nils-herrmann/clean_scirepeval huggingface dataset:
Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis

This study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design.



Twenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%.



Phase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5-30)] than in OA cats [14 (8.5-28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed.



Outcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment.
A Comparison of the pharmacokinetics of the anticancer MET inhibitor foretinib free base tablet formulation to bisphosphate salt capsule formulation in patients with solid tumors

This phase I, open-label, randomized, 2-part crossover study assessed the safety, pharmacokinetics and relative bioavailability of single doses of the anticancer MET inhibitor foretinib (formerly known as GSK1363089, EXEL-2880 and XL-880) free base tablet formulation compared to a bisphosphate salt capsule formulation (Part 1), and assessed the safety, efficacy, and pharmacokinetics of the bisphosphate salt capsule administered 3 times a week in cancer patients (Part 2).  In Part 1, patients were randomized in a crossover manner to receive a single oral dose of foretinib formulated as a bisphosphate salt capsule (240 mg; 183 mg free base equivalent) followed one week later by a single dose of a free base tablet (180 mg), or vice versa where the treatment sequence was reversed. In Part 2, patients self-administered oral doses of bisphosphate salt capsules (200 mg) 3 times a week until disease progression.  Twelve patients with solid tumors were enrolled and completed Part 1, and 10 patients continued into Part 2. Most AEs were mild or moderate in severity. The most common drug-related AEs were fatigue, diarrhea, and nausea. The least-squares (LS) mean total area under the curve was 3144 and 3514 ng*h/mL for the free base tablet and bisphosphate salt capsule, respectively, with a ratio of 0.89 (90% confidence interval, CI: 0.69, 1.16). The LS mean maximal concentration (Cmax) was 81.6 and 98.5 ng/mL for the free base and bisphosphate salt, respectively, with a ratio of 0.83 (90% confidence interval, CI: 0.67, 1.02). The time to reach Cmax was ∼4 h for both formulations. The pharmacokinetics of foretinib were not clinically different between the 2 formulations. Of the 10 patients assessed for efficacy, 3 patients achieved stable disease.  Foretinib was well tolerated as single doses of both the free base and bisphosphate salt formulations. The pharmacokinetics and relative bioavailability of the 2 formulations were not clinically different. The bisphosphate salt formulation was well tolerated on a 3-times a week dosing schedule, and reached steady-state plasma concentration after 2 weeks.
Differential efficacy of cognitive behavioral therapy and psychodynamic therapy for major depression: a study of prescriptive factors.

Minimal efficacy differences have been found between cognitive behavioral therapy (CBT) and psychodynamic therapies for depression, but little is known about patient characteristics that might moderate differential treatment effects. We aimed to generate hypotheses regarding such potential prescriptive factors.



We conducted post-hoc model-based recursive partitioning analyses alongside a randomized clinical trial comparing the efficacy of CBT and short-term psychodynamic supportive psychotherapy (SPSP). Severely depressed patients received additional antidepressant medication. We included 233 adults seeking treatment for a major depressive episode in psychiatric outpatient clinics, who completed post-treatment assessment. Post-treatment mean Hamilton Depression Rating Scale scores constituted the main outcome measure.



While treatment differences (CBT v. SPSP) were minimal in the total sample of patients (d = 0.04), model-based recursive partitioning indicated differential treatment efficacy in certain subgroups of patients. SPSP was found more efficacious among moderately depressed patients receiving psychotherapy only who showed low baseline co-morbid anxiety levels (d = -0.40) and among severely depressed patients receiving psychotherapy and antidepressant medication who reported a duration of the depressive episode of ⩾1 year (d = -0.31), while CBT was found more efficacious for such patients reporting a duration <1 year (d = 0.83).



Our findings are observational and need validation before they can be used to guide treatment selection, but suggest that knowledge of prescriptive factors can help improve the efficacy of psychotherapy for depression. Depressive episode duration and co-morbid anxiety level should be included as stratification variables in future randomized clinical trials comparing CBT and psychodynamic therapy.
A comparison of preemptive versus standard renal replacement therapy for acute kidney injury after cardiac surgery.

The optimal timing of renal replacement therapy (RRT) initiation in patients undergoing cardiac surgery remains controversial. This study aimed to determine whether preemptive RRT or standard RRT was associated with hospital mortality in cardiac surgical patients with acute kidney injury (AKI).



Data were retrospectively collected from patients who underwent cardiac surgery and experienced postoperative AKI requiring RRT at Zhongshan Hospital of Fudan University from September 1, 2006 to December 31, 2013. The patients were divided into two groups according to the RRT strategy applied.



A total of 213 patients were enrolled in this study; 59 patients were categorized into the preemptive RRT group and 154 into the standard RRT group. The preemptive RRT group exhibited significantly lower mortality (33.90% versus 51.95%, P = 0.018) and time to recovery of renal function than the standard RRT group (15.34 ± 14.46 versus 22.88 ± 14.08 d, P = 0.022). Moreover, the preemptive RRT group showed significantly lower serum creatinine levels and higher proportions of recovery of renal function and weaning from RRT at death or discharge than the standard RRT group. There was no significant difference in the duration of mechanical ventilation, RRT, intensive care unit stay, or hospital stay between the two groups.



In patients after cardiac surgery, preemptive RRT was associated with lower hospital mortality and faster and more frequent recovery of renal function than standard RRT. However, preemptive RRT did not affect other patient-centered outcomes including mechanical ventilation time, RRT time, or length of intensive care unit or hospital stay.
Parathyroid Hormone (1-34)-Coated Microneedle Patch System: Clinical Pharmacokinetics and Pharmacodynamics for Treatment of Osteoporosis

To evaluate the clinical PK/PD of PTH(1-34) delivered by a novel transdermal drug-coated microneedle patch system (ZP-PTH) for the treatment of osteoporosis. Phase 1 PK studies evaluated the effect of site of administration, patch wear time and dose in normal volunteers, ages 40–85 yrs. Phase 2 was conducted in post-menopausal women with osteoporosis to determine the patch dose response compared to placebo patch and FORTEO® injection. Phase 1 ZP-PTH patch delivery demonstrated a rapid PTH plasma pulse profile with Tmax 3 times shorter and apparent T1/2 2 times shorter than FORTEO®. In Phase 2, ZP-PTH 20, 30 and 40 µg doses showed a proportional increase in plasma PTH AUC. Inter-subject and intra-subject AUC variability was similar for all patch doses and comparable to injection. All patch doses produced a significant increase in spine bone mineral density. Unexpectedly, ZP-PTH also produced an early increase in hip bone mineral density, an effect not observed with the injection. These studies suggest that this novel ZP-PTH patch system can deliver a consistent and therapeutically relevant PTH PK profile. Based on encouraging Phase 2 safety and efficacy data, the program is advancing into a pivotal Phase 3 clinical study.
Evaluation of a new spacer device for drug inhalation

We have studied the efficacy and acceptability of a new inhalation spacer device. The functional principle of the device, differing from that of conventional spacers, is based on evaporation of the propellant during circular movement of the aerosol in a small spherical chamber. We assessed the bronchodilating effect of salbutamol (SalbuventR) inhaled with the new spacer (RondoR) compared with salbutamol (VentolineR) inhaled with the spacer VolumaticR and with salbutamol (SalbuventR) inhaled with a conventional metered dose actuator using a double-blind cross-over arrangement. Fifteen asthmatic patients were treated over a period of 4 weeks. They used each of the three different devices for 2–3 days every week. Peak expiratory flow rates were recorded every morning after one and after two puffs of the study drugs. The bronchodilator responses to the three treatments were similar within narrow ranges of estimate. By visual analogue scale assessment the new spacer was significantly easier to handle (P<0.05) and more convenient to carry around (P<0.01) than VolumaticR.
Prognostic value of p53 protein expression and clinicopathological factors in infiltrating ductal carcinoma of the breast. A study of 192 patients.

The p53 gene is located on the short arm of chromosome 17. It encodes a 53-kd nuclear protein (p53) found in scant amounts in normal tissue. Mutations of the p53 gene have been reported in different human tumours. In breast cancer, it has been noted that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, although there is a high degree of variability, which may be due to different immunohistochemical techniques, varying assessment of results and the type of monoclonal antibody used. This study is an immunohistochemical analysis of p53 expression in 192 cases of infiltrating ductal carcinoma of the breast, correlating it with clinicopathological factors and the clinical course of the disease. Of all the breast-cancer tissue analysed, stains for p53 antibody were found in 87 tumours (45.3%). The results of multivariate analysis show that the independent predictors related to recurrence are tumour size, lymph-node metastasis and p53, while those related to death are necrosis, lymph-node metastasis and p53. In summary, our series showed prognostic significance between the expression of p53 and shorter survival time and disease-free interval for all patients in general as well as those who presented lymph-node metastases at the time of diagnosis.
A randomised, controlled, double-blind, cross-over pilot study assessing the effects of spironolactone, losartan and their combination on heart rate variability and QT dispersion in patients with chronic heart failure

The blocking of aldosterone or angiotensin II receptors improves mortality in patients with chronic heart failure. We explored whether combining losartan and spironolactone would have any added benefit on the known surrogate of mortality by using heart rate variability (HRV) and QT dispersion as our endpoints.



We designed a three-phase, consecutive, randomised, controlled, double-blind, cross-over pilot study to assess the effects of losartan alone (50 mg/day), spironolactone (25 mg/day) with angiotensin converting enzyme (ACE) inhibitor and, finally, losartan with spironolactone, on HRV and QT dispersion. We enrolled eight patients (aged 47 to 72 years, mean = 63.7 years), with New York Heart Association (NYHA) class II-III heart failure and ejection fraction (EF) < 35%, in the study at a university-affiliated hospital in Dundee, Scotland. Digital 24-hour Holter recordings were analysed for time-domain HRV and the 12-lead ECG was optically scanned and digitised for analysis of QT dispersion. Evaluations were done at baseline, and at six, 12 and 18 weeks from baseline.



Losartan and spironolactone showed statistically significant, favourable effects on HRV, QT dispersion and mean heart rate (p < 0.05).



The data showed that in these patients with heart failure, the addition of spironolactone to an ACE inhibitor, or the use of losartan on its own, or the combination of losartan plus spironolactone induced a favourable sympathovagal balance. The drugs significantly improved HRV indices and QT dispersion further, and the combination appeared to be safe. However, no significant differences were seen between the effects of each of these regimes on HRV and QT dispersion.
The accuracy of the FreeStyle Navigator continuous glucose monitoring system in children with type 1 diabetes.

To evaluate the accuracy and precision of the FreeStyle Navigator continuous glucose monitoring system in children with type 1 diabetes.



In 30 children with type 1 diabetes (mean age 11.2 +/- 4.1 years), the Navigator glucose values were compared with reference serum glucose values of blood samples obtained in an inpatient clinical research center and measured in a central laboratory using a hexokinase enzymatic method and in an outpatient setting with a FreeStyle meter. Median absolute difference (AD) and median relative absolute difference (RAD) were computed for sensor-reference and sensor-sensor pairs.



The median AD and RAD were 17 mg/dl and 12%, respectively, for 1,811 inpatient sensor-reference pairs and 20 mg/dl and 14%, respectively, for 8,639 outpatient pairs. The median RAD between two simultaneous Navigator measurements (n = 1,971) was 13%. Ninety-one percent of sensors in the inpatient setting and 81% of sensors in the outpatient setting had a median RAD < or = 20%.



The Navigator's accuracy does not yet approach the accuracy of current-generation home glucose meters, but it is sufficient to believe that the device has the potential to be an important adjunct to treatment of youth with type 1 diabetes.
Multisite comparison of high-sensitivity multiplex cytokine assays.

The concentrations of cytokines in human serum and plasma can provide valuable information about in vivo immune status, but low concentrations often require high-sensitivity assays to permit detection. The recent development of multiplex assays, which can measure multiple cytokines in one small sample, holds great promise, especially for studies in which limited volumes of stored serum or plasma are available. Four high-sensitivity cytokine multiplex assays on a Luminex (Bio-Rad, BioSource, Linco) or electrochemiluminescence (Meso Scale Discovery) platform were evaluated for their ability to detect circulating concentrations of 13 cytokines, as well as for laboratory and lot variability. Assays were performed in six different laboratories utilizing archived serum from HIV-uninfected and -infected subjects from the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) and commercial plasma samples spanning initial HIV viremia. In a majority of serum samples, interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor alpha were detectable with at least three kits, while IL-1β was clearly detected with only one kit. No single multiplex panel detected all cytokines, and there were highly significant differences (P < 0.001) between laboratories and/or lots with all kits. Nevertheless, the kits generally detected similar patterns of cytokine perturbation during primary HIV viremia. This multisite comparison suggests that current multiplex assays vary in their ability to measure serum and/or plasma concentrations of cytokines and may not be sufficiently reproducible for repeated determinations over a long-term study or in multiple laboratories but may be useful for longitudinal studies in which relative, rather than absolute, changes in cytokines are important.
Prevalence and clinical significance of solitary pulmonary sub-segmental microembolism.

Solitary pulmonary microembolism is rarely discussed as a distinct diagnostic entity. The purpose of this investigation was to determine the prevalence and clinical significance of embolism limited to subsegmental branches in a group of patients discharged from hospital on anticoagulants with a diagnosis of pulmonary embolism based on ventilation-perfusion imaging followed by selective angiography.



Of 29 consecutive patients with classic signs of pulmonary embolism at angiography, we identified a subgroup of 5 patients with sub-segmental embolism, which was solitary in all cases.



Clinical presentation included chest pain (2/5), shortness of breath (2/5, or hypoxemia (1/5). Chest X-rays were normal (2/5), or showed pulmonary oedema (1/5) or atelectasis with (1/5), or without (1/5) pleural effusion. VQ imaging patterns included small subsegmental mismatch (1/5), one segment mismatch (1/5), single (1/5) or triple (2/5) match. The site and size of the microemboli found at angiography were incompatible with the location and severity of symptoms in 4/5 (80%) patients, and with location and extent of Chest X-ray findings and with VQ patterns in all patients. VQ abnormalities were either either disproportionably larger or were non congruent with the vascular territory compromised by the subsegmental embolus.



Sub-segmental pulmonary micro-emboli were always solitary, and not uncommon, comprising 17% of all patients with pulmonary embolism. The location and size of the emboli were inconsistent with clinical, Chest X-ray and scintigraphic findings, suggesting that isolated microemboli are a serendipitous finding, of no clinical significance.
Development and validation of the paediatric cancer coping scale.

The purpose of this study was to develop and test the psychometric properties of the paediatric cancer coping scale in children with cancer.



Coping is a mediator between stressful events and adaptation. However, existing tools cannot be used to assess and understand coping strategies in children with cancer in Taiwan.



A total of 229 children with cancer were recruited from three medical centres in Taiwan in 2008-2009. Internal consistency and test-retest reliability were estimated by Cronbach's alpha and intra-class correlation coefficient respectively. The factor structure was determined by exploratory factor analysis and confirmatory factor analysis. Pearson's correlation coefficient was employed to test the convergent and discriminate validity.



The paediatric cancer coping scale demonstrated internal consistency (α = 0·91) and a 2-week test-retest reliability (intra-class correlation coefficient = 0·86). Its construct validity was confirmed by factor analysis, which extracted and defined three categories of coping strategies: cognitive coping, problem-oriented coping and defensive coping; these three factors explained 40% of the total variance with factor loadings ranging from 0·31 to 0·71. Convergent and discriminate validities were demonstrated by significant correlations among the coping, resilience and anxiety subscales.



The paediatric cancer coping scale is a reliable and valid scale to measure and examine coping strategies in children with cancer.
CT angiography (CTA) and diagnostic performance of noninvasive fractional flow reserve: results from the Determination of Fractional Flow Reserve by Anatomic CTA (DeFACTO) study.

Fractional flow reserve (FFR) computed from standard coronary CT scans (FFRCT) is a novel noninvasive method for determining the functional significance of coronary artery lesions. Compared with CT alone, FFRCT significantly improves diagnostic accuracy and discrimination for patients with and without hemodynamically significant coronary artery stenoses. To date, the impact of CT image quality on diagnostic performance of FFRCT is unknown. We evaluated the impact of patient preparation, CT scan protocol, and factors related to image quality on the diagnostic accuracy of FFRCT.



We studied stable patients with suspected coronary artery disease (CAD), enrolled from 17 centers, who underwent CT, invasive coronary angiography, FFR, and FFRCT. The accuracy of CT and FFRCT for diagnosis of ischemia was compared against an invasive FFR reference standard. Anatomically obstructive CAD was defined by a stenosis value of at least 50 by CT or invasive coronary angiography, whereas ischemia was defined by an FFR or FFRCT of up to 0.80. Ischemia was assessed at the per-patient and per-vessel levels. Diagnostic performance of FFRCT was then evaluated in relation to patient preparation, including administration before CT of a β-blocker or nitroglycerin, as well as in relation to imaging characteristics, including misalignment, noise, motion, and coronary artery calcium.



Among 252 study participants, 137 (54.0%) had an abnormal FFR. Administration of a β-blocker increased FFRCT specificity (51.0% vs 66.0%; p = 0.03) with lower bias (-0.084 vs -0.048; p = 0.008), whereas nitroglycerin pretreatment within 30 minutes of CT was associated with improved specificity (54.0% vs 75.0%; p = 0.013). Misalignment artifacts resulted in impaired sensitivity (43.0% vs 86.0%; p = 0.001) with resultant reductions in overall accuracy (56.0% vs 71.0%; p = 0.03). No differences in diagnostic performance of FFRCT were noted in the presence of coronary motion or increasing coronary artery calcium score.



Use of β-blockade and nitroglycerin administration before CT improve diagnostic performance of FFRCT. Diagnostic accuracy of FFRCT is significantly reduced in the setting of misalignment artifacts.