nils-herrmann/clean_scirepeval huggingface dataset:
Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b&c.

To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT).



The present analysis included 1 000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b&c studies. Tissue microarray sections were stained with immunohistochemistry for p53 and BCL2. Median potential follow-up was 17 years. Clinical endpoints were locoregional recurrence (LRR), distant metastases (DM), overall mortality, and overall survival (OS). Statistical analyses included Kappa statistics, chi(2) or exact tests, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses.



p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan-Meier probability plots showed reduced OS and improved DM and LRR probabilities after PMRT within subgroups of both p53 negative and p53 positive patients. Negative BCL2 expression was significantly associated with increased overall mortality, DM and LRR probability in multivariate Cox regression analyses. Kaplan-Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2 and randomization status. Significant reductions in LRR probability after PMRT were recorded within both the BCL2 positive and BCL2 negative subgroups.



p53 was not associated with survival after radiotherapy in high-risk breast cancer, but BCL2 might be.
Antianginal effects of intravenous nitroglycerin over 24 hours.

To determine the constancy of hemodynamic and antianginal effects of the constant infusion of intravenous nitroglycerin (NTG) and their relationship to infusion rate and plasma NTG concentration, we administered maximal tolerated doses of intravenous NTG (range 10 to 120 micrograms/min, mean = 52 +/- 33 micrograms/min) and placebo to 10 patients with chronic stable angina for 25 hr each in a randomized, double-blind fashion. Sublingual NTG (0.4 mg) was given at 24.5 hr of infusion as a positive control. Bicycle exercise time (NIH protocol), blood pressure, heart rate, exercise ST response, and venous plasma NTG were determined before and at 1, 4, 8, 24, and 24.5 hr. Plasma NTG was linearly related to infusion rate, reached a steady state within 15 min and was unchanged over 24 hr (mean = 5.5 +/- 1.2 ng/ml). Mean plasma NTG clearance was 9.3 liters/min. However, during dose titration, patients demonstrated different relationships between plasma NTG and hemodynamic effects, with widely varying slopes and intercepts. Intravenous NTG produced a sustained reduction in blood pressure and a rise in heart rate at rest, and a reduction in blood pressure during submaximal exercise at as late as 24 hr, associated with reduced submaximal ST segment abnormality. In contrast, exercise tolerance to onset of angina showed a marked initial increase on intravenous NTG but fell progressively and did not differ from that with placebo at 24 hr. Increased exercise tolerance was associated with an increase in maximal heart rate and double product (heart rate X blood pressure), suggesting that direct coronary vasodilation and/or reduced left ventricular volume were the principal determinants of increased exercise tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
Interexaminer reliability of three methods of combining test results to determine side of sacral restriction, sacral base position, and innominate bone position.

Sacroiliac joint dysfunction is diagnosed based on the combined results of several palpatory examinations. Previous studies have compared the interexaminer reliability of only one of these methods of diagnosis.



To compare the interexaminer reliability of three methods of combining palpatory examinations to determine the side of sacroiliac joint dysfunction, sacral base position, and innominate bone position.



Blinded single-cohort reliability study.



Patients with low back pain underwent two identical sets of palpatory examinations given by two physicians, separately, at a university spine center. The results of each set were compiled and interpreted by three methods: using the test result with the highest interexaminer reliability (method 1), requiring at least one test result to be abnormal for the variable to be abnormal (method 2), and requiring all test results to be abnormal for the variable to be abnormal (method 3). The kappa was calculated for each method.



There were 24 subjects (mean age, 68.3 years), of which 15 (62%) were women. The kappa was consistently higher with method 1, at 0.47, 0.08, and 0.32 for the sacral position, innominate bone position, and side of sacroiliac joint dysfunction, respectively. Corresponding values for method 2 were 0.09, 0.4, and 0.16, and for method 3 were 0.16, 0.1, and -0.33.



Using the results of the most reliable examination consistently has the best interexaminer reliability.
Increased waist circumference is independently associated with hypothyroidism in Mexican Americans: replicative evidence from two large, population-based studies

Mexican Americans are at an increased risk of both thyroid dysfunction and metabolic syndrome (MS). Thus it is conceivable that some components of the MS may be associated with the risk of thyroid dysfunction in these individuals. Our objective was to investigate and replicate the potential association of MS traits with thyroid dysfunction in Mexican Americans.



We conducted association testing for 18 MS traits in two large studies on Mexican Americans - the San Antonio Family Heart Study (SAFHS) and the National Health and Nutrition Examination Survey (NHANES) 2007-10. A total of 907 participants from 42 families in SAFHS and 1633 unrelated participants from NHANES 2007-10 were included in this study. The outcome measures were prevalence of clinical and subclinical hypothyroidism and thyroid function index (TFI) - a measure of thyroid function. For the SAFHS, we used polygenic regression analyses with multiple covariates to test associations in setting of family studies. For the NHANES 2007-10, we corrected for the survey design variables as needed for association analyses in survey data. In both datasets, we corrected for age, sex and their linear and quadratic interactions.



TFI was an accurate indicator of clinical thyroid status (area under the receiver-operating-characteristic curve to detect clinical hypothyroidism, 0.98) in both SAFHS and NHANES 2007-10. Of the 18 MS traits, waist circumference (WC) showed the most consistent association with TFI in both studies independently of age, sex and body mass index (BMI). In the SAFHS and NHANES 2007-10 datasets, each standard deviation increase in WC was associated with 0.13 (p < 0.001) and 0.11 (p < 0.001) unit increase in the TFI, respectively. In a series of polygenic and linear regression models, central obesity (defined as WC ≥ 102 cm in men and ≥88 cm in women) was associated with clinical and subclinical hypothyroidism independent of age, sex, BMI and type 2 diabetes in both datasets. Estimated prevalence of hypothyroidism was consistently high in those with central obesity, especially below 45y of age.



WC independently associates with increased risk of thyroid dysfunction. Use of WC to identify Mexican American subjects at high risk of thyroid dysfunction should be investigated in future studies.
The effect of the neutropenic diet in the outpatient setting: a pilot study.

To determine whether use of the neutropenic diet in the outpatient setting decreases the number of febrile admissions and positive blood cultures associated with chemotherapy-induced neutropenia.



Descriptive pilot study.



Outpatient chemotherapy unit of a medical center in a major metropolitan area.


SAMPLE
Convenience sample of 28 patients aged 33-67 years beginning treatment with 1 of 13 chemotherapy regimens.



Twelve-week prospective study beginning on day 1 of chemotherapy cycle 1. Patients received instructions regarding the neutropenic diet before starting chemotherapy. Adherence assessment telephone calls were made at weeks 6 and 12. Hospital admission charts were reviewed at study completion.



Adherence with neutropenic diet, number of febrile admissions, and number of positive blood cultures.



Sixteen patients were compliant with the neutropenic diet, four of which were admitted for neutropenia with gram-negative rods. No significant differences were found in the rates of febrile admissions or positive blood cultures between compliant and noncompliant patients.



Clinical significance in this pilot study is related to the time required for diet education, content of diet education regarding food restrictions, and difficulty adhering to diet requirements given the multitude of side effects (e.g., nausea, vomiting, mouth sores, diarrhea) of chemotherapy.



No clear evidence exists that the neutropenic diet makes a difference in overall rates of infection. Nursing research to compare the neutropenic diet with a less restrictive food safety education-focused diet is needed to guide clinical practice.
Clopidogrel pharmacokinetics and pharmacodynamics vary widely despite exclusion or control of polymorphisms (CYP2C19, ABCB1, PON1), noncompliance, diet, smoking, co-medications (including proton pump inhibitors), and pre-existent variability in platelet function.

This study sought to determine whether known genetic, drug, dietary, compliance, and lifestyle factors affecting clopidogrel absorption and metabolism fully account for the variability in clopidogrel pharmacokinetics and pharmacodynamics.



Platelet inhibition by clopidogrel is highly variable. Patients with reduced inhibition have increased risk for major adverse cardiovascular events. Identification of factors contributing to clopidogrel's variable response is needed to improve platelet inhibition and reduce risk for cardiovascular events.



Healthy subjects (n = 160; ages 20 to 53 years; homozygous CYP2C19 extensive metabolizer genotype; no nicotine for 6 weeks, prescription drugs for 4 weeks, over-the-counter drugs for 2 weeks, and no caffeine or alcohol for 72 h; confined; restricted diet) received clopidogrel 75 mg/day for 9 days, at which time clopidogrel pharmacokinetic and pharmacodynamic endpoints were measured.



At steady-state, clopidogrel active metabolite (clopidogrel(AM)) pharmacokinetics varied widely between subjects (coefficients of variation [CVs] 33.8% and 40.2% for clopidogrel(AM) area under the time-concentration curve and peak plasma concentration, respectively). On-treatment vasodilator stimulated phosphoprotein P2Y(12) platelet reactivity index (PRI), maximal platelet aggregation (MPA) to adenosine phosphate, and VerifyNow P2Y12 platelet response units (PRU) also varied widely (CVs 32% to 53%). All identified factors together accounted for only 18% of intersubject variation in pharmacokinetic parameters and 32% to 64% of intersubject variation in PRI, MPA, and PRU. High on-treatment platelet reactivity was present in 45% of subjects.



Clopidogrel pharmacokinetics and pharmacodynamics vary widely despite rigorous exclusion or control of known disease, polymorphisms (CYP2C19, CYP3A5, ABCB1, PON1), noncompliance, co-medications, diet, smoking, alcohol, demographics, and pre-treatment platelet hyperreactivity. Thus, as yet unidentified factors contribute to high on-treatment platelet reactivity with its known increased risk of major adverse cardiovascular events.
Cross-cultural adaptation of research instruments: language, setting, time and statistical considerations

Research questionnaires are not always translated appropriately before they are used in new temporal, cultural or linguistic settings. The results based on such instruments may therefore not accurately reflect what they are supposed to measure. This paper aims to illustrate the process and required steps involved in the cross-cultural adaptation of a research instrument using the adaptation process of an attitudinal instrument as an example.



A questionnaire was needed for the implementation of a study in Norway 2007. There was no appropriate instruments available in Norwegian, thus an Australian-English instrument was cross-culturally adapted.



The adaptation process included investigation of conceptual and item equivalence. Two forward and two back-translations were synthesized and compared by an expert committee. Thereafter the instrument was pretested and adjusted accordingly. The final questionnaire was administered to opioid maintenance treatment staff (n=140) and harm reduction staff (n=180). The overall response rate was 84%. The original instrument failed confirmatory analysis. Instead a new two-factor scale was identified and found valid in the new setting.



The failure of the original scale highlights the importance of adapting instruments to current research settings. It also emphasizes the importance of ensuring that concepts within an instrument are equal between the original and target language, time and context. If the described stages in the cross-cultural adaptation process had been omitted, the findings would have been misleading, even if presented with apparent precision. Thus, it is important to consider possible barriers when making a direct comparison between different nations, cultures and times.
Automated segmentation of foveal avascular zone in fundus fluorescein angiography.

To describe and evaluate the performance of a computerized automated segmentation technique for use in quantification of the foveal avascular zone (FAZ).  A computerized technique for automated segmentation of the FAZ using images from fundus fluorescein angiography (FFA) was applied to 26 transit-phase images obtained from patients with various grades of diabetic retinopathy. The area containing the FAZ zone was first extracted from the original image and smoothed by a Gaussian kernel (sigma = 1.5). An initializing contour was manually placed inside the FAZ of the smoothed image and iteratively moved by the segmentation program toward the FAZ boundary. Five tests with different initializing curves were run on each of 26 images to assess reproducibility. The accuracy of the program was also validated by comparing results obtained by the program with the FAZ boundaries manually delineated by medical retina specialists. Interobserver performance was then evaluated by comparing delineations from two of the experts.  One-way analysis of variance indicated that the disparities between different tests were not statistically significant, signifying excellent reproducibility for the computer program. There was a statistically significant linear correlation between the results obtained by automation and manual delineations by experts.  This automated segmentation program can produce highly reproducible results that are comparable to those made by clinical experts. It has the potential to assist in the detection and management of foveal ischemia and to be integrated into automated grading systems.
Galactin-3 and brain natriuretic peptide versus conventional echocardiography in the early detection of cirrhotic cardiomyopathy.

Cirrhotic cardiomyopathy (CCM) is defined as an abnormal heart structure and function in cirrhotic patients. CCM includes systolic and diastolic dysfunction, electrophysiological abnormalities, and structural changes, both microscopic and macroscopic. Currently, there is no one diagnostic test that can identify patients with CCM. Evaluation of the validity of galactin-3 and brain natriuretic peptide (BNP) as biomarkers in the early detection of CCM in comparison to conventional echocardiography.



A case control study was carried out in the Departments of internal medicine and tropical Medicine, Assuit University, Egypt. Seventy-one subjects were divided into the following three groups: 26 cirrhotic patients without ascites, 25 cirrhotic patients with ascites, and 20 healthy controls. All groups underwent clinical examination, and laboratory investigation including BNP, galactin-3, and echocardiography.



There was a significant difference between the three groups (p < 0.001) with regard to corrected QT (cQT), BNP and galactin-3. Left ventricular diastolic dysfunction with different grades was the most recorded cardiac abnormality in the patient group I and II (88.5% and 96%; respectively) with significantly increased frequency and severity in ascetic patients and with the advancement of liver cirrhosis. BNP and galactin-3 were sensitive and specific biomarkers for the detection of diastolic dysfunction in cirrhotic patients (77.6%, 95.5%, 89.9% and 86.4%; respectively).



Diastolic dysfunction is a common cardiac abnormality in cirrhotic patients that worsens with the advancement of cirrhosis. BNP and galactin-3 had higher sensitivity and specificity in the early detection of CCM compared with those of conventional echocardiography.
Real-world characterization and differentiation of the Global Initiative for Chronic Obstructive Lung Disease strategy classification

This study aimed to characterize and differentiate the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy 2011 cut points through the modified Medical Research Council dyspnea scale (mMRC) and chronic obstructive pulmonary disease (COPD) assessment test (CAT).



Analysis of COPD patient data from the 2012 Adelphi Respiratory Disease Specific Program was conducted in Europe and US. Matched data from physicians and patients included CAT and mMRC scores. Receiver operating characteristic curves and kappa analysis determined a cut point for CAT and mMRC alignment and thus defined patient movement ("movers") within GOLD groups A-D, depending on the tool used. Logistic regression analysis, with a number of physician- and patient-reported covariates, characterized those movers.



Comparing GOLD-defined high-symptom patients using mMRC and CAT cut points (≥2 and ≥10, respectively), there were 890 (53.65%) movers; 887 of them (99.66%) moved from less symptomatic GOLD groups A and C (using mMRC) to more symptomatic groups B and D (using CAT). For receiver operating characteristic (area under the curve: 0.82, P<0.001) and kappa (maximized: 0.45) recommended CAT cut points of ≥24 and ≥26, movers reduced to 429 and 403 patients, respectively. Logistic regression analysis showed variables significantly associated with movers were related to impact on normal life, age, cough, and sleep (all P<0.05). Within movers, direction of movement was significantly associated with the same variables (all P<0.05).



Use of current mMRC or CAT cut points leads to inconsistencies for COPD assessment classification. It is recommended that cut points are aligned and both tools administered simultaneously for optimal patient care and to allow for closer management of movers. Our research may suggest an opportunity to investigate a combined score approach to patient management based on the worst result of mMRC and CAT. The reduced number of remaining movers may then identify patients who have greater impact of disease and may require a more personalized treatment plan.
Clinical and MRI correlates of cerebral palsy: the European Cerebral Palsy Study.

Magnetic resonance imaging (MRI) findings have been reported for specific clinical cerebral palsy (CP) subgroups or lesion types but not in a large population of children with all CP subtypes. Further information about the causes of CP could help identify preventive strategies.



To investigate the correlates of CP in a population sample and compare clinical findings with information available from MRI brain studies.



Cross-sectional, population-based investigative study conducted in 8 European study centers (North West London and North East London, England; Edinburgh, Scotland; Lisbon, Portugal; Dublin, Ireland; Stockholm, Sweden; Tübingen, Germany; and Helsinki, Finland).



Five hundred eighty-five children with CP were identified who had been born between 1996 and 1999; 431 children were clinically assessed and 351 had a brain MRI scan.



Standardized clinical examination results, parental questionnaire responses, MRI results, and obstetric, genetic, and metabolic data from medical records.



Important findings include the high rate of infections reported by mothers during pregnancy (n = 158 [39.5%]). In addition, 235 children (54%) were born at term while 47 children (10.9%) were very preterm (<28 weeks). A high rate of twins was found, with 51 children (12%) known to be from a multiple pregnancy. Clinically, 26.2% of children had hemiplegia, 34.4% had diplegia, 18.6% had quadriplegia, 14.4% had dyskinesia, 3.9% had ataxia, and 2.6% had other types of CP. Brain MRI scans showed that white-matter damage of immaturity, including periventricular leukomalacia (PVL), was the most common finding (42.5%), followed by basal ganglia lesions (12.8%), cortical/subcortical lesions (9.4%), malformations (9.1%), focal infarcts (7.4%), and miscellaneous lesions (7.1%). Only 11.7% of these children had normal MRI findings. There were good correlations between the MRI and clinical findings.



These MRI findings suggest that obstetric mishaps might have occurred in a small proportion of children with CP. A systematic approach to identifying and treating maternal infections needs to be developed. Multiple pregnancies should be monitored closely, and the causes of infant stroke need to be investigated further so preventive strategies can be formulated. All children with CP should have an MRI scan to provide information on the timing and extent of the lesion.
Sexual behavior, fertility desires and unmet need for family planning among home-based care clients and caregivers in Kenya.

As antiretroviral treatment becomes more available, community home-based care (CHBC) clients may begin to resume normal daily activities including the resumption of sexual relationships. This study examines sexual behavior, contraceptive use, unmet need for family planning and attitudes toward pregnancy in the context of HIV among CHBC participants (clients and caregivers), many of whom are HIV-positive or at risk for HIV, of the COPHIA project in Kenya. The COPHIA project was implemented by Pathfinder International with support from USAID/Kenya. We interviewed 171 CHBC clients and 183 CHBC caregivers and conducted four focus groups with caregivers. Data were collected from randomly selected COPHIA-affiliated CHBC programs in Western Province and in Nairobi between September and November 2004. Forty-four percent of clients and 55% of caregivers had been sexually active in the past six months. The reproductive health needs of this population are complex; a significant percentage of study participants have an unmet need for family planning and some desire more children. A small proportion of study participants were pregnant during the time of the interview. The majority of those who use contraception reported relying solely on the male condom to prevent pregnancy. While vital for HIV prevention and easily distributed by CHBC programs, the male condom is not as effective as other methods in preventing pregnancy. Community home-based care program participants need counseling related to contraception, fertility desires and pregnancy. The promotion of dual method use is crucial to this population. Besides referring participants to family planning services, CHBC programs need to consider how and if they can meet the family planning and other reproductive health needs of their participants.