nils-herrmann/clean_scirepeval huggingface dataset:
Pharmacokinetics of levodopa/carbidopa delivered from gastric-retentive extended-release formulations in patients with Parkinson's disease.

The investigators conducted a single-dose pharmacokinetic (PK) study of levodopa/carbidopa delivered from novel gastric-retentive extended-release (ER) tablets versus a comparator ER tablet (M-ER) in patients with Parkinson's disease. Two levodopa/carbidopa (200 mg/50 mg) gastric-retentive ER formulations (4 hours and 6 hours) and M-ER were administered orally with food. Blood samples were collected for up to 24 hours post dose to determine levodopa and carbidopa concentrations. Tolerability was assessed by monitoring adverse events and measuring vital signs. PK modeling was conducted to estimate the release characteristics for future gastric-retentive ER formulations to achieve a less fluctuating plasma concentration profiles. Compared with M-ER, both gastric-retentive ER formulations exhibited a longer time to reach a lower maximal plasma concentration for levodopa and carbidopa. The 4-hour formulation demonstrated a similar area under the concentration-time curve compared with M-ER, whereas the 6-hour formulation demonstrated a lower area under the concentration-time curve. All formulations were well tolerated. Modeling suggests that a gastric-retentive ER formulation with a longer release duration administered twice daily may achieve a less fluctuating levodopa concentration profile than M-ER administered 3 times daily. This study demonstrates that gastric-retentive ER dosage forms may reduce dose frequency while minimizing the plasma peak-to-trough fluctuation and consequently reduce motor fluctuation in patients with Parkinson's disease.
Does abciximab provide long-term benefit for patients with acute myocardial infarction treated with stents?

The number of revascularization procedures performed has been shown to be reduced when stents are used in primary per cutaneous coronary intervention (PCI) for patients with acute myo cardial infarction (AMI). The Abciximab Before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-term Follow-up (ADMIRAL) trial has already shown that adjunctive glycoprotein IIb/IIIa inhibition with abciximab can effectively lower mortality, the incidence of myocardial infarction (MI) and the number of revascularization procedures at 30 days compared with placebo; however, the long-term effects of abciximab are not known.
Prompt initiation of maintenance treatment following a COPD exacerbation: outcomes in a large insured population

The aim of this study was to extend previous findings and determine the value of prompt initiation of maintenance treatment (MT) following COPD exacerbations requiring hospitalization or an emergency department (ED) visit.



Administrative claims data (collected between January 1, 2009 and June 30, 2012) from an employer-sponsored commercially insured population were retrospectively used to identify patients with a COPD exacerbation resulting in hospitalization or an ED visit. Patients initiating approved MT for COPD within 30 days of discharge/diagnosis (prompt) were compared with those initiating MT within 31-180 days (delayed). COPD-related total, medical, and prescription drug costs during a 1-year follow-up period were evaluated using semilog ordinary least square regressions, controlling for baseline characteristics plus COPD-related costs from the previous year. The odds and number of subsequent COPD-related exacerbations during the follow-up were compared between the prompt and delayed cohorts using logistic regression and zero-inflated negative binomial models, respectively.



A total of 6,521 patients with a COPD-related hospitalization or an ED visit were included, of whom 4,555 received prompt MT and 1,966 received delayed MT. Adjusted COPD-related total and medical costs were significantly lower for the prompt MT than the delayed MT cohorts (US$3,931 vs US$4,857 and US$2,327 vs US$3,087, respectively; both P<0.010), as were COPD-related prescription costs (US$1,526 vs US$1,683, P<0.010) during the 1-year follow-up period. Patients receiving delayed MT were 68% more likely to have a subsequent exacerbation requiring hospitalization and 80% more likely to have an exacerbation requiring an ED visit.



Prompt initiation of MT following a COPD-related hospitalization or an ED visit was associated with a significant reduction in COPD-related costs and odds of exacerbation in the following year compared with delayed initiation.
Competitive Memory Training for treating depression and rumination in depressed older adults: a randomized controlled trial.

Although rumination is an important mediator of depressive symptoms, there is insufficient proof that an intervention that specifically targets rumination ameliorates the clinical condition of, depressed patients. This study investigates whether a time-limited cognitive behavioral intervention (Competitive Memory Training, or COMET for depressive rumination) is an effective treatment for depression and rumination. This intervention was tested in older adult depressed outpatients. A total of 93 patients (aged ≥ 65 years with major depression and suffering from rumination) were treated in small groups according to the COMET protocol in addition to their regular treatment. Patients were randomized to two treatment conditions: 7 weeks of COMET + treatment-as-usual (TAU) versus TAU only. COMET + TAU showed a significant improvement in depression and rumination compared with TAU alone. This study shows that the transdiagnostic COMET protocol for depressive rumination might also be successful in treating depression and rumination in older adults.
Prostate cancer in renal transplant recipients

As patients with end-stage renal disease are receiving renal allografts at older ages, the number of male renal transplant recipients (RTRs) being diagnosed with prostate cancer (CaP) is increasing. Historically, the literature regarding the management of CaP in RTR's is limited to case reports and small case series. To date, there are no standardized guidelines for screening or management of CaP in these complex patients. To better understand the unique characteristics of CaP in the renal transplant population, we performed a literature review of PubMed, without date limitations, using a combination of search terms including prostate cancer, end stage renal disease, renal transplantation, prostate cancer screening, prostate specific antigen kinetics, immunosuppression, prostatectomy, and radiation therapy. Of special note, teams facilitating the care of these complex patients must carefully and meticulously consider the altered anatomy for surgical and radiotherapeutic planning. Active surveillance, though gaining popularity in the general low risk prostate cancer population, needs further study in this group, as does the management of advance disease. This review provides a comprehensive and contemporary understanding of the incidence, screening measures, risk stratification, and treatment options for CaP in RTRs.
Catecholamine production in patients with gastroenteropancreatic neuroendocrine tumors.

Amine precursor uptake and decarboxylation is a classical feature of gastroenteropancreatic (GEP) neuroendocrine tumors (NET). Production of catecholamines was studied in GEP NET and non-NET patients.



A cross-sectional study was undertaken.



We studied catecholamine and metabolite secretion in 115 consecutive GEP NET patients and in 20 patients with non-NET. After specific extraction, vanilmandelic acid, homovanilic acid, catecholamines (norepinephrine, epinephrine, dopamine) and methoxylated derivates (metanephrine, normetanephrine, methoxytyramine) in urinary extracts were analyzed by high performance liquid chromatography. Results were indexed to the 24-h urinary creatinine levels.



Among the 115 patients with NET, 9 (8%) had an increase of at least one urinary catecholamine or metabolite; in 7 out of the 9 the increase was slight being less than twice the upper value of the normal range. Elevated urinary dopamine (3 patients), methoxytyramine (6 patients), norepinephrine (2 patients) and normetanephrine (2 patients) were found. No increased urinary excretion of epinephrine nor metanephrine was observed. An adrenal mass existed in one of these nine patients but metaiodobenzylguanidine scintigraphy was negative as was immunohistochemistry for epithelial markers. None of the 20 patients with non-NET demonstrated an increased excretion of catecholamine or metabolites. No relationships were found between catecholamine and metabolite excretions and patients' tumor and treatment characteristics.



Production of catecholamines and metabolites is a rare event in GEP NET patients. Histological results, including positive immunohistochemistry for epithelial markers may help to diagnose GEP NET.
Phosphorylated α-synuclein in Parkinson’s disease: correlation depends on disease severity

α-Synuclein (α-syn) is a key protein in Parkinson's disease (PD), and one of its phosphorylated forms, pS129, is higher in PD patients than healthy controls. However, few studies have examined its levels in longitudinally collected cerebrospinal fluid (CSF) or in preclinical cases. In this study, CSF and clinical data were contributed by >300 subjects from three cohorts (the longitudinal DATATOP cohort, a large cross-sectional cohort, and a cohort of LRRK2 mutation carriers).



Consistent with our previous observation that CSF pS129 positively correlated with Unified Parkinson's Disease Rating Scale (UPDRS) scores, CSF pS129 in the DATATOP cohort increased over approximately two years of disease progression (mean change 5.60 pg/ml, p = 0.050). Intriguingly, in the DATATOP cohort, pS129 negatively correlated with UPDRS scores at the baseline (R = -0.244, p = 0.017), but not final point, suggesting that this association may depend on disease stage. Reanalysis of our previous cohort with stratification by PD stage, and addition of a cohort of LRRK2 mutation carriers with very early/preclinical PD, supported the idea that the relationship between CSF pS129 and disease severity over a wider range of PD stages might be represented with a U-shaped curve, in which lower pS129 levels correlated with worse clinical condition at early stages, but better condition at later stages.



The observation of a negative-to-positive transition of correlation of pS129 to disease severity as PD progresses could have profound impact on how pS129 is used as a biomarker clinically as well as in modeling PD experimentally.
Scheduled maintenance therapy with infliximab improves the prognosis of Crohn's disease: a single center prospective cohort study in Japan.

The main goal of Crohn's disease (CD) treatment at present is to induce and maintain remission for as long as possible, and several approaches have been used as induction and maintenance therapies. There are no reports that have compared the effects on mid- and long-term prognosis among the induction and maintenance therapies, especially between infliximab, a chimeric antibody to tumor necrosis factor-alpha, and nutritional therapies. A total of 262 CD patients with induced remission were enrolled in the cohort study. Patients who failed to achieve remission, and patients who were lost to follow-up within 12 months were excluded. Induction therapies for CD included total elemental enteral nutrition, total parenteral nutrition, infliximab, prednisolone, and surgical resection. Maintenance therapies included home elemental diet, 5-aminosalicylates, immunomodulators, and scheduled infliximab therapy. We evaluated the possible predictive factors of relapse and surgical recurrence including the clinical backgrounds of the patients and medical therapies, using the Cox multivariate hazard analysis. The main factors that strongly affected the first relapse were scheduled infliximab therapy (hazard ratio (HR) = 0.24, p < 0.0001), surgical induction (HR = 0.19, p < 0.0001) and high frequency of previous relapse (HR = 2.56, p = 0.002). Penetrating (HR = 3.33, p = 0.009) and stricturing (HR = 6.60, p < 0.0001) disease behavior were main risk factors of surgical recurrence. Scheduled infliximab therapy is the most effective maintenance therapy in a real clinical setting with respect to the mid- and long-term prognosis.
The Importance of Cross-layer Considerations in a Standardized WSN Protocol Stack Aiming for IoT: The Internet of Things (Ubiquity symposium)

The Internet of Things (IoT) envisages expanding the current Internet with a huge number of intelligent communicating devices. Wireless sensor networks (WSNs) integrating IoT will rely on a set of the open standards striving to offer scalability and reliability in a variety of operating scenarios and conditions. Standardized protocols will tackle some of the major WSN challenges like energy efficiency, intrinsic impairments of low-power wireless medium, and self-organization. After more then a decade of tremendous standardization efforts, we can finally witness an integral IP-based WSN standardized protocol stack for IoT. Nevertheless, the current state of standards has redundancy issues and can benefit from further improvements. We would like to highlight some of the cross-layer aspects that need to be considered to bring further improvements to the standardized WSN protocol stack for the IoT.
Attitudes of cancer patients, family caregivers, oncologists and members of the general public toward critical interventions at the end of life of terminally ill patients.

Whereas most studies have focused on euthanasia and physician-assisted suicide, few have dealt comprehensively with other critical interventions administered at the end of life. We surveyed cancer patients, family caregivers, oncologists and members of the general public to determine their attitudes toward such interventions.



We administered a questionnaire to four groups about their attitudes toward five end-of-life interventions--withdrawal of futile life-sustaining treatment, active pain control, withholding of life-sustaining measures, active euthanasia and physician-assisted suicide. We performed multivariable analyses to compare attitudes and to identify sociodemographic characteristics associated with the attitudes.



A total of 3840 individuals--1242 cancer patients, 1289 family caregivers and 303 oncologists from 17 hospitals, as well as 1006 members of the general Korean population--participated in the survey. A large majority in each of the groups supported withdrawal of futile life-sustaining treatment (87.1%-94.0%) and use of active pain control (89.0%-98.4%). A smaller majority (60.8%-76.0%) supported withholding of life-sustaining treatment. About 50% of those in the patient and general population groups supported active euthanasia or physician-assisted suicide, as compared with less than 40% of the family caregivers and less than 10% of the oncologists. Higher income was significantly associated with approval of the withdrawal of futile life-sustaining treatment and the practice of active pain control. Older age, male sex and having no religion were significantly associated with approval of withholding of life-sustaining measures. Older age, male sex, having no religion and lower education level were significantly associated with approval of active euthanasia and physician-assisted suicide.



Although the various participant groups shared the same attitude toward futile and ameliorative end-of-life care (the withdrawal of futile life-sustaining treatment and the use of active pain control), oncologists had a more negative attitude than those in the other groups toward the active ending of life (euthanasia and physician-assisted suicide).
Development of a Novel Nomogram to Predict Hypertension Cure After Laparoscopic Adrenalectomy in Patients With Primary Aldosteronism

Primary aldosteronism is the most common curable cause of secondary hypertension. Despite resection, however, many patients with primary aldosteronism continue to require antihypertensive drugs to control their blood pressure. Although many patients with primary aldosteronism want to know the postoperative probability of hypertension cure before surgery, there are no predictive models calculating its probability. We therefore developed a nomogram to predict hypertension cure in patients with primary aldosteronism after laparoscopic adrenalectomy. We retrospectively surveyed 132 Japanese patients with primary aldosteronism who were treated by unilateral laparoscopic adrenalectomy. Hypertension cure was defined as normal blood pressure (<140/90 mmHg) without antihypertensive drugs 6 months postoperatively. We developed a novel nomogram that postoperatively predicted cured hypertension in 105 (80 %) randomly selected patients and validated it with the remaining 27 (20 %). At 6 months, blood pressure had normalized in 42 % of patients without antihypertensive drugs. Duration of hypertension, preoperative number of antihypertensive drug classes, age, and sex were incorporated into a novel nomogram as independent predictors of hypertension cure. The value of the area under the receiver operating characteristics curve for this nomogram was 0.83—which was significantly higher than that of the Aldosteronoma Resolution Score—on internal validation. We developed the first nomogram that can accurately predict postoperative hypertension cure in patients with primary aldosteronism. This nomogram can help clinicians calculate the probability of postoperative hypertension cure in patients with primary aldosteronism and objectively inform them of their hypertension outcome before laparoscopic adrenalectomy.
The Chronic Illness Resources Survey: cross-validation and sensitivity to intervention.

There is great interest in, but few instruments to assess, multiple levels of support and community resources from a social-ecological perspective. This study evaluated the psychometric characteristics of the Chronic Illness Resources Survey (CIRS) and its sensitivity to a multifaceted social-ecological intervention to enhance personally relevant community resources supportive of healthful lifestyles. Participants were 293 post-menopausal women having type 2 diabetes who were part of a multiple-behavior lifestyle change program. Key measures included the CIRS, a validated Food Frequency Questionnaire, the Kristal Fat and Fiber Behavior Questionnaire, the CHAMPS Activities Questionnaire for Older Adults, and other measures of social support. Results revealed that the CIRS displayed good psychometric characteristics in this new sample, was significantly correlated as predicted with established measures of social support, was sensitive to intervention, and partially mediated the effects of intervention on both dietary and physical activity outcomes. The 22-item CIRS scale appears useful for assessing multilevel support resources, predicting successful behavior change and detecting social-ecological intervention effects.
Validation of the Spanish version of the Asthma Control Questionnaire.

The Asthma Control Questionnaire (ACQ) has not been validated in the Spanish population, and the fact that it requires spirometry poses an important limitation on its widespread use in the primary care setting in Spain.



The aim of this study was to evaluate the psychometric properties of the Spanish version of the ACQ.



In this multicenter, prospective study, consecutive adult patients with persistent asthma were recruited at 62 respiratory and allergy units across Spain. Patients were assessed at baseline and at weeks 2 and 6. The following clinical variables were recorded: lung function (forced expiratory volume in 1 second [FEV(1)]), symptoms, exacerbations, concomitant diseases, asthma severity according to the Global Initiative for Asthma international guideline, and asthma control as perceived by patients and physicians through direct ad hoc questions. The latter measures were derived specifically for this study. Patients self-completed the ACQ at all visits before the rest of the study variables were recorded. The ACQ's feasibility, validity, reliability, and sensitivity to change were assessed. Cross-sectional and longitudinal validity was assessed using the relationship between ACQ score and clinical parameters. Sensitivity to change was assessed by estimating the global effect size and the minimal important difference (MID). Reliability was assessed using estimation of the Cronbach alpha coefficient (CCalpha) and intraclass correlation coefficient (ICC).



A total of 607 patients were included. The mean (SD) age was 45.6 (17.1) years and 61.4% of the patients were women. Of these 607, 235 (39%) had mild asthma; 246 (41%), moderate; and 126 (21%), severe. Mean (SD) time to complete the ACQ was 3.9 (4.4) minutes. The Pearson correlation coefficient in the relationship between ACQ and FEV(1) (% predicted value) was -0.23. ACQ was found to be significantly related to asthma severity and intensity and frequency of symptoms (coughing, wheezing, and dyspnea) (both, P < 0.001). Change in ACQ was significantly related to changes in FEV(1), intensity and frequency of symptoms, and number of exacerbations (all, P < 0.001). The global effect size of ACQ was 0.46 and the MID was 0.47 point of a maximum of 6. CCalpha was 0.90 and ICC was 0.86.



In these adults with asthma in Spain, the Spanish version of the ACQ was found to be a reliable and valid questionnaire, suggesting that it can be used in this population as a discriminative and evaluative instrument.
Point-of-care procalcitonin test to reduce antibiotic exposure in patients hospitalized with acute exacerbation of COPD

This study was conducted to investigate whether point-of-care (POC) procalcitonin (PCT) measurement can reduce redundant antibiotic treatment in patients hospitalized with acute exacerbation of COPD (AECOPD).



One-hundred and twenty adult patients admitted with AECOPD were enrolled in this open-label randomized trial. Patients were allocated to either the POC PCT-guided intervention arm (n=62) or the control arm, in which antibiotic therapy followed local guidelines (n=58).



The median duration of antibiotic exposure was 3.5 (interquartile range [IQR] 0-10) days in the PCT-arm vs 8.5 (IQR 1-11) days in the control arm (P=0.0169, Wilcoxon) for the intention-to-treat population. The proportion of patients using antibiotics for ≥5 days within the 28-day follow-up was 41.9% (PCT-arm) vs 67.2% (P=0.006, Fisher's exact) in the intention-to-treat population. For the per-protocol population, the proportions were 21.1% (PCT-arm) vs 73.9% (P<0.00001, Fisher's exact). Within 28-day follow-up, one patient died in the PCT-arm and two died in the control arm. A composite harm end point consisting of death, rehospitalization, or intensive care unit admission, all within 28 days, showed no apparent difference.



Our study shows that the implementation of a POC PCT-guided algorithm can be used to substantially reduce antibiotic exposure in patients hospitalized with AECOPD, with no apparent harm.