nils-herrmann/clean_scirepeval huggingface dataset:
Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma.

We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma.



In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability.



All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue.



Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.
Herbal supplements and skin testing: the lack of effect of commonly used herbal supplements on histamine skin prick testing.

The use of herbal supplements is common, yet little is known about their pharmacologic properties. The purpose of this study was to assess the effects of 23 commonly used herbal supplements on histamine skin prick testing (SPT).



Fifteen healthy volunteers participated in a double-blind, placebo-controlled, single-dose, crossover study. Wheal and flare responses to SPT with histamine phosphate (1 mg/ml) were measured before and 4 h after administration of each of the 23 popular herbal supplements, fexofenadine (60 mg) and placebo. Wheal and flare areas were recorded with tracings performed 10 min after the prick test and measured with a PC-digitizer using stereometric software.



Fexofenadine significantly suppressed the wheal (P < 0.001) and flare (P = 0.02) areas compared with placebo. None of the herbal supplements caused significant suppression of the wheal and flare areas compared with placebo (P > 0.10).



When taken in single-doses, the popular herbal supplements tested did not significantly affect the histamine skin response. Therefore, it seems unnecessary for clinicians to ask patients to discontinue these herbal supplements prior to allergy skin testing.
The validity and reliability of modelled neural and tissue properties of the ankle muscles in children with cerebral palsy.

Spastic cerebral palsy (CP) is characterized by increased joint resistance, caused by a mix of increased tissue stiffness, as well as involuntary reflex and background muscle activity. These properties can be quantified using a neuromechanical model of the musculoskeletal complex and instrumented assessment. The construct validity of the neuromechanical parameters was examined (i.e. the internal model validity, effect of knee angle, speed and age, sensitivity to patients versus controls, spasticity severity and treatment), together with the repeatability. We included 38 children with CP and 35 controls. A motor driven footplate applied two slow (15°/s) and two fast (100°/s) rotations around the ankle joint, at two different knee angles. Ankle angle, torque and EMG of the gastrocnemius (GA), soleus (SO) and tibialis anterior (TA) muscle were used to optimize a nonlinear neuromuscular model. Outcome measures were tissue stiffness, reflex and background activity for GA, SO and TA. The internal model validity showed medium to high parameter confidence and good model fits. All parameter could discriminate between patients with CP and controls according to CP pathology. Other measures of external model validity (effect of test position, speed and age) showed behaviour along the lines of current knowledge of physiology. GA/SO background activity was sensitive to spasticity severity, but reflex activity was not. Preliminary data indicated that reflex activity was reduced after spasticity treatment. The between-trial and -day repeatability was moderate to good. The large variance between patients in the ratio of stiffness and neural resistance indicates that the method could potentially contribute to patient-specific treatment selection.
Increased risk of subarachnoid hemorrhage in patients with systemic lupus erythematosus: a nationwide population-based study.

A relatively common occurrence of spontaneous subarachnoid hemorrhage (SAH) in patients with systemic lupus erythematosus (SLE) has been noted; however, the subsequent studies were conflicting. This nationwide population-based study aimed to evaluate the risk of SAH in patients with SLE.



We identified 16,967 SLE patients from the Taiwan National Health Insurance (NHI) database between 2000 and 2006, and compared the incidence rate of SAH with 16,967 randomly selected age- and sex-matched non-SLE subjects. A Cox multivariable proportional hazards model was used to evaluate the risk factors of SAH in the SLE cohort.



The SLE cohort had a higher risk of SAH, with an incidence rate ratio of 4.84 (P < 0.001). Despite a younger age, the mortality rate after SAH was significantly higher in the SLE cohort compared to all of the non-SLE SAH patients identified from the 1 million NHI beneficiaries (60.0% versus 38.9%; P = 0.007). Age (hazard ratio [HR] 1.03, 95% confidence interval [95% CI] 1.01-1.05), platelet transfusion (HR 2.75, 95% CI 1.46-5.17), red blood cell transfusion (HR 7.11, 95% CI 2.81-17.97), and a mean daily steroid dose >10 mg of prednisolone or equivalent (HR 4.36, 95% CI 2.19-8.68) were independent risk factors for the new onset of SAH.



This study demonstrated that SAH is a rare but associated complication of SLE with a high mortality rate. Other than age, higher mean daily steroid use and a history of platelet or red blood cell transfusion were associated with the occurrence of SAH in patients with SLE.
Evaluation of breast cancer service screening programme with a Bayesian approach: mortality analysis in a Finnish region

Evaluation of long-term effectiveness of population-based breast cancer service screening program in a small geographic area may suffer from self-selection bias and small samples. Under a prospective cohort design with exposed and non-exposed groups classified by whether women attended the screen upon invitation, we proposed a Bayesian acyclic graphic model for correcting self-selection bias with or without incorporation of prior information derived from previous studies with an identical screening program in Sweden by chronological order and applied it to an organized breast cancer service screening program in Pirkanmaa center of Finland. The relative mortality rate of breast cancer was 0.27 (95% CI 0.12–0.61) for the exposed group versus the non-exposed group without adjusting for self-selection bias. With adjustment for selection-bias, the adjusted relative mortality rate without using previous data was 0.76 (95% CI 0.49–1.15), whereas a statistically significant result was achieved [0.73 (95% CI 0.57–0.93)] with incorporation of previous information. With the incorporation of external data sources from Sweden in chronological order, adjusted relative mortality rate was 0.67 (0.55–0.80). We demonstrated how to apply a Bayesian acyclic graphic model with self-selection bias adjustment to evaluating an organized but non-randomized breast cancer screening program in a small geographic area with a significant 27% mortality reduction that is consistent with the previous result but more precise. Around 33% mortality was estimated by taking previous randomized controlled data from Sweden.
Blood pressure control rates with an antihypertensive regimen including trandolapril in a Canadian usual-care setting.

The aim of the study was to assess the effects on blood pressure (BP) levels and control rates in hypertensive subjects receiving trandolapril as monotherapy or as part of an antihypertensive regimen in everyday Canadian clinical practice.



The MAVIKtory study was a multicenter, single-arm observational study in 601 primary-care centers in Canada. Diabetic and nondiabetic subjects were included, who were treated with trandolapril for hypertension in accordance with usual practices and national guidelines. Subjects received trandolapril as a new prescription, alone, or in combination with prior therapy. Treatment regimens were at the discretions of the treating physicians. Subjects were followed for 6 months. The primary outcomes measures were the percentage of subjects reaching BP targets set by their physicians after 6 months of therapy, and the percentage of subjects reaching the guidelines targets (systolic blood pressure [SBP]/diastolic blood pressure [DBP] < 140/90 mm Hg) after 6 months as assessed by their physicians. Other outcomes were the percentage of diabetic subjects reaching BP targets, and tolerability.



A total of 8787 subjects were enrolled and included in the intention-to-treat population. Starting doses of trandolapril were 1 or 2 mg in the majority of subjects and remained unchanged in 51.9% of the population at 6 months. The target of < 140/90 (< 130/80) mm Hg was reached by 67.3% of the population. The lower mean physician-set target of 133.4/83.3 mm Hg for nondiabetic subjects and 128.6/79.3 mm Hg for diabetic subjects was reached by 52.2%. Mean reductions from baseline to month 6 were 19.4 mm Hg (95% CI: [-19.9 to -19.0]) in SBP, and 10.1 mm Hg (95% CI: [-10.4 to -9.8]) in DBP. Cough was the most commonly reported adverse event, reported in 4.2% of all subjects.



Trandolapril demonstrated a favorable safety and effectiveness profile. SBP reductions of approximately 20 mm Hg and control rates > 65% could be achieved over 6 months.
Validation of Synthetic CRISPR Reagents as a Tool for Arrayed Functional Genomic Screening

To date, lentiviral-based CRISPR-Cas9 screens have largely been conducted in pooled format. However, numerous assays are not amenable to pooled approaches, and lentiviral screening in arrayed format presents many challenges. We sought to examine synthetic CRISPR reagents in the context of arrayed screening. Experiments were performed using aberrant DNA replication as an assay. Using synthetic CRISPR RNAs targeting the known control gene GMNN in HCT-116 cells stably expressing Cas9, we observed statistically significant phenotype among the majority of transfected cells within 72 hours. Additional studies revealed near complete loss of GMNN protein and editing of GMNN DNA. We next conducted a screen of synthetic CRISPR RNAs directed against 640 ubiquitin-related genes. Screening identified known and novel DNA replication regulators that were also supported by siRNA gene knockdown. Notably, CRISPR screening identified more statistically significant hits than corresponding siRNA screens run in parallel. These results highlight the possibility of using synthetic CRISPR reagents as an arrayed screening tool.
Outcome assessment of decentralization of antiretroviral therapy provision in a rural district of Malawi using an integrated primary care model.

To assess the effect of decentralization (DC) of antiretroviral therapy (ART) provision in a rural district of Malawi using an integrated primary care model.



Between October 2004 and December 2008, 8093 patients (63% women) were registered for ART. Of these, 3440 (43%) were decentralized to health centres for follow-up ART care. We applied multivariate regression analysis that adjusted for sex, age, clinical stage at initiation, type of regimen, presence of side effects because of ART, and duration of treatment and follow-up at site of analysis.



Patients managed at health centres had lower mortality [adjusted OR 0.19 (95% C.I. 0.15-0.25)] and lower loss to follow-up (defaulted from treatment) [adjusted OR 0.48 (95% C.I. 0.40-0.58)]. During the first 10 months of follow-up, those decentralized to health centres were approximately 60% less likely to default than those not decentralized; and after 10 months of follow-up, 40% less likely to default. DC was significantly associated with a reduced risk of death from 0 to 25 months of follow-up. The lower mortality may be explained by the selection of stable patients for DC, and the mentorship and supportive supervision of lower cadre health workers to identify and refer complicated cases.



Decentralization of follow-up ART care to rural health facilities, using an integrated primary care model, appears a safe and effective way to rapidly scale-up ART and improves both geographical equity in access to HIV-related services and adherence to ART.
The Chromatin Pattern of Cell Nuclei Is of Prognostic Value for Renal Cell Carcinomas

Using a series of 105 renal cell carcinomas (RCCs) we investigated whether features quantitatively describing the appearance of Feulgen-stained nuclei and, more particularly, of their chromatin (on the basis of computer-assisted microscopy) can contribute any significant prognostic information. Thirty morphonuclear and 8 nuclear DNA content-related variables were thus generated. The actual prognostic values of this set of cytometric variables was compared (by means of discriminant statistical analysis) to conventional diagnostic and/or prognostic markers including histopathological grades, tumour invasion levels and the presence or absence of metastases. We obtained complete clinical follow-ups for 49 of the 105 RCC patients under study, making it possible to define a subset of patients with a bad prognosis (i.e., who died in the 12 months following nephrectomy) and a subset of patients with a good prognosis (i.e., who survived at least 24 months following nephrectomy). An original method of data analysis related to artificial intelligence (decision tree induction) enabled a strong prognostic model to be set up. In the case of 10 new patients, this model identified all the dead patients as having a bad survival status, with a total of 8 correct predictions. Another prognostic model similarly generated enabled the correct predictions to be confirmed.
Ameloblastic Fibrosarcoma of the Mandible: A Case Report and Brief Review of the Literature

Ameloblastic fibrosarcoma is an uncommon odontogenic tumor composed of a benign epithelial component and a malignant ectomesenchymal component most frequently seen in the third and fourth decades of life. It mainly presents as a painful maxillary or mandibular swelling. Radiographs show a radiolucent mass with ill-defined borders. Radical surgical excision and long-term follow-up are the suggested treatment. We report the case of a 22-year-old female with a 2-month history of an asymptomatic swelling in her left mandible. Examination revealed an exophytic growth measuring 3 × 3 cm extending from the mandibular left first premolar to the second molar. The patient underwent a left hemimandibular resection. Histopathological examination revealed a biphasic tumor composed of inconspicuous islands of benign odontogenic epithelium and an abundant malignant mesenchymal component with marked cellularity, nuclear pleomorphism, hyperchromatism, and moderate mitotic figures with clear margins; one year after the surgical procedure, the patient is clinically and radiologically disease-free.
Retention in physically demanding jobs of individuals with low back pain: study protocol for a randomised controlled trial

Low back pain is prevalent and is a frequent cause of disability and sick leave among working adults. Individuals with low back pain often consult general practice or other health care providers which often results in a unilateral intervention focussed on their symptoms. Employment is associated with physical and mental well-being, so, patients may benefit from an early additional occupational medicine intervention. For individuals with physically demanding jobs it can be especially challenging to retain their jobs. The aim of the 'GoBack trial' is to develop and evaluate the efficacy and feasibility of an occupational medicine intervention for individuals with low back pain in physically demanding jobs.



We will conduct a randomised controlled trial enrolling 300 participants with difficulty in maintaining physically demanding jobs due to low back pain for a current period of 2 to 4 weeks. Participants will be randomised and stratified according to their age and gender before being allocated in a 1:1 ratio to either control or additional occupational medicine intervention. Both groups will receive conventional treatment for their low back pain during the study. All participants will be thoroughly assessed for causes of low back pain and potential prognostic factors by questionnaires, clinical specialist assessments and magnetic resonance imaging (MRI) scans of the lumbar spine. Primary outcome is the accumulated duration of self-assessed sick leave (in days) due to low back pain during 6 months from baseline. Secondary outcomes include general self-rated back pain, disability and screening for potential prognostic factors: fear avoidance behaviour, disability, health status and degenerative MRI findings. For tertiary purposes selected outcomes will also be assessed after 1 and 2 years from baseline.



Many guidelines exist for the management of low back pain, but they provide limited guidance on occupational aspects. The findings from this randomised trial will provide high-quality evidence for the efficacy and feasibility of an occupational medicine intervention model for individuals with low back pain in physically demanding jobs.
Famotidine for infant gastro-oesophageal reflux: a multi-centre, randomized, placebo-controlled, withdrawal trial.

Gastro-oesophageal reflux afflicts up to 7% of all infants. Histamine-2 receptor antagonists are the most commonly prescribed medications for this disorder, but few controlled studies support this practice.



To evaluate the safety and efficacy of famotidine for infant gastro-oesophageal reflux disease.



Thirty-five infants, 1.3-10.5 months of age, entered an 8-week, multi-centre, randomized, placebo-controlled, two-phase trial: first 4 weeks, observer-blind comparison of famotidine 0.5 mg/kg and famotidine 1.0 mg/kg; second 4 weeks, double-blind withdrawal comparison (safety and efficacy) of each dose with placebo.



No serious adverse events were reported. Eleven patients had 16 non-serious, possibly drug-related adverse experiences: 6 patients with agitation or irritability (manifested as head-rubbing in two), 3 patients with somnolence, 2 patients with anorexia, 2 with headache, 1 patient with vomiting, 1 patient with hiccups, and 1 patient with candidiasis. Of the 35 infants, 27 completed Part I. There were significant score improvements for famotidine 0.5 mg/kg in regurgitation frequency (P = 0.04), and for famotidine 1.0 mg/kg in crying time (P = 0.027) and regurgitation frequency (P = 0.004) and volume (P = 0.01). Eight infants completed Part II on double-blind treatment, which was insufficient for meaningful comparisons.



Histamine-2 receptor antagonists may cause agitation and headache in infants. A possibly efficacious famotidine dose for infants is 0.5 mg/kg (frequency adjusted for age). As 1.0 mg/kg may be more efficacious in some, the dosage may require individualization based on response. Further sizeable placebo-controlled evaluations of histamine-2 receptor antagonists in infants with gastro-oesophageal reflux disease are warranted.
The inferior radiolucent area within the cardiac silhouette: validation as a landmark for coronary sinus catheterization.

Catheterization of the coronary sinus (CS) plays a preponderant role in device implantation and electrophysiology. Nevertheless, catheterization of this structure can be time-consuming and is related to operator experience. An inferior radiolucent area of the cardiac right anterior oblique (RAO) view has been suggested as a landmark to guide CS catheterization. However, the true relationship of this area with the CS ostium (CSO) has not been studied.



Thirty-five consecutive patients who underwent right coronary angiography were prospectively enrolled in the study. Fluoroscopic images of the heart in the right anterior oblique, both immediately before and during the venous phase of right coronary angiography, were recorded and digitally stored. Postprocedure measurements of the inferior radiolucent area within the cardiac silhouette and, subsequently, the distance of this area to the CSO, were performed by two independent observers.



A radiolucent area of 9.5 +/- 3.0 x 11.0 +/- 3.4 mm was identified in the inferior annulus by the two evaluators in all patients. No significant differences in the dimensions of this area were found between the two observers. The CSO was 9.6 +/- 7.2 mm superior and 0.1 +/- 9.0 mm posterior to the radiolucent area and no statistically significant differences were found between the two observers.



An inferior radiolucent area can be identified within the cardiac silhouette in most patients in the RAO view. This area is slightly anterior and inferior to the CSO and can be used for catheterization guidance of this latter structure.
Predictors of Limb Fat Gain in HIV Positive Patients Following a Change to Tenofovir-Emtricitabine or Abacavir-Lamivudine

Antiretroviral treatment (cART) in HIV causes lipoatrophy. We examined predictors of anthropometric outcomes over 96 weeks in HIV-infected, lipoatrophic adults receiving stable cART randomised to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) fixed dose combinations.



The STEAL study was a prospective trial of virologically suppressed participants randomised to either TDF-FTC (n = 178) or ABC-3TC (n = 179). Anthropometric assessment was conducted at baseline, weeks 48 and 96. The analysis population included those with baseline and week 96 data remaining on randomised therapy. Distribution of limb fat change was divided into four categories (≤ 0%, >0-10%, >10-20%, >20%). Baseline characteristics [demographics, medical history, metabolic and cardiovascular biomarkers] were assessed as potential predictors of change in percent subcutaneous limb fat using linear regression. 303 participants (85% of STEAL population) were included. Baseline characteristics were: mean (± SD) age 45 (± 8) years; thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI) duration 4 (± 3) years; limb fat 5.4 (± 3.0)kg; body mass index 24.7 (± 3 .5) kg/m(2). Mean (SD) limb fat gain to week 48 and 96 was 7.6% (± 22.4) and 13.2% (± 27.3), respectively, with no significant difference between groups. 51.5% of all participants had >10% gain in limb fat. Predictors of greater limb fat gain at week 96 were baseline tNRTI (10.3, p = 0.001), glucose >6 mmol/L (16.1, p = 0.04), higher interleukin 6 (IL-6) (2.8, p = 0.004) and lower baseline limb fat (3.8-6.4 kg - 11.2; >6.4 kg - 15.7, p trend<0.001).



Modest peripheral fat gain occurred with both TDF-FTC and ABC-3TC. Baseline factors associated with more severe lipodystrophy (lipoatrophy, baseline tNRTI, raised IL6, and glucose) predicted greater limb fat recovery at 96 weeks.