nils-herrmann/clean_scirepeval huggingface dataset:
The mineralocorticoid receptor agonist, fludrocortisone, differentially inhibits pituitary–adrenal activity in humans with psychotic major depression

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been linked with major depression, particularly psychotic major depression (PMD), with mineralocorticoid receptors (MRs) playing a role in HPA-axis regulation and the pathophysiology of depression. Herein we hypothesize that the MR agonist fludrocortisone differentially inhibits the HPA axis of psychotic major depression subjects (PMDs), non-psychotic major depression subjects (NPMDs), and healthy control subjects (HCs).



Fourteen PMDs, 16 NPMDs, and 19 HCs were admitted to the Stanford University Hospital General Clinical Research Center. Serum cortisol levels were sampled at baseline and every hour from 18:00 to 23:00h, when greatest MR activity is expected, on two consecutive nights. On the second afternoon at 16:00h all subjects were given 0.5mg fludrocortisone. Mean cortisol levels pre- and post-fludrocortisone and percent change in cortisol levels were computed.



There were no significant group differences for cortisol at baseline: F(2,47)=.19, p=.83. There were significant group differences for post-fludrocortisone cortisol: F(2,47)=5.13, p=.01, which were significantly higher in PMDs compared to HCs (p=.007), but not compared to NPMDs (p=.18). There were no differences between NPMD's and HC's (p=.61). Also, PMDs had a lower percent change from baseline in cortisol levels at 2200h than NPMDs (p=.01) or HCs (p=.009).



Individuals with psychotic major depression compared to healthy control subjects have diminished feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis in response to the mineralocorticoid receptor agonist fludrocortisone. To our knowledge, this is the first study to examine HPA axis response to MR stimulation in major depression (with and without psychosis), and only the third study to demonstrate that exogenously administered fludrocortisone can down-regulate the HPA axis in humans.
Feasibility of Transseptal Puncture Using a Nonfluoroscopic Catheter Tracking System.

Radiation exposure in the electrophysiology lab is a major occupational hazard to the electrophysiologists. A catheter localization system (MediGuide Technology, St. Jude Medical Inc., St. Paul, MN, USA) allows the integration of electroanatomical mapping and x-ray imaging, and has been shown to be effective in reducing radiation exposure during several electrophysiological procedures. We intended to evaluate the feasibility of this catheter tracking system to guide transseptal (TS) access.



The feasibility of performing TS puncture with MediGuide (MDG) was assessed in a prospective observational study in 16 patients undergoing radiofrequency ablation for atrial fibrillation. These patients were compared to 16 matched patients undergoing similar procedures during the same time frame using conventional approach. There were no differences in mean age, gender distribution, and body mass index between the two groups. Total duration of fluoroscopic exposure during TS puncture was compared between the two groups.



All patients underwent successful TS puncture. Fluoroscopy time for double TS puncture using the MDG system was significantly lower than the control group (0.48 ± 0.17 minutes vs. 5.9 ± 0.65 minutes; P < 0.0001). No major complications occurred during the procedures in either group.



TS puncture can be successfully performed using MDG, and results in significant reduction in radiation exposure.
Serotonin transporter promoter region polymorphisms do not influence treatment response to escitalopram in patients with major depression

Several studies and meta-analyses have implicated a polymorphism in the promoter region of the serotonin transporter (5-HTT) gene, 5-HTTLPR in treatment outcomes of selective serotonin re-uptake inhibitors in patients with major depression. In this study we investigated the impact of 5-HTTLPR and a functional SNP rs25531 on the treatment outcomes to escitalopram in depressive patients. The study sample consisted of 135 outpatients with major depressive disorder (mean age 31.1+/-11.6 years, 68% females) treated with escitalopram 10-20 mg/day for 12 weeks. There were no significant associations between 5-HTT promoter region polymorphisms and response rate or mean change of depressive symptoms during escitalopram treatment. However we showed that patients carrying S allele of 5-HTTLPR may have increased risk for some side effects, including headache, induced by escitalopram medication.
The efficacy of sublingual immunotherapy for respiratory allergy is not affected by different dosage regimens in the induction phase.

Sublingual administration of allergens is a safe and effective alternative to subcutaneous immunotherapy in patients with respiratory allergies. A drawback to this therapeutic approach is the relatively long and complex management of the induction phase.



To determine whether different induction regimens affect the outcome of sublingual immunotherapy.



Adult and pediatric patients with allergic rhinoconjunctivitis and/or asthma were included in the study. Ten subjects served as controls and received symptomatic treatments. Forty-three subjects were allocated to sublingual immunotherapy, with three different induction protocols (8-, 15- and 20-day, respectively). Symptom and medication scores, skin test results and (in asthmatic patients) FEV1 values were monitored for two years. Adverse effects were recorded. All induction regimens produced a significant improvement in symptom and medication usage (p < 0.0001); skin test scores decreased (p < 0.0001) and FEV1 improved (p < 0.05). In contrast, symptom and skin test scores did not significantly change in controls. No relevant adverse effects were observed with any of the induction regimens.



For patients with respiratory allergies, sublingual immunotherapy with an 8-day induction protocol is safe and effective. Our results encourage the usage of shorter induction regimens, which produce better compliance with this therapy.
A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study

Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) - tiotropium and glycopyrronium. Previous studies have compared glycopyrronium with open-label tiotropium. In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.



In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily. The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: -50 mL). Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George's Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.



657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study. Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: -32, 31 mL). Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0-4 h post-dose versus tiotropium (all p < 0.001). FEV1 area under the curve from 0-4 h (AUC0-4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12. Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant). Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035). Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).



In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.
Aspirin plus calcium supplementation to prevent
superimposed preeclampsia: a randomized trial

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.
Efficient detection of leukemia-related fusion transcripts by multiplex PCR applied on a microelectronic platform

The identification of prognostically relevant fusion genes is required in the routine diagnostic process of most advanced clinical protocols for leukemia patients, either for risk stratification, target-specific treatments, and/or as markers for monitoring Minimal Residual Disease during treatment. However, there is emerging need to implement diagnostics and patient classification based on other biological features, such as expression levels of specific genes or genomic polymorphisms and/or mutations. This advancement would ideally be pursued in a diagnostic laboratory by an unique platform capable of different diagnostic purposes. We developed a rapid, accurate and reproducible assay to screen for the most common fusion gene transcripts in human leukemia, which combines a multiplex RT–PCR approach with the electronic hybridization and fluorescent detection on the Nanogen NanoChip Molecular Biology Workstation. This study demonstrates, as a proof-of-principle, that this microelectronic device, highly effective in detecting single base mutations, is also efficient in the analysis of gene expression, thus providing as a multi-purpose platform for relevant comprehensive diagnostics of hemato-oncology patients.
Polymorphisms of adrenoceptors are not associated with an increased risk of adverse event in heart failure: a MERIT-HF substudy.

Enhanced sympathetic activation has a central role in the development of heart failure (HF). We assessed whether the alpha(2C)-adrenoceptor (Del322-325) polymorphism exclusively or in combination with a beta(1)-adrenoceptor (Arg389) polymorphism, each with known independent effects on sympathetic function, were associated with an increased risk of adverse events in HF.



A total of 526 patients enrolled in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure study were genotyped for both adrenoceptor polymorphisms. The distribution of alpha(2C) genotypes was similar between the event and nonevent groups. However, a reduced prevalence of the Del322-325 allele was found in individuals with ischemic congestive HF (P=.022). Patients possessing both the alpha(2C) Del322-325 and beta(1) Arg389 alleles had no increased risk of events. Adjusting for confounding variables and the beta(1) Arg389Gly polymorphism, the odds ratio of being ins/del + del/del for the alpha(2C) Del322-325 and having an event was 0.89 with 95% CI 0.49-1.63, P=.715. Similarly, adjusting for confounding variables and the alpha(2C) Del322-325 polymorphism the odds ratio of being Arg/Arg or Arg/Gly for the beta(1) Arg389Gly polymorphism and having an event was 1.13 with 95% CI 0.52-2.17, P=.864.



The alpha(2C) Del322-325 polymorphism exclusively or in combination with the beta(1)Arg389 allele is not associated with an increased risk of adverse events in HF.
Safety and tolerability of immune globulin intravenous (human), 10% solution in Japanese subjects with mild to moderate Alzheimer's disease.

Immune globulin intravenous (IGIV), 10% is a donor-derived polyclonal human immunoglobulin G antibody mixture that has potent immune modulatory properties and contains conformation selective anti-amyloid antibodies. We evaluated the safety and tolerability of multiple doses of IGIV, 10% in Japanese patients with mild to moderate Alzheimer's disease.



Among the 16 subjects, 12 subjects were assigned to the IGIV group and 4 subjects to the placebo group. Subjects received a total of six infusions of either IGIV at a dose of 0.2 or 0.4 g/kg, or placebo every 2 weeks.



A total of 33 treatment-emergent adverse events (TEAE) occurred in 14 subjects: 13 TEAE in five subjects in both the IGIV 0.2 and 0.4 g/kg groups, and 7 TEAE in four subjects in the placebo group. The most common TEAE in the IGIV subjects were nasopharyngitis, injection-site swelling, and erythema. All 26 TEAE in the IGIV group were considered to be mild. Only one mild TEAE (rash) was considered to be possibly related to the study drug. There were no significant differences in incidence of TEAE between the treatment groups. Four serious TEAE were reported, and all of these were considered to be unrelated to the study treatment. Other assessments related to safety revealed neither clinically significant abnormal values nor findings in the study.



IGIV is generally safe and well tolerated with multiple intravenous infusions at doses of 0.2 g/kg and 0.4 g/kg in Japanese patients with mild to moderate Alzheimer's disease.
Humanized anti-interleukin-6-receptor antibody (tocilizumab) monotherapy is more effective in slowing radiographic progression in patients with rheumatoid arthritis at high baseline risk for structural damage evaluated with levels of biomarkers, radiography, and BMI: data from the SAMURAI study

Our aim was to assess the ability of tocilizumab monotherapy to reduce progressive structural joint damage in rheumatoid arthritis patients at high risk of progression. This study was a subanalysis from a prospective 1-year, multicenter, X-ray-reader-blinded, randomized controlled trial of tocilizumab [Study of Active Controlled Monotherapy Used for Rheumatoid Arthritis, an IL-6 Inhibitor (SAMURAI) trial]. All patients were categorized into two or three groups according to four independent predictive markers for progressive joint damage [urinary C-terminal crosslinking telopeptide (uCTX-II), urinary pyridinoline/deoxypyridinoline (uPYD/DPD) ratio, body mass index (BMI), and joint-space narrowing (JSN) score at baseline]. One-year progression of joint destruction was assessed in high-risk versus low-risk groups receiving tocilizumab monotherapy and compared with patients receiving conventional disease-modifying antirheumatic drugs (DMARDs) (n = 157 and 145, respectively). In patients at high risk of progression of erosion as estimated by high uCTX-II, uPYD/DPD, or low BMI, and at high risk of progression of JSN as estimated by low BMI or high JSN score, the 52-week changes in radiological erosion and JSN, respectively, were significantly less in patients treated with tocilizumab monotherapy compared with those receiving DMARDs for each type of risk factor. In patients at low risk, those receiving tocilizumab also progressed less than those on DMARDs, although the difference did not reach statistical significance. Tocilizumab monotherapy is more effective in reducing radiological progression in patients presenting with risk factors for rapid progression than in low-risk patients. Patients at high risk for progression may benefit more from tocilizumab treatment.
National outcomes after gastric resection for neoplasm.

That factors affecting outcomes of surgical resection in the treatment of gastric cancer can be identified using a large US database.



Retrospective observational study.



The Nationwide Inpatient Sample from January 1, 1998, through December 31, 2003.



We included 13 354 patient discharges (approximately 66 096 nationally by weighted analysis) who underwent gastric resection for neoplasm.



In-hospital mortality. Univariate analyses were performed by means of chi(2) tests. A multivariate logistic regression was performed to determine which variables were independently predictive of in-hospital mortality.



During the study period, 50 738 patients (approximately 250 420 nationally) were discharged with the diagnosis of gastric neoplasm. Of those, 13 354 (26.3%) underwent gastric resection during their hospitalization. In-hospital mortality for patients undergoing surgery was 6.0%, without significant change from 1998 through 2003. Factors predictive of significantly increased in-hospital mortality included low annual hospital surgical volume (lowest [<or= 4 gastrectomies per year] vs highest [>or= 11 gastrectomies per year], 6.8% vs 4.9%; adjusted odds ratio [OR], 1.5; 95% confidence interval [CI], 1.2-1.8]), older patient age (50-69 vs <50 years, 4.0% vs 2.1%; adjusted OR, 1.5; 95% CI, 1.1-2.2) (>or =70 vs <50 years, 8.6% vs 2.1%; adjusted OR, 2.9; 95% CI, 2.0-4.3), male sex (male vs female, 6.7% vs 5.0%; adjusted OR, 1.3; 95% CI, 1.1-1.5), and procedure type (total gastrectomy vs all other resections, 8.0% vs 5.3%; adjusted OR, 1.4; 95% CI, 1.2-1.7).



Higher annual surgical volume is predictive of lower in-hospital mortality for patients undergoing gastric resection for neoplasm. Other factors significantly associated with superior outcomes after gastric resection included diagnosis type, procedure type, younger age, female sex, and fewer comorbid conditions.
Seed migration in prostate brachytherapy depends on experience and technique.

To determine seed loss and pulmonary migration rate over time in permanent seed prostate brachytherapy.



We analyzed the first 495 patients treated in our department. All patients were treated with loose (125)I seeds with automated seed delivery system and real-time intraoperative planning. Pelvic fluoroscopic imaging was done 30 days after the implant. Patients were divided into five groups of 100 patients according to the order they were treated, and groups were compared using χ(2) test and one-way analysis of variance.



A total of 22.8% of patients lost at least one seed. The highest percentage of patients losing any number of seeds was in the first 100. Thirty-eight percent lost at least one seed. This number decreased gradually and was only 9% in Patients 400-499. The mean total seed loss rate (number of seeds lost/number seeds implanted) changed significantly over time (p<0.001). There was a continuous significant (p<0.001) decline after the first 100 patients (1.25% for the first 100 patients) followed by a rise in Patients 300-399, followed by another decline (0.21% for the last 100 patients). The seed loss rate to the thorax changed significantly over time (p=0.009). It rose after an initial rate of 0.25-0.42% in Patients 200-299 and 300-399 and declined later to a rate of 0.21% in the last 100 patients.



We found a learning curve for seed migration. Avoiding implanting seeds outside of the capsule and modern transrectal ultrasound imaging can help decrease migration.
Efficacy and safety of nicotinamide in the management of hyperphosphatemia in pediatric patients on regular hemodialysis

Hyperphosphatemia is a common problem in patients with end-stage renal disease (ESRD) who are on maintenance hemodialysis (HD) and contributes to the development of secondary hyperparathyroidism and cardiovascular complications. Nicotinamide (NAM) has been shown in some studies to inhibit intestinal and renal sodium/phosphorus co-transporters and reduce serum phosphorus levels. We have therefore evaluated the efficacy and safety of NAM as adjunctive therapy to calcium-based phosphate binders to control hyperphosphatemia in hemodialysis patients. Sixty pediatric HD outpatients were randomly divided into two equally sized groups (30 children each). One group received calcium-based phosphate binder (control group), and the other received both the calcium-based phosphate binder + NAM at a dose of 100 mg twice or three times daily (nicotinamide group). Both groups were followed for a 6-month period. Over the 6-month treatment period, children in the NAM group showed a significant decline in the levels of serum phosphorus (p = 0.0001), serum calcium–phosphorus (Ca × P; p = 0.0001) product and parathyroid hormone (p = 0.02) versus baseline values and those of the control group. After 6 months of NAM treatment, the mean serum high-density lipoprotein cholesterol levels had increased significantly (p = 0.01), and the median serum triglyceride levels had decreased (p = 0.009). There was no significant change in any of these parameters among the children of the control group. The major adverse events associated with the NAM therapy were diarrhea, flushing and nausea. The addition of NAM to therapy with phosphate binders is effective in lowering phosphorus levels and has a beneficial effect on the lipid profile with only mild side effects.