nils-herrmann/clean_scirepeval huggingface dataset:
Prognostic Importance of Changes in Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone.

Limited data exist regarding the impact of aldosterone antagonist therapy on cardiac structure and function in heart failure with preserved ejection fraction and on the prognostic relevance of changes in cardiac structure and function in heart failure with preserved ejection fraction.



Cardiac structure and function were assessed by quantitative echocardiography at baseline and at 12- to 18-month follow-up in 239 patients with heart failure with preserved ejection fraction (left ventricular [LV] ejection fraction [LVEF] ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. The impact of spironolactone therapy on measures of cardiac structure and function was assessed in the study population overall, and change in echocardiographic measures was associated with the subsequent occurrence of the primary composite outcome of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest. Spironolactone was not associated with alterations in cardiac structure and function compared with placebo. Decrease in left atrial volume at follow-up was associated with a lower risk of subsequent occurrence of the primary outcome.



Twelve to 18 months of spironolactone therapy was not associated with alterations in cardiac structure or function in patients with heart failure with preserved ejection fraction. Reduction in left atrial volume at follow-up was associated with a lower risk of subsequent occurrence of the primary composite outcome.
Paclitaxel-ifosfamide-cisplatin as salvage chemotherapy in ovarian cancer patients pretreated with platinum compounds and paclitaxel.

The role of combination chemotherapy regimens in the management of ovarian cancer patients with tumors previously exposed to platinum compounds and paclitaxel has not yet been defined. The present phase II study evaluated the activity and toxicity of a paclitaxel-ifosfamide-cisplatin combination in the aforementioned group of patients. Given the in vitro and in vivo synergism between these three agents, it was believed that using a three drug combination would overcome tumor resistance to cisplatin.



Thirty-five patients were enrolled in the study. The median age was 55 and the median performance status 1. Thirteen (37%) had potentially platinum sensitive, 12 (35%) had primary platinum-resistant and 10 (28%) patients had secondary platinum-resistant tumors. Treatment consisted of paclitaxel 175 mg/m2 as a 3 h i.v. infusion on day 1, cisplatin 75 mg/m2 i.v. over 2 h fractionated over days 1 and 2, and ifosfamide 5 mg/m2 i.v. over 1 h fractionated on days 1-2 with mesna uroprotection. Courses were administered every 3 weeks on an outpatient basis. Granulocyte-colony stimulation factor (G-CSF) was given at a dose of 5 microg/kg/day on days 4-10. A median of 4 cycles were administered with the delivered dose intensity at 85% of the planned dose for the three agents.



Among 35 patients evaluable for response and toxicity, there were 10 partial responses with a response rate of 28.6% (95% confidence interval 12%-45%). Stable disease was recorded in 9 (25.7%) and progressive disease in 16 (45.7%) patients. Subgroup analysis revealed a response rate of 38.5% in potentially platinum-sensitive, 16.5% in primary platinum-resistant and 30% in secondary platinum-resistant tumors. The median response duration was 5 months (range 3-14 months), the median time to progression 6 months (range 3-18 months) and the median survival 12 months (range 3-44 months). Myelotoxicity was significant with neutropenia grade 3 and 4 occurring in 35% and 45% of patients, respectively. Eight episodes (5% of all cycles) of febrile neutropenia were documented and well managed with oral or i.v. antibiotics and G-CSF continuation until complete recovery. Grade 1, 2 and 3 peripheral neuropathy developed in 30%, 30% and 10% of patients, respectively. In conclusion, the three drug combination demonstrated a significant effectiveness in potentially platinum-sensitive tumors and a moderate efficacy in platinum-resistant tumors. The regimen, although myelotoxic, is tolerable with G-CSF support. Further investigation via comparative studies is required to define any superiority of the present regimen over doublets of the three agents in this group of patients.
Comparison of two surgical methods for the treatment of CIN: classical LLETZ (large-loop excision of the transformation zone) versus isolated resection of the colposcopic apparent lesion – study protocol for a randomized controlled trial

In compliance with national and international guidelines, non-pregnant women with cervical intraepithelial neoplasia grade 3 should be treated by cervical conization. According to the definition of the large loop excision of the transformation zone (LLETZ) operation, the lesion needs to be resected, including the transformation zone. It is well known from the literature that the cone size directly correlates with the risk of preterm delivery in the course of a future pregnancy. Thus, it would be highly desirable to keep the cone dimension as small as possible while maintaining the same level of oncological safety.



The aim of this study is to analyze whether resection of the lesion only, without additional excision of the transformation zone, is equally as effective as the classical LLETZ operation regarding oncological outcome. We are performing this prospective, patient-blinded multicenter trial by randomly assigning women who need to undergo a LLETZ operation for cervical intraepithelial neoplasia grade 3 to either of the following two groups at a ratio of 1:1: (1) additional resection of the transformation zone or (2) resection of the lesion only. To evaluate equal oncological outcome, we are performing human papillomavirus (HPV) tests 6 and 12 months postoperatively. The study is designed to consider the lesion-only operation as oncologically not inferior if the rate of HPV high-risk test results is not higher than 5 % compared with the HPV high-risk rate of women undergoing the classical LLETZ operation.



In case that non-inferiority of the "lesion-only" method can be demonstrated, this operation should eventually become standard treatment for all women at childbearing age due to the reduction in risk of preterm delivery.
Modulation of GemOx chemotherapy according to CIRS in elderly patients with advanced pancreatic cancer.

The present study evaluated activity and toxicity of modulated doses of gemcitabine associated to oxaliplatin in patients with secondary CIRS and with locally advanced pancreatic adenocarcinoma (LAPC) and metastatic pancreatic adenocarcinoma (MPC). Since January 2006, untreated LAPC and MPC patients have been assessed with ADL, IADL, CIRS to modulate chemotherapy dosages according to co-morbidity stage. Patiens aged<75 years, co-morbidity stage primary/intermediate, or ≥75 years and co-morbidity stage primary, received gemcitabine 1,000 mg/m² as a 10 mg/m²/min infusion on day 1 and oxaliplatin 70 mg/m² as a 2-h infusion on day 2 every 2 weeks. Patiens aged<75 years, co-morbidity stage secondary or ≥75 years and co-morbidity stage intermediate/secondary patients received gemcitabine 800 mg/m². Primary endpoint was the overall response rate (ORR). Secondary endpoints were disease control rate (DCR), PFS, OS and toxicity. Thirty-one patients were recruited: 26% (8/31) LAPC and 74% (23/31) MPC; median age 69 years. Co-morbidity stage primary/intermediate, 19; secondary, 12. Twenty-seven valuable patients: ORR 30% (CI±0.14); disease control rate 85% (CI±0.18). Median follow-up 13 months: median PFS and OS were 6 and 15 months, respectively. Valuable cycles 140. Grade 3/4 toxicity per patient: leukopenia, 18.5%; neutropenia, 55,5%; thrombocytopenia, 7.4%; SGOT/SGPT, 7.4%; gamma-GT, 7.4%; fever without neutropenia, 3.7%. Median received dose intensity: gemcitabine 400 mg/m2/w; oxaliplatin 35 mg/m2/w. Modulation of GemOx chemotherapy according, to CIRS stage in advanced pancreatic cancer confirms reported efficacy and tolerability.
Outcome, clinical prognostic factors and genetic predictors of adverse reactions of intermittent combination chemotherapy with docetaxel, estramustine phosphate and carboplatin for castration-resistant prostate cancer

Docetaxel-based chemotherapy is effective in patients with castration-resistant prostate cancer (CRPC). This phase II study assessed the outcome and predictive factors for prognosis and toxicity following intermittent chemotherapy with docetaxel, estramustine phosphate, and carboplatin (DEC) in patients with CRPC. Thirty-five patients were treated with a DEC regimen that consisted of a 28-day cycle of drugs as follows: docetaxel (60 mg/m2 on day 1), carboplatin (AUC 5 on day 1) and estramustine phosphate (560 mg daily). Treatment was continued intermittently. The end point was to test the effect of DEC on the response rate and overall survival (OS). Statistical correlations between the outcomes and predictive factors, including clinical parameters and 8 single-nucleotide polymorphisms (SNPs) related to drug metabolism, were assessed. Prostate-specific antigen levels decreased by more than 30% in 65.7% of the patients. The median OS following DEC was 17.8 months, and the median total time of chemotherapy holiday was 7.7 months (range 1.7–35.8). On multivariate analysis, serum lactate dehydrogenase (LDH) was an independent prognostic factor for OS (p = 0.007). On SNP analysis, patients carrying the TT genotype of the ABCB1 C3435T polymorphism showed a significantly more severe leukocytopenia during the first cycle of DEC therapy compared to patients with the CC + CT genotype (p = 0.036). Combination chemotherapy with DEC has a potential effect on CRPC with acceptable toxicity. Serum LDH may be a promising predictor of prognosis, and the ABCB1 C3435T polymorphism may be a genetic predictor of the severity of leukocytopenia in patients with CRPC treated with DEC.
Variable risk of atopic disease due to indoor fungal exposure in NHANES 2005-2006.

Exposure to damp indoor environments is associated with increased risk of eczema, allergy and asthma. The role of dampness-related exposures and risk of allergic diseases are yet to be fully explored in the US population.



We assess whether exposure to fungi, house dust mites and endotoxin increases the risk of eczema, allergy and asthma in children and adults participating in NHANES 2005-2006.



A total of 8412 participants (2849 were children aged between 6 and 17 years) were recruited in the 2005-2006 survey. We used multiple logistic regression to investigate whether mildew/musty odour and increased concentrations of Alternaria alternata allergen, Aspergillus fumigatus antigens, house dust mite and endotoxin antigens increase the risk of eczema, allergy and asthma. We stratified models by total IgE < 170 and ≥ 170 KU/L to assess allergic and non-allergic asthma outcomes. Exposure to multiple biological agents and risk of reporting eczema, allergy and asthma were also investigated.



Reporting of a mildew/musty odour was associated with increased risk of childhood asthma (OR 1.60; 95% CI 1.17-2.19), and adult eczema, allergy and asthma (OR 1.92; 95% CI 1.39-2.63, OR 1.59 95% CI 1.26-2.02 and OR 1.61 95% CI 1.00-2.57, respectively). Risk of asthma was associated with total IgE ≥ 170 KU/L in children (OR 1.81; 95% CI 1.01-3.25) and total IgE < 170 KU/L in adults (OR 1.91; 95% CI 1.07-3.42). Children and adults exposed to more than eight biological agents present in the home were at reduced risk of eczema (OR 0.17; 95% CI 0.04-0.77) and asthma (OR 0.49; 95% CI 0.25-0.97), respectively.



Exposure to a mildew/musty odour, as a proxy for exposure to fungus, was implicated in an increased risk of atopic diseases. Sensitisation may play a different role in children and adults, and exposure to multiple allergens may reduce the risk of atopic disease.
Blockade of hydromorphone effects by buprenorphine/naloxone and buprenorphine

Buprenorphine is an opioid agonist–antagonist used in the treatment of opioid dependence. Naloxone has been combined with buprenorphine to decrease the parenteral abuse potential of buprenorphine. This addition of naloxone may also confer further opioid blockade efficacy.  To test the opioid blockade efficacy of sublingual buprenorphine/naloxone versus buprenorphine alone and determine whether: (1) the blockade efficacy of buprenorphine/naloxone varies between the time of expected maximal and minimal effects of naloxone, (2) the blockade efficacy of buprenorphine/naloxone and buprenorphine varies as a function of maintenance dose level, and (3) there are adaptive changes over time associated with repeated daily dosing of buprenorphine/naloxone and buprenorphine.  Residential subjects (n=6) were maintained on different double-blind dose levels of buprenorphine/naloxone (4/1, 8/2, 16/4, 32/8 mg) and buprenorphine (32 mg) for 6-day periods and challenged with parenteral doses of hydromorphone (12 mg) in laboratory sessions.  There was no evidence of additional opioid blockade efficacy conferred by combining naloxone with buprenorphine. Higher doses of buprenorphine/naloxone provided greater blockade of hydromorphone effects. Changes over time associated with repeated daily dosing of buprenorphine/naloxone and buprenorphine were minimal.  The addition of naloxone to buprenorphine may deter the parenteral abuse of buprenorphine/naloxone, but it does not enhance the therapeutic efficacy of buprenorphine. The blockade efficacy of buprenorphine/naloxone is dose related; however, doses up to 32/8 mg buprenorphine/naloxone provide only partial blockade when subjects receive a high dose of an opioid agonist.
The effects of a tailored cardiac rehabilitation program on depressive symptoms in women: A randomized clinical trial.

Depression is known to co-occur with coronary heart disease (CHD). Depression may also inhibit the effectiveness of cardiac rehabilitation (CR) programs by decreasing adherence. Higher prevalence of depression in women may place them at increased risk for non-adherence.



To assess the impact of a modified, stage-of-change-matched, gender-tailored CR program for reducing depressive symptoms among women with CHD.



A two-group randomized clinical trial compared depressive symptoms of women in a traditional 12-week CR program to those completing a tailored program that included motivational interviewing guided by the Transtheoretical Model of behavior change. Women in the experimental group also participated in a gender-tailored exercise protocol that excluded men. The Center for Epidemiological Studies Depression (CES-D) Scale was administered to 225 women at baseline, post-intervention, and at 6-month follow-up. Analysis of Variance was used to compare changes in depression scores over time.



Baseline CES-D scores were 17.3 and 16.5 for the tailored and traditional groups, respectively. Post-intervention mean scores were 11.0 and 14.3; 6-month follow-up scores were 13.0 and 15.2, respectively. A significant group by time interaction was found for CES-D scores (F(2, 446)=4.42, p=.013). Follow-up tests revealed that the CES-D scores for the traditional group did not differ over time (F(2, 446)=2.00, p=.137). By contrast, the tailored group showed significantly decreased CES-D scores from baseline to post-test (F(1, 223)=50.34, p<.001); despite the slight rise from post-test to 6-month follow-up, CES-D scores remained lower than baseline (F(1, 223)=19.25, p<.001).



This study demonstrated that a modified, gender-tailored CR program reduced depressive symptoms in women when compared to a traditional program. To the extent that depression hinders CR adherence, such tailored programs have potential to improve outcomes for women by maximizing adherence. Future studies should explore the mechanism by which such programs produce benefits.
A single session of resistance exercise enhances insulin sensitivity for at least 24 h in healthy men

The aim of the present study was to determine whether a single session of resistance exercise improves whole-body insulin sensitivity in healthy men for up to 24 h. Twelve male subjects (23±1 years) were studied over a period of 4 days during which they consumed a standardized diet, providing 0.16±0.01 MJ·kg−1·day−1 containing 15±0.1 energy% (En%) protein, 29±0.1 En% fat and 55±0.3 En% carbohydrate. Insulin sensitivity was determined 24 h before and 24 h after a single resistance exercise session (8 sets of 10 repetitions at 75% of 1 repetition maximum for two leg exercise tasks) using an intravenous insulin tolerance test. Insulin sensitivity index was calculated by the decline in arterial blood glucose concentration following intravenous administration of a single bolus of human insulin (0.075 IU·kg−1 fat free mass). Basal glucose and insulin concentrations were not changed up to 24 h after the resistance exercise. However, a substantial 13±5% improvement in whole-body insulin sensitivity was observed, 24 h after the resistance exercise (P<0.05). This study shows that even a single session of resistance exercise improves whole-body insulin sensitivity for up to 24 h in healthy men, which is consistent with earlier observations following endurance exercise tasks.
Safety and efficacy of ezetimibe monotherapy in 1624 primary hypercholesterolaemic patients for up to 2 years.

This report examined the safety and efficacy of treatment for up to 2 years with the cholesterol absorption inhibitor, ezetimibe (EZE).



Two identical, randomised, double-blind trials (starting with 827 and 892 patients), evaluated the efficacy and safety of EZE 10 mg/day vs. placebo for 12 weeks in patients with primary hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) 3.3-5.1 mmol/l]. Upon completion of these base studies, patients were offered a 2-year, open-label extension study. Adverse event (AE) reports for EZE monotherapy-treated patients were summarised for 3-month intervals to allow for comparison with the placebo group of the 3-month base studies. The primary end-point for this analysis was the evaluation of the long-term safety and tolerability of EZE 10 mg monotherapy dosed daily for up to 24 months.



The incidences of new AEs, treatment-related (TR) AEs, serious AEs (SAEs), TRSAEs and discontinuations as a result of AEs during any 3-month interval were comparable with the respective observations in the placebo group of the base studies. The incidences of AEs, TRAEs, SAEs, TRSAEs and discontinuations as a result of AEs decreased in almost every interval compared with earlier intervals throughout the 2-year study. In addition, the incidences of > or = 3-fold consecutive elevations of liver transaminases (0.7%) or > or = 10-fold increases in creatine phosphokinase (0.4%) for the entire 2-year treatment period were comparable with those of the placebo group (0.7% and 0.2% respectively). LDL-C reductions of approximately 18% were maintained throughout the study.



Compared with placebo, treatment with EZE for up to 2 years in 1624 patients showed no evidence of increased incidence of AEs with increased treatment duration, while showing sustained effects on LDL-C reduction.
Early treatment benefits of ropinirole prolonged release in Parkinson's disease patients with motor fluctuations.

We performed a retrospective analysis of the Efficacy And Safety Evaluation in Parkinson's Disease (EASE-PD) Adjunct Study, assessing the minimum time to symptom improvement after initiation of ropinirole prolonged release (2-24 mg/day) versus placebo in patients with moderate-to-advanced PD not optimally controlled with levodopa. Ropinirole prolonged release was superior to placebo at Week 2 for change from baseline in "off" time (adjusted mean treatment difference [AMTD] - 0.7 hours; 95% confidence interval [CI], -1.1, -0.2; P = 0.0029), and "on" time without troublesome dyskinesia (0.4 hours; 95%CI, 0.01, 0.88; P = 0.0444). At Week 4, improvements were seen in change from baseline in Unified Parkinson's Disease Rating Scale total motor score (AMTD, -3.1; 95%CI, -4.4, -1.8; P < 0.0001), activities of daily living score (AMTD, -1.1; 95%CI, -1.7, -0.5; P = 0.0004), and the cardinal symptoms of PD compared with placebo. These analyses indicate that once-daily, adjunctive ropinirole prolonged release can offer PD symptom control 2 weeks after treatment initiation.
Phase I/II study of S-1 combined with carboplatin in recurrent and/or metastatic head and neck cancer as outpatient chemotherapy.

The aims of this study were to determine the recommended dose (RD) in combination chemotherapy of S-1 and carboplatin in recurrent and/or metastatic head and neck cancer (phase I) and to examine response rate and toxicities at RD (phase II).



S-1 was given orally at a fixed dose of 40, 50, or 60 mg twice daily based on the patient's body surface area for 21 days followed by a 14-day rest. In phase I, carboplatin was given intravenously to a cohort of three patients on day 8 at a dose of 2.5, 3.0, 3.5, or 4.0 area under the curve (AUC) values, depending on the dose-limiting toxicities (DLTs).



In phase I, the RD was estimated as 2.5 AUC. In phase II, thrombocytopenia and leukopenia were most commonly found as hematologic DLTs, which were manageable without hospitalization. The response rate was 40.9%.



This regimen is considered to be active against recurrent and/or metastatic head and neck cancer in an outpatient setting.
Adherence and persistence with oral adjuvant chemotherapy in older women with early-stage breast cancer in CALGB 49907: adherence companion study 60104.

Patient adherence is critical in evaluating the effectiveness of an oral therapy. We sought to measure adherence among women randomly assigned to capecitabine in a preplanned substudy of a multicenter clinical trial.



Cancer and Leukemia Group B study CALGB 49907 was a randomly assigned trial comparing standard chemotherapy versus oral chemotherapy with capecitabine in patients age 65 years or older with early-stage breast cancer. We used microelectronic monitoring system (MEMS) caps on participants' capecitabine bottles to record pill bottle openings. Capecitabine was given in two divided daily doses for 14 consecutive days of a 21-day cycle for six cycles. Adherence was calculated as the number of doses taken divided by doses expected, taking into account toxicity-related dosing changes. A participant was defined as adherent if 80% or more of expected doses were recorded by MEMS.



Overall, 161 patients were enrolled. Median age was 71 years (range, 65 to 89 years); 124 patients (83%) persisted with capecitabine to completion of planned protocol therapy. Adherence was 78% across all cycles, and adherence did not vary by cycle (P = .32). Twenty-five percent of participants took fewer than 80% of expected doses and were nonadherent. In a logistic regression model, participants with node-negative disease (P = .01) and mastectomy (P = .01) were more likely to be nonadherent. Adherence was not related to age, tumor stage, or hormone receptor status. Adherence was not significantly associated with relapse-free survival or grade 3 or 4 toxicity.



Most older women with early-stage breast cancer were adherent to short-term oral chemotherapy in a randomized clinical trial. Age was not associated with adherence.