nils-herrmann/clean_scirepeval huggingface dataset:
Association of physical activity with vascular endothelial function and intima-media thickness.

Impairment of vascular endothelial function and increased intima-media thickness (IMT) are important early steps in atherogenesis. Longitudinal data on the effect of physical activity on endothelial function and IMT in healthy adolescents are lacking. We investigated prospectively the association of leisure-time physical activity with endothelial function (brachial artery flow-mediated dilatation; FMD) and aortic IMT in adolescents.



FMD and IMT were measured with ultrasonography at 13 (n=553), 15 (n=531), and 17 (n=494) years of age in adolescents participating in a longitudinal atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children). Mean aortic IMT, maximum FMD, and total FMD response (area under the dilatation curve 40 to 180 seconds after hyperemia) were calculated. Leisure-time physical activity was assessed with a questionnaire, and metabolic equivalent (MET) hours per week of leisure-time physical activity were calculated by multiplying weekly mean exercise intensity, duration, and frequency. Leisure-time physical activity was directly associated with endothelial function (P for maximum FMD=0.0021, P for total FMD response=0.0036) and inversely with IMT (P=0.011) after adjustment for age, sex, body mass index, high-density lipoprotein/total cholesterol, systolic blood pressure, and C-reactive protein and regarding FMD brachial artery diameter. Sedentary adolescents who increased their leisure-time physical activity from <5 to >5 (IMT) or >30 (maximum FMD) MET h/wk between 13 and 17 years of age had an increased maximum FMD (P=0.031) and decreased progression of IMT (P=0.047) compared with adolescents who remained sedentary. IMT progression was attenuated in persistently active adolescents compared with those who became sedentary (P=0.0072).



Physical activity is favorably associated with endothelial function and IMT in adolescents. Importantly, a moderate increase in physical activity is related to decreased progression of IMT. A physically active lifestyle seems to prevent the development of subclinical atherosclerotic vascular changes in healthy adolescents.
A double blind comparison of zuclopenthixol acetate with haloperidol in the management of acutely disturbed schizophrenics.

The aim of this study was to evaluate the efficacy and side effects of zuclopenthixol acetate compared with haloperidol in the management of the acutely disturbed schizophrenic patient. Suitable subjects diagnosed as having schizophreniform disorder or acute exacerbation of schizophrenia admitted to the psychiatric wards Hospital Kuala Lumpur were randomised to receive either zuclopenthixol acetate or haloperidol. They were rated blind for three consecutive days using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) and UKU Side Effects Scale. Apart from repeat injections of the same medication, no other anti-psychotic was given for the duration of the study. 50 subjects entered the study of which 44 completed. 23 were given zuclopenthixol acetate and 21 haloperidol. Both groups significantly reduced BPRS and CGI scores on all 3 days compared to the initial rating (p < 0.001). There was however no difference between the zuclopenthixol acetate and haloperidol group scores on all days (p > 0.05). More subjects on haloperidol than zuclopenthixol required more than 1 injection during the study. Both groups had minimal side effects. Zuclopenthixol acetate was effective in the management of the acutely disturbed schizophrenic.
Medication errors in psychiatric patients boarded in the emergency department.

Patients boarded in the emergency department (ED) with psychiatric complaints may be at risk for medication errors. However, no studies exist to characterize the types of errors and risk factors for errors in these patients.



To characterize medication errors in psychiatric patients boarded in ED, and to identify risk factors associated with these errors.



A prospective observational study conducted in a community ED included all patients seen in the ED for primary psychiatric complaints and remained in the ED pending transfer to a psychiatric facility. An investigator recorded all medication errors requiring an intervention by an emergency pharmacist.



A total of 288 medication errors in 100 patients were observed. Overall, 65 patients had one or more medication errors. The majority of errors (n = 256, 89%) were due to errors of omission. The final severity classification of the medication errors was: Insignificant (n = 77), significant (n = 152), and serious (n = 3). In the multivariate analysis (R-squared 19.6%), increasing number of home medications (OR 1.17, 95% CI 1.01 to 1.36; p = 0.035), and increasing number of comorbidities (OR 1.89, 95% CI 1.10 to 3.27; p = 0.022) were associated with the occurrence of medication errors.



Psychiatric patients boarded in the ED commonly have medication errors that require intervention.
Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF121 (AdVEGF121) versus maximum medical treatment

The demonstration that angiogenic growth factors can stimulate new blood vessel growth and restore perfusion in animal models of myocardial ischemia has led to the development of strategies designed for the local production of angiogenic growth factors in patients who are not candidates for conventional revascularization. The results of recent clinical trials of proangiogenesis gene therapy have been disappointing; however, significant limitations in experimental design, in particular in gene transfer strategies, preclude drawing definitive conclusions. In the REVASC study cardiac gene transfer was optimized by direct intramyocardial delivery of a replication-deficient adenovirus-containing vascular endothelial growth factor (AdVEGF121, 4 × 1010 particle units (p.u.)). Sixty-seven patients with severe angina due to coronary artery disease and no conventional options for revascularization were randomized to AdVEGF121 gene transfer via mini-thoracotomy or continuation of maximal medical treatment. Exercise time to 1 mm ST-segment depression, the predefined primary end-point analysis, was significantly increased in the AdVEGF121 group compared to control at 26 weeks (P=0.026), but not at 12 weeks. As well, total exercise duration and time to moderate angina at weeks 12 and 26, and in angina symptoms as measured by the Canadian Cardiovascular Society Angina Class and Seattle Angina Questionnaire were all improved by VEGF gene transfer (all P-values at 12 and 26 weeks ⩽0.001). However, if anything the results of nuclear perfusion imaging favored the control group, although the AdVEGF121 group achieved higher workloads. Overall there was no significant difference in adverse events between the two groups, despite the fact that procedure-related events were seen only in the thoracotomy group. Therefore, administration of AdVEGF121 by direct intramyocardial injections resulted in objective improvement in exercise-induced ischemia in patients with refractory ischemic heart disease.
A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses.

G207, a mutant herpes simplex virus (HSV) type 1, is safe when inoculated into recurrent malignant glioma. We conducted a phase 1 trial of G207 to demonstrate the safety of stereotactic intratumoral administration when given 24 hours prior to a single 5 Gy radiation dose in patients with recurrent malignant glioma. Nine patients with progressive, recurrent malignant glioma despite standard therapy were included. Patients received one dose of G207 stereotactically inoculated into the multiple sites of the enhancing tumor margin and were then treated focally with 5 Gy radiation. Treatment was well tolerated, and no patient developed HSV encephalitis. The median interval between initial diagnosis and G207 inoculation was 18 months (mean: 23 months; range: 11-51 months). Six of the nine patients had stable disease or partial response for at least one time point. Three instances of marked radiographic response to treatment occurred. The median survival time from G207 inoculation until death was 7.5 months (95% confidence interval: 3.0-12.7). In conclusion, this study showed the safety and the potential for clinical response of single-dose oncolytic HSV therapy augmented with radiation in the treatment of malignant glioma patients. Additional studies with oncolytic HSV such as G207 in the treatment of human glioma are recommended.
Effects of Cognitive Behavioral Therapy on Insomnia of Maintenance Hemodialysis Patients

The objective of the study was to evaluate the effects of cognitive behavioral therapy [sleep-related behavior modification and progressive muscle relaxation on insomnia of maintenance hemodialysis (MHD) patients] on improving insomnia of MHD patients. 103 MHD patients complicated with insomnia were randomly assigned to treatment (n = 52) and control (n = 51) groups. The control group was treated with conventional hemodialysis, and the treatment group was additionally treated with cognitive behavioral therapy for 3 months (sleep-related behavior modification and progressive muscle relaxation). All cases were assessed by Symptom Checklist 90 (SCL-90) and Pittsburgh Sleep Quality Index (PSQI) before and 2, 4, 6, 8, 10, and 12 weeks after treatment. Fifty-one patients in the treatment group and 47 patients in the control group completed the experiments. After treatment, the total mean scores were (1.94 ± 0.50/2.29 ± 0.31); scores of somatization, depression, anxiety, hostility, and additional items were (1.87 ± 0.58/2.56 ± 0.26), (2.25 ± 0.80/2.79 ± 0.50), (1.79 ± 0.26/2.37 ± 0.34), (1.71 ± 0.46/2.25 ± 0.43), and (1.91 ± 0.67/2.26 ± 0.59) in SCL-90, respectively. The total scores for PSQI were (12.63 ± 2.27/16.40 ± 2.16); scores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, hypnotics, and daytime dysfunction which were (1.98 ± 0.76/2.57 ± 0.58), (1.75 ± 0.59/2.60 ± 0.50), (2.10 ± 0.50/2.62 ± 0.53), (2.06 ± 0.47/2.57 ± 0.54), (2.04 ± 0.69/2.45 ± 0.72), (1.02 ± 0.79/1.51 ± 0.98), and (1.69 ± 0.55/2.09 ± 0.58), respectively, were significantly lower in the treatment group compared with the control group. However, there were no significant differences in the scores of factors of obsessive–compulsive (2.26 ± 0.62/2.32 ± 0.38), interpersonal sensitivity (2.23 ± 0.64/2.43 ± 0.47), phobic anxiety (1.98 ± 0.62/2.01 ± 0.67), paranoid ideation (1.55 ± 0.43/1.69 ± 0.39), and psychoticism (1.57 ± 0.46/1.66 ± 0.49). The conclusion is that sleep-related behavior modification in combination with progressive muscle relaxation effectively improved the mental state and sleep quality of MHD patients with insomnia.
Changes in volume of giant intracranial aneurysms treated by surgical strategies other than direct clipping

Giant intracranial aneurysms (GIA) are often not eligible for direct clip occlusion. Surgical alternatives include partial clip occlusion or the placement of a cerebrovascular bypass or the combination of both. These alternative indirect strategies are expected to lead to a decrease in GIA volume over time rather than instantaneously. To examine whether this is the case, we analyzed follow-up imaging results 1 year after surgery. We retrospectively screened the prospective GIA Registry’s imaging database for anterior circulation GIA treated by surgical strategies other than direct clipping. We measured pre- and 1-year post-treatment GIA volume, lateral ventricle volume (LVV), and mid-line shift (MLS) in 19 cases. After a mean follow-up of 466 days (standard deviation ±171) GIA volumes decreased from 9.6 cm3 (interquartile range (IQR) 6.1–14.1) to 4.3 cm3 (IQR 2.9–5.7; p < 0.01). Ipsilateral LVV increased from 8.6 cm3 (IQR 6.4–24.9) to 16.0 cm3 (IQR 9.1–27.2; p < 0.01) while contralateral LVV increased from 10.3 cm3 (IQR 7.3–20.1) to 11.7 cm3 (IQR 8.2–19.4; p = 0.02). MLS changed from 0.1 mm (IQR −1.9 to 2.0) to −0.9 mm (IQR −1.8 to 0.4; p = 0.03). The decrease in GIA volume correlated with the increase in ipsilateral LVV (rs = 0.60; p = 0.01) but not with the changes in MLS (rs = 0.41; p = 0.08). In our patient cohort, surgical strategies other that direct clipping for the treatment of anterior circulation GIA lead to a significant decrease in GIA volume over time. The resulting decrease in mass effect was more sensitively monitored by the measurement of changes in ipsilateral LVV than changes in MLS. http://www.clinicaltrials.gov . Unique identifier: NCT02066493.
Assessment of medication adherence in patients with schizophrenia: the Achilles heel of adherence research.

Measuring medication adherence in patients with schizophrenia is difficult and lacks a gold standard. Consequently, a great number of different methods and instruments have been proposed. Although it has been assumed that they all measure medication adherence, this study demonstrates that instruments differ significantly. Using data from an international multisite study (N = 329), we found that 3 questionnaires, designed to measure medication adherence and typical for instruments used in studies in patients with schizophrenia, do not agree in labeling patients as nonadherent. Further, they seem not to measure the same trait, are related to different established risk factors of nonadherence, and are only weakly related to these established risk factors of nonadherence. If these results are representative of the validity of other measures used in adherence research, this may have serious consequences for the interpretation of, and explanations for discrepancies found in the literature. Researchers should be aware of this problem and continue to combine objective and subjective methods in the hope of increasing the reliability and validity of measures of adherence.
Mesenchymal stem cells for treating autoimmune dacryoadenitis

Autoimmune dacryoadenitis, such as Sjögren syndrome, comprises multifactorial and complex diseases. Inflammation of the lacrimal gland plays a key role in the pathogenesis of diseases. Unfortunately, current treatment strategies, including artificial tears, anti-inflammatory drugs, punctual occlusion, and immunosuppressive drugs, are only palliative, and long-term administration of these strategies is associated with adverse effects that limit their utility. Hence, an effective and safe treatment for autoimmune dacryoadenitis is urgently needed. Mesenchymal stem cells (MSCs) have emerged as a promising tool for treating autoimmune dacryoadenitis, owing to their immunosuppressive properties, tissue repair functions, and powerful differentiation capabilities. A large number of studies have focused on the effect of MSCs on autoimmune diseases, such as autoimmune uveitis, inflammatory bowel disease, and collagen-induced arthritis, but few studies have, to date, unequivocally established the efficacy of MSCs for treating autoimmune dacryoadenitis. In this review, we discuss recent advances in MSC treatment for autoimmune dacryoadenitis.
Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus genotype 1 infection with compensated cirrhosis.

Effective and well-tolerated, interferon-free regimens are needed for treatment of patients with chronic hepatitis C virus (HCV) infection and cirrhosis.



All-oral therapy with daclatasvir (nonstructural protein 5A [NS5A] inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir (nonnucleoside NS5B inhibitor), with or without ribavirin, was evaluated in patients with HCV genotype 1 infection and compensated cirrhosis.



The UNITY-2 study was conducted between December 2013 and October 2014 at 49 outpatient sites in the United States, Canada, France, and Australia. Patients were treated for 12 weeks, with 24 weeks of follow-up after completion of treatment. Adult patients with cirrhosis were enrolled in 2 cohorts: HCV treatment-naive or HCV treatment-experienced. Statistical analyses were based on historical controls; there were no internal controls.



All patients received twice-daily treatment with the fixed-dose combination of daclatasvir (30 mg), asunaprevir (200 mg), and beclabuvir (75 mg). In addition, patients within each cohort were stratified according to HCV genotype 1 subtype (1a or 1b) and randomly assigned (1:1) to receive double-blinded weight-based ribavirin (1000-1200 mg/d) or matching placebo.



Sustained virologic response at posttreatment week 12 (SVR12).



One hundred twelve patients in the treatment-naive group and 90 patients in the treatment-experienced group were treated and included in the analysis. Enrolled patients were 88% white with a median age of 58 years (treatment-naive group) or 60 years (treatment-experienced group); 74% had genotype 1a infection. SVR12 rates were 98% (97.5% CI, 88.9%-100%) for patients in the treatment-naive group and 93% (97.5% CI, 85.0%-100.0%) for those in the treatment-experienced group when ribavirin was included in the regimen. With the fixed-dose combination alone, response rates were 93% (97.5% CI, 85.4%-100.0%) for patients in the treatment-naive group and 87% (97.5% CI, 75.3%-98.0%) for those in the treatment-experienced group. Three serious adverse events were considered to be treatment related and there were 4 adverse event-related discontinuations. Treatment-emergent grade 3 or 4 alanine aminotransferase elevations were observed in 4 patients, of which 1 had concomitant total bilirubin elevation.



In this open-label uncontrolled study, patients with chronic HCV genotype 1 infection and cirrhosis who received a 12-week oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin, achieved high rates of SVR12.
Point-of-care lactate testing predicts mortality of severe sepsis in a predominantly HIV type 1-infected patient population in Uganda.

Prediction of mortality may improve management and outcomes of patients with sepsis in resource-limited settings. Therefore, we evaluated the ability of a hand-held portable whole-blood lactate (PWBL) analyzer to predict mortality of patients who are admitted to the hospital with severe sepsis.



A prospective observational study enrolled 253 patients at a national referral hospital in Uganda. Inclusion criteria required (1) >or=2 systemic inflammatory response syndrome criteria or thermodysregulation, (2) hypotension, and (3) suspected infection. A subset of 72 patients had PWBL and standard laboratory serum lactate measured. The primary measured outcome was in-hospital mortality.



Fifty-nine (81.9%) of 72 evaluated patients were infected with human immunodeficiency virus type 1. The in-hospital mortality rate was 25.7% (18 of 70), and the in- and outpatient mortality at 30 days was 41.6% (30 of 72). PWBL was positively associated with in-hospital but not outpatient mortality (P=.001). The receiver operating characteristic area under the curve for PWBL was 0.81 (P=.081). The optimal PWBL concentration for predicting in-hospital mortality (sensitivity, 88.3%; specificity, 71.2%) was >or=4.0 mmol/L. Patients with a PWBL concentration >or=4.0 mmol/L died while in the hospital substantially more often (50.0%) than did those with a PWBL concentration <4.0 mmol/L (7.5%) (odds ratio, 12.3; 95% confidence interval, 3.5-48.9; [P=.001). Standard laboratory serum lactate results were inconsistent and less predictive of mortality than were those of PWBL in a multiple logistic regression model.



A PWBL concentration >or=4.0 mmol/L predicts with 81% accuracy a 7-fold higher mortality of patients with sepsis than does a PWBL concentration <4.0 mmol/L. PWBL testing would be useful in places where clinical decisions are limited by lack of laboratory infrastructure and poor reliability.
Characteristics of falls producing hip fracture in patients on oral anticoagulants.

To analyze the demographic and clinical characteristics of patients on chronic anticoagulant therapy (CAT) admitted because of a hip fracture secondary to a fall, and to compare with patients not receiving CAT.



A prospective, observational study realized in six hospitals in the Barcelona area. Demographic and clinical characteristics of patients were collected. The index fall characteristics - cause, height, location, and time of occurrence - were evaluated.



Of the 1225 patients included, 99 (8%) patients were on CAT. When we compare with the rest logistic regression analysis showed that patients receiving CAT were more likely to be male (odds ratio 3.7), not institutionalized (odds ratio 3.5), to take more number of drugs (odds ratio 1.3), to have dementia (odds ratio 2.1) and stroke (odds ratio 1.7). Results revealed a higher prevalence of combined factors as the cause of the index fall in the group of patients on anticoagulants.



Characteristics of falls were very similar when comparing the group of patients receiving CAT with those who did not. A prior history of falls should lead physicians to take actions for preventing falls causing hip fracture, in all patients and particularly in these on CAT.
UGT1A1 genotype-guided phase I study of irinotecan, oxaliplatin, and capecitabine

We performed a UGT1A1 genotype-guided study to determine the maximum tolerated dose (MTD) and evaluate the toxicities and pharmacokinetics of the combination of capecitabine (CAP), oxaliplatin (OX), and irinotecan (IRIN).  Patients were screened for UGT1A1 *28 genotype prior to treatment. The starting dose (mg/m2) was IRIN (150), OX (85) and CAP (400), days 2–15. Doses were escalated or de-escalated within each genotype group (*28/*28, *1/*28 and *1/*1). IRIN pharmacokinetics was performed at the MTD.  50 patients were evaluable for toxicity [11 (*28/*28); 18 (*1/*28); 21 (*1/*1)]. UGT1A1 *28/*28 patients experienced hematologic dose limiting toxicity (DLT), requiring dose-de-escalation. The UGT1A1 *28/*28 recommended phase 2 dose (RP2D) was IRIN (75), OX (85), and CAP (400). In contrast, both UGT1A1 *1/*28 and *1/*1 tolerated higher doses of IRIN and non-hematologic toxicity was dose limiting for UGT1A1 *1/*1. The RP2D was IRIN (150), OX (85), and CAP (400) for UGT1A1*1/*28 and IRIN (150), OX (100), and CAP (1600) for UGT1A1 *1/*1. UGT1A1 *1/*28 and *1/*1 patients treated with IRIN (150) had similar AUCs for the active irinotecan metabolite, SN38 (366 +/− 278 and 350 +/− 159 ng/ml*hr, respectively). UGT1A1 *28/*28 patients (n = 3) treated with a lower IRIN dose (100) had non-significantly higher mean SN38 exposures (604 +/− 289 ng/ml*hr, p = 0.14). Antitumor activity was observed in all genotype groups.  UGT1A1 genotype affects the dose and pharmacokinetics of the CAPIRINOX regimen and UGT1A1 genotype-guided dosing of CAPIRINOX is ongoing in a phase II study of small bowel cancer (NCT00433550).