nils-herrmann/clean_scirepeval huggingface dataset:
Standardized discharge orders after stroke: results of the quality improvement in stroke prevention (QUISP) cluster randomized trial.

Proven strategies to reduce risk of stroke recurrence are under-utilized. We sought to evaluate the impact of standardized stroke discharge orders on treatment practices in a cluster-randomized trial.



The Quality Improvement in Stroke Prevention (QUISP) trial randomized 12 hospitals to continue usual care or to receive assistance in the development and implementation of standardized stroke discharge orders. All patients with ischemic stroke were identified during a 12-month period prior to implementation and for 12 months afterward, and were followed for 6 months after discharge. The primary outcome was optimal treatment at 6 months, defined as taking a statin, having blood pressure <140/90mmHg, and receiving anticoagulation if atrial fibrillation was diagnosed. The primary analysis treated the hospital as the unit of analysis, comparing optimal treatment rates-adjusted for race, age, dementia, atrial fibrillation, and history of bleeding-between intervention and non-intervention hospitals using a paired t test.



In the primary analysis with hospital as the unit of analysis, the odds of optimal treatment was not significantly increased at intervention compared to non-intervention hospitals (odds ratio, 1.39; 95% confidence interval, 0.71-2.76; p = 0.27). However, in analyses conducted at the level of the individual patients (N = 3,361), rates of optimal treatment increased from 37% to 45% in the intervention hospitals (p = 0.001) and did not change significantly in the non-intervention hospitals (39% to 40%; p = 0.27).



Implementation of standardized discharge orders after stroke was associated with increased rates of optimal secondary prevention; this improvement was not significant in the primary analysis at the hospital level.
The quality of life of children and adolescents with ADHD undergoing outpatient psychiatric treatment: simple disorders of activity and attention and hyperkinetic conduct disorders in comparison with each other and with other diagnostic groups.

(1) How does the quality of life of patients with ADHD treated in an ambulatory care setting compare to that of other patient groups in child and adolescent psychiatry? (2) Can differences in the quality of life be demonstrated between patients with simple disorders of activity and attention and those with hyperkinetic conduct disorders? (3) How does the quality of life in these patient groups change over one year of treatment? The Inventory for the Assessment of Life Quality in Children and Adolescents (Inventar zur Untersuchung der Lebensqualität von Kindern und Jugendlichen, ILK) was applied to a sample of 726 patients derived from nine different outpatient practices for child and adolescent psychiatry. Among them were 196 patients with a simple disorder of activity and attention and 64 with a hyperkinetic conduct disorder. A comparison between these two groups was the main aim of the study. The mean age of the patients in the sample (all diagnoses) was 8.7 ± 3 years. The two groups of hyperkinetic patients made up 35% of the overall sample, and both of them showed a marked male predominance. The hyperkinetic patients tended to have lower quality-of-life scores than patients in the other diagnostic groups. Longitudinal observation revealed improvements in the quality of life across all patient groups, but the patients with hyperkinetic disorders (both groups) improved the least. The parents of the hyperkinetic patients, too, reported suffering greater stress because of their children's condition than the parents of children with other types of disorders. The ILK instrument has test-metrical qualities that render it usable and capable of holding its own among other, comparable instruments. It can be used to assess the quality of life of children with various diagnoses. Children with ADHD tend to have the least favorable quality-of-life scores, yet they do show some degree of improvement in their quality of life after a year of treatment.
Evaluation of a Primary Prevention Program for Anxiety Disorders Using Story Books with Children Aged 9–12 Years

This article reports the results of a study evaluating a book-supported primary prevention program “Dominique’s Handy Tricks” for anxiety disorders in children aged 9–12 years. This cognitive-behavioural program is delivered using a combination of storybooks and workshop sessions. The originality of the program comes from the use of storybooks that were not developed specifically for anxiety management. Every session is based on a story describing characters facing common stressors and how they manage to cope with their daily problems. In our randomized control trial with 46 children, participation in the program led to a significant improvement in coping skills, perceived self-efficacy, anxiety sensitivity, as well as in symptoms of anxiety and fear. The theoretical and practical elements underlying the delivery of this primary prevention program are described.  It is suggested that such an approach, without any labelling specific to anxiety disorders, can be useful in primary prevention programs.
Health-related quality-of-life evaluation of crohn disease patients after receiving natalizumab therapy.

Crohn disease (CD) is a chronic inflammatory condition without a permanent medical cure and commonly requiring a lifetime of care. This article discusses the impact of natalizumab induction and maintenance therapy on the health-related quality of life (HRQoL) of CD patients. Two natalizumab phase III studies were evaluated: the Efficacy of Natalizumab in Crohn's Disease Response and Remission (ENCORE) study evaluated the HRQoL of CD patients during 12 weeks of natalizumab induction therapy, and the Evaluation of Natalizumab As Continuous Therapy (ENACT-2) trial evaluated the effect of natalizumab maintenance therapy on HRQoL for a period of 48 weeks past a 12-week induction period (ENACT-1). HRQoL assessments were made with the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Short Form-36 (SF-36). In the ENCORE study, induction therapy with natalizumab was demonstrated to significantly increase HRQoL scores at 12 weeks when compared with patients on placebo. During the ENACT-2 trial, IBDQ and SF-36 scale scores of patients who responded to natalizumab induction remained stable whereas those on placebo worsened. At week 60, the mean change from baseline on all scales of the IBDQ and the SF-36 were significantly higher for those who continued to receive natalizumab as compared to those who received placebo (p </= .016 for all scales). Natalizumab significantly improved the patient's clinical status and HRQoL shortly after treatment was initiated, and the effect was maintained for 60 weeks.
Gender-specific, multi-level determinants of outcomes of antihypertensive treatment: a sub-analysis of the Belgian PREVIEW study

Gender-specific determinants of blood pressure (BP) values and control have not been the focus of clinical hypertension research. The purpose of this analysis was to identify gender-specific and multi-level (physician and patient) determinants of BP values and predictors of uncontrolled BP. We completed a subgroup analysis comparing men and women who participated in the Belgian PREVIEW study of second-line treatment effectiveness of valsartan, applying two-level hierarchical modelling of 90-day BP values and guideline-defined BP control. In total, 1665 women and 1525 men were treated by 504 general practitioners. Fewer women than men reached systolic BP (SBP) (P=0.015) and combined BP targets at 90 days (P=0.007). More than 26% of the variance in 90-day SBP (intra-class correlation coefficient (ICC)=0.270) and diastolic BP (DBP) (ICC=0.262) was attributable to physician-level factors for men; the physician-level ICCs for SBP and DBP were 0.259 and 0.268, respectively, for women. Determinants of 90-day BP values and predictors of uncontrolled BP varied considerably by gender. Many of the multi-level determinants of BP by gender are amenable to intervention, and the remainder can serve as warning signs to clinicians that patients may remain vulnerable to poor outcomes associated with sub-optimal BP control.
Calcium channel blockers and mortality in elderly patients with myocardial infarction.

Although calcium channel blockers are a useful therapy in relieving angina, lowering blood pressure, and slowing conduction of atrial fibrillation, growing evidence has cast doubt on their safety in patients with coronary disease.



To examine the association between calcium channel blocker therapy at hospital discharge and mortality in a population-based sample of elderly patients hospitalized with acute myocardial infarction.



Retrospective cohort study using data from medical charts and administrative files.



All acute care hospitals in 46 states.



All Medicare patients with a principal diagnosis of acute myocardial infarction consecutively discharged from the hospital alive during 8-month periods between 1994 and 1995 (N = 141,041).



Mortality at 30 days and 1 year.



Calcium channel blockers were widely prescribed at hospital discharge to elderly patients with myocardial infarction between 1994 and 1995 (n = 51,921), the most commonly prescribed being diltiazem (n = 21,175), nifedipine (n = 12,670), amlodipine (n = 11,683), and verapamil (n = 3639). After adjusting for illness severity and concomitant medication use, patients who were prescribed calcium channel blockers at hospital discharge did not have increased risk for 30-day or 1-year mortality, with the exception of the few (n = 116) treated with bepridil. Bepridil differs from other calcium channel blockers because of its tendency to prolong repolarization, and its association with proarrhythmic effects in elderly patients.



We did not identify a mortality risk in a large consecutive sample of elderly patients with myocardial infarction, which supports the need for additional prospective trials examining calcium channel blocker therapy for ischemic heart disease.
Translational impact of nanoparticle-drug conjugate CRLX101 with or without bevacizumab in advanced ovarian cancer.

Increased tumor hypoxia and hence elevated hypoxia-inducible factor-1α (HIF1α) is thought to limit the efficacy of vascular endothelial growth factor (VEGF) pathway-targeting drugs by upregulating adaptive resistance genes. One strategy to counteract this is to combine antiangiogenic drugs with agents able to suppress HIF1α. One such possibility is the investigational drug CRLX101, a nanoparticle-drug conjugate (NDC) containing the payload camptothecin, a known topoisomerase-I poison.



CRLX101 was evaluated both as a monotherapy and combination with bevacizumab in a preclinical mouse model of advanced metastatic ovarian cancer. These preclinical studies contributed to the rationale for undertaking a phase II clinical study to evaluate CRLX101 monotherapy in patients with advanced platinum-resistant ovarian cancer.



Preclinically, CRLX101 is highly efficacious as a monotherapy when administered at maximum-tolerated doses. Furthermore, chronic low-dose CRLX101 with bevacizumab reduced bevacizumab-induced HIF1α upregulation and resulted in synergistic efficacy, with minimal toxicity in mice. In parallel, initial data reported here from an ongoing phase II clinical study of CRLX101 monotherapy shows measurable tumor reductions in 74% of patients and a 16% RECIST response rate to date.



Given these preclinical and initial clinical results, further clinical studies are currently evaluating CRLX101 in combination with bevacizumab in ovarian cancer and warrant the evaluation of this therapy combination in other cancer types where HIF1α is implicated in pathogenesis, as it may potentially be able to improve the efficacy of antiangiogenic drugs.
Hepatotoxicity with combination of vemurafenib and ipilimumab.

1. Shortt J, Oh DH, Opat SS. ADAMTS13 antibody depletion by bortezomib in thrombotic thrombocytopenic purpura.  2013;368:90-2. 2. Sorvillo N, Pos W, van den Berg LM, et al. The macrophage mannose receptor promotes uptake of ADAMTS13 by dendritic cells. Blood 2012;119:3828-35. 3. Subklewe M, Sebelin-Wulf K, Beier C, et al. Dendritic cell maturation stage determines susceptibility to the proteasome inhibitor bortezomib.  Immunol 2007;68:147-55.
The "syncope and dementia" study: a prospective, observational, multicenter study of elderly patients with dementia and episodes of "suspected" transient loss of consciousness.

Syncope and related falls are one of the main causes and the predominant cause of hospitalization in elderly patients with dementia. However, the diagnostic protocol for syncope is difficult to apply to patients with dementia. Thus, we developed a "simplified" protocol to be used in a prospective, observational, and multicenter study in elderly patients with dementia and transient loss of consciousness suspected for syncope or unexplained falls. Here, we describe the protocol, its feasibility and the characteristics of the patients enrolled in the study.



Patients aged ≥65 years with a diagnosis of dementia and one or more episodes of transient loss of consciousness during the previous 3 months, subsequently referred to a Geriatric Department in different regions of Italy, from February 2012 to May 2014, were enrolled. A simplified protocol was applied in all patients. Selected patients underwent a second-level evaluation.



Three hundred and three patients were enrolled; 52.6% presented with episodes suspected to be syncope, 44.5% for unexplained fall and 2.9% both. Vascular dementia had been previously diagnosed in 53.6% of participants, Alzheimer's disease in 23.5% and mixed forms in 12.6%. Patients presented with high comorbidity (CIRS score = 3.6 ± 2), severe functional impairment, (BADL lost = 3 ± 2), and polypharmacy (6 ± 3 drugs).



Elderly patients with dementia enrolled for suspected syncope and unexplained falls have high comorbidity and disability. The clinical presentation is often atypical and the presence of unexplained falls is particularly frequent.
The Cerebral Microvasculature in Schizophrenia: A Laser Capture Microdissection Study

Previous studies of brain and peripheral tissues in schizophrenia patients have indicated impaired energy supply to the brain. A number of studies have also demonstrated dysfunction of the microvasculature in schizophrenia patients. Together these findings are consistent with a hypothesis of blood-brain barrier dysfunction in schizophrenia. In this study, we have investigated the cerebral vascular endothelium of schizophrenia patients at the level of transcriptomics.



We used laser capture microdissection to isolate both microvascular endothelial cells and neurons from post mortem brain tissue from schizophrenia patients and healthy controls. RNA was isolated from these cell populations, amplified, and analysed using two independent microarray platforms, Affymetrix HG133plus2.0 GeneChips and CodeLink Whole Human Genome arrays. In the first instance, we used the dataset to compare the neuronal and endothelial data, in order to demonstrate that the predicted differences between cell types could be detected using this methodology. We then compared neuronal and endothelial data separately between schizophrenic subjects and controls. Analysis of the endothelial samples showed differences in gene expression between schizophrenics and controls which were reproducible in a second microarray platform. Functional profiling revealed that these changes were primarily found in genes relating to inflammatory processes.



This study provides preliminary evidence of molecular alterations of the cerebral microvasculature in schizophrenia patients, suggestive of a hypo-inflammatory state in this tissue type. Further investigation of the blood-brain barrier in schizophrenia is warranted.
Nebulised salbutamol administered during sputum induction improves bronchoprotection in patients with asthma.

Inhalation of hypertonic or even isotonic saline during sputum induction may cause bronchospasm in susceptible patients with asthma, despite premedication with 400 microg inhaled salbutamol delivered by pressurised metered dose inhaler (pMDI). The bronchoprotection afforded by additional inhaled salbutamol administered through the ultrasonic nebuliser during sputum induction was investigated.



Twenty patients with moderate to severe asthma underwent sputum induction by inhaling saline 4.5% (or 0.9% if post-bronchodilation forced expiratory volume in 1 second (FEV1) <65% predicted) for 10 minutes according to two protocols given 1 week apart in random order. At visit A the patients received 400 microg salbutamol administered through a pMDI+spacer 20 minutes before induction while at visit B the premedication was supplemented by 1500 microg nebulised salbutamol inhaled throughout the induction procedure. Both the investigator and the patients were blind to the nebulised solution used. FEV1 was recorded during sputum induction at 1, 3, 5, and 10 minutes. Sputum cell counts and histamine, tryptase and albumin levels in the supernatants were determined.



The mean (SE) maximal reduction in FEV1 over the 10 minute period of sputum induction was 11.7 (2.8)% at visit A, which was significantly greater than at visit B (2.6 (1.2)%; mean difference 9% (95% CI 2.7 to 15.4), p<0.01). Total and differential sputum cell counts as well as albumin, tryptase, and histamine levels did not differ between the two visits.



The addition of inhaled salbutamol through an ultrasonic nebuliser markedly improves bronchoprotection against saline induced bronchoconstriction in patients with moderate to severe asthma undergoing sputum induction without affecting cell counts and inflammatory markers.
The demethylation of amitriptyline: A cross-over study of steady-state plasma levels of amitriptyline and nortriptyline in depressed patients

Five elderly depressed patients were treated with amitriptyline (AT) and nortriptyline (NT) in turn, in a crossover design. Steady-state plasma drug levels were compared with those calculated for eight healthy subjects of previous single-dose studies. Plasma clearances were on average about 2.5 times lower in the patients than the healthy subjects, but the ratios of the different reaction rates did not differ significantly between the two groups. The interpretation of the ratio of NT levels during AT treatment and NT treatment, in terms of the fraction of AT that is metabolised by demethylation, is discussed. The ratio of NT level to AT level during AT treatment was particularly variable between individuals. This was apparently due to independent variation in (a) the ratio of plasma clearances of AT and NT and (b) the fraction of AT metabolised to NT.
Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation

Ovarian tissue cryopreservation with later reimplantation has been shown to preserve fertility in adult women, but this approach remains unproven and experimental in children and adolescents. We aimed to assess the use of the Edinburgh selection criteria for ovarian tissue cryopreservation in girls and young women with cancer to determine whether we are offering this invasive procedure to the patients who are most at risk of premature ovarian insufficiency.



Cryopreservation of ovarian tissue has been selectively offered to girls and young women with cancer who met the Edinburgh selection criteria since 1996. Between Jan 1, 1996, and June 30, 2012, 410 female patients younger than 18 years at diagnosis were treated for cancer (including leukaemia and brain tumours) at the Edinburgh Children's Cancer Centre, which serves the whole South East of Scotland region. We determined the ovarian status of these patients from review of clinical records and classified them as having premature ovarian insufficiency or not, or as unable to be determined. Patients younger than 12 years at time of data cutoff  2013) were excluded from the analysis.



34 (8%) of the 410 patients met the Edinburgh selection criteria and were offered ovarian tissue cryopreservation before starting cancer treatment. 13 patients declined the procedure and 21 consented, and the procedure was completed successfully in 20 patients. Of the 20 patients who had ovarian tissue successfully cryopreserved, 14 were available for assessment of ovarian function. Of the 13 patients who had declined the procedure, six were available for assessment of ovarian function. Median age at the time of follow-up for the 20 assessable patients was 16·9 years (IQR 15·5-21·8). Of the 14 assessable patients who had successfully undergone ovarian cryopreservation, six had developed premature ovarian insufficiency at a median age of 13·4 years (IQR 12·5-14·6), one of whom also had a natural pregnancy. Of the six assessable patients who had declined the procedure, one had developed premature ovarian insufficiency. Assessment of ovarian function was possible for 141 of the 376 patients who were not offered cryopreservation; one of these patients had developed premature ovarian insufficiency. The cumulative probability of developing premature ovarian insufficiency after treatment was completed was significantly higher for patients who met the criteria for ovarian tissue cryopreservation than for those who did not (15-year probability 35% [95% CI 10-53] vs 1% [0-2]; p<0·0001; hazard ratio 56·8 [95% CI 6·2-521·6] at 10 years).



The results of this analysis show that the Edinburgh selection criteria accurately identify the few girls and young women who will develop premature ovarian insufficiency, and validate their use for selection of patients for ovarian tissue cryopreservation. Further follow-up of this cohort of patients is likely to allow refinement of the criteria for this experimental procedure in girls and young women with cancer.



UK Medical Research Council.
Physical activity and sedentary behavior in breast cancer survivors: New insight into activity patterns and potential intervention targets.

Inactivity and sedentary behavior are related to poorer health outcomes in breast cancer survivors. However, few studies examining these behaviors in survivors have used objective measures, considered activities other than moderate-to-vigorous intensity activity (MVPA) and/or sedentary behavior (i.e. low intensity activities) or compared survivors to healthy controls. The purpose of the present study is to compare accelerometer-measured activity of various intensities (total, light, lifestyle, MVPA) and sedentary behavior between breast cancer survivors and non-cancer controls.



An imputation-based approach of independent sample t-tests adjusting for multiple comparisons was used to compare estimates of participation in each activity and sedentary behavior between survivors [n=398; M(SD)age=56.95 (9.11)] and block-matched non-cancer controls [n=1120; M(SD)age=54.88 (16.11)]. Potential moderating effects of body mass index (BMI), age, and education were also examined.



Breast cancer survivors registered less daily total (282.8 v. 346.9) light (199.1 v. 259.3) and lifestyle (62.0 v. 71.7) activity minutes and more MVPA (21.6 v. 15.9) and sedentary behavior (555.7 v. 500.6) minutes than controls (p<0.001 for all). These relationships were largely consistent across BMI, age and education. On average, survivors spent an estimated 66.4% of their waking time sedentary and 31.1% in light/lifestyle activity and 2.6% in MVPA.



Breast cancer survivors are more sedentary and participate in less low intensity activity than controls. Although survivors registered more MVPA, these levels were insufficient. Future research should explore these differences and potential benefits of targeting low intensity activities and reducing sedentary time in this population.