nils-herrmann/clean_scirepeval huggingface dataset:
Experience with combination of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma

The purpose of this study was to evaluate the efficacy and toxicity of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiation therapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 54 patients (stage IIB: 6, stage III: 24, stage IVA–B: 24) with locoregionally advanced NPC were treated with cisplatin 25 mg/m2 intravenously on days 1–3, and gemcitabine 1,000 mg/m2 of 30-min intravenous infusion on days 1 and 8, every 3 weeks for two cycles as neoadjuvant chemotherapy. Two cycles of the same regimen were administered as adjuvant chemotherapy 28 days after the end of radiotherapy. The prescription doses were 66–70.4 Gy to the gross tumor volume (GTV), 66 Gy to positive neck nodes, 60 Gy to the high-risk clinical target volume and 54 Gy to the low-risk clinical target volume. The overall response rate to neoadjuvant chemotherapy was 88.6%. Toxicity was mainly grade 1/2 myelosuppression. All patients completed IMRT. The median follow-up duration was 30 months (range, 12–60 months). The 3-year locoregional control, metastasis-free rate and overall survival were 94.9%, 86.2% and 87.7%, respectively. Severe late toxicities included grade 3 trismus in one patient, grade 3 hearing impairment in one patient and cranial nerve XII palsy in one patient. No grade 4 late toxicities were observed. A combination of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiotherapy for locoregionally advanced NPC is well-tolerated, convenient, effective and warrants further studies.
Multi-class cancer subtype classification based on gene expression signatures with reliability analysis.

Differential diagnosis among a group of histologically similar cancers poses a challenging problem in clinical medicine. Constructing a classifier based on gene expression signatures comprising multiple discriminatory molecular markers derived from microarray data analysis is an emerging trend for cancer diagnosis. To identify the best genes for classification using a small number of samples relative to the genome size remains the bottleneck of this approach, despite its promise. We have devised a new method of gene selection with reliability analysis, and demonstrated that this method can identify a more compact set of genes than other methods for constructing a classifier with optimum predictive performance for both small round blue cell tumors and leukemia. High consensus between our result and the results produced by methods based on artificial neural networks and statistical techniques confers additional evidence of the validity of our method. This study suggests a way for implementing a reliable molecular cancer classifier based on gene expression signatures.
Radiofrequency catheter ablation maintains its efficacy better than antiarrhythmic medication in patients with paroxysmal atrial fibrillation: On-treatment analysis of the randomized controlled MANTRA-PAF trial.

The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) is a randomized trial comparing radiofrequency catheter ablation (RFA) to antiarrhythmic drugs (AADs) as first-line treatment of paroxysmal atrial fibrillation (PAF). In order to eliminate the clouding effect of crossover we performed an on-treatment analysis of the data.



Patients (n=294) were divided into three groups: those receiving only the assigned therapy (RFA and AAD groups) and those receiving both therapies (crossover group). The primary end points were AF burden in 7-day Holter recordings at 3, 6, 12, 18, and 24 months and cumulative AF burden in all recordings. At 24 months, AF burden was significantly lower in the RFA (n=110) than in the AAD (n=92) and the crossover (n=84) groups (90th percentile 1% vs. 10% vs. 16%, P=0.007), and more patients were free from any AF (89% vs. 73% vs. 74%, P=0.006). In the RFA, AAD and the crossover groups 63%, 59% and 21% (P<0.001) of the patients had no AF episodes in any Holter recording, respectively. Quality of life improved significantly in all groups. There were no differences in serious adverse events between the RFA, AAD and crossover groups (19% vs. 8% vs. 23%) (P=0.10).



In the treatment of antiarrhythmic therapy naïve patients with PAF long-term efficacy of RFA was superior to AAD therapy. Thus, it is reasonable to offer RFA as first-line treatment for highly symptomatic patients who accept the risks of the procedure and are aware of frequent need for reablation(s).
Intake of antioxidants and risk of type 2 diabetes in a cohort of male smokers

Oxidative stress may induce insulin resistance in peripheral tissues and impair insulin secretion from pancreatic β-cells. Antioxidants are suggested to decrease the risk of diabetes through reduction of oxidative stress. However, only a few studies exist on dietary antioxidants and the risk of type 2 diabetes. We investigated the association of dietary antioxidants with incident type 2 diabetes in the α-Tocopherol, β-Carotene Cancer Prevention Study cohort.The study cohort included 29 133 male smokers aged 50–69 years. During a median follow-up of 10.2 years 660 incident cases of diabetes were observed among the 25 505 men with a completed baseline food frequency questionnaire.Dietary α-tocopherol, β-tocopherol and β-tocotrienol were positively associated with the risk of diabetes when adjusted for age and supplementation (relative risk (RR) 1.17 (95% confidence interval (CI) 0.91–1.51) P for trend 0.02; RR 1.31 (95% CI 1.02–1.68) P for trend 0.01; RR 1.28 (95% CI 1.00–1.63) P for trend 0.01, respectively), but the association disappeared after multivariate adjustment (RR 0.92 (95% CI 0.71–1.19) P for trend 0.97; RR 1.06 (95% CI 0.82–1.36) P for trend 0.48; RR 1.04 (95% CI 0.80–1.35) P for trend 0.46, respectively). Other tocopherols and tocotrienols as well as vitamin C, carotenoids, flavonols and flavones had no association with risk of diabetes.Dietary antioxidants were not associated with a decreased risk of incident diabetes in middle-aged male smokers.
Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease.

We aimed to determine the antiviral activity and safety of a new nucleotide analogue, LB80380, in chronic hepatitis B (CHB) patients with lamivudine-resistant virus. Sixty-five patients with lamivudine-resistant virus were randomized to receive five ascending daily doses (30, 60, 90, 150, 240 mg) of LB80380. LB80380 was given together with lamivudine for the first 4 weeks, followed by 8 weeks of LB80380 monotherapy. This was then followed by 24 weeks of adefovir. Hepatitis B virus (HBV) DNA levels, serology, liver biochemistry, and safety were monitored. The extent of the HBV DNA reduction at week 12 was dose-dependent. The mean reduction from baseline was 2.81, 3.21, 3.92, 4.16, and 4.00 log(10) copies/mL for the five ascending dose groups. The dose-proportionate effect was statistically significant (P < 0.001) with a decrease of HBV DNA levels by an average of 1.54 log(10) copies/mL for every 1-unit increase in log(10) dose of LB80380. In 93.4% of patients, HBV DNA decreased by >2 log(10) copies/mL, and 11.5% of patients had undetectable HBV DNA levels (<300 copies/mL) by week 12. HBV DNA suppression was maintained during the 24 weeks of adefovir treatment. Hepatitis B e antigen seroconversion and normalization of alanine aminotransferase were seen in 14.6% and 24.6% of patients, respectively, at week 12; 44.6% of patients experienced mild and self-limiting adverse events, none of which were attributed to the study drug.



LB80380 at doses of up to 240 mg is safe, well tolerated, and effective at reducing viral load in CHB patients with lamivudine-resistant virus for a period of 12 weeks.
Adjunctive oral ziprasidone in patients with acute mania treated with lithium or divalproex, part 2: influence of protocol-specific eligibility criteria on signal detection.

High failure rates of randomized controlled trials (RCTs) are well recognized but poorly understood. We report exploratory analyses from an adjunctive ziprasidone double-blind RCT in adults with bipolar I disorder (reported in part 1 of this article). Data collected by computer interviews and by site-based raters were analyzed to examine the impact of eligibility criteria on signal detection.



Clinical assessments and a remote monitoring system, including a computer-administered Young Mania Rating Scale (YMRS(Comp)) were used to categorize subjects as eligible or ineligible on 3 key protocol-specified eligibility criteria. Data analyses compared treatment efficacy for eligible versus ineligible subgroups. All statistical analyses reported here are exploratory. Criteria were considered "impactful" if the difference between eligible and ineligible subjects on the YMRS change scores was ≥ 1 point.



504 subjects had baseline and ≥ 1 post-randomization computer-administered assessments but only 180 (35.7%) met all 3 eligibility criteria based on computer assessments. There were no statistically significant differences between treatment groups in change from baseline YMRS score on the basis of site-based rater or computer assessments. All criteria tested improved signal detection except the entry criteria excluding subjects with ≥ 25% improvement from screen to baseline.



On the basis of computer assessments, nearly two-thirds of randomized subjects did not meet at least 1 protocol-specified eligibility criterion. These results suggest enrollment of ineligible subjects is likely to contribute to failure of acute efficacy studies.
Impact of animal-assisted therapy for outpatients with fibromyalgia.

Animal-assisted therapy using dogs trained to be calm and provide comfort to strangers has been used as a complementary therapy for a range of medical conditions. This study was designed to evaluate the effects of brief therapy dog visits for fibromyalgia patients attending a tertiary outpatient pain management facility compared with time spent in a waiting room.



Open label with waiting room control.



Tertiary care, university-based, outpatient pain management clinic.



A convenience sample of fibromyalgia patients was obtained through advertisements posted in the clinic.



Participants were able to spend clinic waiting time with a certified therapy dog instead of waiting in the outpatient waiting area. When the therapy dog was not available, individuals remained in the waiting area.  Self-reported pain, fatigue, and emotional distress were recorded using 11-point numeric rating scales before and after the therapy dog visit or waiting room time.



Data were evaluated from 106 therapy dog visits and 49 waiting room controls, with no significant between-group demographic differences in participants. Average intervention duration was 12 minutes for the therapy dog visit and 17 minutes for the waiting room control. Significant improvements were reported for pain, mood, and other measures of distress among patients after the therapy dog visit, but not the waiting room control. Clinically meaningful pain relief (≥2 points pain severity reduction) occurred in 34% after the therapy dog visit and 4% in the waiting room control. Outcome was not affected by the presence of comorbid anxiety or depression.



Brief therapy dog visits may provide a valuable complementary therapy for fibromyalgia outpatients.
Early effect on general interest, and short-term antidepressant efficacy and safety of agomelatine (25-50mg/day) and escitalopram (10-20mg/day) in outpatients with Major Depressive Disorder. A 12-week randomised double-blind comparative study.

A double-blind, randomized, study was conducted in 29 centers in Romania to evaluate the effect of agomelatine 25-50mg/day (n=144 patients) on general interest, overall clinical efficacy, and functionality in comparison with escitalopram 10-20mg/day (n=143 patients) in out-patients diagnosed with moderate to severe Major Depressive Disorder (MDD).



The primary endpoint of the study was the score difference between agomelatine and escitalopram were assessed on the item 13 of the Quick Inventory of Depressive Symptomatology (16-Item) Self-Report (QIDS-SR16) over the first week period. Secondary measures include the primary criterion on the 12-week period, the within-group evolution over 12 weeks of the 17-item Hamilton Depression Scale (HAM-D17) total score, CGI severity of illness (CGI-S) and CGI-I scores, and functionality by using the self-rated Sheehan Disability Scale (SDS).



After one week, the mean General Interest score showed no statistically significant difference between treatments. Over 12 weeks, patients felt more and more interested in other people and activities than before having taken medication. Both agomelatine and escitalopram improved depressive symptoms and symptom-related functional impairment of patients. Both agomelatine and escitalopram were well-tolerated by patients.



The strength of our results would benefit from additional data from trials using a similar design and other active comparators.



There was no difference in week 1 changes of interest between agomelatine and escitalopram. The relatively good tolerability of agomelatine and escitalopram is confirmed.
Efficacy and Safety of Technosphere Inhaled Insulin Compared With Technosphere Powder Placebo in Insulin-Naive Type 2 Diabetes Suboptimally Controlled With Oral Agents   

This double-blind, placebo-controlled, randomized, multicenter, parallel-group study compared the efficacy, safety, and tolerability of Technosphere insulin with Technosphere powder as placebo in insulin-naive type 2 diabetic patients whose diabetes was suboptimally controlled with oral antidiabetic agents.



Patients (n = 126) were randomly assigned to 12 weeks of therapy with Technosphere insulin or Technosphere powder after lifestyle education on nutrition, exercise, and instructions on inhaler use. The primary efficacy outcome was change in A1C from baseline to study end, and the secondary efficacy outcome was area under the curve for postprandial glucose levels during a meal test at treatment weeks 4, 8, and 12.



A1C reduction from a mean baseline of 7.9% was greater with Technosphere insulin than with Technosphere powder (-0.72 vs. -0.30%; P = 0.003). Postprandial glucose excursions were reduced by 56% with Technosphere insulin compared with baseline, and maximal postprandial glucose levels were reduced by 43% compared with Technosphere powder. Incidences of hypoglycemia, hyperglycemia, cough, and other adverse events were low in both groups. Body weight was unchanged in both groups.



Technosphere insulin was well tolerated and demonstrated significant improvement in glycemic control with clinically meaningful reductions in A1C levels and postprandial glucose concentrations after 12 weeks of treatment.
Structured discharge procedure for children admitted to hospital with acute asthma: a randomised controlled trial of nursing practice.

Discharge planning is becoming an important part of the management of childhood asthma in hospital. Readmission to hospital, although often inevitable, might represent a failure of the opportunity for intervention presented by a brief period of supervised care in hospital.



To examine the impact of a structured, nurse-led discharge package for children admitted to hospital with acute asthma on readmission to hospital, reattendance at the accident and emergency (A&E) department, and general practitioner consultations for asthma.



A structured nurse-led discharge package, consisting of a 20 minute patient education programme and self management plan for children with asthma was developed on the wards of a busy children's hospital. A randomised controlled trial was conducted involving 160 children aged 2-16 years admitted for asthma over a 12 month period. Readmission and A&E reattendance's over the six months after discharge from hospital were obtained from the hospital computerised information system and general practitioner consultations from practice records.



Children in the intervention group were significantly less likely to be readmitted to hospital in the next six months than those in the control group (12 of 80 v 30 of 80 patients), and significantly less likely to attend the A&E department (6 of 80 v 31 of 80). Significantly fewer children in the intervention group had visits to their general practitioner for problematic asthma (31 of 78 v 72 of 77 for whom data were available).



By delivering the simplest form of education and support during a child's stay in hospital, readmissions over a six month period were reduced. The programme was designed to be suitable for administration by nursing staff on the children's wards after a brief period of training.
Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina.

Antiplatelet therapy with aspirin and antithrombotic therapy with heparin both prevent the complications of unstable angina; however, no definitive data exist on the relative clinical efficacy of the two drugs.



Aspirin (325 mg bid) or heparin (5000-U intravenous bolus followed by a perfusion titrated to the APTT) were compared in a double-blind randomized trial of 484 patients in two cohorts enrolled sequentially. The study was initiated at admission to hospital at a mean of 8.3 +/- 7.8 hours after the last episode of pain. End points were assessed 5.7 +/- 3.3 days later, when the decision for long-term management was made. Myocardial infarction occurred in 2 (0.8%) of the 240 patients randomized to heparin and in 9 (3.7%) of the 244 randomized to aspirin (P = .035), an odds ratio of 0.22 and a risk difference of 2.9% (95% confidence limits, 0.3% to 5.6%) with heparin. The only death resulted from a myocardial infarction in an aspirin patient. Survival curves with Cox logistic regression analysis showed that the improvement in survival without myocardial infarction with heparin (P = .035) was independent of other baseline characteristics.



This study documents that heparin prevents myocardial infarction better than aspirin during the acute phase of unstable angina.
Predictors of improvement and progression of diabetic polyneuropathy following treatment with α-lipoic acid for 4 years in the NATHAN 1 trial.

We aimed to analyze the impact of baseline factors on the efficacy of α-lipoic acid (ALA) over 4 years in the NATHAN 1 trial.



This was a post-hoc analysis of the NATHAN 1 trial, a 4-year randomized study including 460 diabetic patients with mild-to-moderate polyneuropathy using ALA 600 mg qd or placebo. Amongst others, efficacy measures were the Neuropathy Impairment Score of the lower limbs (NIS-LL) and heart rate during deep breathing (HRDB).



Improvement and prevention of progression of NIS-LL (ΔNIS-LL≥2 points) with ALA vs. placebo after 4 years was predicted by higher age, lower BMI, male sex, normal blood pressure, history of cardiovascular disease (CVD), insulin treatment, longer duration of diabetes and neuropathy, and higher neuropathy stage. Participants treated with ALA who received ACE inhibitors showed a better outcome in HRDB after 4 years.



Better outcome in neuropathic impairments following 4-year treatment with α-lipoic acid was predicted by normal BMI and blood pressure and higher burden due to CVD, diabetes, and neuropathy, while improvement in cardiac autonomic function was predicted by ACE inhibitor treatment. Thus, optimal control of CVD risk factors could contribute to improved efficacy of α-lipoic acid in patients with higher disease burden.
Long-term effect of nonsteroidal anti-inflammatory drugs on the production of cytokines and other inflammatory mediators by blood cells of patients with osteoarthritis

Most of the previous studies dealing with the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the synthesis of inflammatory mediators involved in joint damage have been done in cells culturedin vitro or in blood cells from patients treated for short periods of time. In this work we have evaluated the long-term effect of aceclofenac, a new NSAID, and diclofenac on the production of a series of inflammatory mediators by blood cells from 30 patients with severe knee osteoarthritis. Both aceclofenac and diclofenac significantly inhibited prostaglandin E2 (PGE2) synthesis by blood mononuclear and polymorphonuclear cells after 180 days of treatment. However, no clear effect was noted on leukotriene B4 (LTB4) and platelet activating factor (PAF) production. The generation of O 2 − by polymorphonuclear cells, stimulated with FMLP, was decreased after 15 days of treatment with both drugs, but reached normal values after 180 days. Interleukin-1β (IL-1β) production decreased significantly at 180 days with both drugs in the group of high producer patients. In a few (n=3) patients with high basal mononuclear cell tumor necrosis factor α (TNFα) production, this also decreased on treatment for 180 days with the NSAIDs. In the remaining low TNFα-producing patients, TNFα production tended to increase. Interleukin-6 (IL-6) synthesis was not affected by aceclofenac while it was diminished by diclofenac. The decrease in IL-6 in all treated patients was significantly correlated with a worsening of the clinical condition. On the whole, these data could afford a pathogenetic basic for the long-term employment of these drugs in patients with inflammatory conditions.
Assessing Water Filtration and Safe Storage in Households with Young Children of HIV-Positive Mothers: A Randomized, Controlled Trial in Zambia

Unsafe drinking water presents a particular threat to people living with HIV/AIDS (PLHIV) due to the increased risk of opportunistic infections, diarrhea-associated malabsorption of essential nutrients, and increased exposure to untreated water for children of HIV-positive mothers who use replacement feeding to reduce the risk of HIV transmission. This population may particularly benefit from an intervention to improve water quality in the home.



We conducted a 12-month randomized, controlled field trial in Zambia among 120 households with children <2 years (100 with HIV-positive mothers and 20 with HIV-negative mothers to reduce stigma of participation) to assess a high-performance water filter and jerry cans for safe storage. Households were followed up monthly to assess use, drinking water quality (thermotolerant coliforms (TTC), an indicator of fecal contamination) and reported diarrhea (7-day recall) among children <2 years and all members of the household. Because previous attempts to blind the filter have been unsuccessful, we also assessed weight-for-age Z-scores (WAZ) as an objective measure of diarrhea impact. Filter use was high, with 96% (596/620) of household visits meeting the criteria for users. The quality of water stored in intervention households was significantly better than in control households (3 vs. 181 TTC/100 mL, respectively, p<0.001). The intervention was associated with reductions in the longitudinal prevalence of reported diarrhea of 53% among children <2 years (LPR=0.47, 95% CI: 0.30-0.73, p=0.001) and 54% among all household members (LPR=0.46, 95% CI: 0.30-0.70, p<0.001). While reduced WAZ was associated with reported diarrhea (-0.26; 95% CI: -0.37 to -0.14, p<0.001), there was no difference in WAZ between intervention and control groups.



In this population living with HIV/AIDS, a water filter combined with safe storage was used correctly and consistently, was highly effective in improving drinking water quality, and was protective against diarrhea.