nils-herrmann/clean_scirepeval huggingface dataset:
Music therapy in patients with dementia and behavioral disturbance on an inpatient psychiatry unit: results from a pilot randomized controlled study.

The prevalence of dementia continues to grow worldwide due to an aging population and is projected to affect 65.7 million people by 2030 (World Health Organization, 2012). Behavioral and psychological symptoms of dementia (BPSD), including agitation, anxiety, aggression, depression, and psychosis, can occur in as much as 80% of the affected population, frequently necessitating psychiatric admission. Traditionally BPSD have been treated using pharmacological approaches. However, such medications could have serious adverse effects and additionally have limited efficacy in reducing such symptoms (Ballard et al., 2009).
Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis.

Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism (VTE) in a previous trial. We undertook this study to extend those findings.



In a randomized, double-blind, double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or unfractionated heparin for 5 to 11 days, we compared dabigatran 150 mg twice daily with warfarin. The primary outcome, recurrent symptomatic, objectively confirmed VTE and related deaths during 6 months of treatment occurred in 30 of the 1279 dabigatran patients (2.3%) compared with 28 of the 1289 warfarin patients (2.2%; hazard ratio, 1.08; 95% confidence interval [CI], 0.64-1.80; absolute risk difference, 0.2%; 95% CI, -1.0 to 1.3; P<0.001 for the prespecified noninferiority margin for both criteria). The safety end point, major bleeding, occurred in 15 patients receiving dabigatran (1.2%) and in 22 receiving warfarin (1.7%; hazard ratio, 0.69; 95% CI, 0.36-1.32). Any bleeding occurred in 200 dabigatran (15.6%) and 285 warfarin (22.1%; hazard ratio, 0.67; 95% CI, 0.56-0.81) patients. Deaths, adverse events, and acute coronary syndromes were similar in both groups. Pooled analysis of this study RE-COVER II and the RE-COVER trial gave hazard ratios for recurrent VTE of 1.09 (95% CI, 0.76-1.57), for major bleeding of 0.73 (95% CI, 0.48-1.11), and for any bleeding of 0.70 (95% CI, 0.61-0.79).



Dabigatran has similar effects on VTE recurrence and a lower risk of bleeding compared with warfarin for the treatment of acute VTE.
Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia.

Overexpression of Bcl-2 is a potential mechanism for chemoresistance in acute leukemia and has been associated with unfavorable clinical outcome. We hypothesized that down-regulation of Bcl-2 would restore chemosensitivity in leukemic cells. To test this hypothesis, we performed a phase 1 study of G3139 (Genasense, Genta, Berkeley Heights, NJ), an 18-mer phosphorothioate Bcl-2 antisense, with fludarabine (FL), cytarabine (ARA-C), and granulocyte colony-stimulating factor (G-CSF) (FLAG) salvage chemotherapy in patients with refractory or relapsed acute leukemia. Twenty patients with refractory or relapsed acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) were enrolled. G3139 was delivered by continuous infusion on days 1 to 10. FLAG chemotherapy was administered on days 5 to 10. Common side effects of this combination included fever, nausea, emesis, electrolyte imbalance, and fluid retention that were not dose limiting. Plasma pharmacokinetics of G3139 demonstrated steady-state concentration (Css) within 24 hours. Of the 20 patients, 9 (45%) had disease response, 6 (5 AML, 1 ALL) with complete remission (CR) and 3 (2 AML and 1 ALL) with no evidence of disease but failure to recover normal neutrophil and/or platelet counts or to remain in remission for at least 30 days (incomplete remission). Bcl-2 mRNA levels were down-regulated in 9 of the 12 (75%) evaluable patients. This study demonstrates that G3139 can be administered safely with FLAG chemotherapy and down-regulate its target, Bcl-2. The encouraging clinical and laboratory results justify the current plans for a phase 3 study in previously untreated high-risk AML (ie, age at least 60 years).
A randomized phase II study comparing erlotinib versus erlotinib with alternating chemotherapy in relapsed non-small-cell lung cancer patients: the NVALT-10 study.

Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) administered concurrently with chemotherapy did not improve outcome in non-small-cell lung cancer (NSCLC). However, in preclinical models and early phase noncomparative studies, pharmacodynamic separation of chemotherapy and TKIs did show a synergistic effect.



A randomized phase II study was carried out in patients with advanced NSCLC who had progressed on or following first-line chemotherapy. Erlotinib 150 mg daily (monotherapy) or erlotinib 150 mg during 15 days intercalated with four 21-day cycles docetaxel for squamous (SQ) or pemetrexed for nonsquamous (NSQ) patients was administered (combination therapy). After completion of chemotherapy, erlotinib was continued daily. Primary end point was progression-free survival (PFS).



Two hundred and thirty-one patients were randomized, 115 in the monotherapy arm and 116 in the combination arm. The adjusted hazard ratio for PFS was 0.76 [95% confidence interval (CI) 0.58-1.02; P = 0.06], for overall survival (OS) 0.67 (95% CI 0.49-0.91; P = 0.01) favoring the combination arm. This improvement was primarily observed in NSQ subgroup. Common Toxicity Criteria grade 3+ toxic effect occurred in 20% versus 56%, rash in 7% versus 15% and febrile neutropenia in 0% versus 6% in monotherapy and combination therapy, respectively.



PFS was not significantly different between the arms. OS was significantly improved in the combination arm, an effect restricted to NSQ histology.
Right care, right time, right place: improving outcomes for people with spinal cord injury through early access to intervention and improved access to specialised care: study protocol

Traumatic spinal cord injury is a devastating condition impacting adversely on the health and wellbeing, functioning and independence, social participation and quality of life of the injured person. In Australia, there are approximately 15 new cases per million population per year; economic burden estimates suggest 2 billion dollars annually. For optimal patient outcomes expert consensus recommends expeditious transfer ("<24 hours of injury") to a specialist Spinal Cord Injury Unit, where there is an interdisciplinary team equipped to provide comprehensive care for the many and complex issues associated with traumatic spinal cord injury. No study of this patient population has been undertaken, that assessed the extent to which care received reflected clinical guidelines, or examined the patient journey and outcomes in relation to this. The aims of this study are to describe the nature and timing of events occurring before commencement of specialist care, and to quantify the association between these events and patient outcomes.



The proposed observational study will recruit a prospective cohort over two years, identified at participating sites across two Australian states; Victoria and New South Wales. Included participants will be aged 16 years and older and diagnosed with a traumatic spinal cord injury. Detailed data will be collected from the point of injury through acute care and subacute rehabilitation, discharge from hospital and community reintegration. Items will include date, time, location and external cause of injury; ambulance response, assessments and management; all episodes of hospital care including assessments, vital signs, diagnoses and treatment, inter-hospital transfers, surgical interventions and their timing, lengths of stay and complications. Telephone follow-up of survivors will be conducted at 6, 12 and 24 months.



There is limited population level data on the effect of delayed commencement of specialist care (>24 hours) in a Spinal Cord Injury Unit. Examining current health service and clinical intervention pathways in this Australian population-based sample, in relation to their outcomes, will provide an understanding of factors associated with patient flow, resource utilisation and cost, and patient and family quality of life. Barriers to streamlined effective early-care pathways and facilitators of optimal treatment for these patients will be identified.
An administrative claims model suitable for profiling hospital performance based on 30-day mortality rates among patients with an acute myocardial infarction.

A model using administrative claims data that is suitable for profiling hospital performance for acute myocardial infarction would be useful in quality assessment and improvement efforts. We sought to develop a hierarchical regression model using Medicare claims data that produces hospital risk-standardized 30-day mortality rates and to validate the hospital estimates against those derived from a medical record model.



For hospital estimates derived from claims data, we developed a derivation model using 140,120 cases discharged from 4664 hospitals in 1998. For the comparison of models from claims data and medical record data, we used the Cooperative Cardiovascular Project database. To determine the stability of the model over time, we used annual Medicare cohorts discharged in 1995, 1997, and 1999-2001. The final model included 27 variables and had an area under the receiver operating characteristic curve of 0.71. In a comparison of the risk-standardized hospital mortality rates from the claims model with those of the medical record model, the correlation coefficient was 0.90 (SE=0.003). The slope of the weighted regression line was 0.95 (SE=0.007), and the intercept was 0.008 (SE=0.001), both indicating strong agreement of the hospital estimates between the 2 data sources. The median difference between the claims-based hospital risk-standardized mortality rates and the chart-based rates was <0.001 (25th and 75th percentiles, -0.003 and 0.003). The performance of the model was stable over time.



This administrative claims-based model for profiling hospitals performs consistently over several years and produces estimates of risk-standardized mortality that are good surrogates for estimates from a medical record model.
Synchronization views for event-loop actors

The actor model has already proven itself as an interesting concurrency model that avoids issues such as deadlocks and race conditions by construction, and thus facilitates concurrent programming. The tradeoff is that it sacrifices expressiveness and efficiency especially with respect to data parallelism. However, many standard solutions to computationally expensive problems employ data parallel algorithms for better performance on parallel systems.
 We identified three problems that inhibit the use of data-parallel algorithms within the actor model. Firstly, one of the main properties of the actor model, the fact that no data is shared, is one of the most severe performance bottlenecks. Especially the fact that shared state can not be read truly in parallel. Secondly, the actor model on its own does not provide a mechanism to specify extra synchronization conditions on batches of messages which leads to event-level data-races. And lastly, programmers are forced to write code in a continuation-passing style (CPS) to handle typical request-response situations. However, CPS breaks the sequential flow of the code and is often hard to understand, which increases complexity and lowers maintainability.
 We proposes synchronization views to solve these three issues without compromising the semantic properties of the actor model. Thus, the resulting concurrency model maintains deadlock-freedom, avoids low-level race conditions, and keeps the semantics of macro-step execution.
Trajectories of Glycemic Change in a National Cohort of Adults With Previously Controlled Type 2 Diabetes.

Individualized diabetes management would benefit from prospectively identifying well-controlled patients at risk of losing glycemic control.



To identify patterns of hemoglobin A1c (HbA1c) change among patients with stable controlled diabetes.



Cohort study using OptumLabs Data Warehouse, 2001-2013. We develop and apply a machine learning framework that uses a Bayesian estimation of the mixture of generalized linear mixed effect models to discover glycemic trajectories, and a random forest feature contribution method to identify patient characteristics predictive of their future glycemic trajectories.



The study cohort consisted of 27,005 US adults with type 2 diabetes, age 18 years and older, and stable index HbA1c <7.0%.



HbA1c values during 24 months of observation.



We compared models with k=1, 2, 3, 4, 5 trajectories and baseline variables including patient age, sex, race/ethnicity, comorbidities, medications, and HbA1c. The k=3 model had the best fit, reflecting 3 distinct trajectories of glycemic change: (T1) rapidly deteriorating HbA1c among 302 (1.1%) youngest (mean, 55.2 y) patients with lowest mean baseline HbA1c, 6.05%; (T2) gradually deteriorating HbA1c among 902 (3.3%) patients (mean, 56.5 y) with highest mean baseline HbA1c, 6.53%; and (T3) stable glycemic control among 25,800 (95.5%) oldest (mean, 58.5 y) patients with mean baseline HbA1c 6.21%. After 24 months, HbA1c rose to 8.75% in T1 and 8.40% in T2, but remained stable at 6.56% in T3.



Patients with controlled type 2 diabetes follow 3 distinct trajectories of glycemic control. This novel application of advanced analytic methods can facilitate individualized and population diabetes care by proactively identifying high risk patients.
A validation study of a new classification algorithm to identify rheumatoid arthritis using administrative health databases: case–control and cohort diagnostic accuracy studies. Results from the RECord linkage On Rheumatic Diseases study of the Italian Society for Rheumatology

To develop and validate a new algorithm to identify patients with rheumatoid arthritis (RA) and estimate disease prevalence using administrative health databases (AHDs) of the Italian Lombardy region.



Case-control and cohort diagnostic accuracy study.



In a randomly selected sample of 827 patients drawn from a tertiary rheumatology centre (training set), clinically validated diagnoses were linked to administrative data including diagnostic codes and drug prescriptions. An algorithm in steps of decreasing specificity was developed and its accuracy assessed calculating sensitivity/specificity, positive predictive value (PPV)/negative predictive value, with corresponding CIs. The algorithm was applied to two validating sets: 106 patients from a secondary rheumatology centre and 6087 participants from the primary care. Alternative algorithms were developed to increase PPV at population level. Crude and adjusted prevalence estimates taking into account algorithm misclassification rates were obtained for the Lombardy region.



The algorithms included: RA certification by a rheumatologist, certification for other autoimmune diseases by specialists, RA code in the hospital discharge form, prescription of disease-modifying antirheumatic drugs and oral glucocorticoids. In the training set, a four-step algorithm identified clinically diagnosed RA cases with a sensitivity of 96.3 (95% CI 93.6 to 98.2) and a specificity of 90.3 (87.4 to 92.7). Both external validations showed highly consistent results. More specific algorithms achieved >80% PPV at the population level. The crude RA prevalence in Lombardy was 0.52%, and estimates adjusted for misclassification ranged from 0.31% (95% CI 0.14% to 0.42%) to 0.37% (0.25% to 0.47%).



AHDs are valuable tools for the identification of RA cases at the population level, and allow estimation of disease prevalence and to select retrospective cohorts.
Clinical outcomes of Joint Crisis Plans to reduce compulsory treatment for people with psychosis: a randomised controlled trial

The CRIMSON (CRisis plan IMpact: Subjective and Objective coercion and eNgagement) study is an individual level, randomised controlled trial that compared the effectiveness of Joint Crisis Plans (JCPs) with treatment as usual for people with severe mental illness. The JCP is a negotiated statement by a patient of treatment preferences for any future psychiatric emergency, when he or she might be unable to express clear views. We assessed whether the additional use of JCPs improved patient outcomes compared with treatment as usual.



Patients were eligible if they had at least one psychiatric admission in the previous 2 years and were on the Enhanced Care Programme Approach register. The study was done with 64 generic and specialist community mental health teams in four English mental health care provider organisations (trusts). Hypotheses tested were that, compared with the control group, the intervention group would experience: fewer compulsory admissions (primary outcome); fewer psychiatric admissions; shorter psychiatric stays; lower perceived coercion; improved therapeutic relationships; and improved engagement. We stratified participants by centre. The research team but not participants nor clinical staff were masked to allocation. 
569 participants were randomly assigned (285 to the intervention group and 284 to the control group). No significant treatment effect was seen for the primary outcome (56 [20%] sectioned in the control group and 49 [18%] in the JCP group; odds ratio 0·90 [95% CI 0·58-1·39, p=0·63]) or any secondary outcomes, with the exception of an improved secondary outcome of therapeutic relationships (17·3 [7·6] vs 16·0 [7·1]; adjusted difference -1·28 [95% CI -2·56 to -0·01, p=0·049]). Qualitative data supported this finding.



Our findings are inconsistent with two earlier JCP studies, and show that the JCP is not significantly more effective than treatment as usual. There is evidence to suggest the JCPs were not fully implemented in all study sites, and were combined with routine clinical review meetings which did not actively incorporate patients' preferences. The study therefore raises important questions about implementing new interventions in routine clinical practice.


 UK and the National Institute for Health Research.
Impact of an endothelial progenitor cell capturing stent on coronary microvascular function: comparison with drug-eluting stents

Although drug-eluting stents (DESs) effectively reduce restenosis following percutaneous coronary intervention (PCI), they also delay re-endothelialization and impair microvascular function, resulting in adverse clinical outcomes. Endothelial progenitor cell (EPC) capturing stents, by providing a functional endothelial layer on the stent, have beneficial effects on microvascular function. However, data on coronary microvascular function in patients with EPC stents versus DESs are lacking.



Seventy-four patients who previously underwent PCI were enrolled in this study. Microvascular function was evaluated 6 months after PCI based on the index of microvascular resistance (IMR) and the coronary flow reserve (CFR). IMR was calculated as the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of the hyperemic mean transit time (hTmn). The CFR was calculated by dividing the hTmn by the baseline mean transit time.



Twenty-one patients (age, 67.2 ± 9.6 years; male:female, 15:6) with an EPC stent and 53 patients (age, 61.5 ± 14.7 years; male:female, 40:13) with second-generation DESs were included in the study. There were no significant differences in the baseline clinical and angiographic characteristics of the two groups. Angiography performed 6 months postoperatively did not show significant differences in their CFR values. However, patients with the EPC stent had a significantly lower IMR than patients with second-generation DESs (median, 25.5 [interquartile range, 12.85 to 28.18] vs. 29.0 [interquartile range, 15.42 to 39.23]; p = 0.043).



Microvascular dysfunction was significantly improved after 6 months in patients with EPC stents compared to those with DESs. The complete re-endothelialization achieved with the EPC stent may provide clinical benefits over DESs, especially in patients with microvascular dysfunction.
Predictors of treatment outcome in adults with ADHD treated with OROS<ce:sup loc=post>®</ce:sup> methylphenidate

We conducted a post-hoc analysis of the Long-Acting MethylpheniDate in Adult attention-deficit hyperactivity disorder (LAMDA) study to investigate predictors of response in adults with ADHD randomly assigned to Osmotic Release Oral System (OROS)(®)-methylphenidate hydrochloride (MPH) 18, 36 or 72 mg or placebo.



LAMDA comprised a 5-week, double-blind (DB) period, followed by a 7-week, open-label (OL) period. A post-hoc analysis of covariance and a logistic regression analysis were undertaken to detect whether specific baseline parameters or overall treatment compliance during the double-blind phase contributed to response. The initial model included all covariates as independent variables; a backward stepwise selection method was used, with stay criteria of p<0.10. Six outcomes were considered: change from baseline CAARS:O-SV (physician-rated) and CAARS:S-S (self-report) scores at DB and OL end points, and response rate (≥30% decrease in CAARS:O-SV score from baseline) and normalization of CAARS:O-SV score at DB end point.



Taking into account a significant effect of OROS(®)-MPH treatment versus placebo in the original analysis (p≤0.015), across the outcomes considered in this post-hoc analysis, higher baseline CAARS scores were most strongly predictive of superior outcomes. Male gender and lower academic achievement were also predictive for improved results with certain outcomes.



Several baseline factors may help to predict better treatment outcomes in adults receiving OROS(®)-MPH; however, further research is required to confirm these findings and examine their neurobiological underpinnings.
Patterns of relapse in extrapulmonary small cell carcinoma: retrospective analysis of outcomes from two cancer centres

We conducted a retrospective review of patients with extrapulmonary small cell carcinomas (EPSCCs) to explore the distribution, treatments, patterns of relapse and outcomes by primary site.



We have reviewed the outcomes of one of the largest data sets of consecutive patients with EPSCC identified from two major cancer centres.



Consecutive patients with a histopathological diagnosis of EPSCC from the two institutions were retrospectively identified.



Outcomes were evaluated including stage at presentation, treatments given, sites of relapse, time to distant relapse, progression-free survival and overall survival (OS).



From a total 159 patients, 114 received first-line chemotherapy, 80.5% being platinum-based. Response rate was 48%. Commonest primary sites were genitourinary and gynaecological. 44% of patients presented with metastatic disease. 55.9% relapsed with liver the commonest site, whereas only 2.5% developed brain metastases. Median OS was 13.4 months for all patients, 7.6 months and 19.5 months for those with metastatic and non-metastatic disease, respectively. Gynaecological and head and neck patients had significantly better OS compared to gastrointestinal patients.



EPSCCs demonstrate high response rates to chemotherapy and high rates of distant metastases. Primary sites may influence prognosis, and survival is optimal with a radical strategy. Brain metastases are rare and we therefore do not recommend prophylactic cranial irradiation.