tbuckley/cabot-search huggingface dataset:
Light therapy of late luteal phase dysphoric disorder: an extended study
Authors: B L Parry, A M Mahan, N Mostofi, M R Klauber, G S Lew, J C Gillin
Journal: American Journal of Psychiatry (1993)

Nineteen patients with late luteal phase dysphoric disorder (LLPDD) and 11 healthy comparison subjects underwent a 3-month crossover trial of bright (more than 2500 lux) white morning, bright white evening, and placebo dim (less than 10 lux) red evening light, administered daily for 1 week during the premenstrual phase of the menstrual cycle. All light treatments significantly reduced depressive ratings from baseline levels.
Getting the cost right in cost-effectiveness analyses
Authors: N Wolff, T W Helminiak, J K Tebes
Journal: American Journal of Psychiatry (1997)

The authors examined different ways of measuring unit costs and how methodological assumptions can affect the magnitude of cost estimates and the ratio of treatment costs in comparative studies of mental health interventions. Four methodological choices may bias cost estimates: study perspective, definition of the opportunity cost of resources, cost allocation rules, and measurement of service units.Unit costs for outpatient services, individual therapy, and group therapy were calculated under different assumptions for a single community mental health center (CMHC). Using hypothetical service utilization profiles, the authors used the unit costs to calculate the costs of mental health treatments provided by two programs of the CMHC.The unit costs for an hour of outpatient services ranged from $108 to $538. The unit costs for an hour of therapy varied by 156%; unit costs were lowest if the management perspective was assumed and highest if the economist perspective was assumed. The ratio of the outpatient costs in the two treatment programs ranged from 0.6 to 1.8.The potential errors introduced by methodological choices can bias cost-effectiveness findings based on randomized control trials. These errors go undetected because crucial methodological information is not reported.
More pages should be given to obituaries
Authors: T. Hypher
Journal: BMJ (1995)

EDITOR,—The BMA is an association of doctors, and the BMJ therefore carries a responsibility to publish the obituaries of its members. This is not the case for the Lancet, which is merely a journal. A list of deaths would be insufficient, for it is the details of the lives and achievements that members wish to read. Equally importantly, the publication of the obituary is an important element of the mourning process for the relatives of many of the people who have died.

Liz Crossan and Richard …
<i>PIK3CA</i> mutations in primary HER2-positive and triple negative breast cancer.
Authors: Sibylle Loibl, Carsten Denkert, Sherene Loi, Fabrice Andre, Berit Mueller, Andreas Schneeweiss, Jens U. Blohmer, Christian Jackisch, Guo Sanxing, Stephan Gade, Peter A. Fasching, Christian Schem, Christos Sotiriou, Michael Untch, Gunter Von Minckwitz
Journal: Journal of Clinical Oncology (2013)

11061 Background: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer (BC), PIK3CA mutations being the most common. Mutations are frequently found in hot-spots located in the helical and kinase domains (exons 9 and 20). Reported data is discrepant with regard to prognostic or predictive value of PIK3CA mutations especially in HER2+ve BC. We therefore investigated the frequency and prognostic associations of PIK3CA mutations in HER2+ve and triple negative (TN) primary BC by treated with neoadjuvant therapy. Methods: We prospectively evaluated PIK3CA mutations in the 595 participants of the neoadjuvant Geparsixto study (NCT01426880). The study investigates the effect of adding carboplatin to a liposomal doxorubicin/taxane combination for the treatment of patients with HER2+ve and TN primary BC. All HER2+ve patients received trastuzumab and lapatinib, the TN patients received bevacizumab. HER2, hormone receptors (HR), and Ki67 were centrally assessed. PIK3CAwas genotyped in tumor material from formalin-fixed, paraffin embedded core biopsies taken before therapy using classical Sanger sequencing of exon 9 and 20. Results: From 09/2011 to 11/2012, 595 patients with HER2+ve or TN primary BC have been randomized in the Geparsixto study. Median age was 47 years (range 21-78); most tumors were cT2 (65%); cN0 (57%); ductal invasive (93%), grade 3 (65%); within the HER2+ve group 28% were HR positive. So far, PIK3CA genotype was evaluated in 395 randomized patients - 176 with HER2+ve and 219 with TN disease. Overall, 11.1% were found to have at least one mutation, in HER2+ve: 18.2% and TN BC: 5.5%. An exon 9 mutation was detected in 6.3% of the HER2+ve and 2.7% of the TNBC cases and an exon 20 mutation in 11.9% of the HER2+ve and 3.6% of the TN cases. A mutation in both exons was detected in 2 TN cases. PIK3CAmutations were more frequent in the HER2+ve/HR+ve compared to the HER2+ve/HR-ve group: 22.8% vs 10.6% respectively (p=0.047). Conclusions: PIK3CAmutations are more frequent in HER2+ve then in TN BC which is in line with previous reports. Results on all 595 patients and the correlation with response to therapy (pCR) will be presented at the meeting. The project has been funded within the EU-FP7 project RESPONSIFY No 278659. Clinical trial information: NCT01426880.
Comparative efficacy trials with no placebo group cannot determine efficacy
Authors: C.-W. C. Lin, R. O. Day, I. Harris, C. G. Maher, A. McLachlan
Journal: BMJ (2015)

Cohen and colleagues’ trial of epidural steroids versus gabapentin in patients with lumbosacral radicular pain found no significant difference in the primary outcome.1 There are several problems with their conclusion that a trial with neuropathic drugs might be a first line treatment option. 

Given the lack of a difference between treatment groups, there was no justification for endorsing one treatment over the other. In addition, the trial did not study first line treatment. All …
Singapore tissue network in supporting biomedical research in Singapore
Authors: Tzer Jing Seng, Adrian Pereira, Catherine Phua, Chai Lim Ng, Sharmila Baskaran Nayar, Daphne Donough, Alan Ching, Jun Hao Tan, Ja'far Sadiq, Lee Yan Lim, Wei Yun Heng, Hou Liang Seah, Shiun Han Chew, Daniel Tan, Edison Liu
Journal: Clinical Cancer Research (2007)

B71   The Singapore Tissue Network (STN) is the national bio-repository in facilitating translational and population research in Singapore. Our processes include collection, processing, storage and distribution of human samples while adhering strictly to our quality policy and standard operating procedure in achieving the highest quality. Samples are collected under strict ethical processes with informed consent and confidentiality. Samples archived at STN are used by researchers across the nation to further the advances of biomedical science.  To date, STN has worked on a total of 22 completed and on-going projects. This includes disease specific (e.g., Dengue, Psoriasis, Schizophrenia), cohort study (Singapore Malay Eyes, Diabetic, Multi-Ethic), and cancer tissue collection. The number of biospecimens stored at STN has increased exponentially from 326 (in 664 storage vials) in year 2003 to 37,058 (114,422 storage vials) in July 2007, and the number continue to grow.  Like other biobanks, STN faces many challenges in the biobanking operation. These challenges lead STN to embark on several strategic planning, including maintaining an efficient way of keeping track of samples and the associated clinical data, quality assurance management and quality control of samples, improving on sample processing, storage and distribution logistic, and maintaining a technologically advanced facility.  By adhering to the highest quality standards and with strict adherence to our organizational objectives, timeliness, professionalism and conformance to the Code of Ethics, STN has achieved the ISO9001:2000 certification and is now an internationally recognized biobank. STN shall continue to improve on biobanking processes in support of biomedical research in Singapore.
Abstract A37: MSI is not an important feature in early onset pancreatic carcinoma
Authors: Monica AJ Van Zanten, Marlies JE Kempers, Marjolijn JL Ligtenberg, Iris D. Nagtegaal
Journal: Cancer Research (2015)

Abstract Background and Aim: There is scant information on pancreatic cancer occurring at young age. About 5 to 10 percent of patients with pancreatic cancer have a family history of pancreatic cancer, which is partially due to defined hereditary syndromes like Lynch syndrome. Recently, we have identified deletions of the 3’ end of the EPCAM gene as a novel cause of this hereditary syndrome. In the cohort of patients with EPCAM deletions a relatively high number of pancreatic cancers and duodenal cancers were observed. We therefore aimed to assess whether development of pancreatic or duodenal cancer at young age might be an indication of EPCAM-associated Lynch syndrome. Methods: We searched the Dutch Pathology Registry (PALGA) to identify all patients who were diagnosed with pancreatic carcinoma (PC), ampulla of Vater carcinoma (VC) or duodenal carcinoma (DC) before the age of 50 in The Netherlands between January 2000 and December 2012. Immunohistochemical analysis was used to analyze mismatch repair (MMR)- and EPCAM-protein expression. MS-status was determined by a panel of 5 mononucleotide repeats in cases with an aberrant MMR protein pattern. Furthermore, multiplex ligation-dependent probe amplification will be performed in case of an absent EPCAM staining or loss of MSH2 and MSH6 protein expression. Results: An aberrant MMR-IHC for PMS2 combined with microsatellite instability (MSI) was identified in 1 of 48 (2%) PC diagnosed before age 50. In 24 VC patients, one tumor (4%) showed MSI with absence of both MLH1 and PMS2 staining. This patient had a history of colon carcinoma at the age of 43 years. All patients showed a normal immunohistochemical staining for MSH2 and MSH6. EPCAM protein expression was present in all cases, except one case with an anaplastic pancreas carcinoma where EPCAM was absent in the vimentine-positive area of the tumor. Eight out of 22 DC tumors (36%) showed a MMR-defective phenotype with MSI, of which 2 with an aberrant MSH2 and MSH6 staining and a positive EPCAM protein expression. One of these two patients had a history of colon carcinoma at the age of 24 and 26 years. Conclusion: This nationwide study cohort suggests that early onset pancreatic cancer and ampulla of Vater cancer are at most rarely associated with (EPCAM-associated) Lynch syndrome, in contrast to early onset duodenal cancer. Citation Format: Monica AJ Van Zanten, Marlies JE Kempers, Marjolijn JL Ligtenberg, Iris D. Nagtegaal. MSI is not an important feature in early onset pancreatic carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A37.
Value of the Ventilation/Perfusion Scan in Acute Pulmonary Embolism
Journal: JAMA (1990)

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Autochthonous dengue fever in Croatia, August–September 2010
Authors: I Gjenero-Margan, B Aleraj, D Krajcar, V Lesnikar, A Klobučar, I Pem-Novosel, S Kurečić-Filipović, S Komparak, R Martić, S Đuričić, L Betica-Radić, J Okmadžić, T Vilibić-Čavlek, A Babić-Erceg, B Turković, T Avšić-Županc, I Radić, M Ljubić, K Šarac, N Benić, G Mlinarić-Galinović
Journal: Eurosurveillance (2011)

After information about a dengue case in Germany acquired in Croatia, health professionals and the public in Croatia were alerted to assess the situation and to enhance mosquito control, resulting in the diagnosis of a second case of autochthonous dengue fever in the same area and the detection of 15 persons with evidence of recent dengue infection. Mosquito control measures were introduced. The circumstances of dengue virus introduction to Croatia remain unresolved.
Intraperitoneal carboplatin in icodextrin 4% as first-line treatment for epithelial ovarian cancer: A phase I/II trial
Authors: L. Hofman, J. Sludden, A. V. Boddy, D. J. Murphy, D. R. Ferry
Journal: Journal of Clinical Oncology (2007)

5522 Background: First line intraperitoneal (IP) chemotherapy improves survival in epithelial ovarian cancer (EOC). Problems with IP delivery are not uncommon; in the GOG 172 study, 34% of patients discontinued IP therapy due to catheter complications. Icodextrin 4% is a high molecular weight solution for IP use, which produces a prolonged pharmacological ascites and reduces both post-surgical and post-chemotherapy adhesions. Methods: This phase I study investigated IP carboplatin in icodextrin 4% in optimally debulked EOC. Immediately post operatively, 1.5L Icodextrin 4% was infused IP. This was repeated on a weekly basis. Carboplatin was added 3-weekly, over 6 cycles. Carboplatin target AUC started at 5 mg/ml.min based on 51 Cr EDTA clearance and the Calvert formula, and increased by increments of 1 mg/ml.min until dose limiting toxicity (DLT) was reached. Three to 6 patients were treated per dose level. IP fluid samples and blood samples were obtained immediately prior and after IP administration of carboplatin in icodextrin 4% and 1, 2, 4, 8, 12, 24, 48 h and 1 week after. Results: Fourteen patients were treated; 4 at AUC 5, 3 at AUC 6, 3 at AUC 7, 4 at AUC 8. DLT was reached at AUC 8. Myelosuppression was the DLT. The mean AUCs, measured in plasma ± SEM (and peritoneal fluid ± SEM), were: 5.8 ± 0.80 (55.2 ± 14.3), 4.9 ± 0.92 (43.0, 1 sample), 5.3 ± 1.3 (74.4 ± 25.3) and 7.5 ± 0.28 (135.3 ± 9.48) mg/ml.min for the target AUCs of 5, 6, 7 and 8 respectively. Two patients were withdrawn at the start of the 2 nd cycle due to vaginal leaking of the IP installed icodextrin. The other 12 patients completed all 6 cycles without significant catheter problems or abdominal pain. Conclusions: The pharmacokinetic data suggest that carboplatin in icodextrin 4% is associated with a considerable IP pharmacokinetic advantage. Compared to data obtained on IP carboplatin in 5% glucose, icodextrin 4% does not seem to alter the pharmacokinetics of IP installed carboplatin. Icodextrin 4% appears to be an excellent carrier solution for IP carboplatin, with the potential to reduce catheter associated complications. To complete the phase II part of the study, 20 further patients will be treated at the maximum tolerated dose (MTD), AUC 7 mg/ml.min. No significant financial relationships to disclose.
The effect of peritumoral edema on health-related quality of life in who grade i meningioma patients
Authors: D. van Nieuwenhuizen, L. Bosscher, E. Szymanska, J.J. Heimans, S.M. Peerdeman, M. Klein, J.C. Reijneveld
Journal: Neuro-Oncology (2010)

Times Cited: 0 4 Advances in Inflammatory Bowel Diseases Crohns and Colitis Foundations National Clinical and Research Conference Dec 09-12, 2010 Hollywood, FL
Abstract P175: Impact of Serum Hemoglobin Level for Successful Cardiac Resuscitation
Authors: Masaru Suzuki, Akiko Shiroshita-Takeshita, Masaru Miyaki, Shinya Abe, Shingo Hori, Naoki Aikawa
Journal: Circulation (2008)

Aim: It has been recently recognized that anemia is one of risk factors for major adverse cardiac events among the patients with cardiac diseases. However, it is unknown whether serum hemoglobin le...
Prescrire: France's Choosing Wisely initiative
Authors: B. Toussaint
Journal: BMJ (2015)

We welcome the Choosing Wisely initiative in the UK.1 For more than 30 years the non-profit making organisation Prescrire has helped healthcare professionals and patients choose treatments that minimise the risk of adverse effects on the basis of strong evidence. And to do that wisely, Prescrire editors lack any conflicts of interests …
Nanoparticles for Radiation Therapy Enhancement: the Key Parameters
Authors: Paul Retif, Sophie Pinel, Magali Toussaint, Céline Frochot, Rima Chouikrat, Thierry Bastogne, Muriel Barberi-Heyob
Journal: Theranostics (2015)

This review focuses on the radiosensitization strategies that use high-Z nanoparticles. It does not establish an exhaustive list of the works in this field but rather propose constructive criticisms pointing out critical factors that could improve the nano-radiation therapy. Whereas most reviews show the chemists and/or biologists points of view, the present analysis is also seen through the prism of the medical physicist. In particular, we described and evaluated the influence of X-rays energy spectra using a numerical analysis. We observed a lack of standardization in preclinical studies that could partially explain the low number of translation to clinical applications for this innovative therapeutic strategy. Pointing out the critical parameters of high-Z nanoparticles radiosensitization, this review is expected to contribute to a larger preclinical and clinical development.
Abstract 14542: Impact of MicroRNA Expression in Human Atrial Tissue For Patients With Atrial Fibrillation Undergoing Open Heart Surgery
Authors: Hiroyuki Nishi, Taichi Sakaguchi, Shigeru Miyagawa, Yasushi Yoshikawa, Satsuki Fukushima, Shunsuke Saito, Takayoshi Ueno, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2011)

BACKGROUND Although microRNA (miR) was shown to regulate initiation and/or progression of atrial fibrillation (AF) in a canine AF model, underling mechanism in human tissue and its clinical impact ...
Abstract 5934: Arrhythmogenic Right Ventricular Cardiomyopathy Due to Desmosomal Gene Mutations Is a Progressive Biventricular Disease
Authors: Cristina Basso, Elisa Carturan, Nikos Protonotarios, Barbara Bauce, Alessandra Rampazzo, Adalena Tsatsopoulou, Stefania Rizzo, Aris Anastasakis, Andrea Nava, Gaetano Thiene
Journal: Circulation (2008)

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by a gradual loss of myocytes with fibro-fatty replacement. Mutations of gene encoding desmosomal proteins have been demonstrated in up to 50% of probands. The aim of this study was to assess the morphologic spectrum and the relative role of viruses on genotyped ARVC hearts. Design: Fourteen ARVC hearts (10 M/4 F, age range 7–64, mean 30 yrs), coming from sudden death (8), cardiac transplantation (4), heart failure (1) and extracardiac death (1) were investigated. Familial recurrence of ARVC was ascertained in 12 (86%). Genetic screening identified pathogenetic mutations in plakophilin-2 (5), desmoplakin (4), desmoglein-2 (2) and plakoglobin (3). Five hearts from patients with in ryanodine receptor 2 (Ryr2) gene mutations were also investigated. Morphopathologic investigation consisted of gross examination, histology, immunohistochemistry and molecular pathology (PCR) for cardiotropic viruses. Result: Cardiac involvement was biventricular in all but 1 case, a 7 year old girl who died of extracardiac causes and presented a structurally normal heart. Ventricular myocardium abnormalities consisted of fibro-fatty replacement in 12 cases and of subepicardial myocyte necrosis with acute inflammation and granulation tissue in a 15 year old boy who died suddenly. Inflammatory infiltrates were evident in 93% of cases, either diffuse (23%) or focal (77%), and mostly consisted of T-lymphocytes and macrophages. Molecular investigation was negative in all but one with Hepatitis C virus (7%). Ryr2 gene hearts showed only mild fatty infiltration confined to the antero-apical wall of the right ventricle. Conclusion: ARVC hearts from patients with desmosomal gene mutations are characterized by biventricular myocardial atrophy and fibro-fatty replacement. In early adolescence, the phenotype can be either absent or consistent with acute myocyte damage without fibro-fatty replacement, thus confirming the progressive nature of the disease. While myocarditis is a usual feature, viral genome is exceptionally detected in the myocardium as to support the reactive nature of inflammation. The pathologic features of Ryr2 hearts are not in keeping with ARVC.
The prognostic role of androgen receptor in early-stage breast cancer patients: A meta-analysis.
Authors: Ivana Bozovic-Spasojevic, Dimitrios Zardavas, Evandro De Azambuja, Lieveke Ameye, Christos Sotiriou, Martine J. Piccart-Gebhart, Marianne Paesmans
Journal: Journal of Clinical Oncology (2013)

528 Background: Androgen receptor (AR) expression has been observed in ~70% of breast cancer (BC) patients, but its prognostic role is not established yet. To assess this we performed a meta-analysis of studies that evaluated the impact of AR on disease free survival (DFS) and/or on overall survival (OS) in early stage BC. Methods: Published studies were identified by an electronic search on PubMed using the MeSH terms "breast neoplasm" and "androgen receptor" (up to June 2012). Identified studies were assessed against the following criteria for inclusion in the analysis: early stage BC and reported results of AR status in correlation with clinical outcome. We report combined HRs with 95% confidence intervals (CI) using AR negative patients as reference. Results: Twenty studies were eligible for the meta-analysis out of 493 initially identified and 12 among them, including 6,525 patients, were considered as evaluable (i.e., reporting enough information to allow aggregation of results). AR positivity was associated with lower risk of relapse in all breast cancer patients, and better overall survival in both univariate (U) and multivariate (M) analysis. AR prognostic impact in different subtypes was also assessed (see Table). Conclusions: Our analysis demonstrated that AR delivers prognostic information overall, serving as a positive prognostic factor in early stage BC. Further studies are needed to delineate its prognostic impact within the different subtypes of the disease. [Table: see text]
Abstract 14402: Elevated Plasma Von Willebrand Factor (vWF) Level Predicts Left Atrial Appendage Dysfunction in Patients With Cardioembolic Stroke
Authors: Masahiro Wanezaki, Tetsu Watanabe, Harutoshi Tamura, Satoshi Nishiyama, Shintaro Sasaki, Takanori Arimoto, Hiroki Takahashi, Tetsuro Shishido, Takehiko Miyashita, Takuya Miyamoto, Isao Kubota
Journal: Circulation (2011)

It is well known that left atrial appendage (LAA) dysfunction plays an important role in the occurrence of cardioembolic stroke. As shown in the Virchow's triad, low blood flow, hypercoagulable sta...