nils-herrmann/clean_scirepeval huggingface dataset:
A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors

As tyrosine kinase inhibitors have been associated with cardiotoxicity, we evaluated the effect of pazopanib, an inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit, on electrocardiographic parameters in patients with cancer. This double-blind, placebo-controlled, parallel-group study randomized patients (N = 96) to moxifloxacin (positive control) or placebo on Day 1 followed by pazopanib or placebo 800 mg/day (fasted) on Days 2–8 and 1,600 mg (with food) on Day 9. Treatment effects were evaluated by baseline-adjusted, time-matched, serial Holter electrocardiograms. Sixty-five patients were evaluable for preplanned analyses. On Day 1, the maximum mean difference in baseline-adjusted, time-matched Fridericia-corrected QT (QTcF) interval in moxifloxacin-treated patients versus placebo was 10.6 ms (90 % confidence interval [CI]: 4.2, 17.0). The administration scheme increased plasma pazopanib concentrations approximately 1.3- to 1.4-fold versus the recommended 800 mg once-daily dose. Pazopanib caused clinically significant increases from baseline in blood pressure, an anticipated class effect, and an unexpected reduction in heart rate from baseline that correlated with pazopanib exposure. On Day 9, the maximum mean difference in baseline-adjusted, time-matched QTcF interval in pazopanib-treated patients versus placebo was 4.4 ms (90 % CI: −2.4, 11.2). Mixed-effects modeling indicated no significant concentration-dependent effect of pazopanib or its metabolites on QTcF interval. Pazopanib as administered in this study achieved supratherapeutic concentrations, produced a concentration-dependent decrease in heart rate, and caused a small, concentration-independent prolongation of the QTcF interval.
Cost-effectiveness of mirtazapine compared to amitriptyline and fluoxetine in the treatment of moderate and severe depression in austria.

This study estimated the cost-effectiveness of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in Austria, as well as the costs related to the discontinuation of antidepressant treatment from the perspective of the Austrian Sick Funds (Gebietskrankenkassen). The economic analyses were based on a meta-analysis of four randomised clinical trials comparing mirtazapine with amitriptyline, and on a six week comparative trial of mirtazapine and fluoxetine which was extrapolated to six months using assumptions derived from the literature. Decision models of the treatment paths and associated resource use attributable to managing moderate and severe depression in Austria were developed from clinical trial data, information on Austrian clinical practice obtained from interviews with an Austrian Delphi panel (comprising psychiatrists and GPs), and from published literature. The models were used to estimate the expected costs to the Gebietskrankenkassen of managing a patient with moderate or severe depression, and the indirect cost per patient to Austrian society due to lost productivity. The expected cost to the Gebietskrankenkassen of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment was estimated to be ATS 4,088 over five months, of which hospitalisations accounted for nearly 69% of the cost. Using mirtazapine instead of amitriptyline for 28 weeks increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%), and reduces the expected cost to the Gebietskrankenkassen by ATS 1,112 per patient (from ATS 31,411 to ATS 30,299). Patients treated with mirtazapine and amitriptyline for 28 weeks are expected to miss 4.76 and 5.01 weeks of work respectively, due to their depression. Hence, the expected indirect cost to Austrian society over this period was estimated to be ATS 58, 787 and ATS 61,851 per patient respectively. Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for a negligible additional cost to the Gebietskrankenkassen of ATS 408 per patient (from ATS 29,205 to ATS 29,613). Patients treated with mirtazapine and fluoxetine for six months are expected to miss 4.53 weeks of work, due to their depression. Hence, the expected indirect cost to Austrian society due to lost productivity was estimated to be ATS 55,900 per patient with either antidepressant. In conclusion, this study suggests that despite the differences in acquisition costs, mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine, supporting the adoption of this treatment in the management of moderate and severe depression in Austria.
Plasma vitamin D-binding protein and risk of heart failure in male physicians.

Previous studies have suggested that vitamin D deficiency might contribute to the pathogenesis of heart failure (HF); however, limited data are available on the association of vitamin D-binding protein (VDBP)--a major transport protein for vitamin D--and the development of HF. Thus, we investigated whether plasma VDBP is inversely associated with HF risk. Using a prospective nested case-control design, we selected 464 cases and 464 matched controls from the Physicians' Health Study for the present analyses. VDBP was determined using an enzyme-linked immunoassay. Self-reported HF was obtained through annual follow-up questionnaires and validated in a subsample by a review of the medical records. We used conditional logistic regression analyses to compute the adjusted odds ratios. The mean age was 58.6 years, and the median VDBP was 307.8 μg/ml (interquartile range 265.2 to 354.6). Plasma VDBP was not associated with HF in our study. Across the consecutive quintiles of VDBP, the odds ratio was 1.0 (95% confidence interval [CI] reference), 1.05 (95% CI 0.66 to 1.65), 1.28 (95% CI 0.80 to 2.06), 1.07 (95% CI 0.65 to 1.75), and 1.28 (95% CI 0.76 to 2.15); p for linear trend = 0.41, after adjustment for matching factors, body mass index, diabetes, atrial fibrillation, hypertension, and high-sensitivity C-reactive protein. In conclusion, our data have shown no significant association between the plasma levels of VDBP and HF risk in apparently healthy male physicians.
The cure of cancer: a European perspective.

Cancer survival analyses based on cancer registry data do not provide direct information on the main aim of cancer treatment, the cure of the patient. In fact, classic survival indicators do not distinguish between patients who are cured, and patients who will die of their disease and in whom prolongation of survival is the main objective of treatment. In this study, we applied parametric cure models to the cancer incidence and follow-up data provided by 49 EUROCARE-4 (European Cancer Registry-based study, fourth edition) cancer registries, with the aims of providing additional insights into the survival of European cancer patients diagnosed from 1988 to 1999, and of investigating between-population differences. Between-country estimates the proportion of cured patients varied from about 4-13% for lung cancer, from 9% to 30% for stomach cancer, from 25% to 49% for colon and rectum cancer, and from 55% to 73% for breast cancer. For all cancers combined, estimates varied between 21% and 47% in men, and 38% and 59% in women and were influenced by the distribution of cases by cancer site. Countries with high proportions of cured and long fatal case survival times for all cancers combined were characterised by generally favourable case mix. For the European pool of cases both the proportion of cured and the survival time of fatal cases were associated with age, and increased from the early to the latest diagnosis period. The increases over time in the proportions of Europeans estimated cured of lung, stomach and colon and rectum cancers are noteworthy and suggest genuine progress in cancer control. The proportion of cured of all cancers combined is a useful general indicator of cancer control as it reflects progress in diagnosis and treatment, as well as success in the prevention of rapidly fatal cancers.
Cognitive behaviour therapy for improving social recovery in psychosis: Cost-effectiveness analysis

A randomised trial was conducted in order to estimate the clinical and cost-effectiveness of social recovery orientated cognitive behavioural therapy (SRCBT) for people diagnosed with psychosis, compared to case management alone (CMA). The mean incremental health and social care cost, and the mean incremental quality adjusted life year (QALY) gain, of SRCBT was calculated over the 9 month intervention period. The cost-effectiveness of SCRBT was in turn estimated, and considered in relation to the cost-effectiveness threshold of 20000 UK pounds per QALY. The level of uncertainty associated with that decision was estimated by calculating the cost-effectiveness acceptability curve for SRCBT. N=35 received SRCBT and N=42 received CMA. The mean incremental cost was estimated to be 668 UK pounds, and the mean incremental QALY gain 0.035. SRCBT was estimated to be cost-effective as it had a cost per QALY of 18844 UK pounds, which was more favourable than the assumed cost-effectiveness threshold of 20000 UK pounds per QALY. At that threshold the probability of being cost-effective was however estimated to be 54.3% according to the CEAC, suggesting that further research may be warranted in order to reduce the level of uncertainty associated with the decision as to whether SRCBT is cost-effective.
Treatment of adult asthma: Controlled double-blind clinical trial of oxitropium bromide

Sixteen young adult sufferers from extrinsic paroxysmal asthma with pollen hypersensitivity took part in a therapeutic trial of the synthetic anti-cholinergic agent oxitropium bromide administered by a metered dose inhaler. The study comprised three 3-week periods. The first, run-in period was carried out to confirm the ability of the patients to maintain a daily record of symptoms. During the second and third periods, the patient received 3 × 2 inhalations of drug or placebo in a cross-over design. The medical staff was blind to the nature of the aerosol (drug or placebo), which was given in random order. The run-in clinical score was high. Asymptomatic days were relatively infrequent and daily drug consumption was high. Functional studies between the cross-over periods showed flow-rate values close to normal, with an increase in residual volume and functional residual capacity. During treatment either with placebo or oxitropium, there was a statistically significant decrease in clinical scores. Results for oxitropium bromide treatment were significantly better than the run-in values (p<0.005) and the placebo period (p<0.02). There was no significant change in non-trial drug consumption. Functional values showed no difference in terms of flow rate, although oxitropium did cause a significant improvement in the RV/TLC ratio (p<0.05). No adverse reactions were reported.
Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors.

Adenoid cystic carcinoma (ACC) is a subtype of malignant salivary gland tumors (MSGT), in which 90% of cases express cKIT. Dasatinib is a potent and selective inhibitor of five oncogenic protein tyrosine kinases (PTKs)/kinase families including cKIT. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT.



In a two-stage design, patients with progressive, recurrent/metastatic ACC (+cKIT) and non-ACC MSGT (separate cohort) were treated with dasatinib 70 mg p.o. b.i.d. Response was assessed every 8 weeks using RECIST.



Of 54 patients: 40 ACC, 14 non-ACC (1, ineligible excluded); M:F = 28 : 26, median age 56 years (range 20-82 years), ECOG performance status 0 : 1 : 2 = 24 : 28 : 2, prior radiation: 44, prior chemotherapy: 21. The most frequent adverse events (AEs) (as % of patients, worst grade 2 or higher) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (7%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), neutropenia (6%), and noncardiac chest pain (6%). No grade 4 AE occurred, 15 patients experienced a grade 3 AE, primarily dyspnea (5) and fatigue (4), and cardiac toxicity (1 prolonged QTc). Among ACC patients, best response to dasatinib: 1 patient (2.5%) had partial response, 20 patients (50%) had stable disease (SD) (3-14 months), 12 patients (30%) had PD, 2 withdrew, 3 discontinued therapy due to AE, and 2 died before cycle 2. Median progression-free survival was 4.8 months. Median overall survival was 14.5 months. For 14 assessable non-ACC patients, none had objective response, triggering early stopping rule. Seven had SD (range 1-7 months), 4 PD, 2 discontinued therapy due to AE, and 1 died before cycle 2.



Although there was only one objective response, dasatinib is well tolerated, with tumor stabilization achieved by 50% of ACC patients. Dasatinib demonstrated no activity in non-ACC MSGT.
Spironolactone improves cardiac sympathetic nerve activity and symptoms in patients with congestive heart failure.

We evaluated whether spironolactone would improve cardiac sympathetic nerve activity and symptoms in patients with congestive heart failure (CHF).



Thirty patients with CHF (left ventricular ejection fraction [LVEF] < 40%; mean, 30% +/- 9%) were treated with an angiotensin-converting enzyme inhibitor, a loop diuretic, and, in most cases, digoxin. Fifteen patients (group A) were assigned to additionally receive spironolactone (12.5-50 mg/day), and the remaining 15 patients (group B) continued their current regimen. Patients were studied before and 6 mo after treatment. The delayed heart-to-mediastinum count ratio (H/M ratio), delayed total defect score (TDS), and washout rate (WR) were determined from (123)I-meta-iodobenzylguanidine (MIBG) images. LVEF was determined by echocardiography, and New York Heart Association (NYHA) functional class was estimated.



Before treatment, LVEF, TDS, H/M ratio, WR, and NYHA functional class were similar in both groups. With treatment, LVEF did not significantly improve in either group. However, after treatment in group A, TDS decreased from 37 +/- 9 to 25 +/- 13 (P = 0.0001), H/M ratio increased from 1.62 +/- 0.20 to 1.83 +/- 0.27 (P < 0.0001), and WR decreased from 51 +/- 9 to 40 +/- 15 (P < 0.001). In group B, these parameters did not significantly change. NYHA functional class improved in both groups (in group A, from 3.3 +/- 0.5 to 1.7 +/- 0.5 [P < 0.0001]; in group B, from 3.3 +/- 0.5 to 2.4 +/- 0.6 [P = 0.01]); this was a significantly greater improvement in group A than in group B (P < 0.01).



Spironolactone improves cardiac sympathetic nerve activity and symptoms in patients with CHF.
Reduction in spinal-induced hypotension with ondansetron in parturients undergoing caesarean section: a double-blind randomised, placebo-controlled study.

Subarachnoid block is the preferred method of anaesthesia for caesarean section, but is associated with hypotension and bradycardia, which may be deleterious to both parturient and baby. Animal studies suggest that in the presence of decreased blood volume, 5-HT may be an important factor inducing the Bezold Jarisch reflex via 5-HT3 receptors located in intracardiac vagal nerve endings. In this study, we evaluated the effect of ondansetron, as a 5-HT3 receptor antagonist, on the haemodynamic response following subarachnoid block in parturients undergoing elective caesarean section.



Fifty-two parturients scheduled for elective caesarean section were randomly allocated into two groups. Before induction of spinal anaesthesia Group O (n=26) received intravenous ondansetron 4 mg; Group S (n=26) received normal saline. Blood pressure, heart rate and vasopressor requirements were assessed.



Decreases in mean arterial pressure were significantly lower in Group O than Group S from 14 min until 35 min. Patients in Group O required significantly less vasopressor (P=0.009) and had significantly lower incidences of nausea and vomiting (P=0.049).



Ondansetron 4 mg, given intravenously 5 min before subarachnoid block reduced hypotension and vasopressor use in parturients undergoing elective caesarean section.
Sleep-disordered breathing and asthma: evidence from a large multicentric epidemiological study in China

Previous studies have postulated that sleep-disordered breathing (SDB) may be associated with the occurrence and exacerbation of asthma. However, there was limited quantitative evidence on the topic. This study aimed at investigating the prevalence and predisposing factors of asthma, and quantifying the association between SDB and asthma among school-aged children in China. In addition, a comprehensive meta-analysis of the published evidences and our findings were further conducted.



To test the hypothesis, we conducted a multicentric cross-sectional study involving 22,478 children aged 5-12 years recruited from eight cities in China. Furthermore, a meta-analysis based on both previously published studies and our cross-sectional study was performed.



The prevalence rate of SDB and asthma was 12.0% and 3.5% among our cross-sectional study sample. It was demonstrated that symptoms of SDB, such as habitual snoring (OR = 1.28, 95%CI: 1.01-1.62), and obstructive sleep apnea (OSA) (OR = 1.92, 95%CI: 1.34-2.76), were significantly associated with asthma, after adjusting for potential confounding factors. In the meta-analysis, SDB was correlated with the prevalence of asthma in both children (OR = 1.58, 95%CI: 1.35-1.80) and adults (OR = 1.55, 95%CI: 1.42-1.67).



Our results provide further evidence for the independent association between SDB and asthma. The clinical significance of our findings lies in the emphasis that children undergoing examination or treatment for asthma should be routinely screened for sleep problems. Further systematic study is required to illuminate the underlying mechanism.
Real-life safety and effectiveness of amlodipine/valsartan combination in the treatment of hypertension.

The aim of our study was to evaluate the safety and effectiveness of the free combination of amlodipine/valsartan in patients with arterial hypertension in a real-life setting.



This was a multicenter, open-label, observational, noninterventional, postmarketing surveillance study conducted in 298 centers in China, Malaysia, Pakistan, Bangladesh, Egypt, and Russia. We evaluated changes in heart rate, systolic and diastolic office blood pressure (BP), as well as BP control rate (<140/90 mmHg) overall, and in clinically relevant subgroups of hypertensive patients (BP >140/90 mmHg) after 12 weeks of treatment with 5/10 mg amlodipine and 80/160 mg valsartan combination.



Two thousand seven hundred and eighty-five patients with arterial hypertension were enrolled, 52 discontinued (eight due to adverse events), and four patients' data were missing. In total, 2729 patients completed the study: mean age 57.9 years, 54.5% men, 54.2% Asian, 44.6% Caucasian; 86.5% had prior hypertension treatment (which was discontinued), baseline BP was 163.1/96.2 mmHg. The significant reduction in BP (-33.2/-16.9 mmHg, P<0.0001) was achieved with amlodipine/valsartan treatment resulting in a final BP of 129.9/79.3 mmHg. A dose-dependent effect was observed with the least BP reduction for 5/80 mg (-29.2/-15.1 mmHg, P<0.0001) and the greatest for the 10/160 mg dose regimen (-43.6/-22.4 mmHg, P<0.0001). Treatment response increased with increasing initial severity of hypertension with the least BP reduction in patients with baseline grade 1 hypertension BP level (SBP 140-159 mmHg): -20.0/-13.4 mmHg, P<0.0001, and the greatest BP drops observed in grade 3 hypertensive patients with baseline systolic BP over 200 mmHg: -73.1/-26.3 mmHg, P<0.0001. Patients with isolated systolic hypertension had BP reductions of -24.2/-4.8 mmHg, P<0.0001.



An optimal BP reduction was achieved for all hypertension grades as well as isolated systolic hypertension, providing evidence that most hypertensive patients may benefit from amlodipine/valsartan combination treatment.
Biochemical effects of urapidil on red cell membrane ion transport systems in a population of elderly essential hypertensives.

The aim of our work was to verify the effect of urapidil on membrane ion transport systems. This was a randomized, double-blind, cross-over study which evaluated the clinical and biochemical effects of urapidil (30 mg twice daily in comparison with placebo) in a group of 10 elderly hypertensive patients (3 male, 7 female ranging from 68 to 90 years, mean age 79.2 +/- 7.6 years). For the evaluation in fresh erythrocytes of principal ion transport systems (cotransport Na+/K+, countertransport Na+/Li+, Na+/K+ ATPase pump. intracellular Na+ and K+) we used the nystatin technique. We found that urapidil activated the red cell membrane ions cotransport system (basal values: 83.7 +/- 50.3 mumol Na+ RBC 1-1.h-1, after 1 month of urapidil therapy: 181.5 +/- 89.3 mumol Na+ RBC 1-1.h-1) (P less than 0.01), without significant changes in the other biochemical parameters evaluated. Our data suggest that one of the mechanisms of the urapidil antihypertensive effect could involve an increase in the membrane sodium cotransport system.
Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: a 7-year longitudinal study.

Hypovitaminosis D has been cross-sectionally associated with dementia and stroke. The objective of this longitudinal study was to determine whether serum vitamin D deficiency at baseline could predict the onset of non-Alzheimer dementias (NAD) within 7 years among older women.



Forty high-functioning older women (78.4 years, 76.4/82.0; median, 25th/75th percentile) from the EPIDOS Toulouse study were divided into two groups based on vitamin D deficiency (i.e., serum 25-hydroxyvitamin D <10 ng/ml) at baseline. At the end of the 7-year follow-up period, women matching the DSM-IV but not the NINCDS-ADRDA criteria were diagnosed with NAD while those matching the NINCDS-ADRDA criteria were considered to have Alzheimer's disease (AD). Subtle cognitive impairments at baseline, cardiovascular risk factors and Parkinson's disease were used as potential confounders.



NAD was reported in 6 women (82.8 years, 80.6/86.0) after 7 years of follow-up. More NAD were observed in women with vitamin D deficiency (p = 0.023). There was no between-group difference regarding the onset of AD (p = 0.332). We found an association between vitamin D deficiency at baseline and the onset of NAD (adjusted odds ratio = 19.57, p = 0.042). Conversely, vitamin D deficiency was not associated with AD (p = 0.222).



Baseline vitamin D deficiency predicted the onset of NAD within 7 years among older women.