Repeat emergency department visits by nursing home residents: a cohort study using health administrative data.

BACKGROUND: Nursing home (NH) residents are frequent users of emergency departments (ED) and while prior research suggests that repeat visits are common, there is little data describing this phenomenon. Our objectives were to describe repeat ED visits over one year, identify risk factors for repeat use, and characterize "frequent" ED visitors. METHODS: Using provincial administrative data from Ontario, Canada, we identified all NH residents 65 years or older who visited an ED at least once between January 1 and March 31, 2010 and then followed them for one year to capture all additional ED visits. Frequent ED visitors were defined as those who had 3 or more repeat ED visits. We used logistic regression to estimate risk factors for any repeat ED visit and for being a frequent visitor and Andersen-Gill regression to estimate risk factors for the rate of repeat ED visits. RESULTS: In a cohort of 25,653 residents (mean age 84.5 (SD = 7.5) years, 68.2% female), 48.8% had at least one repeat ED visit. Residents who experienced a repeat ED visit were generally similar to others but they tended to be slightly younger, have a higher proportion male, and a higher proportion with minimal cognitive or physical impairment. Risk factors for a repeat ED visit included: being male (adjusted odds ratio 1.27, (95% confidence interval 1.19-1.36)), diagnoses such as diabetes (AOR 1.28 (1.19-1.37)) and congestive heart failure (1.26 (1.16-1.37)), while severe cognitive impairment (AOR 0.92 (0.84-0.99)) and 5 or more chronic conditions (AOR 0.82 (0.71-0.95)) appeared protective. Eleven percent of residents were identified as frequent ED visitors, and they were more often younger then 75 years, male, and less likely to have Alzheimer's disease or other dementias than non-frequent visitors. CONCLUSIONS: Repeat ED visits were common among NH residents but a relatively small group accounted for the largest number of visits. Although there were few clear defining characteristics, our findings suggest that medically complex residents and younger residents without cognitive impairments are at risk for such outcomes.

Estimating and testing direct genetic effects in directed acyclic graphs using estimating equations.

In genetic association studies, it is important to distinguish direct and indirect genetic effects in order to build truly functional models. For this purpose, we consider a directed acyclic graph setting with genetic variants, primary and intermediate phenotypes, and confounding factors. In order to make valid statistical inference on direct genetic effects on the primary phenotype, it is necessary to consider all potential effects in the graph, and we propose to use the estimating equations method with robust Huber-White sandwich standard errors. We evaluate the proposed causal inference based on estimating equations (CIEE) method and compare it with traditional multiple regression methods, the structural equation modeling method, and sequential G-estimation methods through a simulation study for the analysis of (completely observed) quantitative traits and time-to-event traits subject to censoring as primary phenotypes. The results show that CIEE provides valid estimators and inference by successfully removing the effect of intermediate phenotypes from the primary phenotype and is robust against measured and unmeasured confounding of the indirect effect through observed factors. All other methods except the sequential G-estimation method for quantitative traits fail in some scenarios where their test statistics yield inflated type I errors. In the analysis of the Genetic Analysis Workshop 19 dataset, we estimate and test genetic effects on blood pressure accounting for intermediate gene expression phenotypes. The results show that CIEE can identify genetic variants that would be missed by traditional regression analyses. CIEE is computationally fast, widely applicable to different fields, and available as an R package.

Breast cancer detection among young survivors of pediatric Hodgkin lymphoma with screening magnetic resonance imaging.

BACKGROUND: Female survivors of pediatric Hodgkin lymphoma (HL) who have received chest radiotherapy are at increased risk of breast cancer. Guidelines for early breast cancer screening among these survivors are based on little data regarding clinical outcomes. This study reports outcomes of breast cancer screening with MRI and mammography (MMG) after childhood HL. METHODS: We evaluated the results of breast MRI and MMG screening among 96 female survivors of childhood HL treated with chest radiotherapy. Outcomes measured included imaging sensitivity and specificity, breast cancer characteristics, and incidence of additional imaging and breast biopsy. RESULTS: Median age at first screening was 30 years, and the median number of MRI screening rounds was 3. Ten breast cancers were detected in 9 women at a median age of 39 years (range, 24-43 years). Half were invasive and half were preinvasive. The median size of invasive tumors was 8 mm (range, 3-15 mm), and none had lymph node involvement. Sensitivity and specificity of the screening modalities were as follows: for MRI alone, 80% and 93.5%, respectively; MMG alone, 70% and 95%, respectively; both modalities combined, 100% and 88.6%, respectively. All invasive tumors were detected by MRI. Additional investigations were required in 52 patients, (54%), and 26 patients (27%) required breast biopsy, with 10 patients requiring more than 1 biopsy. CONCLUSIONS: Screening including breast MRI with MMG has high sensitivity and specificity in pediatric HL survivors, with breast cancers detected at an early stage, although it is associated with a substantial rate of additional investigations.

Anti-Müllerian hormone screening to assess ovarian reserve among female survivors of childhood cancer.

PURPOSE: Anti-Müllerian hormone (AMH) is an indicator of oocyte reserve in healthy females. The role of AMH testing in oncology remains investigational, although its sensitivity and stability over the menstrual cycle make it an attractive screening test for fertility assessment among female cancer survivors. We measured AMH level in survivors of childhood cancer and evaluated its association with treatment and patient factors. METHODS: Participants were adult female survivors of childhood malignancy treated with chemotherapy. Serum AMH was measured at a random day of the menstrual cycle. Multivariate analysis was used to evaluate the association between AMH level, alkylating agent exposure using the cyclophosphamide equivalent dose (CED), and other covariates. RESULTS: Sixty-six females with a median attained age of 23.3 years were eligible for analysis. Median AMH was 25.5 pM (range 0.5-108.0), at a median time of 11.5 years (range 1.4-25.1) since cancer diagnosis. Twenty-three patients (34.8%) had low AMH, including a significant proportion that reported normal menstrual cycles. Compared to ALL survivors, sarcoma survivors had significantly lower AMH levels. Among alkylating agents evaluated, procarbazine had the greatest adverse effect on AMH. In multivariate analysis, higher CED (p = 0.001), older age at diagnosis (p < 0.001), and use of oral contraceptive pills (p = 0.04) remained significantly associated with lower AMH. CONCLUSIONS: Random AMH can reveal evidence of oocyte depletion among female survivors reporting normal cycles, although low AMH should be interpreted cautiously among those taking oral contraception. Age at exposure and CED can aid identification of those more likely to have low AMH, although CED may underestimate the effect of procarbazine on oocyte reserve. IMPLICATIONS FOR CANCER SURVIVORS: Measurement of AMH can reveal apparent depletion of ovarian reserve in female childhood cancer survivors reporting normal menstrual cycles. Sarcoma survivors and those exposed to procarbazine may benefit from targeted AMH evaluation in an outpatient setting, and thereby allow appropriate fertility counseling before the onset of premature ovarian failure. The cyclophosphamide equivalent dose may facilitate comparison of the potential effect of different regimens on fertility.

A multi-institutional study of factors influencing the use of stereotactic radiosurgery for brain metastases.

PURPOSE: Stereotactic radiosurgery (SRS) for brain metastases is a relatively well-studied technology with established guidelines regarding patient selection, although its implementation is technically complex. We evaluated the extent to which local availability of SRS affected the treatment of patients with brain metastases. METHODS AND MATERIALS: We identified 3030 patients who received whole-brain radiation therapy (WBRT) for brain metastases in 1 of 7 cancer centers in Ontario. Clinical data were abstracted for a random sample of 973 patients. Logistic regression analyses were performed to identify factors associated with the use of SRS as a boost within 4 months following WBRT or at any time following WBRT. RESULTS: Of 898 patients eligible for analysis, SRS was provided to 70 (7.8%) patients at some time during the course of their disease and to 34 (3.8%) patients as a boost following WBRT. In multivariable analyses, factors significantly associated with the use of SRS boost following WBRT were fewer brain metastases (odds ratio [OR] = 6.50), controlled extracranial disease (OR = 3.49), age (OR = 0.97 per year of advancing age), and the presence of an on-site SRS program at the hospital where WBRT was given (OR = 12.34; all P values were <.05). Similarly, availability of on-site SRS was the factor most predictive of the use of SRS at any time following WBRT (OR = 5.98). Among patients with 1-3 brain metastases, good/fair performance status, and no evidence of active extracranial disease, SRS was provided to 40.3% of patients who received WBRT in a hospital that had an on-site SRS program vs 3.0% of patients who received WBRT at a hospital without SRS (P<.01). CONCLUSIONS: The availability of on-site SRS is the factor most strongly associated with the provision of this treatment to patients with brain metastases and appears to be more influential than accepted clinical eligibility factors.

Comparing the cohort design and the nested case-control design in the presence of both time-invariant and time-dependent treatment and competing risks: bias and precision.

PURPOSE: Observational studies using electronic administrative healthcare databases are often used to estimate the effects of treatments and exposures. Traditionally, a cohort design has been used to estimate these effects, but increasingly, studies are using a nested case-control (NCC) design. The relative statistical efficiency of these two designs has not been examined in detail. METHODS: We used Monte Carlo simulations to compare these two designs in terms of the bias and precision of effect estimates. We examined three different settings: (A) treatment occurred at baseline, and there was a single outcome of interest; (B) treatment was time varying, and there was a single outcome; and C treatment occurred at baseline, and there was a secondary event that competed with the primary event of interest. Comparisons were made of percentage bias, length of 95% confidence interval, and mean squared error (MSE) as a combined measure of bias and precision. RESULTS: In Setting A, bias was similar between designs, but the cohort design was more precise and had a lower MSE in all scenarios. In Settings B and C, the cohort design was more precise and had a lower MSE in all scenarios. In both Settings B and C, the NCC design tended to result in estimates with greater bias compared with the cohort design. CONCLUSIONS: We conclude that in a range of settings and scenarios, the cohort design is superior in terms of precision and MSE. Copyright © 2012 John Wiley & Sons, Ltd.