nils-herrmann/clean_scirepeval huggingface dataset:
Efficacy of olanzapine monotherapy for treatment of bipolar I depression: a randomized, double-blind, placebo controlled study

Depression symptoms are now recognized to be the predominant cause of disability for bipolar disorder (BD) patients. The treatment strategies for the depressed phase of BD remain more anecdotal than data-based. Olanzapine has been investigated as an alternative to antidepressants and a mood stabilizer for acute bipolar depression. The purpose of this study was to assess the efficacy of olanzapine monotherapy for bipolar I depression. Sixty-eight patients with bipolar I depression were randomly assigned to treatment with olanzapine (mean final dose 14.4 mg/day) (n = 34) or placebo (n = 34) in a double-blind parallel-group study design. Planned assessments included Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Clinical Global Impressions-Severity of Illness scale (CGI-S), Clinical Global Impressions-Improvement scale (CGI-I), Hamilton Depression scale (HAMD), Hamilton Anxiety scale (HAMA), and Treatment Emergent Symptom Scale (TESS). Of the 68 patients who were randomly assigned, 57 (83.8 %) completed treatments. Improvements in MADRS total score, CGI-S, CGI-I, and HAMD in the olanzapine group were significantly greater relative to those in the placebo group during the 8-week follow-up period (p < 0.001, p = 0.0017, p = 0.007, and p < 0.001, respectively). Rates of categorical treatment response and remission in the olanzapine group (50.0 % and 35.3 %, respectively) were significantly higher than those in the placebo group (20.6 %, p = 0.011 and 11.8 %, p = 0.022, respectively). At the 8-week treatment, the mean weight and the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels increased significantly in the olanzapine group (p = 0.037, p = 0.029, p = 0.030, and p = 0.028, respectively). Olanzapine is effective in the treatment of bipolar I depression but is associated with significant metabolic side effects.
Effect of thalidomide on clinical remission in children and adolescents with refractory Crohn disease: a randomized clinical trial.

Pediatric-onset Crohn disease is more aggressive than adult-onset disease, has high rates of resistance to existing drugs, and can lead to permanent impairments. Few trials have evaluated new drugs for refractory Crohn disease in children.



To determine whether thalidomide is effective in inducing remission in refractory pediatric Crohn disease.



Multicenter, double-blind, placebo-controlled, randomized clinical trial of 56 children with active Crohn disease despite immunosuppressive treatment, conducted August 2008-September 2012 in 6 pediatric tertiary care centers in Italy.



Thalidomide, 1.5 to 2.5 mg/kg per day, or placebo once daily for 8 weeks. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks.



Primary outcomes were clinical remission at week 8, measured by Pediatric Crohn Disease Activity Index (PCDAI) score and reduction in PCDAI by ≥25% or ≥75% at weeks 4 and 8. Primary outcomes during the open-label follow-up were clinical remission and 75% response.



Twenty-eight children were randomized to thalidomide and 26 to placebo. Clinical remission was achieved by significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26 [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2-12.5]; P = .01; number needed to treat [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs 3/26 [11.5%]; RR, 4.0 [95% CI, 1.2-12.5]; NNT = 2.86; P = .01; and 25% response, 18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI, 1.1-3.9]; NNT = 2.99; P = .01). Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%) subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4-14.1]; NNT = 2.45; P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved clinical remission, and 32 of 49 (65.3%) achieved 75% response. Mean duration of clinical remission in the thalidomide group was 181.1 weeks (95% CI, 144.53-217.76) vs 6.3 weeks (95% CI, 3.51-9.15) in the placebo group (P < .001). Cumulative incidence of severe adverse events was 2.1 per 1000 patient-weeks, with peripheral neuropathy the most frequent severe adverse event.



In children and adolescents with refractory Crohn disease, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and longer-term maintenance of remission in an open-label follow-up. These findings require replication to definitively determine clinical utility of this treatment.
A decrease in serum creatinine after ICU admission is associated with increased mortality

The elevation of serum creatinine (SCr), acute kidney injury (AKI), is associated with an increase of mortality in critically ill patients. However, it is uncertain whether a decrease in SCr in the intensive care unit (ICU) has an effect on outcomes.



In a retrospective study, we enrolled 486 patients who had been admitted to an urban tertiary center ICU between Jan 2014 and Dec 2014. The effect of changes in SCr after ICU admission on 90 day mortality was analyzed. Patients were classified into 3 groups based on change in SCr after ICU admission: a stable SCr group (Δ SCr < 0.3mg/dL during ICU stay), a decreased SCr group (Δ SCr ≥ -0.3 mg/dL during ICU stay) and an increased SCr group with criteria based on the KDIGO AKI criteria.



In total, 486 patients were identified. SCr decreased in 123 (25.3%) patients after ICU admission. AKI developed in 125 (24.4%) patients. The overall 90-day mortality rate was 29.0%. In a Kaplan-Meyer analysis, the mortality of the AKI group was higher than that of other groups (p<0.0001). Patients with a decrease in SCr had a higher mortality rate than those with stable SCr (p<0.0001). A Cox analysis showed that both a decrease in SCR (HR, 3.56; 95% CI, 1.59-7.97; p = 0.002) and an increase in SCr (AKI stage 1, HR, 9.35; 95% CI, 4.18-20.9; p<0.0001; AKI stage 2, HR, 11.82; 95% CI, 3.85-36.28; p<0.0001; AKI stage 3, HR, 17.41; 95% CI, 5.50-55.04; p<0.0001) were independent risk factors for death compared to stable SCr.



Not only an increase in SCr, but also a decrease in SCr was associated with mortality in critically ill patients.
Use of a Real-Time Training Software (Laerdal QCPR®) Compared to Instructor-Based Feedback for High-Quality Chest Compressions Acquisition in Secondary School Students: A Randomized Trial

High-quality chest compressions are pivotal to improve survival from cardiac arrest. Basic life support training of school students is an international priority. The aim of this trial was to assess the effectiveness of a real-time training software (Laerdal QCPR®) compared to a standard instructor-based feedback for chest compressions acquisition in secondary school students. After an interactive frontal lesson about basic life support and high quality chest compressions, 144 students were randomized to two types of chest compressions training: 1) using Laerdal QCPR® (QCPR group- 72 students) for real-time feedback during chest compressions with the guide of an instructor who considered software data for students' correction 2) based on standard instructor-based feedback (SF group- 72 students). Both groups had a minimum of a 2-minute chest compressions training session. Students were required to reach a minimum technical skill level before the evaluation. We evaluated all students at 7 days from the training with a 2-minute chest compressions session. The primary outcome was the compression score, which is an overall measure of chest compressions quality calculated by the software expressed as percentage. 125 students were present at the evaluation session (60 from QCPR group and 65 from SF group). Students in QCPR group had a significantly higher compression score (median 90%, IQR 81.9-96.0) compared to SF group (median 67%, IQR 27.7-87.5), p = 0.0003. Students in QCPR group performed significantly higher percentage of fully released chest compressions (71% [IQR 24.5-99.0] vs 24% [IQR 2.5-88.2]; p = 0.005) and better chest compression rate (117.5/min [IQR 106-123.5] vs 125/min [115-135.2]; p = 0.001). In secondary school students, a training for chest compressions based on a real-time feedback software (Laerdal QCPR®) guided by an instructor is superior to instructor-based feedback training in terms of chest compression technical skill acquisition.
Late-onset moderate to severe acute respiratory distress syndrome is associated with shorter survival and higher mortality: a two-stage association study

To evaluate the association between acute respiratory distress syndrome (ARDS) onset time and prognosis. Patients with moderate to severe ARDS (N = 876) were randomly assigned into derivation (N = 520) and validation (N = 356) datasets. Both 28-day and 60-day survival times after ARDS onset were analyzed. A data-driven cutoff point between early- and late-onset ARDS was determined on the basis of mortality risk effects of onset times. We estimated the hazard ratio (HR) and odds ratio (OR) of late-onset ARDS using a multivariate Cox proportional hazards model of survival time and a multivariate logistic regression model of mortality rate, respectively. Late-onset ARDS, defined as onset over 48 h after intensive care unit (ICU) admission (N = 273, 31%), was associated with shorter 28-day survival time: HR = 2.24, 95% CI 1.48–3.39, P = 1.24 × 10−4 (derivation); HR = 2.16, 95% CI 1.33–3.51, P = 1.95 × 10−3 (validation); and HR = 2.00, 95% CI 1.47–2.72, P = 1.10 × 10−5 (combined dataset). Late-onset ARDS was also associated with shorter 60-day survival time: HR = 1.70, 95% CI 1.16–2.48, P = 6.62 × 10−3 (derivation); HR = 1.78, 95% CI 1.15–2.75, P = 9.80 × 10−3 (validation); and HR = 1.59, 95% CI 1.20–2.10, P = 1.22 × 10−3 (combined dataset). Meanwhile, late-onset ARDS was associated with higher 28-day mortality rate (OR = 1.46, 95% CI 1.04–2.06, P = 0.0305) and 60-day mortality rate (OR = 1.44, 95% CI 1.03–2.02, P = 0.0313). Late-onset moderate to severe ARDS patients had both shorter survival time and higher mortality rate in 28-day and 60-day observations.
Efficacy of glucosamine plus diacerein versus monotherapy of glucosamine: a double-blind, parallel randomized clinical trial

Patented crystalline glucosamine sulfate (pCGS) and diacerein monotherapy have been recommended for treatment of mild to moderate osteoarthritis (OA), but evidence of efficacy for combined treatments is lacking. Therefore, the aim of this study was to compare clinical outcomes (i.e., pain and Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] score) at 6 months as well as the safety profile of treatment with combined pCGS and diacerein versus pCGS alone.



A double-blind, parallel randomized controlled superiority trial was conducted between August 2013 and August 2014 at Ramathibodi Hospital, Bangkok, Thailand. A total of 148 patients (74 patients in each group) was randomly allocated to receive pCGS plus diacerein or pCGS plus placebo daily. Adult patients with OA were eligible if they had a Kellgren-Lawrence grade of 2-3. The primary outcomes were visual analogue scale score (VAS) for pain and WOMAC subscores measured at 24 weeks after receiving treatment, using the intention-to-treat principle (nonresponder imputation).



Among the 148 patients in the study, mean age and body mass index were 60 years and 28.1 kg/m2, respectively. Mean VAS and minimal joint space width at baseline were 5.1 and 2.5 mm, respectively. The mean VAS values measured at 24 weeks were 2.97 and 2.88 in the pCGS plus diacerein and pCGS plus placebo groups, respectively. The estimated mean difference was 0.09 (95 % CI -0.75 to 0.94), which was not statistically significant (P = 0.710). In addition, the mean WOMAC total, pain, function, and stiffness scores for both groups were not significantly different, with corresponding means of 48.59, 12.02, 32.74, and 3.85 for the pCGS plus diacerein group and 48.69, 11.76, 32.47, and 4.16 for the pCGS plus placebo group. The risk of diarrhea and dyspepsia was very similar between the two groups, with risk ratios of 1.03 (95 % CI 0.56-1.89) and 0.91 (95 % CI 0.43-1.92), respectively.



This study did not demonstrate that coadministration of diacerein with pCGS improves pain and WOMAC score compared with pCGS monotherapy in patients with mild to moderate OA of the knee.
Long-Term Safety Outcomes in Patients with Hematological Malignancies Undergoing Autologous Hematopoietic Stem Cell Transplantation Treated with Palifermin to Prevent Oral Mucositis.

The purpose of our study was to compare long-term safety outcomes (overall survival, disease progression, and incidence of secondary malignancies) between palifermin and placebo in the prevention of oral mucositis in patients with hematological malignancies undergoing autologous hematopoietic stem cell transplantation (HSCT). Patients were enrolled between 1997 and 2005 into 4 phase I to III studies (3 double-blind placebo-controlled and 1 open-label) conducted at 31 sites in Australia, Europe, and the United States. Survival outcomes (overall survival, progression-free survival) were compared using hazard ratios (HRs) estimated with a Cox model that included treatment group, baseline age, disease type, Eastern Cooperative Oncology Group performance status, country, and presence of prior radiotherapy as covariates. The incidence of secondary malignancies was compared with a chi-square test. A total of 672 patients were randomized into the studies (428 palifermin and 244 placebo). The median follow-up time for subjects alive at last visit was 7.9 years (range, .1 to 14.9) for palifermin and 8.8 years (range, .1 to 14.8) for placebo. Palifermin-treated patients had overall survival (HR, 1.01; 95% confidence interval [CI], .78 to 1.31; P = .921) and progression-free survival times (HR, 1.04; 95% CI, .83 to 1.31; P = .733) that were comparable with placebo-treated patients. Secondary malignancies were reported by 13% of palifermin-treated patients versus 11% of placebo patients (P = .477). Breakdown into secondary hematological malignancies (7% versus 6%) or solid tumors (6% versus 6%) did not suggest any differences between the treatment groups. After a follow-up of up to 15 years, comparable long-term safety outcomes (overall survival, progression-free survival, and incidence of secondary malignancies) were observed for palifermin- and placebo-treated patients undergoing autologous HSCT.
Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia.

Some studies have suggested that cases of acute myeloid leukemia (AML) with low levels of FLT3 internal tandem duplications (FLT3(ITD)) do not have a worse prognosis if there is a concomitant NPM1 mutation, although this is controversial. To clarify this therapeutically important issue, we have analyzed FLT3(ITD) and NPM1(MUT) levels in 1609 younger adult cases of cytogenetically intermediate-risk AML. The cumulative incidence of relapse was increased in NPM1(MUT) cases by the presence of a FLT3(ITD), but did not differ markedly according to FLT3(ITD) level. This remained true when allowance was made for poor leukemic cell purity by adjustment of the FLT3(ITD) level to the measured NPM1(MUT) level. If consolidation therapies are to be determined by relapse risk, then NPM1(MUT) cases with low-level FLT3(ITD) should not be considered as good risk without further studies. AML 12 and AML 15 are registered at http://www.controlled-trials.com under ISRCTN17833622 and ISRCTN17161961, respectively.
Statins in low doses reduce VEGF and bFGF serum levels in patients with type 2 diabetes mellitus.

Recent experimental research revealed that statins at low doses induce angiogenesis, which in turn may be related to the course of atherosclerosis. There are no clinical studies evaluating the effect of 'low-dose' statins on serum levels of angiogenesis regulators in diabetic subjects. We aimed to explain how low doses of statins modify the serum concentrations of two potent proangiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), in patients with type 2 diabetes.



Measurements of fasting glucose level, HbA1c, 1,5-anhydro-D-glucitol and lipid profile were taken from 47 patients with type 2 diabetes treated with low doses of atorvastatin (10 mg daily) or simvastatin (10-20 mg daily), from 45 statin-free patients with type 2 diabetes and from 23 nondiabetic subjects. Measurements of VEGF and bFGF in serum were taken using the BD™ Cytometric Bead Array.



Statins used in low doses in patients with type 2 diabetes reduce the serum concentration of VEGF and bFGF which suggests antiangiogenic potential of these doses. Nevertheless, this effect could be neutralized by postprandial hyperglycemia.
Noradrenergic response to acute ethanol administration in heathly subjects: comparison with intravenous yohimbine

The effects of oral administration of ethanol [1.1 ml/kg 95% ethanol administered as a 20% (by volume) solution] and intravenous administration of the alpha2 adrenergic receptor antagonist yohimbine hydrochloride (0.4 mg/kg), alone and in combination, were compared using a double-blind, placebo-controlled design. Twelve healthy subjects completed 4 test days during which drug effects on subjective measures of intoxication and anxiety, plasma levels of the norepinephrine (NE) metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and cortisol, and cardiovascular indices were assessed. Acutely administered oral ethanol significantly increased the subjective measures of intoxication and anxiety, plasma MHPG, and sitting systolic blood pressure compared with placebo. Intravenous yohimbine significantly increased subjective measures of intoxication and anxiety, plasma MHPG and cortisol, and blood pressure relative to placebo. The ethanol-induced increase in plasma MHPG was significantly greater than that following yohimbine, whereas yohimbine resulted in significantly greater increases in anxiety, plasma cortisol, and blood pressure measurements than ethanol. The combined administration of ethanol and yohimbine had a clear additive effect of increasing the severity of acute intoxication compared with ethanol or yohimbine alone, and resulted in a significantly greater plasma MHPG response compared with either drug given alone. Although the pharmacokinetic effects of ethanol administration on NE metabolism must be considered, these findings suggest that the intoxicating and anxiogenic effects of acute ethanol administration may be associated with increased NE turnover, as measured by plasma MHPG, in healthy human subjects. In addition, these results indicate that ethanol and yohimbine may act additively to increase ethanol intoxication and that they may increase NE turnover through different physiological mechanisms.
Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into Cancer and Nutrition.

Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country-specific self-administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow-up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country-specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person-years of follow-up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23-1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40-2.24; p = 0.02 for combined vs. estrogen-only). Continuous combined regimens conferred a 43% (95% CI: 19-72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen-only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component.
Magnetization transfer ratio in the delayed-release dimethyl fumarate DEFINE study

We measured changes in brain magnetization transfer ratio (MTR) as a potential indicator of myelin density in brain tissue of patients with relapsing-remitting multiple sclerosis (RRMS) treated with delayed-release dimethyl fumarate (DMF) in the Phase 3 DEFINE study. DEFINE was a randomized, double-blind, placebo-controlled study in which patients with RRMS were randomized 1:1:1 to 2 years of treatment with delayed-release DMF 240 mg twice daily (BID) or three times daily (TID) or placebo. MTR was analyzed in whole brain and normal-appearing brain tissue (NABT) at baseline, week 24, 1 year, and 2 years in a subset of patients. MTR data from 392 patients were analyzed. Mean percentage reduction from baseline to 2 years in median whole brain MTR was −0.386 % in the placebo group vs increases of 0.129 % (p = 0.0027) and 0.096 % (p = 0.0051) in the delayed-release DMF BID and TID groups, respectively. Similarly, mean percentage reduction from baseline in median NABT MTR was −0.392 % with placebo vs increases of 0.190 % (p = 0.0006) and 0.115 % (p = 0.0029) with delayed-release DMF BID and TID, respectively. Post hoc analysis of data from patients with no new or enlarging T2 lesions (n = 147), or who experienced no relapses (n = 238), yielded similar results. In this analysis, increases in MTR in brain tissue most likely reflect increases in myelin density in response to delayed-release DMF. These data in patients with RRMS are consistent with preclinical studies that indicate a potential for cytoprotection and remyelination with delayed-release DMF treatment.