nils-herrmann/clean_scirepeval huggingface dataset:
Stereotactic body radiotherapy for localized prostate cancer: pooled analysis from a multi-institutional consortium of prospective phase II trials.

The effectiveness of stereotactic body radiotherapy (SBRT) for localized prostate cancer is tested.



A total of 1100 patients with clinically localized prostate cancer were enrolled in separate prospective phase 2 clinical trials of SBRT from 8 institutions during 2003-11 and pooled for analysis. SBRT using the CyberKnife delivered a median dose of 36.25Gy in 4-5 fractions. Patients were low-risk (58%), intermediate-risk (30%) and high-risk (11%). A short-course of androgen deprivation therapy (ADT) was given to 14%. PSA relapse defined as a rise >2ng/ml above nadir was analyzed with the Kaplan Meier method.



With a median follow-up of 36months there were 49 patients with PSA failure (4.5%), 9 of whom were subsequently determined to be benign PSA bounces. The 5-year biochemical relapse free survival (bRFS) rate was 93% for all patients; 95%, 83% and 78% for GS ⩽6, 7 and ⩾8, respectively (p=0.001), and 95%, 84% and 81% for low-, intermediate- and high-risk patients, respectively (p<0.001). No differences were observed with ADT (p=0.71) or as a function of total dose (p=0.17). A PSA bounce of >0.2ng/ml was noted among 16% of patients. For 135 patients possessing a minimum of 5years follow-up, the 5-year bRFS rate for low- and intermediate-risk patients was 99% and 93%, respectively.



PSA relapse-free survival rates after SBRT compare favorably with other definitive treatments for low and intermediate risk patients. The current evidence supports consideration of SBRT among the therapeutic options for these patients.
Efficacy and safety of once daily triamcinolone acetonide aqueous nasal spray in adults with non-allergic and allergic rhinitis.

The efficacy of corticosteroid has not been thoroughly studied in the treatment of non-allergic rhinitis. This study was designed to compare the efficacy of nasal corticosteroid in patients with allergic rhinitis (AR), and non-allergic rhinitis (NAR).



The efficacy of triamcinolone acetonide nasal spray (TANS) on total nasal symptom scores (TNSS), and nasal peak inspiratory flow rate (nPIFR) was studied in a six-week parallel-group trial of NAR (n: 25), and AR (n: 16) patients. Health-related quality of life (HRQoL) and Epworth Sleepiness Scale (ESS) were also analysed.



The TNSSs, and symptom scores of conjunctivitis, snoring, and postnasal drainage were significantly improved in both groups, after two and six weeks of treatment. In contrast to AR, patients with NAR had statistically significant improvement in nasal obstruction, and postnasal drainage beginning from two weeks of the treatment. nPIFR slightly increased in both groups. Scores of generic (SF-36), rhinitis specific (MiniRQLQ) and ESS questionnaires generally improved better in AR than NAR. TANS was well-tolerated in AR and NAR groups with minor adverse events including headache, nasal burning, and bitter mouth taste.



Our study disproved the idea of ineffectiveness of corticosteroid treatment in NAR, and showed that triamcinolone acetate may be an alternative drug in the treatment of NAR.
A Phase 2a Study of Benralizumab for Patients with Eosinophilic Asthma in South Korea and Japan.

Airway eosinophils are considered to play an important role in the pathogenesis of asthma. Interleukin-5 is believed to be a key cytokine for the development, proliferation and activation of eosinophils. Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody that depletes blood and airway eosinophils. We conducted a phase 2a study in South Korea and Japan to evaluate the effect of benralizumab in an East Asian population. The primary objective was to evaluate the effect of benralizumab in adults with uncontrolled eosinophilic asthma with 2-6 incidences of exacerbations in the past year using a medium/high dose of inhaled corticosteroids and long-acting β2-agonists.



This was a multicenter, randomized, double-blind, placebo-controlled study. The subjects (n = 106) were randomized into four groups: placebo (n = 27) or benralizumab 2 mg (n = 27), 20 mg (n = 26) and 100 mg (n = 26). Benralizumab or placebo were administered subcutaneously on weeks 0 (day 1), 4, 8, 16, 24, 32 and 40. The primary endpoint was the asthma exacerbation rate at week 52.



The asthma exacerbation rate was reduced by 33, 45 or 36% versus the placebo group when treated with 2, 20 or 100 mg of benralizumab, respectively. The percent mean change in forced expiratory volume at 1 s increased with each of the three doses in subjects treated with benralizumab.



Benralizumab reduced asthma exacerbation and improved lung function and asthma control in adults with uncontrolled eosinophilic asthma.
Topiramate: a prospective study on the relationship between concentration, dosage and adverse events in epileptic patients on combination therapy.

The relationship between topiramate (TPM) concentration, dosage and adverse events in patients with epilepsy is still controversial. We therefore performed a prospective study in patients with poorly controlled epilepsy treated with TPM, predominantly in combination with other antiepileptic drugs. The goal of the study was to investigate the relationship between the occurrence of adverse events due to TPM and its serum concentration or dosage, respectively.



The relationship between the occurrence of adverse events and TPM serum concentration or dosage, respectively, was examined in a group of 42 young adult and adult patients with poorly controlled epilepsy. Within 22 months, all patients treated with TPM had been included in the study. The 8 adverse events occurring most frequently (difference > or = 10%) in TPM-treated patients in 5, double-blind, placebo-controlled, parallel group studies, were checked regularly. This side effect profile has been presented by Reife et al. (1995a). Other possible or probable adverse events were also documented.



The difference in TPM serum concentrations and TPM dosages (mg/kg) for patients without an adverse event, and patients with a given adverse event was statistically significant for "abnormal thinking, impaired concentration, weight loss, dizziness, speech problems, somnolence, ataxia, increased seizure frequency and paresthesia". To avoid adverse events, we recommend an initial "maintenance serum concentration" of below 4 microg/mL. As regards the TPM dosage, our results suggest initial maintenance dosages of 100 TPM or lower, 1.5 mg/kg or lower, respectively. These conclusions are limited by the relatively small number of patients.
Hematopoietic progenitor cell mobilization and harvesting in children with malignancies: do the advantages of pegfilgrastim really translate into clinical benefit?

Our purpose was to assess success rates in children of achieving optimal hematopoietic progenitor cells (HPCs) harvest after mobilization with 300 μg/kg pegfilgrastim. Between January 2005 and January 2007, 26 children with solid malignancies who were referred for HPC collection were consecutively included. Hematopoietic progenitor cell mobilization consisted of one s.c. injection of 300 μg/kg body weight (BW) of pegfilgrastim. The success criterion was defined as at least 5 × 106 CD34+ cells/kg during the first standard apheresis (less than 3 blood volumes processed (BVP)). After 26 inclusions, the Bayesian analysis gave a mean estimated success rate of 60.7% (95% credibility interval: 42.0–78.0%). The first apheresis allowed the collection of 8.3 × 106 CD34+ cells/kg BW (range 0.6–37.8), with a median of 2.8 BVP (range 1.4–3.0). Overall, the median of CD34+ cells collected was 12.4 × 106/kg (range 2.7–37.8). The cumulative dose of anthracyclin was the only variable associated with the total number of CD34+ collected cells (P<0.05). Mobilization was clinically well tolerated in 20 patients. No drug-related adverse events of grade ⩾3 occurred. We conclude that a single injection of 300 μg/kg pegfilgrastim in the hematological steady state is an efficient and well-tolerated method of HPC mobilization in children with solid malignancies.
Tolerance of the VocaLog™ Vocal Monitor by Healthy Persons and Individuals With Parkinson Disease.

To assess subject tolerance of extended use of the VocaLog™ vocal monitor (VM), a device marketed to log calibrated decibel sound pressure level.



Prospective between-subjects design including two age- and sex-matched groups: individuals with Parkinson disease (IWPD) and healthy persons.



After an initial session to calibrate the device and demonstrate its use, participants wore the VM during waking hours for five consecutive days. At a second visit to return the VM, participants completed a survey and a short interview regarding their experience with and perceptions of the device.



Those with PD and control subjects reported relatively few issues with use of the VM. There were no group differences regarding convenience, others' reactions, technical issues, or future participation in similar studies. Participants with PD indicated similar frequency of discomfort issues but higher severity ratings for discomfort during VM use compared with healthy participants.



The VocaLog™ offers a method to monitor vocal loudness during everyday activities for several consecutive days. The device was well tolerated by participants from both groups. IWPD reported greater discomfort than controls, possibly reflecting altered sensory perceptions associated with PD. The current data offer some reassurance that this VM can be tolerated by both healthy persons and those with PD for clinical and research purposes.
Evaluation of the safety, pharmacodynamic, and pharmacokinetic effects following oral coadministration of immediate-release morphine with ethanol in healthy male participants.

This paper aimed to evaluate the effects of coadministered immediate-release morphine and ethanol on safety, pharmacokinetic, and pharmacodynamic measures.



In the first stage of a randomized, double-blind, placebo-controlled, crossover study, 16 healthy men with a history of moderate drinking received morphine 50 mg+ethanol 0.7 g/kg, morphine 50 mg+ethanol placebo, and morphine placebo+ethanol 0.7 g/kg. In the second stage, participants received either a lower (30 mg) or higher (80 mg) morphine dose (alone and in combination with ethanol) depending on their tolerability to treatments in stage 1. Safety, pharmacodynamic (including visual analog scales, pupillometry, capnography, and psychomotor and cognitive measures), and pharmacokinetic assessments were conducted.



With the exception of one severe adverse event (AE), all others were mild or moderate in intensity. Morphine resulted in dose-related increases in AEs. When morphine was administered with ethanol, similar AEs were observed (dizziness, headache, somnolence, nausea, and vomiting), but these were sometimes more frequent compared with those observed with either drug alone. No consistent additive or interaction effects were observed on pharmacodynamic measures. Ethanol had no apparent effects on the pharmacokinetics of morphine or its metabolites.



Coadministration of single doses of morphine and ethanol tested in this study did not affect the safety, pharmacodynamics, or pharmacokinetics of morphine or ethanol administered alone.
Lesotho's Minimum PMTCT Package: lessons learned for combating vertical HIV transmission using co-packaged medicines

Mother-to-child transmission of HIV can be reduced to<5% with appropriate antiretroviral medications. Such reductions depend on multiple health system encounters during antenatal care (ANC), delivery and breastfeeding; in countries with limited access to care, transmission remains high. In Lesotho, where 28% of women attending ANC are HIV positive but where geographic and other factors limit access to ANC and facility deliveries, a Minimum PMTCT Package was launched in 2007 as an alternative to the existing facility-based approach. Distributed at the first ANC visit, it packaged together all necessary pregnancy, delivery and early postnatal antiretroviral medications for mother and infant.



To examine the availability, feasibility, acceptability and possible negative consequences of the Minimum PMTCT Package, data from a 2009 qualitative and quantitative study and a 2010 facility assessment were used. To examine the effects on ANC and facility-based delivery rates, a difference-in-differences analytic approach was applied to 2009 Demographic and Health Survey data for HIV-tested women who gave birth before and after Minimum PMTCT Package implementation.



The Minimum PMTCT Package was feasible and acceptable to providers and clients. Problems with test kit and medicine stock-outs occurred, and 46% of women did not receive the Minimum PMTCT Package until at least their second ANC visit. Providing adequate instruction on the use of multiple medications represented a challenge. The proportion of HIV-positive women delivering in facilities declined after Minimum PMTCT Package implementation, although it increased among HIV-negative women (difference-in-differences=14.5%, p=0.05). The mean number of ANC visits declined more among HIV-positive women than among HIV-negative women after implementation, though the difference was not statistically significant (p=0.09). Changes in the percentage of women receiving≥4 ANC visits did not differ between the two groups.



If supply issues can be resolved and adequate client educational materials provided, take-away co-packages have the potential to increase access to PMTCT commodities in countries where women have limited access to health services. However, efforts must be made to carefully monitor potential changes in ANC visits and facility deliveries, and further evaluation of adherence, safety and effectiveness are needed.
Intranasal oxytocin reduces provoked symptoms in female patients with posttraumatic stress disorder despite exerting sympathomimetic and positive chronotropic effects in a randomized controlled trial

Posttraumatic stress disorder (PTSD) is a severe psychiatric disease accompanied by neuroendocrine changes such as adrenergic overdrive and hence an elevated cardiovascular morbidity. Current pharmacotherapeutic options for PTSD are less than suboptimal, necessitating the development of PTSD-specific drugs. Although the neuropeptide oxytocin has been repeatedly suggested to be effective in PTSD treatment, there are, to our knowledge, only three studies that have assessed its efficacy on the intensity of PTSD symptoms in PTSD patients - among them one symptom provocation study in male veterans.



To evaluate for the first time how oxytocin influences the intensity of provoked PTSD symptoms and, furthermore, cardiac control in female PTSD patients, we assessed their psychic and cardiac response to trauma-script exposure with and without oxytocin pretreatment in a double-blind randomized placebo-controlled study. We used a within-subject design to study 35 female PTSD patients who received oxytocin and placebo in a 2-week interval. Furthermore, we performed a small pilot study to get an idea of the relation of the stress-modulated endogenous oxytocin levels and heart rate - we correlated oxytocin serum levels with the heart rate of 10 healthy individuals before and after exposure to the Trier Social Stress Test (TSST).



Intranasal oxytocin treatment was followed by a reduction of provoked total PTSD symptoms, in particular of avoidance, and by an elevation in baseline and maximum heart rate together with a drop in the pre-ejection period, a marker for sympathetic cardiac control. Furthermore, we found a positive correlation between endogenous oxytocin levels and heart rate both before and after TSST challenge in healthy control subjects.



This study provides the first evidence that oxytocin treatment reduces the intensity of provoked PTSD symptoms in female PTSD patients. The small size of both samples and the heterogeneity of the patient sample restrict the generalizability of our findings. Future studies have to explore the gender dependency and the tolerability of the oxytocin-mediated increase in heart rate. This randomized controlled trial was retrospectively registered at the German Trials Register (DRKS00009399) on the 02 October 2015.
Effect of Aldosterone Antagonism on Exercise Tolerance in Heart Failure With Preserved Ejection Fraction.

We appreciate Mr. Pan’s interest in our trial of spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) (1). Apart from the novel entry criteria using abnormal exercise response as a basis (which allowed more physiologic homogeneity than in previous studies), this study also used functional capacity as the primary endpoint, and it showed both a reduction of exertional filling pressure with and an improvement in exercise tolerance with spironolactone. As clinicians know only too well, the primary concern of these older patients is their impaired functional capacity, and recent guidelines emphasize the importance of this target (2). The finding of improved exercise capacity is consistent with the results of previous studies (3), which are often neglected in the dismay that we have been unable to change the outcome of HFpEF. However, Mr. Pan is referring not just to the selection of patients and the use of exercise as an endpoint, but also to the use of exercise as therapy. We did not study this, but there is no doubt that this consistently provides functional benefit in adherent patients, including in HFpEF (4), with survival benefit being more marked in women (5). The risk of harm with this intervention is extremely low, and it is used far less than it should be. As Mr. Pan points out, the weakness is obtaining adherence, especially among frail older patients. Perhaps better surveillance using wearable devices will help to provide a solution to that problem.
Sirolimus conversion may suppress viral replication in hepatitis C virus-positive renal transplant candidates.

Hepatitis C virus in renal transplant recipients is an independent risk factor for sickness and death. It has been shown that one might limit hepatitis C virus progression in liver transplant recipients with sirolimus-based immunosuppression. The mammalian target of rapamycin is an influential molecule for the anti-hepatitis C virus action of interferon. We report our experience with sirolimus conversion in hepatitis C virus-positive patients with chronic allograft nephropathy regarding hepatic and hematologic effects that might affect its future use.



Twenty-five patients who had received renal transplants with anti-hepatitis C virus-positive and normal liver function were enrolled. Ten patients had allograft dysfunction because of cyclosporine nephrotoxicity. Sirolimus was initiated at 2 mg/d and adjusted to 6 to 8 ng/mL. Cyclosporine was gradually tapered and then stopped; 15 patients were used as a control group. Sirolimus-related hepatitis was defined as a rise in liver transferases or alkaline phosphatase or bilirubin over twice the upper limit of normal. Viral replication was defined as elevated liver enzymes and increasing viral load and/or biopsy-proven hepatitis C virus active hepatitis.



After conversion, there was a reduction of hemoglobin and hematocrit. In 1 patient, the immunosuppressive regimen was changed back to cyclosporine owing to anemia and hepatotoxicity leading to prompt return of hematocrit and liver enzymes to their original values. One of 10 antihepatitis C virus-positive patients (10.0%) developed sirolimus-associated hepatotoxicity, compared with 2 patients in the control group (13%). Sirolimus patients showed a significant decrease in the HCV PCR levels from 700 000 to 400 000 IU/mL; P < .001, compared to 680 000 to 660 000 IU/mL in cyclosporine patients; P = NS, with comparable levels of transaminases



Our data suggest that sirolimus has the potential to suppress viral replication in hepatitis C virus-positive renal transplant candidates.
The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies.

The aim of this study was to test the hypothesis that, without diagnostic changes in serum creatinine, increased neutrophil gelatinase-associated lipocalin (NGAL) levels identify patients with subclinical acute kidney injury (AKI) and therefore worse prognosis.



Neutrophil gelatinase-associated lipocalin detects subclinical AKI hours to days before increases in serum creatinine indicate manifest loss of renal function.



We analyzed pooled data from 2,322 critically ill patients with predominantly cardiorenal syndrome from 10 prospective observational studies of NGAL. We used the terms NGAL(-) or NGAL(+) according to study-specific NGAL cutoff for optimal AKI prediction and the terms sCREA(-) or sCREA(+) according to consensus diagnostic increases in serum creatinine defining AKI. A priori-defined outcomes included need for renal replacement therapy (primary endpoint), hospital mortality, their combination, and duration of stay in intensive care and in-hospital.



Of study patients, 1,296 (55.8%) were NGAL(-)/sCREA(-), 445 (19.2%) were NGAL(+)/sCREA(-), 107 (4.6%) were NGAL(-)/sCREA(+), and 474 (20.4%) were NGAL(+)/sCREA(+). According to the 4 study groups, there was a stepwise increase in subsequent renal replacement therapy initiation-NGAL(-)/sCREA(-): 0.0015% versus NGAL(+)/sCREA(-): 2.5% (odds ratio: 16.4, 95% confidence interval: 3.6 to 76.9, p < 0.001), NGAL(-)/sCREA(+): 7.5%, and NGAL(+)/sCREA(+): 8.0%, respectively, hospital mortality (4.8%, 12.4%, 8.4%, 14.7%, respectively) and their combination (4-group comparisons: all p < 0.001). There was a similar and consistent progressive increase in median number of intensive care and in-hospital days with increasing biomarker positivity: NGAL(-)/sCREA(-): 4.2 and 8.8 days; NGAL(+)/sCREA(-): 7.1 and 17.0 days; NGAL(-)/sCREA(+): 6.5 and 17.8 days; NGAL(+)/sCREA(+): 9.0 and 21.9 days; 4-group comparisons: p = 0.003 and p = 0.040, respectively. Urine and plasma NGAL indicated a similar outcome pattern.



In the absence of diagnostic increases in serum creatinine, NGAL detects patients with likely subclinical AKI who have an increased risk of adverse outcomes. The concept and definition of AKI might need re-assessment.
Diabetes mellitus and tuberculosis: pattern of tuberculosis, two-month smear conversion and treatment outcomes in Guangzhou, China.

There is a high burden of both diabetes (DM) and tuberculosis (TB) in China. We evaluated the association between DM and the pattern of disease, 2-month sputum smear conversion and treatment outcomes of patients with TB in Guangzhou, China.



All patients registered with TB from September 2011 to June 2012 were screened for DM and assessed for treatment outcomes in relation to presence or absence of DM and quality of DM control using patient registers, treatment cards and electronic record systems.



There were 1589 patients with TB of whom 189 (12%) had DM. Among those with DM, there was a significantly higher proportion of men, persons aged 35 years and older and persons with smear-positive pulmonary tuberculosis (PTB) (P < 0.01). In patients with DM and new smear-positive PTB, there was a higher proportion who had positive sputum smears at 2 months (21.7% vs. 5.6%, RR 3.85, 95%CI 2.24-6.63), who were lost-to-follow-up (5.2% vs. 1.7%, RR 3.23, 95%CI 1.08-9.63) and who failed treatment (10.3% vs. 2.3%, RR 4.46, 95%CI 1.96-10.18) compared with patients who had no DM. There was no significant association between these adverse outcomes and DM control as measured by 2 and 6-month fasting blood glucose.



Diabetes mellitus in new smear-positive patients with PTB was associated with failure to sputum smear convert at 2 months and adverse treatment outcomes of loss-to-follow-up and failure. Further research is needed to understand the reasons for these findings and to determine whether the current length of treatment of 6 months is adequate.