nils-herrmann/clean_scirepeval huggingface dataset:
Scoring prevalence and severity in gonarthritis: the suitability of the Kellgren & Lawrence scale

In clinical and epidemiological studies the Kellgren & Lawrence (K&L) scale was mainly used in the past to determine the radiological prevalence and severity of gonarthritis. The dependency of this scoring system on the presence of osteophytes has been criticised, and owing to its varying reliability, its appropriateness in cross-sectional and longitudinal studies is questioned. It was the purpose of this study to test whether the dependency of the K&L scale on the presence of osteophytes is reflected in a higher correlation of the overall score with a separate scoring of ‘osteophytes’ than with other radiological features. Furthermore we compared the inter- and intrarater reliability with the reliability of individual radiological features. Knee radiographs of 40 patients were graded according to the K&L scale and for the presence and severity of five separate radiological features of osteoarthritis. We found a moderate correlation of the K&L scale with the radiological features of ‘osteophytes’, ‘joint space narrowing’ and ‘flattening of condyles’. The intra- and inter-rater reliability of the K&L scale was higher than the reliability of the individual radiological features. The K&L scale seems not to be strongly dependent on the presence of osteophytes, i.e. there is not a higher correlation of the overall score with that feature than with other radiological features.
Osteoarthritis disease progression model using six year follow-up data from the osteoarthritis initiative.

The objective was to develop a quantitative model of disease progression of knee osteoarthritis over 6 years using the total WOMAC score from patients enrolled into the Osteoarthritis Initiative (OAI) study. The analysis was performed using data from the Osteoarthritis Initiative database. The time course of the total WOMAC score of patients enrolled into the progression cohort was characterized using non-linear mixed effect modeling in NONMEM. The effect of covariates on the status of the disease and the progression rate was investigated. The final model provided a good description of the experimental data using a linear progression model with a common baseline (19 units of the total WOMAC score). The WOMAC score decreased by 1.77 units/year in 89% of the population or increased by 1.74 units/year in 11% of the population. Multiple covariates were found to affect the baseline and the rate of progression, including BMI, sex, race, the use of pain medications, and the limitation in activity due to symptoms. A mathematical model to describe the disease progression of osteoarthritis in the studied population was developed. The model identified two sub-populations with increasing or decreasing total WOMAC score over time, and the effect of important covariates was quantified.
Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study.

Although the average age of lung cancer patients is increasing, many elderly patients remain undertreated, mainly because of the fear of higher treatment toxicity in this category of patients. We conducted a study to evaluate the efficacy and tolerability of a combination therapy with carboplatin (C) and etoposide phosphate (EP) in elderly patients with Small-Cell Lung Cancer (SCLC).



Previously untreated patients older than 70 years with stage IIIB/IV SCLC received a combination of EP (100 mg/m2 D1, D2, D3) and C (D1, dose calculated according to the Calvert formula). Response rate, survival and toxicity were assessed.



Thirty-eight patients (mean age 76 years, range 70-88 years) received a total of 162 cycles. Eighteen patients (47%) received the six scheduled cycles. Thirty patients were evaluable for efficacy (2 CR and 20 PR). The median survival was 237 days and the one-year probability of survival was 26%. The most common adverse effect was transient grade 3 or 4 neutropenia, observed during 57% of evaluable cycles, while five episodes of febrile neutropenia also occurred, with one fatal (bacteremia). It is noteworthy that no renal or liver toxicity was observed, and no mucitis was noted. Unfortunately, a relatively high proportion of patients died shortly after the start of the study. Although most deaths seemed unrelated to the treatment, the possibility of its exacerbatory effect on comorbidities, especially cardiovascular, cannot be excluded.



The two-drug regimen of carboplatin and etoposide phosphate is feasible in most elderly patients with an acceptable toxicity, and the overall results suggest that patients even older than 70 years may benefit from full treatment. Therefore, consideration should be given to offering active treatment to most patients with SCLC, regardless of age but with special attention paid to comorbidities.
KRAS mutations predict progression of preneoplastic gastric lesions.

Eight hundred sixty-three subjects with atrophic gastritis were recruited to participate in an ongoing chemoprevention trial in Nariño, Colombia. The participants were randomly assigned to intervention therapies, which included treatment to eradicate Helicobacter pylori infection followed by daily dietary supplementation with antioxidant micronutrients in a 2 x 2 x 2 factorial design. A series of biopsies of gastric mucosa were obtained according to a specified protocol from designated locations in the stomach for each participant at baseline (before intervention therapy) and at year three. A systematic sample of 160 participants was selected from each of the eight treatment combinations. DNA was isolated from each of these biopsies (n = 320), and the first exon of KRAS was amplified using PCR. Mutations in the KRAS gene were detected using denaturing gradient gel electrophoresis and confirmed by sequence analysis. Of all baseline biopsies, 14.4% (23 of 160) contained KRAS mutations. Among those participants with atrophic gastritis without metaplasia, 19.4% (6 of 25) contained KRAS mutations, indicating that mutation of this important gene is likely an early event in the etiology of gastric carcinoma. An important association was found between the presence of KRAS mutations in baseline biopsies and the progression of preneoplastic lesions. Only 14.6% (20 of 137) of participants without baseline KRAS mutations progressed from atrophic gastritis to intestinal metaplasia or from small intestinal metaplasia to colonic metaplasia; however, 39.1% (9 of 23) with baseline KRAS mutations progressed to a more advanced lesion after 3 years [univariate odds ratio (OR), 3.76 (P = 0.05); multivariate OR adjusted for treatment, 3.74 (P = 0.04)]. In addition, the specificity of the KRAS mutation predicted progression. For those participants with G-->T transversions at position 1 of codon 12 (GGT-->TGT), 19.4% (5 of 17) progressed (univariate OR, 2.4); however, 60.0% (3 of 5) of participants with G-->A transitions at position 1 of codon 12 (GGT-->AGT) progressed (univariate OR, 8.7; P = 0.004 using chi2 test).
Cardiac shock wave therapy for chronic refractory angina pectoris. A prospective placebo-controlled randomized trial.

Cardiac shock wave therapy (CSWT) delivered to the myocardium increases capillary density and regional myocardial blood flow in animal experiments. In addition, nonenzymatic nitric oxide production and the upregulation of vascular growth factor's mRNA by CSWT have been described. The aim of the study was therefore to test its potential to relieve symptoms in patients with chronic stable angina pectoris.



Twenty-one patients (mean age 68.2 ± 8.3 years, 19 males) with chronic refractory angina pectoris and evidence of inducible myocardial ischemia during MIBI-SPECT imaging, were randomized into a treatment (n = 11) and a placebo arm (n = 10). The region of exercise-induced ischemia was treated with echocardiographic guidance during nine sessions over a period of 3 months. One session of CSWT consisted of 200 shots/spot (9--12 spots/session) with an energy intensity of 0.09 mJ/mm(2) . In the control group acoustic simulation was performed without energy application. Medication was kept unchanged during the whole treatment period.



In the treatment group, symptoms improved in 9/11 patients, and the ischemic threshold, determined by cardiopulmonary exercise stress testing, increased from 80 ± 28 to 95 ± 28 W (P= 0.036). In the placebo arm, only 2/10 patients reported an improvement and the ischemic threshold remained unchanged (98 ± 23 to 107 ± 23 W; P= 0.141). The items "physical functioning" (P= 0.043), "general health perception" (P= 0.046), and "vitality" (P= 0.035) of the SF-36 questionnaire significantly improved in the treatment arm, whereas in the placebo arm, no significant change was noted. Neither arrhythmias, troponin rise nor complications were observed during treatment.



This placebo controlled trial shows a significant improvement in symptoms, quality of life parameters and ischemic threshold during exercise in patients with chronic refractory angina pectoris treated with CSWT. Thus, CSWT represents a new option for the treatment of patients with refractory AP.
Competing risk analysis of mortality in prostate cancer treated with radical prostatectomy.

To determine the risk of cancer-specific mortality (CSM) versus the competing risk of mortality by other causes (MOC) in patients with localised prostate cancer (LPC) treated with radical prostatectomy (RP).



An observational cohort study of 982 patients with LPC treated with RP selected from our department's PC registry database. A competing risk analysis was performed, calculating the probability of CSM in the presence of the competing risk of MOC. Cumulative incidence curves were constructed, and point estimates were performed at 5, 10 and 15 years. The analysis was stratified by age (≤65 vs. >65 years) and risk group: low (Gleason score ≤6 and pT2abc); intermediate (Gleason score of 7 and pT2abc) and high (Gleason score of 8-10 or pT3ab).



With a median follow-up of 60 months, the overall probability of dying from PC was 3.5%, and the probability of dying from other causes was 9%. A competing effect for MOC was observed. The risk of MOC was almost 3 times greater than that of CSM. This effect remained for all risk groups, although its magnitude decreased progressively according to the risk group level. At 10 years, CSM was only 0%, 1% and 2% for the low, intermediate and high-risk groups, respectively, while the likelihood of MOC was 4%, 4% and 10%, respectively. The mortality risk was shown after 10years of follow-up and was higher for other causes not attributable to PC and for patients older than 65years.



The benefit of RP might be overestimated, given that the risk of MOC is greater than that of CSM, regardless of the age group and risk group, especially after 10years of follow-up. The only parameter that varied was the magnitude of the CSM/MOC ratio. This information could help in choosing the active treatment for patients with LPC and short life expectancies.
A multiscale, model-based analysis of the multi-tissue interplay underlying blood glucose regulation in type I diabetes

A multiscale model for blood glucose regulation in diabetes type I patients is constructed by integrating detailed metabolic network models for fat, liver and muscle cells into a whole body physiologically-based pharmacokinetic/pharmacodynamic (pBPK/PD) model. The blood glucose regulation PBPK/PD model simulates the distribution and metabolization of glucose, insulin and glucagon on an organ and whole body level. The genome-scale metabolic networks in contrast describe intracellular reactions. The developed multiscale model is fitted to insulin, glucagon and glucose measurements of a 48h clinical trial featuring 6 subjects and is subsequently used to simulate (in silico) the influence of geneknockouts and drug-induced enzyme inhibitions on whole body blood glucose levels. Simulations of diabetes associated gene knockouts and impaired cellular glucose metabolism, resulted in elevated whole body blood-glucose levels, but also in a metabolic shift within the cell's reaction network. Such multiscale models have the potential to be employed in the exploration of novel drug-targets or to be integrated into control algorithms for artificial pancreas systems.
Bone strength and density via pQCT in post-menopausal osteopenic women after 9 months resistive exercise with whole body vibration or proprioceptive exercise.

In order to better understand which training approaches are more effective for preventing bone loss in post-menopausal women with low bone mass, we examined the effect of a nine-month resistive exercise program with either an additional whole body vibration exercise (VIB) or balance training (BAL).



68 post-menopausal women with osteopenia were recruited for the study and were randomised to either the VIB or BAL group. Two training sessions per week were performed. 57 subjects completed the study (VIB n=26; BAL n=31). Peripheral quantitative computed tomography (pQCT) measurements of the tibia, fibula, radius and ulna were performed at baseline and at the end of the intervention period at the epiphysis (4% site) and diaphysis (66% site). Analysis was done on an intent-to-treat approach.



Significant increases in bone density and strength were seen at a number of measurement sites after the intervention period. No significant differences were seen in the response of the two groups at the lower-leg.



This study provided evidence that a twice weekly resistive exercise program with either additional balance or vibration training could increase bone density at the distal tibia after a nine-month intervention period in post-menopausal women with low bone mass.
Glycoprotein IIb/IIIa Inhibitors Use and Outcome after Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction

We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors on long-term outcomes following percutaneous coronary intervention (PCI) after non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that these agents are associated with improved short-term outcomes. However, many trials were undertaken before the routine use of P2Y12 inhibitors. Recent studies yield conflicting results and registry data have suggested that GP IIb/IIIa inhibitors may cause more bleeding than what trials indicate.



This retrospective observational study involves 3047 patients receiving dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all-cause mortality. Major adverse cardiac events (MACE) were a secondary outcome. Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes, multivariate analysis (including propensity scoring) showed no benefit for either survival (P = 0.136) or MACE (P = 0.614). GP IIb/IIIa inhibitor use was associated with an increased risk of major bleeding (P = 0.021).



Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk. After multivariate adjustment we observed no improvement in MACE or survival and an increased risk of major bleeding.
Short-term diabetes blood glucose prediction based on blood glucose measurements

Insulin Dependent Diabetes Mellitus (IDDM) is a chronic disease characterized by the inability of the pancreas to produce sufficient amounts of insulin. Daily compensation of the deficiency requires 4–6 insulin injections to be taken daily, the aim of this insulin therapy being to maintain normoglycemia— i.e., a blood glucose level between 4–7 mmol/L. To determine the quantity and timing of these injections, various different approaches are used. Currently, mostly qualitative and semi-quantitative models and reasoning are used to design such a therapy. Here, an attempt is made to show how system identification and control may be used to estimate predictive quantitative models to be used in design of optimal insulin regimens. The system was divided into three subsystems, the insulin subsystem, the glucose subsystem and the insulin-glucose interaction. The insulin subsystem aims to describe the absorbtion of injected insulin from the subcutaneous depots and the glucose subsystem the absorbtion of glucose from the gut following a meal. These subsystems were modeled using compartment models and proposed models found in the literature. Several black-box models and grey-box models describing the insulin/glucose interaction were developed and analysed. These models were fitted to real data monitored by a IDDM patient. Many difficulties were encountered, typical of biomedical systems: Non-uniform and scarce sampling, time-varying dynamics and severe nonlinearities were some of the difficulties encountered during the modeling. None of the proposed models were able to describe the system accurately in all aspects during all conditions. However, all the linear models shared some dynamics. Based on the estimated models, short-term blood glucose predictors for up to two-hour-ahead blood glucose prediction were investigated.
Effect of Whole-Body Vibration on Calcaneal Quantitative Ultrasound Measurements in Postmenopausal Women: A Randomized Controlled Trial

The purpose of this study was to examine the effect of whole-body vibration (WBV) on calcaneal quantitative ultrasound (QUS) measurements; which has rarely been examined. We conducted a single-centre, 12-month, randomized controlled trial. 202 postmenopausal women with BMD T score between −1.0 and −2.5, not receiving bone medications, were asked to stand on a 0.3 g WBV platform oscillating at either 90- or 30-Hz for 20 consecutive minutes daily, or to serve as controls. Calcium and vitamin D was provided to all participants. Calcaneal broadband attenuation (BUA), speed of sound, and QUS index were obtained as pre-specified secondary endpoints at baseline and 12 months by using a Hologic Sahara Clinical Bone Sonometer. 12-months of WBV did not improve QUS parameters in any of our analyses. While most of our analyses showed no statistical differences between the WBV groups and the control group, mean calcaneal BUA decreased in the 90-Hz (−0.4 [95 % CI −1.9 to 1.2] dB MHz−1) and 30-Hz (−0.7 [95 % CI −2.3 to 0.8] dB MHz−1) WBV groups and increased in the control group (1.3 [95 % CI 0.0–2.6] dB MHz−1). Decreases in BUA in the 90-, 30-Hz or combined WBV groups were statistically different from the control group in a few of the analyses including all randomized participants, as well as in analyses excluding participants who had missing QUS measurement and those who initiated hormone therapy or were <80 % adherent. Although there are consistent trends, not all analyses reached statistical significance. 0.3 g WBV at 90 or 30 Hz prescribed for 20 min daily for 12 months did not improve any QUS parameters, but instead resulted in a statistically significant, yet small, decrease in calcaneal BUA in postmenopausal women in several analyses. These unexpected findings require further investigation.
Quality of life of early stage colorectal cancer patients in Morocco

A multicentre cohort study was held in Morocco, designed to evaluate the quality of life of cancer patients. The aim of this paper is to report the assessment of the quality of life of early colorectal cancer patients, before and after cancer treatment, to identify other factors which are related to this quality of life.



We used the third version of the QLQ-C30 questionnaire of the European organization for Research and treatment of Cancer (EORTC) after a transcultural validation. The Data collection was done at inclusion and then every twelve weeks to achieve one year of follow up.



Overall 294 patients presented with early colorectal cancer, the median age was 56 years (range: 21-88). The male-female sex ratio was 1.17. At inclusion, the global health status was the most affected functional dimension. For symptoms: financial difficulties and fatigue scores were the highest ones. Emotional and social functions were significantly worse in rectal cancer. Most symptoms were more present in rectal cancer. At inclusion, global health status score was significantly worse in stage III. Anorexia was significantly more important among colorectal female patients. For Patients over 70 years-old, the difference was statistically significant for the physical function item which was lower. Overall, Functional dimensions scores were improved after chemotherapy. The symptoms scores did not differ significantly for patients treated by radiotherapy, between inclusion and at one year.



Our EORTC QLQ C30 scores are overall comparable to the reference values. Neither chemotherapy, nor radiotherapy worsened the quality of life at one year.
Diabetes mortality in Panama and related biological and socioeconomic risk factors.

To estimate mortality from diabetes mellitus (DM) for the period 2001-2011 in the Republic of Panama, by province/indigenous territory, and determine its relationship with biological and socioeconomic risk factors.



Cases for the years 2001-2011 with DM listed as the principal cause of death were selected from Panama's National Mortality Registry. Crude and adjusted mortality rates were generated by sex, age, and geographic area. Linear regression analyses were performed to determine the relationship between DM mortality and biological and socioeconomic risk factors. A composite health index (CHI) calculated from biological and socioeconomic risk factors was estimated for each province/indigenous territory in Panama.



DM mortality rates did not increase for men or women during 2001-2011. Of the biological risk factors, being overweight had the strongest association with DM mortality. Of the socioeconomic risk factors, earning less than US$ 100 per month had the strongest association with DM mortality. The highest socioeconomic CHI scores were found in a province that is predominantly rural and in areas with indigenous populations. The highest biological CHI scores were found in urban-rural provinces and those with the highest percentage of elderly people.



Regional disparities in the association between DM mortality and DM risk factors reaffirm the heterogeneous composition of the Panamanian population and the uneven distribution of biological and social determinant risk factors in the country and point to the need to vary management strategies by geographic area for this important cause of disability and death in Panama.