nils-herrmann/clean_scirepeval huggingface dataset:
Self-reported calcium use in a cohort of postmenopausal women receiving osteoporosis therapy: results from POSSIBLE US™

Calcium use was common and remained high among women on osteoporosis therapy. Use of calcium-supplemented pharmacologic therapy increased from 65.1 to 76.0 % in these women (mean follow-up, 27.5 months). Over 12 months, calcium discontinuation was fairly similar among women using calcium only (23.7 %) and women supplementing pharmacologic therapy with calcium (22.5 %). Calcium has an important role in bone health. This study describes calcium use and persistence in a postmenopausal osteoporosis treatment cohort. Subject-reported calcium use was analyzed for 3,722 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE USTM) who used calcium either as their sole osteoporosis treatment (calcium only) or to supplement pharmacologic osteoporosis therapy (supplementers). Descriptive analyses were conducted. Kaplan-Meier methods were used to estimate the probability of discontinuing calcium therapy, and logistic regression was used to assess associations (age-adjusted odds ratios) between healthy behaviors and calcium use. At entry, there were 711 calcium-only subjects and 1,960 of 3,011 subjects on pharmacologic osteoporosis therapy also supplementing with calcium (supplementers). The percentage of supplementers increased from 65.1 to 76.0 % during follow-up (mean, 27.5 months). During the first 12 months on study, the probability of calcium discontinuation was 23.7 % (95 % confidence interval [CI], 20.7 − 27.0) among calcium-only subjects and 22.5 % (95 % CI, 20.7–24.5) among supplementers. Supplementers who discontinued pharmacologic therapy were more likely to discontinue calcium than supplementers who continued pharmacologic therapy (34.9 versus 14.8 %). Overall 54.2 % of calcium-only subjects who discontinued calcium and 42.3 % of supplementers who discontinued calcium resumed calcium use during follow-up. Regular exercise was positively correlated with calcium use at study entry. Calcium supplementation in pharmacologically treated subjects increased over time. Persistence with calcium was high. Discontinuation of pharmacologic osteoporosis therapy was associated with an increased likelihood of discontinuing calcium use.
The role of nicotine on respiratory sensory gating measured by respiratory-related evoked potentials.

Respiratory perception can be altered by changes in emotional or psychological states. This may be due to affective (i.e., anxiety) modulation of respiratory sensory gating. Nicotine withdrawal induces elevated anxiety and decreased somatosensory gating. Respiratory sensory gating is evidenced by decreased amplitude of the respiratory-related evoked potentials (RREP) N(1) peak for the second occlusion (S2) when two 150-ms occlusions are presented with a 500-ms interval during an inspiration. The N(1) peak amplitude ratio of the S2 and first occlusion (S1) (S2/S1) is <0.5 and due to central neural sensory gating. We hypothesized that withdrawal from nicotine is anxiogenic and reduces respiratory gating in smokers. The RREP was recorded in smokers with 12-h withdrawal from nicotine and nonsmokers using a paired occlusion protocol. In smokers, the RREP was measured after nicotine withdrawal, then with either nicotine or placebo gum, followed by the second RREP trial. Nonsmokers received only placebo gum. After nicotine withdrawal, the smokers had a higher state anxiety compared with nonsmokers. There was a significant interaction between groups (nonsmokers vs. smokers with nicotine vs. smokers with placebo) and test (pre- vs. posttreatment) in RREP N(1) peak amplitude S2/S1. The S2/S1 in the smokers were larger than in nonsmokers before treatment. After gum treatment, the smoker-with-placebo group had a significantly larger S2/S1 than the other two groups. The S2/S1 was significantly decreased after the administration of nicotine gum in smokers due to significantly decreased S2 amplitudes. The RREP N(f) and P(1) peaks were unaffected. These results demonstrated that respiratory sensory gating was decreased in smokers after nicotine withdrawal. Nicotine increased respiratory sensory gating in smokers with a S2/S1 similar to that of the nonsmokers. Nicotine did not change respiratory sensory information arrival, but secondary information processing in respiratory sensation.
Effect of gradually lowering dialysate sodium concentration on the interdialytic weight gain, blood pressure, and extracellular water in anuric hemodialysis patients.

The majority of hemodialysis (HD) patients are overhydrated and have high interdialytic weight gain (IDWG) which induces increased blood pressure (BP). The positive sodium balance resulting from a high sodium diet, a high dialysate sodium concentration (DNa), or a combination of both is major causes of this disease. We evaluated the effects of lowering DNa on IDWG, BP, and volume status in anuric HD patients with dietary sodium restriction.



Thirty-two patients were enrolled in this study and the period was divided by phase 1 and 2 according to DNa which decreased from 140 to 135 mEq/L at a rate of 1 mEq/L per month; phase 1, 140 mEq/L; phase 2, 135 mEq/L. We compared the IDWG, BP, volume status measured by multifrequency bioimpedance spectroscopy, and adverse events such as intradialytic hypotension, cramps, and headache of both phases.



The IDWG was significantly reduced by 0.39 ± 0.38 kg (p = 0.000). Pre-dialysis BP showed significant reduction (systolic pressure 146 ± 18 vs. 138 ± 22 mmHg; p = 0.012, diastolic pressure 80 ± 10 vs. 75 ± 11 mmHg; p = 0.008). Pre-dialysis extracellular water (ECW) was reduced significantly by 0.13 ± 2.22 L (p = 0.02). There was no significant increase in adverse events (all p > 0.05).



This study showed that gradually lowering DNa could bring a significant reduction in pre-dialysis IDWG, BP, and ECW without increased adverse events. Large and crossover designed study will be needed to demonstrate the clear causal relationship.
The effect of midazolam on transient insomnia

We have assessed the effect of midazolam on sleep in a model of transient insomnia in healthy adults using polysomnographic recordings. The subjects were randomly assigned to one of three treatment groups (placebo or midazolam 7.5 or 15 mg) and spent a single night in the sleep laboratory. Midazolam or placebo were given double-blind immediately, before turning off the lights. Midazolam 15 mg was effective in inducing sleep, while 7.5 mg and 15 mg produced improvemnt in the maintenance of sleep. Subjectively, sleep latency and the number of awakenings were reduced dose-dependently. Midazolam did not impair psychomotor performance on the morning after administration.
Gene expression profiles in circulating tumor cells to predict prognosis in metastatic breast cancer patients.

A circulating tumor cell (CTC) count is an established prognostic factor in metastatic breast cancer (MBC). Besides enumeration, CTC characterization promises to improve outcome prediction and treatment guidance. Having shown the feasibility of quantifying clinically relevant mRNA transcripts in CTCs, we determined the prognostic value of CTC gene expression in MBC.



CTCs were isolated and enumerated from blood of 197 MBC patients who were about to start first-line systemic therapy. Of these, 180 were assessable for quantification of mRNA expression by RT-qPCR in relation to time-to-treatment failure (TTF). A prognostic CTC gene profile was generated by leave-one-out cross validation in a 103 patient discovery set and validated in 77 patients. Additionally, all 180 patients were randomly divided into two equal sets to discover and validate a second prognostic profile.



CTC count predicted for TTF at baseline {≥5 versus <5 CTCs/7.5 ml blood, hazard ratio (HR) 2.92 [95% confidence interval (CI) 1.71-4.95] P < 0.0001}. A 16-gene CTC profile was generated in the first discovery set, which identified patients with death or TTF <9 months versus those with a better outcome. In multivariate analysis, the 16-gene profile was the only factor associated with TTF [HR 3.15 (95% CI 1.35-7.33) P 0.008]. Validation of this profile in the independent patient set pointed into the same direction, but was not statistically significant. A newly generated 8-gene profile showed similarly favorable test characteristics as the 16-gene profile, but did not significantly pass validation either.



A 16-gene CTC profile was identified, which provided prognostic value on top of CTC count in MBC patients. However, validation of this profile in an independent cohort, nor of a second profile, reached statistical significance, underscoring the need to further fine-tune the still promising approach of CTC characterization.
Renal safety in pediatric imaging: randomized, double-blind phase IV clinical trial of iobitridol 300 versus iodixanol 270 in multidetector CT

It is debated whether iso-osmolar and low-osmolar contrast media are associated with different incidences of contrast medium-induced nephropathy (CIN) in patients with renal insufficiency. To compare the incidence of CIN in children undergoing contrast-enhanced multidetector computer tomography (MDCT) with intravenous injection of low-osmolar (iobitridol, Xenetix® 300) or an iso-osmolar (iodixanol, Visipaque® 270) iodinated contrast medium. One hundred forty-six children with normal renal function were included in this multicenter trial and underwent contrast-enhanced MDCT. The primary endpoint was the relative change in creatinine clearance from 48 h pre- to 72 h postcontrast medium administration using a noninferiority analysis in the intent-to-treat (ITT, n = 128) and per protocol (n = 68) populations. Secondary endpoints were incidence of CIN, global image quality, diagnostic efficacy and clinical safety. In the ITT population, the noninferiority of iobitridol over iodixanol was demonstrated. CIN incidence was 4.8% (three cases) with iobitridol and 10.6% (seven cases) with iodixanol (not significant). No statistically significant differences were observed for the secondary endpoints. Comparable satisfactory safety profiles were confirmed for both contrast media, with no significant difference in the incidence of CIN in children with normal renal function.
Influence of clinical and demographic variables on mycophenolic acid pharmacokinetics in antineutrophil cytoplasmic antibody-associated vasculitis.

Mycophenolic acid (MPA) is used off-label to treat many forms of glomerulonephritis.



To evaluate the pharmacokinetics of MPA and its glucuronide (MPAG) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients with renal manifestations and to determine the effects of clinical (urinary protein excretion, serum albumin, creatinine clearance) and demographic (age, race, sex) variables on MPA and MPAG pharmacokinetics.



Twenty-three patients taking MPA at steady-state were evaluated. Plasma and urine samples were collected over 24 hours. Analyses included noncompartmental pharmacokinetics and statistics including Mann-Whitney U test and univariate/multiple regression.



MPA clearance (Cl/F 288 +/- 154 mL/min) was approximately 2-fold higher than previously reported from transplant patients and predicted by weight and race (ranked MPA Cl/F = -11.766 + 0.2035 [wt] + 4.9578 [race]; R(2) 41.8%; p = 0.005). Creatinine clearance (CrCl) less than 60 mL/min resulted in higher MPA exposure, total area under the curve (AUC)(0-12), and AUC(6-12), as well as unbound AUC(0-12). The metabolic ratio (MPAG(AUC)/MPA(AUC)) of 8.67 +/- 5.57 was lower than that previously reported in renal transplant recipients.



Diminished kidney function (eg, CrCl <60 mL/min) demonstrated enhanced MPA and MPAG exposure in patients with ANCA vasculitis. However, unlike renal transplant recipients, patients with ANCA vasculitis had enhanced Cl/F and diminished metabolic ratio, suggesting the need to comprehensively evaluate the role of disease-specific factors on MPA pharmacokinetics.
The influence of volatile anesthetics on alveolar epithelial permeability measured by noninvasive radionuclide lung scan.

Many volatile anesthetics have long been thought to affect pulmonary functions including lung ventilation (LV) and alveolar epithelial permeability (AEP). The purpose of this study is to examine the influence of volatile anesthetics on LV and AEP by noninvasive radionuclide lung imaging of technetium-99m labeled diethylene triamine pentaacetic acid radioaerosol inhalation lung scan (DTPA lung scan). Twenty patients undergoing surgery and receiving volatile anesthesia with 1% halothane were enrolled as the study group 1. The other 20 patients undergoing surgery and receiving volatile anesthesia with 1.5% isoflurane were enrolled as the study group 2. At the same time, 20 patients undergoing surgery with intravenous anesthesia drugs were included as a control group. Before surgery, 1 hour after surgery, and 1 week after surgery, we investigated the 3 groups of patients with DTPA lung scan to evaluate LV and AEP by 99mTc DTPA clearance halftime (T1/2). No significant change or abnormality of LV before surgery, 1 hour after surgery, or 1 week after surgery was found among the 3 groups of patients. In the control group, the 99mTc DTPA clearance T1/2 was 63.5 +/- 16.4, 63.1 +/- 18.4, and 62.8 +/- 17.0 minutes, before surgery, 1 hour after surgery, and 1 week after surgery, respectively. In group 1, it was 65.9 +/- 9.3, 62.5 +/- 9.1, and 65.8 +/- 10.3 minutes, respectively. No significant change in AEP before surgery, 1 hour after surgery, or 1 week after surgery was found. However, in group 2, the 99mTc DTPA clearance T1/2 was 65.5 +/- 13.2, 44.9 +/- 10.5, and 66.1 +/- 14.0 minutes, respectively. A significant transient change in AEP was found 1 hour after surgery, but it recovered 1 week after surgery. We conclude that volatile anesthesia is safe for LV and AEP, and only isoflurane can induce transient change of AEP.
Preoperative plasma TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer: a prospective validation study.

Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent population-based cohort of patients with CRC.



During 2000-2003, plasma and serum were collected preoperatively from 322 patients treated for primary CRC. TIMP-1 and CEA levels were determined by validated ELISA platforms.



High TIMP-1 and CEA levels each associated with poor overall survival (OS); TIMP-1 (hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6-2.7) and CEA (HR 1.2; 95% CI 1.1-1.3), and disease-free survival (DFS); TIMP-1 (HR 2.0; 95% CI: 1.5-2.6) and CEA (HR 1.2; 95% CI: 1.1-1.4) in univariate analyses. In stratified analyses of stages II and III, TIMP-1 levels associated significantly with OS and DFS in stages II and III, associations were not found for CEA. Multivariate analysis for OS, including TIMP-1 and CEA levels and clinico-pathological baseline variables, revealed significant association of TIMP-1 (HR 1.8; 95% CI 1.3-2.4) but not CEA levels.



This independent prospective validation study confirms the significant association between preoperative plasma TIMP-1 levels and survival of CRC patients: TIMP-1 provided stronger prognostic information than CEA. Thus, this study brings plasma TIMP-1 to the next level of evidence for its clinical use as a prognostic marker in CRC patients.
Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432.

Combination vaccines of the NY-ESO-1 protein complexed with cholesteryl pullulan (CHP), CHP-NY-ESO-1, and the truncated 146HER2 protein with CHP, CHP-HER2, were subcutaneously administered with the immuno-adjuvant OK-432 to eight esophageal cancer patients. Vaccination was well-tolerated. NY-ESO-1- and HER2-specific antibody responses were analyzed using the patients' sera and samples from previous single CHP-NY-ESO-1 or CHP-HER2 vaccine trial. The responses to NY-ESO-1 in the combination vaccine study were comparable to the single vaccine. For responses to HER2, there were fewer antibody responses in the combination vaccines. Although there were marked individual variations in the antibody responses to the NY-ESO-1 and HER2 antigens, the reaction patterns to these antigens were comparable within each patient. Antibodies to OK-432 were not augmented. Protein cancer vaccines targeting multiple antigens are feasible.
Can somatosensory system generate frequency following response?

The aim of this study was to establish whether functional characteristics of the somatosensory system structures in man comply with the frequency following response (FFR) generators. Somatosensory cerebral evoked potentials (SsCEP) were recorded by skin electrodes, and spinal somatosensory evoked potentials (SpEP) both by epidural and skin electrodes. In SpEP and SsCEP to trains of electrical or mechanical stimuli, a decrease of the amplutude to subsequent stimuli was found. SpEP were also attenuated by higher stimulation rates. It is highly improbable, therefore, that somatosensory system can contribute to the FFR-like response recorded in profoundly deaf people.
Home blood pressure monitoring alone vs. combined clinic and ambulatory measurements in following treatment-induced changes in blood pressure and organ damage.

Out-of-office blood pressure (BP) measurement using home BP (HBP) or ambulatory BP (ABP) monitoring is often necessary for the accurate evaluation of hypertension. These methods have several similarities but also have major differences. Therefore, they are regarded as complementary, and there is uncertainty on how they should be applied in clinical practice. This study compared hypertension management based on clinic and ABP measurements or on HBP measurements alone.



Untreated subjects with elevated BP were randomized to treatment initiation and titration based on clinic and ABP measurements or on HBP measurements alone. Target organ damage was assessed at baseline and after 1 year of treatment with echocardiographic left ventricular mass index (primary endpoint), pulse wave velocity, and urinary albumin excretion.



A total of 145 subjects were randomized, and 116 completed the study (mean age = 50.7±10.5 years; 69 men (59%); mean follow-up = 13.4±1.4 months). There was no difference between the 2 arms in treatment-induced change in left ventricular mass index (mean difference = 0.50±1.11 g/m2; 95% confidence interval (CI) = -1.70 to 2.70). Moreover, there was no difference between the 2 arms in treatment-induced changes in pulse wave velocity (mean difference = -0.16±0.42 m/s; 95% CI = -0.99 to 0.66), urinary albumin excretion (mean difference = -0.85±4.28 mg/dl; 95% CI = -9.37 to 7.66), HBP and ABP levels, and hypertension control rates.



These data suggest that HBP monitoring alone is as reliable as combined clinic and ABP measurements in monitoring the effects of antihypertensive drug treatment on BP and preclinical target organ damage.
The CD226 gene in susceptibility of type 1 diabetes.

The rs763361 single nucleotide polymorphism (SNP) within the CD226 gene has recently been reported as a novel susceptible locus for type 1 diabetes. The CD226 gene is implicated in the regulation of a number of cells involved in immune mechanisms leading to beta-cell destruction in type 1 diabetes. The aim of the present study was to confirm the association of the CD226 gene with type 1 diabetes in Estonian population. The TT genotype [odds ratio (OR) = 2.29, 95% confidence interval (CI) = 1.25-4.18, P = 0.0071) and the T allele (OR = 1.48, 95% CI = 1.11-1.98, P = 0.0084) of the rs763361 SNP were associated with the risk of type 1 diabetes. The current study replicates the novel association of the rs763361 SNP in susceptibility of type 1 diabetes and supports the CD226 gene as a susceptible candidate locus for type 1 diabetes outside the major histocompatibility complex region.
Safety and efficacy of protease inhibitors to treat hepatitis C after liver transplantation: a multicenter experience.

Protease inhibitors (PI) with peginterferon/ribavirin have significantly improved SVR rates in HCV G1 patients. Their use to treat HCV recurrence after liver transplantation (LT) is a challenge.



This cohort study included 37 liver transplant recipients (male, 92%, age 57 ± 11 years), treated with boceprevir (n=18) or telaprevir (n=19). The indication for therapy was HCV recurrence (fibrosis stage ≥F2 (n=31, 83%) or fibrosing cholestatic hepatitis (n=6, 16%).



Eighteen patients were treatment-naive, five were relapsers and fourteen were non-responders to dual therapy after LT. Twenty-two patients received cyclosporine and fifteen tacrolimus. After 12 weeks of PI therapy, a complete virological response was obtained in 89% of patients treated with boceprevir, and 58% with telaprevir (p=0.06). The end of treatment virological response rate was 72% (13/18) in the boceprevir group and 40% (4/10) in the telaprevir group (p=0.125). A sustained virological response 12 weeks after treatment discontinuation was observed in 20% (1/5) and 71% (5/7) of patients in the telaprevir and boceprevir groups, respectively (p=0.24). Treatment was discontinued in sixteen patients (treatment failures (n=11), adverse events (n=5)). Infections occurred in ten patients (27%), with three fatal outcomes (8%). The most common adverse effect was anemia (n=34, 92%), treated with erythropoietin and/or a ribavirin dose reduction; thirteen patients (35%) received red blood cell transfusions. The cyclosporine dose was reduced by 1.8 ± 1.1-fold and 3.4 ± 1.0-fold with boceprevir and telaprevir, respectively. The tacrolimus dose was reduced by 5.2 ± 1.5-fold with boceprevir and 23.8±18.2-fold with telaprevir.



Our results suggest that triple therapy is effective in LT recipients, particularly those experiencing a severe recurrence. The occurrence of anemia and drug-drug interactions, and the risk of infections require close monitoring.
The Implementation and Appraisal of a Novel Confirmatory HIV-1 Testing Algorithm in the Microbicides Development Programme 301 Trial (MDP301)

We describe the application of a novel HIV confirmatory testing algorithm to determine the primary efficacy endpoint in a large Phase III microbicide trial. 9385 women were enrolled between 2005 and 2009. Of these women, 537 (6%) had at least one positive HIV rapid test after enrolment. This triggered the use of the algorithm which made use of archived serum and Buffy Coat samples. The overall sample set was >95% complete. 419 (78%) of the rapid test positive samples were confirmed as primary endpoints using a combination of assays for the detection of HIV-specific antibodies (EIA's and Western Blot), and for components of the virus itself (PCR for the detection of nucleic acids and EIA for p24 antigen). 63 (12%) cases were confirmed as being HIV-positive at screening or enrolment and 55 (10%) were confirmed as HIV negative. The testing algorithm confirmed the endpoint at the same visit as that of the first positive rapid test in 90% of cases and at the time of the preceding visit in 10% of cases. Of the 63 cases which were subsequently confirmed to be HIV-1 positive at or before enrolment, 54 specimens contained no detectable HIV antibodies at screening or enrolment. However, 43 were positive using an EIA which detects both HIV antigen and antibody and also had a positive p24 antigen or HIV PCR test, which was highly suggestive of acute infection. There were 6 unusual cases which had undetectable HIV-1 DNA or RNA. In 4 of the 6 cases the presence of HIV-1-specific antibodies was confirmed by Western Blot. One of these cases with an indeterminate Western Blot was a previous vaccine trial participant. The algorithm served the objectives of the study well and can be recommended for use in determining HIV as an endpoint in clinical trials.