nils-herrmann/clean_scirepeval huggingface dataset:
Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co‐administered to Chinese patients with type 2 diabetes mellitus

The results of a clinical trial to evaluate the efficacy and safety of initial combination therapy with sitagliptin and metformin in Chinese patients with type 2 diabetes and inadequate glycemic control are reported here.



This was a multicenter, randomized, double-blind, placebo-controlled, parallel group, 24-week clinical trial carried out in China. Patients (n = 744) with type 2 diabetes and inadequate glycemic control (glycated hemoglobin ≥7.5 and ≤11.0%) who were either drug-naïve or washed out of previous therapy were randomized in equal ratios to sitagliptin 100 mg once daily (q.d.; S100), metformin 500 mg twice daily (b.i.d.; M1000), metformin 850 mg b.i.d. (M1700), sitagliptin 50 mg b.i.d. plus metformin 500 mg b.i.d. , sitagliptin 50 mg b.i.d. plus metformin 850 mg b.i.d. (S100/M1700), or placebo.



The mean baseline glycated hemoglobin in randomized patients was 8.7%. Least squares mean changes from baseline in glycated hemoglobin were -0.59% (placebo), -0.99% (S100), -1.29% (M1000), -1.56% (M1700), -1.67% (S100/M1000) and -1.83% (S100/M1700) (P < 0.05 for each active group vs placebo, for S100/M1700 and S100/M1000 vs S100, and for S100/M1000 vs M1000). All treatments were generally well-tolerated. The overall incidence of hypoglycemia (symptomatic or asymptomatic) was higher in the two co-administration groups (S100/M1700 and S100/M1000) compared with the placebo. The incidence of symptomatic hypoglycemia was low, and similar, across all treatment groups. The incidences of gastrointestinal adverse events were generally higher in high-dose metformin groups than in the placebo group.



In Chinese patients with type 2 diabetes, initial combination therapy with sitagliptin and metformin was generally well-tolerated, and provided improvement in glycemic control.
Comparison of cefotaxime plus metronidazole versus cefoxitin for prevention of wound infection after abdominal surgery

In a randomized prospective stratified trial consisting of 1010 patients undergoing abdominal surgery involving the viscera, the efficacy of cefotaxime plus metronidazole was compared to cefoxitin for preventing wound infection. The efficacy of a single dose of antibiotics versus three doses over 24 hours was also evaluated. This study demonstrated that a single-dose antibiotic regimen was as effective as a multiple-dose regimen in the prophylaxis of wound infections following abdominal surgery. In addition it demonstrated that the cefotaxime plus metronidazole regimen is comparable to that of cefoxitin and is more cost-effective. It is concluded that a single dose of cefotaxime plus metronidazole provides effective prophylaxis against postoperative wound infections following abdominal surgery. Dans cette étude randomisée, et stratifiée, on a comparé l'efficacité du céfotaxime combiné au métronidazole et du céfotaxime seul, ainsi que leur efficacité en une seule prise par rapport à trois prises, dans la prévention des infections pariétales chez 1010 patients ayant une intervention abdominale concernant les viscères. Une seule prise est aussi efficace que trois. Il n'y avait pas de différence d'efficacité en ce qui concerne les deux traitements d'antibiotiques. Le céfotaxime combiné au métronidazole a un meilleur rapport coût efficacité. Nous recommandons la combinaison céfotaxime et métronidazole dans la prévention des infections pariétales après chirurgie abdominale. Con el propósito de comparar la eficacia de un régimen de cefotaxime más metronidazol con cefoxitina en la prevención de las infecciones de herida, se realizó un estudio prospectivo y randomizado que cubrió a 1010 pacientes sometidos a cirugía abdominal. También se valoró la eficacia de una dosis única de los antibióticos versus tres dosis en el curso de 24 horas. El estudio demostró que el régimen de dosis única de antibiótico fue tan efectivo como el régimen de dosis múltiples en la profilaxis de la infección de herida en cirugía abdominal y, además, señaló que la combinación de cefotaxime y metronidazol es comparable a la de la cefoxitina y es de mayor costo/eficacia.
Cross-over study of influence of oral vitamin C supplementation on inflammatory status in maintenance hemodialysis patients

Both vitamin C deficiency and inflammation are prevalent in maintenance hemodialysis (MHD) patients. In this study, we aimed to elucidate the effect of oral vitamin C supplementation on inflammatory status in MHD patients with low vitamin C level and high hypersensitive C-reactive protein (hs-CRP) level.



A total of 128 patients were recruited in our present study. Patients were divided into two groups. In group 1 (n = 67), patients were orally administered with 200 mg/day vitamin C in the first 3 months, and then the vitamin C supplementation was withdrawn in the next 3 months. In group 2 (n = 61), patients were not given vitamin C in the first 3 months, and then they were orally administered with 200 mg/day in the next 3 months. Levels of hs-CRP, prealbumin, albumin and hemoglobin as well as the EPO resistance index (ERI) were determined at the baseline and every 3 months throughout the study. Plasma vitamin C level was determined by high-performance liquid chromatography with UV detection.



Among the 128 patients, 28 of them dropped out of the study before completion. Consequently, a total of 100 patients (group 1: n = 48; group 2: n = 52) were included in the final analysis. At the baseline, the plasma vitamin C level of all patients was less than 4 μg/mL. However, this proportion was decreased to 20% after the vitamin C supplementation for 3 months. Compared with patients without the vitamin C supplementation, a decreased level of hs-CRP and an increased level of prealbumin were induced by the vitamin C supplementation for 3 months in both groups. However, levels of these biomarkers returned to their original state after the supplementation was withdrawn. Same beneficial effects on plasma albumin, hemoglobin and ERI response to vitamin C supplementation were observed in the two groups without statistical significance.



The inflammatory status in MHD patients with plasma vitamin C deficiency and high levels of inflammatory markers could be partially improved by long-term oral administration of small doses of vitamin C.
The effect of nicotinic acid and acipimox on lipoprotein(a) concentration and turnover.

This study examines the effect of nicotinic acid (1 g t.d.s.) on serum Lp(a) concentration in a group of patients with type II hyperlipidaemia selected on the basis of a plasma Lp(a) concentration greater than 30 mg/dl. Reductions in total cholesterol, triglyceride, LDL-cholesterol and Lp(a) were 16.3%, 25.5%, 23.7% and 36.4%, respectively, with an increase in HDL cholesterol of 37.3%. The reduction in Lp(a) concentration did not correlate with any other lipoprotein changes. In order to establish the mechanism of the fall in Lp(a) concentration, in vivo turnover of autologous Lp(a) was studied in three subjects before and whilst taking nicotinic acid. The fractional catabolic rate in Lp(a) was unaltered in the subjects on therapy, indicating that nicotinic acid did not increase catabolism of Lp(a) but decreased the synthetic rate. Since nicotinic acid was poorly tolerated we examined the effect of acipimox, an analogue of nicotinic acid on lipoproteins using a placebo controlled double-blind crossover design in a group of hyperlipidaemic patients again selected with plasma Lp(a) concentration greater than 30 mg/dl. Acipimox was better tolerated than nicotinic acid but the percentage changes in lipoprotein concentrations were smaller.
Generalist genes and learning disabilities: a multivariate genetic analysis of low performance in reading, mathematics, language and general cognitive ability in a sample of 8000 12-year-old twins.

Our previous investigation found that the same genes influence poor reading and mathematics performance in 10-year-olds. Here we assess whether this finding extends to language and general cognitive disabilities, as well as replicating the earlier finding for reading and mathematics in an older and larger sample.



Using a representative sample of 4000 pairs of 12-year-old twins from the UK Twins Early Development Study, we investigated the genetic and environmental overlap between internet-based batteries of language and general cognitive ability tests in addition to tests of reading and mathematics for the bottom 15% of the distribution using DeFries-Fulker extremes analysis. We compared these results to those for the entire distribution.



All four traits were highly correlated at the low extreme (average group phenotypic correlation = .58). and in the entire distribution (average phenotypic correlation = .59). Genetic correlations for the low extreme were consistently high (average = .67), and non-shared environmental correlations were modest (average = .23). These results are similar to those seen across the entire distribution (.68 and .23, respectively).



The 'Generalist Genes Hypothesis' holds for language and general cognitive disabilities, as well as reading and mathematics disabilities. Genetic correlations were high, indicating a strong degree of overlap in genetic influences on these diverse traits. In contrast, non-shared environmental influences were largely specific to each trait, causing phenotypic differentiation of traits.
Pharmacokinetics of cyclosporin - a microemulsion in children with idiopathic nephrotic syndrome

We present a prospective study of a microemulsion of cyclosporin to treat idiopathic nephrotic syndrome in ten children with normal renal function who presented cyclosporin trough levels between 50 and 150 ng/ml and achieved complete remission with cyclosporin. To compare the pharmacokinetic parameters of cyclosporin in idiopathic nephrotic syndrome during remission and relapse of the nephrotic state.



The pharmacokinetic profile of cyclosporin was evaluated with the 12-hour area under the time-concentration curve (auc0-12) using seven time-point samples. This procedure was performed on each patient during remission and relapse with the same cyclosporin dose in mg/kg/day. The 12-hour area under the time-concentration curve was calculated using the trapezoidal rule. All of the pharmacokinetic parameters and the resumed 4-hour area under the time-concentration curve were correlated with the 12-hour area under the time-concentration curve. 
There were no significant differences in any parameters of the pharmacokinetic of cyclosporin during remission and relapse, even when the data were normalized by dose. The best correlation with the 12-hour area under the time-concentration curve was the 4-hour area under the time-concentration curve on remission and relapse of the disease, followed by the 2-hour level after cyclosporin (c2) dosing in both disease states.



These data indicate that the same parameters used for cyclosporin therapeutic monitoring estimated during the nephrotic state can also be used during remission. Larger controlled studies are needed to confirm these findings.
Association of variation in hepatic lipase activity with promoter variation in the hepatic lipase gene. The LOCAT Study Invsestigators.

The associations between six genetic polymorphisms in the hepatic lipase (HL) gene (LIPC) and variation in postheparin HL activity and fasting serum lipoproteins were evaluated in 395 male Finnish coronary heart disease patients with HDL cholesterol concentrations </= 1.1 mmol/liter. The LIPC promoter polymorphism at position -514 was highly significantly associated with variation in HL activity (P = 0.0000008), with mean activities of 20.4, 17.5, and 13.2 mumol free fatty acid/ml per hour in subjects having C/C, C/T, and T/T genotypes, respectively. Furthermore, the triglyceride content of low density lipoprotein, intermediate density lipoprotein and HDL, and the cholesterol content of intermediate density lipoprotein were found to be associated with variation at LIPC position -514. However, there was no association of this polymorphism with coronary heart disease. These data suggest that the LIPC promoter variation is likely to be the basis for variation in HL activity, which underlies the variation in serum lipoprotein phenotypes in this sample.
Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma.

Samarium-153 ethylenediamine tetramethylene phosphoric acid (153Sm-EDTMP) is a radiopharmaceutical that has been used to treat osteosarcoma. The authors conducted a phase 2 study to test safety and response of high-risk osteosarcoma to tandem doses of 153Sm-EDTMP and to determine correlation between radiation delivered by low and high administered activities.



Patients with recurrent, refractory osteosarcoma detectable on standard 99mTc bone scan received a low dose of 153Sm-EDTMP (37.0-51.8 MBq/kg), followed upon count recovery by a second, higher dose (222 MBq/kg). Fourteen days later, patients were rescued with autologous hematopoietic stem cells. The authors assessed response to therapy, performed dosimetry to determine the relationship between administered activity and tumor absorbed dose, and investigated whether changes in 2-(fluorine-18) fluoro-2-deoxy-d-glucose (18F-FDG) tumor uptake upon hematologic recovery reflected disease response.



Nine patients were given tandem doses of 153Sm-EDTMP; 2 received only the initial dose because of disease progression. Six patients experienced radiographic disease stabilization, but this was not considered a response, so the study was terminated early. There was a linear relationship between administered activity and tumor absorbed dose, but there was no correlation between change in 18F-FDG positron emission tomography tumor uptake and tumor absorbed dose or time to progression. The median time to progression for the entire group was 79 days.



Tandem doses of 153Sm-EDTMP were safe for this cohort of heavily pretreated patients with very high-risk disease. The strong correlation between absorbed dose and administered activity within each evaluable patient provides a methodology to individually tailor tandem doses of this agent.
Bladder autoaugmentation in adult patients with neurogenic voiding dysfunction

Bladder autoaugmentation offers an alternative to enterocystoplasties for patients with low capacity high pressure bladders caused by non-malignant pathology. In particular for patients with neuropathic hyperreflexive bladders, refractory to less invasive therapy, bladder autoaugmentation will attain comparable results with less impact on life quality compared to other bladder augmentation procedures. The procedure does not preclude later enterocystoplasty or deafferentations. Over the last 7 years, 50 patients were treated by this method, some of them for other than neurogenic voiding dysfunction. Substantial increase of bladder capacity and compliance resulted, at the cost of increased residual urine and the need for intermittent catheterisation in most patients. Some patients are able to perform complete voiding at will. The time lapse between surgery and functional rehabilitation of the bladder (substantial increase of capacity and detrusor compliance) cannot be predicted yet. In most patients this amelioration was observed 1 – 6 months after surgery, but in some the effect was equivocal for a year or longer. Low-dose anticholinergics appear to speed up the therapeutic effect. One patient had enterocystoplasty and one deafferentation later, one had rupture of the bladder, probably from the use of an artificial sphincter, and two are rated as failures because of psychogenic bladder-centred problems. Bladder autoaugmentation is a favourable treatment for patients who are motivated to wait possibly longer for functional changes to occur and are willing to perform intermittent catheterisation afterwards.
Prucalopride Improves Bowel Function and Colonic Transit Time in Patients With Chronic Constipation: An Integrated Analysis

Constipation is often characterized by slow colonic transit, but the relationship between colonic transit time (CTT) and symptoms is unclear. The aims of this study were to investigate the effect of prucalopride, a 5-hydroxytryptamine receptor-4 agonist, on CTT and assess the relationship between CTT and symptoms.This was an integrated analysis of three randomized, placebo-controlled, phase 2 dose-finding trials of prucalopride in patients with chronic constipation (ClinicalTrials.gov identifiers: NCT00617513; NCT00631813; and NCT00596596). Measurements of CTT were analyzed using radio-opaque markers at the start and end (4 or 12 weeks) of treatment. At these visits, patients assessed the presence and severity of their symptoms.In total, 280 patients had CTT measurements before and at the end of treatment and were included in the analysis. Their mean age was 43 years, 93% were women, and mean duration of constipation was 19 years. After a once daily treatment with prucalopride 2 mg (n=98) and 4 mg (n=70), CTT was reduced by 12.0 h (95% confidence interval (CI): –18.9, –5.1) and 13.9 h (95% CI: –20.5, –7.4), respectively; CTT increased by 0.5 h (95% CI: –4.5, 5.5) with placebo (n=112). At the end of the trial, symptoms including bloating/flatulence/distension and straining were rated as severe or very severe by a higher proportion of patients with slow or very slow CTT (>48 h) than by those with normal CTT.Conclusions:There was a clear relationship between increased CTT and increased symptom severity in patients with chronic constipation. Treatment with prucalopride accelerated CTT in these individuals.
Effect of cimetidine on digoxin disposition in peptic ulcer patients

Cimetidine inhibits the renal tubular secretion of creatinine and digoxin is partly excreted by the same pathway. In order to investigate a possible interaction between the two drugs, a randomized cross-over acute study has been conducted. Six patients with duodenal ulcers were given a single dose of digoxin (Dig) 0.75 mg i.v. with and without oral cimetidine 1200 mg/day. Cimetidine significantly reduced creatinine clearance from 157 to 132 ml/min. There was no significant difference in inulin clearance, 99.2 vs 97.5 ml/min, Dig elimination half life 53.9 vs 56.9 h, apparent volume of distribution 11.3 vs 11.6 l/kg, systemic clearance 2.42 vs 2.35 ml/min/kg, renal clearance 1.48 vs 1.62 ml/min/kg or urinary excretion of digoxin 49.5 vs 51.6% of dose without or with cimetidine. These results suggest that cimetidine does not influence the disposition of digoxin.
Effect of self-administered intraperitoneal bemiparin on peritoneal transport and ultrafiltration capacity in peritoneal dialysis patients with membrane dysfunction. A randomized, multi-centre open clinical trial.

Progressive peritoneal membrane injury and dysfunction are feared repercussions of peritoneal dialysis (PD), and may compromise the long-term feasibility of this therapy. Different strategies have been attempted to prevent or reverse this complication with limited success.



We performed a randomized, open multi-centre trial, aimed at scrutinizing the efficacy of self-administered intraperitoneal (i.p.) bemiparin (BM) to modulate peritoneal membrane dysfunction. The main outcome variables were peritoneal creatinine transport and the ultrafiltration (UF) capacity, estimated during consecutive peritoneal equilibration tests. The trial included a control group who did not undergo intervention. The treatment phase lasted 16 weeks with a post-study follow-up of 8 weeks.



Intraperitoneal BM did not significantly improve creatinine transport or the UF capacity, when the whole group was considered. However, we observed a time-limited improvement in the UF capacity for the subgroup of patients with overt UF failure, which was not observed in the control group. Intraperitoneal injection of BM did not carry an increased risk of peritoneal infection or major haemorrhagic complications.



Our data do not support the systematic use of BM for management of peritoneal membrane dysfunction in PD patients. Further studies on the usefulness of this approach in patients with overt UF failure are warranted. Intraperitoneal administration of BM is safe in PD patients, provided regulated procedures are respected.
Triglyceride-lowering effect of marine polyunsaturates in patients with hypertriglyceridemia.

Twenty male patients with primary hypertriglyceridemia were treated for 4 weeks with daily supplements (15 g) of oil, which provided approximately 6 g of polyunsaturated fatty acid (PUFA) either of fish or of vegetable origin. Total plasma cholesterol concentrations were unaffected, but both types of supplement increased high density lipoprotein-3 (HDL3) cholesterol concentrations. The fish, but not the vegetable, oil supplement led to a decrease in plasma triglyceride concentrations. Very low density lipoprotein (VLDL), fatty acid composition, and VLDL triglyceride kinetics were subsequently studied in five patients (four male, one female) before and after 4 weeks of therapy with 15 g of the same fish oil. The fish oil led to increases in the proportion of eicosapentaenoic acid in both the VLDL triglyceride and phospholipid fractions, but the increase was greater in the latter. In contrast, the proportion of docosahexanoic acid was increased only in the VLDL triglycerides. The decrease in plasma triglyceride concentrations that occurred with fish-oil therapy was accompanied by a reduction in the absolute catabolic rate of VLDL triglyceride, implying a concomitant change in synthetic rate; the fractional catabolic rate of VLDL triglyceride was unaltered. It is suggested that polyunsaturated fatty acids of marine origin may be therapeutically useful for hypertriglyceridemia.
The RADAR Study: Week 48 Safety and Efficacy of RAltegravir Combined with Boosted DARunavir Compared to Tenofovir/Emtricitabine Combined with Boosted Darunavir in Antiretroviral-Naive Patients. Impact on Bone Health

NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression.



In the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL) (n = 42) or tenofovir/emtricitabine (TDF/FTC) (n = 43), each with ritonavir-boosted darunavir (DRV/r). Virologic efficacy was assessed at weeks 24 and 48. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) scan at baseline and week 48, and bone turnover markers (BTM) assessed at weeks 0, 16 and 48.



Using an intention-to-treat analysis, 62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL<48 copies/mL) at week 48 (p = 0.045; chi-square test). The proportions of patients achieving VL<200 copies/mL were similar: 72.5% and 86.0% (p = 0.175). Premature treatment discontinuation was the main cause for failure. No treatment-emergent resistance was observed. Changes from baseline in RAL vs. TDF/FTC for CD4+ (+199 vs. +216 cells/µL, p = 0.63), total cholesterol/HDL (-0.25 vs. -0.71 mg/dL (p = 0.270), and eGFR (-4.4 vs. -7.9 ml/min, p = 0.44) were comparable between groups. Changes in subtotal BMD to week 48 were: +9.2 with RAL vs. -7 g/cm2 with TDF/FTC (p = 0.002). Mean CTX changes were +0.04 vs. +0.24 ng/mL (p = 0.001), and mean P1NP changes were +3.59 vs. +30.09 ng/mL (p = 0.023). BTM changes at week 16 predicted change in BMD by week 48 (R = -0.394, p = 0.003 for CTX; and R = -0.477, p<0.001 for P1NP).



The NRTI-sparing regimen RAL+DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC+DRV/r, but was better with regard to markers of bone health.