George O. Agogo

Evaluation of a two-part regression calibration to adjust for dietary exposure measurement error in the Cox proportional hazards model: A simulation study.

Dietary questionnaires are prone to measurement error, which bias the perceived association between dietary intake and risk of disease. Short-term measurements are required to adjust for the bias in the association. For foods that are not consumed daily, the short-term measurements are often characterized by excess zeroes. Via a simulation study, the performance of a two-part calibration model that was developed for a single-replicate study design was assessed by mimicking leafy vegetable intake reports from the multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) study. In part I of the fitted two-part calibration model, a logistic distribution was assumed; in part II, a gamma distribution was assumed. The model was assessed with respect to the magnitude of the correlation between the consumption probability and the consumed amount (hereafter, cross-part correlation), the number and form of covariates in the calibration model, the percentage of zero response values, and the magnitude of the measurement error in the dietary intake. From the simulation study results, transforming the dietary variable in the regression calibration to an appropriate scale was found to be the most important factor for the model performance. Reducing the number of covariates in the model could be beneficial, but was not critical in large-sample studies. The performance was remarkably robust when fitting a one-part rather than a two-part model. The model performance was minimally affected by the cross-part correlation.

Prognostic Value of Lymph Node Yield and Density in Head and Neck Malignancies

Objective Studies have suggested that the lymph node yield and lymph node density from selective or elective neck dissections are predictive of patient outcomes and may be used for patient counseling, treatment planning, or quality measurement. Our objective was to systematically review the literature and conduct a meta-analysis of studies that investigated the prognostic significance of lymph node yield and/or lymph node density after neck dissection for patients with head and neck cancer. Data Sources The Ovid/Medline, Ovid/Embase, and NLM PubMed databases were systematically searched on January 23, 2017, for articles published between January 1, 1946, and January 23, 2017. Review Methods We reviewed English-language original research that included survival analysis of patients undergoing neck dissection for a head and neck malignancy stratified by lymph node yield and/or lymph node density. Study data were extracted by 2 independent researchers (S.C. and M.O.). We utilized the DerSimonian and Laird random effects model to account for heterogeneity of studies. Results Our search yielded 350 nonduplicate articles, with 23 studies included in the final synthesis. Pooled results demonstrated that increased lymph node yield was associated with a significant improvement in survival (hazard ratio, 0.833; 95% CI, 0.790-0.879). Additionally, we found that increased lymph node density was associated with poorer survival (hazard ratio, 1.916; 95% CI, 1.637-2.241). Conclusions Increased nodal yield portends improved outcomes and may be a valuable quality indicator for neck dissections, while increased lymph node density is associated with diminished survival and may be used for postsurgical counseling and planning for adjuvant therapy.

Adjuvant therapy in major salivary gland cancers: Analysis of 8580 patients in the National Cancer Database

BACKGROUND Evidence surrounding the effect of adjuvant treatment in salivary gland cancers is limited. The benefit of adding chemotherapy to adjuvant treatment is also of interest. We investigated the association of these treatments with survival and whether this differed by stage or the presence of adverse features. METHODS A retrospective study of adult salivary gland cancer cases diagnosed from 2004 to 2013 in the National Cancer Data Base (NCDB) was conducted. RESULTS Treatment with adjuvant radiotherapy was associated with improved survival for both patients with early-stage (hazard ratio [HR] 0.744; P = .004) and late-stage (HR 0.688; P < .001) disease with adverse features. Further addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features was not associated with a survival benefit (HR 1.028; P = .705). CONCLUSION Adjuvant radiotherapy is associated with improved survival for patients with adverse features, regardless of stage. The addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features is not associated with improved outcomes.

Use of two-part regression calibration model to correct for measurement error in episodically consumed foods in a single-replicate study design: EPIC case study.

In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model.

Longitudinal patterns of potentially inappropriate medication use following incident dementia diagnosis

Potentially inappropriate medication (PIM) use in older adults with dementia is an understudied area. We assessed longitudinal changes in PIM exposure by dementia type following dementia diagnosis.

A zero-augmented generalized gamma regression calibration to adjust for covariate measurement error: A case of an episodically consumed dietary intake

Measurement error in exposure variables is a serious impediment in epidemiological studies that relate exposures to health outcomes. In nutritional studies, interest could be in the association between long-term dietary intake and disease occurrence. Long-term intake is usually assessed with food frequency questionnaire (FFQ), which is prone to recall bias. Measurement error in FFQ-reported intakes leads to bias in parameter estimate that quantifies the association. To adjust for bias in the association, a calibration study is required to obtain unbiased intake measurements using a short-term instrument such as 24-hour recall (24HR). The 24HR intakes are used as response in regression calibration to adjust for bias in the association. For foods not consumed daily, 24HR-reported intakes are usually characterized by excess zeroes, right skewness, and heteroscedasticity posing serious challenge in regression calibration modeling. We proposed a zero-augmented calibration model to adjust for measurement error in reported intake, while handling excess zeroes, skewness, and heteroscedasticity simultaneously without transforming 24HR intake values. We compared the proposed calibration method with the standard method and with methods that ignore measurement error by estimating long-term intake with 24HR and FFQ-reported intakes. The comparison was done in real and simulated datasets. With the 24HR, the mean increase in mercury level per ounce fish intake was about 0.4; with the FFQ intake, the increase was about 1.2. With both calibration methods, the mean increase was about 2.0. Similar trend was observed in the simulation study. In conclusion, the proposed calibration method performs at least as good as the standard method.

The Impact of Dementia Diagnosis on Patterns of Potentially Inappropriate Medication Use Among Older Adults

Background Use of potentially inappropriate medications (PIM) among people with dementia is common. We assessed the patterns of medication use from 1-year before dementia diagnosis, to 1-year after dementia diagnosis, compared with patterns of medication use in people without dementia. Methods We conducted longitudinal study using the National Alzheimers Coordinating Center data. Adults aged 65 years and older newly diagnosed with dementia (n = 2,418) during 2005-2015 were year, age, and sex matched 1:1 with controls. Generalized estimating equation models weighted for missingness and adjusted for 15 participant characteristics were fit. Results Among participants with dementia, number of medications reported 1-year prediagnosis was 8% lower than at diagnosis year (p < .0001) and 11% higher 1-year postdiagnosis compared with year of diagnosis (p < .0001). Among participants with dementia, the odds of PIM exposure, assessed using the 2015 Beers Criteria, was 17% lower 1-year prediagnosis (p < .0001) and 17% higher 1-year postdiagnosis (p = .006) compared with year of diagnosis. Among controls, there were approximately 6% more medications reported between consecutive years (p < .0001 each comparison) and the odds of PIM exposure increased 11% between consecutive years (p = .006 and p = .047). At each annual follow-up, participants with dementia had lower odds of PIM exposure than their controls (prediagnosis p < .0001, at diagnosis p = .0007, postdiagnosis p = .03, respectively). There were no differences in exposure to anticholinergic medications. Conclusions Number of medications and PIM use increased annually for participants with and without dementia. Persistent challenge of increasing PIM use in this group of older adults is of major concern and warrants interventions to minimize such prescribing.

Treatment of primary non-metastatic melanoma at high-volume academic facilities is associated with improved long-term patient survival

Background: Previous studies of cancer care have demonstrated improved long‐term patient outcomes for those treated at high‐volume centers. The influence of treatment center characteristics on outcomes for primary nonmetastatic melanoma is not currently established. Objective: We aimed to investigate the association of cancer treatment center case volume and academic affiliation with long‐term patient survival for cases of primary nonmetastatic melanoma. Methods: Cases of melanoma diagnosed in US adults from 2004 to 2014 and included in the National Cancer Database were identified. Hospitals were grouped by yearly case‐volume quartile: bottom quartile, 2 middle quartiles, and top quartile. Results: Facility case volume was significantly associated with long‐term patient survival (P < .0001). The 5‐year survival rates were 76.8%, 81.9%, and 86.4% for patients treated at institutions in the bottom, middle, and top quartiles of case volume, respectively. On multivariate analysis, treatment at centers in both middle quartiles (hazard ratio, 0.834; 95% confidence interval, 0.778‐0.895) and in the top quartile (hazard ratio, 0.691; 95% confidence interval, 0.644‐0.741) of case volume was associated with improved survival relative to that of patients treated at hospitals in the bottom quartile of case volume. Academic affiliation was associated with improved outcomes for top‐quartile‐ but not middle‐quartile‐volume facilities. Limitations: Disease‐specific survival was not available. Conclusions: Treatment at a high‐volume facility is associated with improved long‐term patient survival for melanoma. High‐volume academic centers have improved patient outcomes compared with other high‐volume centers.

A method for sensitivity analysis to assess the effects of measurement error in multiple exposure variables using external validation data

BackgroundMeasurement error in self-reported dietary intakes is known to bias the association between dietary intake and a health outcome of interest such as risk of a disease. The association can be distorted further by mismeasured confounders, leading to invalid results and conclusions. It is, however, difficult to adjust for the bias in the association when there is no internal validation data.MethodsWe proposed a method to adjust for the bias in the diet-disease association (hereafter, association), due to measurement error in dietary intake and a mismeasured confounder, when there is no internal validation data. The method combines prior information on the validity of the self-report instrument with the observed data to adjust for the bias in the association. We compared the proposed method with the method that ignores the confounder effect, and with the method that ignores measurement errors completely. We assessed the sensitivity of the estimates to various magnitudes of measurement error, error correlations and uncertainty in the literature-reported validation data. We applied the methods to fruits and vegetables (FV) intakes, cigarette smoking (confounder) and all-cause mortality data from the European Prospective Investigation into Cancer and Nutrition study.ResultsUsing the proposed method resulted in about four times increase in the strength of association between FV intake and mortality. For weakly correlated errors, measurement error in the confounder minimally affected the hazard ratio estimate for FV intake. The effect was more pronounced for strong error correlations.ConclusionsThe proposed method permits sensitivity analysis on measurement error structures and accounts for uncertainties in the reported validity coefficients. The method is useful in assessing the direction and quantifying the magnitude of bias in the association due to measurement errors in the confounders.