nils-herrmann/clean_scirepeval huggingface dataset:
Post-exposure prophylaxis for HIV infection: a clinical trial comparing lopinavir/ritonavir versus atazanavir each with zidovudine/lamivudine.

A clinical trial comparing the rate of discontinuation and tolerability of two post-exposure prophylaxis (PEP) regimens was performed.



A total of 255 individuals attending the emergency rooms of six hospitals for exposure to HIV and criteria to receive PEP were randomized to receive zidovudine/lamivudine plus either lopinavir/ritonavir (n=131) or atazanavir (n=124; day 0). The primary end point was the rate of PEP discontinuation before day 28 of follow-up. Secondary end points were incidence of side effects, follow-up at days 90 and 180 and rate of seroconversions.



A total of 55 patients (29 in lopinavir/ritonavir and 26 in atazanavir arms) did not attend the first scheduled appointment (day 1) and were excluded from the analysis. The rate of discontinuation before day 28 owing to any cause was similar between groups (37/102 [36%] in lopinavir/ritonavir and 35/98 [36%] in atazanavir arms, P=0.82). Adverse events were the reason for discontinuation or switching of PEP in 33 individuals (16/102 [16%] in the lopinavir/ritonavir arm and 17/98 [17%] in the atazanavir arm, P=0.84). Adverse events were reported in 92/200 (46%) of individuals on PEP who attend at least the day 1 appointment (50/102 [49%] in the lopinavir/ritonavir arm and 42/98 [43%] in the atazanavir arm, P=0.38). There were no seroconversions.



The rate of discontinuation of PEP before day 28 was similar with zidovudine/lamivudine plus either lopinavir/ritonavir or atazanavir. The rate of discontinuation of PEP because of adverse events was low in both arms. Almost 50% of the patients of both arms suffered side effects. New strategies are needed to improve the tolerance.
A phase II study of combination therapy with irinotecan and S-1 (IRIS) in patients with advanced colorectal cancer

A combination of irinotecan with continuous infusional 5-fluorouracil (5-FU) is the standard treatment for advanced colorectal cancer. The aim of this study was to determine the efficacy and safety of combining irinotecan and S-1 (IRIS) in patients with advanced colorectal cancer. Irinotecan was administered as an intravenous infusion at a dose of 120 mg/m2 on day 1 and 15. And S-1 was administered orally on days 1–14 of a 28-day cycle. S-1 was given orally at a dose that did not exceed 40 mg/m2 based BSA: BSA < 1.25 m2, 40 mg twice daily; 1.25–1.5 m2, 50 mg twice daily, and BSA > 1.5 m2, 60 mg twice daily, for 14 consecutive days. A total of 38 patients were enrolled. An intent-to-treat analysis showed a complete response and partial response to occur in 13.2% and 50.0%, respectively. The disease control rate was 84.2%. The median progression-free survival and overall survival were 10.0 months and 29.1 months, respectively. The rates of grade 3/4 toxicity over 4 cycles were the following: neutropenia, 15.8%; leucopenia, 7.9%; anorexia, 15.8%; diarrhea, 10.5%.  IRIS is an effective, well tolerated and convenient treatment regimen for patients with advanced colorectal cancer.
Formal and graphical annotations for digital objects

This paper presents graphical tools that facilitate manual building of formal semantic annotations for digital objects. These tools are intended to be integrated in digital object (DO) management systems requiring semantic metadata (e.g. precise indexation, comment, categorization, certification). We define a multidimensional graphical model of semantic annotations that specifically allows contextualization of annotations, and we propose a methodology for building such annotations. The graph-based formalism used (derived from Conceptual Graphs), provides graphical representations that users can easily understand, and are furthermore logically founded. A graphical generic API implementing elements of the SG family has been developed. CoGUI consists of three specialized tools: a tool for defining a CG ontology, another for creating annotations based on a CG ontology, and finally a tool that uses the CoGITaNT platform, for querying an annotated DO base.
Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial

Parkinson's disease is typically treated with oral dopamine replacement therapies; however, long-term treatment leads to motor complications and, occasionally, impulse control disorders caused by intermittent stimulation of dopamine receptors and off-target effects, respectively. We aimed to assess the safety, tolerability, and efficacy of bilateral, intrastriatal delivery of ProSavin, a lentiviral vector-based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease.



We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. All patients were then enrolled in a separate open-label follow-up study of long-term safety. Three doses were assessed in separate cohorts: low dose (1·9×10(7) transducing units [TU]); mid dose (4·0×10(7) TU); and high dose (1×10(8) TU). Inclusion criteria were age 48-65 years, disease duration 5 years or longer, motor fluctuations, and 50% or higher motor response to oral dopaminergic therapy. The primary endpoints of the phase 1/2 study were the number and severity of adverse events associated with ProSavin and motor responses as assessed with Unified Parkinson's Disease Rating Scale (UPDRS) part III (off medication) scores, at 6 months after vector administration. Both trials are registered at ClinicalTrials.gov, NCT00627588 and NCT01856439.



15 patients received ProSavin and were followed up (three at low dose, six mid dose, six high dose). During the first 12 months of follow-up, 54 drug-related adverse events were reported (51 mild, three moderate). Most common were increased on-medication dyskinesias (20 events, 11 patients) and on-off phenomena (12 events, nine patients). No serious adverse events related to the study drug or surgical procedure were reported. A significant improvement in mean UPDRS part III motor scores off medication was recorded in all patients at 6 months (mean score 38 [SD 9] vs 26 , n=15, p=0·0001) and 12 months (38 vs 27 ; n=15, p=0·0001) compared with baseline.



ProSavin was safe and well tolerated in patients with advanced Parkinson's disease. Improvement in motor behaviour was observed in all patients.
Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls.

To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB).



This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV (n=247), HepB (n=247) or HPV co-administered with HepB (HPV+HepB; n=247) at Months 0, 1 and 6. Antibodies against hepatitis B surface antigen (HBs), HPV-16 and HPV-18 were measured, and reactogenicity and safety monitored. Co-primary objectives were to demonstrate non-inferiority of hepatitis B and HPV-16/18 immune responses at Month 7 for co-administered vaccines, compared with vaccines administered alone, in the according-to-protocol cohort.



The pre-defined criteria for non-inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti-HBs seroprotection rates ≥10mIU/mL were achieved by 97.9% and 100% of girls, respectively, following co-administration or HepB alone. Anti-HBs geometric mean titers (GMTs) (95% confidence interval) were 1280.9 (973.3-1685.7) and 3107.7 (2473.1-3905.1) milli-international units/mL, respectively. Anti-HPV-16 and -18 seroconversion rates were achieved by ≥99% of girls following co-administration or HPV alone. Anti-HPV-16 GMTs were 19819.8 (16856.9-23303.6) and 21712.6 (19460.2-24225.6) ELISA units (ELU)/mL, respectively. Anti-HPV-18 GMTs were 8835.1 (7636.3-10222.1) and 8838.6 (7948.5-9828.4) ELU/mL, respectively. Co-administration was generally well tolerated.



The study results support the co-administration of HPV-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine in adolescent girls aged 9-15 years.
The use of text messaging to improve asthma control: a pilot study using the mobile phone short messaging service (SMS).

We have evaluated the feasibility of using the mobile phone short message service (SMS) for symptom monitoring in patients with asthma. All consecutive patients admitted to hospital for asthma during an 11-month period were considered for enrollment (n = 497). Those meeting the inclusion criteria were randomized into a control (n = 60) and intervention group (n = 60). Patients in the intervention group received SMS messages according to a structured workflow, while patients in the control group had no SMS support. In the intervention group, the mean response rate to the messages was 82%. There was an improvement in the Asthma Control Test (ACT) scores in 36 subjects in the intervention group compared to 28 subjects in the control group. There were reductions in the number of nebulizations in 54 subjects in the control group compared to 50 subjects in the intervention group, and reductions in emergency department visits in 57 subjects in the control group compared to 51 subjects in the intervention group. However, none of these differences were significant. There was no reduction in admission rates in either group (P = 0.5). The service was accepted by most patients, but its long-term effectiveness on the management of asthma remains to be determined.
An organ-preserving selective arterial chemotherapy strategy for head and neck cancer.

Squamous cancer of the upper aerodigestive tract is a disheartening disease. Despite our best efforts, the long-term survival rate remains only 15% to 40%, and surgical cures often decrease the quality of life owing to the loss of swallowing and speech organs. A better understanding of tumor dynamics and the discovery that thiosulfate can neutralize cisplatin led us to develop a treatment plan that combines a rapid superselective high-dose intraarterial delivery of cisplatin (CDDP), simultaneous intravenous infusion of its antagonist, thiosulfate, and radiation therapy.



Patients with advanced head and neck squamous cancer were entered into the protocol after a multidisciplinary evaluation that included CT or MR imaging. Forty-two patients constituted the first cohort. After baseline angiography, an arterial acceptance test determined the maximum infusion rate that the tumor's nutrient artery would accept. CDDP was then infused at that rate, usually within 3 to 5 minutes, while the antagonist thiosulfate was given intravenously. In the second cohort of 85 patients with stage 3 or 4 previously untreated and unresectable disease, local radiation was added to the treatment plan. The radiation dose (180-200 cGy/d x 35) was delivered regionally on the basis of the known radiosensitizing effect of CDDP.



Cohort 1 allowed us to develop the infusion technique and to establish a dose quantity and delivery frequency. When 150 mg/m2 was administered weekly for 4 weeks, no severe toxicity was found. In cohort 2, 72 (92%) of the remaining 78 patients had complete disappearance of their tumor. Seventeen severe toxic events were associated with 323 femoral catheterizations. One patient died of pulmonary embolus, precluding follow-up evaluation. Six patients had neurologic sequelae, three with transient and three with permanent strokes.



Rapid superselective chemotherapy with CDDP combined with a circulatory systemic antagonist allowed delivery of an antitumoral drug directly into the lesion while protecting the kidneys and bone marrow from the agent's systemic effects. Use of a dose regimen of 150 mg CDDP/m2 per week for 4 weeks resulted in the disappearance of a large percentage of advanced squamous cancers.
Retention rate of Gabapentin in children with intractable epilepsies at 1 year

Gabapentin (GAB) is a newer second-line antiepileptic drug (AED) used in children. This is a multi-centre retrospective observational study of the efficacy, tolerability and retention rate in 105 children, aged 0-17.5 years (mean 10.1) over a 14 year period. The median age of epilepsy onset was 2.5 years (range 0-14.6). 72% started GAB as at least the 3rd AED, with 43% having been withdrawn from at least 2 AEDs. 77% had focal and 52% symptomatic epilepsies. The maintenance doses for GAB ranged 6.0-87.3 mg/kg/day (mean 43.7). The study comprised 157 person-treatment years for GAB. GAB was well tolerated with 55% remaining on treatment beyond 1 year. No serious adverse events were reported whilst on GAB, but 39% reported possibly and probably related adverse events. Seizure improvement (<50% seizure frequency compared to baseline) at more than 12 months of treatment, was reported in 35% of patients starting GAB, including 6% who remained seizure free. The results demonstrated the efficacy and tolerability of GAB in children with difficult to treat epilepsies, and a good response to treatment beyond 12 months, in both focal and generalised epilepsies.
Subject‐driven titration of biphasic insulin aspart 30 twice daily is non‐inferior to investigator‐driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open‐label, parallel‐group, multicenter trial

The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID).



In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or α-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group.



Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA1c target without confirmed hypoglycemia throughout the trial in the subject-driven and investigator-driven groups, respectively.



Subject-titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision.
Stimulation by hCRF of C-peptide release in type 2 diabetics during concomitant opioid receptor blockade

Administration of synthetic human corticotropin-releasing factor (hCRF, 2 µg/kg body weight) during simultaneous application of the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) produced a significant increase in plasma C-peptide levels of six male Type 2 diabetic patients which even exceeded the postprandial values. This stimulatory effect of hCRF/naloxone on plasma C-peptide was less pronounced in six healthy men. hCRF alone did not provoke any reaction of plasma C-peptide in either group. The possibility of a paracrine, CRF-dependent mechanism in pancreatic islets which somehow involves inhibitory opioid receptors is preferentially discussed. Such a mechanism may underlie the stimulatory action of hCRF/naloxone on B cells and would explain the absent reaction of peripheral venous plasma C-peptide to hCRF alone as well as the amplifying effect of simultaneous opioid receptor blockade.
Home-based telemonitored Nordic walking training is well accepted, safe, effective and has high adherence among heart failure patients, including those with cardiovascular implantable electronic devices: a randomised controlled study.

The benefits of rehabilitation in heart failure (HF) patients are well established. Little is known about Nordic walking (NW) training in HF patients especially in those with cardiovascular implantable electronic devices (CIEDs).



The purpose of this study was to assess safety, effectiveness, adherence to and acceptance of home-based telemonitored NW in HF patients, including those with CIEDs (i.e. cardiac resynchronisation therapy, implantable cardioverter-defibrillator).



The study design was a single-centre, prospective, parallel-group, randomised (2:1), controlled trial among 111 HF patients, New York Heart Association (NYHA) II-III; left ventricular ejection fraction (EF) ≤ 40%. The intervention was a home-based telemonitored eight-week NW (training group (TG) n = 77) five times weekly vs usual care alone (control group (CG) n = 34). Outcome measures included a primary end point of functional capacity assessed by peak oxygen consumption (VO2peak). Secondary end points included: workload duration (t) in cardiopulmonary exercise test (CPET), six-minute walking test (6-MWT) distance and quality of life (QoL), Medical Outcome Survey Short Form 36 (SF-36); safety; adherence to and acceptance of NW. Measurements were made before and after intervention.



NW resulted in significant improvement in: VO2peak (16.1 ± 4.0 vs 18.4 ± 4.1(ml/kg/min), p = 0.0001), t (471 ± 141 vs 577 ± 158 (s), p = 0.0001), 6-MWT(428 ± 93 vs 480 ± 87 (m), p = 0.0001) and QoL (79.0 ± 31.3 vs 70.8 ± 30.3 (score), p = 0.0001). We did not observe favourable results in the CG. The differences between the TG and CG were significant in: ΔVO2peak (Δ2.0 ± 2.4 vs Δ-0.2 ± 2.1, p = 0.0004); Δt (Δ108 ± 108 vs Δ0.94 ± 109, p = 0.0031); Δ6-MWT (Δ53.8 ± 63.9 vs Δ22.0 ± 68.7, p = 0.0483). In neither group were there deaths nor necessity for hospitalisation. We did not observe any intervention from CIEDs during NW. All patients in the TG completed rehabilitation and accepted it well.



In HF patients, including those with CIEDs, home-based telemonitored NW is safe and effective. NW was well accepted by patients and adherence was high and promising.
Effect of low doses of scopolamine on RR interval variability, baroreflex sensitivity, and exercise performance in patients with chronic heart failure.

To study the effect of transdermal scopolamine on heart rate variability, baroreflex sensitivity, and exercise performance in patients with heart failure and age matched healthy volunteers.



Double blind, randomised, placebo controlled, crossover study.



16 patients with chronic, stable heart failure due to ischaemic cardiomyopathy (mean (SEM) age 58 (2) years; mean (SEM) radionuclide left ventricular ejection fraction 28 (2)%; New York Heart Association class II-III) and eight age matched healthy controls.



Transdermal scopolamine (500 micrograms delivered over 72 h) or a placebo patch was administered for 48 h.



Indices of tonic and reflex cardiac vagal activity and exercise performance.



In both groups scopolamine produced a reduction in the 24 h average heart rate and an increase in the time domain measures of heart rate variability. Both the incidence and severity of ventricular arrhythmias remained unchanged. Baroreflex sensitivity, evaluated by the phenylephrine technique, increased significantly (P < 0.001) with scopolamine in patients with heart failure (6.22 (2.81) ms/mm Hg) and in healthy volunteers (5.97 (2.20) ms/mm Hg) as did the amplitude of respiratory sinus arrhythmia, computed by autoregressive spectral analysis of 10 min electrocardiographic recordings (319.9 (123.5) and 657.3 (126.6) ms2 respectively, P < 0.001). While exercise performance did not change, heart rate at submaximal exercise was significantly reduced by scopolamine in each group.



In patients with mild to moderate heart failure low doses of scopolamine increased tonic and reflex cardiac vagal activity. This was achieved without affecting exercise tolerance or the incidence and severity of ventricular arrhythmias.
Higher lung deposition with Respimat® Soft Mist™ Inhaler than HFA-MDI in COPD patients with poor technique

Aerosols delivered by Respimat Soft Mist Inhaler (SMI) are slower-moving and longer-lasting than those from pressurized metered-dose inhalers (pMDIs), improving the efficiency of pulmonary drug delivery to patients. In this four-way cross-over study, adults with chronic obstructive pulmonary disease (COPD) and with poor pMDI technique received radiolabelled Berodual (fenoterol hydrobromide 50 microg/ipratropium bromide 20 microg) via Respimat SMI or hydrofluoroalkane (HFA)-MDI (randomized order) on test days 1 and 2, with no inhaler technique training. The procedure was repeated on test days 3 and 4 after training. Deposition was measured by gamma scintigraphy. All 13 patients entered (9 males, mean age 62 years; FEV1 46% of predicted) inhaled too fast at screening (peak inspiratory flow rate [IF]: 69-161 L/min). Whole lung deposition was higher with Respimat SMI than with pMDI for untrained (37% of delivered dose vs 21% of metered dose) and trained patients (53% of delivered vs 21% of metered dose) (P(Sign-Test) = 0.15; P(ANOVA) < 0.05). Training also improved inhalation profiles (slower average and peak IF as well as longer breath-hold time). Drug delivery to the lungs with Respimat SMI is more efficient than with pMDI, even with poor inhaler technique. Teaching patients to hold their breath as well as to inhale slowly and deeply increased further lung deposition using Respimat SMI.
Effectiveness of a diabetes education and intervention program on blood glucose control for patients with type 2 diabetes in a Turkish community.

This study was undertaken to determine the effects of patient education and other interventions (regular exercise and diet), combined with existing oral antidiabetic therapy, on blood glucose control in patients with type 2 diabetes mellitus (DM). Two out of 16 primary health care centers present in Elazig, an eastern Turkish city, were randomly selected for this study; the patients had type 2 DM, lived in the service area of these health centers. Of a total of 100 participants, 33 were instructed to follow the standard diet for type 2 DM patients, 28 performed exercise in addition to the standard diet, and 39 did not participate in either exercise or follow the diabetic diet; they served as the control group. The percentage of glycosylated hemoglobin (HbA(1C)) was measured before and after the 8-week program and comparisons between the groups were made. At the beginning of the program, the HbA(1C) percentage in the diet-plus-exercise group (9.9 +/- 2.6%) was higher than in the diet (7.8 +/- 2.2%) and control groups (7.5 +/- 2.1%). After the intervention program, the HbA(1C) value of the control group had not changed significantly, while the most dramatic change in this value was obtained in the diet + exercise group, which was significantly reduced to 7.9 +/- 1.5%. The results of this 8-week intervention program indicate that a diabetes education and intervention program involving the combination of exercise and diet enhanced the effectiveness oral therapy on blood glucose control in patients with type 2 DM.