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Age, cardiovascular risk factors and coronary heart disease as determinants of platelet function in men. A multivariate approach.

Older age, the cardiovascular risk factors and arteriosclerosis have been reported to be associated with stimulated platelet function. To evaluate the relative importance of these factors in determining platelet function, a cross-sectional multivariate study in 191 men, 113 healthy subjects and 78 patients with angiographically documented coronary heart disease, was performed. In healthy subjects, stepwise multiple linear regression identified age to be a major determinant of platelet aggregability. After induction with both ADP and collagen the platelet aggregatory response markedly increased with age. In the patients, platelet function was not age dependent. In multivariate analysis of variance, neither smoking status nor hypercholesterolemia (greater than or equal to 240 mg/dl) were determinants of platelet function in either group. An increase in systolic blood pressure was associated with slightly more inhibited ADP induced aggregation in both healthy subjects and patients with coronary heart disease. In patients compared to healthy subjects, aggregation after induction with ADP and collagen was markedly enhanced and the in vitro formation of thromboxane after collagen stimulation increased. Thus, by multivariate analysis, age and the presence or absence of coronary heart disease were found to be major determinants of platelet function. In contrast, the cardiovascular risk factors smoking, hypercholesterolemia and hypertension were associated with only minor or no alterations of platelet function.

Adult↗

The influence of patient race and social vulnerability on urologist treatment recommendations in localized prostate carcinoma.

BACKGROUND: In localized prostate carcinoma (PCa), many studies have found that black subjects receive radical prostatectomy (RP) less often than white subjects. Such disparities involve barriers to health care, comorbid illnesses, tumor characteristics, and patient preferences. It is unclear whether differences in urologist treatment recommendations also might play a role. METHODS: Using a randomized, 2 x 2 factorial design, we presented 2000 urologists with a clinical vignette and asked them to recommend treatment of a healthy 70-year-old patient with low-risk, clinically localized PCa. Options included either RP, external beam radiotherapy, brachytherapy, cryotherapy, observation, or hormonal therapy. There were 2 variables within 4 otherwise-identical versions of the vignette: 1) patient race (black vs. white) and 2) social vulnerability (middle-income and married vs. low-income and widowed). We used multivariable logistic regression to model the effects of patient race, social vulnerability, and their interaction on recommendations for RP versus radiotherapy. RESULTS: The response rate was 66.1% (n = 1313). Race and social vulnerability interacted (P = 0.05) such that the highly vulnerable black patient received an RP recommendation 14.4% less often than his less vulnerable counterpart; the difference between the 2 white patients was 4.2%. DISCUSSION: Race interacts with social vulnerability to influence urologist recommendations for RP. Because PCa tends to be more lethal in blacks, urologists may view such patients as good candidates for RP. However, black race may amplify perceptions of social vulnerability, heightening urologists' concerns about poor surgical outcomes and follow-up. These findings affirm the importance of modeling interactions between race/ethnicity and other social variables in health disparities research.

Black or African American↗

A multivariate analysis of risk factors for anterior atlantoaxial subluxation and an evaluation of the effect of glucocorticoid treatment on the upper rheumatoid cervical spine.

A cross-sectional, retrospective computerized analysis of risk factors for anterior atlantoaxial subluxation (AAS) was performed. Logistic regression performed on the clinical variables involved in 145 cases of rheumatoid arthritis (RA) disclosed a high joint score index and a low blood haemoglobin level as significant independent risk factors. This means that the development of anterior AAS is connected with widespread RA. Linear multiple regression analysis showed an association between the extent of anterior AAS in millimetres and the spread of erosions of the dens of axis and negative correlation with the severity of vertical atlantoaxial dislocation (VD). This suggests that whereas the presence of anterior AAS is connected with the severity of the systemic disease, its actual extent is associated with signs of local involvement, other than severe VD. The duration or cumulative dosage of glucocorticoids were not associated with the development or extent of anterior AAS, nor with the severity of vertical dislocation. This suggests that low dose glucocorticoid treatment is not involved with the development of rheumatoid changes in the upper cervical spine. It should be borne in mind, of course, that although no correlation was found, a causal relation cannot be excluded.

Arthritis, Rheumatoid↗

Maternal-infant bedsharing: risk factors for bedsharing in a population-based survey of new mothers and implications for SIDS risk reduction.

OBJECTIVES: Maternal-infant bedsharing is a common but controversial practice. Little has been published about who bedshares in the United States. This information would be useful to inform public policy, to guide clinical practice and to help focus research. The objective was to explore the prevalence and determinants of bedsharing in Oregon. METHODS: Oregon Pregnancy Risk Assessment Monitoring System (PRAMS) surveys a population-based random sample of women after a live birth. Women were asked if they shared a bed with their infant "always," "almost always," "sometimes" or "never." RESULTS: 1867 women completed the survey in 1998-99 (73.5% weighted response rate). Of the respondents, 20.5% reported bedsharing always, 14.7% almost always, 41.4% sometimes, and 23.4% never. In multivariable logistic regression, Hispanics (adjusted odds ratio [ORa] 1.69, 95% Confidence Interval [CI] 1.17-2.43), blacks (ORa 3.11, 95% CI 2.03-4.76) and Asians/Pacific Islanders (ORa 2.14, 95% CI 1.51-3.03), women who breastfed more than 4 weeks (ORa 2.65, 95% CI 1.72-4.08), had annual family incomes less than $30,000 (ORa 2.44, 95% CI 1.44-4.15), or were single (ORa 1.55, 95% CI 1.03-2.35) were more likely to bedshare frequently (always or almost always). Among Hispanic and black women, bedsharing did not vary significantly by income level. Bedsharing black, American Indian/Alaska Native and white infants were much more likely to be exposed to smoking mothers than Hispanic or Asian/Pacific Islander infants (p < .0001). CONCLUSIONS: Bedsharing is common in Oregon. The women most likely to bedshare are non-white, single, breastfeeding and low-income. Non-economic factors are also important, particularly among blacks and Hispanics. Campaigns to decrease bedsharing by providing cribs may have limited effectiveness if mothers are bedsharing because of cultural norms.

Adolescent↗

An exploration of the relationship between youth assets and engagement in risky sexual behaviors.

PURPOSE: To examine the relationship between specific youth assets and adolescents' engagement in risky sexual behaviors, as measured by an Aggregate Sexual Risk score, and to specifically explore which youth assets and demographic variables were predictive of youth engagement in risky sexual intercourse. METHODS: A total of 2108 sexually active high school students attending public high schools in a southern state completed a self-report questionnaire that measured youth assets. Based upon responses to items measuring risk behaviors, an Aggregate Sexual Risk score was calculated for each student. Unconditional logistic regression and multivariate logistic regression analyses were conducted to examine the relationships between the assets and the Aggregate Risk Score. Four separate analyses (white females, white males, black females, and black males) were conducted. RESULTS: In general, the patterns in all four groups indicated that students who had an Aggregate Risk Score of > or = 3 (high risk) possessed less of the measured youth assets. The assets that were most significantly associated with engagement in risky sexual behaviors included self peer values regarding risky behaviors, quantity of other adult support, and youths' empathetic relationships. Thus, students who reported not having these assets were significantly more likely to engage in the risky sexual behaviors. CONCLUSIONS: Results underscore the relationship of specific youth assets to sexual risk behaviors. Health researcher and practitioners who work to prevent teen pregnancy and sexually transmitted infections among teenagers need to understand and acknowledge these factors within this population so that the assets can be built or strengthened.

Adolescent↗

Comparison of autonomic withdrawal in men with obstructive sleep apnea syndrome, systemic hypertension, and neither condition.

Obstructive sleep apnea syndrome is characterized by obesity, nocturnal breathing abnormalities, arterial hypertension, and an increased number of cardiovascular events. Sympathetic activity is increased during nocturnal apneic episodes, which may mediate the cardiovascular complications of sleep apnea. We studied 15 male subjects with obstructive sleep apnea syndrome and associated hypertension, 54 subjects with mild to moderate essential hypertension, and 25 healthy normotensive men. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability (HRV) during a controlled breathing test and during orthostatic maneuver. Compared with normotensive and hypertensive groups, total power and low- and high-frequency components of HRV during controlled breathing were significantly (analysis of variance, p<0.0001) lower in the obstructive sleep apnea syndrome. During the orthostatic maneuver, the change in total power of HRV was different between the 3 groups (analysis of variance, p = 0.004). The total power of HRV tended to increase in the normotensive (4.11+/-12.29 ms2) and in hypertensive (2.31+/-12.65 ms2) groups, but decreased (1.13+/-1.23 ms2) in the hypertensive group with obstructive sleep apnea syndrome. According to multivariate regression analysis, age and sleep apnea were the major independent determinants of HRV. This study found that an abnormal response to autonomic nervous tests characterizes hypertension in overweight subjects with obstructive sleep apnea syndrome. This could be due to autonomic withdrawal or supersaturation of the end-organ receptors by excessive and prolonged sympathetic stimulation. Our results also show the reduced response of orthostatic maneuver and controlled breathing in the hypertensive group compared with the normotensive group.

Autonomic Nervous System↗

Patient satisfaction and visual symptoms after laser in situ keratomileusis.

PURPOSE: To examine preoperative risk factors for decreased satisfaction and symptoms of glare, halos, and/or starbursts after laser in situ keratomileusis (LASIK). DESIGN: Retrospective, case-control study. PARTICIPANTS: Participants were 604 previously myopic patients who underwent LASIK at least six months prior to completing the questionnaire. METHODS: Questionnaires about satisfaction and night vision symptoms were mailed to 2100 patients from the Northeastern Eye Institute, UCLA, and the University of Pittsburgh. Preoperative and postoperative ocular variables were collected from the medical charts of the 841 subjects who returned the questionnaire. MAIN OUTCOME MEASURES: Responses to various satisfaction and night vision symptom questions were compared to demographic and preoperative ocular variables using multivariate logistic regression. RESULTS: The questionnaire return rate was 42.9%. The mean age for all subjects was 43.0 +/- 10.6 years, and 63% of the subjects were women. Overall, 97% of the subjects would recommend LASIK to a friend. Among subjects who would not recommend LASIK to a friend, a significantly larger percentage reported that they experienced glare, halos, or starbursts (13 of 16 (81.3%) vs. 206 of 388 (53.1%), chi(2) = 4.9, p = 0.03). Also, subjects with flatter preoperative minimum corneal curvature values were more likely to report that they would not recommend LASIK to a friend (OR = 0.71, 95% confidence interval (CI) = (0.52, 0.96), p = 0.03). The median score for satisfaction with vision was 100%, or the maximum value of 127 mm on the visual analog scale. Increasing age was significantly associated with dissatisfaction with vision after LASIK (OR = 1.68, 95% CI = (1.10, 2.56), P = 0.02). Halos were reported by 30%, glare by 27%, and starbursts by 25% of all subjects. Subjects who reported starbursts had a significantly flatter preoperative minimum corneal curvature (43.54 +/- 1.60 D versus 43.92 +/- 1.69 D, t = 2.15, p = 0.03). Also, subjects who had surgical enhancement were more likely to experience glare, halos, and/or starbursts (OR = 2.14, 95% CI = (1.33, 3.46), p = 0.002). CONCLUSIONS: Most subjects are satisfied with their vision after LASIK. Our study suggests, however, that certain factors are associated with decreased satisfaction and night vision symptoms after LASIK. Some of these factors include: increasing age, flatter preoperative minimum corneal curvature, and surgical enhancement.

Adult↗

Immigration and leisure-time physical inactivity: a population-based study.

OBJECTIVE: To investigate the relationship between migration status and sedentary leisure-time physical activity status in the city of Malmö, Sweden. METHODS: The public health survey in 1994 is a cross-sectional study. A total of 5,600 individuals aged 20-80 completed a postal questionnaire. The response rate was 71%. The population was categorized according to country of birth. Multivariate analysis was performed using a logistic regression model to investigate the importance of possible confounders for the differences in sedentary leisure-time physical activity status. RESULTS: The prevalence of a sedentary leisure-time physical activity status was 18.1% among men and 26.7% among women. The odds ratio of a sedentary leisure-time physical activity status was significantly higher among men born in Arabic-speaking countries, in All other countries, and among women born in Yugoslavia, Poland, Arabic-speaking countries, and the category all other countries', compared to the reference group born in Sweden. The multivariate analysis including age, sex, and education did not alter these results. CONCLUSION: There were significant ethnic differences in leisure-time physical activity status. This is a CVD risk factor that could be affected by intervention programs aimed at specific ethnic subgroups of the population.

Cross-Sectional Studies↗

Impact of the University of California, Los Angeles/Charles R. Drew University Medical Education Program on medical students' intentions to practice in underserved areas.

PURPOSE: To estimate the impact of a U.S. inner-city medical education program on medical school graduates' intentions to practice in underserved communities. METHOD: The authors conducted an analysis of secondary data on 1,088 medical students who graduated from either the joint University of California, Los Angeles/Charles R. Drew University Medical Education Program (UCLA/Drew) or the UCLA School of Medicine between 1996 and 2002. Intention to practice in underserved communities was measured using students' responses to questionnaires administered at matriculation and graduation for program improvement by the Association of American Medical Colleges. Multivariate logistic regression analysis was used to compare the odds of intending to practice in underserved communities among UCLA/Drew students with those of their counterparts in the UCLA School of Medicine. RESULTS: Compared with students in the UCLA School of Medicine, UCLA/Drew students had greater adjusted odds of reporting intention to work in underserved communities at graduation, greater odds of maintaining or increasing such intentions between matriculation and graduation, and lower odds of decreased intention to work in underserved communities between matriculation and graduation. CONCLUSIONS: Training in the UCLA/Drew program was independently associated with intention to practice medicine in underserved communities, suggesting that a medical education program can have a positive effect on students' goals to practice in underserved areas.

Adult↗

Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.

We assessed the efficacy of interferon (IFN) alpha-2b plus ribavirin therapy in patients with hepatitis C virus (HCV)-related cirrhosis, and elucidated the risk factors for the development of hepatocellular carcinoma (HCC) to determine whether these therapies might reduce the incidence of HCC. One hundred and thirty-two HCV-cirrhotic patients receiving IFN alpha-2b (3 or 5 MU thrice weekly) and oral ribavirin (1,000-1,200 mg/day) for 24 or 48 weeks were analysed. Cumulative incidence of HCC was estimated by the Kaplan-Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox's regression analysis. A total of 116 patients completed the treatment and 73 (55%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that nongenotype 1b (P < 0.001) and low viral load (P = 0.018) were independent variables of SVR. During a median follow-up period of 37 (12-63) months, HCC developed in 11 patients with non-SVR and five with SVR (P = 0.0178), whereas there was no difference between those with transient biochemical response and nonresponse (P = 0.5970). The Kaplan-Meier method also showed that old age (>or=60 years) (P = 0.0034) and genotype 1b (P = 0.0104) were associated with HCC occurrence. Using Cox's regression analysis, non-SVR (odds ratio = 3.521, P = 0.036), male (odds ratio = 6.269, P = 0.011) and old age (odds ratio = 3.076, P = 0.049) were independent significant risk factors contributing to HCC development. Our results suggest that achieving SVR by IFN alpha-2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV-related cirrhosis.

Adult↗

The relationship between vulnerability factors and breastfeeding outcome.

OBJECTIVE: To determine whether vulnerability factors (confidence with breastfeeding, postpartum depression, supplementation, and perceived adequacy of support) are associated with breastfeeding outcome at 6 weeks postpartum after controlling for age and education. DESIGN: Secondary analysis of a cross-sectional telephone survey at 6 weeks postpartum. SETTING: Ottawa-Carleton, Ontario, Canada. PARTICIPANTS: A proportionate, consecutive sample of breastfeeding women from each of four hospitals in the region (526/554, 95% response rate). METHODS: Stratified bivariate analyses were used to examine the relationship between each factor and breastfeeding outcome. Multivariate logistic regression analyses examined relationships between all factors and breastfeeding outcome. RESULTS: In the logistic regression analyses, confidence with breastfeeding (odds ratio: 1.85, 95% confidence interval: 1.50-2.27, p < .001) and postpartum depression (odds ratio: 0.28, 95% confidence interval: 0.11-0.71, p= .007) were related to breastfeeding after controlling for age and education. CONCLUSIONS: Support for breastfeeding should include assessment of maternal confidence with breastfeeding and postpartum depression. Evaluation of intervention strategies to address these vulnerability factors is a priority.

Adult↗

Aspirin and urinary 11-dehydrothromboxane B(2) in African American stroke patients.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate the relationship between daily aspirin use and urinary excretion of a stable thromboxane metabolite, 11-dehydrothromboxane B(2) (11-DTB2), in African American stroke patients. METHODS: Subjects were a subgroup of those screened for the African American Antiplatelet Stroke Prevention Study. Subjects were within 4 months of noncardioembolic ischemic stroke and were not being treated with anticoagulants. Antithrombotic therapy at the time of urine collection varied according to the practice patterns of various attending physicians who treated the patients during their acute strokes. 11-DTB2 was measured by enzyme immunoassay in random urine samples 1 to 4 months after the stroke. RESULTS: Eighty-seven of 92 patients enrolled were able to give a urine sample at the time of enrollment. There were 51 men and 36 women aged 36 to 87 (mean 62) years. On the basis of antithrombotic treatment before the sample collection, we divided patients into 4 groups: (1) 16 patients treated with no aspirin (no antithrombotic drugs [n=4] or ticlopidine [n=12]), (2) 21 patients treated with 81 to 325 mg aspirin per day (81 mg/d [n=2], 325 mg/d [n=19]), (3) 20 patients treated with 650 mg aspirin per day, and (4) 30 patients treated with 975 to 1300 mg aspirin per day (975 mg/d [n=2] and 1300 mg/d [n=28]). In patients taking daily aspirin at any dose, the median urinary 11-DTB2 was 783 pg/mg creatinine compared with 1386 pg/mg creatinine in patients not taking daily aspirin (P=0.01 by Wilcoxon rank sum test). In multivariate regression analysis, aspirin use remained significantly associated with lower urinary 11-DTB2 (P=0.008). There was no dose-response effect between the 3 aspirin dose groups and urinary 11-DTB2 (P=0.70). CONCLUSIONS: In African American stroke patients, aspirin use is associated with significantly lower urinary 11-DTB2 independent of other vascular factors, and there does not appear to be a dose-response effect for aspirin doses of 325 to 1300 mg daily. The clinical significance of these finding remains to be determined.

Adult↗

Perceived sleepiness of non-shift working men in two different types of work organization.

Increased sleepiness at work is increasingly being focused on as a safety and health issue. However, research on workers' sleepiness is very limited in scope and the characteristics of work organization, including the impact of job stress, have not been fully addressed. A questionnaire survey was conducted to investigate the prevalence of daytime sleepiness and its associated factors among non-shift working men at two manufacturing businesses: Company A, having a rapid rate of development and growth, with 564 workers (19-61 yr old, mean age: 32.7, response rate: 81.4%); and Company B, long established, possessing a huge production facility, with 1,654 workers (20-63 yr old, mean age: 37.1, response rate: 78.2%). The prevalence of daytime sleepiness was 11.3% in company A and 16.8% in company B. Multivariate logistic regression analysis revealed that, in company A, perceived sleepiness was associated with long sleep duration on non-working days and high cognitive demands and, in company B, with insufficient daily sleep, single, and depression. Psychosomatic exhaustion resulting from jobs requiring high adaptivity due to rapid frequency of operational change as in company A may have the potential to become an important factor in perceived sleepiness. However, in a comparatively stable work organization, as in company B, increased sleepiness may be mainly linked to factors outside work. It is suggested that not only lifestyle and sleep habits, but also the characteristics and dynamics of a work organization should be a focus of attention when planning measures to prevent sleepiness at work.

Adult↗

Hierarchical linear models for the quantitative integration of effect sizes in single-case research.

In this article, the calculation of effect size measures in single-case research and the use of hierarchical linear models for combining these measures are discussed. Special attention is given to meta-analyses that take into account a possible linear trend in the data. We show that effect size measures that have been proposed for this situation appear to be systematically affected by the duration of the experiment and fail to distinguish between effects on level and slope. To avoid these flaws, we propose to perform a multivariate meta-analysis on the standardized ordinary least squares regression coefficients from the study-specific regression equations describing the response variable.

Algorithms↗

Association between lactation length and sow reproductive performance and longevity.

OBJECTIVE: To determine whether lactation length was associated with reproductive performance or longevity of sows. DESIGN: Cohort study. SAMPLE POPULATION: Data collected between 1986 and 1992 for sows in 15 breeding herds in Minnesota and Iowa. PROCEDURE: Sows were grouped into 4 genetic line categories according to their sources and 6 parity categories (1, 2, 3, 4, 5 or 6, and > or = 7). Multivariate regression analysis of reproductive performance was conducted, using the general linear model procedure Logistic regression was conducted with a dichotomous response variable for sow longevity (ie, removal from or retention in the herds). Odds ratios were obtained from estimated coefficients of the regression. RESULTS: Herd, genetic line, parity, year, month, and lactation length were significant in statistical models for litter (eg, number of live pigs/litter) and interval (eg, weaning-to-mating interval) traits. Interactions between lactation length and year, lactation length and genetic line, lactation length and parity, and lactation length and genetic line and parity were also significant. Sows removed from herds had a significantly shorter lactation length than did sows of the same parity that were retained in the herds. Sows that had shorter lactation lengths were at higher risk of being removed from the herds than were those that had longer lactation lengths. CLINICAL IMPLICATIONS: Lactation length is associated with reproductive performance and longevity, but genetic line and parity play a role as well. Thus, attention should be paid to genetic lines and parity of sows in the herd when implementing an early weaning production practice.

Animals↗

Predicting neurologic deterioration in patients with cerebellar hematomas.

BACKGROUND: Patients with cerebellar hematomas may appear stable but may worsen suddenly. Whether certain clinical or CT scan findings predict worsening is not known. METHODS: We reviewed clinical and neuroimaging data in 72 patients with cerebellar hematomas at the Mayo Clinic from 1973 through 1993 to identify predictive features for neurologic deterioration. Patients presenting in coma and patients with vascular malformations or malignancies were excluded. Data were analyzed using chi-square or Fisher's exact test, with calculation of odds ratios with 95% confidence intervals. Multivariate logistic regression analysis was performed on appropriate variables. RESULTS: Thirty-three patients (46%) deteriorated, with a decrease in level of consciousness, new brainstem signs, or worsened motor response on the Glasgow Coma Scale. Clinical and neuroradiologic predictors for neurologic deterioration at p < 0.05 were admission systolic blood pressure greater than 200 mm Hg, pinpoint pupils and abnormal corneal or oculocephalic reflexes, hemorrhage extending into the vermis, hematoma size more than 3 cm in diameter, brainstem distortion, intraventricular hemorrhage, upward herniation, and acute hydrocephalus. Multivariate analysis demonstrated that hemorrhage located in the vermis (p = 0.03) and acute hydrocephalus (p = 0.0006) on admission CT scanning independently predicted deterioration. CONCLUSION: Patients with a cerebellar vermian hematoma or acute hydrocephalus are at high risk for neurologic deterioration. These patients should be carefully monitored and are more likely to require consideration for neurosurgical intervention.

Adult↗

Optimization of conformal radiation treatment of prostate cancer: report of a dose escalation study.

PURPOSE: The development of conformal radiation technique including improved patient immobilization has allowed us to test the value of dose escalation in optimizing the radiation treatment of prostate cancer. METHODS AND MATERIALS: Outcome is reported for 233 consecutive patients treated with conformal technique between March 1989 and October 1992. Dose was escalated from 68 Gy to 79 Gy. Patient status is reported at 3 years follow-up, which is available in all alive patients. Pretreatment and serial posttreatment prostate specific antigen (PSA) values are available for all patients. Biochemical freedom of disease (bNED) defines failure as PSA > 1.5 ngm/ml and rising on two consecutive measures. Dose response for bNED control of cancer and late morbidity are represented by logit response models fitted to the data. Kaplan-Meier methods, the log rank test, and Cox Regression models are also used. RESULTS: No dose response is observed for bNED survival for patients with pretreatment PSA <10 ngm/ml comparing patients treated above or below 71.5 Gy or on multivariate analysis. Dose response is observed for bNED survival for pretreatment PSA groups of 10-19.9 ngm/ml and 20+ ngm/ml. The dose associated with 50% bNED survival at 3 years is 64 Gy and 76 Gy, respectively. The slope of the dose responses are 13 and 9%, respectively. Dose response is demonstrated for Grade 2 gastrointestinal (GI), Grade 2 genitourinary (GU), and Grade 3,4 combined GI and GU late morbidity. The slopes of the morbidity responses are steeper than for cancer control (19 to 21%). CONCLUSIONS: Patients with pretreatment PSA < 10 ngm/ml do not benefit from dose escalation, and the serious late morbidity of conformal radiation at 70 Gy is < 3%. Patients with PSA values 10-19.9 ngm/ml and 20+ ngm/ml benefit from dose escalation beyond 70 Gy. Treatment beyond 75 Gy results in > 10% serious morbidity unless special precautions are taken to protect the rectal mucosa. All levels of severity of radiation morbidity show a dose response and combined with the dose response for bNED survival these data allow the optimization of treatment.

Disease-Free Survival↗

Epidermal growth factor receptor mutations in needle biopsy/aspiration samples predict response to gefitinib therapy and survival of patients with advanced nonsmall cell lung cancer.

Recently, mutations in the epidermal growth factor receptor (EGFR) gene in nonsmall cell lung cancer (NSCLC) patients were reported to correlate with gefitinib response. Less than 30% of NSCLC patients are surgically resectable; however, molecular analysis has to rely on nonsurgical diagnostic tissue samples. The objective of this study is to investigate EGFR mutation analysis on needle biopsy/aspiration samples and its correlations with gefitinib response and patients' survival. EGFR mutation was assessed from DNA of 63 paraffin-embedded small needle biopsy/aspiration specimens from 62 patients with NSCLC treated with gefitinib. The peripheral blood lymphocyte DNA of the patients was sequenced to verify the EGFR mutation. EGFR mutations were found in 47% of 62 patients (60% of 20 CT-guided biopsies, 44% of 18 ultrasound-guided biopsies, 31% of 16 endoscopic biopsies and 44% of 9 effusion cell blocks). EGFR mutations were frequently present in females (p = 0.006) and never smokers (p = 0.04). Patients with EGFR mutations had a significantly better response rate compared to that of the nonmutation group (p < 0.001). Multivariate analysis showed that EGFR mutation (p < 0.001) and PS 0-1 (p = 0.02) were independently associated with a better response rate. Cox regression analysis showed that EGFR mutation was the independent prognostic factor for progression-free survival (p = 0.008) and overall survival (p = 0.03). In conclusion, EGFR mutation analysis is feasible in needle biopsy/aspiration paraffin-fixed specimens. EGFR mutation is an independent predictor of gefitinib response and survival in patients of advanced NSCLC treated by gefitinib.

Aged↗