Burden of Obstructive Lung Disease (BOLD) Initiative sites worldwide.
To measure the prevalence of chronic obstructive pulmonary disease (COPD) and its risk factors, investigate variation in ...prevalence across countries and develop standardized methods that can be used in industrialized and developing countries.
Non-institutionalized adults aged > or =40 years were recruited using population-based sampling plans. Each site targeted a minimum of 600 participants (300 women, 300 men), who filled out questionnaires and performed spirometry before and after administration of 200 mug salbutamol using standardized methods. Random effects meta-analysis models were used to estimate pooled prevalence estimates and risk factor effects and to test for heterogeneity across sites and sex.
Data published from 12 sites (n = 8775) showed that the estimated population prevalence of COPD (Global Initiative for Chronic Obstructive Lung Disease GOLD Stage II and higher) was 10.1 +/- SE = 4.8% overall (11.8 +/- 7.9% for men and 8.5 +/- 5.8% for women). Prevalence increased with age and pack-years of smoking, but other less understood risk factors, such as biomass heating and cooking exposures, occupational exposures and tuberculosis, also contribute to the location-specific variations in disease prevalence that BOLD is finding.
BOLD has estimated the social and economic burden of COPD in 12 countries to date. BOLD and the Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar (the PLATINO study) are developing a growing database of COPD prevalence. Cigarette smoking and age are the most important COPD risk factors, but other risk factors should also be explored.
Summary Background Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality worldwide, and accurate estimates of the prevalence of this disease are needed to ...anticipate the future burden of COPD, target key risk factors, and plan for providing COPD-related health services. We aimed to measure the prevalence of COPD and its risk factors and investigate variation across countries by age, sex, and smoking status. Methods Participants from 12 sites (n=9425) completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. COPD prevalence estimates based on the Global Initiative for Chronic Obstructive Lung Disease staging criteria were adjusted for the target population. Logistic regression was used to estimate adjusted odds ratios (ORs) for COPD associated with 10-year age increments and 10-pack-year (defined as the number of cigarettes smoked per day divided by 20 and multiplied by the number of years that the participant smoked) increments. Meta-analyses provided pooled estimates for these risk factors. Findings The prevalence of stage II or higher COPD was 10·1% (SE 4·8) overall, 11·8% (7·9) for men, and 8·5% (5·8) for women. The ORs for 10-year age increments were much the same across sites and for women and men. The overall pooled estimate was 1·94 (95% CI 1·80–2·10) per 10-year increment. Site-specific pack-year ORs varied significantly in women (pooled OR=1·28, 95% CI 1·15–1·42, p=0·012), but not in men (1·16, 1·12–1·21, p=0·743). Interpretation This worldwide study showed higher levels and more advanced staging of spirometrically confirmed COPD than have typically been reported. However, although age and smoking are strong contributors to COPD, they do not fully explain variations in disease prevalence—other factors also seem to be important. Although smoking cessation is becoming an increasingly urgent objective for an ageing worldwide population, a better understanding of other factors that contribute to COPD is crucial to assist local public-health officials in developing the best possible primary and secondary prevention policies for their regions.
The rate of survival after out-of-hospital cardiac arrest is low. It is not known whether this rate will increase if laypersons are trained to attempt defibrillation with the use of automated ...external defibrillators (AEDs).
We conducted a prospective, community-based, multicenter clinical trial in which we randomly assigned community units (e.g., shopping malls and apartment complexes) to a structured and monitored emergency-response system involving lay volunteers trained in cardiopulmonary resuscitation (CPR) alone or in CPR and the use of AEDs. The primary outcome was survival to hospital discharge.
More than 19,000 volunteer responders from 993 community units in 24 North American regions participated. The two study groups had similar unit and volunteer characteristics. Patients with treated out-of-hospital cardiac arrest in the two groups were similar in age (mean, 69.8 years), proportion of men (67 percent), rate of cardiac arrest in a public location (70 percent), and rate of witnessed cardiac arrest (72 percent). No inappropriate shocks were delivered. There were more survivors to hospital discharge in the units assigned to have volunteers trained in CPR plus the use of AEDs (30 survivors among 128 arrests) than there were in the units assigned to have volunteers trained only in CPR (15 among 107; P=0.03; relative risk, 2.0; 95 percent confidence interval, 1.07 to 3.77); there were only 2 survivors in residential complexes. Functional status at hospital discharge did not differ between the two groups.
Training and equipping volunteers to attempt early defibrillation within a structured response system can increase the number of survivors to hospital discharge after out-of-hospital cardiac arrest in public locations. Trained laypersons can use AEDs safely and effectively.
The presence of restrictive lung disease has classically required the measure of total lung capacity to document 'true' restriction, which has limited its detection in large population-based studies.
...We used spirometric data to classify people with restricted spirometry (forced expiratory volume in 1 second FEV(1)/forced vital capacity ≥ 0.70 and FEV(1) < 80% predicted) in the Burden of Lung Disease (BOLD) Study and determined the relation between this finding and demographic factors and the presence of chronic diseases, including diabetes mellitus, hypertension and cardiovascular disease.
Overall, we found that 11.7% of men (546/4664) and 16.4% of women (836/5098) had restricted spirometry. Prevalence varied widely by site, from a low of 4.2% among males in Sydney, Australia, to a high of 48.7% among females in Manila, The Philippines. Compared to people with normal lung function, those with restricted spirometry had a higher prevalence of diabetes (12.2% vs. 4.6%), heart disease (15.0% vs. 7.7%) and hypertension (38.8% vs. 22.8%).
Restricted spirometry is a common finding in population studies. Additional research is needed to better define and describe the mechanisms that lead to restricted spirometry and potential interventions.
Frailty in older adults: evidence for a phenotype Fried, L P; Tangen, C M; Walston, J ...
The journals of gerontology. Series A, Biological sciences and medical sciences,
03/2001, Letnik:
56, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, ...and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established.
To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality.
Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline).
This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.
Frail health in old age has been conceptualized as a loss of physiologic reserve associated with loss of lean mass, neuroendocrine dysregulation, and immune dysfunction. Little work has been done to ...define frailty and describe the underlying pathophysiology.
Frailty status was defined in participants of the Cardiovascular Health Study (CHS), a cohort of 5,201 community-dwelling older adults, based on the presence of three out of five clinical criteria. The five criteria included self-reported weight loss, low grip strength, low energy, slow gait speed, and low physical activity. We examined the spectrum of clinical and subclinical cardiovascular disease in those who were frail (3/5 criteria) or of intermediate frailty status (1 or 2/5 criteria), compared to those who were not frail (0/5). We hypothesized that the severity of frailty would be related to a higher prevalence of reported cardiovascular disease (CVD), as well as to a greater extent of CVD, measured by noninvasive testing.
Of 4,735 eligible participants, 2,289 (48%) were not frail, 299 (6%) were frail, and 2.147 (45%) were of intermediate frailty status. Those who were frail were older (77.2 yrs) compared to those who were not frail (71.5 yrs) or intermediate (73.4 yrs) (p < .001). Frailty status was associated with clinical CVD and most strongly with congestive heart failure (odds ratio OR = 7.51 (95% confidence interval CI = 4.66-12.12). In those without a history of a CVD event (n = 1.259), frailty was associated with many noninvasive measures of CVD. Those with carotid stenosis >75% (adjusted OR = 3.41), ankle-arm index <0.8 (adjusted OR = 3.17) or 0.8-0.9 (adjusted OR = 2.01), major electrocardiography (ECG) abnormalities (adjusted OR = 1.58), greater left ventricular (LV) mass by echocardiography (adjusted OR = 1.16), and higher degree of infarct-like lesions in the brain (adjusted OR = 1.71), were more likely to be frail compared to those who were not frail. The overall associations of each of these noninvasive measures of CVD with frailty level were significant (all p < .05).
Cardiovascular disease was associated with an increased likelihood of frail health. In those with no history of CVD, the extent of underlying cardiovascular disease measured by carotid ultrasound and ankle-arm index, LV hypertrophy by ECG and echocardiography, was related to frailty. Infarct-like lesions in the brain on magnet resonance imaging were related to frailty as well.
Introduction
Low-income populations have elevated exposure to early life risk factors for obesity, but are understudied in longitudinal research. Our objective was to assess the utility of a cohort ...derived from electronic health record data from safety net clinics for investigation of obesity emerging in early life.
Methods
We examined data from the PCORNet ADVANCE Clinical Data Research Network, a national network of Federally-Qualified Health Centers serving >1.7 million safety net patients across the US. This cohort includes patients who, in 2012–2014, had ≥1 valid body mass index measure when they were 0–5 years of age. We characterized the cohort with respect to factors required for early life obesity research in vulnerable subgroups: sociodemographic diversity, weight status based on World Health Organization (<2 years) or Centers for Disease Control (≥2 years) growth curves, and data longitudinality.
Results
The cohort includes 216,473 children and is racially/ethnically diverse (e.g., 17.9% Black, 45.4% Hispanic). A majority (56.9%) had family incomes below the Federal Poverty Level (FPL); 32% were <50% of FPL. Among children <2 years, 7.6 and 5.3% had high and low weight-for-length, respectively. Among children 2–5 years, 15.0, 12.7 and 2.4% were overweight, obese, and severely obese, respectively; 5.3% were underweight. In the study period, 79.2% of children had ≥2 BMI measures. Among 4–5 year olds, 21.9% had >1 BMI measure when they were <2 years.
Discussion
The ADVANCE Early Life cohort offers unique opportunities to investigate early life determinants of obesity in the understudied population of low income and minority children.
Tremelimumab, a fully human cytotoxic T-lymphocyte antigen 4 monoclonal antibody, and PF-3512676, a Toll-like receptor-9 agonist, are targeted immune modulators that elicit durable single-agent ...antitumour activity in advanced cancer.
To determine the maximum tolerated dose (MTD) of these agents combined during this phase I study, patients received intravenous tremelimumab (6.0, 10.0, or 15.0 mg kg(-1)) every 12 weeks plus subcutaneous PF-3512676 (0.05, 0.10, or 0.15 mg kg(-1)) weekly. Primary end points were safety and tolerability; secondary end points included pharmacokinetics and antitumour activity.
Twenty-one patients with stage IV melanoma (n=17) or advanced solid tumours (n=4) were enrolled. Injection-site reactions (n=21; 100%), influenza-like illness (n=18; 86%), and diarrhoea (n=13; 62%) were the most common treatment-related adverse events (TAEs). Grade ≥3 TAEs were reported (n=7; 33%). Dose-limiting toxicities (prespecified 6-week observation) occurred in one of the six patients in the 10 mg kg(-1) tremelimumab plus 0.05 mg kg(-1) PF-3512676 cohort (grade 3 hypothalamopituitary disorder) and two of the six patients in the 15 mg kg(-1) tremelimumab plus 0.05 mg kg(-1) PF-3512676 cohort (grade 3 diarrhoea). Consequently, 15 mg kg(-1) tremelimumab plus 0.05 mg kg(-1) PF-3512676 exceeded the MTD. Two melanoma patients achieved durable (≥170 days) partial response. No human antihuman antibody responses to tremelimumab were observed.
Weekly PF-3512676 (≤0.15 mg kg(-1)) plus tremelimumab (≤10 mg kg(-1) every 12 weeks) was tolerable.
We aimed to examine whether the ventilatory threshold (VT) during an incremental shuttle walk test (ISWT) could be determined using heart rate variability (HRV) analysis. Further aims were to assess ...variables capable of predicting performance in the ISWT and the intensity of this test. Beat-to-beat RR intervals and gas exchange values in 10 healthy subjects (31-83 years; 7 men) were collected during the ISWT. The ventilatory equivalent was used to assess VT from respiratory components. To determine the HRV threshold (HRVT), the instantaneous beat-to-beat variability values of the RR intervals at each stage of exercise were graphically plotted against walking speed (WS). The oxygen consumption at HRVT was calculated (VO2HRVT). No significant differences were found between walking speed (WS) at VT and WS at HRVT (5.04±1.00 vs. 5.10±1.04 km/h; p=0.89). Linear regression analysis revealed a strong correlation between VO2VT and VO2HRVT (r(2)=0.896). The Bland and Altman plot analysis revealed an agreement between VO2VT and VO2HRVT (-0.05; 95%CI: -0.30-0.20 L/min). Thus, the VT can be assessed during the ISWT using a simple heart monitor. The ISWT may be a useful tool to assess exercise capacity and prescribe walking programs.
It remains unclear whether estrogen therapy (with or without progestin) improves endothelial function in older postmenopausal women with or at risk for coronary heart disease. To address this issue, ...we analyzed brachial artery flow-mediated vasodilation in the Cardiovascular Health Study, a longitudinal study of cardiovascular risk factors in subjects over 65 years of age. At the tenth annual Cardiovascular Health Study examination, 1662 women returned for follow-up. Eighteen percent (n=291) were current users of estrogen replacement, most of whom (75.9%, n=221) took unopposed estrogen. Brachial artery ultrasound examinations measuring vasodilation in response to a flow stimulus (hyperemia) were performed on 1636 women. There were no statistical differences in brachial flow-mediated vasodilator responses between users and nonusers, even after adjustment for potential confounders. Absence of an effect was most notable in women over 80 years old and in those with established cardiovascular disease. However, among women without clinical or subclinical cardiovascular disease or its risk factors, there was a significant association between hormone replacement therapy use and flow-mediated vasodilator responses (P=0.01). Among older postmenopausal women, favorable vascular effects of estrogen may be limited to those who have not yet developed atherosclerotic vascular disease. These data emphasize the importance of ongoing efforts to determine the role of hormone replacement therapy for primary prevention of cardiovascular disease.
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