nils-herrmann/clean_scirepeval huggingface dataset:
Improvement of cardiac performance and cardiovascular risk factors in children with GH deficiency after two years of GH replacement therapy: an observational, open, prospective, case-control study.

GH deficiency (GHD) in adults is associated with a cluster of cardiovascular risk factors that may contribute to an increased mortality for cardiovascular disease.



The aim of this study was to evaluate the effect of GHD and GH replacement therapy on cardiac performance, lipid profile, and insulin resistance in children.



This was a 2-yr case-control prospective study.



Thirty children with GHD aged 9.3 +/- 0.5 yr and 30 healthy matched controls were studied.



Children were studied before and after 1 and 2 yr of GH replacement (GHD children) or no treatment (controls).



Lipid profile, serum insulin levels, homeostasis model of assessment (HOMA) index, and left ventricular (LV) mass and function by echocardiography were the main outcome measures.



At study entry, the LV mass index was significantly lower in GHD children (50.2 +/- 1.7) than in controls (60.3 +/- 2.5 g/m(2); P < 0.002), whereas LV systolic and diastolic function, lipid profile, insulin levels, and HOMA index were similar. In GHD children LV mass index significantly increased (66.3 +/- 2.4 g/m(2); P < 0.0001) after 1 yr of GH replacement and remained stable thereafter. LV systolic and diastolic function did not change during treatment. After 2 yr of GH replacement, total cholesterol (P < 0.007) and the atherogenic index (P < 0.0001) significantly decreased, whereas fasting insulin levels (P < 0.001) and HOMA index (P < 0.0001) significantly increased compared with both pretreatment and control values.



GHD in children is associated with a reduced cardiac size but with a normal cardiac function, lipid profile, and insulin sensitivity. Two years of GH replacement normalizes cardiac morphology, improves lipid profile, and slightly impairs insulin sensitivity.
AFQ056 treatment of levodopa-induced dyskinesias: results of 2 randomized controlled trials.

Study objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson's disease patients with levodopa-induced dyskinesia. Two randomized, double-blind, placebo-controlled, parallel-group, in-patient studies for Parkinson's disease patients with moderate to severe levodopa-induced dyskinesia (study 1) and severe levodopa-induced dyskinesia (study 2) on stable dopaminergic therapy were performed. Patients received 25-150 mg AFQ056 or placebo twice daily for 16 days (both studies). Study 2 included a 4-day down-titration. Primary outcomes were the Lang-Fahn Activities of Daily Living Dyskinesia Scale (study 1), the modified Abnormal Involuntary Movement Scale (study 2), and the Unified Parkinson's Disease Rating Scale-part III (both studies). Secondary outcomes included the Unified Parkinson's Disease Rating Scale-part IV items 32-33. The primary analysis was change from baseline to day 16 on all outcomes. Treatment differences were assessed. Fifteen patients were randomized to AFQ056 and 16 to placebo in study 1; 14 patients were randomized to each group in study 2. AFQ056-treated patients showed significant improvements in dyskinesias on day 16 versus placebo (eg, Lang-Fahn Activities of Daily Living Dyskinesia Scale, P = .021 [study 1]; modified Abnormal Involuntary Movement Scale, P = .032 [study 2]). No significant changes were seen from baseline on day 16 on the Unified Parkinson's Disease Rating Scale-part III in either study. Adverse events were reported in both studies, including dizziness. Serious adverse events (most commonly worsening of dyskinesias, apparently associated with stopping treatment) were reported by 4 AFQ056-treated patients in study 1, and 3 patients (2 AFQ056-treated patient and 1 in the placebo group) in study 2. AFQ056 showed a clinically relevant and significant antidyskinetic effect without changing the antiparkinsonian effects of dopaminergic therapy.
Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study.

To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia gene (MLL(+)), we compared the outcome of MLL(+) patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376 patients with a known MLL status in the trial, 297 (79%) were MLL(+). Among the 277 of 297 MLL(+) patients (93%) in first remission (CR), there appeared to be a significant difference in disease-free survival (adjusted by waiting time to HSCT) between the 37 (13%) who received HSCT and the 240 (87%) who received chemotherapy only (P = .03). However, the advantage was restricted to a subgroup with 2 additional unfavorable prognostic features: age less than 6 months and either poor response to steroids at day 8 or leukocytes more than or equal to 300 g/L. Ninety-seven of 297 MLL(+) patients (33%) had such high-risk criteria, with 87 achieving CR. In this group, HSCT was associated with a 64% reduction in the risk of failure resulting from relapse or death in CR (hazard ratio = 0.36, 95% confidence interval, 0.15-0.86). In the remaining patients, there was no advantage for HSCT over chemotherapy only. In summary, HSCT seems to be a valuable option for a subgroup of infant MLL(+) acute lymphoblastic leukemia carrying further poor prognostic factors.
Impaired metabolic control and socio-demographic status in immigrant children at onset of Type 1 diabetes.

The aim of the present study was to compare clinical and socio-demographic conditions at the onset of Type 1 diabetes in children born to immigrant families and children born to Swedish families, and to assess whether those conditions had an impact on metabolic status.



This was an observational nationwide population-based matched cohort study on prospectively recorded registry data of all children with diabetes in Sweden and their families during 2000-2010. Out of a total of 13 415 children from the Swedish Childhood Diabetes Registry (SWEDIABKIDS), 879 children born to immigrant parents were collected. To these we added 2627 children with Swedish-born parents, matched for gender, age and year of onset of Type 1 diabetes.



The proportion of low capillary pH (< 7.30) at onset was higher in the immigrant cohort [25.8% vs. 16.4% in the Swedish cohort (P < 0.001)]. HbA1c was also higher [95 mmol/mol (10.8%) vs. 88 mmol/mol (10.2%), respectively (P < 0.001)]. In a logistic regression model with low pH as the dependent variable, we were unable to reveal any significant association to socio-demographic factors, but the odds ratio for HbA1c was 0.983 (95% CI 0.976-0.991) and for plasma glucose was 0.953 (95% CI 0.933-0.973).



Children born to immigrant parents have lower capillary pH and higher HbA1c at diabetes onset. Immigrant families harbour lower socio-demographic living conditions, but this fact does not seem to influence the inferior metabolic condition at diabetes onset.
Foot health education provision for people with rheumatoid arthritis–an online survey of UK podiatrists’ perceptions

Patient education supports general disease self-management and in relation to foot problems, it is recommended as a key intervention for people with rheumatoid arthritis (RA). Further, it is known what the foot health educational (FHE) needs are in relation to their experiences of foot problems. Podiatrists are the key health professionals who provide the management of RA-related foot pathology and this includes the delivery of FHE. However, we do not know what is currently provided and what podiatrists' perceptions are of this intervention. It is possible that there is a difference between what is provided and what patients need in order to maximise their foot health benefits and hence this may contribute to the persistence of foot problems and symptoms. This study primarily aims to define what UK podiatrists' perceptions of FHE are in relation to; what is delivered, how it is delivered, and the timing of its delivery, in the context of its' accessibility. The secondary aim is to identify any influence of the participants' gender, age and duration of professional qualification on their responses.



An online survey of UK HCPC registered podiatrists was used to capture quantitative data in relation to the perceived; aims, content, methods and effectiveness, timing and barriers to FHE provision to people with RA. Data was analysed to assess significant associations between the participant responses and their gender, age and duration of professional qualification. Free text comments were analysed using thematic analysis.



43 podiatrists across the UK completed the survey. The majority of participants stated that, they provided FHE and agreed with its overall aims. The most common methods of delivery that were perceived to be most effective were: verbal, written and website based information. The best times at which to deliver FHE were thought to be at the point of diagnosis of RA and at any available opportunity of health care delivery. The majority of participants thought they had enough knowledge and access to information resources to effectively deliver FHE, but half of the participants felt that consultation duration limited their ability to do so. Gender and duration of professional qualification influenced participants' perceptions of FHE.



The importance and content of FHE for people with RA has been defined, but time limitations are seen to restrict its delivery. The development of an education needs analysis tool to facilitate efficient identification of patients FHE needs could enable timely and tailored delivery of FHE to people with RA.
Effect of cognitive behavioral therapy on heart rate variability during REM sleep in female rape victims with PTSD.

Six female rape victims with posttraumatic stress disorder (PTSD) were assessed for sleep disturbances. Five responded to cognitive-behavioral therapy (CBT) and one did not complete treatment. Sympatho-vagal balance was measured using heart rate variability (HRV) during rapid eye movement (REM) sleep. The treatment responders significantly decreased on HRV while the noncompleter increased. The responders also significantly decreased on sleep disturbances. The noncompleter remained unchanged. Thus a remission in PTSD symptoms following CBT accompanied a reduction in the HRV indicator of sympathetic predominance in REM sleep.
Association of immune parameters with clinical outcome in stage III colon cancer: results of Southwest Oncology Group Protocol 9009

Levamisole (LMS), utilized in the adjuvant treatment of patients with stage III colon cancer, is immunomodulatory. To determine whether alterations in immune parameters before, during and after 12 months of 5FU/LMS therapy correlate with disease-free survival, 38 patients enrolled on Southwest Oncology Group (SWOG) protocol 8899 received extensive lymphocyte phenotypic analysis prior to therapy and 3, 6, 12 and 15 months after treatment initiation. The median follow-up of patients is 41 months. Significant increases in the proportion and total number of CD56+ natural killer cells were seen, starting at 3 months and continuing until 15 months (P < 0.001). Increases in the total numbers of cells expressing CD25 (interleukin-2 receptor), VLA4 and the combinations of CD4: CD45RA and CD4:CDw29 were not evident during therapy but were seen at 15 months (P < 0.05: CD25, CD4:CDw29, CD4:CD45RA; P < 0.001: VLA4). Low levels of CD8+ cells prior to treatment initiation and after 3 months of therapy correlated with early relapse within the first year of 5FU/LMS treatment. Patients who have remained disease-free (n = 22, median follow-up 45 months) demonstrated increases in the total numbers of CD8+, CD25+, CD56+, VLA4+, CD4: CDw29 and CD4:CD45RA cells, primarily at 15 months. In contrast, patients who relapsed had decreased numbers of CD8+, CD4:CDw29, CD4: CD45RA and VLA4+ cells and minimal increases in CD56+ and CD25+ cells. Statistically significant differences between the late-relapse group and the group remaining disease-free were seen for CD25+, CD4: CD45RA and CD4:CDw29 cells at the 15-month assay time (P = 0.0276, P = 0.0349, P = 0.0178 respectively). In conclusion, multiple alterations in lymphocyte phenotype, with increases in the proportion and total number of cells involved in cell-mediated immune responses, were seen during and especially following completion of therapy with 5FU/LMS. Many of these changes are significantly associated with clinical outcome and may be useful for risk stratification of stage III colon cancer patients following completion of adjuvant therapy.
Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum

In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection. This is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4–12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT). The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy. In LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT) and/or fluorouracil (5FU)-based CRT in a future randomised phase III trial. Clinical trial identifier BACCHUS: NCT01650428
Animal models for screening anxiolytic-like drugs: a perspective

Contemporary biological psychiatry uses experimental animal models to increase our understanding of affective disorder pathogenesis. Modern anxiolytic drug discovery mainly targets specific pathways and molecular determinants within a single phenotypic domain. However, greater understanding of the mechanisms of action is possible through animal models. Primarily developed with rats, animal models in anxiety have been adapted with mixed success for mice, easy-to-use mammals with better genetic possibilities than rats. In this review, we focus on the three most common animal models of anxiety in mice used in the screening of anxiolytics. Both conditioned and unconditioned models are described, in order to represent all types of animal models of anxiety. Behavioral studies require careful attention to variable parameters linked to environment, handling, or paradigms; this is also discussed. Finally, we focus on the consequences of re-exposure to the apparatus. Test-retest procedures can provide new answers, but should be intensively studied in order to revalidate the entire paradigm as an animal model of anxiety.
Optimizing the use of anti-interleukin-6 monoclonal antibody with dexamethasone and 140 mg/m2 of melphalan in multiple myeloma: results of a pilot study including biological aspects

Interleukin-6 (IL-6) is a major survival factor for multiple myeloma (MM) cells preventing apoptosis induced by dexamethasone (DEX) or chemotherapy. In all, 24 consecutive patients with MM in first-line therapy received DEX for 4 days, followed by melphalan (HDM: 140 mg/m2) and autologous stem cell transplantation (ASCT). The anti-IL-6 monoclonal antibody (mAb) (B-E8) was given till haematological recovery, starting 1 day before DEX. Results were historically compared to MM patients treated with HDM 140 and 200 mg/m2. Our results show (1) that B-E8 was able to fully neutralize IL-6 activity in vivo before and after HDM as shown by inhibition of C reactive protein (CRP) production; (2) no haematological toxicity; (3) a significant reduction of mucositis and fever; (4) a median event-free survival of 35 months and an overall survival of 68.2% at 5 years with a median follow-up of 72 months; and (5) the overall daily IL-6 production progressively increased on and after 7 days post-HDM, with the increased serum CRP levels. In the 5/24 patients with uncontrolled CRP production, a large IL-6 production was detected (320 μg/day) that could not possibly be neutralized by B-E8. These data show the feasibility to neutralize IL-6 in vivo with anti-IL-6 mAb in the context of HDM.
Clonazepam use for prevention of acute and delayed vomiting induced by Cisplatin-based chemotherapy for lung cancer.

We investigated the efficacy of clonazepam as an antiemetic in cisplatin-based chemotherapy for lung cancer. Seven patients experienced cisplatin-induced vomiting despite antiemetic therapy including 5-hydroxytryptamine(3) (5-HT(3)) antagonist and dexamethasone. Therefore, the antiemetic therapy including clonazepam, 5-HT(3) antagonist and dexamethasone was subsequently explored in the next course for the same seven patients. We administered clonazepam (0.5 or 1.0 mg/kg) once a day orally for 5 d from day one prior to chemotherapy. The grade of delayed vomiting, evaluated according to Common Terminology Criteria for Adverse Events Version 3.0, in the courses of therapy with clonazepam was significantly lower than without clonazepam (p=0.013). The patients whose serum clonazepam concentrations were below the lower limit of detection (3.0 ng/ml) experienced vomiting in three of three courses, whereas the patients whose serum clonazepam concentrations were higher than 4.3 ng/ml experienced no vomiting in six of seven courses. We observed that the symptom of cisplatin-induced delayed vomiting is controlled with serum clonazepam levels in the order of 10.0 ng/ml.
Partial laryngectomy with imbrication laryngoplasty for glottic carcinoma.

Treatment options for unilateral glottic carcinoma include radiation therapy, partial laryngectomy, and endoscopic cordectomy. We used partial laryngectomy with imbrication laryngoplasty (PLIL) for definitive treatment with curative intent in a select group of patients.



Retrospective multicenter review of 24 patients treated with PLIL. Data collection included demographics, tumor characteristics, time to decannulation, time to oral food intake, local control, survival, voice result as judged by the physician, voice result as judged by the patient, and patient satisfaction.



Five academic medical centers.



PLIL includes a composite resection of the entire vocal fold, with its ligament, muscle, adjacent paraglottic tissues, and the adjacent block of thyroid cartilage. A neocord is reconstructed by imbricating the remaining thyroid cartilage strips and covering them with a false vocal fold flap.



A total of 24 patients (T1, n = 13; T2, n = 10; and T3, n = 1) underwent PLIL. Median time to decannulation was 4 days, and median time to oral food intake was 5 days. Clear margins were achieved in 23 patients (96%). Follow-up ranged from 1 to 11 years (median duration of follow-up, 5.5 years). In the patients who had clear margins at the initial surgery, the rate of overall disease control was 100%. Voice quality was judged by the physician as good or excellent in 100% of the patients who underwent PLIL, and as better than typical hemilaryngectomy in 23 patients (96%). Twenty-three patients (96%) were satisfied with their voice quality.



PLIL provides us with a single modality curative approach to unilateral glottic carcinoma. It also provides rapid recovery of oral and/or nasal airway and swallowing, excellent voice quality, and a disease-control rate similar to or better than other treatment modalities.
Bright light therapy for negative symptoms in schizophrenia: a pilot study.

Sir: Negative symptoms like blunted affect, lack of spontaneity , and emotional and social withdrawal are disabling conditions for many schizophrenic patients. Pharmacologic strategies alone are frequently insufficient in the treatment of negative symptoms. New treatment approaches are therefore required. Bright light therapy is the treatment of choice for seasonal depression , but is now also shown to be efficacious in nonseasonal depression. 1 Until now, no studies of bright light therapy in schizophrenic patients have been published. This is the first study to evaluate the safety and tolerability of bright light therapy in patients diagnosed with the residual subtype of schizophrenia.  Ten patients (8 men and 2 women) with a diagnosis of schizophrenia (DSM-IV criteria) were included in the study, which was conducted from January 2001 to October 2003. At study entry, the mean age of all patients was 41.8 years. Inclusion criteria were residual subtype of schizophrenia (295.6) and stable antipsychotic medication treatment for at least 4 weeks. Antidepressants were not allowed, and any medication inducing photosensitivity was an exclusion criterion. All patients signed informed consent statements before they were enrolled in the study, and the study was approved by the local human subjects research committee. Bright light therapy with 10,000 lux (Chronolux CL–100; Samarit; Aachen, Germany) was applied 1 hour daily, 5 days a week, for 4 weeks. All patients were evaluated with the Positive and Negative Syndrome Scale (PANSS), 2 a visual analog scale (VAS) for mood and a VAS for drive (ranging from 0 mm [abso-lute best mood or drive] to 100 mm [absolute worst mood or drive]), the Clinical Global Impressions scale (CGI), 3 and the Hamilton Rating Scale for Depression (17 items). 4 Measurements were conducted by blinded raters at the screening visit and at weeks 1, 2, and 4, and follow-up examinations were conducted at weeks 8 and 12. Statistical analyses were conducted using SPSS, Version 12 (SPSS Inc.; Chicago, Ill.). The effect of light therapy on the time course of the outcome variables listed above was tested with the Friedman test, as the assumption of normality was not met. Post hoc comparisons between individual time points were performed using the Wilcoxon test. During the treatment period (weeks 1–4), patients were analyzed by an intent-to-treat method, replacing missing data by the last-observation-carried-forward method.  Nine patients concluded 4 weeks of treatment, and 1 patient discontinued after 2 weeks for personal reasons. …