Stratified Odds Ratios Research Articles

Abstract A012: Motherhood and chemotherapy receipt: a population-based study of young women with breast cancer

Abstract Background: Young women, ages 18–39 years, with breast cancer are disproportionately impacted by pronounced socioeconomic disparities, a burden that is exacerbated among mothers as they face competing demands in managing cancer and caregiving responsibilities. Although previous analyses identified 64% of young women with breast cancer as mothers at diagnosis and qualitative studies have reported conflicting views on chemotherapy receipt among mothers, their treatment patterns are not well-defined. Additionally, whether having multiple or young children influences treatment patterns due to increased demands is also unknown. We aimed to determine the association between motherhood or offspring characteristics and chemotherapy receipt by age, stage, race and ethnicity. Methods: We retrospectively linked the Texas Cancer Registry to live birth certificates from 1995 to 2016. Analyses comprised a multicultural, population-based sample of 1,783 mothers who had delivered at least one live birth at diagnosis and 946 young women without children diagnosed with microscopically confirmed invasive breast cancer, between January 1, 2013, and December 31, 2016, at ages 18–39 years. Chemotherapy receipt was based on first course of treatment. Multivariable logistic regression estimated odds ratios (OR) with 95% confidence intervals (CI): model 1 (motherhood), model 2 (number of children), and model 3 (number of young [ages <13 years] children). Model 1 was adjusted for age, stage, insurance, Yost index, receipt of radiation therapy, and surgery type. Models 2 and 3 were adjusted for these covariates plus age of children, number of young children (model 2) and number of children (model 3). Heterogeneity was assessed using single- referent ORs and relative excess risk due to interaction (RERI), and multiplicative models with stratified ORs and likelihood ratio tests (pLRT). Results: Of the 2,729 women, 1,565 (73%) received chemotherapy. There was no association between motherhood (OR=1.00, 95% CI [0.82,1.21]), number of children (OR=0.94, 95% CI [0.72,1.22]), or number of young children (OR =1.07, 95% CI [0.72,1.54]) and chemotherapy receipt. Decreased odds for chemotherapy receipt were observed by race: Non-Hispanic (NH) Black women without children had an ORstratified of 0.57 (95% CI [0.37,0.89]) and NH White mothers had an ORsingle-referent of 0.71 (95% CI [0.51,0.93] and ORstratified of 0.69 (95% CI [0.53,0.95]) compared to NH White women without children (RERI=-0.63, 95% CI [-1.86,-0.09]; pLRT=0.05). Among mothers, those ages >35 years with 2+ young children had an OR of 0.45 (95% CI 0.21,0.98; pLRT=0.39) compared to those with children ages ≥13 years. Conclusion: We found no differences in overall chemotherapy receipt, but observed decreased receipt by race and age, independent of stage, possibly due to unmeasured systemic and clinical factors. Future studies examining detailed tumor characteristics and treatment information could inform targeted interventions to support young women with breast cancer throughout their cancer trajectories. Citation Format: Quiera S Booker, Caitlin C Murphy, Sarah E Messiah, Folefac D. Atem, Bijal S Balasubramanian. Motherhood and chemotherapy receipt: a population-based study of young women with breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A012.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial

Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10mm improvement in STS from baseline at week4. In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n=176) had significantly higher achievement of ≥10mm improvement in STS (35.8% [n=63] versus 17.7% [n=29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p=0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p<0.0001) at week 4 versus the vehicle group (n=164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference:-1.3 [2.20]; 95% CI:-5.64 to 2.99, p=0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Jixing Pharmaceutical Co. Ltd.

Abstract TP157: Utility of CT Angiography in Patients With Intracerebral Hemorrhage

Introduction: Patients with intracerebral hemorrhage (ICH) often undergo CT and CT angiography with the latter being done to identify vascular abnormalities for ICH etiology. It is unclear whether CTA yields are high enough to warrant routine use particularly for subcortical ICH, however. Methods: Retrospective chart review was done on the Loyola Stroke Database of ICH patients over the last 10 years. Data from CT, CTA (and other imaging modalities) regarding ICH size and location, as well as vascular abnormalities, were collected. Demographics, comorbidities, and clinical outcomes were also recorded. Frequencies and percentages are reported to describe overall sample and bivariate associations. Univariate logistic regression estimated unadjusted effects of ICH type, age, hypertension (HTN), and other predictors on the logit of vascular abnormalities. Chi square values are reported for overall interaction effects. Stratified odds ratios (OR) are reported with 95% confidence intervals and p-values. Multivariable binary logistic regression estimated adjusted effects of ICH type on the logit of vascular abnormalities, after adjusting for covariates; OR are reported for adjusted effects. Results: Of 744 ICH cases analyzed, 376 were subcortical (50.54%) and 368 cortical (49.46%). Eighty-one had vascular abnormalities (10.89%); 46 of those being lesion-related (6.18%). Unadjusted odds of lesion-related vascular abnormalities were higher for cortical versus subcortical ICH (OR: 7.04; 95% CI: 3.09, 16.04; p &lt; 0.01). Two-way interaction was non-significant for effects of ICH type and age (p = 0.76), ICH type and HTN (p = 0.68), age and hypertension (p = 0.09), and ICH type and ICH size (p = 0.93) on the logit of lesion-related vascular abnormalities. Thus, these effects did not co-vary significantly with respect to lesion-related vascular abnormalities. Odds of lesion-related vascular abnormalities are significantly higher for cortical versus subcortical ICH, after adjusting for age, HTN ICH size, and CTA (OR: 6.91; 95% CI: 2.93, 16.30; p &lt; 0.01). Conclusion: Our analysis suggests there is decreased utility for CTA in subcortical compared to cortical ICH and CTA should probably not be performed routinely on subcortical ICH.

177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study.

LBA588 Background: Currently, there is no universally accepted first line (1L) therapy for higher grade, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and an unmet medical need remains in these patients (pts). Radioligand therapy (RLT) is an innovative cancer treatment that crosses the traditional domains of systemic, radiation or surgical therapies. The Phase 3 NETTER-2 study (NCT03972488) evaluated [177Lu]Lu-DOTA-TATE (hereafter 177Lu-DOTATATE) as 1L treatment in pts with Grade (G) 2 and G3 advanced GEP-NETs. This is the first trial to assess 1L RLT in any solid tumor. Methods: Eligible pts were newly diagnosed with somatostatin receptor-positive high G2 or G3 (Ki-67 ≥10% and ≤55%) advanced GEP-NETs within the last 6 months prior to enrollment. Pts were randomized (2:1) to receive 4 cycles of 177Lu-DOTATATE (4 × 7.4 GBq) plus 30 mg octreotide long-acting release (LAR) at 8-weekly intervals during 177Lu-DOTATATE treatment then every 4 weeks (177Lu-DOTATATE arm), or 60 mg octreotide LAR every 4 weeks (control arm), stratified by grade (G2 vs G3) and tumor origin (pancreas vs other). The primary endpoint was progression-free survival (PFS), centrally assessed using RECIST 1.1. Objective response rate (ORR), a key secondary endpoint, was tested hierarchically after PFS. Results: Overall, 226 pts were randomized to the 177Lu-DOTATATE (n = 151) or control (n = 75) arms. Most tumors originated in the pancreas (54.4%) or small intestine (29.2%); G3 tumors were reported in 35.0% of pts. Median cumulative dose of 177Lu-DOTATATE was 29.2 GBq, with 87.8% of pts receiving all 4 doses. Median PFS (95% confidence interval [CI]) was significantly prolonged by ~14.3 months from 8.5 months (7.7, 13.8) in the control arm to 22.8 months (19.4, not estimable) in the 177Lu-DOTATATE arm; stratified hazard ratio 0.276 (95% CI: 0.182, 0.418; p &lt; 0.0001). The ORR was significantly higher in the 177Lu-DOTATATE arm (43.0%) vs the control arm (9.3%); stratified odds ratio 7.81 (95% CI: 3.32, 18.4; p &lt; 0.0001). PFS and ORR results were consistent across all pre-specified demographic and prognostic subgroups. Among adverse events of special interest to RLT, G3/4 leukopenia, anemia and thrombocytopenia occurred in ≤3 pts each in the 177Lu-DOTATATE arm. One case of myelodysplastic syndrome was reported (177Lu-DOTATATE arm). Conclusion: 177Lu-DOTATATE significantly prolonged PFS and demonstrated a clinically meaningful ORR, compared with high-dose octreotide LAR, in pts with newly diagnosed advanced G2 and G3 GEP-NETs. Safety was in line with the established profile of 177Lu-DOTATATE. This is the first randomized study to demonstrate efficacy of RLT as 1L treatment in any malignancy and will change clinical practice. Further investigations of RLT as a therapeutic option in other settings is warranted. Clinical trial information: NCT03972488 .

Intersectionality of demographic characteristics in self-reported anorexia nervosa, bulimia nervosa, and probable eating disorders among college students.

To investigate associations between identity intersectionality, with a primary focus on minority identity, and probable eating disorders (EDs) within the US college student population. Data consisting of n = 414,299 college students' responses to the American College Health Association's National College Health Assessment between fall 2015 and spring 2019 were utilized for this study. Overall and stratified adjusted odds ratios (aORs) were used to assess the association between different facets of identity (i.e., race/ethnicity, gender identity, and sexual orientation) and probable EDs. Among all, in our analytic sample, 7.15% reported a probable ED. Interactions between all three identity variables were significant, and thus stratified odds ratios were evaluated. Transgender men were significantly more likely to report probable ED than cisgender male peers within the following racial/ethnic groups: non-Hispanic White (aOR: 3.33; 95% CI: 2.79, 3.96; p < .0001), non-Hispanic Black (aOR: 3.29; 95% CI: 1.72, 6.28; p = .0003), Hispanic (aOR: 2.31; 95% CI: 1.55, 3.43; p < .0001), Asian or Pacific Islander (aOR: 2.19; 95% CI: 1.45, 3.30; p = .0002), Biracial or Multicultural (aOR: 3.36; 95% CI: 2.17, 5.22; p < .0001), and other (aOR: 4.19; 95% CI: 2.25, 7.79; p < .0001). This study underscores the importance of increasing our understanding of interactions between marginalized identities and the ways in which minority identity informs ED risk. The impact of multiple marginalized identities on ED outcomes is not well understood. Our study expands on previous ACHA-NCHA studies by addressing identity intersectionality, looking at more than one identity at a time (i.e., specifically race/ethnicity, gender identity, and sexual orientation). Our results contribute unique risk profiles for students who identify with multiple marginalized groups. Further, they indicate that that these associations vary based on the compounded effect of the demographic factors considered.

Stimulant use disorder diagnosis and opioid agonist treatment dispensation following release from prison: a cohort study

BackgroundConcurrent opioid and stimulant use is on the rise in North America. This increasing trend of use has been observed in the general population, and among people released from prison in British Columbia (BC), who face an elevated risk of overdose post-release. Opioid agonist treatment is an effective treatment for opioid use disorder and reduces risk of overdose mortality. In the context of rising concurrent stimulant use among people with opioid use disorder, this study aims to investigate the impact of stimulant use disorder on opioid agonist treatment dispensation following release from prison in BC.MethodsLinked health and corrections records were retrieved for releases between January 1st 2015 and December 29th 2018 (N = 13,380). Hospital and primary-care administrative health records were used to identify opioid and stimulant use disorder and mental illness. Age, sex, and health region were derived from BC’s Client Roster. Incarceration data were retrieved from provincial prison records. Opioid agonist treatment data was retrieved from BC’s provincial drug dispensation database. A generalized estimating equation produced estimates for the relationship of stimulant use disorder and opioid agonist treatment dispensation within two days post-release.ResultsCases of release among people with an opioid use disorder were identified (N = 13,380). Approximately 25% (N = 3,328) of releases ended in opioid agonist treatment dispensation within two days post-release. A statistically significant interaction of stimulant use disorder and mental illness was identified. Stratified odds ratios (ORs) found that in the presence of mental illness, stimulant use disorder was associated with lower odds of obtaining OAT [(OR) = 0.73, 95% confidence interval (CI) = 0.64–0.84)] while in the absence of mental illness, this relationship did not hold [OR = 0.89, 95% CI = 0.70–1.13].ConclusionsPeople with mental illness and stimulant use disorder diagnoses have a lower odds of being dispensed agonist treatment post-release compared to people with mental illness alone. There is a critical need to scale up and adapt opioid agonist treatment and ancillary harm reduction, and treatment services to reach people released from prison who have concurrent stimulant use disorder and mental illness diagnoses.

Determinants of Hardcore Smoking in a MULTI-ETHNIC Study of Cigarette Smokers in Singapore

ABSTRACT Smokers who are resistant to quitting are not well studied in Asia, particularly in multi-ethnic populations. We compared the characteristics of hardcore smokers in Singapore, a multi-ethnic Asian population, with other daily smokers, and investigated the role of ethnicity as an effect modifier on identified determinants, including cigarette flavor preferences, using cross-sectional data from Singapore Smokers’ Survey (n = 1,501). Multivariable logistic regression was used to assess the association. 22.8% of adult daily smokers were hardcore smokers. Novel findings on hardcore smokers’ preference for regular flavored cigarettes (AOR = 1.54; 95%CI: 1.14, 2.07) suggest there is room for interventions among hardcore smokers through regulation of cigarette flavors and nicotine content. Although ethnicity was not a significant factor, it was an effect modifier with peers’ disapproval of smoking (p-value for interaction = 0.024), significantly lowering odds of Malays being hardcore smokers (stratified odds ratio, AOR stratified, Malay = 0.35; CI: 0.17, 0.71), but not Chinese (AOR stratified, Chinese = 1.27; CI: 0.70, 2.42) and Indian smokers (AOR stratified, Indian = 0.62; CI: 0.18, 2.28), suggesting that smoking cessation policies utilizing social norm change strategies may be more effective when tailored to the differing roles of peer norms among different ethnic groups, in Singapore and other multi-ethnic Asian populations.

Abstract 15754: Coronary Calcification is Associated With Prior GnRH Agonist Therapy in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging

Background: Gonadotropin releasing hormone (GnRH) agonist therapy is associated with major adverse cardiovascular (CV) events in men with prostate cancer. The effect of GnRH agonists on vascular calcification is not known. Methods: Consecutive patients who underwent 18F-fluciclovine positron emission tomography (PET) /computed tomography (CT) at our institution for recurrent prostate cancer were retrospectively identified. Clinical and demographic data were obtained from the medical record. Patients without available data on prior prostate cancer therapies received were excluded (n=25). Coronary calcification was qualitatively assessed on non-gated CT scans using a published scoring system. The association of prior GnRH agonist therapy with coronary calcification was evaluated using stratified odds ratio (OR) analysis in a 2x2 contingency table. Results: Among 186 men included, median age was 69.0 years (IQR 64.3, 74.5) and CV comorbidities were common (72% hypertension, 68% hyperlipidemia, 43% current or former smoking, and 21% diabetes mellitus). 55 patients (30%) received prior hormone therapy, 50 of whom received a GnRH agonist either as single- or multi-agent therapy. Men with prior GnRH agonists were older than those without prior GnRH agonists (71.4 vs. 68.4 years, p=0.025). There were no significant differences in prevalence of CV comorbidities between the two groups. Men with at least mild coronary calcification were more likely to have received prior GnRH agonist therapy (OR=3.0, 95% CI 1.2-7.1, p=0.015 by Fisher’s exact test), with a stronger association seen in younger men (OR=3.9, age &lt;69 years) than in older men (OR=1.8, age ≥69). Conclusions: Coronary calcification is associated with prior GnRH agonist therapy in men with recurrent prostate cancer undergoing PET/CT imaging. The utility of vascular protective therapies including aspirin and statin to mitigate the adverse CV effects of GnRH agonists requires further study.

Outcomes According to ALK Status Determined by Central IHC or FISH in Patients with ALK-Positive NSCLC Enrolled in the Phase III ALEX Study.

We retrospectively examined progression-free survival (PFS) and response by ALK fluorescence in-situ hybridization (FISH) status in patients with advanced ALK immunohistochemistry (IHC)-positive non-small-cell lung cancer (NSCLC) in the ALEX study. 303 treatment-naïve patients were randomized to receive twice-daily alectinib 600 mg or crizotinib 250 mg. ALK status was assessed centrally using Ventana ALK (D5F3) CDx IHC and Vysis ALK Break Apart FISH Probe Kit. Primary endpoint: investigator-assessed PFS. Secondary endpoints of interest: objective response rate (ORR) and duration. Investigator-assessed PFS was significantly prolonged with alectinib versus crizotinib in ALK IHC-positive/FISH-positive tumors (n = 203, 67%) (HR 0.37, 95% CI: 0.25-0.56) and ALK IHC-positive/FISH-uninformative tumors (n = 61, 20%) (HR 0.39, 95% CI: 0.20-0.78), but not ALK IHC-positive/FISH-negative tumors (n = 39, 13%) (HR 1.33, 95% CI: 0.6-3.2). ORRs were higher with alectinib versus crizotinib in ALK IHC-positive/FISH-positive tumors 90.6% versus 81.4%; stratified odds ratio [OR] 2.22, 95% CI: 0.97-5.07) and ALK IHC-positive/FISH-uninformative tumors (96.0% versus 75.0%; OR 9.29, 95% CI: 1.05-81.88), but not ALK IHC-positive/FISH-negative tumors (28.6% versus 44.4%; OR 0.45, 95% CI: 0.12-1.74). Next-generation sequencing (NGS) was performed in 35/39 patients with ALK IHC-positive/FISH-negative tumors; no ALK fusion was identified in 20/35 (57.1%) patients by NGS, but 10/20 (50.0%) had partial response/stable disease. Outcomes of patients with ALK IHC-positive/FISH-positive and ALK IHC-positive/FISH-uninformative NSCLC were similar to the overall ALEX population. These results suggest that Ventana ALK IHC is a standard testing method for selecting patients for treatment with alectinib.

Higher Platelet-to-Lymphocyte Ratio Increased the Risk of Sarcopenia in the Community-Dwelling Older Adults

The platelet-to-lymphocyte ratio (PLR) has been extensively studied in oncologic diseases. However, the correlation between PLR and sarcopenia remains unknown. In this cross-sectional analysis, we enrolled 3,671 non-institutionalized individuals from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) aged ≥60 years and whose complete blood counts (CBCs), body composition measurements, and related demographic information was available. Skeletal muscle mass was assessed using a previously published equation (including age, sex, height, and bioelectrical impedance analysis). PLR values were estimated based on laboratory data. Multiple linear and logistic regression analyses, quartile-based stratified odds ratio comparisons, and trend tests were performed. Elevations in serum PLR values were significantly associated with sarcopenia status and negatively associated with skeletal muscle index. After additionally adjusting for other covariates, the significant negative correlation remained; moreover, participants with highest serum PLR values (≥155) had 2.36 times greater risk of sarcopenia than those with lowest PLR values (<90; odds ratio (OR) = 2.36; 95% confidence interval (CI): 1.21–3.31; p < 0.01). Higher PLR levels are associated with a greater risk of sarcopenia in geriatric populations. Thus, PLR as an inexpensive and easily measurable parameter can be considered as an inflammatory biomarker for sarcopenia.

The stratified win ratio

ABSTRACTThe win ratio was first proposed in 2012 by Pocock and his colleagues to analyze a composite endpoint while considering the clinical importance order and the relative timing of its components. It has attracted considerable attention since then, in applications as well as methodology. It is not uncommon that some clinical trials require a stratified analysis. In this article, we propose a stratified win ratio statistic in a similar way as the Mantel-Haenszel stratified odds ratio, derive a general form of its variance estimator with a plug-in of existing or potentially new variance/covariance estimators of the number of wins for the two treatment groups, and assess its statistical performance using simulation studies. Our simulations show that our proposed Mantel-Haenszel-type stratified win ratio performs similarly to the Mantel-Haenszel stratified odds ratio for the simplified situation when the win ratio reduces to the odds ratio, and our proposed stratified win ratio is preferred compared to the inverse-variance weighted win ratio and unweighted win ratio particularly when the data are sparse. We also formulate a homogeneity test following Cochran’s approach that assesses whether the stratum-specific win ratios are homogeneous across strata, as this method is used frequently in meta-analyses and a better test for the win ratio homogeneity is not available yet.

Being overweight or obese as a risk factor for acute liver injury secondary to acute acetaminophen overdose.

Increased incidences of hepatotoxicity have been observed in obese patients with acute acetaminophen overdose. We evaluate whether the status of being overweight or obese is associated with increase in the development of hepatotoxicity and acute liver injury (ALI) in patients with acute acetaminophen overdose. This was a retrospective cohort study comparing the risk of hepatotoxicity and ALI between overweight or obese patients (body mass index [BMI]≥25) and normal BMI patients (BMI≤24.9) presenting with acute acetaminophen overdose at Siriraj Hospital during January 2004 to June 2012. All patients were treated with intravenous N-acetylcysteine. Psi parameters were calculated. High psi was defined as psi of ≥5.0mM-hour. Data were analyzed using multinomial logistic regressions, odds ratio (OR), stratified OR, and 95% confidence interval (CI). There were 197 patients who fulfilled the criteria for analysis, 35 (17.8%) were obese, 24 (12.2%) were overweight, and 138 (70%) were normal BMI cases. Hepatotoxicity and ALI developed in 25 (12.7%) and 40 (20.3%) cases, respectively. Multinomial logistic regression revealed that the overweight-obesity status and log10 (psi value) were significant risk factors of ALI, with OR (95% CI) of 2.68 (1.21-5.95) and 1.74 (1.27-2.38), respectively, while only log10 (psi) was a significant risk factor of hepatotoxicity with OR (95% CI) 378.51 (39.49-3627.99). From stratification, overweight-obesity had significant odds ratios for ALI in strata with low acetaminophen concentration, early initiation of N-acetylcysteine and low psi. We conclude that being overweight or obese is an independent risk factor of ALI in acute acetaminophen overdoses.

Active trachoma and community use of sanitation, Ethiopia.

ObjectiveTo investigate, in Amhara, Ethiopia, the association between prevalence of active trachoma among children aged 1–9 years and community sanitation usage.MethodsBetween 2011 and 2014, prevalence of trachoma and household pit latrine usage were measured in five population-based cross-sectional surveys. Data on observed indicators of latrine use were aggregated into a measure of community sanitation usage calculated as the proportion of households with a latrine in use. All household members were examined for clinical signs, i.e. trachomatous inflammation, follicular and/or intense, indicative of active trachoma. Multilevel logistic regression was used to estimate prevalence odds ratios (OR) and 95% confidence intervals (CI), adjusting for community, household and individual factors, and to evaluate modification by household latrine use and water access.FindingsIn surveyed areas, prevalence of active trachoma among children was estimated to be 29% (95% CI: 28–30) and mean community sanitation usage was 47% (95% CI: 45–48). Despite significant modification (p < 0.0001), no pattern in stratified ORs was detected. Summarizing across strata, community sanitation usage values of 60 to < 80% and ≥ 80% were associated with lower prevalence odds of active trachoma, compared with community sanitation usage of < 20% (OR: 0.76; 95% CI: 0.57–1.03 and OR: 0.67; 95% CI: 0.48–0.95, respectively).ConclusionIn Amhara, Ethiopia, a negative correlation was observed between community sanitation usage and prevalence of active trachoma among children, highlighting the need for continued efforts to encourage higher levels of sanitation usage and to support sustained use throughout the community, not simply at the household level.

A Survey of Obstetric Healthcare Utilization in the Rural Western Indian Himalayas.

Objectives To determine the socio-economic factors affecting access to antepartum, intrapartum, and postpartum healthcare in the rural Western Indian Himalayas over the past 20years. Methods Face-to-face surveys were conducted with 197 women in Chamoli District, Uttarakhand from October 2011 to May 2012. Participants who gave birth within the past 20years were included in the final analysis (n=158). Stratified odds ratios and analysis of variance were calculated. Results Among women who delivered in the prior 7years, there was a nine-fold increase (95% CI 4-20.8) in institutionalized births compared to women who delivered 8-20years before the study. Among women who delivered 7years prior to the study, low income increased the risk of home delivery (OR 3.07, 95% CI 1.15-8.54). Low caste (OR 2.79, 95% CI 1.04-7.72) and low level of education (OR 3.93 95% CI 1.41-11.81) decreased the use of antepartum medications (vitamins and vaccines). Remote location among all participants was a risk factor for not seeking care for obstetric morbidities (OR 0.44 95% CI 0.2-0.95). Conclusions The incidence of institutionalized delivery has increased over the past decade in rural Uttarakhand. Income, caste, education, and remote location correlated with poor access to antepartum and intrapartum healthcare. These correlations have increased in statistical significance over the past 20years, except for location. This indicates that the Western Himalayas face similar challenges to obstetric service utilization as the north Indian plains and that several of these inequalities in healthcare access have become more pronounced in recent years.

Issue Highlights

Issue Highlights

Evaluating the Role of Birth Weight and Gestational Age on Acute Lymphoblastic Leukemia Risk Among Those of Hispanic Ethnicity

High birth weight is an established risk factor for childhood acute lymphoblastic leukemia (ALL), especially in children younger than 5 years of age at diagnosis. The goal of this study was to explore the association between being born large for gestational age and the risk for ALL by race/ethnicity to determine if the role of this risk factor differed by these characteristics. The authors compared birth certificate data of 575 children diagnosed with ALL who were younger than 5 years and included in the Texas Cancer Registry, Texas Department of Health, between the years 1995 and 2003 with 11,379 controls matched by birth year. Stratified odds ratios were calculated for risk of ALL by birth weight for gestational age, categorized in 3 groups, small, appropriate, and large for gestational age (SGA, AGA, and LGA, respectively), for each race/ethnicity group. The risk of developing ALL was higher among Hispanics who were LGA (odds ratio [OR] = 1.90, 95% confidence interval [CI]: 1.34–2.68) compared with LGA non-Hispanic whites (OR = 1.27, 95% CI: 0.87–1.86) after adjusting for infant gender, year of birth, maternal age, birth order, and presence of Down syndrome. However, the difference was not statistically significant. These results suggest that there may be differences in the association between higher growth in utero and risk of childhood ALL among Hispanics versus non-Hispanic whites.

Increased prevalence of comorbid conditions in women with uterine cancer

ObjectivesTo compare comorbidities of women with uterine cancer (UC) to controls so as to aid in development of survivorship care plans and programs. MethodsRetrospective cohort study using the University HealthSystem Consortium (UHC) database that compared women who had a hysterectomy for UC to women without UC undergoing hysterectomy. Frequencies and odds ratios (ORs) of 26 comorbidities were calculated. Mantel–Haenszel stratified ORs were determined to correct for different age distributions between the UC and control groups using UHC predetermined age groups. Results23,227 patients in the dataset were included in the UC cohort, and 142,601 patients served as controls. Uncorrected ORs≥2 were found for hypertension, diabetes, obesity, congestive heart failure, pulmonary circulatory diseases, peripheral vascular disease, and renal failure. Higher ORs for UC remained significant after stratification by age for hypertension (OR=1.7), diabetes (OR=2.1), obesity (OR=3.3), congestive heart failure (OR=1.5), pulmonary circulatory disorders (OR=1.7), and renal failure (OR=1.2). ConclusionsMultiple comorbid conditions, specifically those related to the metabolic syndrome, were more prevalent in UC survivors than in the general population, and this difference persisted after adjustment for age. UC survivorship programs should plan to allocate resources to account for these differences in healthcare needs.

Talactoferrin alfa versus placebo in patients with refractory advanced non-small-cell lung cancer (FORTIS-M trial)

BackgroundTalactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methodsAn FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). ResultsSeven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. ConclusionsThere was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast cancer risk by estrogen/progesterone receptor status

Genetic polymorphisms of fibroblast growth factor receptor 2 (FGFR2) have been demonstrated to be associated with breast cancer risk, presumably through elevation of FGFR2 expression. Fibroblast growth factor 1 (FGF1) and RNA binding protein fox-1 homolog 2 (RBFOX2), which are functionally related to FGFR2, may also associate with breast cancer risk. We investigated the associations between breast cancer risk and the polymorphisms of FGFR2 rs2981582, FGF1 rs250108, and RBFOX2 rs2051579 among 839 incident breast cancer cases and 863 age-matched controls in the Guangzhou Breast Cancer Study. Stratified odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by estrogen receptor (ER)/progesterone receptor (PR) status using multivariate logistic regression. FGFR2 rs2981582 was confirmed to be significantly associated with the risk of ER-positive but not ER-negative breast cancer. In contrast, FGF1 rs250108 was significantly associated with the risk of ER-negative breast cancer (OR (95% CI) = 1.68 (1.20-2.35) for CT + TT vs. CC genotype) but not ER-positive breast cancer. CA + AA genotypes at RBFOX2 rs2051579 were associated with a reduced risk of ER-negative (0.71 (0.52-0.97)) but not ER-positive breast cancer compared to the CC genotype. Similar results were observed when differentiating breast cancer cases by PR status. Neither of the pairs between the three SNPs had a significant interaction on breast cancer risk. Our findings show a suggestively stronger association between FGFR2 rs2981582 and ER-positive breast cancer risk and suggest a greater association of FGF1 rs250108 and RBFOX2 rs2051579 with ER-negative compared to ER-positive breast cancer.

Associations between serum total bilirubin levels and functional dependence in the elderly

Many studies support the role of bilirubin as a cytoprotector in chronic inflammatory diseases, such as stroke and atherosclerosis. To investigate the relationship between serum total bilirubin levels and functional dependence in older adults. Data from the National Health and Nutrition Examination Survey (1999-2002) pertaining to 2235 old adults were analysed. All participants had given a household interview, providing information of five major domains on self-reported functional status (activities of daily living, instrumental activities of daily living, leisure and social activities, lower extremity mobility and general physical activities), had completed serum total bilirubin measurement, and a questionnaire regarding personal health. Poor performance was defined as experiencing difficulty with one or more items in a given domain. Functional dependence was defined as having three or more poor performances in the five major domains. Multiple logistic regression was performed together with quartile-based stratified odds ratio (OR) comparison and trend tests. The OR of functional dependence for each standard deviation increment in the serum total bilirubin level was 0.56 (P = 0.002). After additional adjustment, the inverse association remained essentially unchanged. In quartile-based analysis, participants with higher quartiles of serum total bilirubin tended to have lower ORs of functional dependence. The trends of lower likelihood of functional dependence across increasing quartiles of the serum total bilirubin level were statistically significant (P < 0.05 for all trends). Higher serum total bilirubin levels were associated with lower likelihood of functional dependence in older adults.