nils-herrmann/clean_scirepeval huggingface dataset:
A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin.

We performed a pilot clinical trial with safingol (L-threo-dihydrosphingosine), a protein kinase C-specific inhibitor that potentiates the effect of doxorubicin (DOX) in tumor-bearing animals. Safingol was initially administered as a 1-h infusion at escalating doses. Fourteen days later, patients received the same dose of safingol in combination with a fixed dose of DOX. The combination was repeated at 3-week intervals. Safingol dose levels ranged from 15 to 120 mg/m2. The plasma levels achieved at the final dose level were comparable to those associated with potentiation of DOX in animals. The mean Cmax and area under the curve for safingol at the 120 mg/m2 dose level were 1040 +/- 196 ng/ml and 1251 +/- 317 mg x h/ml, respectively. The mean plasma half-life for safingol was 3.97 +/- 2.51 h, the mean estimated clearance was 3140 +/- 765 ml/min, and the mean volume of distribution was of 995 +/- 421 liters. Coadministration of a fixed dose of DOX did not significantly change the pharmacokinetics of safingol, nor did increasing doses of safingol significantly affect the pharmacokinetics of DOX. Minor responses were observed in three patients with pancreatic cancer and one patient with angiosarcoma of the scalp. This pilot Phase I study indicates that the protein kinase C inhibitor safingol can be given safely with 45 mg/m2 of DOX at a dose that is potentially pharmacologically active without dose-limiting toxicity.
Which patients do not return to work after total knee arthroplasty?

Total knee arthroplasty (TKA) is increasingly being performed among working patients suffering from knee osteoarthritis. Two out of ten patients do not return to work (RTW) after TKA. Little evidence is available about these patients to guide clinicians. Therefore, this study investigates patients’ characteristics associated with no RTW. A multicenter retrospective cohort study was performed among working patients having undergone a primary TKA during 2005–2010. The following preoperative characteristics were assessed: age at surgery, sex, comorbidity, body mass index (BMI), preoperative sick-leave duration, patient-reported work-relatedness of knee symptoms, and physical job demands. In addition, the Knee injury and Osteoarthritis Outcome Scores (KOOS) after TKA were assessed. Backward stepwise logistic regression analyses were performed to predict no RTW. Seven hundred and sixty-four patients were approached, and 558 patients (73 %) responded. One hundred and sixty-seven met the inclusion criteria and 46 did not RTW. A preoperative sick-leave duration >2 weeks (OR 12.5, 90 % CI 5.0–31.5) was most strongly associated with no RTW. Other associations found were: female sex (OR 3.2, 90 % CI 1.3–8.2), BMI ≥ 30 (OR 2.8, 90 % CI 1.1–7.1), patient-reported work-relatedness of knee symptoms (OR 5.3, 90 % CI 2.0–14.1), and a physically knee-demanding job (OR 3.3, 90 % CI 1.2–8.9). Age and KOOS were not associated with no RTW. Especially obese female workers, with a preoperative sick-leave duration >2 weeks, who perform knee-demanding work and indicate that their knee symptoms are work-related have a high chance for no RTW after TKA. These results stress the importance of a more timely referral for work-directed care of patients at risk for no RTW after TKA.
Grading Aortic Stenosis With Mean Gradient and Aortic Valve Area: A Comparison Between Preoperative Transthoracic and Precardiopulmonary Bypass Transesophageal Echocardiography.

The authors hypothesized that average precardiopulmonary bypass (pre-CPB) transesophageal echocardiographic (TEE) mean gradient (PGm) and aortic valve area (AVA) values would be significantly different from preoperative transthoracic (TTE) values in the same patients and that these changes would affect pre-CPB TEE grading of aortic stenosis (AS).



Retrospective, observational design.



Single university hospital.



The study comprised 92 patients who underwent aortic valve replacement with or without coronary artery bypass grafting between 2000 and 2012 at Duke University Hospital and who had PGm and AVA values recorded in both pre-CPB TEE and preoperative TTE reporting databases.



None.



PGm with pre-CPB TEE was lower by 6.6 mmHg (95% confidence interval, -4.0 to -9.3 mmHg; p<0.001), whereas AVA was higher by 0.10 cm(2) (95% confidence interval, 0.04 to 0.15 cm(2); p<0.001), compared with preoperative TTE values. When using PGm, pre-CPB TEE generated an AS severity 1 grade lower 39.1% of the time and revealed no difference 55.4% of the time compared to preoperative TTE. When using AVA by continuity, pre-CPB TEE generated an AS severity 1 grade lower 14.1% of the time and revealed no difference 81.5% of the time compared to preoperative TTE. When using either PGm or AVA, preoperative TTE exhibited moderate or severe AS for all study patients, whereas, pre-CPB TEE demonstrated mild AS in 5.4% (n = 92) of patients.



The authors confirmed their hypothesis that pre-CPB TEE generates different PGm and AVA values compared with preoperative TTE. These differences often underestimate AS severity. Hemodynamic standardizations or adjustments of pre-CPB TEE PGm and AVA values may be necessary in anesthetized patients before assigning an AS grade using these parameters.
Chronic low back pain clinical outcomes present higher associations with the STarT Back Screening Tool than with physiologic measures: a 12-month cohort study

Stratification strategies based on identifying patient's prognosis in order to guide patient care constitute one of the most prominent and recent approach in low back pain research. The STarT Back Screening Tool (SBST) although promising, has not been studied in patients with chronic low back pain (cLBP). Considering how challenging it is to translate research into practice, the value of integrating a new tool should be thoroughly assessed. The purpose was therefore to assess associations between the short- and long-terms clinical status and two types of variables, physiologic measures and the SBST, in participants with cLBP. The ability of both types of variables to discriminate between participants with and without higher levels of disability, pain, fear of movement and patient's global impression of change was also investigated.



Fifty-three volunteers with cLBP participated in an initial evaluation and follow-ups at 2-, 4-, 6- and 12-month. Physiologic measures (maximal voluntary contraction, maximal endurance and muscle activity evaluated during prone and lateral isometric tasks) and the SBST were assessed at baseline. Disability (Oswestry Disability Index, ODI), pain intensity (101-point Numerical Rating Scale, NRS), fear of movement (Tampa Scale for Kinesiophobia, TSK) and patient's global impression of change (7-point scale, PGIC) were evaluated at baseline and at each follow-up. Aside the use of correlation analyses to assess potential associations; ROC curves were performed to evaluate the discriminative ability of physiologic measures and the SBST.



The SBST allowed for the identification of participants presenting higher levels of disability (ODI ≥24 %), pain (NRS ≥37 %) or fear of movement (TSK ≥41/68) over a 12-month period (AUC = 0.71 to 0.84, ps < 0.05). The SBST score was also correlated with disability at each follow-up (τ = 0.22 to 0.33, ps < 0.05) and with pain intensity and fear of movement at follow-ups. Among physiologic measures, only maximal voluntary contraction was correlated to disability, pain intensity or fear of movement during the follow-up (|τ| = 0.26 to 0.32, ps < 0.05) and none was able to identify participants presenting higher levels of outcomes (AUC ps > 0.05).



Physiologic measures obtained during prone and lateral tests have limited associations with the clinical status over a 12-month period in patients with nonspecific chronic low back pain. On the other hand, the STarT Back Screening Tool is useful for the identification of patients who will present higher levels of disability, pain intensity and fear of movement over a year.
Men under the age of 55 years with screen detected prostate cancer do not have less significant disease compared to older men in a population of patients in Australia

The American Urological Association (AUA) changed their Prostate-Specific Antigen (PSA) screening guidelines in 2013 to not recommend testing in men under 55 years of age without significant risk factors (such as a family history of prostate cancer or African ethnicity). The AUA argues that the rates of 'insignificant' prostate cancer (PC) in men under 55 are so high that the potential harms of PSA-testing in this population (over diagnosis and overtreatment) outweigh the benefits (early detection and treatment). Our study aims to identify and compare the rates of insignificant and high-risk PC in men diagnosed with PC ≤55 years and >55 years in two centres in Sydney, Australia.



Men with an abnormal screening PSA or DRE and diagnosed with PC by prostate biopsy were included in this study. A consecutive series of men were accrued from two major urology centres between the years 2006 and 2014. The analysis was divided into two parts, the first compared PC biopsy characteristics between men aged ≤55 years and those >55 years. The second analysis compared the prostatectomy pathological characteristics between the two groups. Differences were analysed by Chi squared and significance set at p < 0.05.



A total of 598 prostate biopsies and 723 prostatectomy matched subjects were included. On prostate biopsies, 14.0 % of men ≤55 years and 11.9 % of men >55 years had insignificant PC (X(2) = 0.32, df = 1, p = 0.57), whilst 24.7 % of men ≤55 years and 25.1 % of men >55 years had high-risk PC (X(2) = 0.007, df = 1, p = 0.93). On prostatectomy specimens, 9.1 % of men ≤55 years and 6.5 % of men >55 years had insignificant PC (X(2) = 1.25, df = 1, p = 0.26), whilst 20.0 % of men ≤55 years and 24.0 % of men >55 years had high-risk PC (X(2) = 0.83, df = 1, p = 0.36).



We found no significant difference in the rates of insignificant and high-risk PC between men ≤55 years and >55 years, in either the prostate biopsies or prostatectomy specimens. Further trials need to be performed with comparable sample sizes and controlling of risk factors to assess the utility of PSA screening in younger men.
Changing etiology of community-acquired bacterial meningitis in adults: a nationwide multicenter study in Korea

Epidemiologic data on the etiologic organisms is important for appropriate empirical antibiotic treatment of bacterial meningitis. We identified the etiologies of community-acquired bacterial meningitis in Korean adults and the associated epidemiological factors. A retrospective, multicenter nationwide study was carried out. Patients 18 years of age or older with community-acquired bacterial meningitis with a confirmed pathogen were enrolled. Demographic, clinical, and microbiological data were collected. One hundred and ninety-five cases were collected. Streptococcus pneumoniae was the most common pathogen (50.8%), followed by Staphylococcus aureus (10.3%), Klebsiella pneumoniae (7.7%), Listeria monocytogenes (6.7%), and group B Streptococcus (3.1%). The penicillin resistance rate of the S. pneumoniae was 60.3%; 40.0% of the organisms were not susceptible to third-generation cephalosporins. The combination of third-generation cephalosporin with vancomycin was used in 76.3% of cases. Steroids were given before or with the first dose of antibiotics in 37.4% of patients. The 30-day mortality rate was 20.5% and neurological sequelae developed in 15.6% of cases. S. pneumoniae was the most common organism identified in community-acquired bacterial meningitis among Korean adults. S. aureus, K. pneumoniae, L. monocytogenes, and group B Streptococcus were also common. S. pneumoniae had high rates of resistance to penicillin and third-generation cephalosporins.
Blood Coagulation and Asthma Exacerbation in Children.

Recent studies have demonstrated the activation of coagulation pathways in asthmatic airways. This study aimed to determine systemic blood coagulation during asthma exacerbation compared with the stable state in children.



Pediatric patients (aged between 5 and 15 years) suffering from asthma exacerbation were enrolled. von Willebrand factor (vWF), plasminogen activator inhibitor type-1 (PAI-1), protein C, D-dimer, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), and C-reactive protein (CRP) levels were measured during asthma exacerbation and stable state.



A total of 22 patients were enrolled. The median vWF, PAI-1, and CRP during asthma exacerbation were significantly higher than those of the stable state: 147.5% (interquartile range, IQR: 111.05-196.57) versus 94% (IQR: 69.72-109.62, p < 0.001), 41.9 ng/ml (IQR: 21.91-48.61) versus 26.17 ng/ml (IQR: 15.89-34.44, p < 0.03), and 4.46 mg/l (IQR: 2.15-16.23) versus 0.87 mg/l (IQR: 0.20-3.89, p < 0.015), respectively. However, the median protein C during asthma exacerbation was significantly lower than that of the stable state: 99.5% (IQR: 86.75-117) versus 113% (IQR: 94-115.25), p = 0.01. No significant difference was found between the levels of D-dimer, F1 + 2, and TAT during asthma exacerbation and stable state. Ultimately, D-dimer was positively correlated with asthma exacerbation score (R = 0.466, p = 0.027). A significant correlation was observed between vWF and CRP (R = 0.527, p = 0.012).



Evidence was found of increased endothelial activation and increased PAI-1 during asthma exacerbation. This may emphasize the potential role of blood coagulation in asthma exacerbation.
The heart in Friedreich ataxia: definition of cardiomyopathy, disease severity, and correlation with neurological symptoms.

This cross-sectional study provides a practical approach for the clinical assessment of Friedreich ataxia (FA) cardiomyopathy (FA-CM).



A comprehensive cardiac assessment, including standard echocardiography, color Doppler myocardial imaging, cardiac magnetic resonance imaging, ECG, and exercise stress testing, was performed in 205 FA patients. To assess myocardial hypertrophy in FA-CM, the end-diastolic interventricular septal wall thickness (IVSTd) was found to be the best echocardiographic parameter compared with cardiac magnetic resonance imaging-determined left ventricular mass. With the use of this parameter, 4 groups of patients with FA-CM could be defined. Patients with normal values for IVSTd (31.7%) were classified as having no FA-CM. Patients with an IVSTd exceeding the predicted normal IVSTd were classified as having mild FA-CM (40%) if IVSTd exceeded the normal value by <18% or as having intermediate FA-CM (16.1%) if IVSTd exceeded the normal value by ≥18%. Patients with ejection fraction <50% were classified as having severe FA-CM (12.2%). In addition to increased myocardial mass, severe FA-CM was further characterized by dilatation of the left ventricle, reduced systolic strain rate of the posterior wall, and ECG abnormalities. Regional myocardial function correlated negatively with FA-CM groups. Younger patients had a tendency for more advanced FA-CM. Importantly, no clear correlation was found between FA-CM groups and neurological function.



We provide and describe a readily applicable clinical grouping of the cardiomyopathy associated with FA based on echocardiographic IVSTd and ejection fraction data. Because no distinct interrelations between FA-CM and neurological status could be determined, regular follow-up of potential cardiac involvement in FA patients is essential in clinical practice.
Reduction in hospital admissions for acute coronary syndrome after the successful implementation of 100% smoke-free legislation in Argentina: a comparison with partial smoking restrictions.

Several studies have shown a decrease in acute coronary syndrome (ACS) admissions after the implementation of 100% smoke-free legislation. However, no studies have been conducted in developing countries.



We conducted a time series analysis of ACS hospital admissions in Santa Fe province and Buenos Aires city, Argentina. In 2006, Santa Fe implemented a 100% smoke-free law and Buenos Aires implemented a partial law with designated smoking areas and exceptions. Age-standardised ACS admissions rates were compared before and after the implementation of the laws in each district. Smoking prevalence, compliance with legislation and exposure to secondhand smoke (SHS) was also assessed in both districts.



In Santa Fe an immediate decrease in ACS admissions was observed after implementation (-2.5 admissions per 100,000, p=0.03; 13% reduction), compared with no change in Buenos Aires city (rate ratio Santa Fe vs Buenos Aires: 0.74, 95% CI 0.63 to 0.86, p≤0.001). In Santa Fe, the immediate effect was followed by a persistent decrease in admissions due to ACS (-0.26 admissions per 100,000 per month). Smoking prevalence did not change significantly in either district during the same period. In both districts, there was a reduction in self-reported SHS exposure, with a trend towards lower exposure in Santa Fe province. No other comprehensive tobacco control interventions were implemented during the study period.



A 100% smoke-free law was more effective than a partial restriction law in reducing ACS admissions. An immediate effect was followed by a sustained decrease in ACS admissions. Smoke-free initiatives can be also effective in decreasing acute coronary events in developing countries.
Long-term blood pressure variability throughout young adulthood and cognitive function in midlife: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Whether long-term blood pressure (BP) variability throughout young adulthood is associated with cognitive function in midlife remains uncertain. Using data from the Coronary Artery Risk Development in Young Adults (CARDIA), which recruited healthy young adults aged 18 to 30 years (mean age, 25 years) at baseline (Y(0)), we assessed BP variability by SD and average real variability (ARV) for 25 years (8 visits). Cognitive function was assessed with the Digit Symbol Substitution Test (psychomotor speed test), the Rey Auditory Verbal Learning Test (verbal memory test), and the modified Stroop test (executive function test) at follow-up (Y(25)). At the Y(25) examination, participants (n=2326) had a mean age of 50.4 years, 43% were men, and 40% were black. In multivariable-adjusted linear regression models, higher ARV(SBP), ARV(DBP), and SD(DBP) were significantly associated with lower scores of Digit Symbol Substitution Test (β [SE]: -0.025 [0.006], -0.029 [0.007], and -0.029 [0.007], respectively; all P<0.001) and Rey Auditory Verbal Learning Test (β [SE]: -0.016 [0.006], -0.021 [0.007], and -0.019 [0.007], respectively; all P<0.05) after adjustment for demographic and clinical characteristics and with cumulative exposure to BP through Y(0) to Y(25). Neither SDBP nor ARV(BP) was associated with the Stroop score. The associations between ARV(BP) or SD(BP) and each cognitive function test were similar between blacks and whites except for 1 significant interaction between race and SDS(BP) on the Digit Symbol Substitution Test (P<0.05). Long-term BP variability for 25 years beginning in young adulthood was associated with worse psychomotor speed and verbal memory tests in midlife, independent of cumulative exposure to BP during follow-up.
Patient-Reported Outcomes After a Switch to a Single-Tablet Regimen of Rilpivirine, Emtricitabine, and Tenofovir DF in HIV-1-Positive, Virologically Suppressed Individuals: Additional Findings From a Randomized, Open-Label, 48-Week Trial

Patient-reported outcomes (PROs) can provide important information about treatment tolerability in HIV-1-infected patients.



The aim of this study was to evaluate PROs following switching from a boosted protease inhibitor-based regimen to the single-tablet regimen (STR) of rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) in the 48-week open-label Switching Boosted PI to Rilpivirine in Combination with Truvada as a Single-Tablet Regimen (SPIRIT) trial.



In the open-label SPIRIT trial, patients were randomized to receive an STR of RPV/FTC/TDF (n = 317) for 48 weeks or stay on their baseline regimen of a ritonavir-boosted protease inhibitor and two nucleoside/nucleotide analog reverse transcriptase inhibitors (PI + RTV + 2NRTIs, n = 159) for 24 weeks before switching to RPV/FTC/TDF for another 24 weeks. PRO assessments included the HIV Treatment Satisfaction Questionnaire (TSQ) and the HIV Symptom Index Questionnaire (SIQ).



At week 24, the mean HIV TSQ improvement from baseline was significantly greater in the RPV/FTC/TDF group than the PI + RTV + 2NRTIs group (p < 0.001). On the HIV SIQ, the percentage of patients reporting a shift from 'symptom' to 'no symptom' was significantly greater with RPV/FTC/TDF treatment compared with PI + RTV + 2NRTIs for all items (all p ≤ 0.01), with total within-group occurrence of 13/20 symptoms significantly decreasing from baseline for RPV/FTC/TDF patients. In the delayed switch group, significantly fewer patients reported diarrhea and sleep problems at week 48 vs. week 24.



These data suggest that switching to the STR RPV/FTC/TDF from a PI-based multi-pill regimen is associated with greater patient-reported treatment satisfaction and improved tolerability in HIV-1-infected, virologically suppressed individuals.
Continuous flow biphasic positive airway pressure by helmet in patients with acute hypoxic respiratory failure: effect on oxygenation

We investigated the effects of periodical high pressure breaths (SIGH) or biphasic positive pressure ventilation (BIPAP) during helmet continuous positive airway pressure (CPAP) in patients with acute hypoxic respiratory failure. We used a recently developed electromechanical expiratory valve (TwinPAP®, StarMed, Mirandola, Italy), which is time-cycled between two customizable positive end-expiratory pressure (PEEP) levels. We studied 21 patients (67 ± 17 years old) undergoing helmet CPAP. Continuous flow CPAP system was set at 60 l/min flow rate while maintaining clinical FiO2 (51 ± 15%). Five steps, lasting 1 h each, were applied: (1) spontaneous breathing with PEEP 0 cmH2O (SB), (2) CPAP with PEEP 8 cmH2O (CPAPbasal), (3) low PEEP, 8 cmH2O, for 25 s and high PEEP, 25 cmH2O, for 5 s (SIGH), (4) low PEEP, 8 cmH2O, for 3 s and high PEEP, 20 cmH2O, for 3 s (BIPAP), (5) CPAP with PEEP 8 cmH2O (CPAPfinal). We randomized the sequence of SIGH and BIPAP. PaO2 was significantly higher during all steps compared to SB. When compared to CPAPbasal, both SIGH and BIPAP induced a further increase in PaO2. PaO2 during SIGH and BIPAP were not different. The oxygenation improvement was maintained during CPAPfinal. Superimposed, nonsynchronized positive pressure breaths delivered during helmet CPAP by means of the TwinPAP® system may improve oxygenation in patients with acute hypoxemic respiratory failure, even at a rate as low as two breaths per minute.