nils-herrmann/clean_scirepeval huggingface dataset:
Sequential vinorelbine–capecitabine followed by docetaxel in advanced breast cancer: long-term results of a pilot phase II trial

To evaluate the response rate of the combination of capecitabine (C) and vinorelbine (V) followed by Docetaxel (D) in the 1st line treatment of advanced and metastatic breast cancer patients. Patients with measurable disease and no prior chemotherapy in advanced disease were eligible. Pts received V 25 mg/m2 on day 1 and 8 in combination with C 825 mg/m2 twice a day from day 1 to 14 every 3 weeks for four cycles followed by 12 consecutive weeks of D 25 mg/m2/w. Between March 2002 and November 2003, 40 patients were enrolled. Median age was 57 years. Of patients, 77.5% of pts had visceral involvement and 32.5% had more than two metastatic sites. In the adjuvant setting, 62.5% received anthracycline and 10% Taxanes. In the intent-to-treat population, an overall objective response was observed in 25 patients (62.5, 95% CI, 45.8–77.27) and stable disease in 5 (12.5%). Median time till progression (TTP) was 12.3 months (range 1.5–48; 95% CI, 10.05–14.54). The median survival was 35.7 months (range 2–47). Reported grade 3–4 toxicities under Navcap were neutropenia (4 pts), anemia (1 pt), thrombopenia (1 pt) and febrile neutropenia (3 pts). Reported grade 3–4 toxicities under weekly Docetaxel were neutropenia (1 pt), thrombopenia (2 pts), leucopenia (1 pt) and anemia (1 pt). The sequential use of Navcap followed by weekly Docetaxel demonstrated an interesting efficacy with a prolonged TTP and OS and warrants further evaluation.
Fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome: postnatal outcomes of the first 100 patients.

Fetal aortic valvuloplasty can be performed for severe midgestation aortic stenosis in an attempt to prevent progression to hypoplastic left heart syndrome (HLHS). A subset of patients has achieved a biventricular (BV) circulation after fetal aortic valvuloplasty. The postnatal outcomes and survival of the BV patients, in comparison with those managed as HLHS, have not been reported.



We included 100 patients who underwent fetal aortic valvuloplasty for severe midgestation aortic stenosis with evolving HLHS from March 2000 to January 2013. Patients were categorized based on postnatal management as BV or HLHS. Clinical records were reviewed. Eighty-eight fetuses were live-born, and 38 had a BV circulation (31 from birth, 7 converted after initial univentricular palliation). Left-sided structures, namely aortic and mitral valve sizes and left ventricular volume, were significantly larger in the BV group at the time of birth (P<0.01). After a median follow-up of 5.4 years, freedom from cardiac death among all BV patients was 96±4% at 5 years and 84±12% at 10 years, which was better than HLHS patients (log-rank P=0.04). There was no cardiac mortality in patients with a BV circulation from birth. All but 1 of the BV patients required postnatal intervention; 42% underwent aortic or mitral valve replacement. On the most recent echocardiogram, the median left ventricular end-diastolic volume z score was +1.7 (range, -1.3 to +8.2), and 80% had normal ejection fraction.



Short- and intermediate-term survival among patients who underwent fetal aortic valvuloplasty and achieved a BV circulation postnatally is encouraging. However, morbidity still exists, and ongoing assessment is warranted.
Twin Studies and Other Genetical Investigations in the Danish Cancer Registry

League, and working in close collaboration with the National Health Service, is an organization with the primary intention to register all cancer cases, for resbarch purposes. This is done through a voluntary system ; all hospitals noti.y their cancer cases to the registry, and these notifications are supplemented with death certificates for all persons who are known to have suffered from malignant diseases, including leukaemias, myelomata and brain tumours. From Clemmesen's studies on occupational mortality from cancer in Denmark it was clear, already before the start of the Registry, that a complete investigation of the occurrence of cancer demAnded at least an estimation of the role played by heredity in the origin of various cancers. It-was thought to be especially valuable to carry out such an investigation alongside the mapping out of cancer incidence with regard to age, occupation, and other variables, and to compare the hereditary tendency shown by cancers of various sites in the same population and at the same time.
Quantitative assessment of regional myocardial blood flow using oxygen-15-labelled water and positron emission tomography: a multicentre evaluation in Japan

Recently, a method has been proposed for the quantitative measurement of regional myocardial blood flow (MBF) using oxygen-15-labelled water and positron emission tomography (PET). A multicentre project was organized with the intention of evaluating the accuracy of this method, particularly as a multicentre clinical investigative tool. Each of seven institutions performed PET studies on more than five normal volunteers following a specified protocol. The PET study included a transmission scan, a 15O-carbon monoxide static scan and a 15O-water dynamic scan, thereby yielding MBF values which should have been independent of the spatial resolution of the PET scanner employed. Fifty-three subjects (aged 20–63 years, mean±SD 36±12 years) were studied at rest, and 31 of these subjects were also studied after dipyridamole in five institutions. Inter-institution consistency and intra-subject variation in MBF values were then evaluated. MBF averaged for all subjects was 0.93±0.34 ml min–1 g–1 at rest and 3.40±1.73 ml min–1 g–1 after the administration of dipyridamole, and the flow reserve (defined as the ratio of the two MBF values) was 3.82±2.12; these values are consistent with previous reports. Resting MBF values were significantly correlated with the heart rate–blood pressure product (RPP) (y=0.31+6.56E-5 x, P<0.010), and RPP was in resting MBF observed in all institutions was well explained by the age-dependent RPP. No significant difference was observed in resting MBF among the institutions. Except in one institution, no significant difference was seen in dipyridamole MBF or myocardial flow reserve. No significant difference was found among the myocardial segments. Regional variation was reasonably small in five institutions, but was not acceptable in two institutions, which was attributed to the scanner performance. These observations suggest that the 15O-water PET technique is useful for a multicentre clinical study if the PET scanner can provide time-activity data with good count statistics.
Alisporivir plus ribavirin, interferon free or in combination with pegylated interferon, for hepatitis C virus genotype 2 or 3 infection.

Alisporivir is a cyclophilin inhibitor with pan-genotypic anti-hepatitis C virus (HCV) activity and a high barrier to viral resistance. The VITAL-1 study assessed alisporivir as interferon (IFN)-free therapy in treatment-naïve patients infected with HCV genotype 2 or 3. Three hundred forty patients without cirrhosis were randomized to: arm 1, alisporivir (ALV) 1,000 mg once-daily (QD); arm 2, ALV 600 mg QD and ribavirin (RBV); arm 3, ALV 800 mg QD and RBV; arm 4, ALV 600 mg QD and pegylated IFN (Peg-IFN); or arm 5, Peg-IFN and RBV. Patients receiving IFN-free ALV regimens who achieved rapid virological response (RVR) continued the same treatment throughout, whereas those with detectable HCV RNA at week 4 received ALV, RBV, and Peg-IFN from weeks 6 to 24. Overall, 300 patients received ALV-based regimens. In arm 1 to arm 4, the intent-to-treat rates of sustained virological response (SVR) 24 weeks after treatment (SVR24) were from 80% to 85%, compared with 58% (n = 23 of 40) with Peg-IFN/RBV. Per-protocol analysis showed higher SVR24 rates in patients who received ALV/RBV, IFN-free after RVR (92%; n = 56 of 61) than with ALV alone after RVR (72%; n = 13 of 18) or with Peg-IFN/RBV (70%; n = 23 of 33). Both RVRs and SVRs to ALV IFN-free regimens were numerically higher in genotype 3- than in genotype 2-infected patients. Viral breakthrough was infrequent (3%; n = 7 of 258). IFN-free ALV treatment showed markedly better safety/tolerability than IFN-containing regimens.



ALV plus RBV represents an effective IFN-free option for a proportion of patients with HCV genotype 2 or 3 infections, with high SVR rates for patients with early viral clearance. Further investigations of ALV in IFN-free combination regimens with direct-acting antiviral drugs deserve exploration in future trials.
System barriers to the evidence-based care of acute coronary syndrome patients in China: qualitative analysis.

Organizational and wider health system factors influence the implementation and success of interventions.  We performed a qualitative evaluation to examine the system-level barriers to implementing clinical pathways in the dynamic healthcare environment of China.



A qualitative descriptive analysis of 40 in-depth interviews with health professionals conducted in a sample of 10 hospitals purposively selected to explore barriers to implementation of the intervention. Qualitative data were analyzed using the Framework method. In-depth interviews identified 5 key system-level barriers to effective implementation: (1) leadership support for implementing quality improvement, (2) variation in the capacity of clinical services and quality improvement resources, (3) fears of patient disputes and litigation, (4) healthcare funding constraints and high out-of-pocket expenses, and (5) patient-related factors.



System-level barriers affect the ability of acute coronary syndrome clinical pathways to change practice. Addressing these barriers in the context of current and planned national health system reform will be critical for future improvements in the management of acute coronary syndromes, and potentially other hospitalized conditions, in China.
Diaphragm for STI and HIV prevention: is it a safe method for women at high risk?

Female sex workers (n = 140) were enrolled in a 6-month acceptability trial of the diaphragm. We randomized a subset (n = 40) to receive colposcopies after 1 month of diaphragm use or after 1 month of observation before commencing diaphragm use. Adverse events were mild in nature. Frequency of colposcopic findings did not differ between women randomized to immediate versus delayed diaphragm use (P = 0.25).
The relationship between disease activity and depressivesymptoms severity and optimism—results from the IMPROVED study

To assess depressive symptoms severity and dispositional optimism in patients with recent onset arthritis both before and after 4 months treatment. Two hundred twenty-two patients with recent onset RA and undifferentiated arthritis in the IMPROVED study filled out the Beck Depression Inventory (BDI-II) to assess depressive symptoms severity and the Life Orientation Test Revised (LOT-R) to measure optimism before and after 4 months of treatment. All patients were treated with methotrexate 25 mg/week and prednisone 60 mg/day (tapered to 7.5 mg/day in 7 weeks). Linear regression analysis was used to assess the association between the disease activity score (DAS) and its components (tender joint count, general well-being measured with a visual analogue scale (VAS), swollen joint count, and erythrocyte sedimentation rate) with the BDI-II an LOT-R scores. In general, depressive symptoms were mild. The DAS was an independent predictor of depressive symptoms scores both at baseline and after 4 months follow-up, in particular tender joint count and VAS global health. Disease activity was not associated with the level of optimism. Nevertheless, patients who achieved clinical remission improved significantly more in both depression score and optimism score than patients who did not. Patients with early arthritis report improvement in depressive symptoms and optimism with improvement in disease activity and achieving clinical remission. Depression scores are associated with pain and unwell being but not with swollen joint counts and inflammatory parameters.
Effects of long-term biventricular stimulation for resynchronization on echocardiographic measures of remodeling.

Long-term ventricular resynchronization therapy improves symptom status. Changes in left ventricular remodeling have not been adequately evaluated.



Fifty-three patients with systolic heart failure and bundle-branch block underwent implantation of biventricular stimulation (BVS) devices as part of a randomized trial. Echocardiograms were acquired at randomization and at 6-week intervals until completion of 12 weeks of continuous BVS. There were no changes in heart rate or QRS duration after 12 weeks of BVS. Serum norepinephrine values did not change with BVS. After 12 weeks of BVS, left atrial volume decreased. Left ventricular end-systolic and end-diastolic dimensions and left ventricular end-systolic volume also decreased after 12 weeks of BVS. Sphericity index did not change. Measures of systolic function, including left ventricular outflow tract and aortic velocity time integral and myocardial performance index, improved.



Long-term resynchronization therapy results in atrial and ventricular reverse remodeling and improved hemodynamics.
Phase II study of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin

To evaluate the efficacy and safety of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin. The FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m2 on day 1 plus leucovorin (LV) 400 mg/m2 on day 1 plus 5-fluorouracil (5-FU) 400 mg/m2 bolus on day 1 plus 46-hour intravenous infusion of 5-FU 2,400 mg/m2, every 2 weeks as one cycle. The main selection criterion for this study was the advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin. Of the 57 evaluable patients for efficacy, 4 (7.5%) had a partial response, 36 (67.9%) had stable disease, and 13 (24.5%) had progressive disease. Median progression-free survival was 4.8 months (95% CI 3.9–5.7 months), and median overall survival was 7.8 months (95% CI 13.1–16.5 months). Safety analysis was based on the data of 57 evaluable patients. The most frequently observed grade 3 or 4 toxicities were neutropenia 16 (27.8%), nausea/vomiting 7 (12.3%), and diarrhea 1 (1.8%). FOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin in Chinese population.
A case-controlled validation study of a blood-based seven-gene biomarker panel for colorectal cancer in Malaysia

Colorectal cancer (CRC) screening is key to CRC prevention and mortality reduction, but patient compliance with CRC screening is low. We previously reported a blood-based test for CRC that utilizes a seven-gene panel of biomarkers. The test is currently utilized clinically in North America for CRC risk stratification in the average-risk North American population in order to improve screening compliance and to enhance clinical decision making.



In this study, conducted in Malaysia, we evaluated the seven-gene biomarker panel validated in a North American population using blood samples collected from local patients. The panel employs quantitative RT-PCR (qRT-PCR) to analyze gene expression of the seven biomarkers (ANXA3, CLEC4D, TNFAIP6, LMNB1, PRRG4, VNN1 and IL2RB) that are differentially expressed in CRC patients as compared with controls. Blood samples from 210 patients (99 CRC and 111 controls) were collected, and total blood RNA was isolated and subjected to quantitative RT-PCR and data analysis.



The logistic regression analysis of seven-gene panel has an area under the curve (AUC) of 0.76 (95% confidence interval: 0.70 to 0.82), 77% specificity, 61% sensitivity and 70% accuracy, comparable to the data obtained from the North American investigation of the same biomarker panel.



Our results independently confirm the results of the study conducted in North America and demonstrate the ability of the seven biomarker panel to discriminate CRC from controls in blood samples drawn from a Malaysian population.
Acute Effects of Contract-Relax Stretching vs. TENS in Young Subjects With Anterior Knee Pain: A Randomized Controlled Trial.

Valenza, MC, Torres-Sánchez, I, Cabrera-Martos, I, Valenza-Demet, G, and Cano-Cappellacci, M. Acute effects of contract-relax stretching vs. TENS in young subjects with anterior knee pain: A randomized controlled trial. J Strength Cond Res 30(8): 2271-2278, 2016-The aim of this study was to examine the immediate effects on pressure point tenderness, range of motion (ROM), and vertical jump (VJ) of contract-relax stretching vs. transcutaneous electrical nerve stimulation (TENS) therapy in individuals with anterior knee pain (AKP). Eighty-four subjects with AKP were randomly assigned to 1 of 3 different intervention groups: a contract-relax stretching group (n = 28), a TENS intervention group (n = 28), and a control group (n = 28). The participants included in the sample were both sex (37.5% men vs. 62.5% women) at a mean age of 21 years, with mean values of height and weight of 169 cm and 64 kg, respectively. The main outcome measures were knee ROM, pressure pain threshold (PPT), and VJ. The participants were assessed at baseline and immediately after treatment. In the case of VJ, at baseline, immediately after the intervention, at 3 and at 6 minutes posttreatment. The data analysis showed that PPT scores of participants in the stretching and TENS group significantly increased from pretest to posttest (p ≤ 0.05). A significant increase pre- to posttreatment in ROM (p < 0.001) was also observed in both treatment groups. In VJ measures, TENS and stretching groups showed significant differences between preintervention and all postintervention values (p ≤ 0.05), whereas no significant differences were found in the control group. In conclusion, the results show significant pre-to-post-treatment effects in PPT, ROM, and VJ from both contract-relax stretching and TENS in young subjects with AKP.
Early recovery of aggressive cytotoxic cells and improved immune resurgence with post-transplant immunotherapy for multiple myeloma

A phase I/II trial evaluated early administration and dose escalation of interleukin (IL)-2 with granulocyte macrophage colony stimulating factor (GM-CSF) post-transplant. Following melphalan (200 mg/m2) and an autologous transplant, IL-2 was initiated (day 0) and continued for 4 weeks. GM-CSF (250 mcg/m2/day) began on day 5. Fifteen of 19 patients completed therapy. No treatment-related deaths occurred. IL-2 (1 × 106 IU/m2/day) was not tolerated in two of six patients due to ⩾grade 3 fatigue/diarrhea (n=1) or supraventricular tachycardia (n=1). The maximum tolerated dose of IL-2 was 6 × 105 IU/m2/day; this dose was well tolerated by 11 of 13 patients. Neutrophil and platelet engraftment occurred on day 13 (median; range 10–17 days) and day 13 (median; range 0–74 days), respectively. When compared to control patients, there was a marked increase in the number of CD3+ T cells (P=0.005), CD4+ T cells (P=0.01), CD8+ T cells (P=0.001) and CD4+CD25+Treg cells (P=0.015) post-transplant. Cytotoxicity directed against myeloma cells was markedly increased when compared to control patients (P=0.017). This unique trial design using early administration of IL-2 with GM-CSF during the period of lymphodepletion, demonstrated a marked increase in the number and function of early cytotoxic effector T cells, without suppression of engraftment.
Feasibility of fully automated detection of fiducial markers implanted into the prostate using electronic portal imaging: a comparison of methods.

To investigate the feasibility of fully automated detection of fiducial markers implanted into the prostate using portal images acquired with an electronic portal imaging device.



We have made a direct comparison of 4 different methods (2 template matching-based methods, a method incorporating attenuation and constellation analyses and a cross correlation method) that have been published in the literature for the automatic detection of fiducial markers. The cross-correlation technique requires a-priory information from the portal images, therefore the technique is not fully automated for the first treatment fraction. Images of 7 patients implanted with gold fiducial markers (8 mm in length and 1 mm in diameter) were acquired before treatment (set-up images) and during treatment (movie images) using 1MU and 15MU per image respectively. Images included: 75 anterior (AP) and 69 lateral (LAT) set-up images and 51 AP and 83 LAT movie images. Using the different methods described in the literature, marker positions were automatically identified.



The method based upon cross correlation techniques gave the highest percentage detection success rate of 99% (AP) and 83% (LAT) set-up (1MU) images. The methods gave detection success rates of less than 91% (AP) and 42% (LAT) set-up images. The amount of a-priory information used and how it affects the way the techniques are implemented, is discussed.



Fully automated marker detection in set-up images for the first treatment fraction is unachievable using these methods and that using cross-correlation is the best technique for automatic detection on subsequent radiotherapy treatment fractions.
Usefulness of combined risk stratification with heart rate and systolic blood pressure in the management of chronic heart failure. A report from the CHART-2 study.

The appropriate target ranges of heart rate (HR) and systolic blood pressure (SBP) for the management of chronic heart failure (CHF) patients remain to be elucidated in a large-scale cohort study.



We examined 3,029 consecutive CHF patients with sinus rhythm (SR) (mean age, 67.9 years) registered in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 Study (CHART-2; NCT00418041). There were 357 deaths (11.8%) during the median follow-up of 3.1 years. We first performed the classification and regression tree analysis for mortality, identifying SBP <89 mmHg, HR >70 beats/min and SBP <115 mmHg as the primary, secondary and tertiary discriminators, respectively. According to these, we divided the patients into low- (n=1,131), middle- (n=1,624) and high-risk (n=274) groups with mortality risk <10%, 10-20% and >20%, respectively. The low-risk group was characterized by SBP >115 mmHg and HR <70 beats/min and the high-risk group by SBP <89 mmHg regardless of HR values or SBP 89-115 mmHg and HR >76 beats/min. Multivariate Cox regression analysis revealed that the hazard ratio of all-cause death for low-, middle- and high-risk groups was 1.00 (reference), 1.48 (95% confidence interval (CI): 1.10-1.99, P=0.009) and 2.44 (95% CI 1.66-3.58, P<0.001), respectively. Subgroup analysis revealed that age ≥70 years, diabetes, or reduced left ventricular function had higher hazard ratios in the high-risk group.



The results demonstrate the usefulness of combined risk stratification of HR and SBP in CHF patients with SR.