CONFIDENCE INTERVAL ESTIMATION FOR A DIFFERENCE BETWEEN CORRELATED INTRACLASS CORRELATION COEFFICIENTS

The intraclass correlation coefficient (ICC), an index of similarity, plays an important role in a wide range of disciplines, for example in the assessment of instrument reliability. In this case, the study design may involve recruiting a sample of subjects each of whom are assessed severe^ times with a new device and the standard. The ICC estimates for the two devices may then be compared using a test of hypothesis. However it is well known that conclusions drawn from hypothesis testing are confounded by sample size, i.e., a significant p-value can result from a sufficiently large sample size. In such cases, a confidence interval for a difference between two ICCs is more informative since it combines point estimation and hypothesis testing into a single inference statement. The sampling distribution for the ICC is well known to be left-skewed and thus confidence limits are usually constructed using Fisher’s Z-transformation or the F- distribution. Unfortunately, such an approach is not applicable to a difference between two ICCs. The remaining alternative is to apply a simple asymptotic approach, i.e., point estimate plus/minus normal quantile multiplied by the estimate of standard error. However this method is known to perform poorly because it ignores the features of the underlying sampling distribution. In this thesis I develop a confidence interval procedure using the method of variance estimate recovery (MOVER). Specifically, the variance estimates required for the upper and lower limits of a difference are iii recovered from those obtained for separate ICCs. An advantage of this approach is that it provides a confidence interval that reflects the underlying sampling distribution. Simulation results show that the MOVER method performs very well in terms of overall coverage percentage and tail errors. Two data sets are used to illustrate this procedure

CONFIDENCE INTERVAL ESTIMATION FOR A DIFFERENCE BETWEEN CORRELATED INTRACLASS CORRELATION COEFFICIENTS

The intraclass correlation coefficient (ICC), an index of similarity, plays an important role in a wide range of disciplines, for example in the assessment of instrument reliability. In this case, the study design may involve recruiting a sample of subjects each of whom are assessed several times with a new device and the standard. The ICC estimates for the two devices may then be compared using a test of hypothesis. However it is well known that conclusions drawn from hypothesis testing are confounded by sample size, i.e., a significant p-value can result from a sufficiently large sample size. In such cases, a confidence interval for a difference between two ICCs is more informative since it combines point estimation and hypothesis testing into a single inference statement. The sampling distribution for the ICC is well known to be left-skewed and thus confidence limits are usually constructed using Fisher’s Z-transformation or the F- distribution. Unfortunately, such an approach is not applicable to a difference between two ICCs. The remaining alternative is to apply a simple asymptotic approach, i.e., point estimate plus/minus normal quantile multiplied by the estimate of standard error. However this method is known to perform poorly because it ignores the features of the underlying sampling distribution. In this thesis I develop a confidence interval procedure using the method of variance estimate recovery (MOVER). Specifically, the variance estimates required for the upper and lower limits of a difference are recovered from those obtained for separate ICCs. An advantage of this approach is that it provides a confidence interval that reflects the underlying sampling distribution. Simulation results show that the MOVER method performs very well in terms of overall coverage percentage and tail errors. Two data sets are used to illustrate this procedure

Psychosocial risk factors and cardiovascular disease and death in a population-based cohort from 21 low-, middle-, and high-income countries

Importance: Stress may increase the risk of cardiovascular disease (CVD). Most studies on stress and CVD have been conducted in high-income Western countries, but whether stress is associated with CVD in other settings has been less well studied.Objective: To investigate the association of a composite measure of psychosocial stress and the development of CVD events and mortality in a large prospective study involving populations from 21 high-, middle-, and low-income countries across 5 continents.Design, setting, and participants: This population-based cohort study used data from the Prospective Urban Rural Epidemiology study, collected between January 2003 and March 2021. Participants included individuals aged 35 to 70 years living in 21 low-, middle-, and high-income countries. Data were analyzed from April 8 to June 15, 2021.Exposures: All participants were assessed on a composite measure of psychosocial stress assessed at study entry using brief questionnaires concerning stress at work and home, major life events, and financial stress.Main outcomes and measures: The outcomes of interest were stroke, major coronary heart disease (CHD), CVD, and all-cause mortality.Results: A total of 118 706 participants (mean [SD] age 50.4 [9.6] years; 69 842 [58.8%] women and 48 864 [41.2%] men) without prior CVD and with complete baseline and follow-up data were included. Of these, 8699 participants (7.3%) reported high stress, 21 797 participants (18.4%) reported moderate stress, 34 958 participants (29.4%) reported low stress, and 53 252 participants (44.8%) reported no stress. High stress, compared with no stress, was more likely with younger age (mean [SD] age, 48.9 [8.9] years vs 51.1 [9.8] years), abdominal obesity (2981 participants [34.3%] vs 10 599 participants [19.9%]), current smoking (2319 participants [26.7%] vs 10 477 participants [19.7%]) and former smoking (1571 participants [18.1%] vs 3978 participants [7.5%]), alcohol use (4222 participants [48.5%] vs 13 222 participants [24.8%]), and family history of CVD (5435 participants [62.5%] vs 20 255 participants [38.0%]). During a median (IQR) follow-up of 10.2 (8.6-11.9) years, a total of 7248 deaths occurred. During the course of follow-up, there were 5934 CVD events, 4107 CHD events, and 2880 stroke events. Compared with no stress and after adjustment for age, sex, education, marital status, location, abdominal obesity, hypertension, smoking, diabetes, and family history of CVD, as the level of stress increased, there were increases in risk of death (low stress: hazard ratio [HR], 1.09 [95% CI, 1.03-1.16]; high stress: 1.17 [95% CI, 1.06-1.29]) and CHD (low stress: HR, 1.09 [95% CI, 1.01-1.18]; high stress: HR, 1.24 [95% CI, 1.08-1.42]). High stress, but not low or moderate stress, was associated with CVD (HR, 1.22 [95% CI, 1.08-1.37]) and stroke (HR, 1.30 [95% CI, 1.09-1.56]) after adjustment.Conclusions and relevance: This cohort study found that higher psychosocial stress, measured as a composite score of self-perceived stress, life events, and financial stress, was significantly associated with mortality as well as with CVD, CHD, and stroke events

Socioeconomic status and risk of cardiovascular disease in 20 low-income, middle-income, and high-income countries: The prospective urban rural epidemiologic (PURE) study

Background: Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status-wealth and education-differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management.Methods: In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family.Findings: Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96-1·58) for high-income countries, 1·59 (1·42-1·78) in middle-income countries, and 2·23 (1·79-2·77) in low-income countries (pinteraction\u3c0·0001). We observed similar results for all-cause mortality, with HRs of 1·50 (1·14-1·98) for high-income countries, 1·80 (1·58-2·06) in middle-income countries, and 2·76 (2·29-3·31) in low-income countries (pinteraction\u3c0·0001). By contrast, we found no or weak associations between wealth and these two outcomes. Differences in outcomes between educational groups were not explained by differences in risk factors, which decreased as the level of education increased in high-income countries, but increased as the level of education increased in low-income countries (pinteraction\u3c0·0001). Medical care (eg, management of hypertension, diabetes, and secondary prevention) seemed to play an important part in adverse cardiovascular disease outcomes because such care is likely to be poorer in people with the lowest levels of education compared to those with higher levels of education in low-income countries; however, we observed less marked differences in care based on level of education in middle-income countries and no or minor differences in high-income countries.Interpretation: Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education.Funding: Full funding sources are listed at the end of the paper (see Acknowledgments)

Ethnic differences in maternal diet in pregnancy and infant eczema

Background The global prevalence of childhood eczema has increased over the last few decades, with a marked increase in high-income countries. Differences in prevalence of childhood eczema between countries and ethnicities suggest that genetic and early modifiable environmental factors, such as dietary intake, may underlie this observation. To investigate the association between pregnancy diet and infant eczema in a consortium of prospective Canadian birth cohorts predominantly comprised of white Europeans and South Asians. Methods We evaluated the association of maternal dietary patterns reported during pregnancy (assessed at 24–28 weeks gestation using a semi-quantitiative food-frequency questionnaire) with parent-reported physician-diagnosed infant eczema at 1-year from 2,160 mother-infant pairs. Using three dietary patterns (“Western”, “plant-based”, and “Balanced”) previously derived in this cohort using principal component analysis, we used multivariable logistic regression to determine the association of these dietary patterns with infant eczema, adjusted for potential confounders. Results We observed a lower odds of eczema in the full sample combining white Europeans and South Asians with greater adherence to a plant-based (OR = 0.65; 95% CI: 0.55, 0.76; <0.001) and Western dietary pattern (OR = 0.73; 95% CI: 0.60, 0.89; P<0.01), after adjusting for other known predictors of eczema, including ethnicity, which was not significant. No associations were observed for the balanced diet. An interaction between the Western diet and ethnicity was observed (P<0.001). Following stratification by ethnicity, a protective association between the plant-based diet and infant eczema was confirmed in both white Europeans (OR = 0.59; 95% CI: 0.47, 0.74; P<0.001) and South Asians (OR = 0.77; 95% CI: 0.61, 0.97; P = 0.025). In white Europeans only, a Western diet was associated with a lower odds of infant eczema (OR = 0.69; 95% CI: 0.56, 0.87; P = 0.001) while a balanced diet increased the odds of infant eczema (OR = 1.23; 95% CI: 1.02, 1.49; P = 0.03). Beyond a plant-based diet, no significant associations with other dietary patterns were observed in South Asians. Conclusion A plant-based diet during pregnancy is associated with a lowered odds of infant eczema at 1 year in all participants. Future studies of the components of plant-based diet which underlie the lower risk of eczema are needed

Cancer mortality in India: a nationally representative survey.

BACKGROUND: The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001-03 in homes in small areas that were chosen to be representative of all the parts of India. METHODS: At least 130 trained physicians independently assigned causes to 122,429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. FINDINGS: 7137 of 122,429 study deaths were due to cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400 (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300 women). At 30-69 years, the three most common fatal cancers were oral (including lip and pharynx, 45,800 [22·9%]), stomach (25,200 [12·6%]), and lung (including trachea and larynx, 22,900 [11·4%]) in men, and cervical (33,400 [17·1%]), stomach (27,500 [14·1%]), and breast (19,900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84,000) of male and 18·3% (35,700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100,000 were similar in rural (men 95·6 [99% CI 89·6-101·7] and women 96·6 [90·7-102·6]) and urban areas (men 102·4 [92·7-112·1] and women 91·2 [81·9-100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4-115·7] vs most educated 45·7 [37·8-53·6]; women, illiterate 106·7 [99·9-113·6] vs most educated 43·4 [30·7-56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64-0·71] vs 340, 1·06 [1·05-1·08]). INTERPRETATION: Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. FUNDING: Bill & Melinda Gates Foundation and US National Institutes of Health

Comparative effectiveness of transitional care services in patients discharged from the hospital with heart failure: a systematic review and network meta-analysis

Aims To compare the effectiveness of transitional care services in decreasing all-cause death and all-cause readmissions following hospitalization for heart failure (HF). Methods and results We searched PubMed, Embase, CINAHL, and Cochrane Clinical Trials Register for randomized controlled trials (RCTs) published in 2000-2015 that tested the efficacy of transitional care services in patients hospitalized for HF, provided >= 1month of follow-up, and reported all-cause mortality or all-cause readmissions. Our network meta-analysis included 53 RCTs (12 356 patients). Among services that significantly decreased all-cause mortality compared with usual care, nurse home visits were most effective [ranking P-score 0.6794; relative risk (RR) 0.78, 95% confidence intervals (CI) 0.62-0.98], followed by disease management clinics (DMCs) (ranking P-score 0.6368; RR 0.80, 95% CI 0.67-0.97). Among services that significantly decreased all-cause readmission, nurse home visits were most effective [ranking P-score 0.8365; incident rate ratio (IRR) 0.65, 95% CI 0.49-0.86], followed by nurse case management (NCM) (ranking P-score 0.6168; IRR 0.77, 95% CI 0.63-0.95), and DMCs (ranking P-score 0.5691; IRR 0.80, 95% CI 0.66-0.97). There was no significant difference in the comparative effectiveness of services that improved each outcome. Nurse home visits had the greatest pooled cost-savings (3810 USD, 95% CI 3682-3937), followed by NCM (3435 USD, 95% CI 3224-3645), and DMCs (245 USD, 95% CI -70 to 559). Telephone, telemonitoring, pharmacist, and education interventions did not significantly improve clinical outcomes. Conclusion Nurse home visits and DMCs decrease all-cause mortality after hospitalization for HF. Along with NCM, they also reduce all-cause readmissions, with no significant difference in comparative effectiveness. These services reduce healthcare system costs to varying degree

Incidence and Predictors of Heart Failure in Patients With Atrial Fibrillation

Background: Heart failure (HF) is a frequent cause of hospitalization and death in patients with atrial fibrillation (AF). Identifying AF patients at risk of HF hospitalization could help select individuals for intensive follow-up and treatment. Methods: We pooled data from 3 randomized trials (ACTIVE-A, RE-LY, AVERROES) of AF patients, for derivation and internal validation of a risk score for first HF hospitalization. Secondary endpoints were cardiovascular death and a composite of HF hospitalizations and cardiovascular death. Results: In 23,503 patients, the mean age was 71.3 years, and 62% were male. Over a mean follow-up of 2.0 years, 875 patients (3.7%) experienced their first HF hospitalization, and 1037 patients (4.4%) died from cardiovascular causes. Incidence rates per 100 patient-years were 1.85 for HF hospitalizations, 2.15 for cardiovascular death, and 3.71 for the composite. Independent predictors for HF hospitalizations included the following: increased age, weight, heart rate and serum creatinine level, lower height and systolic blood pressure, diabetes, vascular disease, valvular disease, heart rhythm, left ventricular hypertrophy, and intraventricular conduction delay. The C-statistic (95% confidence intervals by bootstrap simulations) was 0.717 (0.705-0.732). At 2 years of follow-up, the incidence rate of the primary outcome increased across risk-score quintiles: 0.49, 0.87, 1.29, 2.44, and 4.51 per 100 patient-years, respectively. Patients in the highest quintile had an absolute risk of 6.8% for the primary endpoint at 2 years. Conclusions: In a large AF population, new-onset HF was common. A combination of characteristics can identify high-risk patients for whom strategies to prevent HF should be considered

Smoking-attributable mortality in Bangladesh:proportional mortality study

To directly estimate how much smoking contributes to cause-specific mortality in Bangladesh

Rivaroxaban plus aspirin in obese and overweight patients with vascular disease in the COMPASS trial

Background: Direct oral anticoagulants are administered in fixed doses irrespective of body weight, but guidelines recommend against their use in patients with extremes of body weight. Objectives: This study determined the effects of dual-pathway inhibition antithrombotic regimen (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg/day) compared with aspirin Halone across a range of patient body mass indexes (BMIs) and body weights. Methods: This was a secondary analysis of the COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) trial, which included patients with chronic coronary artery disease or peripheral artery disease. Efficacy and safety outcomes were studied in relation to BMI: (normal 18.5 ≤BMI &lt;25 kg/m2, overweight 25 ≤BMI &lt;30 kg/m2, obese ≥30 kg/m2) and body weight (≤70 kg, 70 &lt; weight ≤90 kg, and &gt;90 kg; as well as ≤120 kg vs. &gt;120 kg). Results: Among 27,395 randomized patients, 6,459 (24%) had normal BMI, 12,047 (44%) were overweight, and 8,701 (32%) were obese. The combination of rivaroxaban and aspirin compared with aspirin produced a consistent reduction in the primary outcome of cardiovascular death, stroke, or myocardial infarction, irrespective of BMI or body weight. For 18.5 ≤BMI &lt;25 kg/m2: 3.5% vs. 5.0%; hazard ratio (HR): 0.73 (95% credible interval [CrI]: 0.58 to 0.90); 25 ≤ BMI &lt;30 kg/m2: 4.3% vs. 5.1%; HR: 0.80 (95% CrI: 0.66 to 0.96); BMI ≥30 kg/m2: 4.2% vs. 6.1%; HR: 0.71 (95% CrI: 0.57 to 0.86). For body weight ≤70 kg: 4.1% vs. 5.3%; HR: 0.75 (95% CrI: 0.62 to 0.91); 70 &lt; weight ≤90 kg: 4.1% vs. 5.3%; HR: 0.76 (95% CrI: 0.65 to 0.89); &gt;90 kg: 4.2% vs. 5.7%; HR: 0.74 (95% CrI: 0.61 to 0.90). Effects on bleeding, mortality, and net clinical benefit were consistent irrespective of BMI or bodyweight. Conclusions: The effects of dual-pathway antithrombotic therapy are consistent irrespective of BMI or body weight, suggesting no need for dose adjustments in the ranges of weights and BMI of patients enrolled in the COMPASS trial. Further studies need to address this problem in relation to greater extremes of body weight. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease [COMPASS]; NCT01776424