Yolanda Hagar

Interfraction motion of the vaginal apex during postoperative intensity modulated radiation therapy: are we missing the target?

Objective This study aimed to evaluate changes in vaginal cuff position and rectal distention during whole pelvic intensity modulated radiation therapy using daily image guidance for patients with gynecologic malignancies. Materials and Methods We reviewed 145 daily images from 5 patients treated with intensity modulated radiation therapy after total abdominal hysterectomy for endometrial or cervical cancer. A fiducial marker was placed in the vaginal cuff tissue before computed tomographic simulation. The 2008 ASTRO consensus guidelines for delineation of clinical target volumes were used to deliver 45 to 50 Gy to the target structures. Daily megavoltage computed tomographic images were reviewed and changes in position of the fiducial marker as compared to the initial planning scan were recorded in the anterior-posterior (AP), lateral, and superior-inferior dimensions. Changes in rectal distention were also recorded. The position of the fiducial marker relative to the planning target volumes was reviewed on each daily image. Results The average shifts of the gold seed in the AP, lateral, and superior-inferior dimensions were 7 mm (range, 0–28 mm), 3 mm (range, 0–7 mm), and 2.9 mm (range, 0–12 mm), respectively. Distention of the rectum ranged from 20.5 to 60.1 mm and correlated with movement of the gold seed in the AP dimension (R = 0.53). For 2 patients, the fiducial marker was within 5 mm of the planning target volume margin on 8/40 treatments, or outside the planning target volume on 4/40 treatments. This did not significantly impact total delivered dose to the planning target volume. Conclusions Daily image guidance confirms significant interfraction movement of the vaginal cuff tissue, which may exceed suggested guidelines for clinical target volume margins.

Survival analysis with electronic health record data: Experiments with chronic kidney disease

This article presents a detailed survival analysis for chronic kidney disease (CKD). The analysis is based on the electronic health record (EHR) data comprising almost two decades of clinical observations collected at New York-Presbyterian, a large hospital in New York City with one of the oldest electronic health records in the United States. Our survival analysis approach centers around Bayesian multiresolution hazard modeling, with an objective to capture the changing hazard of CKD over time, adjusted for patient clinical covariates and kidney-related laboratory tests. Special attention is paid to statistical issues common to all EHR data, such as cohort definition, missing data and censoring, variable selection, and potential for joint survival and longitudinal modeling, all of which are discussed alone and within the EHR CKD context.

Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana (REACCTING): study rationale and protocol

BackgroundCooking over open fires using solid fuels is both common practice throughout much of the world and widely recognized to contribute to human health, environmental, and social problems. The public health burden of household air pollution includes an estimated four million premature deaths each year. To be effective and generate useful insight into potential solutions, cookstove intervention studies must select cooking technologies that are appropriate for local socioeconomic conditions and cooking culture, and include interdisciplinary measurement strategies along a continuum of outcomes.Methods/DesignREACCTING (Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana) is an ongoing interdisciplinary randomized cookstove intervention study in the Kassena-Nankana District of Northern Ghana. The study tests two types of biomass burning stoves that have the potential to meet local cooking needs and represent different “rungs” in the cookstove technology ladder: a locally-made low-tech rocket stove and the imported, highly efficient Philips gasifier stove. Intervention households were randomized into four different groups, three of which received different combinations of two improved stoves, while the fourth group serves as a control for the duration of the study. Diverse measurements assess different points along the causal chain linking the intervention to final outcomes of interest. We assess stove use and cooking behavior, cooking emissions, household air pollution and personal exposure, health burden, and local to regional air quality. Integrated analysis and modeling will tackle a range of interdisciplinary science questions, including examining ambient exposures among the regional population, assessing how those exposures might change with different technologies and behaviors, and estimating the comparative impact of local behavior and technological changes versus regional climate variability and change on local air quality and health outcomes.DiscussionREACCTING is well-poised to generate useful data on the impact of a cookstove intervention on a wide range of outcomes. By comparing different technologies side by side and employing an interdisciplinary approach to study this issue from multiple perspectives, this study may help to inform future efforts to improve health and quality of life for populations currently relying on open fires for their cooking needs.

Hyperlactatemia Affects the Association of Hyperglycemia with Mortality in Nondiabetic Adults With Sepsis

BACKGROUND Admission hyperglycemia has been reported as a mortality risk factor for septic nondiabetic patients; however, hyperglycemias known association with hyperlactatemia was not addressed in these analyses. OBJECTIVES The objective was to determine whether the association of hyperglycemia with mortality remains significant when adjusted for concurrent hyperlactatemia. METHODS This was a post hoc, nested analysis of a retrospective cohort study performed at a single center. Providers had identified study subjects during their emergency department (ED) encounters; all data were collected from the electronic medical record (EMR). Nondiabetic adult ED patients hospitalized for suspected infection, two or more systemic inflammatory response syndrome (SIRS) criteria, and simultaneous lactate and glucose testing in the ED were enrolled. The setting was the ED of an urban teaching hospital from 2007 to 2009. To evaluate the association of hyperglycemia (glucose > 200 mg/dL) with hyperlactatemia (lactate ≥ 4.0 mmol/L), a logistic regression model was created. The outcome was a diagnosis of hyperlactatemia, and the primary variable of interest was hyperglycemia. A second model was created to determine if coexisting hyperlactatemia affects hyperglycemias association with mortality; the main outcome was 28-day mortality, and the primary risk variable was hyperglycemia with an interaction term for simultaneous hyperlactatemia. Both models were adjusted for demographics; comorbidities; presenting infectious source; and objective evidence of renal, respiratory, hematologic, or cardiovascular dysfunction. RESULTS A total of 1,236 ED patients were included, and the median age was 77 years (interquartile range [IQR] = 60 to 87 years). A total of 115 (9.3%) subjects were hyperglycemic, 162 (13%) were hyperlactatemic, and 214 (17%) died within 28 days of their initial ED visits. After adjustment, hyperglycemia was significantly associated with simultaneous hyperlactatemia (odds ratio [OR] = 4.14, 95% confidence interval [CI] = 2.65 to 6.45). Hyperglycemia and concurrent hyperlactatemia were associated with increased mortality risk (OR = 3.96, 95% CI = 2.01 to 7.79), but hyperglycemia in the absence of simultaneous hyperlactatemia was not (OR = 0.78, 95% CI = 0.39 to 1.57). CONCLUSIONS In this cohort of septic adult nondiabetic patients, mortality risk did not increase with hyperglycemia unless associated with simultaneous hyperlactatemia. The previously reported association of hyperglycemia with mortality in nondiabetic sepsis may be due to the association of hyperglycemia with hyperlactatemia.

Exposures to and origins of carbonaceous PM2.5 in a cookstove intervention in Northern Ghana

REACCTING (Research on Emissions Air Quality, Climate, and Cooking Technologies in Northern Ghana) was a 200-home cookstove intervention study from 2013 to 2015. Study households were divided into four groups: a control group, a group given two locally made rocket stoves, a group given two Philips forced draft stoves, and a group given a locally made rocket stove and a Philips stove. In a subset of study households, 48-hour PM2.5 exposure samples were collected for adults and children, as well as in the primary cooking area. Further, weekly ambient background PM2.5 samples were collected for the first nine months of the study. All PM2.5 samples were analyzed for elemental and organic carbon (EC/OC), and a subset was also analyzed for organics. Mixed effects modeling was applied to quantify differences in PM exposures between the groups and to assess relationships between exposures and cooking area measurements. Results showed that personal OC exposure for the intervention groups was 56.6% lower than the control group (p≤0.01). Both intervention groups given Philips stoves had significantly lower EC exposure than the control group (60.6% reduction, p≤0.02). Only weak relationships were found between personal and cooking area EC or OC. Source apportionment modeling was performed on both the personal/microenvironment and the ambient organics PM2.5 data sets to assess the sources of the observed PM. We identified six PM sources. The identified source factors were similar among the data sets, as well as with previous work in Navrongo. Two sources, one characterized by the presence of methoxyphenols, and one by the presence of polyaromatic hydrocarbons and EC, were associated with biomass burning, and accounted for a median of 9.2% of OC and 15.3% of EC personal exposure. Here, we demonstrate the utility of using the cooking-related source apportionment factors within a mixed effects model for more precise estimation of exposures due to cooking, rather than other combustion sources unrelated to the intervention.

Flexible modeling of the hazard rate and treatment effects in long-term survival studies

The effects of predictors on time to failure may be difficult to assess in cancer studies with longer follow-up, as the commonly used assumption of proportionality of hazards holding over an extended period is often questionable. Motivated by a long-term prostate cancer clinical trial, we contrast and compare four powerful methods for estimation of the hazard rate. These four methods allow for varying degrees of smoothness as well as covariates with effects that vary over time. We pay particular attention to an extended multiresolution hazard estimator, which is a flexible, semi-parametric, Bayesian method for joint estimation of predictor effects and the hazard rate. We compare the results of the extended multiresolution hazard model to three other commonly used, comparable models: Aalen’s additive model, Kooperberg’s hazard regression model, and an extended Cox model. Through simulations and the analysis of a large-scale randomized prostate cancer clinical trial, we use the different methods to examine patterns of biochemical failure and to estimate the time-varying effects of androgen deprivation therapy treatment and other covariates.