97%; 19A, 70%) and SXT (14, 97%; 19A, 87%). CONCLUSION: Even after PCV10 or PCV13 vaccination, children living in a high-risk setting such as PNG continue to experience high levels of pneumococcal colonization, including carriage of highly antimicrobial-resistant PCV serotypes. The study is registered with ClinicalTrials.gov (CTN NCT01619462).

Remote vs In-home Physician Visits for Hospital-Level Care at Home: A Randomized Clinical Trial.

Importance: Home hospital care is the substitutive provision of home-based acute care services usually associated with a traditional inpatient hospital. Many home hospital models require a physician to see patients at home daily, which may hinder scalability. Whether remote physician visits can safely substitute for most in-home visits is unknown. Objective: To compare remote and in-home physician care. Design, Setting, and Participants: This randomized clinical trial assessed 172 adult patients at an academic medical center and community hospital who required hospital-level care for select acute conditions, including infection, heart failure, chronic obstructive pulmonary disease, and asthma, between August 3, 2019, and March 26, 2020; follow-up ended April 26, 2020. Interventions: All patients received acute care at home, including in-home nurse or paramedic visits, intravenous medications, remote monitoring, and point-of-care testing. Patients were randomized to receive physician care remotely (initial in-home visit followed by daily video visit facilitated by the home hospital nurse) vs in-home care (daily in-home physician visit). In the remote care group, the physician could choose to see the patient at home beyond the first visit if it was felt to be medically necessary. Main Outcomes and Measures: The primary outcome was the number of adverse events, compared using multivariable Poisson regression at a noninferiority threshold of 10 events per 100 patients. Adverse events included a fall, pressure injury, and delirium. Secondary outcomes included the Picker Patient Experience Questionnaire 15 score (scale of 0-15, with 0 indicating worst patient experience and 15 indicating best patient experience) and 30-day readmission rates. Results: A total of 172 patients (84 receiving remote care and 88 receiving in-home physician care [control group]) were randomized; enrollment was terminated early because of COVID-19. The mean (SD) age was 69.3 (18.0) years, 97 patients (56.4%) were female, 77 (45.0%) were White, and 42 (24.4%) lived alone. Mean adjusted adverse event count was 6.8 per 100 patients for remote care patients vs 3.9 per 100 patients for control patients, for a difference of 2.8 (95% CI, -3.3 to 8.9), supporting noninferiority. For remote care vs control patients, the mean adjusted Picker Patient Experience Questionnaire 15 score difference was -0.22 (95% CI, -1.00 to 0.56), supporting noninferiority. The mean adjusted 30-day readmission absolute rate difference was 2.28% (95% CI, -3.23% to 7.79%), which was inconclusive. Of patients in the remote group, 16 (19.0%) required in-home visits beyond the first visit. Conclusions and Relevance: In this study, remote physician visits were noninferior to in-home physician visits during home hospital care for adverse events and patient experience, although in-home physician care was necessary to support many patients receiving remote care. Our findings may allow for a more efficient, scalable home hospital approach but require further research. Trial Registration: ClinicalTrials.gov Identifier: NCT04080570.

Effectiveness of 13-valent pneumococcal conjugate vaccine against hypoxic pneumonia and hospitalisation in Eastern Highlands Province, Papua New Guinea: An observational cohort study.

Background: Pneumonia is a leading cause of childhood mortality with Streptococcus pneumoniae a major contributor. Pneumococcal conjugate vaccines (PCVs) have been introduced into immunisation programs in many low- to middle-income countries (LMICs) yet there is a paucity of data evaluating the effectiveness in these settings. We assess the effectiveness of 13-valent PCV (13vPCV) against hypoxic pneumonia, hospitalisation and other clinical endpoints in children <5 years living in Eastern Highlands Province, Papua New Guinea (PNG). Methods: Data from two consecutive prospective observational studies (2013-2019) enrolling children <60 months presenting with pneumonia were included. Hypoxic pneumonia was defined as oxygen saturations <90%. Outcomes included hospitalisation, severe clinical pneumonia and death. 13vPCV status was determined using written records. Logistic regression models were used to estimate the odds ratios of key outcomes by 13vPCV vaccination status adjusted for confounders using inverse probability of treatment weighting. Findings: Data from 2067 children (median age; 9 months [IQR: 5-11]) were included. 739 children (36.1%) were hypoxic and 623 (30.4%) hospitalised. Twelve children (0.6% of total cohort) died in hospital. 670 children (32.7%) were fully 13vPCV-vaccinated. 13vPCV vaccination was associated with a 28.7% reduction (95% confidence interval [CI]: 9.9; 43.6%) in hypoxic pneumonia and a 57.4% reduction (38.0; 70.7%) in pneumonia hospitalisation. Interpretation: 13vPCV vaccination is effective against hypoxic pneumonia and pneumonia hospitalisation in PNG children. Strategies to improve access to and coverage of 13vPCV in PNG and other similar LMICs are urgently required. Funding: Funded by Pfizer Global and the Bill & Melinda Gates Foundation.

Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infants.

BACKGROUND: Papua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity. This study investigated PCV13 impact on serotype-specific pneumococcal carriage prevalence, density, and serotype diversity in PNG infants, who have some of the highest reported rates of pneumococcal carriage and disease in the world. METHODS: Nasopharyngeal swabs were collected at 1, 4 and 9 months of age from PCV13-vaccinated infants (n = 57) and age-/season-matched, unvaccinated infants (at approximately 1 month, n = 53; 4 months, n = 57; 9 months, n = 52). Serotype-specific pneumococcal carriage density and antimicrobial resistance genes were identified by qPCR and microarray. RESULTS: Pneumococci were present in 89% of swabs, with 60 different serotypes and four non-encapsulated variants detected. Multiple serotype carriage was common (47% of swabs). Vaccine type carriage prevalence was similar between PCV13-vaccinated and unvaccinated infants at 4 and 9 months of age. The prevalence of non-vaccine type carriage was also similar between cohorts, with non-vaccine types present in three-quarters of samples (from both vaccinated and unvaccinated infants) by 4 months of age. The median pneumococcal carriage density was high and similar at each age group (~7.0 log10genome equivalents/mL). PCV13 had no effect on overall pneumococcal carriage density, vaccine type density, non-vaccine type density, or the prevalence of antimicrobial resistance genes. CONCLUSION: PNG infants experience dense and diverse pneumococcal colonisation with concurrent serotypes from 1 month of age. PCV13 had no impact on pneumococcal carriage density, even for vaccine serotypes. The low prevalence of vaccine serotypes, high pneumococcal carriage density and abundance of non-vaccine serotypes likely contribute to the lack of PCV13 impact on carriage in PNG infants. Indirect effects of the infant PCV programs are likely to be limited in PNG. Alternative vaccines with broader coverage should be considered.

Virtual Team Rounding: A Cross-Specialty Inpatient Care Staffing Program to Manage COVID-19 Surges.

PROBLEM: The SARS-CoV-2 (COVID-19) pandemic presented numerous challenges to inpatient care, including overtaxed inpatient medicine services, surges in patient censuses, disrupted patient care and educational activities for trainees, underused providers in certain specialties, and personal protective equipment shortages and new requirements for physical distancing. In March 2020, as the COVID-19 surge began, an interdisciplinary group of administrators, providers, and trainees at Brigham and Women's Hospital created an inpatient virtual staffing model called the Virtual Team Rounding Program (VTRP). APPROACH: The conceptual framework guiding VTRP development was rapid-cycle innovation. The VTRP was designed iteratively using feedback from residents, physician assistants, attendings, and administrators from March to June 2020. The VTRP trained and deployed a diverse set of providers across specialties as "virtual rounders" to support inpatient teams by joining and participating in rounds via videoconference and completing documentation tasks during and after rounds. The program was rapidly scaled up from March to June 2020. OUTCOMES: In a survey of inpatient providers at the end of the pilot phase, 10/10 (100%) respondents reported they were getting either "a lot" or "a little" benefit from the VTRP and did not find the addition of the virtual rounder burdensome. During the scaling phase, the program grew to support 24 teams. In a survey at the end of the contraction phase, 117/187 (62.6%) inpatient providers who worked with a virtual rounder felt the rounder saved them time. VTRP leadership collaboratively and iteratively developed best practices for challenges encountered during implementation. NEXT STEPS: Virtual rounding provides a valuable extension of inpatient teams to manage COVID-19 surges. Future work will quantitatively and qualitatively assess the impact of the VTRP on inpatient provider satisfaction and well-being, virtual rounders' experiences, and patient care outcomes.

A SARS-CoV-2 Cluster in an Acute Care Hospital.

BACKGROUND: Little is known about clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in acute care hospitals. OBJECTIVE: To describe the detection, mitigation, and analysis of a large cluster of SARS-CoV-2 infections in an acute care hospital with mature infection control policies. DESIGN: Descriptive study. SETTING: Brigham and Women's Hospital, Boston, Massachusetts. PARTICIPANTS: Patients and staff with cluster-related SARS-CoV-2 infections. INTERVENTION: Close contacts of infected patients and staff were identified and tested every 3 days, patients on affected units were preemptively isolated and repeatedly tested, affected units were cleaned, room ventilation was measured, and specimens were sent for whole-genome sequencing. A case-control study was done to compare clinical interactions, personal protective equipment use, and breakroom and workroom practices in SARS-CoV-2-positive versus negative staff. MEASUREMENTS: Description of the cluster, mitigation activities, and risk factor analysis. RESULTS: Fourteen patients and 38 staff members were included in the cluster per whole-genome sequencing and epidemiologic associations. The index case was a symptomatic patient in whom isolation was discontinued after 2 negative results on nasopharyngeal polymerase chain reaction testing. The patient subsequently infected multiple roommates and staff, who then infected others. Seven of 52 (13%) secondary infections were detected only on second or subsequent tests. Eight of 9 (89%) patients who shared rooms with potentially contagious patients became infected. Potential contributing factors included high viral loads, nebulization, and positive pressure in the index patient's room. Risk factors for transmission to staff included presence during nebulization, caring for patients with dyspnea or cough, lack of eye protection, at least 15 minutes of exposure to case patients, and interactions with SARS-CoV-2-positive staff in clinical areas. Whole-genome sequencing confirmed that 2 staff members were infected despite wearing surgical masks and eye protection. LIMITATION: Findings may not be generalizable. CONCLUSION: SARS-CoV-2 clusters can occur in hospitals despite robust infection control policies. Insights from this cluster may inform additional measures to protect patients and staff. PRIMARY FUNDING SOURCE: None.

National Hospital Initiatives to Improve Performance on Heart Failure Readmission Metrics.

BACKGROUND: The passage of the Hospital Readmissions Reduction Program (HRRP) has been associated with been associated with decreased risk-standardized readmission rates for heart failure (HF) patients. However, some quantitative analyses have shown association between HRRP and increased mortality for hospitalized HF patients. Qualitative information on what hospital programs were actually implemented can help us understand if this trend is a causal effect of the law or an unrelated trend. PURPOSE: To perform a systematic literature review to synthesize evidence on what clinical programs American hospitals implemented in response to HRRP. METHODS: Following PRISMA guidelines, we conducted a systematic review in April 2020 that included a search of PubMed, the Cochrane Library and Cumulative Index to Nursing and Allied Literature (CINAHL) for studies related to hospital strategies to reduce HF readmissions. RESULTS: Of 20 included articles, 8 were qualitative (survey and interviews), 3 were systematic reviews, 5 were single site quality improvement (QI) initiatives, 2 were plans for ongoing randomized control trials (RCTs), one was a plan for a future RCT and one was an observational analysis. We found that interventions hospitals undertook in response to HRRP to reduce HF readmissions fell into four categories: inpatient care, discharge, transitional care and data collection/administration. The majority of interventions were related to transitional care, most commonly scheduling follow up appointments within 7-14 days of discharge, performing post-discharge phone calls and partnering with community physicians. CONCLUSIONS: We did not find any published evidence of practices that could mechanistically be linked to harm to HF patients enacted by hospitals in response to HRRP. For example, no programs encouraged emergency department providers to discharge patients from emergency departments. We found QI initiatives, improved discharge planning and increased post-discharge follow up.

Implementation of a skilled nursing facility readmission review process.

30-day readmissions for patients at skilled nursing facilities (SNF) are common and preventable. We implemented a readmission review process for patients readmitted from two SNFs, involving an electronic review tool and monthly conferences. The electronic review tool captures information related to preventability and factors contributing to readmission. The study included 128 patients, readmitted within 30 days from 1 October 2015 through 1 May 2017, at a tertiary care academic medical centre in Boston, MA, and two partnering SNFs. There was a discrepancy in preventability rating between SNF and hospital reviewers, with 79.7% of cases rated not preventable by the SNF, and 58.6% by the hospital. There was moderate positive correlation between the hospital's and SNFs' preventability ratings (rs=0.652, p<0.001). In most cases, the SNF reviewers felt that no factors contributed (57.8%), and hospital reviewers felt that issues with end-of-life planning (14.1%) and medical complexity (12.5%) were major factors. Despite the lack of strong correlation between SNF and hospital responses, several cross-continuum quality improvement projects were developed. We found that implementation of a SNF readmission review process employing bidirectional review by SNF and hospital was feasible, and facilitated systems-based improvement in the transition from hospital to postacute care.

Relation of Iliac Artery Calcium With Adiposity Measures and Peripheral Artery Disease.

Arterial calcification is associated with cardiovascular morbidity and mortality. To improve the understanding of the pathogenesis involved with iliac artery calcium (IAC), we sought to examine the associations between the burden of IAC with adiposity measures and peripheral artery disease (PAD). Participants (n = 1,236, 52% women, mean age 60 years) were drawn from the Framingham Heart Study Offspring cohort who underwent multidetector computed tomography. The extent of IAC was quantified based on calcified atherosclerotic plaques detected in the iliac arteries. High IAC was defined based on gender-specific 90th percentile cut-off points from a healthy referent subsample. PAD is defined as an ankle-brachial index < 0.9, intermittent claudication, and/or history of lower extremity revascularization. The association between PAD and IAC was assessed using multivariable-adjusted logistic regression models. The burden of high IAC was 20.5% in women and 25.5% in men. High IAC was not associated with generalized (body mass index) or area-specific (waist circumference, and volumes of thoracic periaortic, abdominal subcutaneous, and visceral adipose tissue) adiposity measures (all p ≥0.22). High IAC was associated with increased odds of PAD (odds ratio 10.36, 95% confidence interval 4.28 to 25.09). This association persisted even after additionally adjusting for coronary artery calcium (odds ratio 11.25, 95% confidence interval 4.29 to 29.53). Burden of IAC was associated with an increased risk of PAD.

Adipose Tissue Depots and Their Cross-Sectional Associations With Circulating Biomarkers of Metabolic Regulation.

BACKGROUND: Visceral adipose tissue (VAT) and fatty liver differ in their associations with cardiovascular risk compared with subcutaneous adipose tissue (SAT). Several biomarkers have been linked to metabolic derangements and may contribute to the pathogenicity of fat depots. We examined the association between fat depots on multidetector computed tomography and metabolic regulatory biomarkers. METHODS AND RESULTS: Participants from the Framingham Heart Study (n=1583, 47% women) underwent assessment of SAT, VAT, and liver attenuation. We measured circulating biomarkers secreted by adipose tissue or liver (adiponectin, leptin, leptin receptor, fatty acid binding protein 4, fetuin-A, and retinol binding protein 4). Using multivariable linear regression models, we examined relations of fat depots with biomarkers. Higher levels of fat depots were positively associated with leptin and fatty acid binding protein 4 but negatively associated with adiponectin (all P<0.001). Associations with leptin receptor, fetuin-A, and retinol binding protein 4 varied according to fat depot type or sex. When comparing the associations of SAT and VAT with biomarkers, VAT was the stronger correlate of adiponectin (ß=-0.28 [women]; ß=-0.30 [men]; both P<0.001), whereas SAT was the stronger correlate of leptin (ß=0.62 [women]; ß=0.49 [men]; both P<0.001; P<0.001 for comparing VAT versus SAT). Although fetuin-A and retinol binding protein 4 are secreted by the liver in addition to adipose tissue, associations of liver attenuation with these biomarkers was not stronger than that of SAT or VAT. CONCLUSIONS: SAT, VAT, and liver attenuation are associated with metabolic regulatory biomarkers with differences in the associations by fat depot type and sex. These findings support the possibility of biological differences between fat depots.

Metabolic syndrome and risk of incident peripheral artery disease: the cardiovascular health study.

Prior studies evaluating metabolic syndrome (MetS) and incident peripheral artery disease (PAD) have been limited by use of modified MetS criteria and restriction to clinical PAD end points. We investigated MetS and risk of developing a low ankle-brachial index (ABI) and clinical PAD in the Cardiovascular Health Study, a population-based cohort of adults aged ≥65 years. Participants with MetS met at least 3 of 5 Adult Treatment Panel III criteria. Baseline C-reactive protein-MetS or fibrinogen-MetS were defined as presence of 3 of 6 components, with elevated C-reactive protein (>3 mg/L) or fibrinogen (>341 mg/dL) as a sixth component. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among a subset of 1899 individuals with 2 ABI measurements 6 years apart. Over a median follow-up of 13.7 years, 4632 individuals were followed up for clinical PAD, defined as revascularization or diagnosed claudication. Adult Treatment Panel III MetS was associated with both incident low ABI (risk ratio, 1.26; 95% confidence interval [CI], 1.00-1.58) and clinical PAD (hazard ratio, 1.47; 95% CI, 1.11-1.94). Incorporating C-reactive protein or fibrinogen into Adult Treatment Panel III criteria identified an additional 16% to 20% of individuals as having MetS, and both C-reactive protein-MetS and fibrinogen-MetS were associated with incident low ABI (risk ratio, 1.36; 95% CI, 1.07-1.72 and risk ratio, 1.43; 95% CI, 1.13-1.81, respectively) and clinical PAD (hazard ratio, 1.56; 95% CI, 1.17-2.08 and hazard ratio, 1.55; 95% CI, 1.17-2.07, respectively). Among Adult Treatment Panel III MetS criteria, risk of PAD was most strongly associated with hypertension.

Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality.

OBJECTIVES: The aim of this study was to determine whether ectopic fat depots are prospectively associated with cardiovascular disease, cancer, and all-cause mortality. BACKGROUND: The morbidity associated with excess body weight varies among individuals of similar body mass index. Ectopic fat depots may underlie this risk differential. However, prospective studies of directly measured fat are limited. METHODS: Participants from the Framingham Heart Study (n = 3,086; 49% women; mean age of 50.2 years) underwent assessment of fat depots (visceral adipose tissue, pericardial adipose tissue, and periaortic adipose tissue) using multidetector computed tomography and were followed up longitudinally for a median of 5.0 years. Cox proportional hazards regression models were used to examine the association of each fat depot (per 1 SD increment) with the risk of incident cardiovascular disease, cancer, and all-cause mortality after adjustment for standard risk factors, including body mass index. RESULTS: Overall, there were 90 cardiovascular events, 141 cancer events, and 71 deaths. After multivariable adjustment, visceral adipose tissue was associated with cardiovascular disease (hazard ratio: 1.44; 95% confidence interval: 1.08 to 1.92; p = 0.01) and cancer (hazard ratio: 1.43; 95% confidence interval: 1.12 to 1.84; p = 0.005). Addition of visceral adipose tissue to a multivariable model that included body mass index modestly improved cardiovascular risk prediction (net reclassification improvement of 16.3%). None of the fat depots were associated with all-cause mortality. CONCLUSIONS: Visceral adiposity is associated with incident cardiovascular disease and cancer after adjustment for clinical risk factors and generalized adiposity. These findings support the growing appreciation of a pathogenic role of ectopic fat.

Thoracic periaortic and visceral adipose tissue and their cross-sectional associations with measures of vascular function.

OBJECTIVE: Perivascular fat may have a local adverse effect on the vasculature. We evaluated whether thoracic periaortic adipose tissue (TAT), a type of perivascular fat, and visceral adipose tissue (VAT) were associated with vascular function. DESIGN AND METHODS: TAT and VAT were quantified in Framingham Heart Study participants using multidetector-computed tomography; vascular function was assessed using brachial artery vasodilator function, peripheral arterial tone, and arterial tonometry (n = 2,735; 48% women; mean age, 50 years; mean body mass index [BMI], 27.7 kg/m(2) ). Using multiple linear regression, the relationships between TAT, VAT, and vascular measures was examined while adjusting for cardiovascular risk factors. RESULTS: Mean TAT and VAT volumes were 13.2 and 1763 cm(3) . TAT and VAT were associated with multiple vascular function measures after multivariable adjustment. After BMI adjustment, TAT and VAT remained negatively associated with peripheral arterial tone and inverse carotid femoral pulse wave velocity (P < 0.02); TAT was negatively associated with hyperemic mean flow velocity (P = 0.03). Associations of TAT with vascular function were attenuated after VAT adjustment (all P > 0.06). CONCLUSIONS: Thoracic periaortic and visceral fat are associated with microvascular function and large artery stiffness after BMI adjustment. These findings support the growing recognition of associations between ectopic fat and vascular function.

Insulin resistance and incident peripheral artery disease in the Cardiovascular Health Study.

Type 2 diabetes is a risk factor for peripheral artery disease (PAD), and insulin resistance is a key feature of diabetes and pre-diabetes. No longitudinal epidemiological study has examined the relation between insulin resistance and PAD. Our study analyzed the association of quartiles of the homeostatic model of insulin resistance (HOMA-IR) and the development of PAD defined by two methods. PAD was first defined as the development of an abnormal ankle-brachial index (ABI) (dichotomous outcome) after 6 years of follow-up. PAD was alternatively defined as the development of clinical PAD (time-to-event analysis). The study samples included adults over the age of 65 years who were enrolled in the Cardiovascular Health Study, had fasting measurements of insulin and glucose, had ABI measurements, and were not receiving treatment for diabetes. Multivariable models were adjusted for potential confounders, including age, sex, field center and cohort, body mass index (BMI), smoking status, alcohol use, and exercise intensity. Additional models adjusted for potential mediators, including blood pressure, lipids, kidney function, and prevalent vascular disease. In the ABI analysis (n = 2108), multivariable adjusted models demonstrated a positive relation between HOMA-IR and incident PAD (odds ratio = 1.80 comparing the 4th versus 1st quartile of HOMA-IR, 95% confidence interval [CI] 1.20-2.71). In the clinical PAD analysis (n = 4208), we found a similar relation (hazard ratio = 2.30 comparing the 4th versus 1st quartile of HOMA-IR, 95% CI 1.15-4.58). As expected, further adjustment for potential mediators led to some attenuation of effect estimates. In conclusion, insulin resistance is associated with a higher risk of PAD in older adults.

Prevalence, distribution, and risk factor correlates of high thoracic periaortic fat in the Framingham Heart Study.

BACKGROUND: Thoracic periaortic adipose tissue (TAT) is associated with atherosclerosis and cardiovascular disease (CVD) risk factors and may play a role in obesity-mediated vascular disease. We sought to determine the prevalence, distribution, and risk factor correlates of high TAT. METHODS AND RESULTS: Participants from the Framingham Heart Study (n=3246, 48% women, mean age 51.1 years) underwent multidetector computed tomography; high TAT and visceral adipose tissue (VAT) were defined on the basis of sex-specific 90th percentiles in a healthy referent sample. The prevalence of high TAT was 38.1% in women and 35.7% in men. Among individuals without high VAT, 10.1% had high TAT. After adjustment for age and VAT, both women and men with high TAT in the absence of high VAT were older and had a higher prevalence of CVD (P<0.0001) compared with those without high TAT. In addition, men in this group were more likely to be smokers (P=0.02), whereas women were more likely to have low high-density lipoprotein cholesterol (P=0.005). CONCLUSIONS: Individuals in our community-based sample with high TAT in the absence of high VAT were characterized by an adverse cardiometabolic profile. This adipose tissue phenotype may identify a subset of individuals with distinct metabolic characteristics.

Physical activity and the risk of becoming overweight or obese in middle-aged and older women.

Although public health campaigns stress leisure time physical activity (LTPA) as essential for obesity prevention, few epidemiological studies have focused on the association of specific types and intensities of LTPA and the clinical endpoints of overweight and obesity. Therefore, we prospectively assessed whether moderate- and vigorous-intensity as well as total LTPA were associated with the risk of becoming either overweight or obese using a prospective cohort design of 19,003 women enrolled in the Women's Health Study (WHS). Women reported their participation in walking and LTPA at baseline. During a median follow-up of 11.6 years, 7,865 women became overweight or obese. In multivariable-adjusted models that included demographic, lifestyle, and dietary factors, both vigorous-intensity and total LTPA showed a modest inverse relationship with the development of overweight/obesity. The hazard ratios (HR) and 95% confidence interval (CI) for the highest categories of vigorous-intensity LTPA (>2,000 kcal/week) and total LTPA (>3,000 kcal/week) compared with no LTPA were 0.79 (0.71-0.89) and 0.87 (0.78-0.96), respectively. In addition, a greater percentage of total LTPA spent performing vigorous intensity activities was associated with a lower risk of overweight/obesity (multivariable HR 0.93, 95% CI 0.87-0.98 for performing >50% compared with <50% of activity as vigorous). In conclusion, higher amounts of total LTPA should be encouraged to prevent obesity. Among those willing to participate in vigorous LTPA, and for whom such activities are not contraindicated, vigorous LPTA should be encouraged.