nils-herrmann/clean_scirepeval huggingface dataset:
Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine.

Tamoxifen, a selective estrogen receptor modulator (SERM), is converted to 4-hydroxy-tamoxifen and other active metabolites by cytochrome P450 (CYP) enzymes. Selective serotonin reuptake inhibitors (SSRIs), which are often prescribed to alleviate tamoxifen-associated hot flashes, can inhibit CYPs. In a prospective clinical trial, we tested the effects of coadministration of tamoxifen and the SSRI paroxetine, an inhibitor of CYP2D6, on tamoxifen metabolism.



Tamoxifen and its metabolites were measured in the plasma of 12 women of known CYP2D6 genotype with breast cancer who were taking adjuvant tamoxifen before and after 4 weeks of coadministered paroxetine. We assessed the inhibitory activity of pure tamoxifen metabolites in an estradiol-stimulated MCF7 cell proliferation assay. To determine which CYP isoforms were involved in the metabolism of tamoxifen to specific metabolites, we used CYP isoform-specific inhibitors. All statistical tests were two-sided.



We separated, purified, and identified the metabolite 4-hydroxy-N-desmethyl-tamoxifen, which we named endoxifen. Plasma concentrations of endoxifen statistically significantly decreased from a mean of 12.4 ng/mL before paroxetine coadministration to 5.5 ng/mL afterward (difference = 6.9 ng/mL, 95% confidence interval [CI] = 2.7 to 11.2 ng/mL) (P =.004). Endoxifen concentrations decreased by 64% (95% CI = 39% to 89%) in women with a wild-type CYP2D6 genotype but by only 24% (95% CI = 23% to 71%) in women with a variant CYP2D6 genotype (P =.03). Endoxifen and 4-hydroxy-tamoxifen inhibited estradiol-stimulated MCF7 cell proliferation with equal potency. In vitro, troleandomycin, an inhibitor of CYP3A4, inhibited the demethylation of tamoxifen to N-desmethyl-tamoxifen by 78% (95% CI = 65% to 91%), and quinidine, an inhibitor of CYP2D6, reduced the subsequent hydroxylation of N-desmethyl-tamoxifen to endoxifen by 79% (95% CI = 50% to 108%).



Endoxifen is an active tamoxifen metabolite that is generated via CYP3A4-mediated N-demethylation and CYP2D6-mediated hydroxylation. Coadministration of paroxetine decreased the plasma concentration of endoxifen. Our data suggest that CYP2D6 genotype and drug interactions should be considered in women treated with tamoxifen.
An Intergenerational Approach to Prostate Cancer Education: Findings from a Pilot Project in the Southeastern USA

African Americans (AA) are more likely to develop and die from cancer than any other racial or ethnic group. This study assessed older and younger/middle-aged African-American (AA) men’s (1) knowledge and attitudes about prostate cancer (PrCA) and PrCA screening, (2) participation in clinical research, and (3) health and cancer-related decision making. Twenty-eight AA men (14 older, mean age 59.8; 14 younger/middle age, mean age 30.4) received a PrCA education program and completed pre/post-education program surveys, as well as qualitative post-education interviews. Younger/middle-aged men were more knowledgeable about PrCA and PrCA screening than older men. Older men reported being invited to participate in a clinical trial more often than younger men but were more likely to report that participation in clinical trials was risky and they did not plan to participate in medical research in the future. Younger/middle-aged men were more willing to participate in a clinical trial in the future and reported fewer barriers to participation in clinical research. There is potential for using intergenerational communication strategies with older/younger AA male dyads in PrCA interventions.
Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial.

Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old.



We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine.



The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49-1.35) for survival and of 0.67 (95% CI, 0.42-1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22-1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22-1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40-3.42) and that for disease-free survival was 1.02 (99% CI, 0.40-2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65-2.27) for survival and 1.02 (95% CI, 0.56-1.85) for disease-free survival.



Patients with a donor and candidates for allogeneic stem cell transplantation in first complete remission may have a better disease-free survival than those without a donor in case of myelodysplastic syndromes with intermediate/high-risk cytogenetics. Autologous peripheral blood stem cell transplantation does not provide longer survival than intensive chemotherapy.
Response to potent anti-HBV agents in chronic hepatitis B and combined effect of HBV reverse transcriptase mutations.

Response to nucleos(t)ide analogue therapy against HBV infection depends on a number of factors. One of them is appearance of drug resistance mutations. The present study aimed to investigate the efficacy of ETV and TDF as anti-HBV agents and to analyze the role of HBV-RT mutations in reducing the efficacy of mentioned drugs.



Sixty nine treatment naïve CHB patients (mean age 33.8 ± 11.9 years) were enrolled and treated with ETV or TDF for one year. Complete virological response (CVR) was defined as undetectable serum HBV DNA after 12 months of therapy. Amino acid and nucleotide sequence analyses of HBV-RT region were performed using Geno2pheno HBV drug resistance tool. The 3D model of HBV-RT protein was built by I-TASSER server and RMSD was calculated between wild type and mutated HBV-RT protein.



After 12 months of treatment, four CHB patients did not achieve CVR and all of them were with HBV genotype D. HBeAg seroconversion was achieved in 56% HBeAg positive patients after 12 months of antiviral therapy. The HBV-RT amino acid sequences from these four patients were used for in-silico analysis. It was found that the presence of many mutations in HBV-RT region of HBV isolated from these patients led to a high degree of variation in configuration of atoms of HBV-RT protein and also caused displacement of active site of this protein.



The efficacy of antiviral drugs in inhibiting HBV replication may be reduced by combined effect of many HBV-RT mutations; however, an in vitro study is needed to validate the findings.
[External multicentric validation of two scores predicting the risk of relapse in patients with borderline ovarian tumors: The nomogram of Bendifallah and the score of Ouldamer].

Borderline ovarian tumors are rare and can occur in young women. For these patients, a fertility sparing surgery should be discussed. Two predicting borderline ovarian tumor relapse risk models were developed in 2014 (Nomogram of Bendifallah) and 2017 (Score of Ouldamer). This study aimed to valid in an external population, these two scores using a multi-institutional BOT database.



In this bicentric and retrospective study, all consecutive patients comprising the variable nomogram documented treated between January 2006 and December 2012 for BOT in centre hospitalier de Poissy-Saint-Germain and hôpital René-Huguenin were included. A ROC model was established for each predicting scores.



Sixty-five patients were included in the study. Twelve patients showed a recurrence (19%), three of them experienced an infiltrative cancer (5%). The median time of recurrence was 25 months (range: 8-115). The concordance index for the Nomogram of Bendifallah and the Score of Ouldamer were 0.88 (IC 95% [0.78-0.98]) and 0.87 (IC 95% [0.77-0.96]) respectively.



This study from an independent population valids the Bendifallah nomogram and Ouldamer score for clinical use in predicting borderline ovarian recurrence.
The Effect of Different Feed Delivery Methods on Time to Consume Feed and the Resulting Changes in Postprandial Metabolite Concentrations in Horses by Jenna

KUTZNER-MULLIGAN, JENNA MARIE GILCHRIST. The Effect of Different Feed Delivery Methods on Time to Consume Feed and the Resulting Changes in Post-prandial Metabolite Concentrations in Horses. (Under the direction of Dr. Shannon Pratt-Phillips.) Management techniques that reduce the insulin response to feeding in horses have application in preventing insulin resistance (IR) and potential associations (e. g., laminitis). Eight mature idle horses of BCS between 5 and 6.5 and with no previous indication of IR were fed a meal of concentrate feed under 4 feed delivery treatments in a repeated Latin Square design. Treatments were all based on a bucket of equal dimensions. The treatments included a control (CON) and 3 treatments hypothesized to increase time to consume feed (TIMEfeed): mobile obstacles above the feed (BALL), stationary obstacles below the feed (WAFF), and feed with water added (WTR). Jugular venous blood samples were taken at feed delivery, every 10 min for the first hour, and then every 30 min until 300 min post feed delivery. TIMEfeed was greater (P = 0.004) for BALL and WAFF when compared to CON and WTR. Compared to CON and WTR, average glucose and insulin concentrations tended to decrease due to BALL (P = 0.059) and WAFF (P = 0.072) and the peak glucose concentration was decreased (P = 0.049). Compared to all other treatments, peak insulin concentrations (P = 0.030) and area under the curve of insulin (P = 0.051) were decreased and time to peak insulin was increased (P = 0.031) due to BALL. Therefore, feed delivery methods that include obstacles effectively increase TIMEfeed and attenuate post-prandial glucose and insulin parameters. A second experiment was designed to determine if the TIMEfeed changes associated with BALL and WAFF in Exp. 1 remain effective over 4-d periods. Four horses with no recent or regular history of consuming meals were fed concentrate meals for 4 consecutive days using the same treatments described in Exp. 1 under a Latin Square design. Horses were subject to a 4-d adaptation period (ADP) and were randomly assigned to 4-d treatment periods using the 4 previously described treatments. During ADP, TIMEfeed decreased (P = 0.018). However, following adaptation, TIMEfeed did not decrease significantly over 4 days of any treatment feed delivery method, but BALL and WAFF had higher TIMEfeed when compared to CON and WTR (P < 0.001) and maintained prolonged TIMEfeed after 4 d of use (P = 0.006). Utilizing obstacles to increase TIMEfeed on a daily basis may be an effective method to reduce post-prandial glucose and insulin concentrations, thereby decreasing the risk of insulin resistance development in horses The Effect of Different Feed Delivery Methods on Time to Consume Feed and the Resulting Changes in Post-prandial Metabolite Concentrations in Horses by Jenna Marie Gilchrist Kutzner-Mulligan A thesis submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the Degree of Master of Science
Supportive monitoring and disease management through the internet: an internet-delivered intervention strategy for recurrent depression.

Major depression is a highly prevalent, disabling disorder associated with loss of quality of life and large economic burden for the society. Depressive disorders often follow a chronic or recurrent course. The risk of relapses increases with each additional episode. The internet-deliverable intervention strategy SUMMIT (SUpportive Monitoring and Disease Management over the InTernet) for patients with recurrent depression has been developed with the main objectives to prolong symptom-free phases and to shorten symptom-loaden phases. This paper describes the study design of a six-sites, three-arm, randomized clinical trial intended to evaluate the efficacy of this novel strategy compared to treatment as usual (TAU). Two hundred thirty six patients who had been treated for their (at least) third depressive episode in one of the six participating psychiatric centers were randomized into one of three groups: 1) TAU plus a twelve-month SUMMIT program participation with personal support or 2) TAU plus a twelve-month SUMMIT program participation without personal support, or 3) TAU alone. Primary outcome of this study is defined as the number of "well weeks" over 24months after index treatment assessed by blind evaluators based on the Longitudinal Interval Follow-Up Evaluation. If efficacious, the low monetary and nonmonetary expenditures of this automated, yet individualized intervention may open new avenues for providing an acceptable, convenient, and affordable long-term disease management strategy to people with a chronic mental condition such as recurrent depression.
The effect of oxandrolone on the healing of chronic pressure ulcers in persons with spinal cord injury: a randomized trial.

Anabolic steroids have been reported to improve wound healing.



To determine whether oxandrolone increases the percentage of target pressure ulcers (TPUs) that heal compared with placebo and whether healed ulcers remain closed 8 weeks after treatment.



Parallel-group, placebo-controlled, randomized trial conducted from 1 August 2005 to 30 November 2008. Patients, clinical care providers, study personnel, and statisticians were blinded to treatment assignment. 
16 inpatient spinal cord injury (SCI) services at Veterans Affairs medical centers.



1900 prescreened, 779 screened, and 212 randomly assigned inpatients with SCI and stage III or IV TPUs.



Oxandrolone, 20 mg/d (n = 108), or placebo (n = 104) until the TPU healed or 24 weeks.



The primary outcome was healed TPUs. The secondary outcome was the percentage of TPUs that remained healed at 8-week follow-up.



24.1% (95% CI, 16.0% to 32.1%) of TPUs in oxandrolone recipients and 29.8% (CI, 21.0% to 38.6%) in placebo recipients healed (difference, -5.7 percentage points [CI, -17.5 to 6.8 percentage points]; P = 0.40). At 8-week follow-up, 16.7% (CI, 9.6% to 23.7%) of oxandrolone recipients and 15.4% (CI, 8.5% to 22.3%) of placebo recipients retained a healed TPU (difference, 1.3 percentage points [CI, -8.8 to 11.2 percentage points]; P = 0.70). No serious adverse events were related to oxandrolone. Liver enzyme levels were elevated in 32.4% (CI, 23.6% to 41.2%) of oxandrolone recipients and 2.9% (CI, 0.0% to 6.1%) of placebo recipients (P < 0.001).



Selection of severe wounds may have reduced treatment response. Approximately one third of patients did not complete the study in the treatment and placebo groups. The study was terminated after a futility analysis showed a low probability of detecting a significant difference between the groups.



Oxandrolone showed no benefit over placebo for improving healing or the percentage of TPUs that remained closed after 8 weeks of treatment.
Outcome and prognostic factors in high-risk childhood adrenocortical carcinomas: A report from the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT).

The aim of this retrospective international analysis was to evaluate the role of risk factors in pediatric patients with adrenocortical carcinoma (ACC) observed in European countries (2000-2013) in an attempt to identify factors associated with poor prognosis.


PROCEDURES
Data were retrieved from databases of Germany, France, Poland, and Italy, which form the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT). Patients were less than 18 years old, with at least one of the following tumor-related risk factors: metastases, volume more than 200 cm3 , Cushing syndrome, vascular or regional lymph node invasion, initial biopsy, or incomplete excision. Role of patients' age was also evaluated.



Eighty-two patients were evaluated: 62 with localized disease and 20 with metastases. The 3-year progression-free survival (PFS) and overall survival (OS) were 39% and 55% for the whole population, respectively, and 51% and 73% for localized diseases, respectively. Concerning the whole population, PFS and OS were influenced by distant metastases, tumor volume, lymph node involvement, age, and presence of two or more risk factors. Factors significant only at OS were vascular involvement and incomplete surgery. At multivariable analysis, the main factors at PFS were volume more than 200 cm3 (hazard ratio [HR]: 2.6, 95% confidence interval [CI]: 1.18-5.70) and presence of distant metastases (HR: 8.26, 95% CI: 3.49-19.51). The OS was significantly influenced by the presence of metastases (P < 0.0001). Concerning patients with localized tumors, the only significant prognostic factor was volume more than 200 cm3 with a HR of 4.38 (95% CI: 1.60-12.00) for PFS and of 3.68 (95% CI: 1.02-13.30) for OS.



Distant metastases and large tumor volume were the main unfavorable prognostic factors. Presence of two or more factors related to ACC was associated with an aggressive behavior of disease.
A randomized controlled trial to increase cancer screening among attendees of community health centers.

We assessed the efficacy of the Cancer Screening Office Systems (Cancer SOS), an intervention designed to increase cancer screening in primary care settings serving disadvantaged populations.



Eight primary care clinics participating in a county-funded health insurance plan in Hillsborough County, Fla, agreed to take part in a cluster-randomized experimental trial. The Cancer SOS had 2 components: a cancer-screening checklist with chart stickers that indicated whether specific cancer-screening tests were due, ordered, or completed; and a division of office responsibilities to achieve high screening rates. Established patients were eligible if they were between the ages of 50 and 75 years and had no contraindication for screening. Data abstracted from charts of independent samples collected at baseline (n = 1,196) and at a 12-month follow-up (n = 1,237) was used to assess whether the patient was up-to-date on one or more of the following cancer-screening tests: mammogram, Papanicolaou (Pap) smear, or fecal occult blood testing (FOBT).



In multivariate analysis that controlled for baseline screening rates, secular trends, and other patient and clinic characteristics, the intervention increased the odds of mammograms (odds ratio [OR] = 1.62, 95% confidence interval [CI], 1.07-9.78, P = .023) and fecal occult blood tests (OR = 2.5, 95% CI, 1.65-4.0, P <.0001) with a trend toward greater use of Pap smears (OR = 1.57, 95% CI, 0.92-2.64, P = .096).



The Cancer SOS intervention significantly increased rates of cancer screening among primary care clinics serving disadvantaged populations. The Cancer SOS intervention is one option for providers or policy makers who wish to address cancer related health disparities.
Parkinson's disease: an open label trial of pergolide in patients failing bromocriptine therapy.

Sixty-three patients with Parkinson's disease who failed bromocriptine therapy for various reasons were treated in an open-label trial of pergolide. The data were evaluated in a retrospective manner. Forty-six percent had a good response and tolerated the pergolide. A comparison of the outcomes regarding response and toxicity revealed that bromocriptine and pergolide act differently in individual patients. A trial of pergolide in Parkinsonian patients failing bromocriptine therapy may be therapeutically useful.
Gastroesophageal reflux in laparoscopic sleeve gastrectomy: hiatal findings and their management influence outcome.

Sleeve gastrectomy (SG) has become a definitive treatment for morbid obesity. There is conflicting evidence on the effects of SG on gastroesophageal reflux disease (GERD).



The objective of this study was to assess whether taking an aggressive approach to managing hiatal weakness in patients undergoing SG results in an alteration in GERD symptoms.



Tertiary public hospital and private hospital, Sydney, Australia.



Patients undergoing laparoscopic extended (beginning within 2 cm from pylorus) SG were included. If evidence of weakness was present, an anterior hiatal dissection and tight suture repair was performed. If a hiatus hernia was present, formal repair was undertaken. Patients were questioned and scored on preoperative and postoperative reflux symptom frequency and severity, proton pump inhibitor (PPI) usage, current weight, and satisfaction.



A continuous cohort of 262 patients experienced a significant reduction in heartburn frequency (P = .035) and severity (P = .017). Moderate/severe preoperative reflux (Visick score 3 and 4) often improved whether there was a defect requiring repair or not (no repair P = .02, hiatal suture P = .001, hiatus hernia repair P<.001). The severity of symptoms also improved (no repair P = 0.005, hiatal suture P<.001, hiatus hernia repair P< .001).



Moderate or severe preexisting gastroesophageal reflux improved for most of our obese patients undergoing an extended SG when hiatal defects were routinely repaired. Moderate to severe preoperative reflux also improved in the average obese patient when there was no hiatal defect to repair.