tbuckley/cabot-search huggingface dataset:
Prevalence of Disability and Disability Type Among Adults — United States, 2013
Authors: Elizabeth A. Courtney-Long, Dianna D. Carroll, Qing C. Zhang, Alissa C. Stevens, Shannon Griffin-Blake, Brian S. Armour, Vincent A. Campbell
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Understanding the prevalence of disability is important for public health programs to be able to address the needs of persons with disabilities. Beginning in 2013, to measure disability prevalence by functional type, the Behavioral Risk Factor Surveillance System (BRFSS), added five questions to identify disability in vision, cognition, mobility, self-care, and independent living. CDC analyzed data from the 2013 BRFSS to assess overall prevalence of any disability, as well as specific types of disability among noninstitutionalized U.S. adults. Across all states, disabilities in mobility and cognition were the most frequently reported types. State-level prevalence of each disability type ranged from 2.7% to 8.1% (vision); 6.9% to 16.8% (cognition); 8.5% to 20.7% (mobility); 1.9% to 6.2% (self-care) and 4.2% to 10.8% (independent living). A higher prevalence of any disability was generally seen among adults living in states in the South and among women (24.4%) compared with men (19.8%). Prevalences of any disability and disability in mobility were higher among older age groups. These are the first data on functional disability types available in a state-based health survey. This information can help public health programs identify the prevalence of and demographic characteristics associated with different disability types among U.S. adults and better target appropriate interventions to reduce health disparities.
A CD19/CD3 Bispecific Tandab, AFM11, Recruits T Cells To Potently and Safely Kill CD19+ Tumor Cells
Authors: Eugene Zhukovsky, Uwe Reusch, Carmen Burkhardt, Stefan Knackmuss, Ivica Fucek, Markus Eser, Fionnuala McAleese, Kristina Ellwanger, Melvyn Little
Journal: Blood (2013)
One in 10 patients on antidepressants may have unrecognised bipolar disorder
Authors: Susan Mayor
Journal: BMJ (2016)

Nearly one in 10 younger adults given antidepressants for depression or anxiety may have unrecognised bipolar disorder, a UK primary care study has shown.1

Bipolar disorder often presents with depression and can be difficult to diagnose. Patients tend not to recognise symptoms indicating mania—such as increased energy or being easily distracted—as abnormal, so they may not report them unless asked specifically. As a result they may be given antidepressants but not mood stabilisers, and this can increase the …
Weight, Diet, and the Risk of Symptomatic Gallstones in Middle-Aged Women
Authors: K. Malcolm Maclure, K.C. Hayes, Graham A. Colditz, Meir J. Stampfer, Frank E. Speizer, Walter C. Willett
Journal: New England Journal of Medicine (1989)

To assess the risk factors for symptomatic gallstones, 88,837 women in the Nurses' Health Study cohort (age range, 34 to 59 years) were followed for four years after completing a detailed questionnaire about food and alcohol intake in 1980. A total of 433 cholecystectomies and 179 cases of newly symptomatic, unremoved gallstones, diagnosed by ultrasonographic examination or x-ray films, were reported during the four-year follow-up. The age-adjusted relative risk for very obese women, who had a Quetelet index of relative weight (weight in kilograms divided by the square of the height in meters) of more than 32 kg per square meter, was 6.0 (95 percent confidence interval, 4.0 to 9.0), as compared with women whose relative weight was less than 20 kg per square meter. For slightly overweight women (relative weight, 24 to 24.9 kg per square meter), the relative risk was 1.7 (95 percent confidence interval, 1.1 to 2.7). Overall, we observed a roughly linear relation between relative weight and the risk of gallstones. Among the 59,306 women whose relative weight was less than 25 kg per square meter, a high energy intake (greater than 8200 J per day), as compared with a low energy intake (less than 4730 J per day), was associated with an increased incidence of symptomatic gallstones (relative risk, 2.1; 95 percent confidence interval, 1.4 to 3.3), and an alcohol intake of at least 5 g per day was associated with a decreased incidence as compared with abstention (relative risk, 0.6; 95 percent confidence interval, 0.4 to 0.8). Parity did not appear to be an important risk factor after an adjustment was made for relative weight. These data support a strong association between obesity and symptomatic gallstones and suggest that even moderate overweight may increase the risk.
Basophil Activation and Peanut-Specific IgE Are Not Predictors of Threshold Dose during a Double-Blind Placebo-Controlled Food Challenge (DBPCFC)
Authors: Moira E. Breslin, Deanna K. Hamilton, Rishu Guo, Ping Ye, Xiaotong Jiang, Paul Stewart, Stacy Chin, Edwin H. Kim, A. Wesley Burks
Journal: Journal of Allergy and Clinical Immunology (2016)
Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia
Authors: Lishuang Cao, Aoibhinn McDonnell, Anja Nitzsche, Aristos Alexandrou, Pierre-Philippe Saintot, Alexandre J.C. Loucif, Adam R. Brown, Gareth Young, Malgorzata Mis, Andrew Randall, Stephen G. Waxman, Philip Stanley, Simon Kirby, Sanela Tarabar, Alex Gutteridge, Richard Butt, Ruth M. McKernan, Paul Whiting, Zahid Ali, James Bilsland, Edward B. Stevens
Journal: Science Translational Medicine (2016)

A selective Nav1.7 sodium channel blocker reduced hyperexcitability of iPSC-derived sensory neurons and alleviated pain in a subpopulation of patients with an inherited pain disorder.
A phase I study of TPI287: A third generation taxane administered weekly in patients with advanced cancer
Authors: J. J. Hwang, J. L. Marshall, T. Ahmed, H. Chun, M. Basche, A. Cohn, M. Kurman, G. Tapolsky, G. Tapolsky, E. Allen
Journal: Journal of Clinical Oncology (2007)

2575 Background: TPI 287 is an investigational taxane designed to not be a substrate for mdr-1 and to bind to mutant tubulin. In preclinical studies, TPI 287 demonstrated activity against multiple human tumor xenografts in nude mice, including xenografts that expressed mdr-1 and that were resistant to other taxanes. The safety and tolerability of TPI 287 when administered weekly for 3 weeks followed by a 1 week rest (4 week cycle) was examined in this Phase 1 dose escalation study in patients (pts) with advanced neoplasms. Materials and Methods: TPI 287 was administered over 1 hour weekly for 3 weeks followed by 1 week of no treatment. Treatment cohorts consisted of 3 pts and were expanded to 6 pts in the face of dose-limiting toxicity (DLT); pts could remain on study until the development of progressive disease or an intolerable adverse event. DLT was defined as Gr 4 heme toxicity lasting 7 days; febrile neutropenia, Gr 3 thrombocytopenia with bleeding, Gr 3 elevation of transaminases lasting 7 days or any other Gr 3/4 toxicity other than nausea or vomiting. Results: 25 pts (M:F 16:9, median age 60, range 24 - 86) were enrolled in 7 dose levels ranging from 7–185 mg/m 2 . Pts’ cancers included colorectal (6 pts); NSCLC (2); prostate (2); squamous cell carcinoma (2) and 1 pt each with cervical, breast, ovarian, gastric, pancreatic, bladder endometrial, NSCLC, SCLC, glioblastoma, melanoma, renal cell and hepatocellular carcinoma. All pts but 1 had received prior chemotherapy (median no. prior treatments: 3 (range, 1–7). Drug related adverse events included nausea, vomiting, diarrhea, fatigue, anorexia, rash, anemia and peripheral neuropathy. 1 pt., who was inadvertently treated with inadequate marrow reserve, experienced Gr 4 neutropenia and died of sepsis. DLT of Grade 3 peripheral neuropathy has been observed. PK data to date reveal that AUC is generally dose linear. At a dose of 127.5 mg/m 2 , clearance was 30.2 + 11.9 L/hr/m 2 and t 1/2 8.6 + 1.3 hrs. Results are similar with non-compartmental methods and 2-compartment modeling. Conclusions: TPI 287 can be safely administered in doses of up to 127.5 mg/m 2 weekly x 3. No significant financial relationships to disclose.
Smoking and Adverse Outcomes in Fibromuscular Dysplasia
Authors: Sarah O’Connor, Heather L. Gornik, James B. Froehlich, Xiaokui Gu, Bruce H. Gray, Pamela D. Mace, Aditya Sharma, Jeffrey W. Olin, Esther S.H. Kim
Journal: Journal of the American College of Cardiology (2016)
Aplastic Anemia, Histiocytosis and Erythrodermia in Immunologically Deficient Children
Authors: William E. Hathaway, John H. Githens, Will R. Blackburn, Vincent Fulginiti, C. Henry Kempe
Journal: New England Journal of Medicine (1965)

IMMUNOLOGICALLY tolerant animals that accept a graft of foreign hematopoietic tissue frequently manifest a syndrome characterized by generalized wasting, dermatitis, diarrhea, anemia, aplasia of the bone marrow, lymphoid tissue depletion, histiocytosis and death. This disorder has been called graft-versus-host (GVH) reaction,1 secondary syndrome2 or runt disease.3 To our knowledge the human counterpart of this syndrome has not previously been reported.The purpose of this paper is to describe 2 children with severe progressive vaccinia necrosum who were treated with multiple fresh transfusions containing leukocytes and in whom erythrodermia, hepatomegaly and fatal aplastic anemia subsequently developed. The pathological findings in these . . .
P170 Outcomes following pursuit of a tissue diagnosis in elderly patients with suspected lung cancer
Authors: S Crawley, J Butler, G Lumsden, N O’Rourke, S Sheridan, M Sproule, C Carlin
Journal: Thorax (2015)

<h3>Background</h3> 40% of cases of lung cancer are diagnosed in patients aged 75 years and over. Comorbidities, frailty and poorer tolerance of therapy are challenges for diagnosis and management. We explored clinical outcomes and survival in a cohort of elderly patients in which a tissue diagnosis was pursued. <h3>Methods</h3> 43 patients aged 75 and older who attended between 01/11/2013 and 30/04/2014, where a West Glasgow MDT decision was made to pursue tissue diagnosis were identified from audit data. Survival was reviewed at April 2015. <h3>Results</h3> Mean age was 80 ± 4 yrs; 21 male/22 female; WHO Performance Status (PS) of 0 (2 pts), 1 (27 pts), 2 (5 pts), 3 (5 pts), Not Documented (4 pts). 17 patients had Bronchoscopy +/- EBUS-TBNA, 19 CT-guided lung biopsy, 5 other core biopsy, 2 positive pleural aspiration. Histology was non-small cell lung cancer in thirty-two (74%) patients, small cell lung cancer in three (7%) patients, mesothelioma in three (7%) patients, other malignancy in 3 (7%) patients and non diagnostic in 2 patients (diagnosis registered as clinical lung cancer). Seventeen (40%) patients were treated with <i>curative</i> intent (surgery, radical radiotherapy, chemotherapy for SCLC), sixteen (37%) patients with <i>palliative</i> intent (radiotherapy, chemotherapy, brachytherapy), and ten (23%) patients received <i>best supportive care</i> (BSC) only. Of the five patients with PS 3, one received palliative radiotherapy and the other four BSC. Patients treated with curative intent had 71% survival at six months, 65% survival at 12 months: survival rates significantly higher compared with those receiving palliative treatment or BSC (p = 0.02). There was no survival difference between palliative treatment and BSC (p = 0.81) (Figure 1). <h3>Conclusion</h3> When a tissue diagnosis of lung cancer is pursued in those aged 75 and older, most patients will receive specific cancer treatment and this data informs clinical discussions about curative intent outcomes. In those who are PS 3 at baseline, BSC only is the likely outcome, and pursuing tissue diagnosis may not be appropriate.
Turnover of Epidermal Langerhans' Cells
Authors: Jean Kanitakis, Palmina Petruzzo, Jean-Michel Dubernard
Journal: New England Journal of Medicine (2004)

may reflect changes in enrollment criteria over time.When a patient's history includes a poor response to methotrexate or no response, the question is whether that patient can be randomly assigned to receive that drug alone.Under such circumstances, our opinion is that the use of methotrexate alone is unethical, and consequently, trials designed to make head-to-head comparisons between biologic agents (without a control group treated with methotrexate alone) are far more appropriate than trials based on a methotrexate-only control group.
S67 Vitamin D deficiency drives pulmonary inflammation in a human model of the acute respiratory distress syndrome induced by inhaled lipopolysaccharide in healthy volunteers
Authors: M Fitzgerald, M Shyamsundar, JJ McNamee, DR Thickett, CM O’Kane, DF McAuley
Journal: Thorax (2015)

<h3></h3> The acute respiratory distress syndrome (ARDS) is characterised by exaggerated alveolar inflammation. Vitamin D deficiency in an LPS induced murine model of ARDS results in exaggerated alveolar inflammation. However the role of vitamin D deficiency in pulmonary inflammation in humans is unclear. We hypothesised that in healthy volunteers with vitamin D deficiency, pulmonary inflammation would be increased following LPS inhalation. <h3>Methods</h3> Healthy volunteers inhaled 50 micrograms of LPS and six hours later underwent bronchoalveolar lavage for measurement of cytokines. Plasma was collected at baseline and one day post LPS inhalation for measurement of vitamin D. <h3>Results</h3> 28 participants were included. The mean age of volunteers was 26.2 +/- 5.5 years. All 28 patients were vitamin D deficient (plasma levels &lt;50 nmol/l), with 89% (25/28) patients having severe vitamin D deficiency (&lt;25 nmol/l). Vitamin D levels were significantly higher after LPS inhalation (p &lt; 0.002). Levels of IL-1β in BALF were significantly higher in those with severe deficiency than those with mild/moderate deficiency (Figure 1; p = 0.04). Levels of IL-6, IL-8 or TNF-α did not differ between groups. <h3>Conclusions</h3> Vitamin D deficiency was highly prevalent in this population of healthy volunteers. The rise in vitamin D levels post LPS exposure may represent mobilisation of vitamin D from fat stores during inflammation though vitamin D metabolism and kinetics are complex and may differ in healthy volunteers and the critically ill. Severe deficiency correlated with increased alveolar inflammation.
Treatment of recalcitrant adult alopecia areata universalis with oral azathioprine
Authors: Sergio Vañó-Galván, Ángela Hermosa-Gelbard, Natalia Sánchez-Neila, Laura Miguel-Gómez, David Saceda-Corralo, Rita Rodrigues-Barata, Pedro Jaén
Journal: Journal of the American Academy of Dermatology (2016)
Steady-state pharmacokinetics of fentanyl after administration of a novel non-occlusive transdermal system
Authors: C. Stone, A. J. Humberstone, K. Gard’ner, A. Evans, D. Shaw, G. L. Ludbrook
Journal: Journal of Clinical Oncology (2005)

8199 Background: Transdermal fentanyl patches are widely used to treat chronic pain. However, drawbacks include the variability in fentanyl delivery over the 3 day dosing period and the patches causing skin irritation or falling off. An alternative non-invasive Metered-Dose Transdermal System (MDTS) is being developed, which contains a fast-drying formulation of drug, enhancer and solvent. The primary objective of this study was to determine and compare the steady-state (SS) pharmacokinetics (PK) of fentanyl after administration of a Fentanyl MDTS system every 12, 24 or 48 hours. Methods: The study was a single centre, randomized, multiple dose PK study in 12 healthy male volunteers blocked to opioid effects with naltrexone. The Fentanyl MDTS formulation was administered via a pre-metered single dose applicator. Each volunteer received a dose of 220 μL applied to the inner forearm every 48 hours for 8 days, followed by 220 μL either 24 or 12 hourly for the next 6 days. Intensive blood sampling was performed on Days 7–9 and Days 14–15. Serum fentanyl concentrations were analysed using a validated LC/MS/MS assay. Results: Mean fentanyl steady-state average serum concentrations (Cavg) and maximum and minimum serum concentrations (Cmax and Cmin) are shown in Table 1. There were no serious or unexpected adverse events and no application site reactions. Conclusions: Steady-state serum concentrations over the range 0.4–2.2 ng/mL were achieved with the three different dosage regimens. The accumulation of serum fentanyl concentrations increased progressively as the frequency of dosing increased. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Acrux Ltd Centre for Pharmaceutical Research Acrux Ltd CMAX
High Serum Gamma-Glutamyltransferase Concentrations in a Family
Authors: Michele Bibas, Germano Zampa, Alberto Procopio, Roberto Guaitolini
Journal: New England Journal of Medicine (1994)

To the Editor: Gamma-glutamyltransferase (GGT) is a glycoprotein enzyme that catalyzes the transfer of the gamma-glutamyl group from gamma-glutamyl peptides to other peptides and to l-amino acids. ...
Etiology of Progressive Multifocal Leukoencephalopathy
Authors: Opendra Narayan, John B. Penney, Richard T. Johnson, Robert M. Herndon, Leslie P. Weiner
Journal: New England Journal of Medicine (1973)

Papovaviruses were identified in brains of 13 patients with progressive multifocal leukoencephalopathy, asubacute human demyelinating disease. Fluorescent-antibody staining and electron microscopical agglutination technics demonstrated the JC type of papovavirus in 11 patients. Simian-virus 40 and the virus of progressive multifocal leukoencephalopathy were isolated from the first two patients studied, but all subsequent isolates were of the JC-virus type, and the BK type was not implicated in the disease. The use of monospecific rabbit serums to identify viral antigens in the brain tissue of patients and to serotype by electron microscopy virions extracted directly from brain demonstrates that rapid diagnostic methods can be employed in this disease. (N Engl J Med 289:1278–1282, 1973)
Correction of Rectal Procidentia
Authors: Joseph Berkowitz
Journal: New England Journal of Medicine (1953)

PROCIDENTIA of the rectum is defined as the "abnormal descent of all the coats of the rectum with or without protrusion through the anal orifice." This paper is concerned with the condition in the elderly patient primarily and with the type of procidentia that protrudes through the anus as a large mass in the intergluteal region.Weakness in the musculofascial supports of the pelvic floor and the added factor of increased intraabdominal pressure from any cause constitute the main elements in the etiology of rectal procidentia. This is manifested by invagination of the pelvic peritoneum into the anterior rectal wall, . . .
Noninvasive Diagnosis of Renal-Allograft Rejection by Measurement of Messenger RNA for Perforin and Granzyme B in Urine
Authors: Baogui Li, Choli Hartono, Ruchuang Ding, Vijay K. Sharma, Ravi Ramaswamy, Biao Qian, David Serur, Janet Mouradian, Joseph E. Schwartz, Manikkam Suthanthiran
Journal: New England Journal of Medicine (2001)

Acute rejection is a serious and frequent complication of renal transplantation, and its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for rejection could improve the outcome of transplantation.
Abstract PR01: Identifying clinically important somatic mutations through a knowledge-based approach
Authors: Benjamin J. Ainscough, Malachi Griffith, Jason Kunisaki, Adam Coffman, Joshua F. McMichael, James M. Eldred, Jason R. Walker, Robert S. Fulton, Richard K. Wilson, Obi L. Griffith, Elaine R. Mardis
Journal: Cancer Research (2015)

Abstract Large-scale tumor sequencing projects, like The Cancer Genome Atlas (TCGA), have implicated thousands of somatic mutations in cancer. These initiatives have incentivized many improvements in somatic variant detection. However, we have observed that important pathogenic variants are often missed due to stringent filtering, tumor heterogeneity, tumor contamination of normal, low tumor purity, alignment challenges, and other issues. These idiosyncrasies can impede variant detection algorithms from reliably calling even the most clinically relevant variants. To rescue this missed variation we devised a knowledge based variant identification strategy. We mined the literature and other variant databases for pathogenic variation and assembled them into an integrated Database of Curated Mutations (DoCM - www.docm.info). The DoCM contains 488 variants across 63 genes implicated in 34 cancer types. We developed an algorithm to identify any pathogenic variant signal, for all variants in the DoCM, in aligned sequence data. As a proof of principle, we applied this approach to four cancer types sequenced by TCGA: acute myeloid leukemia (AML), breast cancer, ovarian carcinoma, and uterine corpus endometrial carcinoma. Obvious sequencing and alignment errors, like variants in homopolymer runs, were excluded from subsequent analysis by manual review. Across these four TCGA projects, which includes 1,840 individuals, 1,757 clinically relevant variants were identified, 1,223 of which had not been previously reported in TCGA studies. To validate this approach, custom capture probes were designed for all of the DoCM variants, new libraries constructed and deep sequencing performed on 96 tumor and matched normal samples from the AML and breast cancer TCGA projects. Following this strategy, we were able to confirm the rescue of clinically relevant somatic mutations that were missed in the original TCGA analysis. We propose a knowledge-driven variant detection approach be considered as standard practice to avoid false-negative calls of events likely to be clinically relevant Citation Format: Benjamin J. Ainscough, Malachi Griffith, Jason Kunisaki, Adam Coffman, Joshua F. McMichael, James M. Eldred, Jason R. Walker, Robert S. Fulton, Richard K. Wilson, Obi L. Griffith, Elaine R. Mardis. Identifying clinically important somatic mutations through a knowledge-based approach. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr PR01.
Case 13-1997
Authors: W. Hallowell Churchill, Phuong L. Nguyen
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 32-year-old man was admitted to the hospital because of IgG antibody and Coombs'-positive hemolytic anemia resistant to corticosteroid treatment.The patient had been well until about five months earlier, when he began to have low-grade fever, night sweats, and nonpleuritic pain in the right deltoid region. Laboratory tests were performed at another hospital. The urea nitrogen, creatinine, glucose, total protein, ferritin, and lactate dehydrogenase levels were normal; the results of other tests are shown in Table 1, Table 2 and Table 3. A radiograph of the chest was normal. Microscopical examination of an aspirated bone marrow specimen showed erythroid hyperplasia. . . .