tbuckley/cabot-search huggingface dataset:
Development and Validation of Modified Disease Activity Scores in Rheumatoid Arthritis: Superior Correlation With Magnetic Resonance Imaging–Detected Synovitis and Radiographic Progression
Authors: Joshua F. Baker, Philip G. Conaghan, Josef S. Smolen, Daniel Aletaha, Justine Shults, Paul Emery, Daniel G. Baker, Mikkel Østergaard
Journal: Arthritis & Rheumatology (2013)

Objective To develop and validate composite disease activity scores, based on widely available clinical measures, that would demonstrate improved correlation with detection of synovitis on magnetic resonance imaging (MRI) and radiographic progression, in comparison with conventional measures, in patients with rheumatoid arthritis (RA). Methods This study was conducted as a secondary study of 2 RA clinical trials, GO‐BEFORE (development cohort) and GO‐FORWARD (validation cohort). Generalized estimating equations were used to evaluate independent cross‐sectional associations of component variables (from all time points) with concurrent MRI measures of synovitis and bone edema in the development cohort. Based on regression coefficients, modified versions of the Disease Activity Score in 28 joints (M‐DAS28), Simplified Disease Activity Index (M‐SDAI), and Clinical Disease Activity Index (M‐CDAI) were generated for each subject in the validation cohort. The M‐DAS28, M‐SDAI, and M‐CDAI scores were compared to conventional scores of disease activity with regard to associations with MRI measures of synovitis and radiographic progression, assessed using Pearson's and Spearman's correlations, linear/logistic regression, and receiver operating characteristic analysis. Results Four variables were independently associated with MRI‐detected synovitis and bone edema in the development cohort: C‐reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), swollen joint count in 28 joints (SJC28), and evaluator's global assessment of disease activity using a visual analog scale (EvGA score). Modified disease activity scores were generated using the regression coefficients obtained in the synovitis models for all subjects in the validation cohort; modified scores were calculated as M‐DAS28 = 0.49 × ln(CRP) + 0.15 × SJC28 + 0.22 × EvGA + 1 and M‐SDAI = CRP + SJC28 + EvGA. Both modified and conventional disease activity scores correlated significantly with MRI measures of synovitis. Modified scores showed superior correlation with synovitis, as compared to conventional scores, at all time points ( P &lt; 0.05). Furthermore, the M‐DAS28 and M‐SDAI had superior test characteristics for prediction of radiographic progression at 52 weeks (both P &lt; 0.05). Conclusion Modified disease activity scores demonstrated superior correlation with MRI detection of synovitis at all time points, and more accurately predicted radiographic progression in patients with RA in a clinical trial setting.
HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis
Authors: May Mt, Sterne Ja, Costagliola D, Sabin Ca, Phillips An, Justice Ac, Dabis F, Gill J, Lundgren J, Hogg Rs, de Wolf F, Fätkenheuer G, Staszewski S, d'Arminio Monforte A, Egger M
Journal: The Lancet (2006)
Effect of environmental pollution on the control of bronchial asthma and fractional exhaled nitric oxide (FeNO)
Authors: Miguel Ariza, Ramon Fernandez, Gagatek Sebastian, Marta Iscar, Claudia Madrid, Ana Pando, Mariangeles Montoliu, Pere Casan
Journal: European Respiratory Journal (2013)

Objective: Study the impact that might have the environmental contaminants in the clinical control of asthmatic patients in stable condition.

PATIENTS AND METHODS: (April-August 2012) We recruited from the pulmonary function laboratory, asthmatic patients who came to perform lung function tests for its control. We included patients without exacerbations or need for therapeutic changes in the past four weeks, and that had in the vicinity of their usual housing a measurement point of pollutants (MPP). We analyzed the age, gender, body mass index, smoking, usual treatment, presence of pollutants at home and sensitization to aeroallergens.We localized the patients geographically by their postal code and selected the nearest MPP. The measured pollutants were: particles larger than 10 microns in diameter, ozone and nitrogen dioxide.

RESULTS: 77 cases. Mean age: 33 (19), 46 women (60 %). The mean values of the data analyzed were: FEV1 88% (SD 14), ACT 15.36 (SD 7.47), FeNO 30 ppb (SD 25.7), BMI 26.43 (SD 5.94), 9 patients (12.3%) were active smokers, 63 patients (84%) were receiving treatment with inhaled steroids and 19 patients (25.3%) used anti-leukotrienes. Presence of pollutants were found in 60% of the houses. The correlation study showed significant association between the values of the ACT with the NO2 measured the day of the interview and with the mean values of NO2 of the previous month, and the value of FeNO with the O3 measured the day of the test. There was no association between the rest of the pollutants and the values of ACT, FeNO or lung function.

CONCLUSION:The NO2 seems to be the pollutant most related to the control of the asthma patient not exacerbated.
Extended-Release Guanfacine for Hyperactivity in Children With Autism Spectrum Disorder
Authors: Lawrence Scahill, James T. McCracken, Bryan H. King, Carol Rockhill, Bhavik Shah, Laura Politte, Roy Sanders, Mendy Minjarez, Jennifer Cowen, Jennifer Mullett, Chris Page, Denise Ward, Yanhong Deng, Sandra Loo, James Dziura, Christopher J. McDougle
Journal: American Journal of Psychiatry (2015)

Hyperactivity, impulsiveness, and distractibility are common problems in children with autism spectrum disorder (ASD). Extended-release guanfacine is approved for children with attention deficit hyperactivity disorder but not well studied in ASD.In a multisite, randomized clinical trial, extended-release guanfacine was compared with placebo in children with ASD accompanied by hyperactivity, impulsiveness, and distractibility.Sixty-two subjects (boys, N=53; girls, N=9; mean age=8.5 years [SD=2.25]) were randomly assigned to guanfacine (N=30) or placebo (N=32) for 8 weeks. The guanfacine group showed a 43.6% decline in scores on the Aberrant Behavior Checklist-hyperactivity subscale (least squares mean from 34.2 to 19.3) compared with a 13.2% decrease in the placebo group (least squares mean from 34.2 to 29.7; effect size=1.67). The rate of positive response (much improved or very much improved on the Clinical Global Impression-Improvement scale) was 50% (15 of 30) for guanfacine compared with 9.4% (3 of 32) for placebo. A brief cognitive battery tapping working memory and motor planning showed no group differences before or after 8 weeks of treatment. The modal dose of guanfacine at week 8 was 3 mg/day (range: 1-4 mg/day), and the modal dose was 3 mg/day (range: 2-4 mg/day) for placebo. Four guanfacine-treated subjects (13.3%) and four placebo subjects (12.5%) exited the study before week 8. The most common adverse events included drowsiness, fatigue, and decreased appetite. There were no significant changes on ECG in either group. For subjects in the guanfacine group, blood pressure declined in the first 4 weeks, with return nearly to baseline by endpoint (week 8). Pulse rate showed a similar pattern but remained lower than baseline at endpoint.Extended-release guanfacine appears to be safe and effective for reducing hyperactivity, impulsiveness, and distractibility in children with ASD.
Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma
Authors: Kathryn M. Field, John Simes, Anna K. Nowak, Lawrence Cher, Helen Wheeler, Elizabeth J. Hovey, Christopher S.B. Brown, Elizabeth H. Barnes, Kate Sawkins, Ann Livingstone, Ron Freilich, Pramit M. Phal, Greg Fitt, Mark A. Rosenthal
Journal: Neuro-Oncology (2015)

The optimal use of bevacizumab in recurrent glioblastoma (GBM), including the choice of monotherapy or combination therapy, remains uncertain. The purpose of this study was to compare combination therapy with bevacizumab monotherapy. This was a 2-part randomized phase 2 study. Eligibility criteria included recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, and Eastern Cooperative Oncology Group performance status 0–2. The primary objective (Part 1) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival (PFS) using modified Response Assessment in Neuro-Oncology criteria. Bevacizumab was given every 2 weeks, 10 mg/kg; and carboplatin every 4 weeks, (AUC 5). On progression, patients able to continue were randomized to continue or cease bevacizumab (Part 2). Secondary endpoints included objective radiological response rate (ORR), quality of life, toxicity, and overall survival (OS). One hundred twenty-two patients (median age, 55y) were enrolled to Part 1 from 18 Australian sites. Median follow-up was 32 months, and median on-treatment time was 3.3 months. Median PFS was 3.5 months for each arm (hazard ratio [HR]: 0.92, 95% CI: 0.64–1.33, P = .66). ORR was 14% (combination) versus 6% (monotherapy) (P = .18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82–1.69, P = .38). The incidence of bevacizumab-related adverse events was similar to prior literature, with no new toxicity signals. Toxicities were higher in the combination arm. Part 2 data (n = 48) will be reported separately. Adding carboplatin resulted in more toxicity without additional clinical benefit. Clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies. ACTRN12610000915055.
The drug costs associated with COPD prescription medicine in Denmark
Authors: Peter Lange, Marie Jakobsen, Niels Anker, Jens Dollerup, Peter Bo Poulsen
Journal: European Respiratory Journal (2012)

Background:  Spirometric studies of the general population estimate that 430,000 Danes have chronic obstructive lung disease (COPD). COPD is mainly caused by smoking with smoking cessation being considered the most important intervention to prevent disease progression. Cost-of-illness of COPD in Denmark is significant. However, the use of prescription medicine for COPD has not been analysed for the Danish population.   Aim and objective:  Analyse the societal costs associated with prescription medicine for the treatment of COPD in Denmark.   Methods:  The study was designed as a nation-wide retrospective register study of the drug costs (ATC group R03) associated with COPD from 2001-2010. Data were retrieved from the Prescription Database and the National Patient Register. The population comprised individuals (40+ years) having had at least one prescription of medications (R03) with an indication code indicating COPD. Patients dying were included up to time of death. A societal perspective included both public reimbursement costs and co-payment. Costs were calculated in fixed 2010-prices using a Laypeyres price index (average treatment cost per DDD and DDD amount sold).   Results:  In the period 2001-2010, 292,646 individuals (40+ years) have had at least one prescription of R03 medication. Among these, 124,020 with a COPD diagnosis had been hospitalized, whereas 46,218 have not. The annual average drug cost (R03) was DKK 8,017 per patient (Euro 1,069) with a total average cost per year of 680 million DKK (91 million Euros).   Conclusions:  The annual costs of prescription medicine for COPD in Denmark are significant. For comparison smoking cessation treatment costs, i.e. the primary intervention towards COPD, are much lower.
The anti-proliferative effect of hydrogen sulfide upon human airway smooth muscle in COPD
Authors: Mark Perry, Alice Tu, Gurpreet Sehra, Ian Adcock, Fan Chung
Journal: European Respiratory Journal (2014)

Rationale   Hydrogen sulfide (H 2 S) has emerged as an important gaseous mediator in cellular physiology and pathology. We previously demonstrated that exposure of primary healthy human airway smooth muscle (ASM) cells to H 2 S “donors” inhibited proliferation and CXCL8 release. ASM mass is increased in COPD and these cells contribute to airway inflammation and remodelling by secreting inflammatory cytokines and self-regulation of proliferation. We previously demonstrated that ASM cells in COPD are hyperproliferative and release greater amounts of IL-6 and CXCL8. We investigated the effect of H 2 S on ASM proliferation and CXCL8 release in cell from COPD patients.   Methods   Human primary ASM cells were grown from age-matched healthy non-smokers, healthy smokers and COPD patients ( n  = 9 in each group). Cells were stimulated with TGF-β before treatment with the H 2 S donor NaSH. CXCL8 secretion, cell proliferation and cell viability was assessed. mRNA expression was examined by TaqMan RT-PCR.   Results   TGF-β-induced proliferation and CXCL8 release was inhibited to a greater extent by NaSH in ASM cells from healthy non-smokers compared to the effect on cells from healthy smokers and COPD patients. H 2 S production is dependent upon the enzyme cystathionine-β-synthase (CBS). CBS mRNA expression was reduced in ASM cells from patients with COPD.   Conclusions   Exogenously applied H 2 S can regulate ASM hyperproliferation and inflammatory mediator release from ASM cells in healthy smokers and patients with COPD. However, this effect is less than that seen in cells from healthy non-smokers. COPD cells lack CBS suggesting that the aberrant phenotype seen in these cells may be due to a lack of endogenous H 2 S production.
Intrapulmonary lipoma in children: A case report and literature review
Authors: Chunmei Zhu, Ling Cao
Journal: European Respiratory Journal (2012)

Objective: To help early diagnosis of lipoma in children by reporting a rare case of intrapulmonary lipoma in a child. Case presentation: A 13-month-old boy was hospitalized because of cough and fever. Physical examination revealed rales and wheezing over his lungs. Chest radiograph showed patchy infiltration and consolidation near his left hilar. Chest CT scan showed patchy infiltration and round-shape, hypodense homogeneous lesions located in the lower lobe of right lung without any calcification. After 19 days of antibiotics treatment, his clinic symptoms and signs disappeared, he underwent chest CT scan (Figure 1) again after treatment, and the result showed the patchy infiltration dissolved, however, the lesions in the lower lobe of right lung remained without any change.

![Figure][1] 



He was discharged. One month and one year later he was examined by chest MRI. The lesions were diagnosed as intrapulmonary lipoma by T2 weighted MRI images (Figure 2) with fat suppression.

![Figure][1] 



Conclusions: Intrapulmonary lipoma can also be identified in children. Chest CT scan and MRI are very important for making correct diagnosis.

 [1]: pending:yes
Hybrid Microgels with Thermo‐Tunable Elasticity for Controllable Cell Confinement
Authors: Sebastian Hackelbusch, Torsten Rossow, Dirk Steinhilber, David A. Weitz, Sebastian Seiffert
Journal: Advanced Healthcare Materials (2015)

Stimuli‐responsive hydrogels are able to change their physical properties such as their elastic moduli in response to changes in their environment. If biocompatible polymers are used to prepare such materials and if living cells are encapsulated within these networks, their switchability allows the cell–matrix interactions to be investigated with unprecedented consistency. In this paper, thermo‐responsive macro‐ and microscopic hydrogels are presented based on azide‐functionalized copolymers of poly( N ‐(2‐hydroxypropyl)‐methacrylamide) and poly(hydroxyethyl methacrylate) grafted with poly( N ‐isopropylacrylamide) side chains. Crosslinking of these comb polymers is realized by bio‐orthogonal strain‐promoted azide–alkyne cycloaddition with cyclooctyne‐functionalized poly(ethylene glycol). The resulting hybrid hydrogels exhibit thermo‐tunable elasticity tailored by the polymer chain length and grafting density. This bio‐orthogonal polymer crosslinking strategy is combined with droplet‐based microfluidics to encapsulate living cells into stimuli‐responsive microgels, proving them to be a suitable platform for future systematic stem‐cell research.
Keratin expression in the normal nail unit: markers of regional differentiation
Authors: D. De Berker, F. Wojnarowska, L. Sviland, G.E. Westgate, R.P.R. Dawber, I.M. Leigh
Journal: British Journal of Dermatology (2000)

Differentiation within the nail unit was examined using a range of antikeratin monoclonal antibodies including the recently described antibody LHTric-1, specific to the acidic hair-type keratin Ha1. Keratinocytes of the nail matrix, nail bed and the digit pulp were characterized by different patterns of keratin expression. Nail matrix was the sole site of expression of Ha1, which colocalized in suprabasal matrix epidermis with epidermal keratins K1 and K10. Small amounts of K17 were found at the apex of the matrix in some cases. K6 and K16 were found where the epidermal surface folds forwards to become the ventral aspect of the proximal nail fold. The nail bed was distinguished by the absence of hair-type keratin Ha1 and the absence of markers of cornified epidermis and mucosal differentiation K1/K10 and K4/K13, respectively, while K6, K16 and K17 were detected. The basal keratin conformation marker, LH6, was expressed suprabasally throughout the nail bed. This complement of keratins exists in the nail bed in the absence of notable proliferative activity, and suggests a state of minimally developed differentiation which may be afforded by the physical or biological properties of the overlying nail. Keratins, K6, K16 and K17 were all found in the digit pulp in limited amounts, possibly in association with the epidermal component of the eccrine duct. The simple epithelial keratins, K7, K8 and K18, were found in small amounts in the specimens from younger individuals, mainly in epibasal cells of the apex of the matrix and in putative Merkel cells.
Immunotherapy of Cancer With Nonliving Mycobacteria and Cord Factor (Trehalose-6,6′-dimycolate) in Aqueous Medium
Authors: A. Bekierkunst
Journal: JNCI Journal of the National Cancer Institute (1976)

Heat-killed BCG, cord factor (trehalose-6,6'-dimycolate), or killed BCG plus cord factor in aqueous medium, admixed with tumor cells and injected into the skin of guinea pigs, inhibited the growth of a hepatocellular carcinoma. Intralesional administration of killed BCG or Mycobacterium kansasii coated with cord factor, in the same medium, caused regression of established tumors in 48 and 45% of the treated animals, respectively.
Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia
Authors: Tim D.D. Somerville, Daniel H. Wiseman, Gary J. Spencer, Xu Huang, James T. Lynch, Hui Sun Leong, Emma L. Williams, Edmund Cheesman, Tim C.P. Somervaille
Journal: Cancer Cell (2015)
Shifting to Outpatient Care? Mental Health Care Use and Cost Under Private Insurance
Authors: Douglas L. Leslie, Robert Rosenheck
Journal: American Journal of Psychiatry (1999)

Concern over rising health care costs has put pressure on providers to reduce costs, purportedly by reducing inpatient care and increasing outpatient care.Inpatient and outpatient claims were analyzed for adult users of mental health services (180,000/year on average) from a national study group of 3.9 million privately insured individuals per year from 1993 to 1995. Costs and treatment days per patient were compared across diagnostic groups and stratified by whether patients were hospitalized.Inpatient mental health costs fell $2,507 (30.4%) over the period, driven primarily by decreases in hospital days per patient per year (19.9%), with smaller changes in the proportion of enrollees who received inpatient care (increase of 0.8%) and a decrease in per diem costs (9.1%). Outpatient mental health costs also declined over the period, falling 13.6% for patients also using inpatient services and 14.6% for patients receiving only outpatient care. Patients whose primary diagnosis was mild to moderate depression saw the largest decreases in inpatient cost per patient (42.8%); those diagnosed with schizophrenia experienced the smallest decrease (23.5%). For patients using outpatient services only, those diagnosed with substance abuse experienced the largest decrease in costs (23.5%); those diagnosed with schizophrenia experienced the smallest decrease (8.6%).Substantial cost reductions for mental health services are primarily a result of reductions in inpatient and outpatient treatment days. Declines in inpatient service use were not accompanied by increases in outpatient service use, even for severely ill patients requiring hospitalization. Managed care has not caused a shift in the pattern of care but an overall reduction of care.
Identification of Prognostic Factors in 61 Patients With Posttransplantation Lymphoproliferative Disorders
Authors: Véronique Leblond, Nathalie Dhedin, Marie-France Mamzer Bruneel, Sylvain Choquet, Olivier Hermine, Raphaël Porcher, Stéphanie Nguyen Quoc, Frédéric Davi, Frédéric Charlotte, Richard Dorent, Benoit Barrou, Jean-Paul Vernant, Martine Raphael, Vincent Levy
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Prognostic studies of posttransplantation lymphoproliferative disorders (PTLDs) are hindered by the small number of cases at each transplant center. We analyzed prognostic factors and long-term outcome according to clinical manifestations, pathologic features, and treatment and investigated the prognostic value of the non-Hodgkin’s lymphoma International Prognostic Index (IPI) in 61 patients with PTLD. PATIENTS AND METHODS: We studied 61 patients in two institutions who developed PTLD and analyzed factors influencing the complete remission and survival rates. RESULTS: In univariate analysis, factors predictive of failure to achieve complete remission were performance status (PS) ≥ (P = .0001) and nondetection of Epstein-Barr virus (EBV) in the tumor (P = .01). Only a negative link with PS ≥ 2 was observed in multivariate analysis. In univariate analysis, factors predictive of lower survival were PS ≥ 2, the number of sites (one v &gt; one), primary CNS localization, T-cell origin, monoclonality, nondetection of EBV, and treatment with chemotherapy. The IPI failed to identify a patient subgroup with better survival and was less predictive of the response rate than was a specific index using two risk factors (PS and number of involved sites), which defined three groups of patients: low-risk patients whose median survival time has not yet been reached, intermediate-risk patients with a median survival time of 34 months, and high-risk patients with a median survival time of 1 month. CONCLUSION: PS and the number of involved sites defined three risk groups in our population. The value of these prognostic factors needs to be confirmed in larger cohorts of patients treated in prospective multicenter studies.