nils-herrmann/clean_scirepeval huggingface dataset:
Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48.

The present primary analysis of AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS) compares the efficacy and safety of once-daily darunavir/ritonavir (DRV/r) with that of lopinavir/ritonavir (LPV/r) in treatment-naive patients.



Patients with HIV-1 RNA at least 5000 copies/ml were stratified by HIV-1 RNA and CD4 cell count in a phase III, open-label trial, and randomized to receive DRV/r 800/100 mg qd or LPV/r 800/200 mg total daily dose (bid or qd) plus fixed-dose tenofovir and emtricitabine for 192 weeks. The primary objective was to demonstrate non-inferiority of DRV/r as compared with LPV/r in HIV-1 RNA less than 50 copies/ml per-protocol time-to-loss of virologic response at 48 weeks.



Six hundred and eighty-nine patients were randomized and treated; mean baseline HIV-1 RNA: 4.85 log10 copies/ml and median CD4 count: 225 cells/microl. At 48 weeks, 84% of DRV/r and 78% of LPV/r patients achieved HIV-1 RNA less than 50 copies/ml (estimated difference = 5.6 [95% confidence interval -0.1-11]%), demonstrating non-inferiority of DRV/r as compared with LPV/r (P < 0.001; per-protocol time-to-loss of virologic response). Patients with HIV-1 RNA at least 100 000 copies/ml had a significantly higher response rate with DRV/r (79%) versus LPV/r (67%; P < 0.05). Median CD4 cell count increases (non-completer = failure; cells/mul) were 137 for DRV/r and 141 for LPV/r. DRV/r had a lower incidence of possibly treatment-related grade 2-4 gastrointestinal-related adverse events (7 versus 14%) and treatment-related moderate-to-severe diarrhea (4 versus 10%) than LPV/r. Adverse events leading to discontinuation were DRV/r: 3% and LPV/r: 7%.



DRV/r 800/100 mg qd was non-inferior to LPV/r 800/200 mg at 48 weeks, with a more favorable safety profile. Significantly higher response rates were observed with DRV/r in patients with HIV-1 RNA at least 100 000 copies/ml. DRV/r 800/100 mg offers a new effective and well tolerated once-daily, first-line treatment option for treatment-naive patients.
Prolonged Oral L-carnitine Substitution Increases Bicycle Ergometer Performance in Patients with Severe, Ischemically Induced Cardiac Insufficiency

Acute and chronic L-carnitine application exerts protective effects in a number of cardiac diseases. These favourable effects are attributed to improvements of the energy metabolism and have been found both in animal experiments and in man. In order to investigate the effect of long-time oral L-carnitine substitution on physical performance, 41 patients suffering from class NYHA II or III cardiac insufficiency were recruited for a clinical study. Following the double-blind, randomized, placebo-controlled design of the study, 20 patients were given 3 × 1g L-carnitine daily for 120 days whereas the control group (21 patients) received placebo. Bicycle ergometer tests were used to determine maximum performance, systolic and diastolic blood pressure, heart rate, and ST changes. Four series of tests were carried out: on day 0 (before the first substrate application), on the 60th and the 120th day (during L-carnitine or placebo application), and on the 180th day (60 days after the end of substitution). A significant improvement in performance (significantly higher maximum performance during bicycle ergometry) could be found within the carnitine group on the 60th and 120th day of L-carnitine application; and haemodynamical parameters showed a tendency to improve, too. These effects, which were attributed to L-carnitine, could be detected even 60 days after the end of substitution. No corresponding changes were found in the placebo group. The findings presented in this paper support suggestions of other authors that L-carnitine in combination with the usual medication (digitalis, β-blockers, calcium antagonists, nitrates) improves performance and effort tolerance in patients with cardiac insufficiency. Moreover, the findings suggest a favourable long-term effect, which lasts beyond the actual L-carnitine application, on the performance of patients with advanced cardiac insufficiency.
Interventions to enhance physical and psychological functioning among younger women who are ending nonhormonal adjuvant treatment for early-stage breast cancer.

To conduct a clinical trial to determine if an educational intervention and a nutritional intervention could enhance physical and psychological functioning among younger women completing treatment for early-stage breast cancer.



Younger women (50 years of age or younger, N = 252), within 2 months of having completed active nonhormonal adjuvant therapy, diagnosed with stage 0, I, or II breast cancer with 10 or fewer positive lymph nodes were randomly assigned to a three-arm clinical trial. Women in the control arm of the trial received standard medical care. Women in the two active arms received either an educational intervention, designed to provide information about their illness and enhance adjustment, or a nutritional intervention, designed to promote a more healthy diet. Primary end points included mental functioning, physical functioning, and depressive symptoms. Women were assessed before random assignment, 4 months later (immediately post-intervention), and 13 months later (9 months post-intervention).



Participants assigned to the two active treatment arms had significantly less depressive symptomatology and better physical functioning by 13-month follow-up (differences between the two active arms were nonsignificant). These effects were primarily accounted for by changes in intrusive thoughts, concerns regarding cancer recurrence and mortality, self-concept perceptions, and self-efficacy expectations.  Tailored psychosocial interventions can be effectively designed to enhance adjustment among younger women who are completing nonhormonal adjuvant therapy.
The Effectiveness of a Community Health Program in Improving Diabetes Knowledge in the Hispanic Population: Salud y Bienestar (Health and Wellness)

We evaluated the effectiveness of the Salud y Bienestar program to deliver diabetes education in the Hispanic population in the United States. This program uses a community outreach model where community health promoters are trained and then they deliver education to other community members regarding diabetes disease, risk factors, and ways to prevent and control disease. This intervention applies a one-group pre- and post-test design to improve diabetes knowledge. The intervention carried out in the states of California, Texas, and Washington DC. A total of 1,413 participants were enrolled. Of these, 73 % were females, 46 % were 65 years or older, 59 % were Mexican, 64 % had at least elementary education, 56 % had lived in the US for more than 20 years, and 38 % participants were self-reported diabetic. Among diabetic participants, a significant improvement was observed on diabetes knowledge when comparing pre- and post-test scores (13.7 vs. 18.6, P < 0.001; Cohen’s d = 1.2). Among non-diabetic participants, diabetes knowledge also increased significantly after one-single training session (12.9 vs. 18.2, P < 0.001; Cohen’s d = 1.2). The Salud y Bienestar program conducted by community health workers was effective approach to improving diabetes knowledge in the Hispanic population.
Effectiveness of triple therapy with simeprevir for chronic hepatitis C genotype 1b patients with prior telaprevir failure.

Favourable efficacy and safety profiles for simeprevir in combination with pegylated interferon alpha (PEG-IFNα) and ribavirin (triple therapy) have been shown in clinical trials. This study was carried out to evaluate the effectiveness of simeprevir-based triple therapy for patients with prior telaprevir treatment failure. This multicentre, observational cohort consisted of 345 consecutive Japanese patients infected with HCV genotype 1b, including 20 who had experienced telaprevir-based triple therapy. Amino acid substitutions in the NS3/4A region were identified by direct sequencing at the time of relapse or breakthrough in treatment with telaprevir and at the initiation of treatment with simeprevir. Patients were stratified according to prior response to PEG-IFNα and ribavirin. Of the 20 patients with telaprevir treatment failure, 10 (50.0%) achieved sustained virological response at week 12 after the end of treatment (SVR12). For patients treatment naïve [3/4 (75.0%)] or with prior relapse [1/1 (100%)] or partial response [5/6 (83.3%)] to PEG-IFNα and ribavirin, almost all achieved SVR12, mainly because of the improvement of treatment adherence, especially to direct-acting antiviral agent and ribavirin. However, of the nine patients with prior null response to PEG-IFNα and ribavirin, only one (11.1%) achieved SVR12, despite all having received an adequate treatment dosage, and five (55.6%) achieved rapid virological response. The treatment outcome of simeprevir-based triple therapy for HCV genotype 1b patients with prior telaprevir failure depended on the prior response to PEG-IFNα and ribavirin. For patients with prior null response to PEG-IFNα and ribavirin, retreatment with simeprevir-based triple therapy is not a useful option.
Limited effect of screening for depression with written feedback in outpatients with diabetes mellitus: a randomised controlled trial

The aim of this study was to test the effectiveness of a screening procedure for depression (SCR) vs care as usual (CAU) in outpatients with diabetes. The primary outcome measured was depression score and the secondary outcomes were mental healthcare consumption, diabetes-distress and HbA1c. In a multicentre parallel randomised controlled trial, 223 outpatients with diabetes, who had an elevated depression score, were randomly assigned to SCR (n = 116) or CAU (n = 107), using computer generated numbers. SCR-patients were invited for a Composite International Diagnostic Interview (CIDI) to diagnose depression and/or anxiety (interviewers were not blinded for group assignment). As part of the intervention, patients and their physicians were informed of the outcome of the CIDI in a letter and provided with treatment advice. At baseline and 6 month follow-up, depression and diabetes-distress were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D) and the Problem Areas in Diabetes survey (PAID). HbA1c levels were obtained from medical charts. Mean CES-D depression scores decreased from baseline to 6 months in both groups (24 ± 8 to 21 ± 8 [CAU] and 26 ± 7 to 22 ± 10 [SCR] respectively [p < 0.001]), with no significant differences between groups. Neither diabetes-distress nor HbA1c changed significantly within and between groups. The percentage of patients receiving mental healthcare increased in the SCR group from 20% to 28%, compared with 15% to 18% in the CAU group. Depression screening with written feedback to patient and physician does not improve depression scores and has a limited impact on mental healthcare utilisation, compared with CAU. It appears that more intensive depression management is required to improve depression outcomes in patients with diabetes.
Clinical predictors of termination and clinical outcome of catheter ablation for persistent atrial fibrillation.

This study evaluated the role of pre-procedural clinical variables to predict procedural and clinical outcomes of catheter ablation in patients with long-lasting persistent atrial fibrillation (AF).



Catheter ablation of persistent AF remains a challenging task.



Catheter ablation was performed in 90 patients (76 men, age 57 +/- 11 years) with long-lasting persistent AF. The history of AF, echocardiographic parameters, presence of structural heart disease, and surface electrocardiogram (ECG) AF cycle length (CL) were assessed before ablation and analyzed with respect to procedural termination and clinical outcome. Mean follow-up was 28 +/- 4 months.



Persistent AF was terminated in 76 of 90 patients (84%) by ablation. The duration of continuous AF was shorter (p < 0.0001), the surface ECG AFCL was longer (p < 0.0001), and the left atrium was smaller (p < 0.01) in patients in whom AF was terminated by catheter ablation. The surface ECG AFCL was the only independent predictor of AF termination (p < 0.01). Maintenance of sinus rhythm was associated with a shorter duration of continuous AF (p < 0.0001), a longer surface ECG AFCL (p < 0.001), and a smaller left atrium (p < 0.05) compared with those with recurrent arrhythmia. In multivariate analysis, the surface ECG AFCL and the AF duration predicted clinical success of persistent AF ablation (p < 0.01 and p < 0.05, respectively).



The surface ECG AFCL is a clinically useful pre-ablation tool for predicting patients in whom sinus rhythm can be restored by catheter ablation. The duration of continuous AF and the surface ECG AFCL are predictive of maintenance of sinus rhythm.
Insulin resistance and LVH progression in patients with calcific aortic stenosis: a substudy of the ASTRONOMER trial.

The objective of this substudy of the ASTRONOMER (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin) trial was to examine the association between insulin resistance and progression of left ventricular hypertrophy (LVH) in patients with aortic stenosis (AS).



In a recent cross-sectional study, the authors reported that the metabolic syndrome was associated with an increased prevalence of concentric LVH in patients with AS. As a central feature of the metabolic syndrome, insulin resistance could be an important mediator of this association.



This substudy included 250 of 269 patients enrolled in ASTRONOMER. Follow-up was 3.4 ± 1.3 years. Insulin resistance was evaluated using the homeostatic assessment model (HOMA) index, and patients were dichotomized using the median HOMA index value (1.24). The rate of LVH progression was estimated by calculating the annualized change in LV mass index (LVMi), measured on echocardiography. The presence of LVH was defined as an LVMi >47 g/m(2.7) in women and >49 g/m(2.7) in men.



There was a significant progression of LVH among the patients without LVH at baseline (n = 134; p < 0.0001) but not in those with it (n = 116; p = NS). In those without LVH at baseline, the annualized progression rate of LVMi was significantly faster in the subset with HOMA >1.24 compared to that in the subset with HOMA <1.24 (2.49 ± 4.38 g/m(2.7)/year vs. -0.03 ± 3.90 g/m(2.7)/year; p = 0.001). During follow-up, LVH developed in 46% of patients with HOMA >1.24 compared to 11% of those with HOMA <1.24 (p = 0.0005). Independent predictors of faster LVH progression identified on multivariate analysis were history of hypertension (p = 0.048), degree of aortic valve calcification (p = 0.035), and HOMA index (p = 0.02).



In this ASTRONOMER substudy, insulin resistance was a powerful independent predictor of progression to LVH in patients with AS. Visceral obesity and ensuing insulin resistance may thus present novel therapeutic targets in AS patients.
High dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial.

3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) exhibit antiviral activity against human immunodeficiency virus type 1 (HIV-1) in vitro and may modulate the immune response to HIV infection. Studies evaluating the antiviral activity of statins have yielded conflicting results.



We conducted a randomized, double-blind, placebo-controlled crossover trial to investigate the effect of atorvastatin on HIV-1 RNA (primary objective) and cellular markers of immune activation (secondary objective). HIV-infected individuals not receiving antiretroviral therapy were randomized to receive either 8 weeks of atorvastatin (80 mg) or placebo daily. After a 4-6 week washout phase, participants switched treatment assignments. The study had 80% power to detect a 0.3 log(10) decrease in HIV-1 RNA level. Expression of CD38 and HLA-DR on CD4(+) and CD8(+) T cells was used to measure immune activation.



Of 24 randomized participants, 22 completed the study. Although HIV-1 RNA level was unaffected by the intervention (-0.13 log(10) copies/mL; P = .85), atorvastatin use resulted in reductions in circulating proportions of CD4(+) HLA-DR(+) (-2.5%; P = .02), CD8(+) HLA-DR(+) (-5%; P = .006), and CD8(+) HLA-DR(+) CD38(+) T cells (-3%; P = .03). Reductions in immune activation did not correlate with declines in serum levels of low-density lipoprotein cholesterol.



Short-term use of atorvastatin was associated with modest but statistically significant reductions in the proportion of activated T lymphocytes.
Endoscopic diagnosis of gastric intestinal metaplasia: a prospective multicenter study.

Intestinal metaplasia (IM) of the gastric mucosa has long attracted attention as a premalignant lesion involved in gastric carcinogenesis. However, endoscopic diagnosis of IM has remained unclear for a long time. In recent years, the methylene blue staining technique and narrow-band imaging (NBI) magnifying endoscopy have facilitated clinical diagnosis of IM, although these methods have some problems due to their complexity. Simple methods for diagnosis of IM using conventional endoscopy and the indigo carmine contrast (IC) method are necessary.



This study was a multicenter, prospective, randomized, comparative study involving 10 facilities. The appearance of IM was examined using conventional and IC methods with an electronic endoscope.



Subjects included 163 patients, of whom 87 and 76 underwent conventional and IC methods, respectively. Sensitivity, specificity, and receiver operating characteristic/area under thecurve (ROC/AUC) of conventional and IC methods for the detection of IM in the gastric antrum showed that diagnostic performance of the conventional method was higher, but not significantly, than that of the IC method. Sensitivity, specificity and ROC/AUC of conventional and IC methods for the detection of IM in the gastric body showed that the IC method yielded better (but not significantly better) results than the conventional method.



The diagnostic performance of the conventional method did not significantly differ from that of the IC method. A villous appearance, whitish mucosa, and rough mucosal surface, as observed by both methods, and areae gastricae pattern, as observed by the IC method, were useful indicators for endoscopic diagnosis of IM.
Sensory signalling effects of tegaserod in patients with irritable bowel syndrome with constipation.

Tegaserod relieves overall and multiple individual constipation-predominant irritable bowel syndrome (IBS-C) symptoms. However, mechanisms for the relief of abdominal pain/discomfort are not well understood. The effects of tegaserod on rectal sensitivity to distension were measured by the nociceptive flexion RIII reflex, as evidenced by spinal hyperexcitability (i.e. increase or facilitation of the RIII reflex), in IBS-C patients. A randomized, double-blind, placebo-controlled, parallel study was performed in 30 women with IBS-C. The effects of slow ramp rectal distension on the RIII reflex, recorded from the lower limb, were measured before [first experimental day (D1)] and after 7 days [day 8 (D8)] of placebo (n=15) or 6 mg tegaserod bid (n=15). Pressure-volume and sensation-volume relationships were measured during distension, and patients reported their IBS symptoms daily. On D1, rectal distension facilitated the RIII reflex in both treatment groups. On D8 vs D1 these facilitatory effects were significantly lower (P<0.001, analysis of variance) after tegaserod (mean reduction: -30.3+/-11.9%) than placebo (mean reduction: -10.1+/-12.9%). No significant changes in the volume-sensation relationship or differences in compliance were observed with tegaserod or placebo. In conclusion, tegaserod reduces the facilitatory effects of rectal distension on the RIII reflex in women with IBS-C.
Helical Tomotherapy for Inoperable Breast Cancer: A New Promising Tool

We investigated the feasibility of helical tomotherapy (HT) for inoperable large breast tumors, after failing to achieve adequate treatment planning with conformal radiation techniques.



Five consecutive patients with locally advanced breast cancer (LABC) were treated by preoperative HT. All patients received up-front chemotherapy before HT. Irradiated volumes included breast and nodal areas (45-50 Gy) in 4 patients. One patient received a simultaneous integrated boost (55 Gy) to gross tumor volume (GTV) without lymph node irradiation. Acute toxicity was assessed with Common Toxicity Criteria for Adverse Events v.4. Patients were evaluated for surgery at the end of treatment.



Patients were staged IIB to IIIC (according to the AJCC staging system 2010). HT was associated in 4 patients with concomitant chemotherapy (5-fluorouracil and vinorelbine). Two patients were scored with grade 3 skin toxicity (had not completed HT) and one with grade 3 febrile neutropenia. One patient stopped HT with grade 2 skin toxicity. All patients were able to undergo mastectomy at a median interval of 43 days (31-52) from HT. Pathological partial response was seen in all patients.



HT is feasible with acceptable toxicity profiles, potentially increased by chemotherapy. These preliminary results prompt us to consider a phase II study.
Analysis of the time course of the effect of subthalamic nucleus stimulation upon hand function in Parkinson's patients.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) as treatment for Parkinson's disease has been in use for more than a decade, yet the immediate effect of stimulation upon movement parameters is not well characterized.



The goal of the current study is the identification of the best time point to test hand function after programming DBS devices.



Reaction time, movement time and velocity were measured at multiple time points with a movement-sensitive glove after the deep brain stimulator had been turned on or off, during 'off medication' conditions.



Velocity, movement time and reaction time worsened significantly in the first 20 min after the deep brain stimulator had been turned off. A 'plateau effect' after 20 min was not observed. Initiation of stimulation led to immediate significant increases in movement time and velocity and to a lesser degree a decrease in reaction time. Patients performed more inconsistently over time after onset of stimulation compared to stimulation withdrawal. Intraoperative testing showed an immediate improvement in velocity after placement of the STN deep brain stimulator.



Movement time and velocity already reach their peak changes within 20 min after the deep brain stimulator has been reprogrammed, and therefore, this time point may be used to test the maximal clinical effect of stimulation.