916 resultados para Logistic regression mixture models


Relevância:

100.00% 100.00%

Publicador:

Resumo:

The ratio of cystatin C (cysC) to creatinine (crea) is regarded as a marker of glomerular filtration quality associated with cardiovascular morbidities. We sought to determine reference intervals for serum cysC-crea ratio in seniors. Furthermore, we sought to determine whether other low-molecular weight molecules exhibit a similar behavior in individuals with altered glomerular filtration quality. Finally, we investigated associations with adverse outcomes. A total of 1382 subjectively healthy Swiss volunteers aged 60 years or older were enrolled in the study. Reference intervals were calculated according to Clinical & Laboratory Standards Institute (CLSI) guideline EP28-A3c. After a baseline exam, a 4-year follow-up survey recorded information about overall morbidity and mortality. The cysC-crea ratio (mean 0.0124 ± 0.0026 mg/μmol) was significantly higher in women and increased progressively with age. Other associated factors were hemoglobin A1c, mean arterial pressure, and C-reactive protein (P < 0.05 for all). Participants exhibiting shrunken pore syndrome had significantly higher ratios of 3.5-66.5 kDa molecules (brain natriuretic peptide, parathyroid hormone, β2-microglobulin, cystatin C, retinol-binding protein, thyroid-stimulating hormone, α1-acid glycoprotein, lipase, amylase, prealbumin, and albumin) and creatinine. There was no such difference in the ratios of very low-molecular weight molecules (urea, uric acid) to creatinine or in the ratios of molecules larger than 66.5 kDa (transferrin, haptoglobin) to creatinine. The cysC-crea ratio was significantly predictive of mortality and subjective overall morbidity at follow-up in logistic regression models adjusting for several factors. The cysC-crea ratio exhibits age- and sex-specific reference intervals in seniors. In conclusion, the cysC-crea ratio may indicate the relative retention of biologically active low-molecular weight compounds and can independently predict the risk for overall mortality and morbidity in the elderly.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

BACKGROUND & AIMS The interaction of KIR with their HLA ligands drives the activation and inhibition of natural killer (NK) cells. NK cells could be implicated in the development of liver fibrosis in chronic hepatitis C. METHODS We analysed 206 non-transplanted and 53 liver transplanted patients, selected according to their Metavir fibrosis stage. Several variables such as the number of activator KIR or the HLA ligands were considered in multinomial and logistic regression models. Possible confounding variables were also investigated. RESULTS The KIRs were not significant predictors of the fibrosis stage. Conversely, a significant reduction of the HLA-C1C2 genotype was observed in the most advanced fibrosis stage group (F4) in both cohorts. Furthermore, the progression rate of fibrosis was almost 10 times faster in the subgroup of patients after liver transplantation and HLA-C1C2 was significantly reduced in this cohort compared to non-transplanted patients. CONCLUSION This study suggests a possible role of KIR and their ligands in the development of liver damage. The absence of C1 and C2 ligands heterozygosity could lead to less inhibition of NK cells and a quicker progression to a high level of fibrosis in patients infected by HCV, especially following liver transplantation. This article is protected by copyright. All rights reserved.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Berufsorientierte Bildungssysteme sind auf die Vermittlung von spezialisierten beruflichen Qualifikationen ausgelegt. Werden diese nach Abschluss einer beruflichen Grundbildung auf dem Arbeitsmarkt wenig nachgefragt, riskieren die Absolventen, die erworbenen berufsspezifischen Qualifikationen nicht verwerten zu können. Dies trifft nicht nur zu, wenn Arbeitsmarkteinsteiger arbeitslos werden, sondern auch, wenn sie den Beruf wechseln müssen. Für die drei verschiedenen Optionen des Arbeitsmarkteinstiegs – Arbeit im erlernten Beruf, Berufswechsel und Arbeitslosigkeit – wird erstens untersucht, welche Bedeutung das individuell passende und das fachfremde Stellenangebot hat. Zweitens wird analysiert, wie eine unterschiedlich ausgeprägte Nachfrage nach fachspezifischen Qualifikationen die Bedeutung ausbildungsbezogener und individueller Merkmale für den Berufseinstieg verändert. Die Schweiz mit ihrem berufsorientierten Bildungssystem und berufsfachlich segmentieren Arbeitsmarkt dient als empirische Referenz. Die multinominalen logistischen Regressionsmodelle basieren auf den Daten des Schweizer Jugendpanels PISA2000/TREE. Die Individualdaten von Lehrabgänger werden auf Berufsebene, zeitpunkt- und regionsspezifisch mit dem individuell passenden und fachfremden Stellenangebot verknüpft, das auf den Stelleninseratendaten des Stellenmarktmonitors Schweiz (SMM) beruht. Dank dieser Verknüpfung von Angebot und Nachfrage nach beruflichen Qualifikationen auf der Mikroebene kann zum ersten Mal die grundlegende Bedeutung der Personalnachfrage für den Berufseinstieg nachgewiesen werden.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Little is known about the aetiology of childhood brain tumours. We investigated anthropometric factors (birth weight, length, maternal age), birth characteristics (e.g. vacuum extraction, preterm delivery, birth order) and exposures during pregnancy (e.g. maternal: smoking, working, dietary supplement intake) in relation to risk of brain tumour diagnosis among 7-19 year olds. The multinational case-control study in Denmark, Sweden, Norway and Switzerland (CEFALO) included interviews with 352 (participation rate=83.2%) eligible cases and 646 (71.1%) population-based controls. Interview data were complemented with data from birth registries and validated by assessing agreement (Cohen's Kappa). We used conditional logistic regression models matched on age, sex and geographical region (adjusted for maternal age and parental education) to explore associations between birth factors and childhood brain tumour risk. Agreement between interview and birth registry data ranged from moderate (Kappa=0.54; worked during pregnancy) to almost perfect (Kappa=0.98; birth weight). Neither anthropogenic factors nor birth characteristics were associated with childhood brain tumour risk. Maternal vitamin intake during pregnancy was indicative of a protective effect (OR 0.75, 95%-CI: 0.56-1.01). No association was seen for maternal smoking during pregnancy or working during pregnancy. We found little evidence that the considered birth factors were related to brain tumour risk among children and adolescents.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The purpose of this study is to investigate the effects of predictor variable correlations and patterns of missingness with dichotomous and/or continuous data in small samples when missing data is multiply imputed. Missing data of predictor variables is multiply imputed under three different multivariate models: the multivariate normal model for continuous data, the multinomial model for dichotomous data and the general location model for mixed dichotomous and continuous data. Subsequent to the multiple imputation process, Type I error rates of the regression coefficients obtained with logistic regression analysis are estimated under various conditions of correlation structure, sample size, type of data and patterns of missing data. The distributional properties of average mean, variance and correlations among the predictor variables are assessed after the multiple imputation process. ^ For continuous predictor data under the multivariate normal model, Type I error rates are generally within the nominal values with samples of size n = 100. Smaller samples of size n = 50 resulted in more conservative estimates (i.e., lower than the nominal value). Correlation and variance estimates of the original data are retained after multiple imputation with less than 50% missing continuous predictor data. For dichotomous predictor data under the multinomial model, Type I error rates are generally conservative, which in part is due to the sparseness of the data. The correlation structure for the predictor variables is not well retained on multiply-imputed data from small samples with more than 50% missing data with this model. For mixed continuous and dichotomous predictor data, the results are similar to those found under the multivariate normal model for continuous data and under the multinomial model for dichotomous data. With all data types, a fully-observed variable included with variables subject to missingness in the multiple imputation process and subsequent statistical analysis provided liberal (larger than nominal values) Type I error rates under a specific pattern of missing data. It is suggested that future studies focus on the effects of multiple imputation in multivariate settings with more realistic data characteristics and a variety of multivariate analyses, assessing both Type I error and power. ^

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The purpose of this study was to determine whether depression is a factor in explaining the difference in sex behaviors among adolescents with different ethnic backgrounds, family and school contexts. We hypothesize that adolescents with a higher number of depressive symptoms are more likely to engage in sexual risk behaviors than adolescents with fewer depressive symptoms. Further, adolescent depression and sexual behaviors are mediated or moderated by individual characteristics, family and school contexts. ^ Background. large ethnic disparities exist in adolescent engagement in risky sexual behaviors, yet, there is little in the literature that explains these disparities. Studies of sexual behavior of youths abound; yet, there is little literature on the prevalence and correlates of depression or the association between depression and sexual behaviors among different ethnic groups. Objectives. (1) To determine ethnic differences in the prevalence of depressive symptoms using data collected through the National Longitudinal Study of Adolescent Health (Add Health). (2) To determine predictors of sex risk behaviors among adolescents, including the role of depression. (3) To identify predictors of depression among these adolescents. Methods. Add Health data from wave 1 and wave 2 interviews of 7th–12th graders were analyzed using multivariate models constructed with both depression and sexual behavior as outcome variables. Logistic regression models determined whether and to what extent the independent variables, including depression, sex behaviors, demographic factors, individual and family characteristics, and school context were related to the probability of engaging in risky sexual behaviors. Results. Ethnic differences in depressive symptoms did not persist after demographic and contextual variables were included in the model. Sex behaviors all shared the hypothesized relationship with depressive symptoms. The odds of risky sex behaviors increased as number of depressive symptoms increased. Depression was predicted by marijuana use and having a serious argument with father for males at Wave 1 and by age and future orientation for females. Wave 2 depression was predicted by Wave 1 depression. ^

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Obesity is a complex multifactorial disease and is a public health priority. Perilipin coats the surface of lipid droplets in adipocytes and is believed to stabilize these lipid bodies by protecting triglyceride from early lipolysis. This research project evaluated the association between genetic variation within the human perilipin (PLIN) gene and obesity-related quantitative traits and disease-related phenotypes in Non-Hispanic White (NHW) and African American (AA) participants from the Atherosclerosis Risk in Communities (ARIC) Study. ^ Multivariate linear regression, multivariate logistic regression, and Cox proportional hazards models evaluated the association between single gene variants (rs2304794, rs894160, rs8179071, and rs2304795) and multilocus variation (rs894160 and rs2304795) within the PLIN gene and both obesity-related quantitative traits (body weight, body mass index [BMI], waist girth, waist-to-hip ratio [WHR], estimated percent body fat, and plasma total triglycerides) and disease-related phenotypes (prevalent obesity, metabolic syndrome [MetS], prevalent coronary heart disease [CHD], and incident CHD). Single variant analyses were stratified by race and gender within race while multilocus analyses were stratified by race. ^ Single variant analyses revealed that rs2304794 and rs894160 were significantly related to plasma triglyceride levels in all NHWs and NHW women. Among AA women, variant rs8179071 was associated with triglyceride levels and rs2304794 was associated with risk-raising waist circumference (>0.8 in women). The multilocus effects of variants rs894160 and rs2304795 were significantly associated with body weight, waist girth, WHR, estimated percent body fat, class II obesity (BMI ≥ 35 kg/m2), class III obesity (BMI ≥ 35 kg/m2), and risk-raising WHR (>0.9 in men and >0.8 in women) in AAs. Variant rs2304795 was significantly related to prevalent MetS among AA males and prevalent CHD in NHW women; multilocus effects of the PLIN gene were associated with prevalent CHD among NHWs. Rs2304794 was associated with incident CHD in the absence of the MetS among AAs. These findings support the hypothesis that variation within the PLIN gene influences obesity-related traits and disease-related phenotypes. ^ Understanding these effects of the PLIN genotype on the development of obesity can potentially lead to tailored health promotion interventions that are more effective. ^

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Coronary artery bypass graft (CABG) surgery is among the most common operations performed in the United States and accounts for more resources expended in cardiovascular medicine than any other single procedure. CABG surgery patients initially recover in the Cardiovascular Intensive Care Unit (CVICU). The post-procedure CVICU length of stay (LOS) goal is two days or less. A longer ICU LOS is associated with a prolonged hospital LOS, poor health outcomes, greater use of limited resources, and increased medical costs. ^ Research has shown that experienced clinicians can predict LOS no better than chance. Current CABG surgery LOS risk models differ greatly in generalizability and ease of use in the clinical setting. A predictive model that identified modifiable pre- and intra-operative risk factors for CVICU LOS greater than two days could have major public health implications as modification of these identified factors could decrease CVICU LOS and potentially minimize morbidity and mortality, optimize use of limited health care resources, and decrease medical costs. ^ The primary aim of this study was to identify modifiable pre-and intra-operative predictors of CVICU LOS greater than two days for CABG surgery patients with cardiopulmonary bypass (CPB). A secondary aim was to build a probability equation for CVICU LOS greater than two days. Data were extracted from 416 medical records of CABG surgery patients with CPB, 50 to 80 years of age, recovered in the CVICU of a large teaching, referral hospital in southeastern Texas, during the calendar year 2004 and the first quarter of 2005. Exclusion criteria included Diagnosis Related Group (DRG) 106, CABG surgery without CPB, CABG surgery with other procedures, and operative deaths. The data were analyzed using multivariate logistic regression for an alpha=0.05, power=0.80, and correlation=0.26. ^ This study found age, history of peripheral arterial disease, and total operative time equal to and greater than four hours to be independent predictors of CVICU LOS greater than two days. The probability of CVICU LOS greater than two days can be calculated by the following equation: -2.872941 +.0323081 (age in years) + .8177223 (history of peripheral arterial disease) + .70379 (operative time). ^

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Breast cancer is the most common cancer in women in the United States and is a leading cause of cancer-related deaths (1). Recently, dietary heterocyclic amines (HCAs) have been proposed to be a risk factor for breast cancer (2). This study uses the data collected for a case-control study conducted at the M.D. Anderson Cancer Center to assess the association between breast cancer risk and HCAs {2-amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo [4,5-f] quinoxaline (DiMeIQx) and mutagenicity of HCAs} and to examine if this association is modified by genetic polymorphisms of N-acetyl transferases (NAT1/NAT2). The NAT1/2 genotype was determined using Taqman technology. HCAs were estimated by using a meat preparation questionnaire on meat type, cooking method, and doneness, combined with a quantitative HCA database. Three hundred and fifty patients with breast cancer attending the Diagnostic Radiology Clinic at M. D. Anderson Cancer Center and fulfilling the eligibility criteria were compared to three hundred and fifty patients attending the same clinic for benign breast lesions to answer these questions. Logistic regression models were used to control for known risk factors and showed no statistically significant association between breast cancer versus benign breast cancer lesions and dietary intake of heterocyclic amines. There was no clear difference in their effect after subgroup analyses in different acetylator strata of NAT1/2 and no statistical interactions were found between NAT1/2 genotypes and HCAs, suggesting no effect modification by NAT1/2 acetylator status. These results suggest the need for further research to analyze if these null associations were because of the benign breast lesions sharing the risk factors with breast cancer or any other factors which haven't been explored yet.^

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Purpose. To determine if self-efficacy (SE) changes predicted total fat (TF) and total fiber (TFB) intake and the relationship between SE changes and the two dietary outcomes. ^ Design. This is a secondary analysis, utilizing baseline and first follow up (FFU) data from the NULIFE, a randomized trial. ^ Setting. Nutrition classes were taught in the Texas Medical Center in Houston, Texas. ^ Participants. 79 pre-menopausal, 25--45 year old African American women with an 85% response rate at FFU. ^ Method. Dietary intake was assessed with the Arizona Food Frequency Questionnaire and SE with the Self Efficacy for Dietary Change Questionnaire. Analysis was done using Stata version 9. Linear and logistic regression was used with adjustment for confounders. ^ Results. Linear regression analyses showed that SE changes for eating fruits and vegetables predicted total fiber intake in the control group for both the univariate (P = 0.001) and multivariate (P = 0.01) models while SE for eating fruits and vegetables at first follow-up predicted total fiber intake in the intervention for both models (P = 0.000). Logistic regression analyses of low fat SE changes and 30% or less for total fat intake, showed an adjusted OR of 0.22 (95% CI = 0.03, 1.48; P = 0.12) in the intervention group. The logistic regression analyses of SE changes in fruits and vegetables and 10g or more for total fiber intake, showed an adjusted OR of 6.25 (95% CI = 0.53, 72.78; P = 0.14) in the control group. ^ Conclusion. SE for eating fruits and vegetables at first follow-up predicted intervention groups' TFB intake and intervention women that increased their SE for eating a low fat diet were more likely to achieve the study goal of 30% or less calories from TF. SE changes for eating fruits and vegetables predicted the control's TFB intake and control women that increased their SE for eating fruits and vegetables were more likely to achieve the study goal of 10 g or more from TFB. Limitations are use of self-report measures, small sample size, and possible control group contamination.^

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Background. Lack of coverage, lack of access, and failure to utilize health care services have all been linked to dismal health outcomes in the US. Such consequences have been a longstanding challenge that US minorities are faced with, in the context of a health care system believed to be lacking efficiency and equity. National population surveys in the US suggest that the number of uninsured approaches 50 millions, while some concerns and suspicions are raised by opponents to the growing number of foreign born US residents, many of whom are Hispanic. Research shows that race is a significant predictor of lack of coverage, access, and utilization, while age, gender, education, and income are also linked to these outcomes. We investigated the potential effect of immigration status or duration in the US on the association between coverage, access, use, and race. Methods. Using National Health Interview Survey (NHIS) data of 2006, we selected 22, 667 individuals of Non-Hispanic Black, Hispanic, and Non-Hispanic White descent, at least 18 years of age, US-born and foreign-born who reported their duration of residence in the US. Through complex sample survey logistic regression analysis, we computed odds ratios, beta coefficients, and 95% confidence intervals using models which excluded then included immigration status. Results. Although a significant predictor of the outcomes, immigration status did not change the relationship between each of the dependent variables (coverage, access, utilization), and the factor race, while adjusting for age, gender, education, and income. Our results show that Hispanics were least likely to have coverage (OR=.58; 95% CI[.49, .68]), access (OR=.62; 95% CI[.50, .76]), and to utilize services (OR=.60; 95% CI[.46, .79]) followed by Non-Hispanic Blacks, and Non-Hispanic Whites. These results were not changed by stratification, or the inclusion of interaction terms to eliminate the potential effect of relationships between independent variables. Recent immigrants (<5 years in US) were 0.12 times less likely to be insured, but also 0.26 times less likely to utilize services (p<0.001), and in addition they represented only 7.3% of the uninsured and 1.9% of the US population in 2006. Furthermore, 12% of the Non-Hispanic White population in the US was not covered, and 65% of the uninsured individuals were US-Born Citizens. Other predictors of lack of coverage, access and use were age below 45, male gender, education at high school or below, and income of less than $20,000. Conclusion. This investigation shows that the high percentage of uninsured was not directly caused by Hispanics, and immigration status alone could not explain racial differences in coverage, access, and utilization. An immigration reform may not be the solution to the healthcare crisis, and more specifically, will not stop the increase in the number of uninsured in the US, nor reduce the cost of health care. As a better alternative, universal health insu rance coverage should be considered, when aiming to eliminate racial disparities, and to solve the health care crisis. ^ Keywords. health insurance, coverage, access, utilization, race, immigration, disparities.^

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Objectives. The purpose of this thesis is to understand the underlying socioeconomic characteristics affecting dental insurance coverage, yearly dental visits, and factors related to visiting a dentist in Mexico among border region residents. Methods. Using data from the Border Epidemiological Study of Aging, dental utilization in the previous 12 months, dental visits to Mexico, and dental insurance (proxy) were calculated utilizing logistic regression. Three different models were utilized for the dependent variables adjusting for diverse socioeconomic characteristics such as gender, age, marital status, income, education, years of residence in the United States (for immigrants), English proficiency, general health status, employment and dental insurance. Results. After adjustment, diverse variables were significant for the three different models calculated. Conclusion. Although the Mexican health market constitutes a viable option for dental services for border residents, dental insurance and dental yearly visits were lower in this region when compared to national averages. ^

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Introduction. Cervical cancer is the most common and lethal cancer among Mexican women. A nationwide cervical cancer screening program established in 1974 has had little impact on cervical cancer incidence or mortality rates. This case-control study was designed to determine the association between knowledge factors and structural, organizational, and sociocultural perceptions related to adherence to cervical cancer screening guidelines among women living and working in Monterrey, Mexico.^ Methods. Cases were defined as sexually active female store clerks ages 18-64 who do not adhere to cervical cancer screening guidelines in accordance with the Official Mexican Standard (Norma Oficial Mexicana, NOM 014-SSA2-1994). Controls were defined as sexually active female store clerks ages 18-64 who do adhere to cervical cancer screening guidelines in accordance with the NOM. Participants (N = 229) answered survey questions regarding cervical cancer screening practices as well as their knowledge and perceptions about screening for cervical cancer. Two multivariate logistic regression models were built to analyze (1) knowledge factors and (2) perceptions significantly associated with adherence in univariate analysis.^ Results. Having no or inaccurate knowledge of national cervical cancer screening guidelines (OR = 11.05, 95%CI: 4.28, 28.54) and no knowledge of the utility of the Papanicolaou (Pap) exam (OR = 6.77, 95%CI: 0.99, 46.43) were risk factors for non-adherence to cervical cancer screening guidelines. Perceptions of fear or embarrassment of the Pap exam (OR = 16.17, 95%CI: 5.08, 51.49) and lower levels of spousal or partner acceptance of the Pap exam (OR = 5.82, 95%CI: 1.34, 25.31) were risk factors for non-adherence to cervical cancer screening guidelines.^ Conclusion. Knowledge factors and sociocultural perceptions related to cervical cancer screening were strong predictors of adherence to screening guidelines. Future studies may be able to further explore these findings with larger sample sizes and in other populations in Mexico. By identifying these factors, future population-specific recommendations and interventions to increase screening rates can be formulated with the long-term goal of reducing morbidity and mortality from cervical cancer among Mexican women.^

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Background. The purpose of this study was to describe the risk factors and demographics of persons with salmonellosis and shigellosis and to investigate both seasonal and spatial variations in the occurrence of these infections in Texas from 2000 to 2004, utilizing time series analyses and the geographic information system digital mapping methods. ^ Methods. Spatial Analysis: MapInfo software was used to map the distribution of age-adjusted rates of reported shigellosis and salmonellosis in Texas from 2000–2004 by zip codes. Census data on above or below poverty level, household income, highest level of educational attainment, race, ethnicity, and urban/rural community status was obtained from the 2000 Decennial Census for each zip code. The zip codes with the upper 10% and lower 10% were compared using t-tests and logistic regression to determine whether there were any potential risk factors. ^ Temporal analysis. Seasonal patterns in the prevalence of infections in Texas from 2000 to 2003 were determined by performing time-series analysis on the numbers of cases of salmonellosis and shigellosis. A linear regression was also performed to assess for trends in the incidence of each disease, along with auto-correlation and multi-component cosinor analysis. ^ Results. Spatial analysis: Analysis by general linear model showed a significant association between infection rates and age, with young children aged less than 5 and those aged 5–9 years having increased risk of infection for both disease conditions. The data demonstrated that those populations with high percentages of people who attained a higher than high school education were less likely to be represented in zip codes with high rates of shigellosis. However, for salmonellosis, logistic regression models indicated that when compared to populations with high percentages of non-high school graduates, having a high school diploma or equivalent increased the odds of having a high rate of infection. ^ Temporal analysis. For shigellosis, multi-component cosinor analyses were used to determine the approximated cosine curve which represented a statistically significant representation of the time series data for all age groups by sex. The shigellosis results show 2 peaks, with a major peak occurring in June and a secondary peak appearing around October. Salmonellosis results showed a single peak and trough in all age groups with the peak occurring in August and the trough occurring in February. ^ Conclusion. The results from this study can be used by public health agencies to determine the timing of public health awareness programs and interventions in order to prevent salmonellosis and shigellosis from occurring. Because young children depend on adults for their meals, it is important to increase the awareness of day-care workers and new parents about modes of transmission and hygienic methods of food preparation and storage. ^

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Objectives. Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish (AJ) BRCA founder mutations, compared to sporadic ovarian cancer patients. The purpose of this study was to determine if this association exists in ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations. In addition, we sought to account for possible "survival bias" by minimizing any lead time that may exist between diagnosis and genetic testing. ^ Methods. Patients with stage III/IV ovarian, fallopian tube, or primary peritoneal cancer and a non-Ashkenazi Jewish BRCA1 or 2 mutation, seen for genetic testing January 1996-July 2007, were identified from genetics and institutional databases. Medical records were reviewed for clinical factors, including response to initial chemotherapy. Patients with sporadic (non-hereditary) ovarian, fallopian tube, or primary peritoneal cancer, without family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, year of diagnosis, and vital status at time interval to BRCA testing. When possible, 2 sporadic patients were matched to each BRCA patient. An additional group of unmatched, sporadic ovarian, fallopian tube and primary peritoneal cancer patients was included for a separate analysis. Progression-free (PFS) & overall survival (OS) were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were calculated for variables of interest. Matched pairs were treated as clusters. Stratified log rank test was used to calculate survival data for matched pairs using paired event times. Fisher's exact test, chi-square, and univariate logistic regression were also used for analysis. ^ Results. Forty five advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations, 86 sporadic-matched and 414 sporadic-unmatched patients were analyzed. Compared to the sporadic-matched and sporadic-unmatched ovarian cancer patients, non-AJ BRCA mutation carriers had longer PFS (17.9 & 13.8 mos. vs. 32.0 mos., HR 1.76 [95% CI 1.13–2.75] & 2.61 [95% CI 1.70–4.00]). In relation to the sporadic- unmatched patients, non-AJ BRCA patients had greater odds of complete response to initial chemotherapy (OR 2.25 [95% CI 1.17–5.41]) and improved OS (37.6 mos. vs. 101.4 mos., HR 2.64 [95% CI 1.49–4.67]). ^ Conclusions. This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations, confirming the previous studies in the Jewish population. Our efforts to account for "survival bias," by matching, will continue with collaborative studies. ^