nils-herrmann/clean_scirepeval huggingface dataset:
Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer

The purpose of this study were firstly to characterize the population pharmacokinetics of artesunate (ARS) and its active metabolite dihydroartemisinin (DHA) in patients with metastatic breast cancer during long-term (>3 weeks) daily oral ARS administration and secondly to study the relationship between salivary and plasma concentrations of DHA. Drug concentration-time data from 23 patients, receiving oral ARS (100, 150, or 200 mg OD), was analyzed using nonlinear mixed effects modeling. A combined drug-metabolite population pharmacokinetic model was developed to describe the plasma pharmacokinetics of ARS and DHA in plasma. Saliva drug concentrations were incorporated as being directly proportional to plasma concentrations. A first-order absorption model for ARS linked to a combined two-compartment disposition model for ARS and one-compartment disposition model for DHA provided the best fit to the data. No covariates were identified that could explain between-subject variability. A time-dependent increase in apparent elimination clearance of DHA was observed. Salivary DHA concentrations were proportionally correlated with total DHA plasma concentrations, with an estimated slope factor of 0.116. Population pharmacokinetics of ARS and DHA in patients with breast cancer was well described by a combined drug-metabolite model without any covariates and with an increase in apparent elimination clearance of DHA over time. The estimated DHA saliva/plasma ratio was in good agreement with the reported DHA unbound fraction in human plasma. Saliva ARS concentrations correlated poorly with plasma concentrations. This suggests the use of saliva sampling for therapeutic drug monitoring of DHA. However, further studies are warranted to investigate the robustness of this approach.
The effect of medical male circumcision on urogenital Mycoplasma genitalium among men in Kisumu, Kenya.

We determined the prevalence of urethral Mycoplasma genitalium (MG) infection and whether infection was associated with circumcision status among men enrolled in the randomized trial of medical male circumcision to prevent HIV acquisition in Kisumu, Kenya.



MG and Trichomonas vaginalis were detected in first void urine by APTIMA transcription-mediated amplification assay. first void urine and urethral swabs were assessed for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) by polymerase chain reaction assay. Herpes simplex virus type 2 antibodies were detected by IgG ELISA. Multivariable logistic regression identified factors associated with MG infection.



Specimens were collected between July and September 2010, and 52 (9.9%; 95% confidence interval [CI]: 7.3%-12.4%) MG infections were detected among 526 men. N. gonorrhoeae and T. vaginalis were not associated with MG. CT coinfection was 5.8% in MG-infected men, and 0.8% among MG-uninfected men (P = 0.02). MG infection was predominantly asymptomatic (98%). The prevalence of MG was 13.4% in uncircumcised men versus 8.2% in circumcised men (P = 0.06). Being circumcised nearly halved the odds of MG (adjusted odds ratio [aQR] = 0.54; 95% CI: 0.29-0.99), adjusted for other variables significant at the P < 0.05 level: herpes simplex virus type 2 infection (aOR = 2.05; 95% CI: 1.05-4.00), CT infection (aOR = 2.69; 95% CI: 1.44-5.02), and washing the penis ≤1 hour after sex (aOR = 0.47; 95% CI: 0.24-0.95).



MG infection was reduced among men who were circumcised, adding to the benefits of male circumcision in preventing several sexually transmitted infections.
Use of a standardized diagnostic approach improves the prognostic information of histopathologic factors in pancreatic and periampullary adenocarcinoma

Variability in reported histopathology parameters in operated periampullary adenocarcinomas may affect the prognostic weight of the parameters. Standardized axial sectioning produces a higher incidence of involved margins and also seems to produce a lower relative incidence of pancreatic compared with distal bile duct origin and a higher incidence of involved lymph nodes, compared with non-standardized procedure. The aims of this study were to 1) assess how a previously not described standardized pathology procedure, with longitudinal sectioning along the distal bile duct, affects reported tumour origin, margin status and involved lymph nodes, compared with non-standardized procedure, 2) assess if re-evaluation of microscopic slides affects the prognostic value of margin status and 3) compare the results of this standardized procedure with reported results of other standardized and non-standardized procedures.



One hundred seventy-five consecutive pancreaticoduodenectomy specimens with primary adenocarcinomas, operated during 2001 - 2011 at the University hospitals of Lund and Malmö, Sweden, were re-evaluated histologically, and parameters relevant for classification and prognosis were assessed, with 1 mm as a threshold for involved or uninvolved margins. Follow-up lasted until 31 December 2013. Five-year overall survival (OS) and hazard ratios (HR) were calculated for the margin status stated in the original reports and margin status after re-evaluation.



Compared with non-standardized cases (n = 129), standardized cases (n = 46) had more involved lymph nodes in the specimens (median 3 vs 1), a higher fraction of distal bile duct origin (39% vs 21%) and a higher fraction of involved margins (74% vs 47%). The prognostic value of uninvolved margins increased by re-evaluation of slides (p < 0.001) and the adjusted HR for involved margins increased from 1.6 (95% CI 1.1 - 2.4) to 3.3 (95% CI 1.5 - 7.0). Uninvolved margins remained a significant predictor of OS in adjusted analysis.



Both the method of sectioning the specimen and the microscopic assessment affect prognostic pathology parameters significantly. The results of the herein described standardized method are similar to the results of other standardized procedures. The 1-mm threshold for involved margins in pancreaticoduodenectomies is relevant for OS, and margin status is an independent prognostic parameter.



The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1056639379120615.
Self-monitoring of physical activity: effects on self-efficacy and behavior in people with type 2 diabetes.

The purpose of this study was to test the effect of keeping daily activity records on physical activity levels and self-efficacy for physical activity in adults with type 2 diabetes, and to examine the feasibility and acceptability of this intervention from the perspective of the participants.



This intervention study included 58 individuals with type 2 diabetes aged 40 to 65 years. Participants were randomly assigned: individuals in the intervention group kept daily activity records for 6 weeks, mailed to the researcher every 2 weeks. Data collection was completed at the beginning of the study and 6 weeks later, using the habitual physical activity index and the self-efficacy for exercise scale. Participants in the intervention group also completed the perceived feasibility checklist.



The intervention resulted in enhanced self-efficacy. Physical activity improved in both the intervention and control groups. Activity recording was judged to be acceptable and feasible.



Daily activity recording can be used as part of a program to increase physical activity self-efficacy levels. Focused interactions between health care providers and patients may be enough to motivate people to higher levels of physical activity. The relationship between self-efficacy and behavior is complex and should be the subject of further research.
Ultra-high-pressure liquid chromatography tandem mass spectrometry method for the determination of 9 organophosphate flame retardants in water samples

Few methods are available for comprehensive organophosphate flame retardants (PFRs) detection in water and wastewater. Gas chromatography has been employed previously, but this approach is less selective, not amenable for use with deuterated standards and can suffer unfavorable fragmentation. Ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-QqQ-MS/MS) has become the most promising platform, already applied successfully for analysis of selected PFRs in some environmental matrices like water and wastewater. However, the presence of some interferences from the dissolvent, the equipment and the used materials should be taken into account. The procedure involves: •The first determination of PFRs by UHPLC-QqQ-MS/MS using a trap column to distinguish the interferences coming from the instrument and mobile phases.•The optimization of the LC separation to distinguish all target compounds and their interferences.•This method coupled to a solid-phase extraction (SPE) improve the detection and quantification of PFRs.
Educational level and the quality of life of heart failure patients: a longitudinal study.

Lower education in heart failure (HF) patients is associated with high levels of anxiety, limited physical functioning, and an increased risk of hospitalization. We examined whether educational level is related to longitudinal differences in quality of life (QoL) in HF patients.



This research is a substudy of the Coordinating study evaluating Outcomes of Advising and Counselling in Heart failure (COACH). QoL of 553 HF patients (mean age 69, 38% female, mean left ventricular ejection fraction 33%) was assessed during their hospitalization and at 4 follow-up measurements after discharge. In total 32% of the patients had very low, 24% low, 32% medium, and 12% high education. Patients with low educational levels reported the worst QoL. Significant differences between educational groups (P < .05) were only reported in physical functioning, social functioning, energy/fatigue, pain, and limitations in role functioning related to emotional problems. Longitudinal results show that a significantly higher proportion of high-educated patients improved in functional limitations related to emotional problems over time compared with lower-educated patients (P < .05).



Patients with low educational levels reported the worst physical and functional condition. High-educated patients improved more than the other patients in functional limitations related to emotional problems over time. Low-educated patients may require different levels of intervention to improve their physical and functional condition.
The effects of the monoamine stabilizer (-)-OSU6162 on craving in alcohol dependent individuals: A human laboratory study

Alcohol dependence is associated with a dysregulated dopamine system modulating reward, craving and cognition. The monoamine stabilizer (-)-OSU6162 (OSU6162) can counteract both hyper- and hypo-dopaminergic states and we recently demonstrated that it attenuates alcohol-mediated behaviors in long-term drinking rats. The present Phase II exploratory human laboratory study investigated to our knowledge for the first time the effects of OSU6162 on cue- and priming-induced craving in alcohol dependent individuals. Fifty-six alcohol dependent individuals were randomized to a 14-day-treatment period of OSU6162 or placebo after their baseline impulsivity levels had been determined using the Stop Signal Task. On Day 15, participants were subjected to a laboratory alcohol craving test comprised of craving sessions induced by: i) active - alcohol specific cues, ii) neutral stimuli and iii) priming - intake of an alcoholic beverage (0.20g ethanol/kg bodyweight). Subjective ratings of alcohol craving were assessed using the shortened version of the Desire for Alcohol Questionnaire and visual analog scales (VAS). OSU6162 treatment had no significant effect on cue-induced alcohol craving, but significantly attenuated priming-induced craving. Exploratory analysis revealed that this effect was driven by the individuals with high baseline impulsivity. In addition, OSU6162 significantly blunted the subjective liking of the consumed alcohol (VAS). Although the present 14-day-treatment period, showed that OSU6162 was safe and well tolerated, this exploratory human laboratory study was not designed to evaluate the efficacy of OSU6162 to affect alcohol consumption. Thus a larger placebo-controlled efficacyclinical trial is needed to further investigate the potential of OSU6162 as a novel medication for alcohol dependence.
The burden of treatment failure in type 2 diabetes.

In type 2 diabetes, therapies to maintain blood glucose control usually fail after several years. We estimated the glycemic burden that accumulates from treatment failure and describe the time course and predictors of failure.



A prospective, population-based study using retrospective observational data. We identified all 7208 complete courses of treatment with nondrug therapy, sulfonylurea monotherapy, metformin monotherapy, and combination oral antihyperglycemic therapy between 1994 and 2002, inclusive, among members of the Kaiser Permanente Northwest Region. We calculated mean cumulative glycemic burden, defined as HbA(1c)-months >8.0 or 7.0% for each treatment. We then measured the likelihood that the next HbA(1c) would exceed 8.0 and 7.0% after HbA(1c) exceeded each of ten hypothetical treatment thresholds. Finally, we estimated multivariate logistic regression models to predict when HbA(1c) would continue to deteriorate.



In this well-controlled population, the average patient accumulated nearly 5 HbA(1c)-years of excess glycemic burden >8.0% from diagnosis until starting insulin and about 10 HbA(1c)-years of burden >7.0%. Whenever patients crossed the American Diabetes Association-recommended treatment threshold of 8.0%, their next HbA(1c) result was as likely to be <8.0 as >8.0%. Multivariate prediction models had highly statistically significant coefficients, but predicted <10% of the variation in future HbA(1c) results.



Clinicians should change glucose-lowering treatments in type 2 diabetes much sooner or use treatments that are less likely to fail. An action point at 7.0% or lower is more likely to prevent additional deterioration than the traditional action point of 8.0%.
Oropharyngeal Contamination Predisposes to Complications after Neck Dissection: An Analysis of 9462 Patients.

While neck dissection is important in the treatment of head and neck cancer, there is a paucity of studies evaluating outcomes. We sought to compare preoperative variables and outcomes between clean and contaminated neck dissections, using the 2006-2011 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data sets.



Retrospective review of prospectively maintained database.



Multicenter (university hospitals; tertiary referral centers).



A retrospective review was performed of the NSQIP database to identify patients undergoing neck dissection in clean vs oropharyngeal contaminated cases. Clinical factors, comorbidities, epidemiologic factors, and procedural characteristics were analyzed to identify factors associated with 30-day postoperative adverse events, including medical and surgical complications, unplanned reoperation, and mortality. Bivariate and multivariable analyses were performed for the outcome of one or more adverse events.



In total, 8890 patients had clean neck dissections, while 572 patients had neck wound contamination with oropharyngeal flora. On multivariable regression analysis, oropharyngeal contamination was a significant risk factor for surgical complications (odds ratio [OR], 3.42; 95% confidence interval [CI], 1.96-5.96; P < .001). However, medical complications and mortality were not significantly different between the 2 cohorts. This finding persisted after subgroup analysis, with removal of all thyroidectomy patients from analysis (OR, 2.33; 95% CI, 1.25-4.36; P = .008).



Using the ACS-NSQIP data set, this study found an increased risk of surgical complications in the setting of contaminated neck dissections. These data should be used for patient risk stratification, informed consent, and to guide further research.
Pulmonary Hypertension Associated with Idiopathic Pulmonary Fibrosis: Current and Future Perspectives

Pulmonary hypertension (PH) is commonly present in patients with chronic lung diseases such as Chronic Obstructive Pulmonary Disease (COPD) or Idiopathic Pulmonary Fibrosis (IPF) where it is classified as Group III PH by the World Health Organization (WHO). PH has been identified to be present in as much as 40% of patients with COPD or IPF and it is considered as one of the principal predictors of mortality in patients with COPD or IPF. However, despite the prevalence and fatal consequences of PH in the setting of chronic lung diseases, there are limited therapies available for patients with Group III PH, with lung transplantation remaining as the most viable option. This highlights our need to enhance our understanding of the molecular mechanisms that lead to the development of Group III PH. In this review we have chosen to focus on the current understating of PH in IPF, we will revisit the main mediators that have been shown to play a role in the development of the disease. We will also discuss the experimental models available to study PH associated with lung fibrosis and address the role of the right ventricle in IPF. Finally we will summarize the current available treatment options for Group III PH outside of lung transplantation.
The Effect of Start and Stop Age at Screening on the Risk of Being Diagnosed with Prostate Cancer.

We investigated the effect of age and number of screens on the risk of prostate cancer diagnosis.



Since 1995 the Göteborg randomized population based prostate cancer screening trial has invited men biennially for prostate specific antigen testing, until the upper age limit of 70 years. Men with a prostate specific antigen above the threshold of 2.5 ng/ml were recommended further evaluation including 10-core biopsy (sextant before 2009). The present study comprises 9,065 men born between 1930 and 1943 (1944 excluded due to different screening algorithm). Complete attendees were defined as men who accepted all screening invitations (maximum 3 to 9 invitations). The cumulative incidence of prostate cancer was calculated using standard methods.



Of the 3,488 (38%) complete attendees 667 were diagnosed with prostate cancer (followup 1995 to June 30, 2014). At age 70 years there was no significant difference in prostate cancer risk among those who started screening at the age of 52 (9 screens), 55 (7 screens) or 60 (5 screens) years. However, the cumulative risk of prostate cancer diagnosis increased dramatically with age, and was 7.9% at age 60, 15% at age 65 and 21% at age 70 for men who had been screened 4 or more times.



There was no clear association between risk of prostate cancer and the number of screens. Starting screening at an early age appears to advance the time of prostate cancer diagnosis but does not seem to increase the risk of being diagnosed with the disease. Age at termination of screening is strongly associated with the risk of being diagnosed with prostate cancer.
Clinical characteristics of Pneumocystis pneumonia in non-HIV patients and prognostic factors including microbiological genotypes

The number of patients with non-HIV Pneumocystis pneumonia (PCP) is increasing with widespread immunosuppressive treatment. We investigated the clinical characteristics of non-HIV PCP and its association with microbiological genotypes.



Between January 2005 and March 2010, all patients in 2 university hospitals who had been diagnosed with PCP by PCR were enrolled in this study. Retrospective chart review of patients, microbiological genotypes, and association with 30-day mortality were examined.



Of the 82 adult patients investigated, 50 patients (61%) had inflammatory diseases, 17 (21%) had solid malignancies, 12 (15%) had hematological malignancies, and 6 (7%) had received transplantations. All patients received immunosuppressive agents or antitumor chemotherapeutic drugs. Plasma (1→3) β-D-glucan levels were elevated in 80% of patients, and were significantly reduced after treatment in both survivors and non-survivors. However, β-D-glucan increased in 18% of survivors and was normal in only 33% after treatment. Concomitant invasive pulmonary aspergillosis was detected in 5 patients. Fifty-six respiratory samples were stored for genotyping. A dihydropteroate synthase mutation associated with trimethoprim-sulfamethoxazole resistance was found in only 1 of the 53 patients. The most prevalent genotype of mitochondrial large-subunit rRNA was genotype 1, followed by genotype 4. The most prevalent genotype of internal transcribed spacers of the nuclear rRNA operon was Eb, followed by Eg and Bi. Thirty-day mortality was 24%, in which logistic regression analysis revealed association with serum albumin and mechanical ventilation, but no association with genotypes.



In non-HIV PCP, poorer general and respiratory conditions at diagnosis were independent predictors of mortality. β-D-glucan may not be useful for monitoring the response to treatment, and genotypes were not associated with mortality.
[Clinical efficacy of neoadjuvant M-VAC chemotherapy for invasive bladder cancer].

We clinically evaluated the efficacy of neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) therapy followed by radical cystectomy. A total of 21 patients with locally invasive bladder cancer received neoadjuvant M-VAC therapy with an average of 2.4 courses (range 2-4). Of the 21 patients, 4 had stage T2N0M0, 11 had stage T3aN0M0, 5 had stage T3bN0M0 and 1 had stage T4N0M0 at diagnosis. Of the 21 patients, 3 had clinically complete responses (cCR) and 12 had partial responses (cPR), for an overall response rate of 71.4%. The patients who responded to the chemotherapy (cCR + cPR) had a 2-year disease free rate of 80.0% in contrast to 50.0% for the remaining patients who did not respond. A pathological response (pT0, pT1) was achieved in 6 (28.6%) of the 21 patients. The 5 patients in this group remain free of disease for 15 to 79 months (mean 58.8 months). These preliminary results suggest that the patients who achieve either a complete or partial response, in particular those had pathological stage of pT0 or pT1, may have a favorable clinical course.
Folate and vitamin B12 levels in levodopa-treated Parkinson's disease patients: their relationship to clinical manifestations, mood and cognition.

We tested the hypothesis that mood, clinical manifestations and cognitive impairment of levodopa-treated Parkinson's disease (PD) patients are associated with vitamin B12 and folate deficiency. To this end, we performed this cross-sectional study by measuring serum folate and vitamin B12 blood levels in 111 consecutive PD patients. Levodopa-treated PD patients showed significantly lower serum levels of folate and vitamin B12 than neurological controls, while depressed patients had significantly lower serum folate levels as compared to non-depressed. Cognitively impaired PD patients exhibited significantly lower serum vitamin B12 levels as compared to cognitively non-impaired. In conclusion, lower folate levels were associated with depression, while lower vitamin B12 levels were associated with cognitive impairment. The effects of vitamin supplementation merit further attention and investigation.
Non-overlapping Partitions, Continued Fractions, Bessel Functions and a Divergent Series

The counting sequence of a special class of set partitions leads to special numbers called Bessel numbers. The corresponding ordinary generating function has a simple continued fraction expansion related to Bessel functions. We determine here the asymptotic form of Bessel numbers and discuss their relation to Bell numbers. The estimation problem is of some methodological interest as it is necessary to find the asymptotic form of coefficients in an asymptotic but divergent expansion.