nils-herrmann/clean_scirepeval huggingface dataset:
Evaluation of 5 versus 10 granulocyteaphaeresis sessions in steroid-dependent ulcerative colitis: a pilot, prospective, multicenter, randomized study.

To evaluate the efficacy of 5 compared to 10 granulocyteaphaeresis sessions in patients with active steroid-dependent ulcerative colitis.



In this pilot, prospective, multicenter randomized trial, 20 patients with moderately active steroid-dependent ulcerative colitis were randomized to 5 or 10 granulocyteaphaeresis sessions. The primary objective was clinical remission at wk 17. Secondary measures included endoscopic remission and steroid consumption.



Nine patients were randomized to 5 granulocyteaphaeresis sessions (group 1) and 11 patients to 10 granulocyteaphaeresis sessions (group 2). At wk 17, 37.5% of patients in group 1 and 45.45% of patients in group 2 were in clinical remission. Clinical remission was accompanied by endoscopic remission in all cases. Eighty-six percent of patients achieving remission were steroid-free at wk 17. Daily steroid requirements were significantly lower in group 2. Eighty-nine per cent of patients remained in remission during a one year follow-up. One serious adverse event, not related to the study therapy, was reported.



Granulocyteaphaeresis is safe and effective for the treatment of steroid-dependent ulcerative colitis. In this population, increasing the number of aphaeresis sessions is not associated with higher remission rates, but affords a significant steroid-sparing effect.
Enzyme Polymorphism in Warfarin Dose Management After Pediatric Cardiac Surgery

Warfarin is an anticoagulant and is widely used for the prevention of thromboembolic events. Genetic variants of the enzymes that metabolize warfarin, i.e. cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various warfarin doses. There is, however, a dearth of data on the role of these variants during initial anticoagulation in pediatric patients.



We aimed to evaluate the role of genetic variants of warfarin metabolizing enzymes in anticoagulation in a pediatric population.



In this prospective cohort study, 200 pediatric patients, who required warfarin therapy after cardiac surgery, were enrolled and divided into two groups. For 50 cases, warfarin was prescribed based on their genotyping (group 1) and for the remaining 150 cases, warfarin was prescribed based on our institute routine warfarin dosing (group 2). The study endpoints were comprised of time to reach the first therapeutic international normalization ratio (INR), time to reach a stable warfarin maintenance dose, time with over-anticoagulation, bleeding episodes, hospital stay days and stable warfarin maintenance dose.



There was no significant difference concerning the demographic data between the two groups. The time to stable warfarin maintenance dose and hospital stay days were significantly lower in group 1 (P <0.001). However, there was no statistically significant difference in time to reach the first therapeutic INR, time with over-anticoagulation and bleeding episodes, between the two groups.



The determination of warfarin dose, based on genotyping, might reduce the time to achieve stable anticoagulation of warfarin dose and length of hospital stay.
Combination of highly purified human leukocyte interferon α and 13-cis-retinoic acid for the treatment of metastiatic melanoma

The effect of 13-cis-retinoic acid and highly purified human leukocyte interferon α (Alphaferon) therapy for metastatic melanoma was studied. A group of 17 patients with disseminated malignant melanoma were treated over a 6-month period. They received 60 mg 13-cis-retinoic acid/day continuously and ten cycles of interferon α (IFNα). IFN was administered by subcutaneous injection, at a daily dose of 6×106 IU Alphaferon. The 5-day treament period was followed by an IFN-free interval of 2 weeks. We were able to observe an overall response rate of 30% with 12% complete responses (2 out of 17 patients). Sites of response included the skin, lung, liver and lymph nodes. All responses have now lasted over 6 months. Therapy was generally well tolerated and could be performed on an outpatient basis. Side-effects of this combination therapy did not exceed the established side-effects of the two substances. We also studied 2′-5′-oligoadenylate synthetase, β2-microglobulin and neopterin levels during the whole treatment course. All patients were within the normal range before treatment and a sharp rise occurred during each IFN cycle. The maximum being observed 24 h after the third injection. This indicates a high biological activity of IFNα administered cyclicly during the whole treatment course. This finding also corresponds well with the absence of neutralizing antibodies before and after the whole treatment period.
α-Lactalbumin-enriched and probiotic-supplemented infant formula in infants with colic: growth and gastrointestinal tolerance

Studies undertaken with α-lactalbumin-enriched formulae never addressed infants with colic. This study evaluated the nutritional adequacy, the gastrointestinal tolerance and the effect on colic of an α-lactalbumin-enriched and probiotic-supplemented formula. A double-blind, placebo-controlled study enrolled 66 healthy infants with colic, aged 3 weeks to 3 months, fed during 1 month with the either experimental formula (EF, Modilac Digest 1) or control formula (CF) and evaluated for efficacy and safety parameters at days 15 and 30. Weight and height gains were identical in the two groups and complied with standards (1023.4±360.4 g (EF) and 1047.4±372.1 g (CF), NS; 4.2±1.4 cm (EF) and 4.3±1.9 cm (CF), NS). No differences were found between groups for crying duration. ‘Feeding-related’ gastrointestinal side effects were significantly lower with EF than with CF (P=0.011). An α-lactalbumin-enriched and probiotic-supplemented formula guaranteed good weight and length gains to infants with colic and seemed to provide good gastrointestinal tolerance.
Proteinuria patterns and their association with subsequent end-stage renal disease in IgA nephropathy.

Proteinuria (UP) >1.0 g/24 h at diagnosis is a well-known indicator of progressive renal disease in patients with IgA nephropathy (IgAN). To determine if persistent UP is a more sensitive marker for later progression of IgAN, the hypothesis was tested that the prior level and trend (slope) in UP for 1 year was better at predicting later end-stage renal disease (ESRD) (dialysis or transplant) than a current 24-h UP, serum creatinine (SC), SC slope, hypertension, or total glomerular histopathological score on index renal biopsy in an observational study of 154 high-risk patients enrolled in two clinical trials (IgAN 1, IgAN 2).



Measurements of 24-h UP and SC were made at time 0, 6 weeks, 6 months and 1 year in all patients, who were then followed for an additional 5.76 years and 1.63 years in the two studies, respectively. The Cox proportional hazards model was used to identify predictors of ESRD following the 1-year visit.



Adjusting only for randomized treatment, nearly all UP variables (number of high readings, 1-year level, slopes), SC at 1 year, and SC trends (slopes) over the prior year were significantly associated with subsequent ESRD (all P values <0.05) in both studies. However, among the UP variables, the 1-year readings had the strongest association with ESRD in IgAN 1 (hazard ratio (HR), 95% CI, for a 1g increase: 1.5, 1.2,1.9), and the second strongest association (similar to UP trends) in IgAN 2 (1.4, 1.2,1.6). Males had lower rates of ESRD in both studies (IgAN 1 HR: 0.5, 0.2,1.2, P=0.11; IgAN 2 HR: 0.2, 0.1,0.6, P=0.002). In the multivariate analyses that examined all clinical and histological variables, 1-year levels of 24-h UP and SC, and female gender were independently associated with subsequent ESRD.



In a high-risk patient with IgAN, the current 24-h UP and SC measurements are as good predictors of subsequent ESRD as UP and SC trends and levels over the prior year. Additionally, it appears that females have poorer outcomes than males.
Combined versus single effect of fosinopril and hydrochlorothiazide in hypertensive patients.

The antihypertensive effect and safety of fosinopril and hydrochlorothiazide combined were compared with each drug singly and placebo in a controlled manner. After a 4- to 5-week placebo lead-in period, 67 mild to moderate essential hypertensive patients (seated diastolic blood pressure > or = 95 and < or = 110 mm Hg) were randomized in a double-blind fashion into four parallel treatment groups: 20 mg fosinopril plus 12.5 mg hydrochlorothiazide, 20 mg fosinopril, 12.5 mg hydrochlorothiazide, and placebo during 8 weeks. Patients were seen biweekly. Sitting diastolic blood pressure was the outcome variable defining therapeutic response. The efficacy of fosinopril plus hydrochlorothiazide as a combined therapy was superior to any single drug (P < .05) and placebo (P < .01) in the treatment of mild to moderate essential hypertension. Mean adjusted systolic/diastolic blood pressure decrements at week 8 were -18.8/-13.7, -12.9/-11.8, -8.5/-9.3, and -2.7/-6.9 mm Hg for the fosinopril plus hydrochlorothiazide, fosinopril, hydrochlorothiazide, and placebo groups, respectively. Clinical adverse events and laboratory changes documented throughout the study were similar to placebo and were mild in severity in all groups.
Motivational deficits and cognitive test performance in schizophrenia.

Motivational and cognitive deficits are core features of schizophrenia, both closely linked with functional outcomes. Although poor effort and decreased motivation are known to affect performance on cognitive tests, the extent of this relationship is unclear in patients with schizophrenia.



To evaluate the association between intrinsic motivation and cognitive test performance in patients with schizophrenia.



Cross-sectional and 6-month prospective follow-up study performed at 57 sites in the United States, including academic and community medical treatment centers, participating in the Clinical Antipsychotic Trials of Intervention Effectiveness study. The primary sample included 431 stable patients with a DSM-IV diagnosis of schizophrenia currently receiving a stable medication regimen.



Cognitive performance and intrinsic motivation were evaluated using a comprehensive neuropsychological test battery and a derived measure from the Heinrichs-Carpenter Quality of Life Scale, respectively. Symptom severity and functional status were also assessed.



The primary outcome variable was global neurocognition. Individual domains of cognition were also evaluated for their association with motivation.



Level of intrinsic motivation was significantly and positively correlated with global cognitive test performance, a relationship that held for each domain of cognition evaluated (correlation range, 0.20-0.34; P < .001). This association was found to be reliable after statistically accounting for positive, negative, depressive, and overall symptom severity (P < .05) and after accounting for community functioning (P < .001). The relationship between motivation and cognitive performance also remained significant after controlling for antipsychotic dose (P < .05). Prospective increase in motivation during the 6-month follow-up was also found to be significantly related to improvement in global cognitive performance (P < .05).



The present findings provide strong support for a robust and reliable relationship between motivation and cognitive performance and suggest that test performance is not purely a measure of ability. Future studies assessing cognition in patients with schizophrenia should consider potential moderating variables such as effort and motivation. Implications for the assessment and interpretation of cognitive impairment based on neuropsychological test measures in schizophrenia are discussed, especially in the case of clinical trials for cognition-enhancing treatments.
Marginal structural models for the estimation of the risk of Diabetes Mellitus in the presence of elevated depressive symptoms and antidepressant medication use in the Women’s Health Initiative observational and clinical trial cohorts

We evaluate the combined effect of the presence of elevated depressive symptoms and antidepressant medication use with respect to risk of type 2 diabetes among approximately 120,000 women enrolled in the Women's Health Initiative (WHI), and compare several different statistical models appropriate for causal inference in non-randomized settings.



Data were analyzed for 52,326 women in the Women's Health Initiative Clinical Trials (CT) Cohort and 68,169 women in the Observational Study (OS) Cohort after exclusions. We included follow-up to 2005, resulting in a median duration of 7.6 years of follow up after enrollment. Results from three multivariable Cox models were compared to those from marginal structural models that included time varying measures of antidepressant medication use, presence of elevated depressive symptoms and BMI, while adjusting for potential confounders including age, ethnicity, education, minutes of recreational physical activity per week, total energy intake, hormone therapy use, family history of diabetes and smoking status.



Our results are consistent with previous studies examining the relationship of antidepressant medication use and risk of type 2 diabetes. All models showed a significant increase in diabetes risk for those taking antidepressants. The Cox Proportional Hazards models using baseline covariates showed the lowest increase in risk , with hazard ratios of 1.19 (95 % CI 1.06 - 1.35) and 1.14 (95 % CI 1.01 - 1.30) in the OS and CT, respectively. Hazard ratios from marginal structural models comparing antidepressant users to non-users were 1.35 (95 % CI 1.21 - 1.51) and 1.27 (95 % CI 1.13 - 1.43) in the WHI OS and CT, respectively - however, differences among estimates from traditional Cox models and marginal structural models were not statistically significant in both cohorts. One explanation suggests that time-dependent confounding was not a substantial factor in these data, however other explanations exist. Unadjusted Cox Proportional Hazards models showed that women with elevated depressive symptoms had a significant increase in diabetes risk that remained after adjustment for confounders. However, this association missed the threshold for statistical significance in propensity score adjusted and marginal structural models.



Results from the multiple approaches provide further evidence of an increase in risk of type 2 diabetes for those on antidepressants.
Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury.

Sensitive and specific biomarkers are needed to detect early kidney injury. The objective of the present work was to develop a sensitive quantitative urinary test to identify renal injury in the rodent to facilitate early assessment of pathophysiological influences and drug toxicity. Two mouse monoclonal antibodies were made against the purified ectodomain of kidney injury molecule-1 (Kim-1), and these were used to construct a sandwich Kim-1 ELISA. The assay range of this ELISA was 50 pg/ml to 5 ng/ml, with inter- and intra-assay variability of <10%. Urine samples were collected from rats treated with one of three doses of cisplatin (2.5, 5, or 7.5 mg/kg). At one day after each of the doses, there was an approximately three- to fivefold increase in the urine Kim-1 ectodomain, whereas other routinely used biomarkers measured in this study [plasma creatinine, blood urea nitrogen (BUN), urinary N-acetyl-beta-glucosaminidase (NAG), glycosuria, proteinuria] lacked the sensitivity to show any sign of renal damage at this time point. When rats were subjected to increasing periods (10, 20, 30, or 45 min) of bilateral ischemia, there was an increasing amount of urinary Kim-1 detected. After only 10 min of bilateral ischemia, Kim-1 levels on day 1 were 10-fold higher (5 ng/ml) than control levels, whereas plasma creatinine and BUN were not increased and there was no glycosuria, increased proteinuria, or increased urinary NAG levels. Thus urinary Kim-1 levels serve as a noninvasive, rapid, sensitive, reproducible, and potentially high-throughput method to detect early kidney injury in pathophysiological studies and in preclinical drug development studies for risk-benefit profiling of pharmaceutical agents.
Replacing carbamazepine slow-release tablets with carbamazepine suppositories: a pharmacokinetic and clinical study in children with epilepsy.

A suppository for rectal administration of carbamazepine has been developed for situations in which it is unsuitable to use the oral route of administration. In an open, controlled, within-patient study, the pharmacokinetics, clinical efficacy, and tolerability of carbamazepine slow-release tablets were compared with those of carbamazepine suppositories in children with epilepsy. The pharmacokinetic part of the study comprised 22 children, and an additional nine children were included in the clinical part of the study. Treatment with slow-release tablets was replaced for 7 days with carbamazepine suppositories in bioequivalent dosage. Clinical factors such as the rate of seizures and the local tolerability were studied, and an overall assessment of efficacy was made. In the pharmacokinetic part, 24-hour plasma concentration curves for carbamazepine and carbamazepine-10,11-epoxide were recorded. The plasma concentration profiles (minimum, maximum, and mean concentrations, fluctuation index, and area under the curve) for carbamazepine and the other metabolites did not show any significant differences between oral and rectal administration when the suppository dose was increased by 25% compared to the tablets. No increase in seizure frequency was detected, and the overall assessment was very good to good in 25 of the 29 epileptic children. Increased flatulence during treatment with suppositories was noted in two children, one had anal irritation, and one had nausea/vomiting. Treatment with carbamazepine slow-release tablets in children with epilepsy can be replaced by carbamazepine suppositories in 25% higher dosage, with good clinical effect and appropriate pharmacokinetic values, when it is unsuitable to use the common oral route of administration.
Determination of trace elements in normal and diabetic whole blood by neutron activation analysis

The concentration of 10 trace elements in samples of normal and diabetic whole blood were investigated by neutron activation analysis (NAA). Instrumental NAA (INAA) was used for determination of Co, Cr, Hg, Rb, Se, and Zn, whereas NAA with radiochemical separation (RNAA) was employed for determination of Al, Cu, Mg, and Mn. The results for normal blood compare well with literature values. Co, Cr, Se, and Zn show lower values in diabetes than in the normal blood samples.
Protocol for the ADDITION-Plus study: a randomised controlled trial of an individually-tailored behaviour change intervention among people with recently diagnosed type 2 diabetes under intensive UK general practice care

The increasing prevalence of type 2 diabetes poses both clinical and public health challenges. Cost-effective approaches to prevent progression of the disease in primary care are needed. Evidence suggests that intensive multifactorial interventions including medication and behaviour change can significantly reduce cardiovascular morbidity and mortality among patients with established type 2 diabetes, and that patient education in self-management can improve short-term outcomes. However, existing studies cannot isolate the effects of behavioural interventions promoting self-care from other aspects of intensive primary care management. The ADDITION-Plus trial was designed to address these issues among recently diagnosed patients in primary care over one year.



ADDITION-Plus is an explanatory randomised controlled trial of a facilitator-led, theory-based behaviour change intervention tailored to individuals with recently diagnosed type 2 diabetes. 34 practices in the East Anglia region participated. 478 patients with diabetes were individually randomised to receive (i) intensive treatment alone (n = 239), or (ii) intensive treatment plus the facilitator-led individual behaviour change intervention (n = 239). Facilitators taught patients key skills to facilitate change and maintenance of key behaviours (physical activity, dietary change, medication adherence and smoking), including goal setting, action planning, self-monitoring and building habits. The intervention was delivered over one year at the participant's surgery and included a one-hour introductory meeting followed by six 30-minute meetings and four brief telephone calls. Primary endpoints are physical activity energy expenditure (assessed by individually calibrated heart rate monitoring and movement sensing), change in objectively measured dietary intake (plasma vitamin C), medication adherence (plasma drug levels), and smoking status (plasma cotinine levels) at one year. We will undertake an intention-to-treat analysis of the effect of the intervention on these measures, an assessment of cost-effectiveness, and analyse predictors of behaviour change in the cohort.



The ADDITION-Plus trial will establish the medium-term effectiveness and cost-effectiveness of adding an externally facilitated intervention tailored to support change in multiple behaviours among intensively-treated individuals with recently diagnosed type 2 diabetes in primary care. Results will inform policy recommendations concerning the management of patients early in the course of diabetes. Findings will also improve understanding of the factors influencing change in multiple behaviours, and their association with health outcomes.
The feasibility of nipple aspiration and duct lavage to evaluate the breast duct epithelium of women with increased breast cancer risk.

Nipple aspiration (NA) and duct lavage (DL) are modalities for obtaining breast duct fluid for biomarker analyses. The aim of this study was to assess the feasibility of obtaining serial NA and DL samples at consecutive patient visits for cytology assessment and the creation of a biobank.



Seventy eligible subjects were enroled at a single institution in the United Kingdom as part of an international multicentre study. Entry criteria were based on a 5-year Gail model risk of ≥2% or Claus score lifetime risk of ≥26%. Women underwent NA and DL in an outpatient clinic under local anaesthesia.



The mean patient age was 48 (range 41-69)years. Sixty seven out of 70 women (96%) attended three consecutive 6 monthly visits and follow-up for 2 years. Three women withdrew due to intolerance of the DL procedure. 56/67 (83%) women produced NA fluid from at least one duct. 204/264 (77%) of ducts declared by NA were cannulated for DL. 170/204 (83%) produced DL samples with adequate cellularity. By the final visit 52/67 (78%) women produced DL, 28/52 (54%) of whom were premenopausal and 24/52 (46%) were postmenopausal. 50/52 women (96%) underwent repeated DL of 81 ducts on 3 consecutive visits.



NA and DL are well tolerated for repeated assessment to obtain material for cytology and to create a biobank for future biomarker studies in women at high breast cancer risk.