nils-herrmann/clean_scirepeval huggingface dataset:
Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma.

Immunotherapy for the treatment of metastatic melanoma remains a major clinical challenge. The melanoma microenvironment may lead to local T cell tolerance in part through downregulation of costimulatory molecules, such as B7.1 (CD80). We report the results from the first clinical trial, to our knowledge, using a recombinant vaccinia virus expressing B7.1 (rV-B7.1) for monthly intralesional vaccination of accessible melanoma lesions. A standard 2-dose-escalation phase I clinical trial was conducted with 12 patients. The approach was well tolerated with only low-grade fever, myalgias, and fatigue reported and 2 patients experiencing vitiligo. An objective partial response was observed in 1 patient and disease stabilization in 2 patients, 1 of whom is alive without disease 59 months following vaccination. All patients demonstrated an increase in postvaccination antibody and T cell responses against vaccinia virus. Systemic immunity was tested in HLA-A*0201 patients who demonstrated an increased frequency of gp100 and T cells specific to melanoma antigen recognized by T cells 1 (MART-1), also known as Melan-A, by ELISPOT assay following local rV-B7.1 vaccination. Local immunity was evaluated by quantitative real-time RT-PCR, which suggested that tumor regression was associated with increased expression of CD8 and IFN-gamma. The local delivery of vaccinia virus expressing B7.1 was well tolerated and represents an innovative strategy for altering the local tumor microenvironment in patients with melanoma.
Alternative strategies for stroke care: cost-effectiveness and cost-utility analyses from a prospective randomized controlled trial.

Although stroke units reduce mortality and institutionalization, their comparative cost-effectiveness is unknown.



Healthcare, social services, and informal care costs were compared for 447 acute stroke patients randomly assigned to stroke unit, stroke team, or domiciliary stroke care. Prospective and retrospective methods were used to identify resource use over 12 months after stroke onset. Cost-effectiveness and cost-utility analyses were undertaken.



Mean healthcare and social care costs over 12 months were 11 450 pounds sterling for stroke unit, 9527 pounds sterling for stroke team, and 6840 pounds sterling for domiciliary care. More than half the costs were for the initial episode of care. Institutionalization was a large proportion of follow-up costs. Inclusion of informal care increased costs considerably. When informal care was excluded, the incremental cost-effectiveness ratio per percentage point in deaths or institutionalizations avoided in the first year was 496 pounds sterling for the stroke unit over domiciliary care; incremental cost per quality-adjusted life year quality-adjusted life year gained was 64 097 pounds sterling between these 2 groups. The stroke team was dominated by domiciliary care.



Cost perspectives, especially those related to long-term and informal care, are important when stroke services are evaluated. Improved health outcomes in the stroke unit come at a higher cost.
Loss to follow-up in an international, multicentre observational study.

The aim of this work was to assess loss to follow-up (LTFU) in EuroSIDA, an international multicentre observational cohort study.



LTFU was defined as no follow-up visit, CD4 cell count measurement or viral load measurement after 1 January 2006. Poisson regression was used to describe factors related to LTFU.



The incidence of LTFU in 12 304 patients was 3.72 per 100 person-years of follow-up [95% confidence interval (CI) 3.58-3.86; 2712 LTFU] and varied among countries from 0.67 to 13.35. After adjustment, older patients, those with higher CD4 cell counts, and those who had started combination antiretroviral therapy all had lower incidences of LTFU, while injecting drug users had a higher incidence of LTFU. Compared with patients from Southern Europe and Argentina, patients from Eastern Europe had over a twofold increased incidence of LTFU after adjustment (incidence rate ratio 2.16; 95% CI 1.84-2.53; P<0.0001). A total of 2743 patients had a period of >1 year with no CD4 cell count or viral load measured during the year; 743 (27.1%) subsequently returned to follow-up.



Some patients thought to be LTFU may have died, and efforts should be made to ascertain vital status wherever possible. A significant proportion of patients who have a year with no follow-up visit, CD4 cell count measurement or viral load measurement subsequently return to follow-up.
Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis.

The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown.



Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both P<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (r(2)=0.540, P<0.001), with a more modest increase observed for 18F-FDG (r(2)=0.218, P<0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (r(2)=0.174, P<0.001).



Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF.
Patterns of Stroke Between University Hospitals and Nonuniversity Hospitals in Mainland China: Prospective Multicenter Hospital-Based Registry Study.

In China, stroke has risen to the first commonest cause of death. Currently published data on stroke come mainly from university hospitals and less from community hospitals, especially lacking information on stroke focusing on the differences between university hospitals and nonuniversity hospitals. Therefore we aimed to investigate the patterns and differences of acute stroke between university hospitals and nonuniversity hospitals in China.



The survey was conducted in 281 hospitals in China: 62 in the west, 85 in the middle, and 134 in the eastern regions. The participating hospitals were sorted into university hospitals (n = 93) and nonuniversity hospitals (n = 118). We prospectively registered patients with acute stroke within 7 days of symptom onset between 1 April and 20 May 2006. The diagnosis of stroke was defined by World Health Organization criteria, and the pathologic types of stroke were determined by clinical and computed tomography/magnetic resonance imaging findings. The demographic data, pathologic types of stroke, and outcomes (death or disability) at discharge (or 30 days if not discharged) were collected. Disability was defined as modified Rankin Scale (mRs) score >2. Basic characteristics, pathologic types of stroke, and functional outcomes were compared between university hospitals and nonuniversity hospitals.



We enrolled 5273 patients (3135 males; mean age, 65 ± 12 years), of which ischemic stroke accounted for 70.8% (3733), intracranial hemorrhage for 25.7% (1357), and subarachnoid hemorrhage for 3.5% (183). Most of the patients (3555, or 67.4%) were from nonuniversity hospitals, and 1718 patients (32.6%) came from university hospitals. There were no significant differences between university hospitals and nonuniversity hospitals in terms of age, sex, pathologic types of stroke, and history of stroke (all P > 0.05), except the less stroke severity (mRS) on admission (3.1 ± 1.4 vs. 3.2 ± 1.3; P = 0.005) in patients from nonuniversity hospitals. After adjustment for age, sex, and mRS on admission, only patients with intracranial hemorrhage from nonuniversity hospitals had significantly lower proportions of disability (40.8% vs. 47.1%; P = 0.005) and death/disability (49.9% vs. 57.1%; P = 0.008) at discharge than those from university hospitals.



This survey comparing stroke patients treated in university and nonuniversity hospitals in China showed that both cohorts were largely comparable including most demographic features, such as age and gender, history of stroke, and stroke subtypes. It may be concluded that patient cohorts treated on stroke units in university and nonuniversity hospitals are similar and stroke units in both types of institutions are also comparable in terms of workload and most patient outcomes.
Relationship between mental health and spiritual wellbeing among hemodialysis patients: a correlation study.

The stress of living with a terminal disease has a negative impact on the mental health of hemodialysis (HD) patients. Spirituality is a potential coping mechanism for stressful experiences. Studies on the relationship between spirituality and mental health among HD patients are scarce. The purpose of this study was to evaluate the relationship between mental health and spiritual well-being among HD patients.



Cross-sectional observational study on hemodialysis patients at a single center in Brazil, between January and December 2011.



Mental health was assessed using the General Health Questionnaire and spiritual wellbeing was assessed using the Spiritual Wellbeing Scale; 150 HD patients participated in the study.



A significant correlation was found between mental health and spiritual wellbeing (P = 0.001). Spiritual wellbeing was the strongest predictor of mental health, psychological distress, sleep disturbance and psychosomatic complaints.



Poor mental health was associated with lower spiritual wellbeing. This has important implications for delivery of palliative care to HD patients.
The Improvement of Sleep by Oral Intake of GABA and Apocynum venetum Leaf Extract.

The effects of two food materials, γ-aminobutyric acid (GABA) produced by natural fermentation and Apocynum venetum leaf extract (AVLE), on the improvement of sleep were investigated in humans. The electroencephalogram (EEG) test revealed that oral administration of GABA (100 mg) and AVLE (50 mg) had beneficial effects on sleep. GABA shortened sleep latency by 5.3 min and AVLE increased non-rapid eye movement (REM) sleep time by 7.6%. Simultaneous intake of GABA and AVLE shortened sleep latency by 4.3 min and increased non-REM sleep time by 5.1%. The result of questionnaires showed that GABA and AVLE enabled subjects to realize the effects on sleep. These results mean that GABA can help people to fall asleep quickly, AVLE induces deep sleep, and they function complementarily with simultaneous intake. Since both GABA and AVLE are materials of foods and have been ingested for a long time, they can be regarded as safe and appropriate for daily intake in order to improve the quality of sleep.
Clinical and biochemical effects of spironolactone administered once daily in primary hypertension. Multicenter Sweden study.

In a prospective, double-blind, intraindividual, cross-over, placebo-controlled multicenter study, clinical and biochemical effects of once daily postprandial dose regimens of 50, 100, and 200 mg spironolactone were investigated in 45 outpatients with primary hypertension, WHO (World Health Organization) Stage I-II. Each of the three active therapy periods, which were randomly allocated to patients, were of 2 months' duration, with intervening placebo periods, Clinical and biochemical parameters, including furosemide-stimulated plasma renin activity (PRA), were recorded at regular intervals. All three spironolactone doses resulted in statistically significant blood pressure (BP) reductions independent of initial pretreatment levels and yielded satisfactory BP control in more than half of the patients. The 200 mg daily dose of spironolactone was found to be more effective than 50 but not 100 mg. When, correlating blood pressure response (delta MAP) to PRA, the profiling for positive spironolactone responders was characterized by high age and low PRA, irrespective of sex. Spironolactone therapy resulted in decreased serum sodium and magnesium values; potassium, creatinine, urate, and triglyceride levels were increased. However, all treatment values were within normal ranges. Side effects were infrequent and mainly of endocrine nature.
Randomized study comparing vitamin D3 and 1α-Hydroxyvitamin D3 in combination with pegylated interferon/ribavirin therapy for chronic hepatitis C.

An intention-to-treat prospective randomized study was carried out to compare the potentiation of antiviral efficacies between cholecalciferol, non-activated vitamin D3 supplement, and alfacalcidol, activated 1α-Hydroxyvitamin D3 [1α (OH)-vitamin D3].



Chronic hepatitis patients with genotype 1b hepatitis C virus (HCV) infection showing serum HCV-RNA levels greater than 5 Log IU/mL received oral administration of cholecalciferol (2000 IU/day) or alfacalcidol (0.5 μg/day) for 4 weeks, and then they were given pegylated interferon (Peg-IFN)-α2a plus ribavirin therapy in combination with either vitamin D3 for 48 or 72 weeks according to the response-guided manner.



A total of 36 patients were evaluated. Serum 25-hydroxyvitamin D3 [25(OH)-D3] levels were increased only in patients in the cholecalciferol group during the lead-in vitamin D administration, and the levels at 4 weeks were higher in these patients than in those in the alfacalcidol group (P < 0.001), while serum 1α,25-dihydroxyvitamin D3 [1α,25(OH)2 -D3] levels were not different between both groups. Rapid virological response was obtained in six (33%) patients in the cholecalciferol group; the ratio was higher than that in the alfacalcidol group (one patient; 6%, P < 0.05). Serum HCV-RNA level decline at 4 weeks of combined Peg-IFN-α2a plus ribavirin therapy compared with the baseline levels were greater in the cholecalciferol group (4.6 Log IU/mL) than in the alfacalcidol group (3.5 Log IU/mL) (P < 0.05), when four patients showing null response to the therapy was excluded. However, both complete early virological response and sustained viral response rates were not different between both groups.



Cholecalciferol produced superior potentiation of the antiviral activity than alfacalcidol only during the initial periods of combined Peg-IFN-α2a plus ribavirin therapy through upregulation of serum 25(OH)-D3 levels.
Neonatal abstinence syndrome in European and North American neonates: differences in clinical characteristics derived from a prospective randomized trial.

Due to the steady increase of substance-dependent pregnant women the neonatal abstinence syndrome has become an increasingly important issue in neonatology. The present study investigates site-specific differences of detailed symptoms and treatment of neonatal abstinence syndrome within the context of an international multicenter clinical trial.



Site specific neonatal data analyses from a prospective randomized, double-blind, double-dummy clinical trial (MOTHER study) was performed. A standardized NAS rating and treatment protocol was applied, while non-pharmacological care of NAS symptoms differed across the sites.



Urban US neonates exhibited most neurological symptoms (p<0.001) while in Europe autonomous, respiratory and gastrointestinal symptoms were found significantly more often compared to urban and/or rural US (p<0.05). Methadone produced significantly greater scores than buprenorphine in neurological, behavioural and respiratory symptoms regardless of the sites (ps<0.05). NAS treatment rates in all site clusters were similar for methadone-exposed neonates, while in Europe significantly more buprenorphine-exposed neonates were treated (p=0.001) than in US site clusters. Urban US neonates had significantly higher NAS scores (p<0.01) compared to rural US and European neonates, and needed significantly higher morphine doses (p<0.05) with longer treatment duration. Birth weight, length and head circumference did not differ significantly among the site clusters, but APGAR scores were significantly higher in European (p<0.01) neonates.



In addition to intrauterine medication exposure other aspects such as different addiction severity of the mothers, different treatment modalities including rooming-in as well as the frequency of NAS ratings may be influencing the course of NAS.
Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.



This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.



There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.



Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.


Not applicable when study undertaken.
Setting, patient, and doctor effects on drug response in neurotic patients

Diazepam was compared to placebo and phenobarbital sodium in a double-blind study with 472 anxious psychoneurotic patients. Patients were treated in 3 settings — medical clinic, general practice, and private psychiatric practice. The treatment setting was found to be at least as important as the medication in producing a treatment response. Drug effects were pronounced. Compared to phenobarbital patients, diazepam patients more often completed the study, followed prescribed dosage, and reported fewer side reactions. Diazepam patients did not differ from placebo patients in dosage intake or side effects, only in higher completion rate. Population effects indicated clinic patients to drop out and deviate from dosage more than private patients. General practice patients reported the most and private psychiatric patients reported the least side effects. These differences are explained in terms of patient background and behavioral patterns and of a medical as opposed to a psychiatric orientation toward treatment.
Telmisartan on top of antihypertensive treatment does not prevent progression of cerebral white matter lesions in the prevention regimen for effectively avoiding second strokes (PRoFESS) MRI substudy.

High blood pressure is one of the main risk factors for cerebral white matter lesions (WMLs). There is limited evidence from one randomized trial that blood pressure-lowering is able to slow WML progression. We investigated whether telmisartan prevents WML progression in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.



This predefined substudy comprised 771 patients (mean age, 65 years) with recent ischemic stroke of noncardioembolic origin who received telmisartan or placebo during a mean follow-up of 27.9 (SD, 7.6) months and had 2 evaluable MRI examinations after index stroke and at study closeout. All MRI scans were centrally adjudicated for progression of periventricular and subcortical WML by 2 neuroradiologists blinded to treatment allocation.



Mean blood pressure was 3.0/1.3 mm Hg lower with telmisartan compared with placebo at follow-up MRI. There was no statistically significant difference in progression of the mean periventricular WML score (least squares mean difference, 0.14; 95% CI, -0.12 to 0.39; P=0.29) and mean subcortical WML diameter (least squares mean difference, -0.35 mm; 95% CI, -1.00 to 0.31 mm; P=0.30) during follow-up between patients on telmisartan and placebo.



Treatment with telmisartan on top of existing antihypertensive medication did not result in significant blood pressure-lowering and did not prevent the progression of WML in patients with a recent ischemic stroke in this patient cohort. Our analysis is limited by the relatively short follow-up period.
Seemingly minor changes to a questionnaire can make a big difference to mean scores: a cautionary tale

It is not unusual for researchers to make apparently minor modifications to existing instruments without checking if this alters psychometric properties. Equivalent items on child mental health from two different versions of the Rutter parent questionnaire were compared: items from the standard version and from a modified version. The parents of 400 children aged 5–7 years were randomised into two groups: each group completed one version of the Rutter as well as an independent measure of psychopathology (the Strengths and Difficulties Questionnaire; SDQ). The mean psychopathology scores of the two groups were comparable according to the SDQ but differed markedly between the two Rutter versions, principally because of changes in the response categories. Nevertheless, the validity of the two versions of the Rutter was similar as judged from Rutter-SDQ correlations. Seemingly minor changes in the wording of a measure can have a major impact on mean scores, thereby making it harder to compare or combine the results of studies using the original and the modified measure.