tbuckley/cabot-search huggingface dataset:
Phase 2 study of concurrent radiotherapy and temozolomide followed by temozolomide and lomustine in the treatment of children with high-grade glioma: a report of the Children's Oncology Group ACNS0423 study
Authors: Regina I. Jakacki, Kenneth J. Cohen, Allen Buxton, Mark D. Krailo, Peter C. Burger, Marc K. Rosenblum, Daniel J. Brat, Ronald L. Hamilton, Sandrah P. Eckel, Tianni Zhou, Robert S. Lavey, Ian F. Pollack
Journal: Neuro-Oncology (2016)

The prognosis for children with malignant glioma is poor. This study was designed to determine whether lomustine and temozolomide following radiotherapy and concurrent temozolomide improves event-free survival (EFS) compared with historical controls with anaplastic astrocytoma (AA) or glioblastoma (GBM) and whether survival is influenced by the expression of O6-methylguanine-DNA-methyltransferase (MGMT). Following maximal surgical resection, newly diagnosed children with nonmetastatic high-grade glioma underwent involved field radiotherapy with concurrent temozolomide. Adjuvant chemotherapy consisted of up to 6 cycles of lomustine 90 mg/m2 on day 1 and temozolomide 160 mg/m2/day ×5 every 6 weeks. Among the 108 eligible patients with AA or GBM, 1-year EFS was 0.49 (95% CI, 0.39–0.58), similar to the original CCG-945-based design model. However, EFS and OS were significantly improved in ACNS0423 compared with the 86 AA or GBM participants treated with adjuvant temozolomide alone in the recent ACNS0126 study (1-sided log-rank P = .019 and .019, respectively). For example, 3-year EFS was 0.22 (95% CI, 0.14–0.30) in ACNS0423 compared with 0.11 (95% CI, 0.05–0.18) in ACNS0126. Stratifying the comparison by resection extent, the addition of lomustine resulted in significantly better EFS and OS in participants without gross-total resection (P = .019 and .00085 respectively). The difference in EFS and OS was most pronounced for participants with GBM (P = .059 and 0.051, respectively), and those with MGMT overexpression (P = .00036 and .00038, respectively). The addition of lomustine to temozolomide as adjuvant therapy in ACNS0423 was associated with significantly improved outcome compared with the preceding COG ACNS0126 HGG study in which participants received temozolomide alone.
Evidence for atypical depression in Parkinson's disease
Authors: R B Schiffer, R Kurlan, A Rubin, S Boer
Journal: American Journal of Psychiatry (1988)

The Research Diagnostic Criteria were applied to 16 depressed patients with Parkinson's disease and 20 depressed multiple sclerosis patients. Diagnoses of anxiety and panic disorder were significantly more frequent among the patients with Parkinson's disease. These patients may experience atypical depression.
Epilepsy: A Functional Mental Illness, Its Treatment.
Journal: JAMA (1926)

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Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility
Authors: Michael P. Diamond, Richard S. Legro, Christos Coutifaris, Ruben Alvero, Randal D. Robinson, Peter Casson, Gregory M. Christman, Joel Ager, Hao Huang, Karl R. Hansen, Valerie Baker, Rebecca Usadi, Aimee Seungdamrong, G. Wright Bates, R. Mitchell Rosen, Daniel Haisenleder, Stephen A. Krawetz, Kurt Barnhart, J.C. Trussell, Dana Ohl, Yufeng Jin, Nanette Santoro, Esther Eisenberg, Heping Zhang
Journal: New England Journal of Medicine (2015)

The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates.We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies.After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P=0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P=0.15) or clomiphene alone (8 of 85, 9%; P=0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P=0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications.In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.).
The effects of omega-3 fatty acids on chemotherapy-induced neuropathy and inflammation in patients with breast cancer.
Authors: Ali Esfahani, Zohreh Ghoreishi, Bina Eftekharsadat, Mohammad Asghari Jafarabadi
Journal: Journal of Clinical Oncology (2014)

1039 Background: Axonal sensoryperipheral neuropathy is the major dose-limiting side effect of paclitaxel. Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. Methods: This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing the incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN). Fifty seven eligible patients with node positive breast cancer were randomly assigned to take omega-3 fatty acid soft gel capsules, 640 mg t.i.d during chemotherapy with paclitaxel for 12 weeks or sun flower soft gel capsules as placebo. Incidence and severity of PIPN, serum level of inflammatory markers: IL-1 beta, IL- 6, TNF-alpha and HsCRP, as well as concentrations of EPA and DHA in the serum phospholipids of the patients, were assessed before the onset of chemotherapy and after the cessation of therapy. Results: Twenty one patients (70%) of the group taking omega-3 fatty acid supplement did not develop PN while it was 40.7 %( 11 patients) in the placebo group. A significant difference was seen in PN incidence (OR=0.3, .95% CI= (0.10-0.88), p=0.029), but there was not a statistically significant difference of PIPN severity between the two study groups. The serum levels of aforementioned inflammatory markers were not statistically different between the active group and the control group but, a considerable difference was observed according to the serum concentrations of EPA and DHA after the end of the supplementation period (P<0.001). Conclusions: Omega-3 fatty acids may be an efficient neuroprotective supplement for prophylaxis against PIPN. They were able to reduce the incidence of PIPN in these study patients. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the quality of life of these cancer patients. Clinical trial information: NCT01049295.
Activity and safety of pembrolizumab in patients with metastatic non-small cell lung cancer with untreated brain metastases.
Authors: Sarah B. Goldberg, Scott N. Gettinger, Amit Mahajan, Roy S. Herbst, Anne C. Chiang, A. John Tsiouris, Alexander Vortmeyer, Lucia Jilaveanu, Stephanie Speaker, Matthew Madura, Elin Rowen, Heather Gerrish, Elizabeth Knapp-Perry, Xiaopan Yao, Veronica Chiang, Harriet M. Kluger
Journal: Journal of Clinical Oncology (2015)

8035 Background: Brain metastases (BrMs) are common among patients (pts) with advanced non-small cell lung cancer (NSCLC) and local therapy such as surgery and radiation can add toxicity and delay systemic treatment. Pembrolizumab is a monoclonal anti-programmed death 1 (PD-1) antibody that relieves inhibition of anti-tumor immunity. In a Phase I trial of pembrolizumab, pts with advanced NSCLC showed a 21% response rate with good tolerability and durable responses, however pts were required to have local therapy to BrMs prior to enrollment. This trial aims to determine the activity and safety of pembrolizumab in patients with advanced NSCLC and untreated BrMs. Methods: This is a Phase II trial with 2 independent arms: one for pts with advanced NSCLC (reported here) and the other for pts with metastatic melanoma (NCT02085070). Pts are eligible if they have ≥ 1 BrM that is previously untreated or progressing after prior local therapy. BrMs must be between 5mm and 20mm, asymptomatic, and not requiring immediate local therapy or corticosteroids. Tumor biopsy demonstrating PD-Ligand 1 (PD-L1) expression is required. Pts are treated with pembrolizumab 10mg/kg intravenously every 2 weeks. Extra-cerebral response is determined by RECIST 1.1, and BrM response is determined by modified RECIST (mRECIST), in which brain lesions ≥ 5mm are considered measurable and up to 5 target lesions are allowed. The primary endpoint is BrM response rate (RR) by mRECIST. Results: Ten NSCLC pts were accrued between April and December 2014, 9 of whom were evaluable for response. BrM RR was 44% (4/9 partial responses, 2 unconfirmed due to limited follow-up time); 34% (3/9) had progressive disease (PD) as their best BrM response, and 22% were unevaluable in the brain due to rapid systemic progression. Systemic RR was 34% (3/9, 1 unconfirmed); only 1 pt who responded systemically had PD in the brain. There were no grade ≥ 3 adverse events that were considered treatment-related or attributed to BrMs. Conclusions: Pembrolizumab shows promising clinical activity in patients with NSCLC and untreated BrMs with a favorable safety profile. Recruitment for this Phase II trial and correlative analysis from tumor tissue is ongoing. Clinical trial information: NCT02085070.
A Randomized Trial of a Cervical Pessary to Prevent Preterm Singleton Birth
Authors: Kypros H. Nicolaides, Argyro Syngelaki, Liona C. Poon, Gemma Picciarelli, Natasa Tul, Aikaterini Zamprakou, Evdoxia Skyfta, Mauro Parra-Cordero, Ricardo Palma-Dias, Jesus Rodriguez Calvo
Journal: New England Journal of Medicine (2016)

Preterm birth is the leading cause of neonatal and infant death and of disability among survivors. It is unclear whether a pessary inserted around the cervix reduces the risk of preterm singleton birth.We conducted a multicenter, randomized, controlled trial comparing pessary placement with expectant management (control) in girls and women who were pregnant with singletons (singleton pregnancies) and who had a cervical length of 25 mm or less at 20 weeks 0 days to 24 weeks 6 days of gestation. Participants in either group who had a cervical length of 15 mm or less, at randomization or at subsequent visits, received treatment with vaginal progesterone. The primary outcome was spontaneous delivery before 34 weeks of gestation.In an intention-to-treat analysis, there was no significant difference between the pessary group (465 participants) and the control group (467 participants) in the rate of spontaneous delivery before 34 weeks (12.0% and 10.8%, respectively; odds ratio in the pessary group, 1.12; 95% confidence interval, 0.75 to 1.69; P=0.57). There were no significant differences in the rates of perinatal death (3.2% in the pessary group and 2.4% in the control group, P=0.42), adverse neonatal outcome (6.7% and 5.7%, respectively; P=0.55), or neonatal special care (11.6% and 12.9%, respectively; P=0.59). The incidence of new or increased vaginal discharge was significantly higher in the pessary group than in the control group.Among girls and women with singleton pregnancies who had a short cervix, a cervical pessary did not result in a lower rate of spontaneous early preterm delivery than the rate with expectant management. (Funded by the Fetal Medicine Foundation; Current Controlled Trials number, ISRCTN01096902.).
Preliminary data on the relationship between nortriptyline plasma level and response in depressed children
Authors: B Geller, T B Cooper, E C Chestnut, J A Anker, M D Schluchter
Journal: American Journal of Psychiatry (1986)

Twenty-two subjects 6-12 years old who met Research Diagnostic Criteria and DSM-III criteria for major depressive disorder received a fixed daily dose of nortriptyline during an 8-week protocol. Weekly plasma levels were measured; the raters performing behavioral assessments were blind to these levels. There was a highly significant difference between the mean steady-state plasma levels and the milligram-per-kilogram doses of the responders and nonresponders. The data suggest that the lower limit of the therapeutic range of nortriptyline in children (over 60 ng/ml) is similar to that reported for adults. The disadvantages of the use of a milligram-per-kilogram dose rather than a pharmacokinetic approach are discussed.
Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer: American Society of Clinical Oncology Endorsement of Cancer Care Ontario Guideline Recommendations
Authors: N. Lynn Henry, Mark R. Somerfield, Vandana G. Abramson, Kimberly H. Allison, Carey K. Anders, Diana T. Chingos, Arti Hurria, Thomas H. Openshaw, Ian E. Krop
Journal: Journal of Clinical Oncology (2016)

An American Society of Clinical Oncology (ASCO) panel considered the Cancer Care Ontario (CCO) recommendations on the role of patient and disease factors in selecting adjuvant therapy for women with early-stage breast cancer for endorsement.ASCO staff reviewed the CCO guideline for methodologic rigor, and an ASCO panel of content experts reviewed the content of the recommendations.For making decisions regarding adjuvant therapy, nodal status, tumor size, estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) status, tumor grade, and lymphovascular invasion are relevant; Oncotype DX score and Adjuvant! Online may be used as risk stratification tools; and age, menopausal status, and medical comorbidities should be considered. Chemotherapy should be considered for patients with positive lymph nodes, ER-negative disease, HER2-positive disease, Adjuvant! Online mortality greater than 10%, grade 3 lymph node-negative tumors (T > 5 mm), triple-negative (ER-negative, PgR-negative, HER2-negative) tumors, lymphovascular invasion positivity, or estimated distant relapse risk of greater than 15% at 10 years based on Oncotype DX recurrence score (RS). Chemotherapy may not be beneficial or required for small node-negative tumors (T < 5 mm) without high-risk features or for patients with HER2-negative, strongly ER-positive, and PgR-positive cancer with micrometastatic nodal disease, T less than 5 mm, or Oncotype DX RS with an estimated distant relapse risk of less than 15% at 10 years.The ASCO panel endorses the recommendations with minor suggested revisions and highlights three areas that warrant further consideration: tumor histology and adjuvant therapy recommendations, risk stratification tools and proposed Oncotype DX RS thresholds to guide decisions about chemotherapy, and patient factors in decision making.
Early detection of pancreatic cancer
Authors: Stephen P Pereira, Lucy Oldfield, Alexander Ney, Phil A Hart, Margaret G Keane, Stephen J Pandol, Debiao Li, William Greenhalf, Christie Y Jeon, Eugene J Koay, Christopher V Almario, Christopher Halloran, Anne Marie Lennon, Eithne Costello
Journal: The Lancet. Gastroenterology & hepatology (2020)
Recent mental health litigation: a critical perspective
Authors: A A Stone
Journal: American Journal of Psychiatry (1977)

The author considers the effect of recent mental health litigation involving involuntary confinement, the right to refuse treatment, the least restrictive alternative, and the right to treatment on the role of the psychiatrist and the provision of mental health care. His thesis is that the implicit analogies between psychiatrists and agents of the criminal justice system and between patients and criminal defendants are misleading and that the recent changes in the law based on these analogies adversely affect the provision of mental health care.
Simultaneous automatic insufﬂation and smoke-evacuation system in flexible gastrointestinal endoscopy
Authors: Hidekazu Takahashi, Masashi Hirota, Tsuyoshi Takahashi, Makoto Yamasaki, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Shuji Takiguchi, Masaki Mori, Yuichiro Doki, Kiyokazu Nakajima
Journal: Endoscopy (2016)

<b>Background and aims:</b> Automatic smoke evacuation has not been feasible inside the gastrointestinal tract as evacuation collapses pneumoviscera. As previously reported, steady pressure automatically controlled endoscopy (SPACE) may resolve this problem. The aims of this study were to clarify the potential dangers of surgical smoke, and to evaluate the feasibility and potential usefulness of automatic smoke evacuation in flexible gastrointestinal endoscopy. <b>Methods:</b> Seven pigs were enrolled. SPACE was established by using a flexible endoscope, an overtube, and a surgical CO<sub>2</sub> insufflator. Smoke was generated by gastric mucosal ablation for component analysis and was evacuated by a commercially available surgical-use smoke evacuator connected to an additional line attached to the endoscope. Endoscopic images with evacuation were evaluated subjectively in comparison to those from cases without evacuation. After each session, the residual intraluminal smoke was collected by a smoke testing device for objective evaluation. <b>Results:</b> Ten chemical compounds were detected. Smoke evacuation was achieved without collapse of the pneumostomach. Smoke was significantly reduced with the use of evacuation. <b>Conclusions:</b> Surgical smoke generated inside the gut lumen was potentially hazardous. Automatic evacuation was feasible and potentially useful in conjunction with SPACE technology.
Neurotic depressions: a systematic analysis of multiple criteria and meanings
Authors: G L Klerman, J Endicott, R Spitzer, R M Hirschfeld
Journal: American Journal of Psychiatry (1979)

Neurotic depression, the most commonly used psychiatric diagnosis, has multiple meanings that are often used interchangeably in clinical practice. The authors identify six different meanings of neurotic depression and present data from a study of 90 depressed inpatients to determine how many patients met several different criteria; 16 patients met four sets of criteria. The overlap that exists between the different meanings is higher than chance alone but not sufficiently high to allow complete interchangeability. Until new diagnostic classes are developed, the authors recommend that the term "neurotic depression" no longer be used clinically because of its vagueness.
Comparison of screening questionnaires to identify psoriatic arthritis in a primary-care population: a cross-sectional study
Authors: L.C. Coates, L. Savage, R. Waxman, A.R. Moverley, S. Worthington, P.S. Helliwell
Journal: British Journal of Dermatology (2016)

Many questionnaires are available for assessment of psoriatic arthritis (PsA), but there is little evidence comparing them. To test the proposed CONTEST questionnaire, which was developed to identify patients with psoriasis who have undiagnosed PsA, and compare it with the validated Psoriasis Epidemiology Screening Tool (PEST) questionnaire in a primary‐care setting. A random sample of adult patients with psoriasis and no diagnosis of arthritis was identified from five general practice surgeries in Yorkshire, U.K. Consenting patients completed both questionnaires and were assessed by a dermatologist and rheumatologist. Diagnosis of PsA was made by the assessing rheumatologist. Receiver operator characteristic (ROC) curve analysis examined the sensitivity and specificity of potential cut points. In total 932 packs were sent to recruit 191 (20·5%) participants. Of these, 169 (88·5%) were confirmed to have current or previous psoriasis. Using physician diagnosis 17 (10·1%) were found to have previously undiagnosed PsA, while 90 (53·3%) had another musculoskeletal complaint and 62 (36·7%) had no musculoskeletal problems. Using ROC curve analysis, all of the questionnaires showed a significant ability to identify PsA. The area under the curve (AUC) for the CONTEST questionnaires was slightly higher than that of PEST (0·69 and 0·70 vs. 0·65), but there was no significant difference identified. Examining the sensitivities and specificities for the different cut points suggested that a PEST score ≥ 2 would perform better in this dataset, and the optimal scores for CONTEST and CONTEST plus joint manikin were 3 and 4, respectively. The accuracy of the questionnaires to identify PsA appeared similar, with a slightly higher AUC for the CONTEST questionnaires. The optimal cut points in this study appeared lower than in previous studies.
Continuous Glucose Monitoring in the Self-management of Type 2 Diabetes: A Paradigm Shift
Authors: Daniel J. Cox, Ann G. Taylor, Matthew Moncrief, Anne Diamond, William S. Yancy, Shefali Hegde, Anthony L. McCall
Journal: Diabetes Care (2016)

Conventional lifestyle modification for type 2 diabetes involves 7% weight loss, avoidance of high-energy foods, and 150 min of weekly exercise (1). Although effective at preventing and treating diabetes, this approach is not appropriate for those who do not need or want to lose weight or who cannot maintain weight loss. An alternative may be to target postprandial glucose (PPG), the major contributor to HbA1c (2). The GEM (glycemic load, exercise, and monitoring blood glucose) lifestyle modification program focuses on diminishing PPG by selecting low–glycemic load foods to prevent PPG spikes, reducing PPG with postprandial exercise, and using systematic self-monitoring of blood glucose (SMBG). Systematic SMBG educates individuals about the impact of different foods and physical activities on PPG, activates them to take action when glucose is outside of desired limits, and motivates them to repeat choices that produce desired glucose levels. Therefore, GEM represents a paradigm shift from reducing insulin resistance through reducing fat to reducing …
Met Tumor Expression and Mutational Analysis in Bladder Cancer Patients (Pts) Receiving Cabozantinib
Authors: A.B. Apolo, D.P. Bottaro, M.J. Merino, L. Xi, Y.H. Lee, B.A. Weinberg, J.J. Wright, W.L. Dahut, H.L. Parnes, M. Raffeld
Journal: Annals of Oncology (2014)