nils-herrmann/clean_scirepeval huggingface dataset:
[Revision of systematic treatment enhancement program for bipolar disorder (STEP-BD)].

The STEP-BD is a public initiative, created to generate data, obtained in pragmatic or real life research environments, from the bipolar disorder. The primary objectives are: to investigate the effectiveness of therapeutic interventions in bipolar disorder, the impact on the disease course of these interventions in the 'real life' and to raise the knowledge about the disease. This program included in six years, n = 4361 patients. This program is not a study in phases but an infrastructure for more than 40 published studies and 30 conference presentations. These studies aim to capture the heterogeneity of the disease in their different clinical presentations, treatments, comorbidities, functionality and quality of life. Patients entering the program have a common assessment. The program consists of two main pathways: the standard treatment and randomized treatment of acute bipolar depression, bipolar depression and refractory relapse prevention. In addition several studies completed the program in an attempt to give coherence to the different clinical presentations of this disease, different treatments and interventions for similar clinical phenomena.
protocolThe SINS trial : A randomised controlled trial of excisional surgery versus imiquimod 5 % cream for nodular and superficial basal cell carcinoma

Basal cell carcinoma is the commonest human cancer. Despite increasing incidence it remains poorly researched. While not life threatening it can cause significant cosmetic disfigurement. Imiquimod, a cream which enhances the body's immune response, may help deal with the number of cases that occur in low-risk sites, especially when good cosmetic results and home use without surgery are needed. This study aims 1. To compare excisional surgery with imiquimod cream for nodular or superficial basal cell carcinoma in low risk sites, with respect to 3 year clinical clearance, cost-effectiveness and cosmetic results. 2. To ascertain if certain phenotypic features and gene polymorphisms predict tumour responsiveness to treatment.  Five hundred participants with low risk nodular or superficial basal cell carcinoma will be recruited from hospitals to this multi-centre, randomised, parallel group, controlled phase III trial. Treatment in the imiquimod group is for 6 weeks for superficial basal cell carcinoma and 12 weeks for nodular basal cell carcinoma. Both treatment groups are followed up in clinic for 3 years.  the proportion of participants with clinical evidence of success (no recurrence) at 3 years. The primary outcome will be compared between the two treatment groups. Secondary outcomes include: i) clinical success at 1, 2 and 5 years, ii) time to first recurrence, iii) cosmetic appearance of lesion site after treatment, iv) level of pain, and v) cost-effectiveness. Safety and tolerability data will also
Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction.

We investigated the effects of enalapril therapy on plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with acute myocardial infarction.



Macrophages express TF in human coronary atherosclerotic plaques. Both TF and TFPI are major regulators of coagulation and thrombosis. Monocyte chemoattractant protein-1 is a monocyte and macrophage chemotactic and activating factor.



In a randomized, double-blind, placebo-controlled study beginning about two weeks after myocardial infarction, 16 patients received four weeks of placebo (placebo group) and another 16 patients received four weeks of enalapril 5 mg daily therapy (enalapril group). We performed blood sampling after administration of the doses.



There were no significant differences in the serum angiotensin-converting enzyme (ACE) activity, plasma TF, free TFPI or MCP-1 levels before administration between the enalapril and placebo groups. In the enalapril group, ACE activity (IU/liter) (14.0 before, 5.2 on day 3, 5.8 on day 7, 6.3 on day 28), TF levels (pg/ml) (223, 203, 182, 178) and MCP-1 levels (pg/ml) (919, 789, 790, 803) significantly decreased by day 28. However, the free TFPI levels (ng/ml) (28.2, 26.5, 26.8, 28.4) did not change. These four variables were unchanged during the study period in the placebo group.



This study demonstrated that administration of enalapril reduces the increased procoagulant activity in patients with myocardial infarction associated with inhibition of the activation and accumulation of macrophages and monocytes.
Trastuzumab for treatment of refractory/relapsed HER2-positive adult B-ALL: results of a phase 2 GRAALL study.

The aim of this phase 2 study was to evaluate the efficacy and safety of trastuzumab, a humanized monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2), for adult patients with relapsed/refractory HER2-positive B-ALL. Fifteen patients, with a median age of 62 years, received trastuzumab according to the schedule approved for breast cancer patients (ie, 4 mg/kg intravenous loading dose followed by 2 mg/kg weekly). The overall response rate was 13% with 2 patients achieving partial response and partial remission cytolytic response, respectively. Two other patients were documented with blast clearance. Only 1 reversible grade 3 cardiac toxic event occurred. This phase 2 study showed that trastuzumab monotherapy can allow for some responses in a very high-risk refractory/relapsed HER2-positive adult B-ALL population. Combination of trastuzumab with chemotherapy or other therapeutic monoclonal antibodies should be tested in the future.
The Global ECT-MRI Research Collaboration (GEMRIC): Establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy

Major depression, currently the world's primary cause of disability, leads to profound personal suffering and increased risk of suicide. Unfortunately, the success of antidepressant treatment varies amongst individuals and can take weeks to months in those who respond. Electroconvulsive therapy (ECT), generally prescribed for the most severely depressed and when standard treatments fail, produces a more rapid response and remains the most effective intervention for severe depression. Exploring the neurobiological effects of ECT is thus an ideal approach to better understand the mechanisms of successful therapeutic response. Though several recent neuroimaging studies show structural and functional changes associated with ECT, not all brain changes associate with clinical outcome. Larger studies that can address individual differences in clinical and treatment parameters may better target biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we summarize the ECT sample characteristics from currently participating sites, and the common data-repository and standardized image analysis pipeline developed for this initiative. This includes data harmonization across sites and MRI platforms, and a method for obtaining unbiased estimates of structural change based on longitudinal measurements with serial MRI scans. The optimized analysis pipeline, together with the large and heterogeneous combined GEMRIC dataset, will provide new opportunities to elucidate the mechanisms of ECT response and the factors mediating and predictive of clinical outcomes, which may ultimately lead to more effective personalized treatment approaches.
The natural history of adult pulmonary Langerhans cell histiocytosis: a prospective multicentre study

The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported.



In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders.



The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients.



Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs.
Leukocyte-reduced red blood cell transfusions in patients with anemia and human immunodeficiency virus infection: the Viral Activation Transfusion Study: a randomized controlled trial.

Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospective studies suggest that transfusions adversely affect the clinical course of HIV. Data in selected non-HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells (RBCs).



To compare the effects of leukoreduced and unmodified RBC transfusions on survival, complications of acquired immunodeficiency syndrome, and relevant laboratory markers in HIV-infected patients.



Double-blind randomized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999, with a median follow-up of 12 months (24 months in survivors).



A total of 531 persons infected with HIV and CMV, aged 14 years or older, who required transfusions for anemia; 259 received leukoreduced transfusions and 262 received unmodified transfusions (10 did not receive the planned transfusion).



Survival and change in plasma HIV RNA level 7 days after transfusion, compared by type of transfusion.



At entry, the groups were similar in demographic, clinical, and relevant laboratory characteristics. A total of 3864 RBC units were transfused. Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusion; 138 with unmodified transfusion); median survival was 13.0 and 20.5 months, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P =.12). Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction (RH, 1.35; 95% CI, 1.06-1.72). There was no difference in time to new opportunistic event/death or frequency of transfusion reactions. No changes in plasma HIV RNA level were seen in either group at days 7, 14, 21, or 28, even in patients not taking antiretroviral drugs. There were no differences in trends between groups in CMV DNA, CD4 cell counts, activated (CD38% or human leukocyte antigen-DR) CD8 cell counts, or plasma cytokine levels.



We found no evidence of HIV, CMV, or cytokine activation following blood transfusion in patients with advanced HIV infection. Leukoreduction provided no clinical benefit in these patients. These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different patient populations, since smaller studies in other patient populations have suggested leukoreduction may be beneficial.
Non-invasive evaluation of the effect of metoprolol on the atrioventricular node during permanent atrial fibrillation

The aim of this study was to evaluate changes in AV nodal properties during administration of metoprolol, using a novel ECG-based method for parameter estimation. The AV nodal parameters account for the probability of an impulse not passing through the fast pathway, the absolute refractory periods of the slow and fast pathways (aRPs and aRPf), representing the functional refractory period, and related prolongation in the respective refractory periods. Twenty patients (age 71 ± 8 years, 14 men) with permanent AF from the RATe control in Atrial Fibrillation (RATAF) database were included in this study. Recordings during baseline and metoprolol administration were analyzed. Furthermore, simulated RR series were generated mimicking metoprolol administration. During metoprolol administration, aRP was significantly prolonged in both pathways (aRPs: 342 ± 39 vs. 408 ± 81 ms, p<;0.001; aRPf: 432 ± 74 vs. 527 ± 83 ms, p<;0.001). Similar results were found for the simulated RR series: both aRPs and aRPf were significantly prolonged with metoprolol. The AV nodal parameters reflect expected changes after metoprolol administration, i.e., a prolongation in functional refractory period. The simulations suggest that aRP may serve as an estimate of the functional refractory period.
Positron Emission Tomography of Regional Brain Metabolic Responses to a Serotonergic Challenge in Major Depressive Disorder with and without Borderline Personality Disorder

Previous neuroimaging studies of major depression have not controlled for the presence of personality disorders characterized by impulsive aggressive behavior, such as borderline personality disorder (BPD). Using positron emission tomography (PET), we studied regional glucose uptake in response to fenfluramine (FEN) in depressed subjects with BPD (n=11) and depressed patients without Cluster B Axis II disorders (n=8). Subjects were scanned while medication-free after a single blind placebo administration and after FEN on a second day. Brain responses were measured by PET imaging of [18F]fluorodeoxyglucose (FDG) and serial prolactin levels. Scans were compared at a voxel level using statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical measures were assessed. Depressed borderline patients had greater relative activity in parietotemporal cortical regions (BA 40, BA 22, and BA 42) before and after FEN activation compared to those without BPD. They also had less relative uptake in the anterior cingulate cortex (BA 32) at baseline compared to depressed patients without BPD and FEN abolished this difference. Impulsivity was positively correlated with rCMRglu in superior and middle frontal cortex (BA 6 and 44). Hostility was positively correlated with rCMRglu in temporal cortical regions (BA 21 and 22). In conclusions, borderline pathology in the context of a Major Depressive Disorder is associated with altered activity in parietotemporal and anterior cingulate cortical regions. Controlling for the presence of BPD in future imaging studies of mood disorders may elucidate similarities and differences in regional serotonergic function in these two often comorbid disorders.
Model-based insulin and nutrition administration for tight glycaemic control in critical care.

Present a new model-based tight glycaemic control approach using variable insulin and nutrition administration.



Hyperglycaemia is prevalent in critical care. Current published protocols use insulin alone to reduce blood glucose levels, require significant added clinical effort, and provide highly variable results. None directly address both the practical clinical difficulties and significant patient variation seen in general critical care, while also providing tight control.



The approach presented manages both nutritional inputs and exogenous insulin infusions using tables simplified from a model-based, computerised protocol. Unique delivery aspects include bolus insulin delivery for safety and variable enteral nutrition rates. Unique development aspects include the use of simulated virtual patient trials created from retrospective data. The model, protocol development, and first 50 clinical case results are presented.



High qualitative correlation to within +/-10% between simulated virtual trials and published clinical results validates the overall approach. Pilot tests covering 7358 patient hours produced an average glucose of 5.9 +/- 1.1 mmol/L. Time in the 4-6.1 mmol/L band was 59%, with 84% in 4.0-7.0 mmol/L, and 92% in 4.0-7.75 mmol/L. The average feed rate was 63% of patient specific goal feed and the average insulin dose was 2.6U/hour. There was one hypoglycaemic measurement of 2.1 mmol/L. No departures from protocol or clinical interventions were required at any time.



Modulating both low dose insulin boluses and nutrition input rates challenges the current practice of using only insulin in larger doses to reduce hyperglycaemic levels. Clinical results show very tight control in safe glycaemic bands. The approach could be readily adopted in any typical ICU.
A comparative study of pulsed 532-nm potassium titanyl phosphate laser and electrocoagulation in the treatment of spider nevi.

To assess the clinical efficacy and safety of potassium titanyl phosphate (KTP) laser treatment and electrocoagulation (EC) for the treatment of spider nevi (SN).



A randomized single-blind intrapatient comparison study was performed. A blinded observer and patients reported the clinical treatment outcome and pain on a visual analogue scale (0-10). Side effects were noted if present.



Mean physician-rated clinical efficacy scores+/-standard error of the mean were 7.7+/-0.7 for KTP laser and 6.2+/-0.9 for EC treatment (p=.05). Patient-rated mean clinical efficacy of KTP laser was 8.3+/-0.6 and of EC was 7.3+/-0.7 (p=.09). Stratification for potential confounding bias, such as location of SN, central bulging vein, and diameter (p=.25) of the treated SN did not reveal any statistically significant differences between the treatments. Treatment with KTP or EC did not result in scarring or pigmentary changes. Pain was reported for KTP treatment (3.1+/-0.4) and EC (6.4+/-0.7) (p<.05).



Clinical efficacy of KTP laser and EC for SN is comparable, although there is a tendency toward an advantage in favor of the KTP laser. KTP laser treatment was less painful.
Evidence-based target recall rates for screening mammography.

To retrospectively identify target recall rates for screening mammography on the basis of how sensitivity shifts with recall rate.



The study group included 1 872 687 subsequent and 171 104 first screening mammograms from 1996 to 2001 from 172 and 139 facilities, respectively, in six sites of the Breast Cancer Surveillance Consortium. Institutional review board (IRB) approval was obtained from each site. Informed consent requirements of the IRBs were followed. The study was HIPAA compliant. Recall rate was defined as the percentage of screening studies for which further work-up was recommended by the radiologist. Sensitivity was defined as the proportion of cancers that were detected at screening mammography. Piecewise linear regression was used to model sensitivity as a function of recall rate. This model allows detection of critical recall rates in which significant changes (shifts) occurred in the rates that sensitivity increased with increasing recall rate. Rates were interpreted as number of additional work-ups per additional cancer detected (AW/ACD) or, in other words, the estimated number of additional women needed to be recalled at a given rate to detect one additional cancer.



For first mammograms, a single shift in the estimated AW/ACD rate occurred at a recall rate of 10.0%, with the rate jumping dramatically from 35 to 172. For subsequent mammograms, four shifts were identified. At a recall rate of 6.7%, the estimated AW/ACD increased from 80 to 132, which rendered it the highest desirable target recall rate. At a recall rate of 12.3%, the estimated AW/ACD was 304, which suggests little benefit for any higher recall rate.



Recall rates of 10.0% for first and 6.7% for subsequent mammograms are recommended targets on the basis of their AW/ACD rates (less than 100).
Impact of foods enriched with n-3 long-chain polyunsaturated fatty acids on erythrocyte n-3 levels and cardiovascular risk factors.

Consumption of fish or fish oils rich in the n-3 long chain PUFA EPA and DHA may improve multiple risk factors for CVD. The objective of this study was to determine whether regular consumption of foods enriched with n-3 long-chain PUFA can improve n-3 long-chain PUFA status (erythrocytes) and cardiovascular health. Overweight volunteers with high levels of triacylglycerols (TG; >1.6 mmol/l) were enrolled in a 6-month dietary intervention trial conducted in Adelaide (n 47) and Perth (n 39), and randomised to consume control foods or n-3-enriched foods to achieve an EPA + DHA intake of 1 g/d. Test foods were substituted for equivalent foods in their regular diet. Erythrocyte fatty acids, plasma TG and other CVD risk factors were monitored at 0, 3 and 6 months. There were no significant differences between groups for blood pressure, arterial compliance, glucose, insulin, lipids, C-reactive protein (CRP) or urinary 11-dehydro-thromboxane B2 (TXB2) over 6 months, even though regular consumption of n-3-enriched foods increased EPA + DHA intake from 0.2 to 1.0 g/d. However, the n-3 long-chain PUFA content of erythrocytes increased by 35 and 53 % at 3 and 6 months, respectively, in subjects consuming the n-3-enriched foods. These increases were positively associated with measures of arterial compliance and negatively associated with serum CRP and urinary 11-dehydro-TXB2 excretion. Sustainable increases in dietary intakes and erythrocyte levels of n-3 long-chain PUFA can be achieved through regular consumption of suitably enriched processed foods. Such increases may be associated with reduced CV risk.