Tulay Koru-Sengul

How spiritual values and worship attendance relate to psychiatric disorders in the Canadian population.

Objective: Research into risk and protective factors for psychiatric disorders may help reduce the burden of these conditions. Spirituality and religion are 2 such factors, but research remains limited. Using a representative national sample of respondents, this study examines the relation between worship frequency and the importance of spiritual values and DSM-IV psychiatric and substance use disorders. Method: In 2002, the Canadian Community Health Survey obtained data from about 37 000 individuals aged 15 years or older. While controlling for demographic characteristics, we determined odds ratios for lifetime, 1-year, and past psychiatric disorders, with worship frequency and spiritual values as predictors. Results: Higher worship frequency was associated with lower odds of psychiatric disorders. In contrast, those who considered higher spiritual values important (in a search for meaning, in giving strength, and in understanding lifes difficulties) had higher odds of most psychiatric disorders. Conclusion: This study confirms an association between higher worship frequency and lower odds of depression and it expands that finding to other psychiatric disorders. The association between spiritual values and mood, anxiety, and addictive disorders is complex and may reflect the use of spirituality to reframe life difficulties, including mental disorders.

Comparison of in-hospital and one-year outcomes in patients with left ventricular ejection fractions ≤40%, 41% to 49%, and ≤50% having percutaneous coronary revascularization

Outcome studies of percutaneous coronary intervention (PCI) with conventional balloon angioplasty have established increased in-hospital and 1-year mortality in patients with left ventricular (LV) dysfunction compared with others. It is unclear whether recent PCI practice innovations, including stents and adjunctive pharmacotherapy, have made PCI safer and more effective in patients with LV dysfunction. We evaluated the influence of LV ejection fraction (EF) indexes on in-hospital and 1-year outcomes in 1,458 patients within the National Heart, Lung, and Blood Institute-sponsored Dynamic Registry. Patients (n = 300) with acute myocardial infarction were excluded. The remaining 1,158 patients were subdivided into 3 categories: group 1, EF <or=40% (n = 166); group 2, EF 41% to 49% (n = 126); and group 3, EF >or=50% (n = 866). We determined the frequency of individual and composite adverse events (death/myocardial infarction [MI]/coronary artery bypass grafting) at discharge and 1 year. In the Dynamic Registry patients, mean EF in the 3 groups was 32%, 45%, and 62% and in-hospital mortality was 3.0%, 1.6%, and 0.1%, respectively (p <0.001). The composite end point of death/MI was also significant, but other in-hospital adverse events did not differ between groups. The respective mortality rates were 11.0%, 4.5%, and 1.9% (p <0.001) after 1 year. The composite end points of death/MI and death/MI/coronary artery bypass grafting also occurred more frequently in group 1 patients. Thus, significant LV dysfunction was still associated with increased in-hospital and 1-year mortality in patients having contemporary PCI.

Murine neonatal recent thymic emigrants are phenotypically and functionally distinct from adult recent thymic emigrants

In contrast to adults, the murine neonatal CD4+ compartment contains a high frequency of recent thymic emigrants (RTEs). However, the functional capabilities of these cells in neonates are relatively unknown. Moreover, it has not been determined whether RTEs from neonates and adults are comparable. Here we have directly compared neonatal and adult CD4+ RTEs for the first time, using a transgenic mouse strain that allows for the identification and purification of RTEs. Our data demonstrate that RTEs from murine neonates and adults are phenotypically and functionally distinct. In particular, although the magnitude of RTEs cytokine responses from both age groups is dependent on the conditions of activation, neonatal RTEs always exhibited higher levels of effector Th1/Th2 cytokine production than adult RTEs. In addition, neonatal, but not adult, RTEs showed early proliferation in response to stimulation with interleukin-7 alone. This was associated with faster kinetics of interleukin-7Ralpha down-regulation and higher levels of pSTAT5 in neonatal RTEs. These quantitative and qualitative differences in the neonatal and adult RTEs populations may at least partially explain the diverse responses that are elicited in vivo in neonates in response to different conditions of antigen exposure.

Estimating treatment effects from longitudinal clinical trial data with missing values: comparative analyses using different methods

The selection of a method for estimating treatment effects in an intent-to-treat analysis from clinical trial data with missing values often depends on the field of practice. The last observation carried forward (LOCF) analysis assumes that the responses do not change after dropout. Such an assumption is often unrealistic. Analysis with completers only requires that missing values occur completely at random (MCAR). Ignorable maximum likelihood (IML) and multiple imputation (MI) methods require that data are missing at random (MAR). We applied these four methods to a randomized clinical trial comparing anti-depressant effects in an elderly depressed group of patients using a mixed model to describe the course of the treatment effects. Results from an explanatory approach showed a significant difference between the treatments using LOCF and IML methods. Statistical tests indicate violation of the MCAR assumption favoring the flexible IML and MI methods. IML and MI methods were repeated under the pragmatic approach, using data collected after termination of protocol treatment and compared with previously reported results using piecewise splines and rescue (treatment adjustment) pragmatic analysis. No significant treatment differences were found. We conclude that attention to the missing-data mechanism should be an integral part in analysis of clinical trial data.

Low-Dose Fractionated Radiation Potentiates the Effects of Cisplatin Independent of the Hyper-Radiation Sensitivity in Human Lung Cancer Cells

In this study, the role of hyper-radiation sensitivity (HRS) in potentiating the effects of cisplatin by low-dose fractionated radiation (LDFRT) was evaluated in four human non–small cell lung cancer cell lines. Presence of HRS and cisplatin enhancement ratio (CER) by LDFRT/2 Gy was assessed using colony-forming and apoptotic assays. Cell-cycle disturbances were studied by flow cytometry. Expression of genes involved in apoptosis was assessed using real-time reverse transcriptase PCR arrays. H-157 cells showed a distinct HRS region, followed by UKY-29 and A549 cells, whereas it was absent in H460 cells, which when lack HRS showed maximum CER with LDFRT (4 × 0.5 Gy) both by clonogenic inhibition and by apoptosis compared with single fraction of 2 Gy whereas the most radioresistant A549 cells had the least CER, with no significant differences between LDFRT or 2 Gy. Interestingly, in H-157 cells, a more pronounced CER was observed with LDFRT when assessed by apoptosis but clonogenic inhibition-CER was higher with 2 Gy than with LDFRT. Excluding H-157 cells, the CER by LDFRT was inversely proportional to radioresistance [(determined by D0, the dose to reduce survival by 67% from any point on the linear portion of the survival curve or surviving fraction (SF) at 2 Gy (SF2)] of the cells. LDFRT alone or in combination with cisplatin induced larger number of proapoptotic genes than 2 Gy or cisplatin + 2 Gy in cells showing HRS when compared to H460 cells that lack HRS. These findings indicate that chemopotentiation by LDFRT is correlated more with the intrinsic radiation sensitivity of the non–small lung cancer cells than the HRS phenomenon whereas the mode of cell killing is both through apoptosis and clonogenic inhibition. Mol Cancer Ther; 10(2); 292–302. ©2011 AACR.

Survival disparities in non-small cell lung cancer by race, ethnicity, and socioeconomic status.

PurposeNon–small cell lung cancer (NSCLC) is among the leading causes of cancer death in the United States. Previous studies found mixed results regarding disparities in survival by race, ethnicity, and socioeconomic status (SES). However, race comparisons were usually limited, with comparisons made between black and white patients only or by merging race and ethnicity together as non-Hispanic black, non-Hispanic white, and Hispanic patients. Even fewer studies included race, ethnicity, and SES together while controlling for extensive confounding variables. Thus, because we have access to a large and unique population-based database that includes tumor characteristics and patient comorbidities, the purpose of this study was to explore disparities in NSCLC survival. MethodsWe linked data from the 1996 to 2007 Florida Cancer Data System registry to the Florida’s Agency for Health Care Administration and the US Census (n = 98,541). Survival time was from date of diagnosis to death or last contact. Race was white, black, Native American, Asian, Pacific Islander, Asian Indian/Pakistani, or other. Ethnicity was non-Hispanic or Hispanic. Socioeconomic status was measured as percentage of the participant’s census tract living below the federal poverty line. Median survival and survival rates were calculated by Kaplan-Meier method. Cox proportional hazards regression models produced unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). ResultsThe majority of patients were white (91.9%) and non-Hispanic (94.1%). Blacks had the lowest median survival (8.4 months). At 5 years after diagnosis, survival rate was highest in whites (16.3%) and lowest for Pacific Islanders (6.4%). In the adjusted model, Asians had significantly improved survival compared with whites (HR, 0.85; 95% CI, 0.76–0.95). Patients in middle-low (HR, 0.96; 95% CI, 0.94–0.99), middle-high (HR, 0.92; 95% CI, 0.89–0.94), and highest (HR, 0.87; 95% CI, 0.84–0.91) SES areas had significantly improved survival compared with those in lowest areas. Significantly worse survival was found for patients with complicated diabetes (HR, 1.05; 95% CI, 1.01–1.08), weight loss (HR, 1.08; 95% CI, 1.06–1.11), fluid and electrolyte disorders (HR, 1.08; 95% CI, 1.06–1.11), and alcohol abuse (HR, 1.11; 95% CI, 1.07–1.14). DiscussionWe found strong evidence for racial and socioeconomic disparities in Floridian NSCLC survival. Asians had improved survival compared with whites, a novel finding. Our findings confirmed that patients living in lower socioeconomic neighborhoods have worse outcomes than their wealthier neighborhood counterparts. Finally, we found an association between some modifiable factors/comorbidities and worse survival. Clinicians may be able to use this information to improve patients’ likelihood of better outcomes.

Performance of creatinine clearance equations on the original Cockcroft-Gault population

BACKGROUND Prediction of endogenous creatinine clearance by mathematical equations such as the Cockcroft-Gault formula is used in clinical practice in spite of the reported concern for their limited predictability. The aim of this study is to determine whether the measured creatinine clearance can be predicted accurately by a number of published equations including the recently modified Cockcroft-Gault formula = Cockcroft-Gault formula x 1.73 m2/body surface area from the original Cockcroft-Gault population. METHODS The performance of the mathematical equations in patients with different creatinine clearance and body mass indices was assessed by computing accuracy at different percentiles, bias and precision from the original Cockcroft-Gault data. RESULTS Refitting the modified formula to the Cockcroft-Gault data gave superior results compared to the original Cockcroft-Gault formula with an overall accuracy in the general and subgroup analysis above 70% agreement within 30% estimate of the measured creatinine clearance. On the other hand, analysis of the other equations, including the original Cockcroft-Gault, demonstrated a limited accuracy to predict creatinine clearance particularly in patients with creatinine clearance below 50 ml/min with an overall accuracy in less than 1/3 of the calculated creatinine clearance within 30% range from the measured creatinine clearance. CONCLUSION The current creatinine clearance equations and even the original Cockcroft-Gault formula did not accurately predict the measured creatinine clearance. Normalization for body surface area in the original Cockcroft-Gault formula demonstrated more accuracy to estimate creatinine clearance, particularly in patients with diminished renal function and is recommended to physicians who wish to use the Cockcroft-Gault formula in their practice until more credible formulas are developed.

Stereotactic body radiotherapy in patients with stage i non-small-cell lung cancer aged 75 years and older: Retrospective results from a multicenter consortium

BACKGROUND This study was a retrospective analysis of elderly patients treated with stereotactic body radiotherapy (SBRT) in the setting of a multi-institutional consortium. PATIENTS AND METHODS Three institutions pooled data on patients aged ≥ 75 years who received SBRT for stage I non-small-cell lung cancer (NSCLC). Forty-seven tumors in 46 patients were analyzed in patients aged 75 to 92 years (median, 82 years). Treatment was delivered during 2007 to 2009, with a median follow-up of 12.4 months. All patients underwent staging positron emission tomography-computed tomography (PET-CT), and 87% of tumors were confirmed by biopsy results. Total doses were 35 to 60 Gy, mainly in 3 to 5 fractions. All tumors were treated using a linear accelerator, with 96% of patients receiving 3-dimensional (3D) conformal RT and 4% undergoing intensity modulated RT (IMRT). RESULTS At the time of analysis, the local failure rate was 2% (1 of 47). The regional failure rate was 9% (4 of 47). The distant failure rate was 6% (3 of 47). The combined failure rate was 15% (7 of 47) because 1 patient experienced both regional and distant failure. Among 20 tumors with any acute toxicity, there were no ≥ grade 3 toxicities. Pneumonitis (n = 10) grades 1 (n = 3) and 2 (n = 2) was seen in 15% and 10% of patients, respectively; these data were missing for 25% of patients. CONCLUSION SBRT in patients aged ≥ 75 years with stage I NSCLC proved tolerable, with toxicity rates comparable to those in younger patients. Excellent rates of local, regional, and distant control were achieved at a median follow-up of 12.4 months. This patient population represents a rapidly growing segment of the early lung cancer population, and SBRT appears to be a safe and effective treatment option for patients who are not optimal candidates for surgery.

Differences in clinical presentation of deep vein thrombosis in men and women.

Summary.  Background: As assessment of clinical pretest probability is the first step in the diagnostic evaluation of deep vein thrombosis (DVT), it is important to know if the clinical features of DVT are the same in men and women. Objectives: To compare the prevalence and clinical characteristics of DVT, and the accuracy of clinical pretest probability assessment, between men and women with suspected DVT. Methods: A retrospective analysis of individual patient data from three prospective studies by our group that evaluated diagnostic tests for a suspected first episode of DVT. Clinical characteristics, clinical pretest probability for DVT, and prevalence and extent of DVT was assessed in a total of 1838 outpatients. Results: The overall prevalence of DVT was higher in men than in women (14.4% vs. 9.4%) (P = 0.001). The prevalence of DVT was higher in men than in women who were categorized as having a clinical pretest probability that was low (6.9% vs. 3.5%; P = 0.025) or moderate (16.9% vs. 8.7%; P = 0.04), but similar in patients in the high category (40.2% vs. 44.0%; P = 0.6). In patients diagnosed with DVT, swelling of the entire leg occurred more often (41.5% vs. 15.7%; P < 0.001), and thrombosis was more extensive (involvement of both popliteal and common femoral veins in 47.9% vs. 21.6%), in women than in men. Conclusions: In outpatients with suspected DVT, the overall prevalence of thrombosis and the prevalence of thrombosis in those with a low or a moderate clinical pretest probability were higher in men than in women.

Breast cancers from black women exhibit higher numbers of immunosuppressive macrophages with proliferative activity and of crown-like structures associated with lower survival compared to non-black Latinas and Caucasians

Abstract Racial disparities in breast cancer incidence and outcome are a major health care challenge. Patients in the black race group more likely present with an early onset and more aggressive disease. The occurrence of high numbers of macrophages is associated with tumor progression and poor prognosis in solid malignancies. Macrophages are observed in adipose tissues surrounding dead adipocytes in “crown-like structures” (CLS). Here we investigated whether the numbers of CD163+ tumor-associated macrophages (TAMs) and/or CD163+ CLS are associated with patient survival and whether there are significant differences across blacks, non-black Latinas, and Caucasians. Our findings confirm that race is statistically significantly associated with the numbers of TAMs and CLS in breast cancer, and demonstrate that the highest numbers of CD163+ TAM/CLS are found in black breast cancer patients. Our results reveal that the density of CD206 (M2) macrophages is a significant predictor of progression-free survival univariately and is also significant after adjusting for race and for HER2, respectively. We examined whether the high numbers of TAMs detected in tumors from black women were associated with macrophage proliferation, using the Ki-67 nuclear proliferation marker. Our results reveal that TAMs actively divide when in contact with tumor cells. There is a higher ratio of proliferating macrophages in tumors from black patients. These findings suggest that interventions based on targeting TAMs may not only benefit breast cancer patients in general but also serve as an approach to remedy racial disparity resulting in better prognosis patients from minority racial groups.