nils-herrmann/clean_scirepeval huggingface dataset:
An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study).

This phase II, open-label, multicentre study aimed to evaluate changes in cell proliferation and biomarkers, as well as efficacy of lapatinib in treatment-naïve patients with HER-2-negative primary breast cancer.



Patients received 1500 mg lapatinib for 28-42 days before surgery with repeat biopsies and measurements. The primary end point was inhibition of cell proliferation measured by Ki67; the secondary end points included clinical response, adverse events and changes in FOXO3a, FOXM1, p-AKT and HER-3.



Overall, there was no significant reduction in Ki67 with treatment (assessment carried out in 28 of 31 subjects enrolled). However, four patients (14%) showed a reduction in Ki67 ≥50%. Four of 25 patients (16%) had a partial response to treatment judged by sequential ultrasound measurements. Response, in terms of either Ki67 or ultrasound, did not relate to changes in any biomarker assessed at baseline, including the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). However, all four clinical responders were HER-3 positive, as were three of four Ki67 responders.



Overall, a pre-surgical course of lapatinib monotherapy had little effect on this group of patients; however, in subsets of patients, especially those with HER-3-positive tumors, we observed either reduction in proliferation (Ki67) or tumor size; EGFR/ER status had no impact.
Lack of benefit of a primary care-based nurse-led education programme for people with osteoarthritis of the knee

Osteoarthritis (OA) is the commonest cause of locomotor disability and forms a major element of the workload of the primary care team. There is evidence that patient education may improve quality of life, physical functioning, mental health and coping as well as reducing health service use. The aim of this study was to evaluate the effectiveness of a primary care-based patient education programme (PEP) using a randomised controlled trial. A cluster randomised controlled trial, involving 22 practices, was used to determine the efficacy of a nurse-led education programme. The programme consisted of a home visit and four 1-h teaching sessions. Patients were assessed at baseline and then 1, 3, 6 and 12 months post intervention using 36-item Short Form (SF-36), Western Ontario and McMaster Universities Arthritis Index (WOMAC), arthritis helplessness index and a patient knowledge questionnaire. Direct interviews were used at baseline and at the 12-month follow-up. There were no differences in depression, OA knowledge, pain or physical ability at either 1 month or 1 year between the two groups. Control practices (65 patients from 12 practices) recruited significantly fewer patients than intervention practices (105 patients from ten practices, p=0.02). Control practices had more doctors (p=0.02), more non-white patients (p=0.007), fewer patients living alone (p=0.005) and lower levels of disability (p=0.008). We detected a lack of benefit of PEP for people with OA of the knee. This was thought to be due in part to the short intervention time employed and the heterogeneous nature of the disease and the population studied.
Short-term Results of Birmingham Hip Resurfacing in the United States.

Previous data on the survivorship of the Birmingham Hip Resurfacing (BHR) implant have come from design surgeons and large national databases outside of the United States, and there is a lack of reported outcomes of surface replacement arthroplasty from US centers. A retrospective study was undertaken of 1271 hips treated with a BHR system (Smith & Nephew, Memphis, Tennessee) between June 2006 and September 2008 at 6 high-volume total joint centers in the United States. Demographic features, Harris Hip Score (HHS), and radiographic findings were recorded. Patients who did not have a 2-year follow-up visit were contacted by telephone. All patients were asked about complications, reoperations, or failure of the implants. Of the treated hips, 1144 (90%) had a minimum of 2 years of clinical follow-up (mean, 2.9 years; range, 1.8-4.2 years). Mean age was 52.3 years, and 75% of patients were men. Mean HHS improved from 55.8 preoperatively to 97.4 at the most recent follow-up (P<.001). There were 16 (1.4%) revisions to total hip arthroplasty (THA) for fracture (7), early dislocation (3), acetabular component malpositioning with pain (3; 1 with metallosis), infection (1), femoral loosening (1), and pseudotumor (1). There were 9 additional complications (0.8%) that did not require revision, including 3 dislocations treated with closed reduction, 2 fractures, 3 nerve injuries, and 1 pseudotumor. At 2 to 4 years of follow-up, the revision rate and the major complication rate with the BHR system were similar to those in previous reports of primary THA. Excellent clinical results were observed, but further follow-up is necessary to assess mid- and long-term results with the BHR system in US patients.
Leptin before and after insulin therapy in children with new-onset type 1 diabetes.

Serum leptin levels reflect the amount of body fat. However, several reports suggest that insulin may also regulate serum leptin levels. This study was aimed at testing whether leptin levels are low in newly diagnosed patients with type 1 diabetes and increase after institution of insulin therapy. Nineteen children with new-onset type 1 diabetes were studied. Serum leptin levels were measured at presentation before insulin therapy was initiated (day 0), 1 day after insulin therapy (day 1), 3-5 days after insulin therapy (day 3-5), and at 3 months of follow-up (3 months). The control group consisted of 19 healthy children matched for age and body mass index. On day 0 leptin levels were lower in the patients compared with those in controls (3.3 +/- 0.2 vs. 6.2 +/- 0.9 ng/mL; P < 0.005). After insulin therapy, leptin levels increased significantly by day 1 without significant weight change and became comparable to control values by days 3-5. Before insulin therapy, leptin did not correlate with weight, body mass index, or hemoglobin A1c. After insulin therapy, leptin levels on days 3-5 correlated with insulin dose (r = 0.43; P = 0.03). The results of this study demonstrate that children with new-onset type 1 diabetes have low leptin levels before insulin therapy. Leptin levels increase within 24 h of insulin therapy and become comparable to nondiabetic levels by 3-5 days. This rapid increase in leptin after 24 h of insulinization is independent of changes in body weight and is postulated to be due to a stimulatory effect of insulin on leptin production, nutritional replenishment, or both factors together.
Preventing depression and promoting resilience: feasibility study of a school-based cognitive-behavioural intervention.

The limited reach and effectiveness of psychological treatments for adolescent depression have fuelled interest in alternative approaches designed to promote resilience. Schools offer a convenient location for the widespread delivery of depression prevention programmes, although little research has evaluated the feasibility of delivering interventions in this setting.



To investigate the feasibility of delivering and evaluating a universal school-based depression prevention programme for children aged 12-16 years.



A three-arm pilot study was conducted in one UK secondary school (n = 834).



Interventions had good reach (96%), with high rates of consent (89%) and reasonable retention (78%). The majority of intervention sessions were delivered as intended, with 85% of students attending seven or more sessions. The programme was acceptable to students and teachers, with the specific content of the active intervention being rated differently from the control programmes.



Delivering and undertaking methodologically robust evaluations of universal school-based depression programmes is feasible.
Care evaluation scale-patient version: measuring the quality of the structure and process of palliative care from the patient's perspective.

Recently, greater emphasis has been placed on patient-reported outcomes. However, there are only a few measures to evaluate the quality of care from the patient's perspective.



To report the development of a scale to measure the quality of the structure and process in palliative care from the patient's perspective and examine the reliability and validity of the scale.



A cross-sectional anonymous questionnaire was administered to cancer patients who were being treated on an oncology inpatient ward, who visited an oncology outpatient clinic at Saitama Medical University International Medical Center, or who were in an inpatient palliative unit in Japan between August 2007 and March 2008.



A total of 405 cancer patients participated in the study. Factor analysis revealed that the Care Evaluation Scale-Patient version (CES-P) consisted of 23 items with eight subscales: physical care by physicians, physical care by nurses, psychoexistential care, help with decision making for patients, environment, cost, availability, and coordination/consistency. The total CES-P score was correlated with satisfaction (r = 0.63) but not with quality of life (r = 0.18). The Cronbach α coefficient of the total score was 0.97, and the intraclass correlation coefficient of the total score was 0.67. The CES-P total score was not significantly correlated with the self-reported Eastern Cooperative Oncology Group performance status (ρ = -0.05).



The CES-P has sufficient validity and reliability. In addition, this scale is independent of the general physical condition of the patient.
Regional and seasonal influence in patient’s toxicity to adjuvant chemotherapy for early breast cancer

Results from multinational clinical trials are globally adopted into the routine clinical practice in most countries. Changes in the natural history and incidence of certain diseases as well as in drugs toxicities related to yearly seasons have been reported, however, variations related to climate have never been described. In our study, we assessed whether yearly seasons and climate could influence the chemotherapy toxicity profile. We analyzed the toxicities recorded in the phase III GEICAM 9906 study which was run in different geographically and climatically/seasonally regions in Spain. In this trial 1246 patients were randomized and eligible to receive FEC90 ×6 cycles or FEC90 ×4 cycles followed by eight doses of weekly paclitaxel (T). The results showed differences in hematological and non-hematological toxicities in relation to the season of the year and the climate of the area in which the treatment was administered. We found a higher hematological toxicity in warm seasons (spring and summer) and in Oceanic climate regions (Neutropenia G4: 7.8 vs. 1.0 vs. 1.0%, P < 0.0001). Asthenia was greater frequency in the summer period (FEC90: 21.1%, T: 15.3%) as well as in the Mediterranean areas (FEC: 28% T: 27.2%). Also we observed liver transaminase elevations were more frequent in the summer and in the Oceanic areas. Myalgias and secondary sensory neuropathy to paclitaxel were recorded more frequently during autumn. Climate should be considered a significant variable in toxicity to chemotherapy.
PREVENTION OF INTRAVENTRICULAR HAEMORRHAGE IN PRETERM INFANTS BY PHENOBARBITONE: A Controlled Trial

Sixty infants with birth-weights less than 1500 g and who were less than 6 h old were randomly assigned to a group given phenobarbitone or a control group. Intravenous phenobarbitone was given in doses sufficient to achieve anticonvulsant serum levels within 12-18 h. Maintenance therapy was continued for one week. Periventricular/intraventricular haemorrhage (IVH) occurred in 13.3% (4/30) of the phenobarbitone group and in 46.7% (14/30) of the control group. The occurrence of risk factors related to IVH was similar in the two groups. Phenobarbitone may reduce the incidence of IVH in small preterm infants.
Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms

High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients.



In the present study, we correlated the occurrence of variants at three such SNPs (rs12979860, rs12980275, and rs8099917) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO) involving 253 Caucasian patients. The favorable SNP variants (CC, AA, and TT, respectively) were associated with lower baseline IP-10 (P = 0.02, P = 0.01, P = 0.04) and were less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P = 0.01). Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants (P = 0.0013, P = 0.029, P = 0.0004 respectively). Among HCV genotype 1 infected carriers of the favorable C, A, or T alleles, IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 (first phase decline), which translated into increased rates of RVR (62%, 53%, and 39%) and SVR (85%, 76%, and 75% respectively) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients, baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR, which in turn independently predicted SVR.



Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA, RVR, and final therapeutic outcome.
Using computer based data acquisition and analysis system for nasal potential difference measurement in cystic fibrosis.

Nasal potential difference (PD) measurement has been used as a diagnostic test for cystic fibrosis (CF). It has been shown that large differences in reproducibility of nasal PD measurement can exist between different study sites. These differences reduce the validity of studies. In our study we tried to measure nasal PD values for a group of Turkish CF patients by using a computer based data acquisition system, which could eliminate the bias due to using different voltmeters. The CF group (n=40, mean age 9.3 years) value was -39.21+/-1.74 mV, and the control group (n=36, mean age 17.08 years) value was -18.24+/-1.48 mV (mean+/-SEM). Using the electronic data acquisition and analysis systems gave reliable results with high specificity (92%), sensitivity (79%), positive predictive value (95%) and negative predictive value (72%). Computer based data acquisition and analysis system provides suitable monitoring and continuous recording during measurements and facilitates repeat readings at the same distances along the nasal floor. Using electronic data acquisition may help to minimize the subjectivity in voltmeter measurements and hand analysis.
Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers.

Mutations in LMNA are variably expressed and may cause cardiomyopathy, atrioventricular block (AVB), or atrial arrhythmias (AAs) and ventricular arrhythmias (VA). Detailed natural history studies of LMNA-associated arrhythmic and nonarrhythmic outcomes are limited, and the prognostic significance of the index cardiac phenotype remains uncertain.



This study sought to describe the arrhythmic and nonarrhythmic outcomes of LMNA mutation carriers and to assess the prognostic significance of the index cardiac phenotype.



The incidence of AVB, AA, sustained VA, left ventricular systolic dysfunction (LVD) (= left ventricular ejection fraction ≤50%), and end-stage heart failure (HF) was retrospectively determined in 122 consecutive LMNA mutation carriers followed at 5 referral centers for a median of 7 years from first clinical contact. Predictors of VA and end-stage HF or death were determined.



The prevalence of clinical manifestations increased broadly from index evaluation to median follow-up: AVB, 46% to 57%; AA, 39% to 63%; VA, 16% to 34%; and LVD, 44% to 57%. Implantable cardioverter-defibrillators were placed in 59% of patients for new LVD or AVB. End-stage HF developed in 19% of patients, and 13% died. In patients without LVD at presentation, 24% developed new LVD, and 7% developed end-stage HF. Male sex (p = 0.01), nonmissense mutations (p = 0.03), and LVD at index evaluation (p = 0.004) were associated with development of VA, whereas LVD was associated with end-stage HF or death (p < 0.001). Mode of presentation (with isolated or combination of clinical features) did not predict sustained VA or end-stage HF or death.



LMNA-related heart disease was associated with a high incidence of phenotypic progression and adverse arrhythmic and nonarrhythmic events over long-term follow-up. The index cardiac phenotype did not predict adverse events. Genetic diagnosis and subsequent follow-up, including anticipatory planning for therapies to prevent sudden death and manage HF, is warranted.
A phase I dose-escalation and pharmacokinetic study of enzastaurin and erlotinib in patients with advanced solid tumors

Enzastaurin, an oral serine/threonine kinase inhibitor, targets the protein kinase C and AKT pathways with anti-tumor and anti-angiogenic effects. Erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has activity in solid tumors. Based on the promising combination of EGFR inhibitors and anti-angiogenic agents, this phase I trial was initiated. This single-institution, open-label, non-randomized trial used a standard 3 + 3 dose-escalation model in patients with advanced solid malignancies including non-small-cell lung cancer (NSCLC). Two dose levels of enzastaurin (with loading doses) were explored: 250 mg daily and 500 mg daily. Erlotinib was given at 150 mg daily. Sixteen patients were enrolled in this study (median age, 64 years). Most patients were heavily pre-treated, female, and Caucasian and had NSCLC. The highest dose of enzastaurin, 500 mg daily, was tolerated with no unexpected adverse events and no alteration in the pharmacokinetics of either drug at this dose level. The mean clearance was 5.75 L/h for erlotinib and 53.8 L/h for enzastaurin. The most common possibly drug-related grade 3–4 adverse events included diarrhea (25.0%), neurologic symptoms (18.8%), and vomiting (18.8%). Activity was noted, with a partial response in one patient and prolonged disease stability for >12 cycles in three patients. The combination of enzastaurin 500 mg daily and erlotinib 150 mg daily is well tolerated and does not alter the pharmacokinetics of the individual drugs, with clinical activity seen. A phase II trial of this combination has been initiated in patients with advanced-stage NSCLC.
Cost-effectiveness of a nurse-based intervention (AIMS) to improve adherence among HIV-infected patients: design of a multi-centre randomised controlled trial

Non-adherence to HIV-treatment can have a negative impact on patients treatment success rates, quality of life, infectiousness, and life expectancy. Few adherence interventions have shown positive effects on adherence and/or virologic outcomes. The theory- and evidence-based Adherence Improving self-Management Strategy (AIMS) is an intervention that has been demonstrated to improve adherence and viral suppression rates in a randomised controlled trial. However, evidence of its cost-effectiveness is lacking. Following a recent review suggesting that cost-effectiveness evaluations of adherence interventions for chronic diseases are rare, and that the methodology of such evaluations is poorly described in the literature, this manuscript presents the study protocol for a multi-centre trial evaluating the effectiveness and cost-effectiveness of AIMS among a heterogeneous sample of patients.



The study uses a multi-centre randomised controlled trial design to compare the AIMS intervention to usual care from a societal perspective. Embedded in this RCT is a trial-based and model-based economic evaluation. A planned number of 230 HIV-infected patients are randomised to receive either AIMS or usual care. The relevant outcomes include changes in adherence, plasma viral load, quality of life, and societal costs. The time horizon for the trial-based economic evaluation is 12-15 months. Costs and effects are extrapolated to a lifetime horizon for the model-based economic evaluation.



The present multicentre RCT is designed to provide sound methodological evidence regarding the effectiveness and cost-effectiveness of a nurse-based counselling intervention (AIMS) to support treatment adherence among a large and heterogeneous sample of HIV-infected patients in the Netherlands. The objective of the current paper is to describe the trial protocol in sufficient detail to allow full evaluation of the quality of the study design. It is anticipated that, if proven cost-effective, AIMS can contribute to improved evidence-based counselling guidelines for HIV-nurses and other health care professionals.
A randomized controlled behavioral intervention trial to improve medication adherence in adult stroke patients with prescription tailored Short Messaging Service (SMS)-SMS4Stroke study

The effectiveness of mobile technology to improve medication adherence via customized Short Messaging Service (SMS) reminders for stroke has not been tested in resource poor areas. We designed a randomized controlled trial to test the effectiveness of SMS on improving medication adherence in stroke survivors in Pakistan.



This was a parallel group, assessor-blinded, randomized, controlled, superiority trial. Participants were centrally randomized in fixed block sizes. Adult participants on multiple medications with access to a cell phone and stroke at least 4 weeks from onset (Onset as defined by last seen normal) were eligible. The intervention group, in addition to usual care, received reminder SMS for 2 months that contained a) Personalized, prescription tailored daily medication reminder(s) b) Twice weekly health information SMS. The Health Belief Model and Social Cognitive theory were used to design the language and content of messages. Frontline SMS software was used for SMS delivery. Medication adherence was self-reported and measured on the validated Urdu version of Morisky Medication Adherence Questionnaire. Multiple linear regression was used to model the outcome against intervention and other covariates. Analysis was conducted by intention-to-treat principle.



Two hundred participants were enrolled. 38 participants were lost to follow-up. After 2 months, the mean medication score was 7.4 (95 % CI: 7.2-7.6) in the intervention group while 6.7 (95 % CI: 6.4-7.02) in the control group. The adjusted mean difference (Δ) was 0.54 (95 % CI: 0.22-0.85). The mean diastolic blood pressure in the intervention group was 2.6 mmHg (95 % CI; -5.5 to 0.15) lower compared to the usual care group.



A short intervention of customized SMS can improve medication adherence and effect stroke risk factors like diastolic blood pressure in stroke survivors with complex medication regimens living in resource poor areas.