The use of complete-case and multiple imputation-based analyses in molecular epidemiology studies that assess interaction effects

Abstract Background In molecular epidemiology studies biospecimen data are collected, often with the purpose of evaluating the synergistic role between a biomarker and another feature on an outcome. Typically, biomarker data are collected on only a proportion of subjects eligible for study, leading to a missing data problem. Missing data methods, however, are not customarily incorporated into analyses. Instead, complete-case (CC) analyses are performed, which can result in biased and inefficient estimates. Methods Through simulations, we characterized the performance of CC methods when interaction effects are estimated. We also investigated whether standard multiple imputation (MI) could improve estimation over CC methods when the data are not missing at random (NMAR) and auxiliary information may or may not exist. Results CC analyses were shown to result in considerable bias and efficiency loss. While MI reduced bias and increased efficiency over CC methods under specific conditions, it too resulted in biased estimates depending on the strength of the auxiliary data available and the nature of the missingness. In particular, CC performed better than MI when extreme values of the covariate were more likely to be missing, while MI outperformed CC when missingness of the covariate related to both the covariate and outcome. MI always improved performance when strong auxiliary data were available. In a real study, MI estimates of interaction effects were attenuated relative to those from a CC approach. Conclusions Our findings suggest the importance of incorporating missing data methods into the analysis. If the data are MAR, standard MI is a reasonable method. Auxiliary variables may make this assumption more reasonable even if the data are NMAR. Under NMAR we emphasize caution when using standard MI and recommend it over CC only when strong auxiliary data are available. MI, with the missing data mechanism specified, is an alternative when the data are NMAR. In all cases, it is recommended to take advantage of MI's ability to account for the uncertainty of these assumptions

Pegylated Interferon Pharmacokinetics and Self-Reported Depressive Symptoms During Antiviral Treatment for Chronic Hepatitis C

Pegylated interferon-2a (PegIFN-2a) + ribavirin treatment for chronic hepatitis C is often associated with depressive symptoms. Previous studies have failed to explore whether PegIFN-2a pharmacokinetic variability plays an etiologic role in PegIFN-2a-induced mood disorders. The objective of this investigation was to evaluate the association between trough PegIFN-2a concentration at treatment week 4 (“PegIFN-2a Cmin4”) and an increase in depressive symptoms

Self-reported daily stress, squelching of anger and the management of daily stress and the prevalence of uterine leiomyomata: The ultrasound screening study

Self-reported daily stress, ways of managing stress and squelching anger were examined in association with uterine leiomyomata (aka fibroids). These stress factors were obtained from 560 Black and 375 White women enrolled in the National Institute of Environmental Health Sciences Uterine Fibroid Study. Race-specific prevalence differences (PD) and 95% confidence intervals (95% CI) were calculated. Black women with severe stress had a prevalence of fibroids that was 11% higher (95% CI: 0%, 21%) than those in the no or mild stress group (referent). White women with severe stress, compared to the referent, had a non-significantly (NS) higher prevalence of fibroids [PD = 7%; 95% CI: (-10%, 21%)]. For both groups, moderate daily stress was associated with a weak elevation (NS) in fibroid prevalence. Black women who reported squelching their anger had an elevated prevalence of fibroids (8%) compared to non-squelchers [95% CI: (-0%, 15%)] while there was no association for White women. Women with symptomatic fibroids had higher stress than those without, but exclusion of symptomatic women only slightly attenuated the associations. Consistent with a previous report, symptomatic fibroids may cause stress. However, further research is warranted to prospectively investigate a possible aetiologic role for stress in the development of fibroids

A Comparison of the Occurrence and Perceived Stress of Major Life Events in Black and White Women

To describe the occurrence and perceived stress of major life events (MLE), and to investigate whether adjusting for socioeconomic status (SES) reduced race/ethnicity differences

S100A9 is not essential for disease expression in an acute (K/BxN) or chronic (CIA) model of inflammatory arthritis

S100A8 (calgranulin A, MRP8) and S100A9 (calgranulin B, MRP14) are calcium-binding proteins highly expressed by activated myeloid cells and thought to be involved in the pathogenesis of inflammatory diseases. Circulating levels of S100A8/S100A9 are elevated in both human and experimental models of autoimmune disease, including rheumatoid arthritis (RA)

Barriers to accessing care in patients with chronic hepatitis C: the impact of depression: Barriers to accessing healthcare for chronic hepatitis C

Patients with hepatitis C viral (HCV) may perceive barriers to accessing speciality care for HCV, and these barriers may be related to depressive symptoms

Patient-centric trials for therapeutic development in precision oncology

An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

Development and Testing of a Tool for Assessing and Resolving Medication-Related Problems in Older Adults in an Ambulatory Care Setting: The Individualized Medication Assessment and Planning (iMAP) Tool

Medications are one of the most important interventions for improving the health of older adults, yet have great potential for causing harm. Clinical pharmacists are well positioned to engage in medication assessment and planning. The individualized Medication Assessment and Planning (iMAP) tool was developed to aid clinical pharmacists in documenting medication-related problems (MRPs) and associated recommendations