nils-herrmann/clean_scirepeval huggingface dataset:
Leucocyte Interferon-alpha for Patients with Chronic Hepatitis C Intolerant to Other alpha-Interferons

Alpha-interferon (α-IFN) is the treatment of choice for chronic hepatitis C but most patients experience adverse effects which sometimes lead to the suspension of therapy. Recently, higher doses of α-IFN or prolonged therapy have increased the number of cases of intolerance. In this open study we evaluated the efficacy and safety of leucocyte interferon-alpha (IFNα) [6MU three times a week] in 43 patients with chronic hepatitis C who had been intolerant to previous treatment courses with recombinant or lymphoblastoid IFNα. All patients were treated for 6 months and followed-up for an additional 6 months. End of treatment responders were patients in whom hepatitis C virus (HCV)-RNA had been eradicated from the blood by the end of treatment, sustained responders were those patients who maintained negative HCV-RNA at the end of follow-up, and the remaining patients were considered non-responders. Adverse effects were monitored by interviews, laboratory and clinical examinations. Five patients (11.6%) discontinued the treatment, four due to the reappearance of previous adverse effects, and one due to an ex novo adverse effect. In six patients the dose had to be halved. At the end of treatment 11 patients (25.6%) had negative serum HCV-RNA. After discontinuation of therapy, disease flared in four patients, thus seven patients were sustained responders. This study shows that leucocyte IFNα at a dose of 6MU three times a week is well tolerated in patients previously intolerant to recombinant or lymphoblastoid IFNα, allowing a high percentage of them to complete a course of treatment in terms of duration and dose.
Higher level of systemic C-reactive protein is independently predictive of coronary heart disease in older community-dwelling adults: the three-city study.

To assess the association between systemic C-reactive protein (CRP) and incident coronary heart disease (CHD) in community-dwelling elderly people.



A French population-based multicenter prospective cohort study.



Three cities in France: Bordeaux in the southwest, Dijon in the northeast, and Montpellier in the southeast.



After 4 years of follow-up, a case-cohort study was designed including 1,004 subjects randomly selected from the initial cohort of 9,294 subjects free of CHD at baseline and 174 subjects who developed first CHD events during follow-up.



Hazard ratios (HRs) were estimated using a Cox proportional hazard model adapted for the case-cohort design using a CRP level less than 1 mg/L as the reference category.



Of the random sample, 24.3% had a CRP level less than 1.0 mg/L, 45.8% had a CRP level of 1.0 to 2.9 mg/L, and 29.9% had a CRP level of 3.0 to 10.0 mg/L. The HRs for CHD, adjusted for age, sex, and study center, were 1.69 (95% confidence interval (CI)=1.04-2.75) for CRP from 1.0 to 2.9 mg/L and 2.32 (95% CI=1.41-3.82) for CRP from 3.0 to 10.0 mg/L (P for trend <.001). After additional adjustment for smoking, body mass index, diabetes mellitus, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, statin use, and antihypertensive treatment, a baseline CRP of 3.0 to 10.0 mg/L remained associated with risk of CHD (HR=1.87, 95% CI=1.09-3.25), although CRP did not improve the discriminative ability of a predicting model based on traditional risk factors (receiver operating characteristic curves from 0.740 to 0.749).



CRP is an independent CHD risk marker but does not improve CHD risk prediction in community-dwelling elderly people.
Genital shedding of HIV after scheduled treatment interruption.

This study assessed genital shedding of HIV in patients on intermittent combination antiretroviral therapy (cART) and assessed predictors of having detectable genital HIV RNA in 156 Thai patients with CD4 > 350 cells/μL and HIV RNA ≤50 copies/mL who were randomized to continuous therapy (CT, n = 65) or CD4-guided cART (n = 91). There were 383 matched genital and plasma HIV RNA samples (CT: 158, CD4 guided: 225). In 14 samples collected within eight weeks of treatment interruption, detectable HIV RNA was present in 29% of genital samples and 71% of plasma samples. In 55 samples collected after eight weeks of treatment interruption, detectable HIV RNA was present in 60% of genital samples and 98% of plasma samples. In 110 samples collected up to 96 weeks after treatment re-initiation, detectable genital HIV RNA was found in 8% of samples and all of these were within the first 17 weeks. Independent predictors of detectable genital HIV RNA were increasing age and increasing concentrations of HIV RNA in plasma. These findings support the role of cART in maintaining undetectable HIV RNA in genital secretions.
Neuropsychological and Quality of Life Changes Following Unilateral Thalamic Deep Brain Stimulation in Parkinson's Disease: A One-Year Follow-up

The long-term neuropsychological and quality of life (QOL) outcomes of unilateral thalamic deep brain stimulation (DBS) in patients with intractable Parkinson's disease (PD) have not heretofore been described. Six patients diagnosed with PD underwent unilateral DBS implantation into a verified thalamic VIM nucleus target. Participants completed presurgical neuropsychological evaluation and follow-up assessment at approximately one year postsurgery. Compared to their presurgical scores, PD patients exhibited significant improvement on measures of conceptualization, verbal memory, emotional adjustment, and QOL at one-year follow-up. A few nominal declines were observed across the battery of tests. These data provide preliminary support for the long-term neurocognitive safety and QOL improvements following thalamic stimulation in patients with PD.
Darunavir, ritonavir, and etravirine pharmacokinetics in the cervicovaginal fluid and blood plasma of HIV-infected women.

We report darunavir, ritonavir, and etravirine pharmacokinetics in cervicovaginal fluid and blood plasma for women from the Gender, Race and Clinical Experience (GRACE) study. Eight women received darunavir-ritonavir (600/100 mg) twice daily (b.i.d.); two also received etravirine (200 mg) b.i.d. Week 4 paired blood plasma and cervicovaginal fluid samples were collected over 12 h. Darunavir and etravirine cervicovaginal fluid exposures were higher than blood plasma exposures; ritonavir cervicovaginal fluid exposure was lower than blood plasma exposure. The high exposures of darunavir and etravirine in cervicovaginal fluid warrant further evaluation of these drugs for use in HIV-1 prevention.
High prevalence of fragility vertebral fractures in patients hospitalised in Internal Medicine Units. Results of the POINT (Prevalence of Osteoporosis in INTernal medicine) study.

Osteoporotic vertebral fractures (VFs) often go unrecognised in both healthy individuals and in pathological conditions. Few data exist on VFs in patients hospitalised in Internal Medicine Units (IMUs), who often suffer from multiple concomitant chronic disorders.



This multicentre cross-sectional study was aimed at assessing the prevalence of VFs in an unselected population of patients referring to IMUs. Correlations between VFs and the main coexisting diseases were also investigated.



Information on demographic, clinical and laboratory findings, and on the presence of known risk factors for osteoporosis was recorded. The Genant's semi-quantitative method was used to evaluate, in a central reading centre, the presence and severity of VFs in the thoracic and lumbar spine.



A cohort of 995 patients was evaluated. At least one VF of any grade was found in 47.5% of patients, with similar prevalence between females (48.1%) and males (46.7%). Older age, chronic obstructive pulmonary disease, and previous diagnosis of osteoporosis showed a significant association with VFs in multivariable analysis. However, 79.7% of the VFs were observed in patients without previous diagnosis of osteoporosis. Moreover, a VF of grade 2 or greater was found in 20.8% of patients.



Fragility VFs is a very frequent finding in patients hospitalised in IMUs. Consequently, more attention should be devoted in this clinical setting to this comorbidity, which is known to be an additional factor for mortality and, when localised in the thoracic part of the spine, may negatively influence a concomitant respiratory insufficiency.
Increased mortality in paroxysmal atrial fibrillation: report from the Stockholm Cohort-Study of Atrial Fibrillation (SCAF).

Whether paroxysmal atrial fibrillation (PxAF) affects survival is poorly recognized. Results have been conflicting in the few previously published studies. To describe mortality in patients with PxAF and to identify risk factors amenable to treatment.



All patients (n=2824) treated for atrial fibrillation during 2002 at one of Scandinavia's largest hospitals were followed prospectively for a mean of 4.6 years. Information about type of AF, comorbidity, and medication was acquired from medical records and national registers. Information about deaths was obtained from the National Cause of Death Register. One-third (n=888) of the patients had PxAF (mean age 73 years). During follow-up, 267 of them died. The mean annual mortality rate was 7%. Compared with the general population, the standardized mortality ratio (SMR) was 1.6 (95% CI 1.4-1.8) for all-cause mortality, 2.4 (95% CI 1.4-3.7) for death from myocardial infarction, and 2.6 (95% CI 1.3-5.2) for death from heart failure. Warfarin treatment was associated with improved survival both in comparison with the general population (SMR 1.1 with warfarin, SMR 2.2 without warfarin) and after propensity score matching for odds to receive warfarin (HR 0.5, 95% CI 0.3-0.9). The improvement of survival could not be explained by stroke reduction alone.



PxAF is associated with increased mortality, which mostly appears to be related to concomitant cardiovascular risks. Treatment with warfarin is associated with improved survival in PxAF patients.
Arming the Melanoma Sentinel Lymph Node through Local Administration of CpG-B and GM-CSF: Recruitment and Activation of BDCA3/CD141(+) Dendritic Cells and Enhanced Cross-Presentation.

Melanoma-induced suppression of dendritic cells (DC) in the sentinel lymph node (SLN) interferes with the generation of protective antitumor immunity. In an effort to strengthen immune defense against metastatic spread, we performed a three-arm phase II study comprising 28 patients with stage I-II melanoma randomized to receive intradermal injections around the primary tumor excision site of saline or low-dose CpG-B, alone or combined with GM-CSF, before excision of the SLNs. After pathologic examination, 5 patients were diagnosed with stage III melanoma based on the presence of tumor cells in the SLNs. Combined CpG/GM-CSF administration resulted in enhanced maturation of all identifiable conventional (cDC) and plasmacytoid (pDC) DC subsets and selectively induced increased frequencies of SLN-resident BDCA3/CD141(+) cDC subsets that also expressed the C-type lectin receptor CLEC9A. Correlative in vivo analyses and in vitro studies provided evidence that these subsets were derived from BDCA3(+) cDC precursors in the blood that were recruited to the SLNs in a type I IFN-dependent manner and subsequently matured under the combined influence of CpG and GM-CSF. In line with their reported functional abilities, frequencies of in vivo CpG/GM-CSF-induced BDCA3/CD141(+) DCs correlated with increased ex vivo cross-presenting capacity of SLN suspensions. Combined local CpG/GM-CSF delivery thus supports protective antimelanoma immunity through concerted activation of pDC and cDC subsets and recruitment of BDCA3(+) cDC subsets with T cell-stimulatory and cross-priming abilities.
Testosterone therapy during exercise rehabilitation in male patients with chronic heart failure who have low testosterone status: a double-blind randomized controlled feasibility study.

This study assessed the feasibility of a 12-week program of exercise, with and without intramuscular testosterone supplementation, in male patients with chronic heart failure (CHF) and low testosterone status and collected preliminary data for key health outcomes.



Male patients with CHF (n = 41, age 67.2 years, range 51-84 years) with mean ± SD testosterone levels of 10.7 ± 2.6 nmol/L (309 ± 76 ng/dL) were randomly allocated to exercise with testosterone or placebo groups. Feasibility was assessed in terms of recruitment, intervention compliance, and attrition. Outcomes included an incremental shuttle walk test, peak oxygen uptake, muscular strength, echocardiographic measures, N-terminal pro-brain natriuretic peptide, inflammatory markers, depression (Beck Depression Inventory), and health-related quality of life (Minnesota Living with Heart Failure Questionnaire and Medical Outcomes Study Short-Form).



Attrition was 30% but with 100% compliance to exercise and injections in patients who completed the study. Similar improvements in shuttle walk test (18% vs 19%), body mass (-1.3 kg vs -1.0 kg), and hand grip strength (2.1 kg vs 2.5 kg) from baseline were observed in both groups. The exercise with testosterone group showed improvements from baseline in peak oxygen uptake (P < .01), Beck Depression Inventory (P < .05), leg strength (P < .05), and several Medical Outcomes Study Short-Form quality of life domains (P < .05), which were generally not apparent in the exercise with placebo group. Echocardiographic measures, N-terminal pro-brain natriuretic peptide, and inflammatory markers were mostly unchanged.



This study shows for the first time that testosterone supplementation during a program of exercise rehabilitation is feasible and can positively impact on a range of key health outcomes in elderly male patients with CHF who have a low testosterone status.
Vedolizumab as induction and maintenance therapy for ulcerative colitis.

Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.



We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.



Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore >1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups.



Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).
Modified constraint-induced therapy combined with mental practice: thinking through better motor outcomes.

Modified constraint-induced therapy (mCIT) is an outpatient therapy encouraging repetitive, task-specific practice with the affected arm. mCIT has shown efficacy in all stages poststroke. Given its efficacy when combined with other therapy regimens, the current study examined the efficacy of mental practice when combined with mCIT versus mCIT only using randomized, controlled methods.



Ten patients with chronic stroke (7 males; mean age, 61.4+/-3.02 years; age range, 48 to 79 years; mean time since stroke, 28.5 months; range, 13 to 42 months) exhibiting stable, affected arm motor deficits were administered mCIT, consisting of: (1) structured therapy emphasizing affected arm use in functional activities 3 days/week for 10 weeks; and (2) less affected arm restraint 5 days/week for 5 hours. Both of these components were administered during a 10-week period. Subjects randomly assigned to the mCIT+mental practice experimental condition also received 30-minute mental practice sessions provided directly after therapy sessions. These mental practice sessions required daily cognitive rehearsal of the activities of daily living practiced during mCIT clinical sessions.



No pre-existing differences were found between groups on any demographic variable or movement scale. All subjects exhibited marked reductions in affected arm impairment and functional limitation. However, subjects in the mCIT+mental practice group exhibited significantly larger changes on both movement measures after intervention: Action Research Arm Test, +15.4-point change versus +8.4-point change for mCIT only subjects (P<0.001); Fugl-Meyer, +7.8-point change versus +4.1-point change for the mCIT only subjects (P=0.01). These changes were sustained 3 months after intervention.



mCIT remains a promising motor intervention. However, its efficacy appears to be enhanced by use of mental practice provided directly after mCIT clinical sessions.
Cost Effectiveness of Targeted High-dose Atorvastatin Therapy Following Genotype Testing in Patients with Acute Coronary Syndrome

Results from the PROVE IT trial suggest that patients with acute coronary syndrome (ACS) treated with atorvastatin 80 mg/day (A80) have significantly lower rates of cardiovascular events compared with patients treated with pravastatin 40 mg/day (P40). In a genetic post hoc substudy of the PROVE IT trial, the rate of event reduction was greater in carriers of the Trp719Arg variant in kinesin family member 6 protein (KIF6) than in noncarriers. We assessed the cost effectiveness of testing for the KIF6 variant followed by targeted statin therapy (KIF6 Testing) versus not testing patients (No Test) and treating them with P40 or A80 in the USA from a payer perspective. A Markov model was developed in which 2-year event rates from PROVE IT were extrapolated over a lifetime horizon. Costs and utilities were derived from published literature. All costs were in 2010 US dollars except the cost of A80, which was in 2012 US dollars because the generic formulation was available in 2012. Expected costs and quality-adjusted life-years (QALYs) were estimated for each strategy over a lifetime horizon. Lifetime costs were US$31,700; US$37,100 and US$41,300 for No Test P40, KIF6 Testing and No Test A80 strategies, respectively. The No Test A80 strategy was associated with more QALYs (9.71) than the KIF6 Testing (9.69) and No Test P40 (9.57) strategies. No Test A80 had an incremental cost-effectiveness ratio (ICER) of US$232,100 per QALY gained compared with KIF6 Testing. KIF6 Testing had an ICER of US$45,300 per QALY compared with No Test P40. Testing ACS patients for KIF6 carrier status may be a cost-effective strategy at commonly accepted thresholds. Treating all patients with A80 is more expensive than treating patients on the basis of KIF6 results, but the modest gain in QALYs is achieved at a cost/QALY that is generally considered unacceptable compared with the KIF6 Testing strategy. Compared with treating all patients with P40, the KIF6 Testing strategy had an ICER below US$50,000 per QALY. The conclusions from this study are sensitive to the price of generic A80 and the effect on adherence of knowing KIF6 carrier status. The results were based on a post hoc substudy of the PROVE IT trial, which was not designed to test the effectiveness of KIF6 testing.
Benefits and risks of raloxifene by vertebral fracture status.

Women without versus those with vertebral fracture may have different benefits and risks during raloxifene treatment. Our objective was to compare the effects of raloxifene to decrease risk for vertebral fracture and invasive breast cancer with its effect to increase risk for venous thromboembolism in postmenopausal women without or with baseline vertebral fracture.



The Multiple Outcomes of Raloxifene Evaluation trial included postmenopausal women with osteoporosis randomized to placebo, raloxifene 60 mg/day, or raloxifene 120 mg/day for 4 years. The protocol specified subgroups based on whether or not patients had a vertebral fracture at baseline. Absolute differences between placebo and raloxifene 60 mg/day (the approved dose) for endpoints in these groups were defined as the incidence in the raloxifene group minus the incidence in the placebo group.



Raloxifene decreased the incidence of vertebral fracture and invasive breast cancer while increasing the incidence of venous thromboembolism. All treatment by vertebral fracture status interaction p-values were greater than 0.13, indicating that the effect of raloxifene on these outcomes was not significantly different between patients without versus those with vertebral fractures. In women without baseline vertebral fracture, absolute risk differences between the raloxifene and placebo group included vertebral fracture -2.83%, invasive breast cancer -1.21%, and venous thromboembolism +0.28%. In women with baseline vertebral fracture, absolute risk differences between raloxifene and placebo group included vertebral fracture -8.21%, invasive breast cancer -0.75% and venous thromboembolism +0.91%. The analysis had limited power to test whether raloxifene had a significantly different effect on venous thromboembolism in women without versus those with a vertebral fracture.



In women without and in those with vertebral fractures at baseline, the effects of raloxifene to decrease vertebral fracture and invasive breast cancer were greater than its effects to increase venous thromboembolism.