nils-herrmann/clean_scirepeval huggingface dataset:
Is it time to shift to better characterization of patients in trials assessing novel antidepressants? An example of two relapse prevention studies with agomelatine.

The present paper reports in parallel the findings of the two studies that evaluated the efficacy of agomelatine in preventing relapse of depression. It describes the methodological adjustments made between the first and the second trial, particularly in relation to patient selection and accuracy of diagnosis of depression. Patients with major depressive disorder who responded to an 8/10-week course of agomelatine 25-50 mg treatment were randomly assigned to receive continuation treatment with agomelatine or placebo during a 24-week, randomized, double-blind treatment period with an optional 18- or 20-week double-blind extension period. The cumulative probability of relapse was calculated using the Kaplan-Meier method of survival analysis. Study 1 lacked assay sensitivity because of an unexpectedly low relapse rate in the placebo arm, but was instructive in showing that the agomelatine effect was better than placebo only in those patients with higher symptom levels at baseline. Study 2 showed a robust benefit of agomelatine - a two-fold reduction in the relapse rate - observed at least up to 10 months in both the overall population and the more severely depressed patients. The methodological adjustments introduced in study 2 (e.g. a minimum subscore calculated from eight specific Hamilton Depression Rating Scale items, the use of the self-rating questionnaire Hospital Anxiety Depression Scale and the Sheehan questionnaire) have assured an adequate severity of depression not only on the basis of ratings of symptom severity but also on measures of functional impairment. We did not find increased severity of symptoms in study 2, but we hypothesize that the increased demands on investigators improved the quality of recruitment to represent more real-world patients. Adopting these innovations could contribute towards lower failure rates for future placebo-controlled clinical trials in the field.
Diagnostic accuracy of endometrial thickness for the detection of intra-uterine pathologies and appropriateness of performed hysteroscopies among asymptomatic postmenopausal women.

To measure the diagnostic accuracy of endometrial thickness for the detection of intra-uterine pathologies among asymptomatic postmenopausal women, and to test the diagnostic accuracy and appropriateness of performed hysteroscopies.



Prospective study of 268 asymptomatic postmenopausal women with endometrial thickness ≥4 mm referred to diagnostic hysteroscopy. The diagnostic accuracy of various endometrial thickness cut-off values was tested. Histological and hysteroscopic results were compared to measure the diagnostic accuracy of outpatient hysteroscopies.



No endometrial thickness cut-off values had optimal diagnostic accuracy [positive likelihood ratio (LR+) >10 and negative likelihood ratio (LR-) <0.1]. The best endometrial thickness cut-off value for the detection of all intra-uterine pathologies was ≥8 mm (LR+ 10.05 and LR- 0.22). An endometrial thickness cut-off value ≥10 mm did not miss any cases of endometrial cancer. The success rate of diagnostic hysteroscopy was 89%, but 97% of these revealed a benign intra-uterine pathology. The diagnostic accuracy of hysteroscopy was optimal for all intra-uterine pathologies, except endometrial hyperplasia (LR- 0.52).



Using an endometrial thickness cut-off value ≥4 mm, only 3% of performed hysteroscopies were useful for the detection of pre-malignant or malignant lesions. Despite the finding that endometrial thickness did not show optimal diagnostic accuracy, using the best cut-off value (≥8 mm) may be helpful to decrease the number of false-positive results. No cases of endometrial cancer were diagnosed in asymptomatic postmenopausal women with endometrial thickness <10mm.
Effects of three-times-per-week versus on-demand tadalafil treatment on erectile function and continence recovery following bilateral nerve sparing radical prostatectomy: results of a prospective, randomized, and single-center study.

Erectile dysfunction (ED) and urinary incontinence after bilateral nerve-sparing radical prostatectomy (BNSRP) still remain major causes of morbidity. Phosphodiesterase type 5 inhibitors (PDE5-Is) have a role in the treatment of ED after BNSRP. Several studies in patients with ED and lower urinary tract symptoms demonstrated that PDE5-Is could improve both erectile function and urinary symptoms. The aim of this study was to compare the efficacies of two dosing regimens of 20 mg tadalafil (on-demand and 3 times per week) and to assess the role of tadalafil in recovery of erectile function and continence after BNSRP. We conducted a single-center, prospective, randomized controlled trial of three times per week versus on-demand tadalafil 20 mg and a control group after BNSRP. A total of 129 preoperatively potent and continent patients were included in the study. The patients were evaluated at 6 weeks and 12 months postoperatively for erectile function and continence status. There was no significant difference between all three groups with respect to erectile function at 6 weeks after the surgery. Twelve months after the surgery, the International Index of Erectile Function score was significantly higher in the group using tadalafil 20 mg three times per week. However, there was no significant difference between the treated groups and the control group with respect to the continence status at 12 months after the surgery. There was no correlation between incontinence and ED after the surgery in all groups. Tadalafil 20 mg three times per week is an efficacious and well-tolerated treatment option for ED after BNSRP. Treatment with 20 mg tadalafil either three times per week or on demand cannot improve continence recovery after BNSRP compared with the control group.
Reduced parahippocampal and lateral temporal GABAA-[11C]flumazenil binding in major depression: preliminary results

Major depressive disorder (MDD) has been related to both a dysfunctional γ-amino butyric acid (GABA) system and to hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA). Although GABA has been suggested to inhibit HPA axis activity, their relationship has never been studied at the level of the central GABAA-benzodiazepine receptor in depressed patients or in relation to antidepressant treatment. Eleven depressed outpatients were compared, before and after treatment with citalopram, with nine age-matched healthy controls. The subjects were scanned using the positron emission tomography (PET) tracer [11C]flumazenil ([11C]FMZ). Parametric voxel-by-voxel Logan plots were compared with methods based on regions of interest (ROI), to provide volume of distribution (VT) and binding potential (BPND) values. Plasma GABA levels were determined and a dexamethasone-corticotropin releasing hormone (DEX-CRH) test was performed. In MDD, parametric voxel-by-voxel Logan plots showed bilateral reduced [11C]FMZ binding in the parahippocampal gyrus and right lateral superior temporal gyrus (p uncorrected ≤0.001). In the temporal area, [11C]FMZ binding showed a strong inverse correlation with HPA axis activity. Plasma GABA did not discriminate MDD from controls, but correlated inversely with [11C]FMZ binding in the right insula. Following treatment with citalopram, voxel-based analysis revealed reduced binding in the right lateral temporal gyrus and dorsolateral prefrontal cortex. The bilateral reduction in limbic parahippocampal and right temporal [11C]FMZ binding found in MDD indicates decreased GABAA-benzodiazepine receptor complex affinity and/or number. The inverse relationship between GABAA binding in the temporal lobe and HPA axis activity, suggests that HPA axis hyperactivity is partly due to reduced GABA-ergic inhibition.
Higher Lipoprotein (a) Levels Are Associated with Better Pulmonary Function in Community-Dwelling Older People – Data from the Berlin Aging Study II

Reduced pulmonary function and elevated serum cholesterol levels are recognized risk factors for cardiovascular disease. Currently, there is some controversy concerning relationships between cholesterol, LDL-cholesterol, HDL-cholesterol, serum triglycerides and lung function. However, most previous studies compared patients suffering from chronic obstructive pulmonary disease (COPD) with healthy controls, and only a small number examined this relationship in population-based cohorts. Moreover, lipoprotein a [Lp(a)], another lipid parameter independently associated with cardiovascular diseases, appears not to have been addressed at all in studies of lung function at the population level. Here, we determined relationships between lung function and several lipid parameters including Lp(a) in 606 older community-dwelling participants (55.1% women, 68±4 years old) from the Berlin Aging Study II (BASE-II). We found a significantly lower forced expiration volume in 1 second (FEV1) in men with low Lp(a) concentrations (t-test). This finding was further substantiated by linear regression models adjusting for known covariates, showing that these associations are statistically significant in both men and women. According to the highest adjusted model, men and women with Lp(a) levels below the 20th percentile had 217.3ml and 124.2ml less FEV1 and 239.0ml and 135.2ml less FVC, respectively, compared to participants with higher Lp(a) levels. The adjusted models also suggest that the known strong correlation between pro-inflammatory parameters and lung function has only a marginal impact on the Lp(a)-pulmonary function association. Our results do not support the hypothesis that higher Lp(a) levels are responsible for the increased CVD risk in people with reduced lung function, at least not in the group of community-dwelling older people studied here.
A phase II, randomized, blinded study of the farnesyltransferase inhibitor tipifarnib combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy

This study assessed the clinical efficacy of the farnesyltransferase inhibitor, tipifarnib, combined with letrozole in patients with advanced breast cancer and disease progression following antiestrogen therapy. Postmenopausal women with estrogen-receptor-positive advanced breast cancer that had progressed after tamoxifen were given 2.5 mg letrozole once daily and were randomly assigned (2:1) to tipifarnib 300 mg (TL) or placebo (L) twice daily for 21 consecutive days in 28-day cycles. The primary endpoint was objective response rate. Of 120 patients treated with TL (n = 80) or L (n = 40), 113 were evaluable for response. Objective response rate was 30% (95% CI; 20–41%) for TL and 38% (95% CI; 23–55%) for L. There was no significant difference in response duration, time to disease progression or survival. Clinical benefit rates were 49% (TL) and 62% (L). Tipifarnib was generally well tolerated; a higher incidence of drug-related asymptomatic grade 3/4 neutropenia was observed for TL (18%) than for L (0%). Tipifarnib population pharmacokinetics were similar to previous studies, with no significant difference in trough letrozole concentrations between the TL and L groups. Adding tipifarnib to letrozole did not improve objective response rate in this population of patients with advanced breast cancer.
Long-term outcome for men with teratoma found at postchemotherapy retroperitoneal lymph node dissection.

Patients with pure teratoma within the postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen traditionally have been considered at low risk for disease progression. The objectives of this study were to determine the disease-related outcomes of patients who had pure teratoma identified at the time of PC-RPLND and to examine the prognostic value of clinical variables that were identified previously as important predictors of disease recurrence in these patients.



Between 1980 and 2003, 97 patients with metastatic nonseminomatous germ cell tumor and pure teratoma histology at the time of PC-RPLND were identified. The medical records of these patients were reviewed retrospectively for pertinent clinical and treatment-related outcomes.



At a median follow-up of 7.4 years, 21 patients (22%) developed recurrent disease after PC-RPLND. The 5-year and 10-year probabilities (+/-standard error) of freedom from disease recurrence were 81%+/-4% and 76%+/-5%, respectively. The postchemotherapy alpha-fetoprotein (AFP) level and mediastinal involvement at presentation were statistically significant predictors of disease recurrence on multivariate analysis. Nine of 97 patients (9.3%) died from testis cancer, and 4 patients died from other causes.



In patients with pure teratoma histology at PC-RPLND, mediastinal involvement at presentation and the presence of an elevated AFP level before PC-RPLND predicted an unfavorable outcome. The absence of mediastinal involvement and normal AFP level, however, did not confirm freedom from disease recurrence. Patients who had teratoma at the time of PC-RPLND remained at considerable risk for disease progression because of the unpredictable nature of teratoma and the presence of unrecognized, active germ cell disease outside the retroperitoneum.
Chemotherapy interruptions in relation to symptom severity in advanced breast cancer

Interruptions in medical treatment such as dose delays, reductions, or stoppages can lead to suboptimal treatment of cancer. Knowing how and for whom symptom severity and symptom interference with activities of daily living (ADL) are associated with treatment interruptions can guide behavioral interventions for supportive care. The purpose of this analysis is to inform research and clinical practice by bringing attention to specific patient symptoms that may hinder dose completion. A secondary analysis of data collected in a randomized clinical trial (RCT) of reflexology for symptom management was performed. The trial enrolled women with advanced breast cancer undergoing treatment (N = 385). Outcome data were collected at baseline, weeks 5 and 11 using valid and reliable measures. Medical records provided data on treatment interruptions and metastasis. The association between alterations in medical treatment during the study period with symptom severity, symptom interference with ADLs, and metastatic status were tested using generalized estimating equation (GEE) models. The relationship between dose delays and dose reductions and symptom severity was differential according to metastatic status, with the higher strength of association among women with distant metastasis compared to those with loco-regional disease (p = 0.02). The interaction of symptom interference and metastatic status was also significantly related to dose delays and reductions (p = 0.04). Severity of pain was a stronger predictor of dose delays or reductions among patients with distant metastasis compared to those with loco-regional disease (p < 0.01). The analysis highlights the importance of understanding symptom outcomes that impact research, practice, and treatment decisions.
The impact of haemodialysis on the outcomes of catheter ablation in patients with paroxysmal atrial fibrillation.

The outcomes of catheter ablation (CA) in patients with paroxysmal atrial fibrillation (PAF) who are undergoing haemodialysis (HD) have not been fully elucidated. This study aimed to determine the impact of HD on CA outcome in these patients.



We examined 1364 consecutive PAF patients (mean age, 61 ± 10 years) who underwent CA, including 32 (2.3%) patients undergoing HD. The patients undergoing HD had a significantly lower body mass index (P < 0.0001), higher CHADS2 score (P = 0.006), and higher prevalence of structural heart disease (P < 0.0001), hypertension (P = 0.002), and congestive heart failure (P = 0.02). Echocardiography indicated a larger left atrial diameter (P < 0.0001) and left ventricular diameter (P = 0.0002) in the HD patients. Haemodialysis was a significant predictor of AF recurrence (hazard ratio 2.56; 95% confidence interval 1.56-4.03; P = 0.0004) in the overall population. Sinus rhythm maintenance rates in the HD patients at 1, 3, and 5 years were 42.3, 37.6, and 19.7%, respectively, after the first procedure, and 64.7, 54.9, and 47.1%, respectively, after the final procedure (median, 2; range, 1-2 procedures); these rates were significantly lower than those in the non-HD patients (P < 0.0001). The 5-year survival rate was 78.1% in the HD patients.



Haemodialysis was significantly associated with AF recurrence after CA for PAF. However, an ∼50% success rate for sinus rhythm maintenance without antiarrhythmic drug therapy in HD patients suggested that CA could be an option for the treatment of AF.
Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the three-city study.

To determine whether adding cognitive impairment to frailty improves its predictive validity for adverse health outcomes.



Four-year longitudinal study.



The French Three-City Study.



Six thousand thirty community-dwelling persons aged 65 to 95.



Frailty was defined as having at least three of the following criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. Subjects meeting one or two criteria were prefrail and those meeting none as nonfrail. The lowest quartile in the Mini-Mental State Examination (MMSE) and the Isaacs Set Test (IST) was used to identify subjects with cognitive impairment. The predictive validity of frailty for incident disability, hospitalization, dementia, and death was calculated first for frailty subgroups and then rerun after stratification according to the presence or absence of cognitive impairment.



Four hundred twenty-one individuals (7%) met frailty criteria. Cognitive impairment was present in 10%, 12%, and 22% of the nonfrail, prefrail, and frail subjects, respectively. Those classified as frail scored lower on the MMSE and IST than those classified as prefrail and nonfrail. After adjustment, frail persons with cognitive impairment were significantly more likely to develop disability in activities of daily living (ADLs) and instrumental ADLs over the following 4 years. The risk of incident mobility disability and hospitalization was marginally greater. Incident dementia was greater in the groups with cognitive impairment irrespective of their frailty status. Conversely, frailty was not a significant predictor of mortality.



Cognitive impairment improves the predictive validity of the operational definition of frailty, because it increases the risk of adverse health outcomes in this particular subgroup of the elderly population.
Wet Chemical Synthesis and Screening of Thick Porous Oxide Films for Resistive Gas Sensing Applications

A method of wet chemical synthesis suitable for high throughput and combinatorial applications has been developed for the synthesis of porous resistive thickfilm gas sensors. This method is based on the robot-controlled application of unstable metal oxide suspensions on an array of 64 inter-digital electrodes positioned on an Al2O3 substrate. SnO2, WO3, ZrO2, TiO2, CeO2, In2O3 and Bi2O3 were chosen as base oxides, and were optimised by doping or mixed oxide formation. The parallel synthesis of mixed oxide sensors is illustrated by representative examples. The electrical characteristics and the sensor performance of the films were measured by high-throughput impedance spectroscopy while supplying various test gases (H2, CO, NO, NO2, propene). Data collection, data mining techniques applied and the best potential sensor materials discovered are presented.
VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy.

Anti-vascular endothelial growth factor therapy (VEGF) is an important new treatment modality in oncology. We sought to determine the efficacy and safety of the humanized monoclonal anti-VEGF antibody, bevacizumab, and vinorelbine as treatment for refractory breast cancer and to explore the role of plasma VEGF as a predictor of treatment outcome.



Eligible patients had received one or two prior chemotherapy regimens for metastatic breast cancer or recurred within 12 months of adjuvant therapy and had measurable disease and adequate end-organ function. Patients received bevacizumab 10 mg/kg every 2 weeks, and vinorelbine each week, until tumor progression or prohibitive toxicity. Plasma VEGF was measured at baseline.



Among 56 women treated on protocol, bevacizumab and vinorelbine yielded a 34% response rate (95% confidence interval, 22-48%) and median time to progression of 5.5 months. Activity was observed regardless of tumor hormone receptor status or type or extent of prior chemotherapy. Side effects included uncomplicated neutropenia, hypertension, nasal congestion/epistaxis, and neuropathy, consistent with well-described side effects of the respective agents. Three patients had impaired wound healing following surgical procedures. There were only rare instances of thrombosis or clinically significant proteinuria. Lower levels of baseline VEGF were associated with longer time to progression.



Bevacizumab and vinorelbine are well tolerated and effective as treatment for refractory breast cancer. Plasma VEGF warrants further evaluation as a prognostic marker for treatment outcome in advanced breast cancer patients receiving anti-VEGF therapy.
Knowledge, attitude and practices of healthcare providers towards deep vein thrombosis prophylaxis in five teaching hospitals of Rawalpindi.

Prophylaxis of deep vein thrombosis (DVT) is underutilised in Pakistan. This cross-sectional survey was designed to evaluate knowledge, attitude and practices of healthcare providers towards DVT prophylaxis in teaching hospitals in and around Rawalpindi.



Knowledge, attitude and practices was assessed by a 12-item questionnaire filled-in by healthcare providers in five teaching hospitals. Eleven out of 12 questions were multiple-choice type and one was open ended.



One hundred-sixty-nine, out of 200 questionnaires were returned and were analysed. Total 43.2% of the respondents were house-officers. Although 98.8% agreed that DVT prophylaxis is clinically important, but 39.4% actually prescribed it themselves. Out of these, only 10.3% respondents did it routinely. Low molecular weight heparin (LMWH) was the preferred prophylaxis used (36.7%). Most of the respondents underestimated the prevalence and consequences of DVT in hospitalised patients.



Knowledge and practices of healthcare providers about DVT prophylaxis in hospitalised patients is less than ideal. Hospitals need to develop their own guidelines for DVT prophylaxis.
The changing pattern of adherence to antiretroviral therapy assessed at two time points, 12 months apart, in a cohort of HIV-infected children.

In a previous multicentre study including 129 HIV-infected children, non-adherence to antiretroviral therapy was detected in 16% of patients and was mainly related to psychosocial rather than clinical or demographic features. The aim of this study was to explore the evolving pattern of adherence and its determinants in the same population of children.



An observational, cross-sectional multicentre study was done through a structured interview to the caregivers of HIV-infected children. Adherence was quantitatively evaluated through a 4-day recall adherence instrument.



One hundred and twelve children were included. Nineteen (17%) omitted more than 5% of doses in the preceding 4 days and were considered non-adherent. Of these, 10 had been found non-adherent and nine adherent in the previous study. In parallel, nine of the originally non-adherent children had become adherent. Adherence rates were higher in children receiving therapy from foster parents than in children receiving therapy from biological parents. Dose number significantly correlated with adherence.



Adherence to antiretroviral therapy is a dynamic phenomenon that changes with time. The evolving pattern shows a fairly constant distribution of adherence because a similar number of patients gain and lose adherence. Psychosocial rather than clinical features are major determinants of adherence.