tbuckley/cabot-search huggingface dataset:
Anxiety disorders in mid-adolescence: a community sample
Authors: J H Kashani, H Orvaschel
Journal: American Journal of Psychiatry (1988)

The authors report the 6-month period prevalence of anxiety disorders in a community sample of 150 adolescents 14 to 16 years old. Diagnoses were based on structured psychiatric interviews, DSM-III criteria, and a psychiatrist's review of the data. Additional measures of affect, self-concept, and coping were also obtained for all subjects. Seventeen percent of the adolescents met criteria for one or more anxiety diagnoses and 8.7% were identified as "cases" of anxiety disorder. A significant relationship was found between anxiety and depression. The authors discuss the distribution and expression of anxiety disorders among adolescents in the community.
Abstract 18371: Higher Treatment Persistence of Non-Vitamin K Antagonist Oral Anticoagulants than Vitamin K Antagonists at 1 Year in Non-Valvular Atrial Fibrillation in Real-World Practice
Authors: Carlos Martinez, Christopher Wallenhorst, Anja Katholing, Ben Freedman
Journal: Circulation (2014)

Introduction: Oral anticoagulants (OAC) are under-utilised in atrial fibrillation (AF). Even patients prescribed an OAC may stop taking the drug soon after treatment initiation, particularly with Vitamin K Antagonists (VKA). The Non-VKA OAC (NOAC) drugs offer greater ease of use, and persistence is likely to be higher. Aim: To determine persistence on treatment in the first year after inception of NOACs and VKA in incident AF in real-world clinical practice. Methods: We studied 24,467 OAC-naïve patients with incident non-valvular AF diagnosed between Jan 2011-Feb 2014, mean age 73.9 ± 12.5, 45.6% female, in a very large UK primary care database (Clinical Practice Research Datalink, CRPD), with full linkage to medication use. Follow up was for a mean of 1.2 ± 0.9 years. The proportion of OAC initiation in the 90 days after first-time AF and of those remaining on OAC one year after initiation were estimated using competing risk survival analyses censoring for use of alternative OAC. Results: NOAC drugs prescribed included Rivaroxaban, Dabigatran and Apixaban. Overall, 12,579 (51.4%) were commenced on an OAC: 11,888 on VKA and 691 on NOAC, within 90 days after incident AF. Amongst all OAC users, the proportion taking NOAC increased from 0.3% in 2011 to 12.3% in 2014. Persistence, defined as the proportion still taking the OAC after one year, declined over the 12 months to 54.3% for VKA and 80.7% for NOAC (Table). Persistence was significantly greater for NOAC than VKA at all time points. Conclusions: There is a progressive fall in VKA use amongst OAC naïve patients with AF in real-world practice to only 54% at 1 year. This contributes to under-utilisation of anticoagulation in AF and would result in an increased rate of stroke. Persistence was significantly improved with NOACs compared to VKA, and this factor alone could lead to reduced stroke burden with increasing uptake of the NOACs.
Impaired Suppressive Capacity of Activation‐Induced Regulatory B Cells in Systemic Lupus Erythematosus
Authors: Nele Gao, Julia Dresel, Volker Eckstein, Rimma Gellert, Hannah Störch, Ram K. C. Venigalla, Vedat Schwenger, Regina Max, Norbert Blank, Hanns‐Martin Lorenz, Theresa Tretter
Journal: Arthritis & Rheumatology (2014)

B cells with immunoregulatory properties (Breg cells) have been described in mice, but their role in the control of human immune responses is not well defined. We recently identified a human population of activated FSC(high) B cells that exhibited regulatory activity toward T helper cells. The aim of the present study was to test such induced Breg (iBreg) cells in patients with autoimmune disease. Purified CD19+FSC(high) B cells derived from patients with systemic lupus erythematosus (SLE) or from healthy donors, which were activated via their B cell receptor, were cocultured with CD3-stimulated CD4+ T helper cells from SLE patients or healthy donors. (3) H-thymidine incorporation, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were used to analyze proliferation, cytokine secretion, and surface marker expression. Although under costimulatory conditions, FSC(high) SLE B cells supported the proliferation of healthy donor T cells to a similar extent as donor B cells, their regulatory function was significantly diminished in B cell suppressor assays. Similar effects were seen when SLE T cells were used, confirming that SLE T cells were equally susceptible to iBreg cell signals as healthy donor T cells and that SLE iBreg cell defects were independent of T cell origin. B cell viability and expression of surface markers (CD25, CD80, and B7-H1) or cytokines (interleukin-6 [IL-6], tumor necrosis factor α, and IL-10) were comparable in the two B cell populations. There was no correlation between the extent of iBreg cell-induced inhibition and disease activity. CD19+FSC(high) B cells from patients with another systemic autoimmune disease, granulomatosis with polyangiitis (Wegener's) (GPA), exhibited no regulatory defects, which suggests that the iBreg cell defects were SLE-specific and not a general consequence of autoimmunity or inflammation. Induced Breg cells from SLE patients, but not GPA patients, are less effective in the control of T helper cell proliferation, which supports the reported skewed B cell repertoire in SLE. The malfunctioning SLE iBreg cells might allow the overstimulation of immune responses and contribute to the initiation and/or perpetuation of disease.
Abstract 3717: Therapeutic strategies to overcome the crizotinib resistance in ROS1-rearranged lung cancers
Authors: Ryohei Katayama, Yuka Kobayashi, Sumie Koike, Naoya Fujita
Journal: Cancer Research (2014)

Abstract ROS1 fusion oncogene represent a novel molecular target in a small subset of non-small cell lung cancers (NSCLC).The ROS1 fusion oncogene, such as CD74-ROS1, leads to constitutive ROS1 activation with potent transforming activity. In the ongoing phase 1 clinical trial, the response rate of crizotinib, ALK/MET/ROS1 tyrosine kinase inhibitor (TKI), in the patients with NSCLC harboring ROS1 fusions was around 60%. However, despite crizotinib has shown remarkable initial responses, cancers eventually develop resistance to crizotinib. In a recent report of a clinical resistance to crizotinib, G2032R mutation in ROS1 kinase domain was identified, which is analogous to the G1202R mutation found in crizotinib-resistant ALK-rearranged lung cancers. To further identify the mechanism of resistance to crizotinib in ROS1 fusion positive NSCLC, we established a model of acquired resistance by ENU mutagenesis screening using CD74-ROS1 addicted Ba/F3 cell line models. As the results, we identified several novel crizotinib resistance mutations including G2032R mutation. To overcome the resistance, we performed the drug screening with small molecular inhibitors, and identified several inhibitors including Foretinib, cMET/VEGFR inhibitor, effectively inhibit the survival of CD74-ROS1 expressing cells. Furthermore, we also identified that some of those inhibitors can overcome the resistance caused by G2032R mutation. Thus, we have developed a comprehensive model of acquired resistance to crizotinib in ROS1 fusion harboring NSCLC and identified therapeutic strategies to overcome the resistance. Citation Format: Ryohei Katayama, Yuka Kobayashi, Sumie Koike, Naoya Fujita. Therapeutic strategies to overcome the crizotinib resistance in ROS1-rearranged lung cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3717. doi:10.1158/1538-7445.AM2014-3717
Association of angiotensin‐converting enzyme inhibitor‐associated angioedema with transplant and immunosuppressant use
Authors: J. B. Byrd, A. Woodard‐Grice, E. Stone, A. Lucisano, H. Schaefer, C. Yu, A. E. Eyler, N. E. Salloum, N. J. Brown
Journal: Allergy (2010)

To cite this article: Byrd JB, Woodard‐Grice A, Stone E, Lucisano A, Schaefer H, Yu C, Eyler AE, Salloum NE, Brown NJ. Association of angiotensin‐converting enzyme inhibitor‐associated angioedema with transplant and immunosuppressant use. Allergy 2010; 65 : 1381–1387. Abstract Background: Immunosuppressants decrease circulating dipeptidyl peptidase IV (DPPIV) activity in transplant patients, and decreased DPPIV activity has been associated with angiotensin‐converting enzyme (ACE) inhibitor‐associated angioedema. One study has reported an increased incidence of ACE inhibitor‐associated angioedema among transplant patients compared to published rates, while several case series report angioedema in patients taking specific immunosuppressant agents. Objective: To test the hypothesis that transplant patients are at increased risk of ACE inhibitor‐associated angioedema. Methods: We assessed the proportion of transplant patients in 145 cases with ACE inhibitor‐associated angioedema and 280 ACE inhibitor‐exposed controls. We measured the relationship between case–control status, transplant status, and immunosuppressant use and circulating DPPIV activity. We also assessed the incidence of angioedema among consecutive patients who underwent renal or cardiac transplant and were treated with an ACE inhibitor. Results: Transplant patients were significantly overrepresented among ACE inhibitor‐associated angioedema cases compared to controls (odds ratio 18.5, 95% CI 2.3–147.2, P = 0.0004). Immunosuppressant use, chronic renal failure, seasonal allergies and smoking were also associated with ACE inhibitor‐associated angioedema in univariate analysis. The association of transplant status with ACE inhibitor‐associated angioedema was no longer significant after inclusion of immunosuppressant therapy in a multivariate analysis. Dipeptidyl peptidase IV activity was significantly decreased in sera from cases compared to ACE inhibitor‐exposed controls, as well as in individuals taking immunosuppressants. Two of 47 ACE inhibitor‐treated renal transplant patients and one of 36 ACE inhibitor‐treated cardiac transplant patients developed angioedema. Conclusion: Transplant patients are at increased risk of ACE inhibitor‐associated angioedema possibly because of the effects of immunosuppressants on the activity of DPPIV.
Dramatic response to topical timolol lotion of a large hemifacial infantile haemangioma associated with PHACE syndrome
Authors: N. Khunger, M. Pahwa
Journal: British Journal of Dermatology (2010)

Funding sources: none. Conflicts of interest: none declared. Madam, The PHACE syndrome is an uncommon condition seen in a subgroup of children, particularly associated with large segmental facial haemangiomas. It is an acronym coined by Frieden et al.1 for the association of Posterior fossa defects, Haemangiomas, Arterial anomalies, Cardiac defects and Coarctation of the aorta, and Eye anomalies. The ‘S’ in PHACES syndrome signifies associated Sternal clefting and/or Supraumbilical raphe. The haemangiomas associated with PHACE syndrome are typically large, prone to ulceration, and generally require treatment. Traditional treatment options for haemangiomas include observation, systemic and intralesional corticosteroids, interferon alfa‐2a, vascular lasers, sclerotherapy, embolization, immunomodulators and surgery.2 3–4 The first use of a beta blocker, oral propranolol, for infantile haemangiomas was reported in 2008.5 However, systemic propranolol carries a risk of serious adverse effects including bradycardia, arrhythmias, hypotension and hypoglycaemia.6 Children with PHACES syndrome may have cerebrovascular anomalies and oral propranolol can be a contraindication in these patients owing to the risk of cerebral ischaemia.6 The use of another beta blocker, topical timolol, was reported in the treatment of a thin eyelid haemangioma.7 To the best of our knowledge, this therapy has not been previously reported in the treatment of a large ulcerating haemangioma with PHACE syndrome.
Pilot study of effectiveness of home rehabilitation for homebound patients with severe COPD
Authors: David Coultas, John Sloan, Dan Willson
Journal: European Respiratory Journal (2011)

Introduction: While pulmonary rehabilitation is efficacious, available evidence is not generalizable to patients who are homebound with severe impariment.

Objective: To test the effectiveness of home-based rehabilitation for homebound patients with physician-diagnosed COPD and severe functional impairment.

Methods: Homebound patients, defined as not driving independently and requiring taxing effort to leave home, were enrolled from primary care and pulmonary clinics. Patients were randomly assigned to one of two interventions comprised of education and physical therapy emphasizing either aerobic activity (A) or strengthening (S). The interventions were delivered over 8 weeks with up to 20 sessions. Pre- and post-intervention outcome measures were collected at 8 and 16 weeks using the Chronic Respiratory Questionnaire (CRQ) and 2-minute walk distance (2MWD).

Results: Of 41 patients enrolled 24 completed the 8 week intervention period with mean age 74.4 (SD 10.7) years, 45.8% female, FEV1 0.75L [30% predicted]). Baseline 2MWDs (mean, SD) were 56.0m (23.3) and 69.3m (34.0) for groups A and S, respectively. After 16 weeks all CRQ domains improved in both groups with the largest improvements in CRQ-dyspnea (A=1.85 [p=0.02] and S=2.21 [p=0.003]). Overall, the proportion of patients reporting clinically significant improvements in CRQ-dyspnea was 80% in group A and 71% in group S. Moreover, 2MWD increased in Group A but declined in Group S.

Conclusions: These results suggest that among homebound patients with severe COPD 8-weeks of either aerobic or strength training are effective for improving quality of life, but aerobic training may be needed to improve walking distance.
Smoking Cessation—Reply
Authors: Steven A. Schroeder
Journal: JAMA (2005)

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Abstract 673: A Monoclonal Antibody, MORAb-075, Targeting Claudin-3 &amp; Claudin-4 Inhibits human ovarian, pancreatic and prostate cancer progression in mice
Authors: Jian-Min Lin, allis soto, Christopher maddage, earl Albone, yuhong zhou, luigi grasso
Journal: Cancer Research (2014)

Abstract Claudin (CLDN) is a family of integral membrane proteins. They are crucial for tight junction formation and functions. Studies have found CLDN3 and CLDN4 proteins are overexpressed in majority of primary ovarian, prostate, and pancreatic cancers. We have generated a rat-human chimeric monoclonal antibody, MORAb-075, which binds to CLDN3 and CLDN4 with high affinity in vitro. In order to evaluate its therapeutic potential in vivo, we have established a number of human cancer models where the tumors are grown orthotopically in nude mice. These tumors were confirmed positive for human CLDN3 or/and CLDN4 expressions via immunohistochemistry staining. The models include a CLDN3/4-expressing prostate cancer PC-3; a CLDN4-expressing pancreatic cancer, BxPc-3; a CLDN3-expressing ovarian cancer, IGROV-1. In these orthotopic tumor models, MORAb-075 demonstrated significant antitumor activities. When the mAb was administered intravenously at 25 mg/kg, twice weekly for 4 weeks, the tumor growth inhibition (TGI) of PC-3 tumors reached 50%; TGI of BxPC-3 tumors was nearly 60% and TGI of IGROV-1 tumors was greater than 75%. Our findings demonstrate the potency of MORAb-075, as a single agent, in inhibiting solid tumor growth in these models. These results suggest that mAb therapy targeting CLDN3 &amp; CLDN4 is a valuable option for therapeutic application in cancer therapy that may be improved in combination with standard of care chemotherapies for CLDN3 or CLDN4 positive cancers. Citation Format: Jian-Min Lin, allis soto, Christopher maddage, earl Albone, yuhong zhou, luigi grasso. A Monoclonal Antibody, MORAb-075, Targeting Claudin-3 &amp; Claudin-4 Inhibits human ovarian, pancreatic and prostate cancer progression in mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 673. doi:10.1158/1538-7445.AM2014-673
Copying letters to patients
Authors: G. K Murray
Journal: BMJ (2003)

Editor—From April 2004 patients will receive copies of all correspondence between clinicians working in the NHS as a matter of course.1,2 Previous research supports the view reported in Eaton's news item that patients appreciate this practice3–5; however, the way its national introduction will affect doctors' work is much less clear. We audited how psychiatrists' practice is affected when letters are to be copied to patients.

All 76 new patients who attended two general psychiatry outpatient clinics (one rural, one inner city) from January 2002 to July 2002 were included in the pilot study, as were all eight psychiatrists who worked in these clinics during this time. After the assessment patients were sent a copy of the psychiatrist's letter to the general practitioner and asked to complete a short questionnaire on their evaluation of the letter. Psychiatrists were asked whether anything of importance had been omitted from the letter that they would usually have included, and if so, the reason and how the omitted information would be communicated to general practitioners.

Fifty six of the 76 letters (74%) were sent to the patient in an unaltered form (table). In three cases the psychiatrists thought it inappropriate for the patient to receive a copy of the letter, citing concerns over patients' distress. In 17 cases clinicians made omissions, mainly of parts of the history. Sixteen of these 17 patients were treated by just two of the eight doctors. 

Reasons cited for omission were fear of distressing the patient (14 instances), concern about people other than the patient having access to information (four instances), and protection of information supplied by third parties (two instances). General practitioners were informed of the omitted information, either by letter or in person.

Forty patients (55%) responded to the questionnaires. Most patients (33 out of 40) wished to continue receiving copies of correspondence.

Sending patients a copy of the letter to the general practitioner after a psychiatric consultation is valued and appreciated by patients; some doctors are, however, worried about distressing patients by what they write and consequently tend to omit information. Some training and reassurance about this practice may be needed before implementation.
Abstract 18096: Screening of Abdominal Aortic Aneurysm during Transthoracic Echocardiography
Authors: Takao Kato, Masahiro Kimura, Moritoshi Funasako, Eisaku Nakane, Toshiaki Izumi, Tetsuya Haruna, Moriaki Inoko
Journal: Circulation (2014)

Introduction: We previously reported that the prevalence of abdominal aortic aneurysm (AAA) in patients who underwent scheduled transthoracic echocardiography (TTE) was higher than that of AAA in patients who underwent abdominal ultrasonography (AUS). However, the patient backgrounds differed significantly between the two groups. Hypothesis: We hypothesized TTE detected AAA as similarly as AUS, one of standard methods for the screening of AAA. Methods: A total of 7,619 patients who were scheduled for TTE from 2009 to 2010 in our hospital were prospectively included. The abdominal aorta was evaluated at the end of the routine protocol. All patients who received scheduled abdominal ultrasonography (AUS) during the same period, a total of 15,433 patients, were included. The patients with known AAA and those without consent were excluded. In order to compare the TTE group to AUS group, we developed a propensity score for profiles of patients who received TTE or AUS for potential confounding bias. Specifically, a multivariate logistic regression model was fit with TTE or AUS as a dependent variable, which included age, sex, numbers of comorbidities, and the presence of each comorbidity. Consequently, 4,388 patients in each group were matched for analyses. Results: In propensity-matched patients, AAA was detected in 59 patients of TTE group and 48 patients of AUS group and the prevalence of the detection of AAA was not different between TTE and AUS (p=0.331). Positive associations were observed between AAA detected and male sex (adjusted odds ratio [OR], 3.25; 95% CI, 2.05-5.15; P&lt;.001), older age (adjusted OR, 1.029; 95% CI, 1.01-1.046; P&lt;.001), having ischemic heart disease (adjusted OR, 1.78; 95% CI, 1.04-3.03; P=0.033), and having hypertension (adjusted OR, 2.16; 95% CI, 1.38-3.38; P=001). Conclusions: TTE detected AAA as similarly as AUS. This result suggested that additional examination of the abdominal aorta during scheduled TTE was efficient for the screening of AAA.
Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis
Authors: Yaoqin Gong, Deborah Krakow, Jose Marcelino, Douglas Wilkin, David Chitayat, Riyana Babul-Hirji, Louanne Hudgins, Cor W. Cremers, Frans P.M. Cremers, Han G. Brunner, Kent Reinker, David L. Rimoin, Daniel H. Cohn, Frances R. Goodman, William Reardon, Michael Patton, Clair A. Francomano, Matthew L. Warman
Journal: Nature Genetics (1999)
Abstract 12564: Nitric Oxide Production and Endothelium-dependent Vasorelaxation Induced by 1-methylnicotinamide in Human Blood Vessels
Authors: Teresa B Domagala, Agata Szeffler, Lawrence W Dobrucki, Magdalena Leszczynska-Wiloch, Katarzyna Kotula-Horowitz, Andrzej Szczeklik, Leszek Kalinowski
Journal: Circulation (2010)

Background: Until recently N1-methylnicotinamide (MNA+) has been believed to be a biologically inactive product of nicotinamide metabolism in the pyridine nucleotides pathway. Latest observations s...