nils-herrmann/clean_scirepeval huggingface dataset:
Placebo controlled pilot trial to study the remyelinating potential of intravenous immunoglobulins in multiple sclerosis.

Currently there is no treatment available to improve a stable deficit in multiple sclerosis. It was shown in animal models that intravenous immunoglobulins (IVIg) can enhance central nervous remyelination, and the first open trials were promising. We therefore conducted a double blind, placebo controlled pilot study to evaluate the effect of IVIg treatment in patients with multiple sclerosis with a stable clinical deficit. The primary outcome parameter was the change in central motor conduction time as an indirect measure of central myelination. Secondary outcome parameters were neurological examinations including the expanded disability status scale (EDSS), neurological rating scale (NRS), and manual muscle testing (MMT). Ten patients were treated first with placebo and then with IVIg (0.4 g/kg body weight on 5 consecutive days), the two treatments being separated by an interval of 6 weeks. There was no difference in the central motor conduction times measured before and 6 weeks after each treatment. Clinically there was a small improvement after IVIg treatment, but there was no significant difference when compared with placebo. In conclusion, our data do not support a role for IVIg in the remyelination of stable multiple sclerosis lesions as measured by central conduction time. The importance of the small clinical benefit is currently not clear.
Gabapentin extended release for the treatment of painful diabetic peripheral neuropathy: efficacy and tolerability in a double-blind, randomized, controlled clinical trial.

Efficacy and tolerability in a double-blind, randomized, controlled clinical trial A randomized, double-blind, placebo controlled study was conducted in 147 patients to determine the efficacy and safety of gabapentin extended release (g-ER) in treating pain associated with diabetic peripheral neuropathy (DPN). Gabapentin, an immediate-release formulation, has demonstrated clinical efficacy in DPN patients but also a relatively high incidence of somnolence and dizziness at the doses required for effective treatment of DPN pain (1,2). Using the polymer-based AcuForm technology , g-ER tablets have been formulated to handle the saturable transport mechanism responsible for the lack of dose pro-portionality seen with gabapentin. When administered with a meal, g-ER tablets gradually expand and release the drug to the upper gastrointestinal tract over an extended period of time (3). This enables g-ER to be administered once or twice daily, versus three times daily or more (4) for regular gabapentin, while providing equivalent or improved bioavailability and potentially improving tolerability, convenience, and minimized incidence of adverse events. In this clinical trial, g-ER was dosed as either a single dose in the evening or as an asymmetrically divided dose regimen with the larger dose in the evening. It was hypothesized that this would provide maximum pain relief at night, when it is most needed, and that the commonly observed adverse events of dizziness and somnolence would be less burdensome because they would be more likely to occur while the patient was asleep. Patients with a clinical diagnosis of DPN were queried about symmetrical painful symptoms in distal extremities (minimum 1–5 years) and baseline average daily pain (ADP) score (Ն4) using a questionnaire. Randomized patients received 3,000 mg g-ER, as either a single evening daily dose or a divided dose (1,200 mg in the morning and 1,800 mg in the evening), or placebo for 4 weeks. g-ER was rapidly titrated from 300 to 3,000 mg/day over 2 weeks, followed by two additional weeks at 3,000 mg/day. Efficacy measures included changes from baseline to end point in ADP and daily sleep interference scores. Most patients were male (55.1%), white (68.7%), and type 2 diabetic (95.2%), with a mean DPN duration of 3.4 years and a mean age of 59 years. Baseline mean pain scores for patients in the g-ER single-dose and divided-dose groups and placebo were 6.8, 6.7, and 6.9, respectively. Neuropathic pain was most often reported in the foot.
Measurement of gray and white matter atrophy in dementia with Lewy bodies using diffeomorphic anatomic registration through exponentiated lie algebra: A comparison with conventional voxel-based morphometry.

DLB is recognized as the second major form of dementia in the elderly. The regional pattern of GM atrophy in DLB highly overlaps that in AD. The aim of this study was to identify the critical pattern of atrophy in DLB by using DARTEL, which provides improved registration accuracy compared with that of conventional VBM.



We evaluated 51 patients with probable AD, 43 patients with probable DLB, and 40 age-matched healthy controls. The pattern of GM atrophy in each group was compared by using conventional VBM and VBM-DARTEL.



Regional patterns of atrophy identified by using conventional VBM differed significantly from those identified by using VBM-DARTEL. A decrease in GM volume in the MTLs in both AD and DLB was identified with VBM-DARTEL; the decrease was greater in patients with AD than in those with DLB. Comparisons with healthy controls revealed that the WM volume of the whole brain was preserved in patients with DLB. In contrast, a severe bilateral decrease in WM in the MTLs was detected in patients with AD.



VBM-DARTEL provided more accurate results, and it enabled the identification of more localized morphologic alterations than did conventional VBM. Analysis of WM preservation in DLB could help to differentiate this condition from AD.
Hypothermia in comatose survivors from out-of-hospital cardiac arrest: pilot trial comparing 2 levels of target temperature.

It is recommended that comatose survivors of out-of-hospital cardiac arrest should be cooled to 32° to 34°C for 12 to 24 hours. However, the optimal level of cooling is unknown. The aim of this pilot study was to obtain initial data on the effect of different levels of hypothermia. We hypothesized that deeper temperatures will be associated with better survival and neurological outcome.



Patients were eligible if they had a witnessed out-of-hospital cardiac arrest from March 2008 to August 2011. Target temperature was randomly assigned to 32°C or 34°C. Enrollment was stratified on the basis of the initial rhythm as shockable or asystole. The target temperature was maintained during 24 hours followed by 12 to 24 hours of controlled rewarming. The primary outcome was survival free from severe dependence (Barthel Index score ≥60 points) at 6 months. Thirty-six patients were enrolled in the trial (26 shockable rhythm, 10 asystole), with 18 assigned to 34°C and 18 to 32°C. Eight of 18 patients in the 32°C group (44.4%) met the primary end point compared with 2 of 18 in the 34°C group (11.1%) (log-rank P=0.12). All patients whose initial rhythm was asystole died before 6 months in both groups. Eight of 13 patients with initial shockable rhythm assigned to 32°C (61.5%) were alive free from severe dependence at 6 months compared with 2 of 13 (15.4%) assigned to 34°C (log-rank P=0.029). The incidence of complications was similar in both groups except for the incidence of clinical seizures, which was lower (1 versus 11; P=0.0002) in patients assigned to 32°C compared with 34°C. On the contrary, there was a trend toward a higher incidence of bradycardia (7 versus 2; P=0.054) in patients assigned to 32°C. Although potassium levels decreased to a greater extent in patients assigned to 32°C, the incidence of hypokalemia was similar in both groups.



The findings of this pilot trial suggest that a lower cooling level may be associated with a better outcome in patients surviving out-of-hospital cardiac arrest secondary to a shockable rhythm. The benefits observed here merit further investigation in a larger trial in out-of-hospital cardiac arrest patients with different presenting rhythms.
Effectiveness of sensor-augmented pump therapy in children and adolescents with type 1 diabetes in the STAR 3 study.

Maintenance of appropriate A1C values and minimization of hyperglycemic excursions are difficult for many pediatric patients with type 1 diabetes. Continuous glucose monitoring (CGM) sensor-augmented pump (SAP) therapy is an alternative to multiple daily injection (MDI) therapy in this population.



Sensor-augmented pump therapy for A1C reduction (STAR 3) was a 1-yr trial that included 82 children (aged 7-12) and 74 adolescents (aged 13-18) with A1C values ranging from 7.4 to 9.5% who were randomized to either SAP or MDI therapy. Quarterly A1C values were obtained from all subjects. CGM studies were carried out at baseline, 6 months, and 12 months to quantify glycemic excursions [calculated as area under the glucose concentration-time curve (AUC)] and variability. In the SAP group, sensor compliance was recorded.



Baseline A1C values were similar in subjects randomized to the SAP (8.26 ± 0.55%) and MDI groups (8.30 ± 0.53%). All subsequent A1C values showed significant (p < 0.05) treatment group differences favoring SAP therapy. Compared with the MDI group, subjects in the SAP group were more likely to meet age-specific A1C targets and had lower AUC values for hyperglycemia with no increased risk of hypoglycemia. Glucose variability improved in the SAP group compared to the MDI group. Children wore CGM sensors more often and were more likely to reach age-specific A1C targets than adolescents.



SAP therapy allows both children and adolescents with marginally or inadequately controlled type 1 diabetes to reduce A1C values, hyperglycemic excursions, and glycemic variability in a rapid, sustainable, and safe manner.
Automatic Identification of Wet and Dry Cough in Pediatric Patients with Respiratory Diseases

Cough is the most common symptom of several respiratory diseases. It is a defense mechanism of the body to clear the respiratory tract from foreign materials inhaled accidentally or produced internally by infections. The identification of wet and dry cough is an important clinical finding, aiding in the differential diagnosis especially in children. Wet coughs are more likely to be associated with lower respiratory track bacterial infections. At present during a typical consultation session, the wet/dry decision is based on the subjective judgment of a physician. It is not available for the non-trained person, long term monitoring or in the assessment of treatment efficacy. In this paper we address these issues and develop an automated technology to classify cough into ‘wet’ and ‘dry’ categories. We propose novel features and a Logistic regression model (LRM) for the classification of coughs into wet/dry classes. The performance of the method was evaluated on a clinical database of pediatric coughs (C = 536) recorded using a bed-side non-contact microphone from N = 78 patients. Results of the automatic classification were compared against two expert human scorers. The sensitivity and specificity of the LRM in picking wet coughs were between 87 and 88% with 95% confidence interval on training/validation dataset (310 cough events from 60 patients) and 84 and 76% respectively on prospective dataset (117 cough events from 18 patients). The kappa agreement with two expert human scorers on prospective dataset was 0.51. These results indicate the potential of the method as a useful clinical tool for cough monitoring, especially at home settings.
The study of once- and twice-daily biphasic insulin aspart 30 (BIAsp 30) with sitagliptin, and twice-daily BIAsp 30 without sitagliptin, in patients with type 2 diabetes uncontrolled on sitagliptin and metformin-The Sit2Mix trial.

Investigate efficacy and tolerability of intensifying diabetes treatment with once- or twice-daily biphasic insulin aspart 30 (BIAsp 30) added to sitagliptin, and twice-daily BIAsp 30 without sitagliptin in patients with type 2 diabetes (T2D) inadequately controlled on sitagliptin.



Open-label, three-arm, 24-week trial; 582 insulin-naïve patients were randomized to twice-daily BIAsp 30+sitagliptin (BIAsp BID+Sit), once-daily BIAsp 30+sitagliptin (BIAsp QD+Sit) or twice-daily BIAsp 30 without sitagliptin (BIAsp BID), all with metformin.



After 24 weeks, HbA1c reduction (%) was superior with BIAsp BID+Sit vs. BIAsp QD+Sit (BIAsp BID+Sit minus BIAsp QD+Sit difference: -0.36 [95% CI -0.54; -0.17], P<0.001) and BIAsp BID (BIAsp BID minus BIAsp BID+Sit difference: 0.24 [0.06; 0.43], P=0.01). Observed final HbA1c values were 6.9%, 7.2% and 7.1% (baseline 8.4%), and 59.8%, 46.5% and 49.7% of patients achieved HbA1c <7.0%, respectively. Confirmed hypoglycaemia was lower with BIAsp QD+Sit vs. BIAsp BID (P=0.015); rate: 1.17 (BIAsp QD+Sit), 1.50 (BIAsp BID+Sit) and 2.24 (BIAsp BID) episodes/patient-year. Difference in bodyweight change favoured BIAsp QD+Sit vs. both BID groups (P<0.001).



Adding BIAsp 30 to patients with T2D poorly controlled with sitagliptin and metformin is efficacious and well tolerated; however, while BIAsp BID+Sit showed superior glycaemic control, BIAsp QD+Sit had a lower rate of hypoglycaemia and showed no weight gain.
Use of a Transanal Drainage Tube for Prevention of Anastomotic Leakage and Bleeding after Anterior Resection for Rectal Cancer

The aim of the present study was to investigate the usefulness of the transanal drainage tube for prevention of anastomotic leakage and bleeding after anterior resection for rectal cancer. Between January 2007 and May 2011 a nonrandomized prospective study of patients undergoing anterior resection for rectal cancer was done. The patients were divided into the transanal drainage tube (TDT) and non-transanal drainage tube (NTDT) groups according to whether the transanal drainage tube was used in the operation. Clinical characteristics and postoperative complications were compared between the TDT and NTDT groups. The study included 81 patients in the TDT group and 77 patients in the NTDT group. In the TDT group, anastomotic leakage occurred in 2 patients and no anastomotic bleeding occurred. In the NTDT group, anastomotic leakage occurred in 7 patients and anastomotic bleeding occurred in 2 patients. The TDT group had significantly fewer anastomotic complications compared with the NTDT group (2.5 vs 11.7 %; P = 0.029). Furthermore, the TDT group showed an obvious reduction in the rate of anastomotic leakage and anastomotic bleeding compared with the NTDT group (2.5 vs 7.8 % and 0.0 vs 2.6 %), but because the number of cases is relatively small, the difference did not reach statistical significance (P = 0.160 and P = 0.236). The use of a transanal drainage tube in anterior resection for rectal cancer may be a simple, safe, and effective means of preventing or reducing the occurrence of anastomotic leakage and bleeding. A larger-scale single or multi-center prospective randomized study or a meta-analysis including similar studies is necessary for further elucidation of this issue.
Population-based p16 and HPV positivity rates in oropharyngeal cancer in Southeast Scotland.

We assessed a population-based cohort of patients diagnosed with oropharyngeal squamous cell carcinoma in Southeast Scotland over 13 months. p16 and human papilloma virus (HPV) expression were determined, and correlated with stage, treatment, smoking and alcohol history, and disease outcomes. Retrospective analysis was performed on 60 patients. p16 immunohistochemistry and HPV genotyping were performed on formalin-fixed paraffin-embedded tissues. HPV infection (as defined by p16 positivity and/or HPV PCR positivity) was identified in 57% of samples, while dual positives were detected in 45% of cases. HPV16 was most prevalent of the HPV types and was associated with 90% of positive samples. Cause-specific 1-year and 2-year survivals were 82.5% and 78.2%, respectively. The p16-positive and HPV-positive groups demonstrated significantly increased cause-specific survival in comparison with their negative counterparts.
A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury.

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or cervical (C4-T1) SCI were sequentially recruited for this dose-ranging (0.3 mg to 9 mg Cethrin), multi-center study of 48 patients with complete American Spinal Injury Association assessment (ASIA) A. Vital signs; clinical laboratory tests; computed tomography (CT) scans of the spine, head, and abdomen; magnetic resonance imaging (MRI) of the spine, and ASIA assessment were performed in the pre-study period and in follow-up periods out to 1 year after treatment. The treatment-emergent adverse events that were reported were typical for a population of acute SCI patients, and no serious adverse events were attributed to the drug. The pharmacokinetic analysis showed low levels of systemic exposure to the drug, and there was high inter-patient variability. Changes in ASIA motor scores from baseline were low across all dose groups in thoracic patients (1.8±5.1) and larger in cervical patients (18.6±19.3). The largest change in motor score was observed in the cervical patients treated with 3 mg of Cethrin in whom a 27.3±13.3 point improvement in ASIA motor score at 12 months was observed. Approximately 6% of thoracic patients converted from ASIA A to ASIA C or D compared to 31% of cervical patients and 66% for the 3-mg cervical cohort. Although the patient numbers are small, the observed motor recovery in this open-label trial suggests that BA-210 may increase neurological recovery after complete SCI. Further clinical trials with Cethrin in SCI patients are planned, to establish evidence of efficacy.
Therapeutic effects of add-on low-dose dextromethorphan plus valproic acid in bipolar disorder

Changes in inflammatory cytokines and dysfunction of the neurotrophic system are thought to be involved in the pathology of bipolar disorder (BP). We investigated whether inflammatory and neurotrophic factors were changed in BP. We also investigated whether treating BP with valproic acid (VPA) plus low-dose (30 or 60 mg/day) dextromethorphan (DM) is more effective than treating it with VPA only, and whether DM affects plasma cytokines and brain derived neurotrophic factor (BDNF) levels. In a 12-week, randomized, double-blind study, patients were randomly assigned to the VPA+DM30, VPA+DM60, or VPA+Placebo groups. The Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) were used to evaluate symptom severity, and ELISA to analyze plasma cytokine and BDNF levels. We recruited 309 patients with BP and 123 healthy controls. Before treatment, patients with BP had significantly higher plasma cytokine and lower plasma BDNF levels than did healthy controls. After treatment, HDRS and YMRS scores in each group showed significant improvement. Plasma cytokine levels tended to decline in all groups. Changes in plasma BDNF levels were significantly greater in the VPA+DM60 group than in the VPA+Placebo group.



patients with BP have a certain degree of systemic inflammation and BDNF dysfunction. Treatment with VPA plus DM (60 mg/day) provided patients with BP significantly more neurotrophic benefit than did VPA treatment alone.
The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.



In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays.



Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells.



Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.
Influence of Software Tool and Methodological Aspects of Total Metabolic Tumor Volume Calculation on Baseline [18F]FDG PET to Predict Survival in Hodgkin Lymphoma

To investigate the respective influence of software tool and total metabolic tumor volume (TMTV0) calculation method on prognostic stratification of baseline 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET) in newly diagnosed Hodgkin lymphoma (HL).



59 patients with newly diagnosed HL were retrospectively included. [18F]FDG-PET was performed before any treatment. Four sets of TMTV0 were calculated with Beth Israel (BI) software: based on an absolute threshold selecting voxel with standardized uptake value (SUV) >2.5 (TMTV02.5), applying a per-lesion threshold of 41% of the SUV max (TMTV041) and using a per-patient adapted threshold based on SUV max of the liver (>125% and >140% of SUV max of the liver background; TMTV0125 and TMTV0140). TMTV041 was also determined with commercial software for comparison of software tools. ROC curves were used to determine the optimal threshold for each TMTV0 to predict treatment failure.



Median follow-up was 39 months. There was an excellent correlation between TMTV041 determined with BI and with the commercial software (r = 0.96, p<0.0001). The median TMTV0 value for TMTV041, TMTV02.5, TMTV0125 and TMTV0140 were respectively 160 (used as reference), 210 ([28;154] p = 0.005), 183 ([-4;114] p = 0.06) and 143 ml ([-58;64] p = 0.9). The respective optimal TMTV0 threshold and area under curve (AUC) for prediction of progression free survival (PFS) were respectively: 313 ml and 0.70, 432 ml and 0.68, 450 ml and 0.68, 330 ml and 0.68. There was no significant difference between ROC curves. High TMTV0 value was predictive of poor PFS in all methodologies: 4-years PFS was 83% vs 42% (p = 0.006) for TMTV02.5, 83% vs 41% (p = 0.003) for TMTV041, 85% vs 40% (p<0.001) for TMTV0125 and 83% vs 42% (p = 0.004) for TMTV0140.



In newly diagnosed HL, baseline metabolic tumor volume values were significantly influenced by the choice of the method used for determination of volume. However, no significant differences were found in term of prognosis.