nils-herrmann/clean_scirepeval huggingface dataset:
Clozapine serum levels and side effects during steady state treatment of schizophrenic patients: a cross-sectional study

Serum clozapine (S-Cloza) and serum desmethyl-clozapine concentrations (S-Descloza) were measured in 30 chronic schizophrenic in- and outpatients on a variable dose regimen. All patients were in steady state with respect to clozapine therapy and in a stable condition with respect to psychotic illness. The 24-h clozapine dose (median with interquartile range in parenthesis) was 350 (228–425) mg/24 h (range 100–700). There was a weak positive correlation between doses and the BPRS total score (r=0.44,P<0.05). The median S-Cloza was 1076 (706–1882) nmol/l (range 196–5581 corresponding to 64–1824 ng/ml). The S-Cloza was linearly correlated to dose but with a high interindividual variation at equal doses, e.g. a factor of 8 at 400 mg/24 h, but a low intraindividual variability of 20%. The S-Descloza averaged 77% of the S-Cloza and was highly correlated to S-Cloza (r=0.90;P<0.001). The S-Descloza/dose ratio increased with age and duration of treatment. The side effects registered were EEG abnormalities (83%), tachycardia (23%), increased liver enzyme activity (60%), orthostatic hypotension (17%), and moderate leucocytosis (17%). Only EEG changes were correlated to S-Cloza (r=0.43;P<0.05). The score values of the UKU Side Effect Scale were weakly (r=0.36) correlated to S-Cloza. No side effects were correlated to S-Descloza, doses, or treatment duration. The frequency of side effects was higher than in studies using lower mean doses indicating a correlation between doses or S-Cloza and the frequency of side effects. It is concluded that clozapine fulfils the criteria for therapeutic drug monitoring. TDM may contribute to finding the lowest effective dose with the fewest possible side effects.
Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery.

Dabigatran, an oral once-daily unmonitored thrombin inhibitor, has been tested elsewhere using enoxaparin 40 mg once daily. We used the North American enoxaparin 30 mg BID regimen as the comparator. This was a double-blind, centrally randomized trial. Unilateral total knee arthroplasty patients were randomized to receive oral dabigatran etexilate 220 or 150 mg once daily, or enoxaparin 30 mg SC BID after surgery, blinded. Dosing stopped at contrast venography, 12 to 15 days after surgery. Among 1896 patients, dabigatran 220 and 110 mg showed inferior efficacy to enoxaparin (venous thromboembolism rates of 31% [P = .02 vs enoxaparin], 34% [P < .001 vs enoxaparin], and 25%, respectively). Bleeding rates were similar, and no drug-related hepatic illness was recognized. Dabigatran, effective compared to once-daily enoxaparin, showed inferior efficacy to the twice-daily North American enoxaparin regimen, probably because of the latter's more intense and prolonged dosing.
Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.

Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.



We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause.



A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.



The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).
Development of a German version of the Oswestry Disability Index. Part 1: cross-cultural adaptation, reliability, and validity

Patient-orientated assessment methods are of paramount importance in the evaluation of treatment outcome. The Oswestry Disability Index (ODI) is one of the condition-specific questionnaires recommended for use with back pain patients. To date, no German version has been published in the peer-reviewed literature. A cross-cultural adaptation of the ODI for the German language was carried out, according to established guidelines. One hundred patients with chronic low-back pain (35 conservative, 65 surgical) completed a questionnaire booklet containing the newly translated ODI, along with a 0–10 pain visual analogue scale (VAS), the Roland Morris Disability Questionnaire, and Likert scales for disability, medication intake and pain frequency [to assess ODI’s construct (convergent) validity]. Thirty-nine of these patients completed a second questionnaire within 2 weeks (to assess test–retest reliability). The intraclass correlation coefficient for the test–retest reliability of the questionnaire was 0.96. In test–retest, 74% of the individual questions were answered identically, and 21% just one grade higher or lower. The standard error of measurement (SEM) was 3.4, giving a “minimum detectable change” (MDC95%) for the ODI of approximately 9 points, i.e. the minimum change in an individual’s score required to be considered “real change” (with 95% confidence) over and above measurement error. The ODI scores correlated with VAS pain intensity (r=0.78, P<0.001) and Roland Morris scores (r=0.80, P<0.001). The mean baseline ODI scores differed significantly between the surgical and conservative patients (P<0.001), and between the different categories of the Likert scales for disability, medication use and pain frequency (in each case P<0.001). Our German version of the Oswestry questionnaire is reliable and valid, and shows psychometric characteristics as good as, if not better than, the original English version. It should represent a valuable tool for use in future patient-orientated outcome studies in German-speaking lands.
The genetics of alcohol dependence: Twin and SNP-based heritability, and genome-wide association study based on AUDIT scores.

Alcohol dependence (AD) is among the most common and costly public health problems contributing to morbidity and mortality throughout the world. In this study, we investigate the genetic basis of AD in a Dutch population using data from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA). The presence of AD was ascertained via the Alcohol Use Disorders Identification Test (AUDIT) applying cut-offs with good specificity and sensitivity in identifying those at risk for AD. Twin-based heritability of AD-AUDIT was estimated using structural equation modeling of data in 7,694 MZ and DZ twin pairs. Variance in AD-AUDIT explained by all SNPs was estimated with genome-wide complex trait analysis (GCTA). A genome-wide association study (GWAS) was performed in 7,842 subjects. GWAS SNP effect concordance analysis was performed between our GWAS and a recent AD GWAS using DSM-IV diagnosis. The twin-based heritability of AD-AUDIT was estimated at 60% (55-69%). GCTA showed that common SNPs jointly capture 33% (SE = 0.12, P = 0.002) of this heritability. In the GWAS, the top hits were positioned within four regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019 (P = 7.58 × 10(-7) ). This first GWAS of AD using the AUDIT measure found results consistent with previous genetic studies using DSM diagnosis: concordance in heritability estimates and direction of SNPs effect and overlap with top hits from previous GWAS. Thus, the use of appropriate questionnaires may represent cost-effective strategies to phenotype samples in large-scale biobanks or other population-based datasets.
Hand bone loss in patients with psoriatic arthritis: posthoc analysis of IMPACT II data comparing infliximab and placebo.

In rheumatoid arthritis (RA), anti-tumor necrosis factor (anti-TNF) treatment is shown to reduce but not to arrest the rate of hand bone loss. This has not been assessed in psoriatic arthritis (PsA). Our objective was to examine changes in cortical hand bone density in patients with PsA treated with placebo or infliximab (IFX).



Patients in IMPACT II (Induction and Maintenance Psoriatic Arthritis Clinical Trial 2) were randomized to placebo or IFX. After Week 24, all received IFX. In a subset of 120 patients, cortical hand bone density was assessed at Weeks 0, 24, and 54 by digital X-ray radiogrammetry (dxr-BMD) on the same radiographs scored for joint damage.



Changes from baseline to 24 weeks in dxr-BMD were -0.30% (SD 1.1%) in the placebo group and -0.08% (SD 1.4%) in the IFX group (p = 0.63). Between baseline and 54 weeks the changes were -0.71% (SD 2.1%) in the placebo group and 0.15% (SD 1.7%) in the IFX group (p = 0.07), and between 24 and 54 weeks -0.41% (SD 1.4%) and 0.23% (SD 0.8%), respectively (p = 0.05). No significant correlation was found between change in dxr-BMD and radiographic damage.



This pilot study indicates that hand bone loss in PsA patients treated with anti-TNF can be arrested. Assessment of hand bone density may thus be a potential outcome measure for bone involvement and a response variable to treatment in PsA.
Concurrent validity of the pediatric attention disorders diagnostic screener for children with ADHD.

The present study examined the concurrent validity of a new computer-assisted ADHD screening system, the Pediatric Attention Disorders Diagnostic Screener (PADDS; Pedigo, Pedigo, & Scott, 2006) in relation to the Test of Variables of Attention (TOVA; Greenberg, 1999), the Conner's Continuous Performance Test- II (CPT-II; Conners & MHS Staff, 2000), and the Behavior Rating Inventory of Executive Function (BRIEF; Gioia, Isquith, Guy, & Kenworthy, 2000) in three clinically referred samples of children 6 to 12 years of age. The PADDS is a recently published multidimensional screening measure that incrementally merges computer-administered executive tasks with parent and teacher behavior ratings to aid in the diagnostic decision-making process for youth with attention disorders. To date, no published study has examined the concurrent validity of the PADDS. In a clinic-referred sample of 217 subjects diagnosed with ADHD concurrent validity was assessed through correlation coefficients, paired t-tests (p < .001), and Cohen's d effect sizes. In comparison to the TOVA, the CPT-II, and the BRIEF scales, the PADDS demonstrated strong concurrent validity between conceptually similar scales, providing initial evidence for the concurrent validity of the PADDS. Relative to other measures, the PADDS appears to have some unique scales designed to assess attention and various aspects of executive functioning.
Plasma choline depletion is associated with decreased peripheral blood leukocyte acetylcholine in children with cystic fibrosis.

Choline is an important constituent of acetylcholine. Choline is needed for acetylcholine in the nonneuronal acetylcholine system that includes epithelial cells of the lung and intestine, endothelial cells, and immune cells. Plasma free choline concentrations are low in children with cystic fibrosis (CF), but the implications for acetylcholine are unknown.



We determined the relation between plasma free choline and related metabolites and leukocyte acetylcholine in children with CF and in a control group of healthy children without CF.



This was a cross-sectional study in 34 children with CF who were pancreatic insufficient and taking pancreatic enzyme-replacement therapy and in 16 healthy children. Plasma free choline, betaine, dimethylglycine, methionine, homocysteine, and leukocyte acetylcholine concentrations were quantified by using isotope-dilution HPLC-tandem mass spectrometry.



Mean (±SE) plasma free choline was 9.30 ± 0.37 and 6.54 ± 0.38 μmol/L (P < 0.05) and leukocyte acetylcholine was 1.21 ± 0.016 and 0.077 ± 0.011 pmol leukocyte acetylcholine/10(6) cells (P < 0.05) in control children and children with CF, respectively. Leukocyte acetylcholine was positively correlated with plasma free choline concentration in children with CF (r = 0.412, P < 0.05) but not in control children. Plasma betaine, dimethylglycine, and methionine concentrations were also lower in children with CF than in control children (P < 0.05).



A low free choline and methyl status in children with CF is associated with reduced acetylcholine in leukocytes. Whether these changes are explained by a mutation in the CF transmembrane conductance regulator or disturbances in choline metabolism and the implications for immune cell dysfunction in CF are unknown.
Hepatic arterial embolization versus chemoembolization in the treatment of liver metastases from well-differentiated midgut endocrine tumors: a prospective randomized study.

Liver surgery is the best treatment for endocrine liver metastases, but it is often impossible due to diffuse disease. Systemic chemotherapy is poorly effective. Hepatic arterial embolization (HAE) and chemoembolization (HACE) have shown efficacy but have never been compared.



Patients with progressive unresectable liver metastases from midgut endocrine tumors were randomly assigned to receive HAE or HACE (two procedures at 3-month interval). The primary end point was the 2-year progression-free survival (PFS) rate. Secondary end points were response rates, overall survival, and safety.



Twelve patients were assigned to receive HACE and 14 to receive HAE. The patient characteristics were well matched across the treatment arms. The 2-year PFS rates were 38 and 44% in the HACE and HAE arms, respectively (p = 0.90). Age, gender, previous resection of the primary tumor or liver metastases, extent of liver involvement, and concomitant treatment with somatostatin analogues were not associated with changes in PFS, whereas elevated baseline urinary 5-HIAA and serum chromogranin A levels were associated with shorter PFS. The 2-year overall survival rates were 80 and 100% in the HACE and HAE arms, respectively (p = 0.16). The disease control rate on CT scan was 95%. Grade 3 toxicity occurred in 19% of patients, with no treatment-related deaths and no differences in the treatment arms.



HACE and HAE are safe and permit tumor control in 95% of patients with progressive liver metastases from midgut endocrine tumors. The 2-year PFS was not higher among patients receiving HACE, not favoring the hypothesis of an additive efficacy of arterial chemotherapy or embolization alone.
Randomized Controlled Trial of Home-Based Telehealth Versus In-Person Prolonged Exposure for Combat-Related PTSD in Veterans: Preliminary Results.

Telehealth technology may reduce the effect of treatment barriers and improve participation in treatment for veterans with posttraumatic stress disorder (PTSD). The present study is an ongoing randomized controlled trial comparing the effectiveness of prolonged exposure (PE) delivered via in person or home-based video telehealth modalities.



A total of 52 veterans with combat-related PTSD were randomized to receive 8-12 weeks of PE through either home-based telehealth or standard in-person office-based care.



Participants evinced significant reductions in symptoms of PTSD, depression, and anxiety from pre- to posttreatment across both conditions. Analyses conducted within a noninferiority framework suggested nonsignificant treatment outcome differences in clinician-reported PTSD and self-reported anxiety between the conditions. Results were inconclusive for self-reported PTSD and depression symptoms. Patient satisfaction ratings did not significantly differ between the two groups.



Results suggest that PE can be delivered via home-based telehealth with outcomes and satisfaction ratings comparable to in-person practices for certain symptoms, however additional research is needed. This modality has the potential to address stigma- and geographic-related barriers to treatment, such as travel time and cost.
Electrical cardioversion of persistent atrial fibrillation: acute and long-term results stratified according to arrhythmia duration.

Current definition of persistent atrial fibrillation (PAF) enrolls a heterogeneous population with different atrial fibrillation (AF) exposure and degree of atrial substrate. Study aims were to evaluate acute and long-term results of electrical cardioversion (ECV) and to identify temporal cutoff of previous AF exposure to reclassify PAF in subgroups with different chance of sinus rhythm (SR) maintenance.



Five hundred twenty-one patients (66% men; age 69 ± 10 years) with PAF undergoing ECV, were divided in four groups according to AF duration at the time of ECV: group A with AF ≤2 months (141 patients); group B with AF >2 and ≤4 months (176 patients); group C with AF >4 and ≤6 months (89 patients); and group D with AF >6 months and <1 year (115 patients).



There was no difference in term of acute success among groups (98.5% vs 97.1% vs 98.9% vs 96.5%, respectively, P = 0.95). At 5-year follow-up, 198 (41%) patients were in SR: 50% in group A, 44% in group B, 42% in group C, and 25% in group D (P < 0.001). At the multivariate analysis, previous ECV (hazard ratio [HR] 1.55, P < 0.001), left atrium enlargement (HR 1.39, P = 0.013), and AF duration >6 months at time of procedure (HR 1.59, P = 0.001) independently predict ECV failure.



ECV is associated with high acute success rate and low complications rate. Long-term results are strongly related with AF duration at time of ECV: a cutoff of >6 months helps in selecting patients that can take greater advantage of the procedure.
Pharmacokinetics of single-dose oral stavudine in subjects with renal impairment and in subjects requiring hemodialysis.

Two open-label studies assessed the pharmacokinetics of single orally administered doses of 40 mg of stavudine in subjects with renal impairment. In one study (study I), 15 subjects with selected degrees of renal impairment, but not requiring hemodialysis, were stratified into three groups of five subjects each according to creatinine clearance (CL(CR)) normalized by body surface area (ml/min/1.73 m(2)): mild (CL(CR), 60 to 80), moderate (30 to 50), and severe (</=20) renal impairment. Five healthy subjects (CL(CR) >/= 90) were also enrolled. The stavudine area under the curve from 0 h to infinity (AUC(0-infinity)) increased nonlinearly with declining renal function: 1,864, 2,215, 3,609, and 5,928 ng. h/ml for normal renal function and for mild, moderate, and severe renal impairment, respectively (P = 0.0001 between renal impairment groups). The following stavudine dosage recommendations for renal impairment were proposed for subjects weighing >/=60 kg: CL(CR) of >50 ml/min/1.73 m(2), 40 mg every 12 h; CL(CR) of 21 to 50 ml/min/1. 73 m(2), 20 mg every 12 h; and CL(CR) of 10 to 20 ml/min/1.73 m(2), 20 mg every 24 h. For subjects weighing <60 kg, the proposed doses were 30, 15, and 15 mg, respectively, with the same dosing intervals specified above. In a second study (study II), 12 subjects with end-stage renal disease requiring hemodialysis three times a week were enrolled in a randomized, open-label crossover study (dialysis 2 h after dosing and lasting 4 h or dosing without dialysis). There were no statistically significant differences for AUC(0-infinity), AUC(2-6), time to maximum concentration of drug in serum, half-life, or apparent oral clearance when the two treatment dosage regimens were compared. As a result of study II, the recommended dosing rate for subjects requiring hemodialysis was the same as that proposed for those with severe renal impairment not requiring hemodialysis; however, dosing was recommended to follow hemodialysis and to occur at the same time each day.
Detection of bladder cancer using a point-of-care proteomic assay.

A combination of methods is used for diagnosis of bladder cancer because no single procedure detects all malignancies. Urine tests are frequently part of an evaluation, but have either been nonspecific for cancer or required specialized analysis at a laboratory.



To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could enhance detection of malignancy in patients with risk factors or symptoms of bladder cancer.



Twenty-three academic, private practice, and veterans' facilities in 10 states prospectively enrolled consecutive patients from September 2001 to May 2002. Participants included 1331 patients at elevated risk for bladder cancer due to factors such as history of smoking or symptoms including hematuria and dysuria. Patients at risk for malignancy of the urinary tract provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy.



The diagnosis of bladder cancer, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to cancer detection. Testing for the NMP22 tumor marker was conducted in a blinded manner.



Bladder cancer was diagnosed in 79 patients. The NMP22 assay was positive in 44 of 79 patients with cancer (sensitivity, 55.7%; 95% confidence interval [CI], 44.1%-66.7%), whereas cytology test results were positive in 12 of 76 patients (sensitivity, 15.8%; 95% CI, 7.6%-24.0%). The specificity of the NMP22 assay was 85.7% (95% CI, 83.8%-87.6%) compared with 99.2% (95% CI, 98.7%-99.7%) for cytology. The proteomic marker detected 4 cancers that were not visualized during initial endoscopy, including 3 that were muscle invasive and 1 carcinoma in situ.



The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the accuracy of cystoscopy, with test results available during the patient visit.