nils-herrmann/clean_scirepeval huggingface dataset:
NASHA hyaluronic acid vs. methylprednisolone for knee osteoarthritis: a prospective, multi-centre, randomized, non-inferiority trial.

To compare NASHA hyaluronic acid gel as single-injection intra-articular (IA) treatment for knee osteoarthritis (OA) against methylprednisolone acetate (MPA).



This was a prospective, multi-centre, randomized, active-controlled, double-blind, non-inferiority clinical trial. A unique, open-label extension phase (OLE) was undertaken to answer further important clinical questions. Subjects with painful unilateral knee OA were treated and followed for 26 weeks (blinded phase). All patients attending the clinic at 26 weeks were offered NASHA treatment, with a subsequent 26-week follow-up period (extension phase). The primary objective was to show non-inferiority of NASHA vs MPA in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain responder rate (percentage of patients with ≥40% improvement from baseline in WOMAC pain score and an absolute improvement of ≥5 points) at 12 weeks.



In total, 442 participants were enrolled. The primary objective was met, with NASHA producing a non-inferior response rate vs MPA at 12 weeks (NASHA: 44.6%; MPA: 46.2%; difference [95% CI]: 1.6% [-11.2%; +7.9%]). Effect size for WOMAC pain, physical function and stiffness scores favoured NASHA over MPA from 12 to 26 weeks. In response to NASHA treatment at 26 weeks, sustained improvements were seen in WOMAC outcomes irrespective of initial treatment. No serious device-related adverse events (AEs) were reported.



This study shows that single-injection NASHA was well tolerated and non-inferior to MPA at 12 weeks. The benefit of NASHA was maintained to 26 weeks while that of MPA declined. An injection of NASHA at 26 weeks conferred long-term improvements without increased sensitivity or risk of complications.  (www.clinicaltrials.gov).
Acute and nine-month clinical outcomes after "suboptimal" coronary stenting: results from the STent Anti-thrombotic Regimen Study (STARS) registry.

This registry collected the 30-day and 9-month clinical outcomes of patients whose coronary stent implantation was suboptimal, and compared them with the cohort of patients with "optimal" stenting in the randomized portion of the STent Anti-thrombotic Regimen Study (STARS) trial.



Although "optimal" stenting combined with an aspirin and ticlopidine regimen carries a low (0.5%) incidence of subacute stent thrombosis, only limited data are available for patients in whom stents are deployed suboptimally.



In the STARS, 312 (15.9%) of 1,965 patients enrolled were excluded from participation in the randomized trial based on a perceived "suboptimal" result of coronary stenting. Of these, 265 patients met prespecified criteria for suboptimal stenting, and were followed in a parallel registry, which was compared with the randomized STARS optimal stenting cohort. The primary end point was a 30-day composite of death, emergent target lesion revascularization, angiographic thrombosis of the target vessel without revascularization and nonfatal myocardial infarction (MI) unrelated to direct procedural complications.



Registry patients had a similar frequency of the primary end point compared with the overall randomized cohort (3.0% vs. 2.2%), with this end point correlating to use of multiple stents, smaller final lumen diameter and absence of ticlopidine from the poststent regimen. Overall 30-day mortality (1.1% vs. 0.06%, p = 0.009) and periprocedural non-Q wave MI (8.7% vs. 4.2%, p = 0.003) were more frequent in registry patients, and appeared to be related to acute procedural complications. Clinical restenosis was significantly higher for registry patients (26.8% vs. 16.0%, p = 0.001), relating to greater prevalence of independent predictors such as smaller final lumen diameter and multiple stent use.



In the STARS registry, the inability to perform optimal stenting correlated with smaller final lumen diameter and longer stent length. With ticlopidine-containing regimens, the acute clinical results of "suboptimal" stent deployment are clinically acceptable, although they are not quite as good as those of optimal stenting using similar drug therapy.
Autologous umbilical cord blood infusion followed by oral docosahexaenoic acid and vitamin D supplementation for C-peptide preservation in children with Type 1 diabetes.

We sought to determine if autologous umbilical cord blood (UCB) infusion followed by 1 year of supplementation with vitamin D and docosahexaenoic acid (DHA) can preserve C-peptide in children with type 1 diabetes. We conducted an open-label, 2:1 randomized study in which 15 type 1 diabetes subjects with stimulated C-peptide > .2 pmol/mL received either (1) autologous UCB infusion, 1 year of daily oral vitamin D (2000 IU), and DHA (38 mg/kg) and intensive diabetes management or (2) intensive diabetes management alone. Primary analyses were performed 1 year after UCB infusion. Treated (N = 10) and control (N = 5) subjects had median ages of 7.2 and 6.6 years, respectively. No severe adverse events were observed. Although the absolute rate of C-peptide decline was slower in treated versus control subjects, intergroup comparisons failed to reach significance (P = .29). Area under the curve C-peptide declined and insulin use increased in both groups (P < .01). Vitamin D levels remained stable in treated subjects but declined in control subjects (P = .01). DHA levels rose in treated subjects versus control subjects (P = .003). CD4/CD8 ratio remained stable in treated subjects but declined in control subjects (P = .03). No changes were seen in regulatory T cell frequency, total CD4 counts, or autoantibody titers. Autologous UCB infusion followed by daily supplementation with vitamin D and DHA was safe but failed to preserve C-peptide. Lack of significance may reflect small sample size. Future efforts will require expansion of specific immunoregulatory cell subsets, optimization of combined immunoregulatory and anti-inflammatory agents, and larger study cohorts.
A phase I trial and pharmacokinetic evaluation of CI-980 in patients with advanced solid tumors

CI-980 is a synthetic mitotic inhibitor that binds to the colchicine binding site of tubulin. It demonstrates broad activity against human and marine tumor models and shows no cross resistance with tumor models whose mechanism of resistance is mediated by P-glycoprotein (MDR-1). A phase I study was completed in 25 patients with solid tumors using a 24-hour infusion schedule, with courses repeated every 3 weeks. Eight dose levels were tested between 1.2 and 15.6 mg/m2. The maximum tolerated dose was 14.4 mg/m2. Neutropenia was dose-related but not dose-limiting; thrombocytopenia was infrequent. CNS toxicities were dose-limiting and consisted of dizziness, headache, loss of coordination, loss of consciousness, nervousness, and other symptoms. These events occurred near the end of the infusion and were reversible, usually within 24 hours. One patient who was to be treated at dose level 8 (intended dose was 19.2 mg/m2; actual dose was 15.6 mg/m2) became encephalopathic prior to completion of the infusion. Other adverse events included gastrointestinal toxicities (nausea, vomiting, anorexia, constipation, stomatitis, dyspepsia, bleeding, cheilitis), IV site erythema, fever, and fatigue. A partial response was observed in one patient with colon cancer and reductions in CA-125 levels were observed in 2 patients with ovarian cancer. Pharmacokinetics were linear and dose-proportional. Results indicate high systemic clearance and wide tissue distribution. Mean pharmacokinetic parameter values: T2 = 5.52 hours, plasma clearance 1163 mL/min/m2, and Vdss 376 L/m2.
The Diabetes Excess Weight Loss (DEWL) Trial: a randomised controlled trial of high-protein versus high-carbohydrate diets over 2 years in type 2 diabetes

To compare the effectiveness of low-fat high-protein and low-fat high-carbohydrate dietary advice on weight loss, using group-based interventions, among overweight people with type 2 diabetes. Multicentre parallel (1:1) design, blinded randomised controlled trial. Individuals with type 2 diabetes aged 30–75 years and a BMI >27 kg/m2 were randomised, by an independent statistician using sequentially numbered sealed envelopes, to be prescribed either a low-fat high-protein (30% of energy as protein, 40% as carbohydrate, 30% as fat) or a low-fat high-carbohydrate (15% of energy as protein, 55% as carbohydrate, 30% as fat) diet. Participants attended 18 group sessions over 12 months. Primary outcomes were change in weight and waist circumference assessed at baseline, 6 and 12 months. Secondary outcomes were body fatness, glycaemic control, lipid profile, blood pressure and renal function. A further assessment was undertaken 12 months after the intervention. Research assessors remained blinded to group allocation throughout. Intention-to-treat analysis was performed. A total of 419 participants were enrolled (mean ± SD age 58 ± 9.5 years, BMI 36.6 ± 6.5 kg/m2 and HbA1c 8.1 ± 1.2% (65 mmol/mol)). The study was completed by 70% (294/419). No differences between groups were found in change in weight or waist circumference during the intervention phase or the 12-month follow-up. Both groups had lost weight (2–3 kg, p < 0.001) and reduced their waist circumference (2–3 cm, p < 0.001) by 12 months and largely maintained this weight loss for the following 12 months. By 6 months, the difference in self-reported dietary protein between groups was small (1.1% total energy; p < 0.001). No significant differences between groups were found in secondary outcomes: body fatness, HbA1c, lipids, blood pressure and renal function. There were no important adverse effects. In a ‘real-world’ setting, prescription of an energy-reduced low-fat diet, with either increased protein or carbohydrate, results in similar modest losses in weight and waist circumference over 2 years.
Adherence to Antihypertensive Medication in Treatment-Resistant Hypertension Undergoing Renal Denervation.

Adherence to medication has been repeatedly proposed to represent a major cause of treatment-resistant hypertension (TRH); however, treatment decisions such as treating TRH with renal denervation depend on accurate judgment of adherence. We carefully analyzed adherence rates to medication before and after renal denervation and its effect on blood pressure (BP) control.



Eighty patients with TRH were included in 2 prospective observational studies that assessed the difference of potential antihypertensive and nephroprotective effects of renal denervation. To compare prescribed with actual medication intake (representing a measure of adherence), we analyzed urine samples collected at baseline and at 6 months after renal denervation for antihypertensive compounds or metabolites (by liquid chromatography-mass spectrometry). In addition to office BP, 24-hour ambulatory BP and central hemodynamics (central systolic pressure, central pulse pressure) were assessed. Informed consent for analyses of urine metabolites was obtained from 79 of 80 patients. Actual intake of all antihypertensive drugs was detected at baseline and at 6 months after renal denervation in 44 (56%) and 52 (66%) patients, respectively; 1 drug was missing in 22 (28%) and 17 (22%) patients, respectively, and ≥2 drugs were missing in 13 (16%) and 10 (13%) patients, respectively. At baseline, 24-hour ambulatory BP (P=0.049) and central systolic BP (P=0.012) were higher in nonadherent patients. Adherence did not significantly change overall (McNemar-Bowker test, P=0.362). An increase in adherence was observed in 21 patients, and a decrease was observed in 11 patients. The decrease in 24-hour ambulatory BP was not different in those with stable adherence 6 months after renal denervation (n=41, -7±13 mm Hg) compared with those with increased adherence (n=21, -10±13 mm Hg) and decreased adherence (n=11, -7±14 mm Hg) (P>0.20). Our study is limited by the relatively small sample size and potentially by the specific health environment of our university center (Northern Bavaria, Germany).



Nonadherence to medication among patients with TRH was relatively low: ≈1 of 6 patients with TRH did not take ≥2 of the prescribed drugs. Adherence pattern did not change significantly after renal denervation and had no impact on the overall observed BP changes, supporting the concept that renal denervation is an effective treatment in patients with TRH.
Higher cost sharing for visiting general hospitals and the changing trend in the first-visited healthcare organization among newly diagnosed hypertension patients

Unnecessary use of high-quality resources in general hospitals hinders treatment of patients with urgent and complicated conditions. Thus, the Korean Government has sought to reduce general hospital visiting of patients with 52 mild diseases, including hypertension. The higher cost sharing for medical expenses and medications from general hospitals were enacted in 2009 and 2011, respectively.We determined whether these regulations were effective through evaluating changing trends in first-visited healthcare organizations and defined the first visiting healthcare organization level (primary clinics, hospital, and general hospital) as an outcome measure.Data of 32,830 mild hypertension patients from 2004 to 2013 were retrieved from the Korean National Health Insurance Service National Sample Cohort. This was a retrospective study involving a large national cohort with patient samples (representing 2% of the total Korean population) stratified on the basis of sociodemographic information.Mutinomial logistic regression were performed for the first visiting to different health organizations, compared to the first visiting to primary clinics.Patients in 2012 and 2013 had significantly lower odds ("2012": 0.68, 95% confidence interval [CI]: 0.56-0.81/"2013": 0.66, 95% CI 0.54-0.81) of first visiting general hospitals compared with those in 2008, although decreased tendencies (albeit nonsignificant) were already evident in 2010 and 2011.Thus, government health policies for cost-containment seem effective in decreasing first visiting of general hospitals among patients with mild essential hypertension. These policies have since extended to Medical Aid beneficiaries; thus, it is needed to continue monitor their results carefully.
Fuzzy J-Means and VNS methods for clustering genes from microarray data

In the interpretation of gene expression data from a group of microarray experiments that include samples from either different patients or conditions, special consideration must be given to the pleiotropic and epistatic roles of genes, as observed in the variation of gene coexpression patterns. Crisp clustering methods assign each gene to one cluster, thereby omitting information about the multiple roles of genes.



Here, we present the application of a local search heuristic, Fuzzy J-Means, embedded into the variable neighborhood search metaheuristic for the clustering of microarray gene expression data. We show that for all the datasets studied this algorithm outperforms the standard Fuzzy C-Means heuristic. Different methods for the utilization of cluster membership information in determining gene coregulation are presented. The clustering and data analyses were performed on simulated datasets as well as experimental cDNA microarray data for breast cancer and human blood from the Stanford Microarray Database.


AVAILABILITY
The source code of the clustering software (C programming language) is freely available from Nabil.Belacel@nrc-cnrc.gc.ca
The Functional Living Index-Cancer is a reliable and valid instrument in Chinese cancer patients

To evaluate the linguistic and psychometric properties of the Functional Living Index-Cancer (FLIC) in assessing the quality of life of Chinese cancer patients. The English FLIC was translated into Traditional Chinese by the standard forward–backward procedure. After cognitive debriefing, a Traditional Chinese FLIC was administered to 500 cancer patients in a major public hospital in Hong Kong. Of which, 200 were invited to complete the questionnaire in 2 weeks. To identify a scale structure appropriate to Chinese, exploratory and confirmatory factor analyses were performed on two randomly split halves of the sample. We identified five scales of the Traditional Chinese FLIC which assess the physical, psychological, hardship, nausea and social aspects. These five scales and the overall scale demonstrated satisfactory fit and had the alpha coefficient ranged from 0.68 to 0.92. The intra-class correlation coefficient ranged from 0.67 to 0.88. In addition, all FLIC scales were negatively associated with the Eastern Cooperative Oncology Group performance status and, also except for the psychological scale, had lower scores in patients who were treated by chemotherapy. The Traditional Chinese FLIC is an appropriate health indicator for Chinese cancer patients.
Effects of de-alcoholised wines with different polyphenol content on DNA oxidative damage, gene expression of peripheral lymphocytes, and haemorheology: an intervention study in post-menopausal women.

Epidemiological studies suggest that a moderate consumption of wine is associated with a reduced risk of cardiovascular diseases and with a reduced mortality for all causes, possibly due to increased antioxidant defences. The present intervention study was undertaken to evaluate the in vivo effects of wine polyphenols on gene expression in humans, along with their supposed antioxidant activity.



Blood haemorheology and platelet function were also evaluated. In order to avoid interferences from alcohol, we used de-alcoholised wine (DAW) with different polyphenol content. A randomised cross-over trial of high-proanthocyanidin (PA) red DAW (500 mL/die, PA dose = 7 mg/kg b.w.) vs. low-PA rosé DAW (500 mL/die, PA dose = 0.45 mg/kg) was conducted in 21 post-menopausal women in Florence, Italy. Oxidative DNA damage by the comet assay and gene expression by microarray was measured in peripheral blood lymphocytes, collected during the study period. Blood samples were also collected for the evaluation of haematological, haemostatic, haemorheological, and inflammatory parameters.



The results of the present study provide evidence that consumption of substantial amounts of de-alcoholised wine for 1 month does not exert a protective activity towards oxidative DNA damage, nor modifies significantly the gene expression profile of peripheral lymphocytes, whereas it shows blood-fluidifying actions, expressed as a significant decrease in blood viscosity. However, this effect does not correlate with the dosage of polyphenols of the de-alcoholised wine.



More intervention studies are needed to provide further evidence of the health-protective effects of wine proanthocyanidins.
Pilot study of modified FOLFOX6 adjuvant chemotherapy for high-risk rectal cancer treated with neoadjuvant chemoradiotherapy

Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision is considered the standard of care for patients with locally advanced adenocarcinoma of the middle/low rectum. The present study evaluated the feasibility of using modified FOLFOX6 regimen as an adjuvant treatment for high-risk patients with locally advanced rectal cancer (LARC) treated with neoadjuvant CRT. Forty patients with LARC (ypT3–4 or N+) treated with neoadjuvant CRT were enrolled at Kyungpook National University Medical Center (Daegu, Korea) between December 2011 and December 2012. All the patients underwent rectal surgery with curative intent 8 weeks after the end of the neoadjuvant treatment. Adjuvant chemotherapy using modified FOLFOX6 regimen was then delivered for 3 months. The treatments were generally well tolerated. Dose reduction was recorded in 11 of the 40 patients (27.5 %). The incidence of febrile neutropenia was 5 %, the incidence of grade 3 or 4 asthenia was 10 %, and the incidence of grade 3 gastrointestinal adverse events was 5 % during treatment. Treatment discontinuation caused by toxic effects or any other reasons was observed in six patients (15 %). The reasons for discontinuation were asthenia (n = 2, 5 %), diarrhea (n = 2, 5 %), acute renal failure (n = 1, 2.5 %), and relapse during chemotherapy (n = 1, 2.5 %). With a median follow-up duration of 18 months, six patients (15 %) relapsed and one patient (2.5 %) died of disease progression. The estimated 3-year disease-free survival and overall survival rates were 84.2 and 97.3 %, respectively. Postoperative adjuvant modified FOLFOX6 regimen was found to be feasible for patients with LARC treated with neoadjuvant CRT.
Experimental hypoglycemia is a human model of stress-induced hyperalgesia

Hypoglycemia is a physiological stress that leads to the release of stress hormones, such as catecholamines and glucocorticoids, and proinflammatory cytokines. These factors, in euglycemic animal models, are associated with stress-induced hyperalgesia. The primary aim of this study was to determine whether experimental hypoglycemia in humans would lead to a hyperalgesic state. In 2 separate 3-day admissions separated by 1 to 3 months, healthy study participants were exposed to two 2-hour euglycemic hyperinsulinemic clamps or two 2-hour hypoglycemic hyperinsulinemic clamps. Thermal quantitative sensory testing and thermal pain assessments were measured the day before and the day after euglycemia or hypoglycemia. In contrast to prior euglycemia exposure, prior hypoglycemia exposure resulted in enhanced pain sensitivity to hot and cold stimuli as well as enhanced temporal summation to repeated heat-pain stimuli. These findings suggest that prior exposure to hypoglycemia causes a state of enhanced pain sensitivity that is consistent with stress-induced hyperalgesia. This human model may provide a framework for hypothesis testing and targeted, mechanism-based pharmacological interventions to delineate the molecular basis of hyperalgesia and pain susceptibility.
Safety and efficacy of selective retina therapy (SRT) for the treatment of diabetic macular edema in Korean patients

Selective retina therapy (SRT) stimulates retinal pigment epithelium (RPE) cell migration and proliferation into irradiated areas. The objective of this study was to evaluate the efficacy and safety of SRT in Korean patients with clinically significant diabetic macular edema (DME). Prospective non-randomized interventional case series study. Twenty-three eyes of 21 patients with clinically significant DME were treated with SRT and followed for 6 months. Patients underwent an evaluation of best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Microperimetry was employed to measure macular sensitivity within the central 10° field, and the central macular thickness (CMT) and maximum macular thickness (MMT) were measured. An improvement in BCVA of one to two ETDRS lines was observed in 41.2 % of patients and an improvement of greater than two lines in 29.4 %. Although there was no significant change in CMT (P > 0.05), MMT decreased from 465.8 ± 87.4 μm to 434.3 ± 83.9 μm (P = 0.006), and mean macular sensitivity increased from 20.8 ± 3.4dB to 22.5 ± 3.5dB (P = 0.02). The gains in BCVA and improvement in macular sensitivity demonstrated that SRT may be used as an effective and safe treatment modality in Korean patients with clinically significant DME.