tbuckley/cabot-search huggingface dataset:
MPs say health department broke rules when it gave contract to Dr Foster
Authors: Michael Day
Journal: BMJ (2007)

The Department of Health broke guidelines on competitive tendering in handing a £12m (€18m; $24m) research contract “on a plate” to the private health information firm Dr Foster LLP, a parliamentary committee report has said.

In a highly critical report the Committee of Public Accounts (PAC) said that the “degree of favouritism in the choice of company and the haste with which the deal was concluded show a disregard for the rules governing the use of public money.”

The committee's chairman, Edward Leigh, added: “Without the competitive pressure inherent in a tender process, the department's Information Centre simply cannot demonstrate that it paid the best price for its 50% share of the joint …
Do Oral Contraceptives Prevent Rheumatoid Arthritis?
Authors: Deborah J. del Junco, John F. Annegers, Harvinder S. Luthra, Carolyn B. Coulam, Leonard T. Kurland
Journal: JAMA (1985)

Two studies have suggested that the risk of rheumatoid arthritis in women using oral contraceptives is less than half that of nonusers. When a third study from the Mayo Clinic failed to confirm these findings, it was criticized for inclusion of ineligible subjects, misclassification of oral contraceptive use, and inadequate statistical power. Recent expansion of the Mayo Clinic's data resources provided a unique opportunity to resolve the controversy, and a new population-based case-control study was undertaken. In comparison with the previous study, the new investigation had 2.2 times as many eligible cases and more complete ascertainment of oral contraceptive use via access to the records of Planned Parenthood of Minnesota. Comparing any prior use of oral contraceptives with never having used them, the relative risk of rheumatoid arthritis estimated from 182 cases and their 182 matched controls was 1.1 (95% confidence interval, 0.7 to 1.7). The relative risk for current use was 1.3 (95% confidence interval, 0.7 to 2.4). The lack of a protective effect was independent of age, disease severity, and disease end point (date of confirmed diagnosis or symptom onset). (<i>JAMA</i>1985;254:1938-1941)
Braces in Spinal Curvature. A Discussion of a Few Points found in an Editorial of Sept. 10, 1898, in the Journal of the American Medical Association.
Authors: A. M. Phelps
Journal: JAMA (1898)

New York, Oct. 31, 1898. <h3>To the Editor:</h3> —I observe in theJournalof September 10 an editorial on "Curvature of the Spine," which is so far at variance with clinical observations, scientific facts, and known truths, that I believe, in the interest of the profession and the unfortunate individuals afflicted with this deformity, that a short discussion of the editoral and its subject-matter, will not be wholly out of place. I quote from the editorial: "What greater mistake can there be in medicine than that of fitting a brace to a child suffering from spinal curvature?"... "What folly, what total lack of reason it would seem to put a splint on a weak muscle!"... "The fault is entirely one of nutrition and development." These statements are misleading, both to the profession and to the patient. They are arbitrary in their inception, empiric and unscientific as an edict. These statements
Effectiveness of Primary Androgen-Deprivation Therapy for Clinically Localized Prostate Cancer
Authors: Arnold L. Potosky, Reina Haque, Andrea E. Cassidy-Bushrow, Marianne Ulcickas Yood, Miao Jiang, Huei-Ting Tsai, George Luta, Nancy L. Keating, Matthew R. Smith, Stephen K. Van Den Eeden
Journal: Journal of Clinical Oncology (2014)

Purpose Primary androgen-deprivation therapy (PADT) is often used to treat clinically localized prostate cancer, but its effects on cause-specific and overall mortality have not been established. Given the widespread use of PADT and the potential risks of serious adverse effects, accurate mortality data are needed to inform treatment decisions. Methods We conducted a retrospective cohort study using comprehensive utilization and cancer registry data from three integrated health plans. All men were newly diagnosed with clinically localized prostate cancer. Men who were diagnosed between 1995 and 2008, were not treated with curative intent therapy, and received follow-up through December 2010 were included in the study (n = 15,170). We examined all-cause and prostate cancer-specific mortality as our main outcomes. We used Cox proportional hazards models with and without propensity score analysis. Results Overall, PADT was associated with neither a risk of all-cause mortality (hazard ratio [HR], 1.04; 95% CI, 0.97 to 1.11) nor prostate-cancer–specific mortality (HR, 1.03; 95% CI, 0.89 to 1.19) after adjusting for all sociodemographic and clinical characteristics. PADT was associated with decreased risk of all-cause mortality but not prostate-cancer–specific mortality. PADT was associated with decreased risk of all-cause mortality only among the subgroup of men with a high risk of cancer progression (HR, 0.88; 95% CI, 0.78 to 0.97). Conclusion We found no mortality benefit from PADT compared with no PADT for most men with clinically localized prostate cancer who did not receive curative intent therapy. Men with higher-risk disease may derive a small clinical benefit from PADT. Our study provides the best available contemporary evidence on the lack of survival benefit from PADT for most men with clinically localized prostate cancer.
Enhanced function of pancreatic islets co-encapsulated with ECM proteins and mesenchymal stromal cells in a silk hydrogel
Authors: Nicolynn E. Davis, Liese N. Beenken-Rothkopf, Annie Mirsoian, Nikola Kojic, David L. Kaplan, Annelise E. Barron, Magali J. Fontaine
Journal: Biomaterials (2012)
THE BRITANNICA AND OSTEOPATHY
Authors: William Y. Ward
Journal: JAMA (1926)

To the Editor:  —Your London correspondent (The Journal, Dec. 12, 1925, p. 1901) complains of the new activities of osteopaths. Referring to a letter from the vice president of the British Osteopathic Association, published in the Times , he says that the writer  the audacity to describe osteopathy as 'a system which has scientifically classified the entire field of mechanicotherapeutics' and refers to the manifesto of his association in which osteopathy is defined as 'that system of the art of healing which regards the structural integrity of the body as the most important single factor in the maintenance of health.'  Perhaps your correspondent is unaware of the part played by the Encyclopaedia Britannica in the sale of osteopathy to the British public. The supplementary volumes of the eleventh edition, published in 1922, contain a long article, signed with the initials G. W. Ri. The writer is George Washington Riley, Ph.B.,
Uncertainty in sample estimates: sampling error
Authors: P. Sedgwick
Journal: BMJ (2015)

The effects of a shared care obesity management programme on body mass index (BMI) and related outcomes in obese children were investigated using a randomised controlled trial. The intervention consisted of general practice surveillance for childhood obesity, followed by obesity management across primary and tertiary care settings using a shared care model. The intervention was delivered over one year. The control treatment consisted of “usual care.” Participants were children aged 3-10 years who had a BMI above the 95th centile for their age and sex. The setting was Melbourne, Australia. In total, 118 children were recruited through their general practice and randomised to the intervention (n=62) or control (n=56).1 The primary outcome was BMI. Measurements of BMI were transformed to z scores. At the end of follow-up, the intervention group had a smaller mean BMI z score than the control group, although the difference was not significant (2.0 (standard deviation 0.5) v 2.0 (0.4); adjusted mean difference −0.05, 95% confidence interval −0.14 to 0.03; P=0.2). No evidence of a significant difference was found for any secondary outcome, including body fat percentage, waist circumference, physical activity, quality of diet, and health related quality of life. It was concluded that the shared care model of primary and tertiary care management had no effect on BMI and related outcomes in obese children. Which of the following statements, if any, are true?
Regression of Microalbuminuria in Type 1 Diabetes
Authors: Bruce A. Perkins, Linda H. Ficociello, Kristen H. Silva, Dianne M. Finkelstein, James H. Warram, Andrzej S. Krolewski
Journal: New England Journal of Medicine (2003)

In the present study, we aimed to determine the frequency of a significant reduction in urinary albumin excretion and factors affecting such reduction in patients with type 1 diabetes and microalbuminuria.
Significance of anti-entactin antibodies in patients with systemic lupus erythematosus and related disorders.
Authors: R Saxena, G Sturfelt, O Nived, J Wieslander
Journal: Annals of the Rheumatic Diseases (1994)

To further evaluate the association of anti-entactin antibodies with clinical manifestations in patients with systemic lupus erythematosus (SLE) and related disorders.Sera were analysed for anti-entactin antibodies from 79 patients with SLE, 38 patients with rheumatoid arthritis, 20 patients with progressive systemic sclerosis and five with Behçet's syndrome. Sera from 150 healthy blood donors and 20 patients with pneumonia were analysed as controls. To study the association of anti-entactin antibodies with severity and activity in SLE, 30 patients were assigned into three groups with 10 patients in each: (1) with mild manifestations; (2) severe disease without renal involvement and (3) frank lupus nephritis. Two blood samples from each patient were analysed, one from the active and the other from the inactive phase of the disease. Additionally, serial sera from 12 patients with SLE were also analysed.Thirty one patients with SLE (39%) had IgG, IgM or both anti-entactin antibodies. Twenty three of these patients (29%) had biopsy verified glomerulonephritis and 12 (50%) were positive for anti-entactin antibodies. Of the remaining 56 patients without apparent renal involvement, 18 (36%) were positive for anti-entactin antibodies. (chi squared = 2.77, p > 0.05). With the exception of rheumatoid arthritis where six patients (24%) had IgM anti-entactin antibodies, the antibodies were present much less frequently in other diseases (two patients with systemic vasculitis whilst none of the patients with PSS or Behçet's syndrome). Only one patient with pneumonia and none of the 150 sera from healthy blood donors had anti-entactin antibodies. Among Group 1, three (30%) were positive for IgG or IgM anti-entactin antibodies. Six (60%) patients in group 2, and five patients (50%) in group 3 were positive for anti-entactin antibodies. However, the difference between the presence of anti-entactin antibodies between group 1 and 2 or between group 1 and 3 was not significant (p = 0.15 and 0.19 respectively). There was no significant correlation between the titres of anti-entactin antibodies and total serum concentration of IgG (r = 0.141, p > 0.10) and IgM. (r = 0.130, p > 0.10). Furthermore, no significant correlation was observed between SLE disease activity index (SLEDAI) scores and the titres of IgG (r = 0.067, p > 0.10) or IgM (r = -0.033, p > 0.10) anti-entactin antibodies.The study demonstrates that anti-entactin antibodies are present in a significant number of patients with SLE and tend to be more common in those with severe disease, with or without nephritis, than in patients with mild disease manifestations. There is no correlation between the titre of anti-entactin antibodies and severity or activity of SLE.
New Drugs: Bromocriptine and Endocrine Disorders
Authors: Richard F. Spark, Gabriel Dickstein
Journal: Annals of Internal Medicine (1979)

Bromocriptine, a dopaminergic agonist, has been used to treat many endocrine disorders. In hyperprolactinemia associated with galactorrhea, amenorrhea, oligospermia, and impotence, bromocriptine reduces prolactin levels to normal and allows for satisfactory return of sexual and reproductive function in 90% of patients. In acromegaly, bromocriptine brings about subjective improvement in 75% of patients with reduction in growth-hormone levels to normal in 22% of patients. Bromocriptine has been used in premenstrual tension, functional infertility, Nelson's syndrome, and Cushing's disease with variable benefit. In low doses, side-effects are minimal. In higher doses, digital vasospasm and gastrointestinal bleeding have occurred. Although bromocriptine has been used in a wide variety of endocrine disorders, it appears to be most useful in treatment of male and female infertility associated with hyperprolactinemia.
Abstract 3263: Acceleration of mammary tumorigenesis by PDK1 and peroxisome proliferator-activated receptorδ
Authors: Claire B. Pollock, Yuzhi Yin, Hongyan Yuan, Xiao Zeng, Sruthi King, Levy Kopelovich, Robert I. Glazer
Journal: Cancer Research (2010)

Abstract The 3-phosphoinositide-dependant kinase-1 (PDK1) is a master regulator of least 23 members of the AGC protein kinase family, including protein kinase B (PKB/Akt). Genetic alterations which activate PI3K/AKT signaling are common in cancer, and elevated expression of PDK1 has been detected in various cancer types, including breast cancer. To assess the effect of PDK1 over-expression in mammary gland function and tumorigenesis, transgenic mice were generated that express PDK1 in the mammary epithelium under the control of the MMTV promoter. PDK1 over-expression resulted in increased pT308Akt and pS9GSK3β and PPARδ expression, but did not affect the phosphorylation of other targets, such as RSK2, S6K and BAD. Transgenic mice exhibited a moderate acceleration of tumor induction by progestin/DMBA in comparison to wild-type mice, and GW501516 treatment accelerated tumorigenesis in both transgenic and wild-type animals. GW501516 promoted the formation of highly keratinized squamous cell carcinomas in both PDK1 transgenic and wild-type mice, and exhibited a profile of elevated pT308Akt and PPARδ expression. Treatment of wild-type mice with PPARδ agonist GW501516 alone increased PDK1 and pT308Akt expression in mammary epithelium. Thus, MMTV-PDK1 mice provide a model in which PDK1 enhances mammary carcinogenesis through activation of Akt and PPARδ to elicit a cooperative effect in promoting tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3263.
Simvastatin as a novel therapeutic agent for venous ulcers: a randomized, double-blind, placebo-controlled trial
Authors: M.T.P. Evangelista, M.F.A. Casintahan, L.L. Villafuerte
Journal: British Journal of Dermatology (2014)

Although the standard treatment for venous ulcers is compression, drugs may be used as adjunctive therapy. Simvastatin has shown potential wound-healing properties; however, no studies have investigated its use in venous ulcers.To assess the efficacy and safety of simvastatin in venous ulcer healing when combined with standard treatment for ulcers.This was a randomized, double-blind, placebo-controlled trial. Outcome measures were the proportion of healed ulcers, healing time, total surface area healed and Dermatology Life Quality Index (DLQI) scores.Sixty-six patients were randomized into two groups: a simvastatin (n = 32) and a control (n = 34) group. Among ulcers ≤ 5 cm, 100% were healed in the simvastatin group, and 50% were healed in the control group [relative risk (RR) 0·10, 95% confidence interval (CI) 0·0141-0·707]. The average healing times for ulcers ≤ 5 cm were 6·89 ± 0·78 weeks and 8·40 ± 1·13 weeks for the simvastatin and control groups, respectively (P < 0·001). Among ulcers > 5 cm, 67% closed in the simvastatin group, with a mean healing time of 9·17 ± 1·07 weeks. No ulcers of this size closed in the control group (RR 0·33, 95% CI 0·132-0·840). The simvastatin group had lower DLQI scores (P < 0·001) post-treatment. No adverse effects were documented.Simvastatin 40 mg daily, in addition to standard wound care and compression, is associated with a significant improvement in healing rate and time, as well as an improved patient quality of life when compared with placebo in the management of venous ulcers.
Pharmacokinetic, pharmacodynamic, and pharmacogenetic determinants of osteonecrosis in children with acute lymphoblastic leukemia
Authors: Jitesh D. Kawedia, Sue C. Kaste, Deqing Pei, John C. Panetta, Xiangjun Cai, Cheng Cheng, Geoffrey Neale, Scott C. Howard, William E. Evans, Ching-Hon Pui, Mary V. Relling
Journal: Blood (2010)
Abstract 4419: Pilot toxicology study of the B-cell lymphoma drug candidate SH7139 demonstrates lack of toxicity in beagles.
Authors: Rod Balhorn, Saphon Hok, Monique Balhorn
Journal: Cancer Research (2013)

Abstract A group of small molecule drug candidates for non-Hodgkin's lymphoma, called Selective High Affinity Ligands (SHALs), have been developed to target the cell surface antigen HLA-DR10 that is known to be over expressed on many B-cell derived malignancies. These compounds are created by chemically linking together two or three small molecule “recognition elements” that have been identified to bind to neighboring unique sites on the surface of the target protein. One of these compounds, SH7139, has been shown previously to be effective in treating human B cell lymphoma in a mouse xenograft model at extremely low doses (5μg/kg). Earlier experiments conducted in mice have also shown the compound to exhibit no signs of toxicity at 2000 times (10mg/kg) this dose. In an effort to obtain preliminary toxicology and safety data on SH7139 and assess the reversibility or persistence of any potential toxic effects prior to its being evaluated in a pet dog B-cell lymphoma trial for treating canine B-cell lymphomas, a pilot 28-day toxicology study was performed in three naïve Beagles. SH7139 was administered intravenously in three doses injected on days 0, 7 and 14. The dose tested, 50μg/kg, was ten times the dose required to cure 69% of mice carrying Raji xenografts. During the in-life period, animals were observed daily for mortality, moribundity, and food consumption, detailed clinical examinations were conducted on the days of dose, 24 hrs post-dose and weekly thereafter, and individual body weights and temperatures were recorded on the days of dosing and selected days after dosing. Clinical pathology samples (urinalysis, hematology, coagulation, clinical chemistry) were collected prior to dose administration on the days of dose and during the recovery phase (Days 21 and 28). On Day 29, all animals were euthanized and a complete necropsy was conducted with tissue collection and preservation. The key tissues were embedded in paraffin, H&amp;E stained and examined microscopically by a board-certified pathologist. The results of this study show the treatment with SH7139 is well tolerated by healthy, naïve dogs. No treatment-related effects on body weight, body temperature, food consumption or clinical pathology parameters were observed. In addition, the lack of significant changes in hematology, clinical chemistry, urinalysis or coagulation parameters also indicate SH7139 exhibited no apparent systemic toxicity or side effects. Citation Format: Rod Balhorn, Saphon Hok, Monique Balhorn. Pilot toxicology study of the B-cell lymphoma drug candidate SH7139 demonstrates lack of toxicity in beagles. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4419. doi:10.1158/1538-7445.AM2013-4419
Avoiding spurious hyperkalaemia
Authors: R. Gama, M. Cornes, C. Ford
Journal: BMJ (2009)

A common but often unrecognised cause of spurious hyperkalaemia1 is sample contamination with potassium ethylenediaminetetraacetic acid (kEDTA), a widely used sample tube anticoagulant for laboratory assays. kEDTA contamination may account for 25% of samples with unexpected hyperkalaemia from patients in both primary and secondary care,2 3 and if unrecognised …
Abstract B34: Overcoming resistance to EGFR-Tyrosine Kinase Inhibitor therapy in non-small cell lung cancer
Authors: Rafael Sierra, Anderson Chang, Jason Moffat, Benjamin G. Neel, Ming-Sound Tsao
Journal: Clinical Cancer Research (2012)

Abstract Lung cancer is the leading cause of cancer death in developed countries both for men and women; and the second most common type of cancer diagnosed, with less than 15% of patients surviving beyond 5 years. Since more than 60% of lung adenocarcinomas and more than 90% of lung squamous cell carcinomas express high levels of EGFR mRNA and protein, it has been the focus of efforts to develop new agents that target the EGFR pathway. Clinical trials have demonstrated that patient selection plays a major role for patient response. Patients that present amplification or activating mutations (L878R or exon 19 deletions) of EGFR, have higher response rates. Selection improved response rates from less than 10% to over 60–80%. Despite the promising results, all patients that receive TKI therapy develop resistance to treatment in less than one year. The mechanisms of resistance to EGFR TKi's described so far are those dependant on the overactivation/amplification of other receptor tyrosine kinases (RTK) capable to sustain anti-apoptotic signaling pathways. Our study proposes the use of genome-wide screenings using an 80,000 shRNA library on EGFR resistant cells can identify new genes that mediate the resistance to EGFR targeted therapy and provide the basis for designing new therapeutic approaches to avoid the emergence of resistance. So far, we have generated a shortlist of gene candidates that confer synergistic synthetic lethal interactions with EGFR targeted therapies and that are also highly expressed in resistant cells. We are currently overexpressing candidate genes in sensitive cells searching for those that can confer resistance to EGFR targeted therapies. Our study proposes target genes that can synergize with the current treatments to create new therapeutical strategies that can avoid the acquisition of resistance to targeted therapies. Overall, the information gained from this type of study can be applicable to tumors where ERBB receptor(s) play an important role and targeted therapies are currently used.