tbuckley/cabot-search huggingface dataset:
Progress in the Fight Against Multidrug-Resistant Bacteria? A Review of U.S. Food and Drug Administration–Approved Antibiotics, 2010–2015
Authors: Dalia Deak, Kevin Outterson, John H. Powers, Aaron S. Kesselheim
Journal: Annals of Internal Medicine (2016)

A weak antibiotic pipeline and the increase in drug-resistant pathogens have led to calls for more new antibiotics. Eight new antibiotics were approved by the U.S. Food and Drug Administration (FDA) between January 2010 and December 2015: ceftaroline, fidaxomicin, bedaquiline, dalbavancin, tedizolid, oritavancin, ceftolozane–tazobactam, and ceftazidime–avibactam. This study evaluates the development course and pivotal trials of these antibiotics for their innovativeness, development process, documented patient outcomes, and cost. Data sources were FDA approval packages and databases (January 2010 to December 2015); the Red Book (Truven Health Analytics); Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations (FDA); and supplementary information from company filings, press releases, and media reports. Four antibiotics were approved for acute bacterial skin and skin-structure infection. Seven had similar mechanisms of action to those of previously approved drugs. Six were initially developed by small to midsized companies, and 7 are currently marketed by 1 of 3 large companies. The drugs spent a median of 6.2 years in clinical trials (interquartile range [IQR], 5.4 to 8.8 years) and 8 months in FDA review (IQR, 7.5 to 8 months). The median number of patients enrolled in the pivotal trials was 666 (IQR, 553 to 739 patients; full range, 44 to 1005 patients), and median trial duration was 18 months (IQR, 15 to 22 months). Seven drugs were approved on the basis of pivotal trials evaluating noninferiority. One drug demonstrated superiority on an exploratory secondary end point, 2 showed decreased efficacy in patients with renal insufficiency, and 1 showed increased mortality compared with older drugs. Seven of the drugs are substantially more expensive than their trial comparators. Limitations are that future research may show benefit to patients, new drugs from older classes may show superior effectiveness in specific patient populations, and initial U.S. prices for each new antibiotic were obtained from public sources. Recently marketed antibiotics are more expensive but have been approved without evidence of clinical superiority.
Can off-field ‘brains’ provide a competitive advantage in professional football?
Authors: Alan McCall, Michael Davison, Chris Carling, Matthew Buckthorpe, Aaron J Coutts, Gregory Dupont
Journal: British Journal of Sports Medicine (2016)

‘Working-fast and working-slow’ in sport describes the concept that practice and research can be integrated to improve high-performance outcomes and enhance professional practice.1 ‘Working-fast’ is the task of the fast-thinking, intuitive practitioner operating on ‘the ground’ at a frenetic pace, interacting with coaches and athletes, and delivering the daily preparation programme. ‘Working-slow’ is key for the team's deliberate, focused researcher acting as the resident sceptic, operating behind the scenes on tasks that the ‘fast-practitioner’ may not have time and/or skills to undertake. Such hidden, but important, tasks include determining measurement noise/error in performance tests, establishing proof of concept for new ideas and ensuring validity of methods. Embedding research into the fast environment of high-performance football may provide a competitive advantage using ethical and evidence-based methods.1 

Football teams can learn from many of the world's largest technology companies,2 which embed research within their organisations to improve efficiency and enhance productivity. Such a strategy is coined ‘Research and Development’ (R&D), and defined as: ‘work directed toward the innovation, introduction and improvement of processes’.3 However, …
Problems Lists
Authors: WALLACE J. MULLIGAN
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 November 1973Problems ListsWALLACE J. MULLIGAN, M.D.WALLACE J. MULLIGAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-5-763_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recent exchange of letters (Ann Intern Med, August, 1973) in the continuing debate about the pros and cons of the problem-oriented health record is discouraging; perhaps it is a too-literal interpretation of Dr. Weed's pleas for problem listing.In the first place, the simple listing of the problems is often enough to upgrade the quality of care. If, for example, "anemia" is a diagnosis, then listed on the problem sheet should be mention of a peripheral blood smear, stool guaiac test, and so on. There should then emerge a meaningful diagnosis on which reasonable therapy is... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Project Hope Sage Memorial Hospital Ganado, Arizona PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA 1 November 1973Volume 79, Issue 5Page: 763-763KeywordsAnemiaElectronic medical recordsHealth care qualityHematologic tests Issue Published: 1 November 1973 PDF downloadLoading ...
Outbreak of influenza, Madagascar, July-August 2002
Authors: None WHO-GOARN investigation team
Journal: Eurosurveillance (2002)

Preliminary investigation found that a large outbreak of influenza-like illness occurred in Madagascar during July-August 2002, with 30 304 cases and 754 deaths reported. Most cases were reported from the highland regions of Fianarantsoa Province, in centre Madagascar. The majority of the cases lived in rural areas, and children under five years and adults 60 years and older were the most affected. The outbreak was attributable to an A/Panama/2007/99-like (H3N2) virus, which has been circulating worldwide for several years.
Behavioral change in a cancer patient following intrathecal beta- endorphin administration
Authors: D Pickar, M Dubois, M R Cohen
Journal: American Journal of Psychiatry (1984)

A patient with a disseminated malignancy received 3 mg of synthetic beta-endorphin administered intrathecally by lumbar puncture. A marked behavioral syndrome characterized by confusion, hypomanic/manic behavior, and psychosis followed drug administration and persisted for more than 2 days.
Standardized Added Metabolic Activity Predicts Survival After Intra-arterial Resin-Based 90Y Radioembolization Therapy in Unresectable Chemorefractory Metastatic Colorectal Cancer to the Liver
Authors: Faramarz Edalat, Juan C. Camacho, Nima Kokabi, Ayse T. Kendi, James R. Galt, Hyun S. Kim
Journal: Clinical Nuclear Medicine (2015)

Standardized added metabolic (SAM) activity is a functional objective measurement of the total tumoral metabolic activity that avoids partial volume effect and thresholding, which limit conventional PET parameters. The purpose of this study is to investigate the role of SAM in predicting survival in unresectable, chemorefractory colorectal hepatic metastatic disease treated with resin-based Y radioembolization.This is a prospective correlative study of patients with unresectable, chemorefractory colorectal liver metastasis who underwent F-FDG PET/CT and CT/MRI before and after Y. Target RECIST, PERCIST, change in total glycolytic activity (ΔTGA), and ΔSAM treatment response were assessed. Percentage changes in diameter, SUVpeak, TGA, and SAM were calculated pre- and post-Y therapy and objective response was defined as >30% change (responders). Survival analysis by Kaplan-Meier, log-rank, and Cox proportional hazard models were performed and significance was set at <0.05.Sixteen patients (mean age of 61.6) were enrolled and performed a total of 20 Y therapies. After Y, target ΔSAM showed an objective response rate of 40% vs. 35%, 30%, and 22.2% based on target ΔTGA, PERCIST, and RECIST criteria, respectively. Median overall survival (OS) of the cohort after Y was 9.2 months (CI 95% 2.2-16.2). Patients demonstrating objective response based on ΔSAM had a median OS of 22.7 months (CI 95% 12.4-33.0) vs. 6.7 (CI 95% 4.2-9.2) in non-responders (P = 0.007). On multivariate analysis, hazard ratios for the objective response group based on target ΔSAM were 0.01 (P = 0.03) vs. 0.05 (P = 0.08), 0.20 (P = 0.29), and 0.91 (P = 0.98) based on target ΔTGA, PERCIST, and RECIST criteria, respectively.In unresectable colorectal liver metastatic disease refractory to standard chemotherapy, ΔSAM predicted OS for assessment of response following Y radioembolization therapy, whereas RECIST, PERCIST, and ΔTGA did not.
Community mental health center legislation: flight of the phoenix
Authors: F M Ochberg
Journal: American Journal of Psychiatry (1976)

The author describes the history and implications of recent legislation affecting community mental health centers. New legislative requirements will result in centers seeing typically underserved populations (children, the elderly, and drug and alcohol abusers) as part of 7 new essential services. The impact of new grant mechanisms and the role of the National Institute of Mental Health in assisting and evaluating centers are examined. The author concludes that as a result of legislative and other trends in mental health care, psychiatrists will be seeing sicker patients for shorter periods, role confusion in the mental health professions will lessen, and centers will be forced to devote much time and effort to financial concerns and appropriate allocation of manpower.
Health education centers. Their role in medical education
Authors: M. S. Gordon
Journal: JAMA (1971)

The uneven distribution of physicians and other health personnel in the United States is a familiar problem and a matter of grave concern to all those interested in overcoming shortages of health manpower. In 1965, the number of active non-federal physicians per 100,000 population ranged from 89 in the East South Central states to 171 in the Middle Atlantic states.<sup>1</sup>If we consider data for individual states (excluding the District of Columbia), we find that the differences tend to be even more pronounced, ranging from 69 in Alaska and Mississippi to 199 in New York in 1967.<sup>2</sup>Similar differences are found for other health manpower categories, such as dentists and nurses. In general, states with low ratios of health manpower to population tend to be characterized by low per capita income or sparse population or both. Multivariate analyses of factors associated with differences in physician-population ratios, summarized by
Prevention of Lower Limb Paralysis by Neutralization of Type-C RNA Virus in Wild Mice2
Authors: Brian E. Henderson, Murray B. Gardner, Ray V. Gilden, John D. Estes, Robert J. Huebner>
Journal: JNCI Journal of the National Cancer Institute (1974)

We demonstrated earlier that a paralytic disease observed in wild mice could be experimentally transmitted by a type-C RNA virus. With specific mouse and guinea pig antisera, we neutralized the paralytic effect of type-C virus. Wild mouse type-C viruses appeared to have related envelope antigens, but even isolates from the same trapping area could be differentiated in neutralization tests.
PWE-275 Early discharge within 72 hours of elective colorectal cancer resections using simple discharge criteria is safe and effective
Authors: A Emmanuel, J Ellul
Journal: Gut (2015)

<h3>Introduction</h3> There is a lack of evidence guiding which discharge criteria to apply to patients following elective colorectal cancer resections. Many centres and authors advocate strict criteria which usually include a return of gastrointestinal function before discharge. However, this can lead to unnecessary delays in discharge which has particular relevance to a healthcare system strained by bed shortages. This study reports the experience of a single laparoscopic colorectal surgeon using simple discharge criteria on an enhanced recovery program to enable early discharge within 72 h. <h3>Method</h3> A retrospective review of a single laparoscopic colorectal surgeon’s experience. Unselected consecutive patients from January 2010 to August 2014 were included. Patients were managed with an enhanced recovery program and simple discharge criteria were applied including stable vital signs, absence of vomiting, pain controlled on oral analgesia and tolerating a solid diet. Passing flatus or faeces was not used as a criteria for discharge. <h3>Results</h3> 192 elective colorectal cancer resections were performed of which 168 were completed laparosocpically. The median length of stay was 3 days (range 1–72). 55% of patients were discharged within 72 h overall (laparoscopic 60%, open 17%). 27 patients were readmitted of which 10 had initially been discharged within 72 h. Among those readmitted who had initial hospital stays longer than 72 h, six required major abdominal re-operations whilst only one patient who had an initial stay under 72 h required abdominal surgery. The readmission rate for patients who were discharged within 72 h was 9% vs. 20% for patients with initial stays longer than 72 h (p = 0.02). In the final year of the study, 71% of patients were discharged within 72 h vs. 50% for the earlier years (p = 0.007). <h3>Conclusion</h3> Early discharge within 72 h of elective colorectal cancer resections using simple criteria is safe and effective. Patients discharged early do not suffer worse outcomes than those with longer stays. There was a significant increase in the proportion of patients discharged within 72 h in the final year of the study reflecting increased awareness of the feasibility of this process. This could have significant benefits in a resource stretched healthcare system. <h3>Disclosure of interest</h3> None Declared.
AB0411 Cutaneous and Pulmonary Sarcoidosis-Like Reaction Associated with Adalimumab: A Case Report
Authors: A. Bilgici, M. Unsal, O. Kuru
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The paradoxical adverse effects of necrosisi factor-alpha (TNF-alpha) antagonists have been described frequently as a result of the widespread use of these drugs. New onset or exacerbation of cutaneous psoriasis, cutaneous vasculitis and sarcoidosis have been reported with various TNF-alpha inhibitors. <h3>Objectives</h3> We report the case of a patient with AS who developed pulmonary and cutaneous sarcoidosis following treatment with adalimumab. <h3>Methods</h3> A 47-year-old woman with a history of Ankilosing Spondylitis (AS), treated with adalimumab for 2years developed erythema nodosum in her upper and lower limbs, and bilateral hilar adenopathy on chest radiograph. Patient presented general sings such as weight loss and fatique or fever. <h3>Results</h3> Her pulmonary examination was normal, and her abdomen did not have organomegaly. Multiple erythema nodosum lesions were observed on her legs and arms. C-reactive protein and standart blood tests were normal. The results of vasculitis tests, including ANA, anti-neutrophilic cytoplasmic antibodies (ANCAs), C3, and C4 were normal. The skin biopsy confirmed the diagnosis of a ‘sarcoidosis-like’ reaction. A Computed tomography (CT) of the chest showed patchy bilateral infiltrates with increased hilar and mediastinal lymphadenopathy. A bronchoscopy was performed but was normal. She was diagnosed with Sarcoidosis. Adalimumab was discontinued in the patient and she was treated with prednisolon 20mg/day. Her pulmonary and cutaneous symptoms improved rapidly in 6 weeks and corticosteroids were progressively tapered to 5mg/day. <h3>Conclusions</h3> Sarcoidosis in anti-TNF therapy is a rare paradoxical inflammatory phenomenon. Genetic variations of the TNF-alpha gene is emerging as an important factor in determining sarcoidosis predisposition. We reported the development of cutaneous lesions of sarcoidosis in a patient with AS after 2years under adalimumab. The improvement of clinical manifestations after suspension of the treatment suggest a possible triggering role of the adalimumab. The physiopathology of sarcoidosis remains unknown, although some observations have suggested the role of genetic inheritance, the environment and infectious agents. Anti-TNF-alpha therapy could promote sarcoid-like granulomatosis by enhancing the level of triggering infectious antigens and/or modification of the cytokine environment and cellular recruitment within the tissues. A beter understanding of the pathogenic role of TNF-alpha in sarcoidosis and of its therapeutic blocking action will help to explain this phenomenon. <h3>References</h3> Dhaille F, Viseux V, Caudron A, Dadban A, Tribout C, Boumier P, Clabaut A. Cutaneous sarcoidosis occuring during Anti-TNF-Alpha treatment: Report of two cases. Dermatology 2010; 220: 234-237. <h3>Disclosure of Interest</h3> None declared
Rural health care systems
Authors: V. E. Wilson
Journal: JAMA (1971)

Rural health is a problem of two basic dimensions. These are financial status and geographic location. As to financial status, rural areas are characterized by below-average incomes and considerable poverty. The great majority of the poorest counties in the United States are rural. As to geographic location, rural areas generally have a cluster of factors that are adverse to adequate health services. Along with population densities that range from low to sparse, rural areas usually have a limited tax base, scarce and widely dispersed health facilities, extreme shortages of health manpower, and negative attraction for new manpower. And yet, despite this somewhat grim summary, I think that the outlook for rural health is more encouraging than at any previous time. The most encouraging development on the income dimension is a growing realization that abject poverty is a national disgrace. No country as affluent as the United States can knowingly tolerate
American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America
Authors: Henry M Blumberg, William J Burman, Richard E Chaisson, Charles L Daley, Sue C Etkind, Lloyd N Friedman, Paula Fujiwara, Malgosia Grzemska, Philip C Hopewell, Michael D Iseman, Robert M Jasmer, Venkatarama Koppaka, Richard I Menzies, Richard J O'Brien, Randall R Reves, Lee B Reichman, Patricia M Simone, Jeffrey R Starke, Andrew A Vernon
Journal: American Journal of Respiratory and Critical Care Medicine (2003)
AB0984 Development of a Juvenile Systemic Sclerosis Response Index (JSSRI): Table 1
Authors: I. Foeldvari, Z. Györgyi, E. Baildam, E.D. Batu, M. Blakley, M. Cakan, M. Curran, K. Fligelstone, L. Mouthon, D. Nemcova, C. Pilkington, N. Ruperto, M. Tsinti, E. Tsitsami, K. Urbanvica, T. Constantin
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Juvenile systemic sclerosis (jSSc) is an orphan disease. We have currently new promising effective medication to treat systemic sclerosis, but no valid outcome measures to assess the activity of the disease. <h3>Objectives</h3> In the frame of the juvenile scleroderma working group of Paediatric Rheumatology European Society (PRES JSWG), we developed a provisional response index for jSSc. <h3>Methods</h3> The facilitating committee designed a 3-round Delphi-exercise to obtain a core set of disease activity measures in jSSc. In Round 1, they were asked to add unique items in 21 preleminary domains. Round 2 judged the items9 applicability and importance using a 1-10 scale. Previous respondents were asked to re-rate uncertain (score 4-7) items in Round 3. The aforementioned were followed by a face-to-face Nominal Group discussion to decide final items and domain structure. <h3>Results</h3> 52 participants of Round 1 suggested a total of 131 items for the 21 domains. In round 2, 56 responders rated the significance of the items. The Nominal Group accepted 11 main domains for further validation containing 41 items (see table 1). <h3>Conclusions</h3> We reached consensus and developed a Response Index, which should help to conduct clinical trials in jSSc. The validation of the JSSRI is planned in the frame of the Juvenile Scleroderma Inception Cohort. <h3>Disclosure of Interest</h3> None declared
mRNA Levels For Human Nucleolar Protein P120 in Tumor and Nontumor Cells
Authors: Jeff Hazlewood, Anna Fonagy, Dale Henning, James W. Freeman, Rose K. Busch, Harris Busch
Journal: Cancer Communications (1989)

A monoclonal antibody to a human tumor nucleolar 120 kD protein was developed by Freeman et al. (Cancer Res. 48: 1244-1251, 1988). Its complementary DNA (cDNA) has been isolated and sequenced (Fonagy et al., submitted). To determine the relative messenger RNA (mRNA) level for protein p120, cellular mRNA was extracted, slot-blotted onto nitrocellulose filters, and hybridized to radioactive p120 cDNA fragments. Human tumor cells contained 15-60 times more p120 mRNA than human term placenta. The rat Novikoff hepatoma ascites cell mRNA hybridized to the p120 cDNA probes, but the p120 monoclonal antibody did not react with the Novikoff hepatoma proteins. Novikoff hepatoma mRNA contained 8 times as much p120 mRNA as normal rat liver. As a control, a cDNA was used for protein B23, an abundant nucleolar protein; there were 3.5, 29, and 14 times more B23 mRNA than p120 mRNA in normal rat liver, Novikoff hepatoma ascites cells, and HeLa cells, respectively. Whereas the increased levels of the mRNA and protein B23 reflect increased activity of the nucleolus for any increment of nucleolar function, the increased levels of p120 mRNA and the p120 protein reflect the activity of the G1 phase of the cell cycle. The elevated level of p120 mRNA in tumors may reflect the heightened G1 cascade in transformed cells.
A Progressive Radiorenographic (99mTc-DTPA) Presentation of Surgically Induced Renal Vein Hypertension in Baboons
Authors: F Van Wyk, I C Dormehl, W P Pilloy, M Maree, H Bosman, D J Du Plessis, C Van Zandwyk, M P Van der Merwe, L Dreyer
Journal: European Urology (1988)