nils-herrmann/clean_scirepeval huggingface dataset:
Effect of pain control in suspected acute appendicitis on the diagnostic accuracy of surgical residents.

To determine the influence of early pain relief for patients with suspected appendicitis on the diagnostic performance of surgical residents.



A prospective randomized, double-blind, placebo-controlled trial was conducted for patients with suspected appendicitis. The patients were randomized to receive placebo (normal saline intravenous [IV]) infusions over 5 minutes or the study drug (morphine 5 mg IV). All of the clinical evaluations by surgical residents were performed 30 minutes after administration of the study drug or placebo. After obtaining the clinical probability of appendicitis, as determined by the surgical residents, abdominal computed tomography was performed. The primary objective was to compare the influence of IV morphine on the ability of surgical residents to diagnose appendicitis.



A total of 213 patients with suspected appendicitis were enrolled. Of these patients, 107 patients received morphine, and 106 patients received placebo saline. The negative appendectomy percentages in each group were similar (3.8% in the placebo group and 3.2% in the pain control group, p=0.62). The perforation rates in each group were also similar (18.9% in the placebo group and 14.3% in the pain control group, p=0.75). Receiver operating characteristic analysis revealed that the overall diagnostic accuracy in each group was similar (the area under the curve of the placebo group and the pain control group was 0.63 v. 0.61, respectively, p=0.81).



Early pain control in patients with suspected appendicitis does not affect the diagnostic performance of surgical residents.
Equivalent beneficial effects of unilateral and bilateral prefrontal cortex transcranial magnetic stimulation in a large randomized trial in treatment-resistant major depression.

Repetitive transcranial magnetic stimulation treatment (rTMS) is an effective treatment for depression but the optimal methods of administration have yet to be determined. Recent studies have produced conflicting results as to whether unilateral rTMS is more or less effective than sequentially applied bilateral rTMS. To address this we conducted a trial comparing sequential bilateral rTMS to right-sided unilateral rTMS using a priming protocol. Patients with treatment-resistant depression (n = 179) were enrolled in a two-arm randomized controlled trial across a 4-wk time period. The primary outcome assessment was the Hamilton Depression Rating Scale. Overall, there was a substantial response rate of >50% (and a 40% remission rate); however, there were no significant differences in clinical response between the two treatment groups. rTMS was well tolerated with a very low discontinuation rate. There was no relationship between response in the current trial and previous response, or non-response, to electroconvulsive therapy. We found no significant differences in clinical response between sequential bilateral rTMS and right-sided unilateral rTMS applied with a priming protocol. The results of this study do not support superior efficacy of bilateral rTMS and instead suggest that other approaches should be explored to increase treatment efficacy.
Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study.

Few studies have been reported that support the efficacy of adjunctive therapy for patients with bipolar I depression who have had an insufficient response to monotherapy with mood-stabilizing agents. The authors investigated the efficacy of lurasidone, a novel antipsychotic agent, as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression.  Patients were randomly assigned to receive 6 weeks of double-blind adjunctive treatment with lurasidone (N=183) or placebo (N=165), added to therapeutic levels of either lithium or valproate. Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP), respectively.  Lurasidone treatment significantly reduced mean MADRS total score at week 6 compared with the placebo group (-17.1 versus -13.5; effect size=0.34). Similarly, lurasidone treatment resulted in significantly greater endpoint reduction in CGI-BP depression severity scores compared with placebo (-1.96 versus -1.51; effect size=0.36) as well as significantly greater improvement in anxiety symptoms and in patient-reported measures of quality of life and functional impairment. Discontinuation rates due to adverse events were 6.0% and 7.9% in the lurasidone and placebo groups, respectively. Adverse events most frequently reported for lurasidone were nausea, somnolence, tremor, akathisia, and insomnia. Minimal changes in weight, lipids, and measures of glycemic control were observed during treatment with lurasidone.  In patients with bipolar I depression, treatment with lurasidone adjunctive to lithium or valproate significantly improved depressive symptoms and was generally well tolerated.
Viral load monitoring and antiretroviral treatment outcomes in a pediatric HIV cohort in Ghana

HIV-infected children in sub-Saharan Africa may be at a high risk of staying on a failing first-line regimen and developing drug-resistance HIV variants due to lack of routine viral load monitoring. We investigated whether cumulative viral load, measured as viremia copy-years (VCY) could predict morbidity in a setting where viral load is not routinely monitored.



This was a single-center prospective observational longitudinal study of HIV-infected children initiating antiretroviral therapy (ART) at the Pediatric HIV/AIDS Care program at Korle-Bu Teaching Hospital in Accra, Ghana. The main outcome was morbidity measured as frequency of hospitalizations, opportunistic infections, and outpatient sick visits. The main explanatory variable was viral load measured as VCY.



The study included 140 children who initiated ART between September 2009 and May 2013 and had at least 2 viral load measurements. There were 184 hospitalizations, with pneumonia being the most common cause (22.8 %). A total of 102 opportunistic infections was documented, with tuberculosis being the most common opportunistic infection (68 %). A total of 823 outpatient sick visits was documented, with upper respiratory infections (14.2 %) being the most common cause. Forty-four percent of our study participants had >4 log10 VCY. Children in this sub-cohort had a higher frequency of sick visits compared with those with <4 log10 VCY (p = 0.03). Only 6.5 % of children with >4 log10 VCY had been identified as treatment failure using WHO clinical and immunological treatment failure criteria.



High level of cumulative viral load may translate to virological failure and subsequent increased all-cause morbidity. Our finding of potential utility of VCY in pediatrics warrants further investigations. VCY may be a good alternate to routine viral load measurement as its determination may be less frequent and could be personalized to save cost.
A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine.

This study was conducted to determine the toxicity profile, maximum tolerated dose (MTD) and pharmacokinetics of the putative histone deacetylase inhibitor CI-994 in combination with capecitabine.



Fifty-four patients were treated according to three different dosing schemes in which the capecitabine dose was fixed and the CI-994 dose was escalated. Capecitabine was administered in twice daily divided doses, and CI-994 was given as a single daily dose. In schedule A, 26 patients were treated with capecitabine 1650 mg/m2/day and CI-994 for 2 weeks of a 3-week cycle. In schedule B, six patients received capecitabine 1650 mg/m2/day for two 3-week cycles and CI-994 for 5 of 6 weeks. In schedule C, 22 patients were treated with capecitabine 2000 mg/m2/day and CI-994 for 2 of 3 weeks.



At the MTD, the principal dose-limiting toxicity was thrombocytopenia. The pharmacokinetics of CI-994 were unaltered by capecitabine, and there was no correlation between body surface area and major pharmacokinetic parameters. Platelet count nadir was best predicted by the observed maximal concentration (C(max)) of CI-994.



The recommended phase II dose is 6 mg/m2 (or 10 mg) of CI-994 in combination with capecitabine 2000 mg/m2/day for 2 weeks of a 3-week cycle.
A phase II study on the efficacy and safety of procedural analgesia with fentanyl buccal tablet in cancer patients for the placement of indwelling central venous access systems

Pain in cancer patients is often related to oncologic therapies and diagnostic procedures. The placement of fully implantable venous access systems is a very common procedure in oncology patients. Local anaesthesia is the method most commonly used to overcome pain related to this surgical procedure, but the local anaesthetic may be unable to completely eradicate all pain. This study investigates the effectiveness and safety of fentanyl buccal tablet (FBT), administered by OraVescent® technology, in reducing procedural pain related to the placement of indwelling central venous access systems (Ports) in opioid-naïve cancer patients. Inpatients who required an indwelling vascular access (Port) were preoperatively assessed with a self-assessment questionnaire on anxiety and pain. A 100 μg FBT was administered 10 min before preparation of the operating field. A self-assessment scale for pain experienced during the procedure was administered at the end of the procedure. Vital signs and the presence of any side effects or bothersome symptoms were monitored during the procedure, at the end, and 4 h later. From October 2012 to June 2014, 65 patients were enrolled in the study. A total of 61 (93.9 %) patients perceived no or a little pain during the procedure. Four patients (6.2 %) reported a lot of pain. No patient reported very severe pain. This data is significant in terms of the lower than expected presence of pain (Fisher test p = 0.0018) as assessed in our previous experience without procedural analgesia. The most common side effects of FBT was drowsiness, experienced by 28 patients at the end of the procedure (43.1 %), significantly reduced (p < 0.01) to 8 patients after 4 h (12.5 %). Nausea was present in 6 cases at the end of the procedure (9.2 %) and in 7 cases 4 h later (10.9 %). Vomiting was present in 3 cases at the end (4.7 %) and in 2 other patients after 4 h (7.8 %). No significant change of vital parameters was observed between the baseline and the subsequent measurements in all patients studied. The significant improvement in the number of patients experiencing little or no pain, accompanied by a lower number of non-severe side effects, suggests that FBT is a valid, practical and safe method of procedural analgesia. It will be necessary to perform further studies, taking into account the need for standard antiemetic pre-medication to minimise the incidence of nausea and vomiting.
An imatinib-only window followed by imatinib and chemotherapy for Philadelphia chromosome-positive acute leukemia: long-term results of the CMLALL1 trial.

We report long-term results in 40 patients with Philadlephia chromosome-positive (Ph+) acute leukemia who received an imatinib monotherapy window to evaluate in vivo effects on BCR-ABL signaling prior to induction chemotherapy. The first 25 patients (cohort 1) received the LALA-94 protocol without further imatinib (newly diagnosed Ph+ acute lymphoblastic leukemia [ALL]) or induction chemotherapy followed by single-agent imatinib. Subsequent patients (cohort 2) continued imatinib concurrently with either LALA-94 (newly diagnosed Ph + ALL) or other intensive chemotherapy regimens. Cohort 2 had a complete response (CR) rate of 93% and 5-year survival of 69%. For newly diagnosed Ph+ ALL, survival was superior in cohort 2 compared with cohort 1. Toxicity was similar to that expected for chemotherapy alone. Among 10 evaluable patients, rapid loss of phospho-CRKL occurred during the imatinib window in seven patients (all achieved CR) and incomplete inhibition in three patients (none with CR). In summary, a pharmacodynamic window design permitted biomarker assessment of BCR-ABL targeting without compromising clinical outcomes.
Phase I study of 5-fluorouracil and leucovorin by a 14-day circadian infusion in metastatic adenocarcinoma patients

Initial experimental and clinical studies have indicated that 5-fluorouracil (5-FU) toxicity can be reduced by delivering 5-FU at around 4 a.m. More recent data have suggested that the toxicity might be reduced even more with delivery at around 9–10 p.m. The current study determined the maximum tolerated dose (MTD) for 5-FU and leucovorin (LV) delivered as a continuous circadian infusion over 14 days every 28 days, with the peak of the infusion occurring at around 3–4 a.m. The peak drug delivery was shifted to 9–10 p.m. in all patients developing toxicity of ≥grade II (Eastern Cooperative Oncology Group) to determine if this timing further reduced toxicity and enabled increased dose intensity. A total of 14 patients with metastatic adenocarcinoma received an admixture of 5-FU and LV via a programmable portable infusion pump, with 62.5% of the 24-h dose being given over 7 h around the infusion peak. The starting dose level of 5-FU (200 mg/m2 daily) and LV (5 mg/m2 daily) was that established as the highest tolerable dose rate in a previously reported phase I study using a 14-day flat infusion of 5-FU and LV. The LV dose was first escalated to 20 mg/m2 daily, followed by escalations of the 5-FU dose. A total of 51 courses were evaluable for toxicity. The dose-limiting toxicity was oral mucositis and hand-foot syndrome. More dose intensity could be delivered using a circadian infusion peaking at around 3–4 a.m. than was possible with a flat infusion of these drugs. Toxicity was redouced even further with peak drug delivery at around 9–10 p. m. The recommended dose for phase II studies using this schedule is 250 mg/m2 5-FU daily and 20 mg/m2 LV daily with the peak of the infusion occurring at 9–10 p.m. This is a 300% and 25% higher dose for LV and 5-FU, respectively, than was found to be safe for a flat infusion.
What We Have Lost/What We Have Gained: Embodied Interfaces for Live Performance and Art Exhibitions

This paper examines the use of embodied interface design in experiential systems sculpture for art exhibitions, using the piece What We Have Lost / What We Have Gained as an example. Looking at musical instruments and MIDI devices for live electronic music performance as a starting point led to developing an interface that allows for more expressive physical gestures, and in turn functions in the area of interactive art. This paper demonstrates how HCI can be applied to and included within art disciplines to increase engagement with the artworks by transforming viewers into participants, players, and co-creators.
Does a ‘direct’ transfer protocol reduce time to coronary angiography for patients with non-ST-elevation acute coronary syndromes? A prospective observational study

National guidelines recommend 'early' coronary angiography within 96 h of presentation for patients with non-ST elevation acute coronary syndromes (NSTE-ACS). Most patients with NSTE-ACS present to their district general hospital (DGH), and await transfer to the regional cardiac centre for angiography. This care model has inherent time delays, and delivery of timely angiography is problematic. The objective of this study was to assess a novel clinical care pathway for the management of NSTE-ACS, known locally as the Heart Attack Centre-Extension or HAC-X, designed to rapidly identify patients with NSTE-ACS while in DGH emergency departments (ED) and facilitate transfer to the regional interventional centre for 'early' coronary angiography.



This was an observational study of 702 patients divided into two groups; 391 patients treated before the instigation of the HAC-X pathway (Pre-HAC-X), and 311 patients treated via the novel pathway (Post-HAC-X). Our primary study end point was time from ED admission to coronary angiography. We also assessed the length of hospital stay.



Median time from ED admission to coronary angiography was 7.2 (IQR 5.1-10.2) days pre-HAC-X compared to 1.0 (IQR 0.7-2.0) day post-HAC-X (p<0.001). Median length of hospital stay was 3.0 (IQR 2.0-6.0) days post-HAC-X v 9.0 (IQR 6.0-14.0) days pre-HAC-X (p<0.0005). This equates to a reduction of six hospital bed days per NSTE-ACS admission.



The introduction of this novel care pathway was associated with significant reductions in time to angiography and in total hospital bed occupancy for patients with NSTE-ACS.
Effect of beta-blocking drugs on beta-cell function and insulin sensitivity in hypertensive non-diabetic patients

The effects of two beta-blocking drugs on endogenous insulin secretion and insulin sensitivity were investigated in a double blind cross-over study in 13 hypertensive patients. The patients were randomly allocated to each of three 2-week treatment periods with propranolol 80 mg b.i.d., atenolol 50 mg b.i.d. and placebo b.i.d. Endogenous insulin secretion was assessed by measuring serum insulin and C-peptide before and 6 min after iv administration of glucagon; insulin sensitivity was determined by measuring insulin binding to erythrocytes, and as the glucose disappearance rate (KITT) after i.v. insulin. Fasting concentrations of serum free fatty acids (S-FFA) and plasma gastric inhibitory polypeptide (P-GIP) were also recorded during the three study periods. Both propranolol and atenolol reduced blood pressure, heart rate and S-FFA concentrations compared to placebo, and all patients showed measurable plasma concentrations of propranolol and atenolol. The results can be considered representative, therefore, of clinical beta-blockade. The two drugs did not significantly influence the fasting blood glucose level. There was an increase in fasting and glucagon-stimulated serum C-peptide concentration during propranolol therapy compared with placebo (p=0.037 and p=0.030, respectively), although this was not reflected by a significant change in serum insulin. Propranolol and atenolol did not significantly influence insulin binding to erythrocytes, but they clearly reduced the glucose disappearance rate KITT was compared to placebo (p=0.0036 and p=0.0003, respectively). The findings support the view that beta-blocking drugs can influence glucose metabolism by mechanisms other than inhibition of endogenous insulin secretion.
Absence of sustained hyperlactatemia in HIV-infected patients with risk factors for mitochondrial toxicity.

The prevalence of asymptomatic hyperlactatemia among HIV-infected individuals has been reported to be 4% to 36%. This variability may reflect differences in the definition of and risk factors for hyperlactatemia and/or techniques for venous lactate collection.



We examined the prevalence of elevated venous lactate collected in accordance with Adult AIDS Clinical Trials Group (AACTG) guidelines among HIV-infected and nucleoside analogue-treated subjects with risk factors associated with hyperlactatemia. Sustained hyperlactatemia was defined as 2 consecutive levels >or=1.5 but <or=4 times the upper limit of normal (ULN) within 30 days.



Eighty-three subjects were enrolled. Two thirds had >or=2 risk factors, with 11% having >4 risk factors. The median entry venous lactate level was 1.2 mmol/L (range: 0.7-5.1 mmol/L). Two subjects had a lactate level >1.5 times the ULN: 1 with a value of 2.1 times the ULN at entry and a week 2 level of 1.2 times the ULN and a second subject with a week 2 value of 1.9 times the ULN but an entry level of 1.4 times the ULN. The latter subject developed symptomatic lactic acidosis 3 weeks following study discontinuation.



Sustained asymptomatic hyperlactatemia among subjects with risk factors associated with hyperlactatemia was not observed when venous lactate was measured in a standardized fashion. One case of hyperlactatemia that evolved into symptomatic lactic acidosis was diagnosed soon after the completion of the study, however. Our findings indicate that asymptomatic hyperlactatemia is either very rare or an artifact of collection technique.
The influence of gender and atopy in the relationship between obesity and asthma in childhood.

The objective of the study was to examine the relationship between asthma and overweight-obesity in Spanish children and adolescents and to determine whether this relationship was affected by gender and atopy.



The study involves 8607 Spanish children and adolescents from the International Study of Asthma and Allergies in Childhood phase III. Unconditional logistic regression was used to obtain adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for the association between asthma symptoms and overweight-obesity in the two groups. Afterwards, it was stratified by sex and rhinoconjunctivitis.



The prevalence of overweight and obesity in 6-7-year-old children was 18.6% and 5.2% respectively and in 13-14 year-old teenagers was 11.4% and 1.1% respectively. Only the obese children, not the overweight children, of the 6-7 year old group had a higher risk of any asthma symptoms (wheezing ever: OR 1.68 [1.15-2.47], asthma ever: OR 2.29 [1.43-3.68], current asthma 2.56 [1.54-4.28], severe asthma 3.18 [1.50-6.73], exercise-induced asthma 2.71 [1.45-5.05]). The obese girls had an increased risk of suffering any asthma symptoms (wheezing ever: OR 1.73 [1.05-2.91], asthma ever: OR 3.12 [1.67-5.82], current asthma 3.20 [1.65-6.19], severe asthma 4.83[1.94-12.04], exercise-induced asthma 3.68 [1.67-8.08]). The obese children without rhinoconjunctivitis had a higher risk of asthma symptoms.



Obesity and asthma symptoms were associated in 6-7 year-old children but not in 13-14 year-old teenagers. The association was stronger in non-atopic children and obese girls.
Treatment of lymphangiomas with OK-432 (Picibanil) sclerotherapy: a prospective multi-institutional trial.

To describe and to determine the robustness of our study evaluating the efficacy of OK-432 (Picibanil) as a therapeutic modality for lymphangiomas.



Prospective, randomized trial and parallel-case series at 13 US tertiary care referral centers.



Thirty patients diagnosed as having lymphangioma. Ages in 25 ranged from 6 months to 18 years. Twenty-nine had lesions located in the head-and-neck area.



Every patient received a 4-dose injection series of OK-432 scheduled 6 to 8 weeks apart unless a contraindication existed or a complete response was observed before completion of all injections. A control group was observed for 6 months.



Successful outcome of therapy was defined as a complete or a substantial (>60%) reduction in lymphangioma size as determined by calculated lesion volumes on computed tomographic or magnetic resonance imaging scans.



Overall, 19 (86%) of the 22 patients with predominantly macrocystic lymphangiomas had a successful outcome.



OK-432 should be efficacious in the treatment of lymphangiomas. Our study design is well structured to clearly define the role of this treatment agent.