nils-herrmann/clean_scirepeval huggingface dataset:
Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: A randomised controlled trial in patients with schizophrenia and healthy controls

The objective of this study was to examine exercise effects on global brain volume, hippocampal volume, and cortical thickness in schizophrenia patients and healthy controls. Irrespective of diagnosis and intervention, associations between brain changes and cardiorespiratory fitness improvement were examined. Sixty-three schizophrenia patients and fifty-five healthy controls participated in this randomised controlled trial. Global brain volumes, hippocampal volume, and cortical thickness were estimated from 3-Tesla MRI scans. Cardiorespiratory fitness was assessed with a cardiopulmonary ergometer test. Subjects were assigned exercise therapy or occupational therapy (patients) and exercise therapy or life-as-usual (healthy controls) for six months 2h weekly. Exercise therapy effects were analysed for subjects who were compliant at least 50% of sessions offered. Significantly smaller baseline cerebral (grey) matter, and larger third ventricle volumes, and thinner cortex in most areas of the brain were found in patients versus controls. Exercise therapy did not affect global brain and hippocampal volume or cortical thickness in patients and controls. Cardiorespiratory fitness improvement was related to increased cerebral matter volume and lateral and third ventricle volume decrease in patients and to thickening in the left hemisphere in large areas of the frontal, temporal and cingulate cortex irrespective of diagnosis. One to 2h of exercise therapy did not elicit significant brain volume changes in patients or controls. However, cardiorespiratory fitness improvement attenuated brain volume changes in schizophrenia patients and increased thickness in large areas of the left cortex in both schizophrenia patients and healthy controls.
Phase I trial of volasertib, a Polo-like kinase inhibitor, in Japanese patients with advanced solid tumors

This trial evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical effects of volasertib, a selective Polo-like kinase inhibitor that induces mitotic arrest and apoptosis, in Japanese patients with advanced solid tumors (NCT01348347; 1230.15).  In this phase I, open-label, dose-escalation trial, sequential patient cohorts (3 + 3 dose-escalation design) received volasertib (200–350 mg) as a single dose by intravenous infusion over 2 h on day 1 every 21 days until disease progression or unacceptable toxicity. The primary endpoint was the MTD of volasertib in Japanese patients with an advanced solid tumor; secondary endpoints included safety, pharmacokinetics, and clinical benefit.  Fifteen patients with an advanced solid tumor were treated. Dose-limiting toxicities of grade 4 neutropenia for ≥7 days and grade 4 thrombocytopenia were both experienced by 2/6 patients in the 350 mg cohort. The MTD of volasertib in Japanese patients was 300 mg. The most common (≥3 patients) drug-related non-hematologic adverse events included fatigue, decreased appetite, and nausea. Exposure to volasertib and its metabolite increased with increasing doses. A partial response in a patient with gastric cancer and stable disease in eleven patients were observed.  Volasertib had a manageable safety profile up to the MTD determined as 300 mg. Exposure to volasertib and its metabolite increased with increasing doses. The safety profile of volasertib in Japanese patients is comparable with those previously obtained in Caucasian patients. These data support enrollment of Japanese patients in global clinical trials without dose modification.
Development of Two Barthel Index-Based Supplementary Scales for Patients with Stroke

The Barthel Index (BI) assesses actual performance of activities of daily living (ADL). However, comprehensive assessment of ADL functions should include two other constructs: self-perceived difficulty and ability.



The aims of this study were to develop two BI-based Supplementary Scales (BI-SS), namely, the Self-perceived Difficulty Scale and the Ability Scale, and to examine the construct validity of the BI-SS in patients with stroke.



The BI-SS was first developed by consultation with experts and then tested on patients to confirm the clarity and feasibility of administration. A total of 306 participants participated in the construct validity study. Construct validity was investigated using Mokken scale analysis and analyzing associations between scales. The agreement between each pair of the scales' scores was further examined.



The Self-perceived Difficulty Scale consisted of 10 items, and the Ability Scale included 8 items (excluding both bladder and bowel control items). Items in each individual scale were unidimensional (H ≥ 0.5). The scores of the Self-perceived Difficulty and Ability Scales were highly correlated with those of the BI (rho = 0.78 and 0.90, respectively). The scores of the two BI-SS scales and BI were significantly different from each other (p<.001). These results indicate that both BI-SS scales assessed unique constructs.



The BI-SS had overall good construct validity in patients with stroke. The BI-SS can be used as supplementary scales for the BI to comprehensively assess patients' ADL functions in order to identify patients' difficulties in performing ADL tasks, plan intervention strategies, and assess outcomes.
Sacral nerve modulation for defaecation and micturition disorders in patients with spina bifida.

Sacral nerve modulation is a well accepted method for the treatment of defaecation disorders and voiding dysfunction. Results of sacral nerve modulation in patients with spinal cord lesions are not well assessed, but preliminary results look poor. Therefore, the purpose of this study was to assess the effectiveness of sacral nerve modulation for defaecation disorders and voiding dysfunction in patients with spina bifida.



Consecutive patients with spina bifida suffering from a myelomeningocele and combined faecal and urinary functional disorders that were eligible for peripheral nerve evaluation (PNE) were studied. A permanent sacral nerve modulation implantation was performed after successful PNE.



Ten patients (four female) were included in this study with a median age of 26.4 (range 11.1-41.0) years. In two the PNE was not possible. The median faecal incontinence days (6.0 vs 3.5) and episodes (8.5 vs 3.5) per 21 days decreased significantly during the 3-week period of PNE (P = 0.033). Only 3/10 (30%) patients had a more than 50% improvement and proceeded to a permanent sacral nerve modulation implantation. In one patient it was not possible to perform the permanent implant.



Preliminary results of sacral nerve modulation in a subgroup of spina bifida patients with combined faecal and urinary functional disorders look promising, but long-term results in larger patient groups need to be studied.
Autoregulation of Cerebral Blood Flow in Fetuses with Congenital Heart Disease: The Brain Sparing Effect

Fetuses with congenital heart disease (CHD) have circulatory abnormalities that may compromise cerebral oxygen delivery. We believe that some CHD fetuses with decreased cerebral oxygen supply have autoregulation of blood flow that enhances cerebral perfusion (brain sparing). We hypothesize that cerebral autoregulation occurs in CHD fetuses, and the degree of autoregulation is dependent on the specific CHD and correlates with intrauterine head circumferences. CHD fetuses were compared to normal fetuses. Data included cardiac diagnosis, cerebral and umbilical artery Doppler, head circumference, weight, and gestational age. The cerebral-to-placental resistance ratio (CPR) was assessed as a measure of cerebral autoregulation. CPR = cerebral/umbilical resistance index (RI) and RI = systolic–diastolic/systolic velocity (normal CPR>1). CPR>1 was found in 95% of normal vs 44% of CHD fetuses. The incidence of CPR<1 was greatest in hypoplastic left or right heart fetuses. Compared to normal, cerebral RI was decreased in CHD fetuses. The CPR vs gestational age relationship, and the relationship among weight, head circumference, and CPR differed across normal and CHD fetuses. Fetuses > 2 kg with CHD and a CPR<1 had smaller head circumferences than normal. Brain sparing occurs in CHD fetuses. Fetuses with single ventricular physiology are most affected. Inadequate cerebral flow in CHD fetuses, despite autoregulation, may alter brain growth.
Androgen deprivation in males is associated with decreased central arterial compliance and reduced central systolic blood pressure

The higher incidence of coronary artery disease in men is often attributed to androgens. Arterial compliance or ‘stiffness’ is increasingly regarded as a modifiable risk factor for cardiovascular disease. We wanted to look at the effects of complete androgen withdrawal, on arterial compliance in men. We performed arterial compliance studies on 12 men with complete androgen deprivation as treatment for prostate cancer, and on 12 age-matched healthy controls. Central pulse wave velocities were significantly higher in the androgen-deprived men (14.2 ± 2.7 vs 11.8 ± 1.6 m/sec, P = 0.02). The cases tended to have higher brachial systolic pressures than controls though this difference was not significant (P = 0.2). We conclude that androgen withdrawal is associated with a reduction in central arterial compliance. Conversely androgen withdrawal does not affect peripheral arterial compliance. It is unlikely that the presence of normal concentrations of androgens can explain the sex difference in mortality rates. Longitudinal studies are needed for further evaluation.
Post-Hospital Outcomes of Patients With Acute Myocardial Infarction With Cardiogenic Shock: Findings From the NCDR.

Many patients with acute myocardial infarction (AMI) and cardiogenic shock survive hospitalization; little is known about their subsequent prognosis.



This study sought to evaluate the associations between cardiogenic shock and post-discharge mortality and all-cause hospitalization among hospital survivors.



We included patients ≥65 years of age with AMI from the ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines) who survived hospitalization and linked these patients with Medicare claims data. We used proportional hazards models to test the association between cardiogenic shock and outcomes, adjusting for patient and hospital characteristics. Hazard ratios (HRs) are reported for early (1 to 60 days) and late (61 to 365 days) post-discharge time periods.



Among 112,668 AMI survivors, 5% had cardiogenic shock during hospitalization. The rate of death was significantly higher among patients with cardiogenic shock at 60 days (9.6% vs. 5.5%) and 1 year (22.4% vs. 16.7%). After accounting for baseline characteristics, the risk of death remained higher for cardiogenic shock patients in the first 60 days after discharge (adjusted HR: 1.62; 95% confidence interval [CI]: 1.46 to 1.80), but was similar to nonshock patients thereafter (adjusted HR: 1.08 for days 61 to 365; 95% CI: 1.00 to 1.18). The rate of all-cause hospitalization or death was significantly higher among shock patients at 60 days (33.9% vs. 24.9%) and 1 year (59.1% vs. 52.3%). After adjustment, the risk of this outcome was also clustered in the first 60 days (adjusted HR: 1.28; 95% CI: 1.21 to 1.35) and was similar thereafter (adjusted HR: 0.95 for days 61 to 365; 95% CI: 0.89 to 1.01).



Hospital survivors of AMI who had cardiogenic shock have a higher risk of death and/or hospitalization during the first year after discharge. The risk is time-dependent and is clustered in the early post-discharge period, after which the prognosis is similar in patients with and without cardiogenic shock.
A pilot study of the multiherb Kampo medicine bakumondoto for cough in patients with chronic obstructive pulmonary disease.

To evaluate the effect of bakumondoto, Kampo medicine, on cough in patients with chronic obstructive pulmonary disease (COPD).



A 16-week, randomized, open-labeled, cross-over design.



Outpatient clinics at one university hospital and two general hospitals in Japan from May 2007 to March 2009.



Twenty-four elderly patients (14 men and 9 women aged over 65) with COPD.



Treatment with or without bakumondoto for 8 weeks in a cross-over design.



The primary outcome measurements were the frequency and intensity of cough assessed by a visual analogue scale (VAS) and a daily cough diary. Secondary outcome measurements were quality of life (QOL) assessed using St. George's Respiratory Questionnaire (SGRQ) and lung functions measured using spirometry.



Treatment with bakumondoto significantly improved cough severity during the first treatment period (week 0 vs. week 8, p=0.004) and showed a trend to decrease during the second treatment period (week 8 vs. week 16, p=0.129) assessed by the VAS. Neither QOL nor lung function was affected by the treatment with bakumondoto.



Bakumondoto may be effective in suppressing cough in elderly patients with COPD. To further confirm the efficacy, a larger and placebo-controlled study with objective cough assessment is necessary.
Renin-Angiotensin System Inhibitors, Type 2 Diabetes and Fibrosis Progression: An Observational Study in Patients with Nonalcoholic Fatty Liver Disease

The clinical determinants of fibrosis progression in nonalcoholic fatty liver disease (NAFLD) are still under definition.



To assess the clinical determinants of fibrosis progression rate (FPR) in NAFLD patients with baseline and follow-up histological evaluation, with a special focus on the impact of pharmacological therapy.



In an observational cohort of 118 Italian patients from tertiary referral centers, liver histology was evaluated according to Kleiner. Independent predictors of FPR were selected by a stepwise regression approach.



Median follow-up was 36 months (IQR 24-77). Twenty-five patients (18%) showed some amelioration, 63 (53%) had stability, 30 (25%) had progression of fibrosis. Patients with nonalcoholic steatohepatitis (NASH) had similar demographic and anthropometric features, but a higher prevalence of type 2 diabetes (T2D; p = 0.010), and use of renin-angiotensin axis system (RAS) inhibitors (p = 0.005). Fibrosis progression was dependent of the length of follow-up, and was associated with, but did not require, the presence of NASH (p<0.05). Both fibrosis progression and faster FPR were independently associated with higher APRI score at follow-up, absence of treatment with RAS inhibitors, and T2D diagnosis at baseline (p<0.05). There was a significant interaction between use of RAS inhibitors and T2D on FPR (p = 0.002). RAS inhibitors were associated with slower FPR in patients with (p = 0.011), but not in those without (p = NS) T2D.



NASH is not required for fibrosis progression in NAFLD, whereas T2D seems to drive fibrogenesis independently of hepatic inflammation. Use of RAS inhibitors may contrast fibrosis progression especially in high-risk patients affected by T2D.
Efficacy and safety of adding pioglitazone or sitagliptin to patients with type 2 diabetes insufficiently controlled with metformin and a sulfonylurea.

To evaluate the efficacy and safety of add-on pioglitazone versus sitagliptin in patients with type 2 diabetes inadequately controlled on metformin and a sulfonylurea (SU).



This 24-week, randomized, open-label study compared pioglitazone (30 mg daily, n = 59) and sitagliptin (100 mg daily, n = 60) in patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0% to <11.0%) while receiving a stable dose of metformin (≥1,500 mg daily) and an SU (≥half-maximal dose).



The mean changes in HbA1c from baseline was -0.94 ± 0.12% with pioglitazone and -0.71 ± 0.12% with sitagliptin, for a between-groups difference of -0.23 ± 0.16% (P = .16). The mean change in fasting plasma glucose (FPG) were -35.7 ± 4.0 mg/dL with pioglitazone and -22.8 ± 4.0 mg/dL with sitagliptin, for a between-groups difference of -12.9 ± 5.7 mg/dL (P = .02). Pioglitazone was associated with a significant decrease in high-sensitive C-reactive protein (hs-CRP), but sitagliptin did not. The mean weight gain was higher in the pioglitazone group, with a between-group difference of 1.6 kg (P<.01). Overall adverse events (AEs) were similar in both groups. However, the incidence of edema was higher with pioglitazone, and the incidence of gastrointestinal AEs was higher with sitagliptin.



Pioglitazone and sitagliptin achieved similar improvements in overall glycemic control in patients with type 2 diabetes inadequately controlled with metformin and an SU. However there were some differences in terms of FPG, hs-CRP, lipids, body-weight change, and AEs.
Cholesterol metabolism in patients with hemodialysis in the presence or absence of coronary artery disease.

Little is known about the interrelationship between the lipid profile, cholesterol metabolism, and coronary risk factors in patients with hemodialysis (HD) in the presence or absence of coronary artery disease (CAD).



Ninety-five patients with HD were selected (HD group). Fifty-eight age-, gender-, and body mass index (BMI)-matched patients who had at least 1 cardiovascular risk factor were selected as a non-HD group. Total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and the ratio of LDL-C to HDL-C (L/H) in the HD group were significantly lower than those in the non-HD group. All markers of cholesterol absorption (campesterol/TC, sitosterol/TC, and cholestanol/TC) and the ratio of campesterol to lathosterol in the HD group were significantly higher. In addition, in the HD group, L/H was negatively correlated with lathosterol/TC, campesterol/TC, sitosterol/TC, and cholestanol/TC. Finally, CAD was significantly associated with lathosterol/TC (P=0.028), which was positively associated with BMI in the HD group, whereas CAD was significantly associated only with hypertension (P=0.020) in the non-HD group.



HD patients showed lower cholesterol concentrations than non-HD patients, and, as compensation, their cholesterol absorption might be accelerated. However, higher cholesterol synthesis, which was correlated with higher BMI, might be an independent predictor for the presence of CAD in HD patients.
Risk of recurrence after a first unprovoked venous thromboembolism: external validation of the Vienna Prediction Model with pooled individual patient data.

In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated.



To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors.



Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods.



The ability of the VPM to distinguish patients' risk for recurrent VTE in the validation cohort was at least as good as in the original cohort, with a calibration slope of 1.17 (95% confidence interval 0.71-1.64; P = 0.456 for the hypothesis of a significant difference from 1), and a c-statistic of 0.626 (vs. 0.651 in the original derivation cohort). The VPM absolute predictions in terms of cumulative rates tended to underestimate the observed recurrence rates at 12 months.



By using a pooled individual patient database as a validation cohort, we confirmed the ability of the VPM to stratify patients with a first unprovoked VTE according to their risk of recurrence.
Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study.

To compare the efficacy, safety and tolerability of linagliptin or placebo administered for 24 weeks in combination with pioglitazone in patients with type 2 diabetes mellitus (T2DM) exhibiting insufficient glycaemic control (HbA1c 7.5-11.0%).



Patients were randomized to receive the initial combination of 30 mg pioglitazone plus 5 mg linagliptin (n = 259) or pioglitazone plus placebo (n = 130), all once daily. The primary endpoint was change from baseline in HbA1c after 24 weeks of treatment, adjusted for baseline HbA1c and prior antidiabetes medication.



After 24 weeks of treatment, the adjusted mean change (±s.e.) in HbA1c with the initial combination of linagliptin plus pioglitazone was -1.06% (±0.06), compared with -0.56% (±0.09) for placebo plus pioglitazone. The difference in adjusted mean HbA1c in the linagliptin group compared with placebo was -0.51% (95% confidence interval [CI] -0.71, -0.30; p < 0.0001). Reductions in fasting plasma glucose (FPG) were significantly greater for linagliptin plus pioglitazone than with placebo plus pioglitazone; -1.8 and -1.0 mmol/l, respectively, equating to a treatment difference of -0.8 mmol/l (95% CI -1.2, -0.4; p < 0.0001). Patients taking linagliptin plus pioglitazone, compared with those receiving placebo plus pioglitazone, were more likely to achieve HbA1c of <7.0% (42.9 vs. 30.5%, respectively; p = 0.0051) and reduction in HbA1c of ≥0.5% (75.0 vs. 50.8%, respectively; p < 0.0001). β-cell function, exemplified by the ratio of relative change in adjusted mean HOMA-IR and disposition index, improved. The proportion of patients that experienced at least one adverse event was similar for both groups. Hypoglycaemic episodes (all mild) occurred in 1.2% of the linagliptin plus pioglitazone patients and none in the placebo plus pioglitazone group.



Initial combination therapy with linagliptin plus pioglitazone was well tolerated and produced significant and clinically meaningful improvements in glycaemic control. This combination may offer a valuable additive initial treatment option for T2DM, particularly where metformin either is not well tolerated or is contraindicated, such as in patients with renal impairment.