nils-herrmann/clean_scirepeval huggingface dataset:
Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients

After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy.



The scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation.



A total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse effects (p=0.008) in renal transplant recipients receiving tacrolimus and mycophenolic acid compared to the cyclosporine regimen. This finding demonstrated construct validity. Intra-class correlation was 0.81 (95% confidence interval: 0.65-0.90) and Kappa statistic of 0.68 ± 0.25 for all 18 adverse effects and verified substantial inter-rater reliability.



This immunosuppressive adverse effects scoring system in stable renal transplant recipients was evaluated and substantiated face, content and construct validity with inter-rater reliability. The scoring system may facilitate prospective, standardized clinical monitoring of immunosuppressive adverse drug effects in stable renal transplant recipients and improve medication adherence.
Spatially distributed sequential stimulation reduces muscle fatigue during neuromuscular electrical stimulation

A critical limitation with neuromuscular electrical stimulation (NMES) approach is the rapid onset of muscle fatigue during repeated contractions, which results in the muscle force decay and slowing of muscle contractile properties. In our previous study, we demonstrated that spatially distributed sequential stimulation (SDSS) show a drastically greater fatigue-reducing ability compared to a conventional, single active electrode stimulation (SES) with an individual with spinal cord injury when applied for plantar flexors. The purpose of the present study is to explore the fatigue-reducing ability of SDSS for major lower limb muscle groups in the able-bodied population as well as individuals with spinal cord injury (SCI). SDSS was delivered through four active electrodes applied to the muscle of interest, sending a stimulation pulse to each electrode one after another with 90° phase shift between successive electrodes. For comparison, SES was delivered through one active electrode. For both modes of stimulation, the resultant frequency to the muscle as a whole was 40 Hz. Using corresponding protocols for the fatiguing stimulation, we demonstrated the fatigue-reducing ability of SDSS by higher fatigue indices as compared with single active electrode setup for major leg muscles in both subject groups. The present work verifies and extends reported findings on the effectiveness of using spatially distributed sequential stimulation in the leg muscles to reduce muscle fatigue. Application of this technique can improve the usefulness of NMES during functional movements in the clinical setup.
Closed kinetic chain alone compared to combined open and closed kinetic chain exercises for quadriceps strengthening after anterior cruciate ligament reconstruction with respect to return to sports: a prospective matched follow-up study

Rehabilitation after anterior cruciate ligament (ACL) reconstruction has focused over the past decade on closed kinetic chain (CKC) exercises due to presumably less strain on the graft than with isokinetic open kinetic chain exercises (OKC); however, recent reports suggest that there are only minor differences in ACL strain values between some CKC and OKC exercises. We studied anterior knee laxity, thigh muscle torque, and return to preinjury sports level in 44 patients with unilateral ACL; group 1 carried out quadriceps strengthening only with CKC while group 2 trained with CKC plus OKC exercises starting from week 6 after surgery. Anterior knee laxity was determined with a KT-1000 arthrometer; isokinetic concentric and eccentric quadriceps and hamstring muscle torque were studied with a Kin-Com dynamometer before and 6 months after surgery. At an average of 31 months after surgery the patients answered a questionnaire regarding their current knee function and physical activity/sports to determine the extent and timing of their recovery. No significant differences in anterior knee laxity were noted between the groups 6 months postsurgery. Patients in group 2 increased their quadriceps torque significantly more than those in group 1, but no differences were found in hamstring torque between the groups. A significantly higher number of patients in group 2 (n=12) than in group 1 (n=5) returned to sports at the same level as before the injury (P<0.05). Patients from group 2 who returned to sports at the same level did so 2 months earlier than those in group 1. Thus the addition of OKC quadriceps training after ACL reconstruction results in a significantly better improvement in quadriceps torque without reducing knee joint stability at 6 months and also leads to a significantly higher number of athletes returning to their previous activity earlier and at the same level as before injury.
Behavioral effects of l-Dopa in schizophrenic patients

As part of an investigation of the possible role of dopaminergic mechanisms in some psychoses, the behavioral effects of administration of l-Dopa to schizophrenic patients was assessed. l-Dopa was administered in dosages of 3–6 g/day to 10 such patients who had been maintained off neuroleptic drugs for approximately a week. Behavioral worsening occurred in all 10 patients. Three showed non-specific stimulation while the remaining 7 showed a combination of both stimulation and worsening of pre-existent symptoms or the development of new symptomatology. The significance of these findings is discussed with regard to those of other investigators.
Double blind randomized comparative evaluation of nimesulide and paracetamol as antipyretics.

To compare the efficacy and safety of nimesulide and paracetamol as antipyretic agents.



Double blind, randomized clinical trial.



Hospitalized patients having fever due to a variety of infections were given either drug in a randomized manner. (Nimesulide group = 49, Paracetamol group = 50). Serial axillary temperature was recorded after drug administration and side effects monitored.



The mean temperature after one hour of drug administration was significantly lower in nimesulide group (p < 0.05). Significantly fewer doses of nimesulide were required to bring down the temperature on the first day (p < 0.001). The mean maximum temperature recorded on second and third day was significantly lower in the nimesulide group (p < 0.05). Adverse reactions were seen in the form of epigastric pain and vomiting in one patient in Nimesulide group and three in paracetamol group.



Nimesulide is more effective than paracetamol as an antipyretic agent and is safe for use in infants and children.
Anatomically constrained region deformation for the automated segmentation of the hippocampus and the amygdala: Method and validation on controls and patients with Alzheimer’s disease

We describe a new algorithm for the automated segmentation of the hippocampus (Hc) and the amygdala (Am) in clinical Magnetic Resonance Imaging (MRI) scans. Based on homotopically deforming regions, our iterative approach allows the simultaneous extraction of both structures, by means of dual competitive growth. One of the most original features of our approach is the deformation constraint based on prior knowledge of anatomical features that are automatically retrieved from the MRI data. The only manual intervention consists of the definition of a bounding box and positioning of two seeds; total execution time for the two structures is between 5 and 7 min including initialisation. The method is evaluated on 16 young healthy subjects and 8 patients with Alzheimer's disease (AD) for whom the atrophy ranged from limited to severe. Three aspects of the performances are characterised for validating the method: accuracy (automated vs. manual segmentations), reproducibility of the automated segmentation and reproducibility of the manual segmentation. For 16 young healthy subjects, accuracy is characterised by mean relative volume error/overlap/maximal boundary distance of 7%/84%/4.5 mm for Hc and 12%/81%/3.9 mm for Am; for 8 Alzheimer's disease patients, it is 9%/84%/6.5 mm for Hc and 15%/76%/4.5 mm for Am. We conclude that the performance of this new approach in data from healthy and diseased subjects in terms of segmentation quality, reproducibility and time efficiency compares favourably with that of previously published manual and automated segmentation methods. The proposed approach provides a new framework for further developments in quantitative analyses of the pathological hippocampus and amygdala in MRI scans.
The Effect of Patient Reminders on the Use of Screening Mammography in an Urban Health Department Primary Care Setting

Mammography screening continues to be under-utilized, especially among women from lower socioeconomic groups. In order to determine whether having direct access to health care services has an effect on mammography use among low income women, we conducted a randomized trial of two alternative letter reminders among 1,717 women who were enrolled at two locations of a multi-site inner city health department in Detroit. All participants were 39 1/2 years of age and older and were due for a screening mammogram at randomization. A physician-directed reminder form was placed in each of the participant’s medical records at the beginning of the study. In addition participants were randomized to receive either a letter directing them to visit their primary care physician, a letter directing them to contact the clinic directly to schedule a mammogram, or no letter. Study participants were predominantly African–American, two-thirds of whom were over age 50, and who had minimal health insurance coverage. During the intervention year, mammograms were completed by 179 out of 967 study women at site one (18.5%), and 90 out of 750 study women at site two (12%). A multivariate model controlling for the simultaneous effect of age, insurance type, visit history and past mammography use, showed no significant independent effect of either type of letter reminder on mammography completion during the study year. In conclusion, letters targeted at women due for screening mammograms did not have a beneficial effect on mammography utilization above and beyond that of a physician medical record reminder.
Elevated γ-glutamyltransferase in implantable cardioverter defibrillator patients

Erhöhte γ-Glutamyltransferase (GGT) Plasmaspiegel korrelieren mit kardiovaskulären Erkrankungen, aber nichts ist bekannt über eine mögliche Assoziation mit dem gehäuften Auftreten von ventrikulären Tachyarrhythmien. Weiters stellt sich die Frage, ob erhöhte GGT Werte auch bei ICD-Patienten mit einer erhöhten Sterblichkeit verbunden sind.  Aufgrund der geschlechtsspezifischen Normalwerte von GGT wurden nur männliche Patienten in die Analyse eingeschlossen. In einer retrospektiven Studie an 743 Patienten konnte gezeigt werden, dass erhöhte GGT Werte mit einer signifikant erhöhten Gesamtmortalität, nicht aber mit einer gehäuften Notwendigkeit von appropriater ICD-Therapie (antitachykardes Pacing, Schockabgabe) assoziiert sind. In einer Cox Regressionsanalyse bestätigte sich ein erhöhter GGT Wert (>56 U/L) als unabhängiger Risikofaktor für erhöhte Sterblichkeit, vor allem wenn dieser in Kombination mit einer eingeschränkten Nierenfunktion (GFR <60 ml/min/1,73 m2) auftritt.  Erhöhte GGT Werte sind trotz ICD Therapie mit einer erhöhten Gesamtsterblichkeit assoziiert. Es bleibt zu überprüfen, ob dieser Routineparameter in der verbesserten Patientenselektion zur ICD Therapie eine Rolle spielen kann.  Elevated γ-glutamyltransferase (GGT) is a new risk factor for cardiovascular diseases, but its impact on ventricular tachyarrhythmia occurrence and survival in patients with an implantable cardioverter defibrillator (ICD) is unknown.  Considering that GGT levels are gender-dependent, female ICD recipients were excluded from our database because of the low incidence of events. In a retrospective analysis, appropriate ICD therapy (both shocks and antitachycardia pacing due to ventricular tachyarrhythmias) occurred in 31.9% of 320 male patients who had received an ICD for primary prevention (median follow-up of 2.3 years), and in 55.1% of 423 male patients who had received an ICD for secondary prevention (median follow-up of 3.9 years). Compared to normal low GGT plasma levels (below 28 U/L), total mortality but not risk for appropriate ICD therapy was elevated for higher GGT categories (p for trend = 0.004 in primary prevention and p for trend = 0.002 in secondary prevention, respectively). In Cox regression analysis, elevated GGT (>56 U/L) remained an independent predictor of death both in primary (p = 0.011) and in secondary prevention (p = 0.006). Patients with elevated GGT and renal insufficiency defined by an estimated glomerular filtration rate <60 ml/min/1.73 m2 suffered from excess total mortality jeopardizing the benefit of ICD therapy.  Elevation of GGT is an important adverse prognostic parameter in ICD patients. A possible role of GGT for improved patient selection for ICD therapy deserves further investigation.
Does intermediate high-altitude level affect major cardiovascular outcomes of patients with acute myocardial infarction treated by primary coronary angioplasty? Preliminary results of observational study.

dilate kardiyomiyopati ve Sturge-Weber sendromunun birlikteliğinin rastlantısal olduğunu düşünmüyoruz. Sonuç olarak, her ne kadar bu birlikteliği açıklayabilecek bir patofizyolojik mekanizmamız olmasa da; nörokütanöz sendrom tanısı olan hastaların kalp yetmezliğinin erken teşhis ve tedavisinde transtorasik ekokardiyografi ile kontrol edilmesinin hastaların yaşamına olumlu katkı sağlayabileceği düşüncesindeyiz.
Saffron aqueous extract prevents metabolic syndrome in patients with schizophrenia on olanzapine treatment: a randomized triple blind placebo controlled study.

The aim of this study was to assess whether saffron aqueous extract (SAE) or its active constituent, crocin, prevents olanzapine-induced metabolic syndrome (MetS) and insulin resistance in patients with schizophrenia.



66 patients diagnosed with schizophrenia who were on olanzapine treatment (5-20 mg daily) were randomly allocated to receive a capsule of SAE (n=22; 30 mg daily), crocin (n=22; 30 mg daily) or placebo (n=22) in a 12-week triple-blind trial. Patients were screened not to have MetS at baseline and further assessment was done at weeks 6 and 12. Measurement of fasting blood glucose (FBS) and serum lipids were repeated at weeks 2, 6 and 12. Fasting blood levels of insulin and HbA1c were also measured at baseline and week 12. HOMA-IR and HOMA-β were determined to evaluate insulin resistance.



61 patients completed the trial and no serious adverse effects were reported. Time-treatment interaction showed a significant difference in FBS in both SAE and crocin groups compared to placebo (p=0.004). In addition, SAE could effectively prevent reaching the criteria of metabolic syndrome (0 patients) compared to crocin (9.1%) and placebo (27.3%) as early as week 6.



SAE could prevent metabolic syndrome compared to crocin and placebo. Furthermore, both SAE and crocin prevented increases in blood glucose during the study.
Evaluating patient-reported outcome measurement comparability between paper and alternate versions, using the lung function questionnaire as an example.

The goal of this study was to provide recommended steps to assess measurement comparability using a crossover study design and to demonstrate these steps using a short patient-reported outcome (PRO) instrument as an example.



The example PRO instrument was administered via paper, Web, interactive voice response system, and interview; a randomized crossover design was used to gather data across the multiple administration types. Participants completed the PRO instrument, demographic and health questions, and a short preference questionnaire. Evaluation included comparisons of the item-level responses and agreement, comparison of mean scale scores, score classifications, and questions designed to collect usability and administration preference. Here the authors provide a four-step evaluation guide to evaluate measurement comparability and illustrate these steps using a case-finding tool.



In the example, item-level kappa statistics between the paper and the alternate versions ranged from good to excellent, intraclass correlation coefficient for mean scores were above 0.70, and the rate of disagreement ranged from 2% to 14%. In addition, although participants had an administration preference, they reported few difficulties with the versions they were assigned.



The steps described in this article provide a guide for evaluating whether to combine scores across administration versions to simplify analyses and interpretation under a crossover design. The guide recommends the investigation of item-level responses, summary scores, and participant usability/preference when comparing versions, with each step providing unique information to support comprehensive evaluation and informed decisions regarding whether to combine data.
Effect of acarbose on platelet-derived microparticles, soluble selectins, and adiponectin in diabetic patients

Platelet-derived microparticles (PDMP), selectins, and adiponectin play an important role in the development of atherosclerosis in diabetes. Acarbose has been shown to have a beneficial effect on postprandial hyperglycemia in diabetic patients. However, its influence on PDMP, selectins, and adiponectin in these patients is poorly understood. We investigated the effect of acarbose on circulating levels of PDMP, selectins, and adiponectin in patients with type 2 diabetes. Acarbose (300 mg/day) was administered for 3 months. Levels of PDMP, sP-selectin, sL-selectin, and adiponectin were measured by ELISA at baseline and after 1 and 3 months of treatment. The levels of PDMP, sP-selectin, and sL-selectin were higher in diabetic patients than in hypertensive patients (PDMP; 35.1 ± 34.2 vs. 53.3 ± 56.7 U/ml, P < 0.05: sP-selectin; 134 ± 52 vs. 235 ± 70 ng/dl, P < 0.01: sL-selectin; 569 ± 183 vs. 805 ± 146 ng/ml, P < 0.05), while there were no significant differences between hypertensive and hyperlipidemic patients. Before acarbose treatment, the adiponectin level of diabetic patients was lower than that of hypertensive patients. Acarbose therapy significantly decreased the plasma PDMP level relative to baseline. Acarbose also caused a significant decrease of sP-selectin and sL-selectin. On the other hand, acarbose therapy led to a significant increase of adiponectin after 3 months of administration compared with baseline (adiponectin: diabetes versus hypertension, 3.61 ± 1.23 vs. 5.87 ± 1.92 μg/ml, P < 0.05; diabetes versus controls, 2.81 ± 0.95 vs. 6.13 ± 1.24 μg/ml, P < 0.01). Twelve of the 30 diabetic patients had a history of thrombotic complications. Furthermore, the reduction of PDMP and selectins during acarbose therapy was significantly greater in the thrombotic group (12 of 30) than in the nonthrombotic group (18 of 30) of diabetic patients. Acarbose may be beneficial for primary prevention of atherothrombosis in patients with type 2 diabetes. However, it requires a large clinical trial to test this hypothesis.
Bone-related Parameters are the Main Prognostic Factors for Overall Survival in Men with Bone Metastases from Castration-resistant Prostate Cancer.

Previous studies have reported on prognostic factors for castration-resistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC.



To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset.



The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009.



We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time.



The median (95% confidence interval) overall survival was 20 (18, 21) mo. The final model included 12 of the 15 potential prognostic variables evaluated (concordance index 0.72). Seven bone-related variables were associated with longer survival in the final model: alkaline phosphatase ≤143 U/l (p<0.0001); bone-specific alkaline phosphatase (BSAP) <146 U/l (p<0.0001); corrected urinary N-telopeptide (uNTx) ≤50 nmol/mmol (p=0.0008); mild or no pain (Brief Pain Inventory-Short Form [BPI-SF] score ≤4) (p<0.0001); no previous skeletal-related event (SRE; p=0.0002); longer time from initial diagnosis to first bone metastasis (p<0.0001); and longer time from first bone metastasis to randomization (p<0.0001). Other significant predictors of improved survival included prostate-specific antigen (PSA) level <10 ng/ml (p<0.0001), hemoglobin >128g/l (p<0.0001), absence of visceral metastases (p<0.0001), Eastern Co-operative Oncology Group (ECOG) score ≤1 (p=0.017), and younger age (p=0.008). Nomograms were generated based on the parameters included in the final validated models (with/without uNTx and BSAP). One limitation was that lactate dehydrogenase (LDH) levels, a known prognostic factor, were not available in this study.



Bone-related parameters are strong prognostic variables for overall survival in patients with bone metastases from CRPC.



Survival time is variable in patients with bone metastases from prostate cancer. We found that factors related to bone help to predict how long a patient will live.