A Cautionary Note About Estimating Effects of Secondary Exposures in Cohort Studies

Cohort studies are often enriched for a primary exposure of interest to improve cost-effectiveness, which presents analytical challenges not commonly discussed in epidemiology. In this paper, we use causal diagrams to represent exposure-enriched cohort studies, illustrate a scenario wherein the risk ratio for the effect of a secondary exposure on an outcome is biased, and propose an analytical method for correcting for such bias. In our motivating example, maternal smoking (Z) is a cause of fetal growth restriction (X), which subsequently affects preterm birth (Y) (i.e., Z → X → Y); strong positive associations exist between both Z, X and X, Y; and enrichment for X increases its prevalence from 10% to 50%. In the X-enriched cohort, unadjusted and X-adjusted analyses lead to bias in the risk ratio for the total effect of Z on Y. After application of inverse probability weights, the bias is corrected, with a small loss of efficiency in comparison with a same-sized study without X-enrichment. With increasing interest in conducting secondary analyses to reduce research costs, caution should be employed when analyzing studies that have already been enriched, intentionally or unintentionally, for a primary exposure of interest. Causal diagrams can help identify scenarios in which secondary analyses may be biased. Inverse probability weights can be used to remove the bias

Telomere shortening occurs in Asian Indian Type 2 diabetic patients

Aim: Telomere shortening has been reported in several diseases including atherosclerosis and Type 1 diabetes. Asian Indians have an increased predilection for Type 2 diabetes and premature coronary artery disease. The aim of this study was to determine whether telomeric shortening occurs in Asian Indian Type 2 diabetic patients. Methods: Using Southern‐blot analysis we determined mean terminal restriction fragment (TRF) length, a measure of average telomere size, in leucocyte DNA. Type 2 diabetic patients without any diabetes‐related complications (n = 40) and age‐ and sex‐matched control non‐diabetic subjects (n = 40) were selected from the Chennai Urban Rural Epidemiology Study (CURES). Plasma level of malondialdehyde (MDA), a marker of lipid peroxidation, was measured by TBARS (thiobarbituric acid reactive substances) using a fluorescence method. Results: Mean (± SE) TRF lengths of the Type 2 diabetic patients (6.01 ± 0.2 kb) were significantly shorter than those of the control subjects (9.11 ± 0.6 kb) (P = 0.0001). Among the biochemical parameters, only levels of TBARS showed a negative correlation with shortened telomeres in the diabetic subjects (r = −0.36; P = 0.02). However, telomere lengths were negatively correlated with insulin resistance (HOMA‐IR) (r = −0.4; P = 0.01) and age (r = −0.3; P = 0.058) and positively correlated with HDL levels (r = 0.4; P = 0.01) in the control subjects. Multiple linear regression (MLR) analysis revealed diabetes to be significantly (P < 0.0001) associated with shortening of TRF lengths. Conclusions: Telomere shortening occurs in Asian Indian Type 2 diabetic patients

Associations of sitting accumulation patterns with cardio-metabolic risk biomarkers in Australian adults

Backgroun

Sitting time, fidgeting and all-cause mortality in the UK Women's Cohort Study

Introduction: Sedentary behaviours (including sitting) may increase risk of mortality independently of physical activity level. Little is known about how fidgeting behaviours might modify the association. Methods: Data were drawn from the UK Women’s Cohort Study. In 1999/2002, 12,778 women (age 37 to 78) provided data on average daily sitting time, overall fidgeting (irrespective of posture), and a range of relevant covariates including physical activity, diet, smoking status and alcohol consumption. Participants were followed for mortality over a mean of 12 years. Proportional hazards Cox regression models were used to estimate the relative risk of mortality in the high (vs. low) and medium (vs. low) sitting time groups. Results: Fidgeting modified the risk associated with sitting time (p value for interaction = 0.04), leading us to separate groups for analysis. Adjusting for a range of covariates, sitting for 7+ hours/day (vs. <5 hours/day) was associated with 30% increased risk of all-cause mortality (HR = 1.30, 95% CI 1.02, 1.66) only among women in the low fidgeting group. Among women in the high fidgeting group, sitting for 5/6 (vs. <5 hrs/day) was associated with decreased risk of mortality (HR = 0.63, 95% CI 0.43, 0.91), adjusting for a range of covariates. There was no increased risk of mortality from longer sitting time in the middle and high fidgeting groups. Conclusions: Fidgeting may reduce the risk of all-cause mortality associated with excessive sitting time. More detailed and better validated measures of fidgeting should be identified in other studies in order to replicate these findings and identity mechanisms, particularly measures that distinguish fidgeting in a seated from standing posture

Serum uric acid in relation to endogenous reproductive hormones during the menstrual cycle: findings from the BioCycle study

Do uric acid levels across the menstrual cycle show associations with endogenous estradiol (E2) and reproductive hormone concentrations in regularly menstruating women

Does long-term care use within primary health care reduce hospital use among older people in Norway? A national five-year population-based observational study

<p>Abstract</p> <p>Background</p> <p>Population ageing may threaten the sustainability of future health care systems. Strengthening primary health care, including long-term care, is one of several measures being taken to handle future health care needs and budgets. There is limited and inconsistent evidence on the effect of long-term care on hospital use. We explored the relationship between the total use of long-term care within public primary health care in Norway and the use of hospital beds when adjusting for various effect modifiers and confounders.</p> <p>Methods</p> <p>This national population-based observational study consists of all Norwegians (59% women) older than 66 years (N = 605676) (13.2% of total population) in 2002-2006. The unit of analysis was defined by municipality, age and sex. The association between total number of recipients of long-term care per 1000 inhabitants (LTC-rate) and hospital days per 1000 inhabitants (HD-rate) was analysed in a linear regression model. Modifying and confounding effects of socioeconomic, demographic and geographic variables were included in the final model. We defined a difference in hospitalization rates of more than 1000 days per 1000 inhabitants as clinically important.</p> <p>Results</p> <p>Thirty-one percent of women and eighteen percent of men were long-term care users. Men had higher HD-rates than women. The crude association between LTC-rate and HD-rate was weakly negative. We identified two effect modifiers (age and sex) and two strong confounders (travel time to hospital and mortality). Age and sex stratification and adjustments for confounders revealed a positive statistically significant but not clinically important relationship between LTC-rates and hospitalization for women aged 67-79 years and all men. For women 80 years and over there was a weak but negative relationship which was neither statistically significant nor clinically important.</p> <p>Conclusions</p> <p>We found a weak positive adjusted association between LTC-rates and HD-rates. Opposite to common belief, we found that increased volume of LTC by itself did not reduce pressure on hospitals. There still is a need to study integrated care models for the elderly in the Norwegian setting and to explore further why municipalities far away from hospital achieve lower use of hospital beds.</p

Basic Subsistence Needs and Overall Health Among Human Immunodeficiency Virus-infected Homeless and Unstably Housed Women

Some gender differences in the progression of human immunodeficiency virus (HIV) infection have been attributed to delayed treatment among women and the social context of poverty. Recent economic difficulties have led to multiple service cuts, highlighting the need to identify factors with the most influence on health in order to prioritize scarce resources. The aim of this study was to empirically rank factors that longitudinally impact the health status of HIV-infected homeless and unstably housed women. Study participants were recruited between 2002 and 2008 from community-based venues in San Francisco, California, and followed over time; marginal structural models and targeted variable importance were used to rank factors by their influence. In adjusted analysis, the factor with the strongest effect on overall mental health was unmet subsistence needs (i.e., food, hygiene, and shelter needs), followed by poor adherence to antiretroviral therapy, not having a close friend, and the use of crack cocaine. Factors with the strongest effects on physical health and gynecologic symptoms followed similar patterns. Within this population, an inability to meet basic subsistence needs has at least as much of an effect on overall health as adherence to antiretroviral therapy, suggesting that advances in HIV medicine will not fully benefit indigent women until their subsistence needs are met

Determinants of short and long term functional recovery after hospitalization for community-acquired pneumonia in the elderly: role of inflammatory markers

BACKGROUND: Hospitalization for older patients with community-acquired pneumonia (CAP) is associated with functional decline. Little is know about the relationship between inflammatory markers and determinants of functional status in this population. The aim of the study is to investigate the association between tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and Activities of Daily Living, and to identify risk factors associated with one year mortality or hospital readmission. METHODS: 301 consecutive patients hospitalized for CAP (mean age 73.9 ± 5.3 years) in a University affiliated hospital over 18 month period were included. All patients were evaluated on admission to identify baseline demographic, microbiological, cognitive and functional characteristics. Serum levels for TNF-α and CRP were collected at the same time. Reassessment of functional status at discharge, and monthly thereafter till 3 months post discharge was obtained and compared with preadmission level to document loss or recovery of functionality. Outcome was assessed by the composite endpoint of hospital readmission or death from any cause up to one year post hospital discharge. RESULTS: 36% of patients developed functional decline at discharge and 11% had persistent functional impairment at 3 months. Serum TNF-α (odds ratio [OR] 1.12, 95% CI 1.08–1.15; p < 0.001) and the Charlson Index (OR = 1.39, 95% CI 1.14 to 1.71; p = 0.001) but not age, CRP, or cognitive status were independently associated with loss of functionality at the time of hospital discharge. Lack of recovery in functional status at 3 months was associated with impaired cognitive ability and preadmission comorbidities. In Cox regression analysis, persistent functional impairment at 3 months, impaired cognitive function, and the Charlson Index were highly predictive of one year hospital readmission or death. CONCLUSION: Serum TNF-α levels can be useful in determining patients at risk for functional impairment following hospitalization from CAP. Old patients with impaired cognitive function and preexisting comorbidities who exhibit delay in functional recovery at 3 months post discharge may be at high risk for hospital readmission and death. With the scarcity of resources, a future risk stratification system based on these findings might be proven helpful to target older patients who are likely to benefit from interventional strategies

Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development - the LIFE Study: The LIFE Study

Buck Louis GM, Schisterman EF, Sweeney AM, Wilcosky TC, Gore-Langton RE, Lynch CD, Boyd Barr D, Schrader SM, Kim S, Chen Z, Sundaram R, on behalf of the LIFE Study. Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development – the LIFE Study. Paediatric and Perinatal Epidemiology 2011; 25: 413–424