nils-herrmann/clean_scirepeval huggingface dataset:
Effects of vildagliptin/metformin therapy on patient-reported outcomes: work productivity, patient satisfaction, and resource utilization.

Type 2 diabetes mellitus (T2DM) is associated not only with high direct healthcare costs, but also with indirect costs, as diabetic complications and the disease itself result in loss of productivity. Vildagliptin is a novel dipeptidyl peptidase-4 inhibitor that is given either alone or in combination with oral hypoglycemic drugs, including metformin. The study was designed to assess the hypothesis that fixed-combination vildagliptin/metformin improves work productivity measured as Work Productivity and Activity Impairment (WPAI) scores. Secondary objectives were the assessment of patient satisfaction by means of the Diabetes Treatment Satisfaction Questionnaire (DTSQs), the change in anthropometric measurements and in glucose control (glycated hemoglobin [HbA1c]), and the evaluation of resource utilization (Resources Utilization Questionnaire).



This study was an addendum to a mandatory, prospective, observational study carried out by the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]) in 49 diabetes centers in Italy. The addendum included 1,046 adult outpatients with a diagnosis of T2DM, who were no longer responding to metformin monotherapy. Patients were observed for up to 1 year.



Mean activity impairment improved by 40.6% (15.4±17.4 vs. 26.1±24.4; P<0.0001), absenteeism by 49.9% (2.0±9.4 vs. 3.8±13.3; P=0.0076), and total work productivity by 37.6% (14.9±15.9 vs. 21.5±24.6; P<0.0001). This resulted in a reduction of the annual indirect cost due to impaired productivity of €400 per working patient and €135 per patient in general. The DTSQ score increased by 30.2% (29.6±5.6 vs. 22.8±6.9; P<0.0001). The satisfaction rate increased from baseline by 44.7%; the hyperglycemia-free or almost hyperglycemia-free perception rate by 37.9%; and the hypoglycemia-free or almost hypoglycemia-free rate by 15.2%. Mean healthcare costs per patients diminished by 19.2% in the second semester of treatment.



This observational study suggests that the fixed combination of vildagliptin/ metformin increases work productivity, reducing indirect costs, and improves quality of life, especially in terms of perception of blood glucose variability, in patients with T2DM.
Effect of myofascial techniques for treatment of upper limb dysfunctions in breast cancer survivors: randomized controlled trial

Besides pain, myofascial dysfunctions may contribute to the presence of upper limb impairments such as impaired range of motion, decreased strength, lymphedema, and altered postures and kinematics. Therefore, the aim of this study was to investigate the effect of myofascial therapy in addition to a standard physical therapy program for treatment of upper limb dysfunctions in breast cancer survivors. Fifty women treated for a unilateral breast cancer with pain and myofascial dysfunctions at the upper limb region. The intervention group received 12 sessions of myofascial therapy consisting of release techniques on myofascial trigger points and adhesions in addition to a standard physical therapy program for 3 months. The control group received 12 sessions of a placebo intervention in addition to the same standard physical therapy program during the 3 months. Outcome parameters are active shoulder range of motion (inclinometer); arm lymphedema (perimeter); upper limb strength (handheld dynamometer); scapular statics and dynamics (acromion-table and pectoralis minor index, inclinometer); shoulder function (Disability of Shoulder, Arm and Hand questionnaire); and quality of life (Short Form 36). Measures were taken before and after the intervention at 6 and 12 months follow-up. No differences between groups were found for all outcome parameters over the course of 1 year. However, overall beneficial effects of the standard physical therapy program for active shoulder range of motion and shoulder function were found in both groups up to 1 year follow-up. Myofascial therapy has no additional beneficial effect for improvement of upper limb function in breast cancer survivors.
Corrigendum to “Strategy for the Management of Diabetic Macular Edema: The European Vitreo-Retinal Society Macular Edema Study”

To compare the efficacy of different therapies in the treatment of diabetic macular edema (DME).



Nonrandomized, multicenter clinical study.



86 retina specialists from 29 countries provided clinical information on 2,603 patients with macular edema including 870 patients with DME.



Reported data included the type and number of treatment(s) performed, the pre- and posttreatment visual acuities, and other clinical findings. The results were analyzed by the French INSEE (National Institute of Statistics and Economic Studies).



Mean change of visual acuity and mean number of treatments performed.



The change in visual acuity over time in response to each treatment was plotted in second order polynomial regression trend lines. Intravitreal triamcinolone monotherapy resulted in some improvement in vision. Treatment with threshold or subthreshold grid laser also resulted in minimal vision gain. Anti-VEGF therapy resulted in more significant visual improvement. Treatment with pars plana vitrectomy and internal limiting membrane (ILM) peeling alone resulted in an improvement in vision greater than that observed with anti-VEGF injection alone. In our DME study, treatment with vitrectomy and ILM peeling alone resulted in the better visual improvement compared to other therapies.
Effects of labeling patients as prehypertensive.

Labeling patients as hypertensive has some negative effects. The effects of being labeled as having prehypertension are unknown. We examined whether the label of prehypertension exerts a negative effect on patients' perceived health and whether it motivates people to adopt lifestyle recommendations to prevent hypertension.



We randomized 97 prehypertensive adults to either a labeling message or a generic (no label) message. At 3 months we assessed self-reports of change in perceived health and reported adoption of lifestyle recommendations to try to prevent hypertension.



Except for more participants with asthma in the label group, the 2 groups were similar at baseline. Among the 70 participants who provided 3-month follow-up data, 18 people (56%) in the no-label group and 22 people (58%) in the label group reported their health as the same; 13 people (41%) in the no label group and 16 people (42%) in the label group reported health as better; and 1 person (in no label group) reported his health as worse. At 3 months there were no differences in reports of changing eating habits (risk ratio [RR], 1.06; 95% CI, 0.86-1.31), cutting down on salt (RR, 0.99; 95% CI, 0.84-1.15), reducing alcohol intake (RR, 1.23; 95% CI, 0.80-1.90), or exercising (RR, 1.17; 95% CI, 0.91-1.51) to try to prevent hypertension.



Being labeled as prehypertensive seems to exert neither harmful nor helpful effects.
THC reduces the anticipatory nucleus accumbens response to reward in subjects with a nicotine addiction

Recent evidence has implicated the endocannabinoid (eCB) system in nicotine addiction. The eCB system also has an important role in reward mechanisms, and nicotine addiction has been associated with aberrant reward processing. Motivated by this evidence, we tested the hypothesis that eCB modulation of reward processing is altered in subjects with a nicotine addiction (NAD). For this purpose, we compared reward-related activity in NAD with healthy controls (HC) in a pharmacological magnetic resonance imaging (MRI) study using Δ9-tetrahydrocannabinol (THC) administration to challenge the eCB system. Eleven HC and 10 NAD participated in a 3-T functional MRI (fMRI) study with a double-blind, cross-over, placebo-controlled design, using a Monetary Incentive Delay (MID) paradigm with three reward levels. Reward activity in the nucleus accumbens (NAcc) and caudate putamen during anticipation and feedback of reward was compared after THC and placebo. fMRI results indicated a significant reduction of reward anticipation activity in the NAcc in NAD after THC administration, which was not present in HC. This is indicated by a significant group by drug by reward interaction. Our data show that THC significantly reduces the NAcc response to monetary reward anticipation in NAD. These results suggest that nicotine addiction is associated with altered eCB modulation of reward processing in the NAcc. This study adds important human data to existing evidence implicating the eCB system in nicotine addiction.
Bone marrow or peripheral blood for reduced-intensity conditioning unrelated donor transplantation.

There have been no randomized trials that have compared peripheral blood (PB) with bone marrow (BM) grafts in the setting of reduced-intensity conditioning (RIC) transplantations for hematologic malignancy. Because immune modulation plays a significant role in sustaining clinical remission after RIC, we hypothesize that higher graft-versus-host disease (GVHD) associated with PB transplantation may offer a survival advantage.



The primary outcome evaluated was overall survival. Cox regression models were built to study outcomes after transplantation of PB (n = 887) relative to BM (n = 219) for patients with acute myeloid leukemia, myelodysplastic syndrome, or non-Hodgkin lymphoma, the three most common indications for unrelated RIC transplantation. Transplantations were performed in the United States between 2000 and 2008. Conditioning regimens consisted of an alkylating agent and fludarabine, and GVHD prophylaxis involved a calcineurin inhibitor (CNI) with either methotrexate (MTX) or mycophenolate mofetil (MMF).



After adjusting for age, performance score, donor-recipient HLA-match, disease, and disease status at transplantation (factors associated with overall survival), there were no significant differences in 5-year rates of survival after transplantation of PB compared with BM: 34% versus 38% with CNI-MTX and 27% versus 20% with CNI-MMF GVHD prophylaxis.



Survival after transplantation of PB and BM are comparable in the setting of nonirradiation RIC regimens for hematologic malignancy. The effect of GVHD prophylaxis on survival merits further evaluation.
Grading brainstem involvement in multiple sclerosis - by means of electro-oculography.

One of the most frequent disorders of the brainstem in multiple sclerosis (MS) is internuclear opthalmoplegia (INO). The aim of this study is to show how it is possible to monitor the course of MS grading INO on the basis of electro-oculographic findings. We selected 130 patients with a diagnosis of clinically defined multiple sclerosis (78 males and 52 females, mean age 43.5 years) from a population of 354 MS patients. Both saccadic eye movements and spontaneous, vestibular (VOR), visuo-vestibular (VVOR) and optokinetich nystagmus (OKN) were assessed. Slowing of the adducting eye was considered as a sign of lesion of the interocular pathways. Statistical analyses showed that the most sensitive test was VVOR, the least sensitive being randomised saccades. An impairment of random saccades was always associated with abnormal results on all other tests. It seems thus possible to grade the involvement of the medial longitudinal fasciculi (MLF) in MS from an abnormality limited to the VVOR test up to an impairment of randomised saccadic movements. Grading brainstem involvement in MS is particularly important in therapeutic trials and during rehabilitation.
Contribution of glucocerebrosidase mutation in a large cohort of sporadic Parkinson's disease in Taiwan.

The association between glucocerebrosidase (GBA) mutations and Parkinson's disease (PD) is attracting increased attention worldwide. In patients of Chinese ethnicity, other than the common L444P mutation, a few mutations have been reported. However, the contribution of GBA to PD can be answered only by a thorough investigation of its mutations in a unique large population.



We enrolled 1747 participants: 967 PD patients and 780 healthy individuals. We screened entire GBA coding regions and exon-intron boundaries in 30 randomly chosen PD patients, followed by testing five variants (L444P, D409H, R120W, L174P, and Q497R) in all participants. The G2385R and R1628P in LRRK2 had been previously studied in almost all participants.


In total, 36 patients (3.72%) carried a heterozygous mutant GBA allele (27 L444P, 7 RecNciI, and 2 D409H). Only two controls (0.26%) carried heterozygous GBA mutation (1 L444P and 1 RecNciI). In PD group, the mean age at onset in carriers was younger than in non-carriers. The difference in percentage of mutation frequencies between patients and controls was highly significant for the L444P mutation (P < 0.0001). One L444P carrier was also associated with LRRK2 G2385R variant, but no atypical Parkinsonism was observed.



The present study ascertains that L444P mutation in GBA gene may contribute to an earlier onset of development of PD in Han/Chinese population. Following LRRK2 variants, GBA is the second most frequent mutations indicated for sporadic PD development in the Han/Chinese population. These GBA carriers are associated with an earlier onset of Parkinsonism.
The potential therapeutic effect of melatonin in gastro-esophageal reflux disease

Gastro-Esophageal Reflux Disease (GERD) defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Many drugs are used for the treatment of GERD such as omeprazole (a proton pump inhibitor) which is a widely used antiulcer drug demonstrated to protect against esophageal mucosal injury. Melatonin has been found to protect the gastrointestinal mucosa from oxidative damage caused by reactive oxygen species in different experimental ulcer models. The aim of this study is to evaluate the role of exogenous melatonin in the treatment of reflux disease in humans either alone or in combination with omeprazole therapy.



36 persons were divided into 4 groups (control subjects, patients with reflux disease treated with melatonin alone, omeprazole alone and a combination of melatonin and omeprazole for 4 and 8 weeks) Each group consisted of 9 persons. Persons were subjected to thorough history taking, clinical examination, and investigations including laboratory, endoscopic, record of esophageal motility, pH-metry, basal acid output and serum gastrin.



Melatonin has a role in the improvement of Gastro-esophageal reflux disease when used alone or in combination with omeprazole. Meanwhile, omeprazole alone is better used in the treatment of GERD than melatonin alone.



The present study showed that oral melatonin is a promising therapeutic agent for the treatment of GERD. It is an effective line of treatment in relieving epigastric pain and heartburn. However, further studies are required to confirm the efficacy and long-term safety of melatonin before being recommended for routine clinical use.
Correspondences between Classical, Intuitionistic and Uniform Provability

Based on an analysis of the inference rules used, we provide a characterization of the situations in which classical provability entails intuitionistic provability. We then examine the relationship of these derivability notions to uniform provability, a restriction of intuitionistic provability that embodies a special form of goal-directedness. We determine , first, the circumstances in which the former relations imply the latter. Using this result, we identify the richest versions of the so-called abstract logic programming languages in classical and intuitionistic logic. We then study the reduction of classical and, derivatively, intuitionistic provability to uniform provability via the addition to the assumption set of the negation of the formula to be proved. Our focus here is on understanding the situations in which this reduction is achieved. However, our discussions indicate the structure of a proof procedure based on the reduction, a matter also considered explicitly elsewhere.
Quantitative reverse transcription-PCR assay for detection of mRNA encoding full-length human tissue kallikrein 7: prognostic relevance of KLK7 mRNA expression in breast cancer.

The human tissue kallikrein gene family (KLK1 to KLK15) encodes a group of 15 serine proteases (hK1 to ), several of which have been implicated in cancer-related processes.



We established a specific quantitative reverse transcription-PCR assay for full-length KLK7 mRNA that excluded amplification of the exon 2 deletion splice variant (the latter does not encode a functional protease), and evaluated full-length KLK7 mRNA expression [normalized to human glucose-6-phosphate dehydrogenase (h-G6PDH)] in tumor tissue specimens from 155 breast cancer patients.



High KLK7 mRNA expression (continuous) was significantly associated with a better patient outcome according to both univariate (P = 0.005) and multivariate (P = 0.046) Cox survival analysis. Separation of patients by optimized dichotomization revealed a significantly better prognosis for patients with high KLK7 mRNA status (n = 89) compared with patients with low KLK7 mRNA status (n = 66) [univariate hazard ratio (HR) = 0.45 (P = 0.001); multivariate HR = 0.50 (P = 0.005)]. In the subgroup of patients not receiving adjuvant treatment (n = 69), KLK7 mRNA status was a significant prognosticator [univariate HR = 0.29 (P = 0.002); multivariate HR = 0.40 (P = 0.034)]. This subgroup was least influenced by postoperative treatment and thus best showed the impact of KLK7 expression on the natural course of breast cancer disease.



Expression of full-length KLK7 mRNA may represent a new prognostic marker in breast cancer disease.
Midregional proadrenomedullin predicts mortality and major adverse cardiac events in patients presenting with chest pain: results from the CHOPIN trial.

Chest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR-proADM) in prediction of mortality and major adverse cardiac events (MACE).



This was a subanalysis of the CHOPIN study, a 16-center prospective trial that enrolled 2,071 patients presenting with chest pain within 6 hours of onset. The primary endpoint was 6-month all-cause mortality and the secondary endpoint was 30-day and 6-month MACE: ED visits or hospitalization for acute myocardial infarction, unstable angina, reinfarction, revascularization, and heart failure.



MR-proADM performed similarly to troponin (cTnI; c-statistic = 0.845 and 0.794, respectively) for mortality prediction in all subjects and had similar results in those with noncardiac diagnoses. MR-proADM concentrations were stratified by decile, and the cohort in the top decile had a 9.8% 6-month mortality risk versus 0.9% risk for those in the bottom nine deciles (p < 0.0001). MR-proADM, history of coronary artery disease (CAD), and hypertension were predictors of short-term MACE, while history of CAD, hypertension, cTnI, and MR-proADM were predictors of long-term MACE.



In patients with chest pain, MR-proADM predicts mortality and MACE in all-comers with chest pain and has similar prediction in those with a noncardiac diagnosis. This exploratory analysis is primarily hypotheses-generating and future prospective studies to identify its utility in risk stratification should be considered.
Anxiety and Depression Increase in a Stepwise Manner in Parallel With Multiple FGIDs and Symptom Severity and Frequency

Anxiety and depression occur frequently in patients with functional gastrointestinal disorders (FGIDs), but their precise prevalence is unknown. We addressed this issue in a large cohort of adult patients and determined the underlying factors.In total, 4,217 new outpatients attending 2 hospitals in Hamilton, Ontario, Canada completed questionnaires evaluating FGIDs and anxiety and depression (Hospital Anxiety and Depression scale). Chart review was performed in a random sample of 2,400 patients.Seventy-six percent of patients fulfilled Rome III criteria for FGIDs, but only 57% were diagnosed with FGIDs after excluding organic diseases, and the latter group was considered for the analysis. Compared with patients not meeting the criteria, prevalence of anxiety (odds ratio (OR) 2.66, 95% confidence interval (CI): 1.62–4.37) or depression (OR 2.04, 95% CI: 1.03–4.02) was increased in patients with FGIDs. The risk was comparable to patients with organic disease (anxiety: OR 2.12, 95% CI: 1.24–3.61; depression: OR 2.48, 95% CI: 1.21–5.09). The lowest prevalence was observed in asymptomatic patients (OR 1.37; 95% CI 0.58–3.23 and 0.51; 95% CI 0.10–2.48; for both conditions, respectively). The prevalence of anxiety and depression increased in a stepwise manner with the number of co-existing FGIDs and frequency and/or severity of gastrointestinal (GI) symptoms. Psychiatric comorbidity was more common in females with FGIDs compared with males (anxiety OR 1.73; 95% CI 1.35–2.28; depression OR 1.52; 95% CI 1.04–2.21). Anxiety and depression were formally diagnosed by the consulting physician in only 22% and 9% of patients, respectively.Psychiatric comorbidity is common in patients referred to a secondary care center but is often unrecognized. The prevalence of both anxiety and depression is influenced by gender, presence of organic diseases, and FGIDs, and it increases with the number of coexistent FGIDs and frequency and severity of GI symptoms.
QT dispersion has no prognostic value in patients with symptomatic heart failure: an ELITE II substudy.

This study prospectively investigated 3,118 standard 12-lead ECGs recorded in 1,804 patients, who participated in the Losartan Heart Failure Survival Study--ELITE II clinical trial. After exclusion of patients with rhythms other than sinus, or atrioventricular block, or poor quality ECGs, 986 (703 men, mean age 71 +/- 7 years) with baseline ECGs were retained, of whom 615 patients had follow-up ECGs 4 months after randomization. QT intervals were manually measured with a digitizing board. Heart rate, QRS duration, maximum QT and JT intervals, QT and JT dispersion (the interval ranges across all measurable ECG leads) were analyzed. In the overall population, there were 140 (14%) deaths from all causes, including 119 (12%) cardiac and 59 (6%) sudden deaths during a follow-up of 540 +/- 153 days. The mean heart rate was significantly faster in nonsurvivors than in survivors (77 +/- 16 vs 74 +/- 14 beats/min, P = 0.006), and in patients who died of cardiac death (76 +/- 16 beats/min, P = 0.04 vs survivors). Mean QRS duration was significantly longer in nonsurvivors (107 +/- 25 ms), and in the subgroups who died of cardiac (107 +/- 24 ms) or sudden death (112 +/- 23 ms) than in survivors (99 +/- 24 ms, P < 0.01 for all). The maximum and corrected (QTc) QT intervals were similar for nonsurvivors, regardless of cause of death, and in survivors (P = NS for all comparisons). Significantly shorter maximum and corrected (JTc) JT intervals were observed in victims of any mode of death compared to survivors (P < 0.05 for all). There was no significant difference in QT or JT dispersion between patients with any mode of death and survivors (P > 0.1 for all). Neither losartan nor captopril significantly modified QT or JT dispersion. In conclusion, increased QT dispersion is not associated with increased mortality in patients with heart failure, and is not suitable to examine drug efficacy in these patients.