nils-herrmann/clean_scirepeval huggingface dataset:
Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with <ce:italic>BRCA1</ce:italic> or <ce:italic>BRCA2</ce:italic> mutations and advanced breast cancer: a proof-of-concept trial

Olaparib, a novel, orally active poly(ADP-ribose) polymerase (PARP) inhibitor, induced synthetic lethality in BRCA-deficient cells. A maximum tolerated dose and initial signal of efficacy in BRCA-deficient ovarian cancers have been reported. We therefore assessed the efficacy, safety, and tolerability of olaparib alone in women with BRCA1 or BRCA2 mutations and advanced breast cancer.



Women (aged >or=18 years) with confirmed BRCA1 or BRCA2 mutations and recurrent, advanced breast cancer were assigned to two sequential cohorts in a phase 2 study undertaken in 16 centres in Australia, Germany, Spain, Sweden, the UK, and the USA. The first cohort (n=27) was given continuous oral olaparib at the maximum tolerated dose (400 mg twice daily), and the second (n=27) was given a lower dose (100 mg twice daily). The primary efficacy endpoint was objective response rate (ORR). 
Patients had been given a median of three previous chemotherapy regimens (range 1-5 in cohort 1, and 2-4 in cohort 2). ORR was 11 (41%) of 27 patients (95% CI 25-59) in the cohort assigned to 400 mg twice daily, and six (22%) of 27 (11-41) in the cohort assigned to 100 mg twice daily. Toxicities were mainly at low grades. The most frequent causally related adverse events in the cohort given 400 mg twice daily were fatigue (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), nausea (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), vomiting (grade 1 or 2, three [11%]; grade 3 or 4, three [11%]), and anaemia (grade 1 or 2, one [4%]; grade 3 or 4, three [11%]). The most frequent causally related adverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, 11 [41%]; none grade 3 or 4) and fatigue (grade 1 or 2, seven [26%]; grade 3 or 4, one [4%]).



The results of this study provide positive proof of concept for PARP inhibition in BRCA-deficient breast cancers and shows a favourable therapeutic index for a novel targeted treatment strategy in patients with tumours that have genetic loss of function of BRCA1-associated or BRCA2-associated DNA repair. Toxicity in women with BRCA1 and BRCA2 mutations was similar to that reported previously in those without such mutations.
Treated glycosylated hemoglobin levels in individuals with diabetes mellitus vary little by health status

As choosing wisely has raised the issue of whether some individuals with type 2 diabetes may be overtreated, we examined the intensity of glycemic control across health status strata defined by comorbidities or frailty.This is a retrospective cohort study of commercially insured patients from 50 US states (Clinformatics Data Mart). We evaluated treated HbA1c levels in adults with new diabetes diagnosed between January 2004 and December 2009 who had HbA1C measured after at least 1 year of follow-up.Of 191,590 individuals with diabetes, 78.5% were otherwise healthy, 10.6% had complex health status (3 or more chronic conditions), and 10.9% were very complex (Johns Hopkins Adjusted Clinical Groups frailty marker or end-stage chronic disease). The proportion of patients who were tightly controlled (HbA1C <7%) was similar in otherwise healthy patients (66.1%) and in complex patients (65.8%, P = 0.37), and although it was lower (60.9%, P < 0.0001) in very complex patients, the magnitude of the difference was small. A substantial proportion of complex/very complex patients were taking sulfonylurea or insulin despite being at an increased risk for adverse effects from these agents and having tightly controlled HbA1C: 40.6% had HbA1C <7% and 24% had HbA1C <6.5%. Among patients with HbA1C <7%, use of insulin or sulfonylureas was associated with an increased risk for all-cause hospitalization [aHR 1.54, 95% confidence interval (95% CI) 1.45-1.64] and for emergency room visits (aHR 1.44, 95% CI 1.35-1.53) over the subsequent median 6 months follow-up.Diabetic control was similar regardless of comorbidity burden and frailty status. Despite being at a higher risk for adverse effects, nearly half of complex and very complex patients were still receiving insulin or sulfonylureas despite having treated HbA1C levels <7%, and these patients did exhibit higher risk of all-cause hospitalizations or emergency visits subsequently.
Satisfaction with life, self-esteem and evaluation of mental health in people with tattoos or piercings.

The aim of the study was to determine the level of life satisfaction and the various dimensions of self-esteem of pierced or tattooed people, and evaluate their mental health, compared to those without similar body modifications.



The study was conducted on a sample of 449 people aged 16-58 years (mean age 26.7 ± 6.35), of whom 308 had body modifications: tattoo (n = 90), body piercings in places other than the ear lobe (n = 53), or both tattoos and piercings (n = 165). The control group consisted of 141 people without such modifications. The participants completed a questionnaire concerning their socio-demographic status, as well as the following psychological tests: The Satisfaction with Life Scale (SWLS), Multidimensional Self-Esteem Inventory (MSEI) and General Health Questionnaire (GHQ-28).



Our findings show no significant differences in terms of life satisfaction between the group with tattoos or piercings and the control group. People with body modifications were characterized by higher self-esteem, with regard to their competence and leadership abilities. They also display fewer symptoms of social impairment and sleep disorders than the control group.



Tattoos and piercings should not be considered as indicators of psychopathology.
Effect of increased exercise in school children on physical fitness and endothelial progenitor cells: a prospective randomized trial.

The aim of this prospective, randomized study was to examine whether additional school exercise lessons would result in improved peak oxygen uptake (primary end point) and body mass index-standard deviation score, motor and coordinative abilities, circulating progenitor cells, and high-density lipoprotein cholesterol (major secondary end points).



Seven sixth-grade classes (182 children, aged 11.1+/-0.7 years) were randomized to an intervention group (4 classes with 109 students) with daily school exercise lessons for 1 year and a control group (3 classes with 73 students) with regular school sports twice weekly. The significant effects of intervention estimated from ANCOVA adjusted for intraclass correlation were the following: increase of peak o(2) (3.7 mL/kg per minute; 95% confidence interval, 0.3 to 7.2) and increase of circulating progenitor cells evaluated by flow cytometry (97 cells per 1 x 10(6) leukocytes; 95% confidence interval, 13 to 181). No significant difference was seen for body mass index-standard deviation score (-0.08; 95% confidence interval, -0.28 to 0.13); however, there was a trend to reduction of the prevalence of overweight and obese children in the intervention group (from 12.8% to 7.3%). No treatment effect was seen for motor and coordinative abilities (4; 95% confidence interval, -1 to 8) and high-density lipoprotein cholesterol (0.03 mmol/L; 95% confidence interval, -0.08 to 0.14).



Regular physical activity by means of daily school exercise lessons has a significant positive effect on physical fitness (o(2)max). Furthermore, the number of circulating progenitor cells can be increased, and there is a positive trend in body mass index-standard deviation score reduction and motor ability improvement. Therefore, we conclude that primary prevention by means of increasing physical activity should start in childhood.
The CONECSI trial: Results of a randomized controlled trial of a multidisciplinary cognitive behavioral program for coping with chronic neuropathic pain after spinal cord injury

Many people with spinal cord injury (SCI) rate chronic neuropathic pain as one of the most difficult problems to manage. The aim of the CONECSI (COping with NEuropathiC Spinal cord Injury pain) trial was to evaluate a multidisciplinary cognitive behavioral treatment program for persons with chronic neuropathic pain after SCI. The intervention consisted of educational, cognitive, and behavioral elements. A total of 61 people were randomized to either the intervention group or the waiting list control group in 4 Dutch rehabilitation centers. Primary outcomes were pain intensity and pain-related disability (Chronic Pain Grade questionnaire), and secondary outcomes were mood (Hospital Anxiety and Depression Scale), participation in activities (Utrecht Activities List), and life satisfaction (Life Satisfaction Questionnaire). Measurements were performed at baseline, and at 3, and 6 months follow-up. The primary statistical technique was random coefficient analysis. The analyses showed significant changes over time on both primary (t1-t2), and 2 out of 4 secondary outcomes (both t1-t2 and t1-t3). Significant intervention effects (Time*Group interactions) were found for anxiety and participation in activities, but not for the primary outcomes. Subsequent paired t tests showed significant changes in the intervention group that were not seen in the control group: decrease of pain intensity, pain-related disability, anxiety, and increase of participation in activities. This study implies that a multidisciplinary cognitive behavioral program might have beneficial effects on people with chronic neuropathic SCI pain.
Randomized Controlled Trial of Strain-Specific Probiotic Formulation (Renadyl) in Dialysis Patients

Primary goal of this randomized, double-blind, placebo-controlled crossover study of Renadyl in end-stage renal disease patients was to assess the safety and efficacy of Renadyl measured through improvement in quality of life or reduction in levels of known uremic toxins. Secondary goal was to investigate the effects on several biomarkers of inflammation and oxidative stress.



Two 2-month treatment periods separated by 2-month washout and crossover, with physical examinations, venous blood testing, and quality of life questionnaires completed at each visit. Data were analyzed with SAS V9.2.



22 subjects (79%) completed the study. Observed trends were as follows (none reaching statistical significance): decline in WBC count (-0.51 × 10(9)/L, P = 0.057) and reductions in levels of C-reactive protein (-8.61 mg/L, P = 0.071) and total indoxyl glucuronide (-0.11 mg%, P = 0.058). No statistically significant changes were observed in other uremic toxin levels or measures of QOL.



Renadyl appeared to be safe to administer to ESRD patients on hemodialysis. Stability in QOL assessment is an encouraging result for a patient cohort in such advanced stage of kidney disease. Efficacy could not be confirmed definitively, primarily due to small sample size and low statistical power-further studies are warranted.
Effects of inverse ratio ventilation versus positive end-expiratory pressure on gas exchange and gastric intramucosal PCO(2) and pH under constant mean airway pressure in acute respiratory distress syndrome.

In patients with acute respiratory distress syndrome, whether inverse ratio ventilation differs from high positive end-expiratory pressure (PEEP) for gas exchange under a similar mean airway pressure has not been adequately examined. The authors used arterial oxygenation, gastric intramucosal partial pressure of carbon dioxide (PiCO(2)), and pH (pHi) to assess whether pressure-controlled inverse ratio ventilation (PC-IRV) offers more benefits than pressure-controlled ventilation (PCV) with PEEP.



Seventeen acute respiratory distress syndrome patients were enrolled and underwent mechanical ventilation with a PCV inspiratory-to-expiratory ratio of 1:2, followed by PC-IRV 1:1 initially. Then, they were randomly assigned to receive PC-IRV 2:1, then 4:1 or 4:1, and then 2:1, alternately. The baseline setting of PCV 1:2 was repeated between the settings of PC-IRV 2:1 and 4:1. Mean airway pressure and tidal volume were kept constant by adjusting the levels of peak inspiratory pressure and applied PEEP. In each ventilatory mode, hemodynamics, pulmonary mechanics, arterial and mixed venous blood gas analysis, PiCO(2), and pHi were measured after a 1-h period of stabilization.



With a constant mean airway pressure, PC-IRV 2:1 and 4:1 decreased arterial and mixed venous oxygenation as compared with baseline PCV 1:2. Neither the global oxygenation indices with oxygen delivery and uptake nor PiCO(2) and pHi were improved by PC-IRV. During PC-IRV, applied PEEP was lower, and auto-PEEP was higher.



When substituting inverse ratio ventilation for applied PEEP to keep mean airway pressure constant, PC-IRV does not contribute more to better gas exchange and gastric intramucosal PiCO(2) and pHi than does PCV 1:2 for acute respiratory distress syndrome patients, regardless of the inspiratory-to-expiratory ratios.
Pretreatment frontal EEG and changes in suicidal ideation during SSRI treatment in major depressive disorder.

We investigated frontal quantitative EEG (QEEG) as predictor of changes in suicidal ideation (SI) during SSRI treatment in major depressive disorder (MDD).



Eighty-two subjects meeting DSM-IV criteria for MDD entered an 8-week, prospective, open-label treatment with flexible dose SSRIs and completed at least 4 weeks of treatment. We assessed MDD severity with the 17-item Hamilton Depression Rating Scale (HAM-D-17); change in SI was measured with HAM-D item no. 3. We recorded four-channel EEGs (F7-Fpz, F8-Fpz, A1-Fpz, A2-Fpz) before treatment.



During the first 4 weeks of treatment 9 (11%) subjects experienced worsening SI. Left-right asymmetry of combined theta + alpha power correlated significantly with change in SI from baseline, even when adjusting for changes in depression severity (HAM-D-17) and for the SSRI utilized.



Frontal QEEG parameters before treatment may predict worsening SI during SSRI treatment in MDD.
Decreases in levels of serum fibronectin predict the severity of vascular leak syndrome in patients treated with ricin A chain-containing immunotoxins.

The major dose-limiting adverse effect of ricin A chain-containing immunotoxin (IT) therapy is vascular leak syndrome (VLS). Since plasma fibronectin (Fn) plays a role in maintaining microcirculatory integrity and since the gradient between plasma and tissue Fn can be altered in various pathological situations, we determined whether the administration of IT-ricin A chain to patients resulted in changes in the levels of serum Fn and, if so, whether these changes correlated with the severity of VLS. We also measured the serum levels of tumor necrosis factor alpha (TNFalpha), a proinflammatory cytokine which has been implicated in tissue damage and in interleukin 2-mediated VLS. Our results indicate that the most severe manifestations of VLS were associated with the highest pretreatment levels of Fn, the largest decreases in Fn immediately after starting IT therapy, increases in the levels of serum TNFalpha, higher concentrations of circulating IT, and the lowest numbers of circulating tumor cells. These parameters should, therefore, be useful for predicting which patients will have severe VLS.
HIV-Infected Liver and Kidney Transplant Recipients : 1-and 3-Year Outcomes

Improvements in human immunodeficiency virus (HIV)-associated mortality make it difficult to deny transplantation based upon futility. Outcomes in the current management era are unknown. This is a prospective series of liver or kidney transplant recipients with stable HIV disease. Eleven liver and 18 kidney transplant recipients were followed for a median of 3.4 years (IQR [interquartile range] 2.9–4.9). Oneand 3year liver recipients’ survival was 91% and 64%, respectively; kidney recipients’ survival was 94%. Oneand 3-year liver graft survival was 82% and 64%, respectively; kidney graft survival was 83%. Kidney patient and graft survival were similar to the general transplant population, while liver survival was similar to the older population, based on 1999–2004 transplants in the national database. CD4+ T-cell counts and HIV RNA levels were stable; and there were two opportunistic infections (OI). The 1and 3-year cumulative incidence (95% confidence intervals [CI]) of rejection episodes for kidney recipients was 52% (28–75%) and 70% (48–92%), respectively. Two-thirds of hepatitis C virus (HCV)-infected patients, but no patient with hepatitis B virus (HBV) infection, recurred. Good transplant and HIV-related outcomes among kidney transplant recipients, and reasonable outcomes among liver recipients suggest that transplantation is an option for selected HIV-infected patients cared for at centers with adequate expertise.
The effect of telephone social support and education on adaptation to breast cancer during the year following diagnosis.

To find the most effective methods of providing social support for women diagnosed with breast cancer by testing the effectiveness of a telephone social support and education intervention to promote emotional and interpersonal adaptation to breast cancer.



Multisite, two-group experimental study with repeated measures.



Arkansas and New Jersey.


SAMPLE
The Arkansas sample consisted of 106 women who entered the study two to four weeks postsurgery for nonmetastatic breast cancer and were randomly assigned to an experimental or control group. The comparison group consisted of 91 women from New Jersey who had participated in a previously completed study that used the same interventions and found that telephone support resulted in more positive, statistically significant adaptation to the disease.



The experimental group received 13 months of telephone social support and education. Both groups received educational materials via a mailed resource kit. The Profile of Mood States; Visual Analogue Scale-Worry; Relationship Change Scale; University of California, Los Angeles, Loneliness Scale-Version 3; and the modified Symptom Distress Scale provided data regarding the variables of interest. Data analysis included descriptive statistics, t tests, and multivariate analysis of variance with repeated measures.



Mood, worry, relationships with significant others, loneliness, and symptoms.



Data analysis showed no significant differences between groups, and both improved on some of the outcomes. Significant time-by-location interaction effects were found when comparing the Arkansas and New Jersey samples, thereby supporting the need to consider regional differences when developing interventions.



The mailed educational resource kit alone appeared to be as effective as the telephone social support provided by oncology nurses in conjunction with the mailed resource kit.



Mailed educational resource kits may be the most efficient and cost-effective way to provide educational support to newly diagnosed patients with breast cancer, but their effect may differ according to region.
Randomised controlled feasibility trial on the use of medical grade honey following microvascular free tissue transfer to reduce the incidence of wound infection.

The aim of this study was to assess the feasibility of using Leptospermum honey in a randomised trial to reduce the incidence of wound infection after microvascular free tissue reconstruction for cancer of the head and neck. During the one-year study period 70 consecutive patients were admitted to the regional maxillofacial ward for free tissue reconstruction. Of these, 56 (80%) consented to be randomised and 49 (70%) were actually randomised, 25 into the honey dressings group, and 24 into the conventional dressings group (control). Six patients were missed when consent was required, 8 did not consent, and 7 who had given consent were missed at the randomisation stage in theatre. Results of wound swabs were positive in 36% of the honey group and 38% of the control group. Methicillin-resistant Staphylococcus aureus (MRSA) was found in 28% and 25%, respectively. Of these, 38% were deemed to require intervention. Honey dressings were acceptable to both patients and nurses. There was a reduction (p<0.05) in duration of hospital stay in the honey group (median 12 days, IQR 10-21) compared with the control (median 18 days, IQR 13-28). The cost of standard and honey dressings was similar. This feasibility study has shown that a randomised controlled trial (RCT) is possible and that several hundreds of patients would be required to show a clinical benefit for honey. Further research is needed to confirm a shorter duration of hospital admission and if so, whether this is due to more rapid healing.
Randomised controlled trial comparing laparoscopic and robot-assisted radical prostatectomy.

The advantages of robot-assisted radical prostatectomy (RARP) over laparoscopic radical prostatectomy (LRP) have rarely been investigated in randomised controlled trials.



To compare RARP and LRP in terms of the functional, perioperative, and oncologic outcomes. The main end point of the study was changes in continence 3 mo after surgery.



From January 2010 to January 2011, 120 patients with organ-confined prostate cancer were enrolled and randomly assigned (using a randomisation plan) to one of two groups based on surgical approach: the RARP group and the LRP group.



All RARP and LRP interventions were performed with the same technique by the same single surgeon.



The demographic, perioperative, and pathologic results, such as the complications and prostate-specific antigen (PSA) measurements, were recorded and compared. Continence was evaluated at the time of catheter removal and 48 h later, and continence and potency were evaluated after 1, 3, 6, and 12 mo. The student t test, Mann-Whitney test, χ(2) test, Pearson χ(2) test, and multiple regression analysis were used for statistics.



The two groups (RARP: n=60; LRP: n=60) were comparable in terms of demographic data. No differences were recorded in terms of perioperative and pathologic results, complication rate, or PSA measurements. The continence rate was higher in the RARP group at every time point: Continence after 3 mo was 80% in the RARP group and 61.6% in the LRP group (p=0.044), and after 1 yr, the continence rate was 95.0% and 83.3%, respectively (p=0.042). Among preoperative potent patients treated with nerve-sparing techniques, the rate of erection recovery was 80.0% and 54.2%, respectively (p=0.020). The limitations included the small number of patients.



RARP provided better functional results in terms of the recovery of continence and potency. Further studies are needed to confirm our results.
Role of adjuvant chemotherapy in patients with early stage uterine papillary serous cancer.

Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer. We studied survival outcomes in patients with stages I/II UPSC.



A retrospective, multi-institutional study of patients with stages I/II UPSC was conducted. Patients underwent surgical staging followed by observation, adjuvant platinum-based chemotherapy (CT), or radiation therapy (RT). Continuous variables were compared via Wilcoxon rank sum test; Fisher exact test was used for the unordered categorical variables. Kaplan-Meier curves were used to estimate survival.



Thirty-nine women were diagnosed with stage I (n = 30) or II (n = 9) UPSC, with a median follow-up of 52 months. Of the 26 patients who did not receive adjuvant CT, 9 developed recurrences and 8 died of their disease. Of the 10 patients with no myometrial invasion who did not receive adjuvant CT, 3 developed recurrences and died. Of the 7 patients who underwent RT, 2 developed distant recurrences and died. Of the 13 patients who underwent CT, 1 developed vaginal recurrence. The 5-year overall (OS) and progression-free survival (PFS) rates for the adjuvant CT group were 100% and 92%, respectively, compared with 69% and 65% for those who did not receive CT (P = 0.002 OS, P = 0.002 PFS). The 5-year OS and PFS rates for RT group were both 71%.



Patients with stages I/II UPSC are at significant risk for distant recurrence and poor survival. Platinum-based adjuvant CT may decrease recurrence rate and improve survival in women with early and well-staged UPSC.