nils-herrmann/clean_scirepeval huggingface dataset:
Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy.

The use of raltegravir in human immunodeficiency virus (HIV)-infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women.



An open-label, multicenter, phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were obtained in the third trimester and postpartum along with cord and maternal delivery concentrations. Safety and virologic efficacy were evaluated.



Twenty-two patients were included, of which 68% started raltegravir during pregnancy. Approaching delivery, 86% of the patients had an undetectable viral load (<50 copies/mL). None of the children were HIV-infected. Exposure to raltegravir was highly variable. Overall area under the plasma concentration-time curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma concentrations in the third trimester were on average 29% and 36% lower, respectively, compared with postpartum: Geometric mean ratios (90% confidence interval) were 0.71 (.53-.96) for AUC0-12h and 0.64 (.34-1.22) for C12h. The median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range, 1.02-2.17; n = 9).



Raltegravir was well tolerated during pregnancy. The pharmacokinetics of raltegravir showed extensive variability. The observed mean decrease in exposure to raltegravir during third trimester compared to postpartum is not considered to be of clinical importance. Raltegravir can be used in standard dosages in HIV-infected pregnant women.
Correlations between acoustic rhinometry, subjective symptoms, and endoscopic findings in symptomatic children with nasal obstruction.

Nasal obstruction is common in children and difficult to quantify objectively. Symptom quantification is paramount for surgical and medical decision making. Acoustic rhinometry is a relatively new technique aimed at the objective assessment of nasal obstruction. There is no standardized method for the objective assessment of the pediatric nasal airway.



To explore the correlations between acoustic rhinometry (AR), subjective symptoms, and endoscopic findings in children presenting with nasal obstruction.



A cross-sectional, exploratory, diagnostic study of prospectively collected data from a multidisciplinary airway clinic (pulmonology, orthodontics, and otolaryngology) database at a tertiary academic referral center. Data were collected over a 2-year period (2010-2012) from 65 nonsyndromic children (38 boys) 7 years and older (mean [SD] age, 10.3 [2.5] years [range, 7-14 years]), presenting with persistent nasal obstructive symptoms for at least 1 year, without signs and symptoms of sinus disease.



We collected patient demographics and medical history information including allergy, asthma, and sleep-disordered breathing. Subjective nasal obstruction was scored using a visual analog scale (VAS). Sleep-disordered breathing was assessed using overnight pulse oximetry. The adenoid size, septal position, and visual severity of chronic rhinitis (endoscopic rhinitis score [ERS]) were rated on nasal endoscopy by 2 independent reviewers and validated by agreement. Acoustic rhinometry (AR) was undertaken before and after use of a decongestant.



Correlation and multiple regression analyses were performed to explore interrelationships between subjective nasal obstruction VAS, AR, and nasal endoscopy.



Among the 65 patients, 28 (43%) had symptoms of sleep-disordered breathing, 14 (22%) had allergic rhinitis, 10 (15%) had asthma, 27 (41%) had grade 3 or 4 adenoidal obstruction, 28 (43%) had an ERS of 2, 6 (9%) had an ERS of 3, and 19 (29%) had septal deviation. Significant correlations were found between subjective nasal obstruction VAS score and ERS (r = -0.364, P = .003), ERS and minimal cross-sectional area before decongestion (r = -0.278, P = .03), and adenoid size and calculated nasal resistance after decongestion (r = 0.430, P < .001). Multiple regression analysis showed that the ERS was the only significant predictor of VAS score (β of -22.089; 95% CI, -35.56 to -8.61 [P = .002]). No predictors were identified for AR variables.



Among the evaluated tools, endoscopy appears to be the most reliable tool to estimate the degree of subjective nasal symptoms.
Factors associated with seronegative chronic hepatitis C virus infection in HIV infection.

Chronic seronegative hepatitis C virus (HCV) infection is defined as being HCV antibody (anti-HCV) negative, but HCV RNA positivity occurs in individuals infected with human immunodeficiency virus (HIV). However, associated factors are not well established because of the small number of reported cases.



Multivariate logistic regression analysis of HIV-infected subjects from 4 cohorts (Tien et al., 2006; Bonacini et al., 2001; George et al., 2002; and Hall et al., 2004) determined factors associated with HCV RNA positivity in anti-HCV-negative subjects. HCV enzyme immunoassay 2.0 was used to determine anti-HCV status.



Among 1174 anti-HCV-negative, HIV-infected subjects, the prevalence of seronegative HCV infection was 3.2% (95% confidence interval [CI], 2.2%-4.3%). History of injection drug use (IDU; OR, 5.8; 95% CI, 2.7-12.8), higher alanine aminotransferase (ALT) level (OR, 2.0 per doubling; 95% CI, 1.3-3.2), and CD4 cell count <200 cells/ micro L (OR, 2.3; 95% CI, 1.1-4.8) were associated with HCV RNA positivity in anti-HCV-negative subjects. Among those with a history of IDU who had either a CD4 cell count <200 cells/ micro L or an ALT level greater than the upper limit of normal, the prevalence of seronegative HCV infection was 24% (95% CI, 13%-39%).



Detectable HCV RNA in the context of a negative HCV enzyme immunoassay 2.0 result in HIV-infected patients is low, but higher than the reported prevalence in HIV-uninfected patients. Our findings suggest that HCV RNA testing should be performed in anti-HCV-negative, HIV-infected patients, especially those with a history of IDU and either a CD4 cell count <200 cells/ micro L or an abnormal ALT level.
A latent variable approach in simultaneous modeling of longitudinal and dropout data in schizophrenia trials

Dropouts impact clinical trial outcome analyses. Ignoring missing data is not an acceptable option when planning, conducting or interpreting the analysis of a clinical trial. Treatment related efficacy and safety data observed in the trial may not always be sufficient in explaining the dropouts' mechanism. Nevertheless, these dropout data may carry important treatment-related information and present as an outcome by itself. Traditional analyses involve the use of the time-to-event approach assuming that the dropouts' hazard is solely related to the efficacy or safety profiles observed in a study. A latent variable approach was developed to generalize this approach and to implement a more flexible dropout hazard function in a schizophrenia trial. This unobserved latent variable was used to jointly model the longitudinal efficacy data and dropout profiles across treatments. The analysis provides a framework to model informative dropouts simultaneously with primary efficacy outcomes and make intelligent decisions in drug development.
Recent methodological contributions to clinical trials.

This paper is concerned with the maximum that can be achieved in clinical trials using optimal methodologies if such exist, i.e., with strategy and not tactics. It might be thought that strategy so defined is too vague and too general to be fruitfully discussed, but I hope to convince you of the contrary. Considerations of strategy will involve us in controversial questions about the foundations of statistics, but this prospect shall not inhibit us any more than it would have Reed or Frost. A point of view about statistical methods that was once universal and is still very common is that it provides unique, unequivocal answers to problems of analysis and design—that all statisticians faced with the same problem will, or at least should, provide the same answer. R. A. Fisher's writing, in particular, reflects this view, with continual glimpses furnished by such phrases as "uniquely superior" methods of "absolute validity," "canons of valid inference," "rigorous but uncertain conclusions," etc. His Design of Experiments was dazzling in its self-assurance and clarity and gave statisticians in many fields the inspiration and confidence to apply these unequivocal procedures, and to develop new ones. The extensions to clinical trials have been numerous and important, the key figure being Bradford Hill. In the opinion of the President of the Royal College of Surgeons they constitute as crucial a contribution to medicine as the discovery of penicillin (1). One would naturally have expected that continuing methodological advances would have accompanied these extensions. The statistical literature on
How should teaching modeling and programming intertwine?

This paper refers to 15 years experience in teaching object-oriented (OO) software development for undergraduate students. Our teaching approach includes modeling with UML and programming with Java. In a first course we introduce the students to OO analysis and OO design including using selected design patterns as well as to OO programming including UML2Java transformation based on small applications. In the subsequent project course students have to implement a mid-size application in a work-sharing software development process. Although the topics of the courses have basically not changed over the years we experimented with two basic didactic approaches in the introductory first course. The underlying issue is how should modeling and programming intertwine to educate both modelers and programmers. In this paper we evaluate both didactic approaches based on statistical results of written exams.
Optimization of Storage and Manufacture Conditions for Imidapril Hydrochloride in Solid State as a Way to Reduce Costs of Antihypertensive Therapy

The effect of temperature and relative humidity (RH) on the stability of imidapril hydrochloride (IMD) in solid state was investigated. The main aim of this study was to determine the most appropriate conditions of storage and manufacture of IMD so that the efficiency of the technological process could be improved and its costs could be minimized. A reversed-phase high-performance liquid chromatography was validated and applied for the determination of IMD degradation samples under the following operating conditions: stationary phase, LiChrospher 100 RP-18 (size 5 μm) 250 × 4 mm I.D., and mobile phase, acetonitrile–methanol–phosphate buffer, pH 2.0, 0.035 mol L−1 (60:10:30 v/v/v). The effect of temperature on IMD degradation rate was analyzed under increased RH ∼76.4% (within temperature range of 70–90°C) and decreased RH ∼0% (within temperature range of 90–110°C). The influence of RH was investigated under 90°C within RH range of 25.0–76.4%. IMD degradation accords with autocatalytic reaction model, and RH has no influence on its mechanism yet it increases its rate. The reaction also accelerates under high temperatures and in the presence of IMD degradation product. Pure IMD is more stable than other structurally related angiotensin-converting enzyme inhibitors, such as enalapril maleate, but it still should be stored in tightly closed containers and protected from moisture and high temperatures.
Prevalence and management of uncontrolled hypertension in French patients aged over 80 years.

The rate of uncontrolled hypertensives aged >80 years is not well known. The available literature on this topic has used the threshold <140/90 mmHg, whereas there is now a consensus for a different target: systolic blood pressure (SBP)<150 mmHg.



This prospective observational population-based study sought to assess the frequency and management of uncontrolled hypertension in French patients aged ≥80 years.



Nine hundred and seventy-one treated hypertensive outpatients were evaluable (204 recruited by cardiologists, 767 by general practitioners [GPs]; mean age 84.8 ± 3.8 years; 57.8% women).



The frequency of SBP ≥ 150 mmHg was 36.6% (44.6% in cardiologists' patients and 34.4% in GPs' patients). The frequency of satisfaction with SBP ≥ 150 mmHg was 22.0% for cardiologists (32.6% if diastolic blood pressure [DBP] <90 mmHg and 9.5% if ≥90 mmHg; P=0.008) and 30.4% for GPs (51.7% if DBP <90 mmHg and 13.2% if ≥90 mmHg; P<0.0001). Non-diabetic status (for cardiologists) and DBP <90 mmHg (for cardiologists and GPs) were independent determinants of SBP being considered acceptable. Accordingly, in patients with an SBP level ≥ 150 mmHg that was considered too high, treatment was reinforced more often if DBP was ≥90 mmHg (82.3%) than <90 mmHg (68.5%).



In France, hypertension is uncontrolled in more than one in three elderly hypertensives. Physicians are aware that SBP should be lowered to <150 mmHg in patients aged>80 years, but when the target is not reached they are less likely to increase treatment if DBP is <90 mmHg.
Associations of Protein Intake and Protein Source with Bone Mineral Density and Fracture Risk: A Population-Based Cohort Study.

High dietary protein has been hypothesized to cause lower bone mineral density (BMD) and greater fracture risk. Previous results are conflicting and few studies have assessed potential differences related to differing protein sources.



To determine associations between total protein intake, and protein intake by source (dairy, non-dairy animal, plant) with BMD, BMD change, and incident osteoporotic fracture.



Prospective cohort study (Canadian Multicentre Osteoporosis Study).  Protein intake was assessed as percent of total energy intake (TEI) at Year 2 (1997-99) using a food frequency questionnaire (N=6510). Participants were contacted annually to ascertain incident fracture. Total hip and lumbar spine BMD was measured at baseline and Year 5. Analyses were stratified by group (men 25-49 y, men 50+ y, premenopausal women 25-49 y, and postmenopausal women 50+ y) and adjusted for major confounders. Fracture analyses were limited to those 50+ y.



Intakes of dairy protein (with adjustment for BMI) were positively associated with total hip BMD among men and women aged 50+ y, and in men aged 25-49. Among adults aged 50+ y, those with protein intakes of <12% TEI (women) and <11% TEI (men) had increased fracture risk compared to those with intakes of 15% TEI. Fracture risk did not significantly change as intake increased above 15% TEI, and was not significantly associated with protein source.



In contrast to hypothesized risk of high protein, we found that for adults 50+ y, low protein intake (below 15% TEI) may lead to increased fracture risk. Source of protein was a determinant of BMD, but not fracture risk.
Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis.

Microparticles released into the bloodstream upon activation or apoptosis of CD4(+) and CD8(+) T cells correlate with inflammation as determined by histologic analysis in patients with chronic hepatitis C (CHC). Patients with nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH) can be differentiated from those with CHC based on activation of distinct sets of immune cells in the liver.



We compared profiles of circulating microparticles from patients with NAFL and NASH (n = 67) to those of CHC (n = 42), with healthy individuals (controls) using flow cytometry; the profiles were correlated with inflammation grade and fibrosis stage based on histologic analyses. We assessed the ability of the profiles to determine the severity of inflammation and fibrosis based on serologic and histologic analyses.



Patients with CHC had increased levels of microparticles from CD4(+) and CD8(+) T cells; the levels correlated with disease severity based on histologic analysis and levels of alanine aminotransferase. Patients with NAFL or NASH had significant increases in numbers of microparticles from invariant natural killer T cells and macrophages/monocytes (CD14(+)), which mediate pathogenesis of NASH. Microparticles from CD14(+) and invariant natural killer T cells correlated with levels of alanine aminotransferase and severity of NASH (based on histology). Levels of microparticles could differentiate between patients with NAFL or NASH and those with CHC, or either group of patients and controls (area under the receiver operating characteristic curves ranging from 0.56 to 0.99).



Quantification of immune cell microparticles from serum samples can be used to assess the extent and characteristics of hepatic inflammation in patients with chronic liver disease.
1000 consecutive venous anastomoses using the microvascular anastomotic coupler in breast reconstruction.

Microvascular anastomosis is one of the more critical aspects of free flap surgery. A safe, effective, and expedient method for venous anastomosis minimizes flap ischemia time, is easier on the surgical team, and saves costly operating room time. The authors report on their experience using the Synovis microvascular anastomotic coupling device in 1000 consecutive venous anastomoses in free flap breast reconstruction.



The authors retrospectively reviewed 1000 consecutive venous anastomoses that were performed using the microvascular anastomotic coupler between July of 2002 and July of 2008. Data were obtained on flap type, recipient vessel, coupler size, incidence of venous thrombosis, timing of venous thrombosis, and morbidity as a result of venous thrombosis.



All anastomoses were performed in an end-to-end fashion. There were 460 unilateral cases and 270 bilateral cases of breast reconstruction. Flap types included muscle-sparing free transverse rectus abdominis myocutaneous, deep inferior epigastric perforator, superficial inferior epigastric artery, superior gluteal artery perforator, and inferior gluteal artery perforator. The vast majority of the recipient vessels were the internal mammary or thoracodorsal vessels. Most of the couplers that were used were either 3 or 2.5 mm in diameter. Overall, there were six instances of venous thrombosis (rate of 0.6 percent). There were no total flap losses due to venous thrombosis in this series, although two patients had partial flap necrosis.



The patency rate for venous anastomoses performed with the microvascular coupler is excellent when compared with standard suture techniques and has the advantage of overall easier application.
Omission of adjuvant radiation therapy in elderly patients with low risk breast cancer undergoing breast-conserving surgery--two center experience.

Breast cancer is, now often diagnosed in patients older than 70 years due to longer life expectancy. The usual treatment is mastectomy to obviate radiotherapy or breast-conserving surgery followed by radiotherapy. The aim of this study was to investigate the need for adjuvant radiotherapy in older patients and the consequences of omitting radiotherapy following conservative surgery.



An extensive database search was made of patients who had been treated for breast cancer at the Department of Oncology, University Hospital Olomouc and the Atlas Hospital in Zlin (2004-2008). We identified 738 patients of whom 190 patients (25.7%) were older than 70 years of age. These were followed up for progression-free and overall survival. The cause of death was checked for breast cancer relapse.



In total only 9 patients undergoing breast saving surgery were ultimately identified. No patient had confirmed local recurrence during the follow up period: Two patients have died due to distant metastasis without local relapse and one patient has died for reasons other than breast cancer.



Omitting radiotherapy after breast saving surgery provides an opportunity for women to undergo breast saving surgery and avoid 7 weeks of radiotherapy. This could significantly improve patient quality of life. In our of many years experience and from published randomized data, this procedure is safe for a select group of patients 70 years of age and older.
Acute kidney injury in critical ill patients affected by influenza A (H1N1) virus infection

Little information exists about the impact of acute kidney injury (AKI) in critically ill patients with the pandemic 2009 influenza A (H1N1) virus infection.



We conducted a prospective, observational, multicenter study in 148 Spanish intensive care units (ICUs). Patients with chronic renal failure were excluded. AKI was defined according to Acute Kidney Injury Network (AKIN) criteria.



A total of 661 patients were analyzed. One hundred eighteen (17.7%) patients developed AKI; of these, 37 (31.4%) of the patients with AKI were classified as AKI I, 15 (12.7%) were classified as AKI II and 66 (55.9%) were classified as AKI III, among the latter of whom 50 (75.7%) required continuous renal replacement therapy. Patients with AKI had a higher Acute Physiology and Chronic Health Evaluation II score (19.2 ± 8.3 versus 12.6 ± 5.9; P < 0.001), a higher Sequential Organ Failure Assessment score (8.7 ± 4.2 versus 4.8 ± 2.9; P < 0.001), more need for mechanical ventilation (MV) (87.3% versus 56.2%; P < 0.01, odds ratio (OR) 5.3, 95% confidence interval (CI) 3.0 to 9.4), a greater incidence of shock (75.4% versus 38.3%; P < 0.01, OR 4.9, 95% CI, 3.1 to 7.7), a greater incidence of multiorgan dysfunction syndrome (92.4% versus 54.7%; P < 0.01, OR 10.0, 95% CI, 4.9 to 20.21) and a greater incidence of coinfection (23.7% versus 14.4%; P < 0.01, OR 1.8, 95% CI, 1.1 to 3.0). In survivors, patients with AKI remained on MV longer and ICU and hospital length of stay were longer than in patients without AKI. The overall mortality was 18.8% and was significantly higher for AKI patients (44.1% versus 13.3%; P < 0.01, OR 5.1, 95% CI, 3.3 to 7.9). Logistic regression analysis was performed with AKIN criteria, and it demonstrated that among patients with AKI, only AKI III was independently associated with higher ICU mortality (P < 0.001, OR 4.81, 95% CI 2.17 to 10.62).



In our cohort of patients with H1N1 virus infection, only those cases in the AKI III category were independently associated with mortality.