tbuckley/cabot-search huggingface dataset:
Impact of a Clinical Trial Initiative on Clinical Trial Enrollment in a Multidisciplinary Prostate Cancer Clinic
Authors: Lydia T. Madsen, Deborah A. Kuban, Seungtaek Choi, John W. Davis, Jeri Kim, Andrew K. Lee, Delora Domain, Larry Levy, Louis L. Pisters, Curtis A. Pettaway, John F. Ward, Christopher Logothetis, Karen E. Hoffman
Journal: Journal of the National Comprehensive Cancer Network (2014)

Clinical oncology trials are hampered by low accrual rates, with fewer than 5% of adult patients with cancer treated on study. Clinical trial enrollment was evaluated at The University of Texas MD Anderson Cancer Center's Multidisciplinary Prostate Cancer Clinic (MPCC) to assess whether a clinical trial initiative, introduced in 2006, impacted enrollment. The trial initiative included posting trial-specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial-specific educational information. The investigators evaluated the frequency of clinical trial enrollment for men with newly diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment. The median age of the 1370 men was 64 years; 32% had low-risk, 49% had intermediate-risk, and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (from 25% to 80%), quality-of-life studies (from 10% to 26%), and studies evaluating investigational treatments and systemic agents (from 6% to 15%) after the trial initiative. In multivariate analysis, younger men (P<.001) and men seen after implementation of the clinical trial initiative (P<.001) were more likely to enroll in trials. Clinical trial enrollment in the MPCC was substantially higher than that seen nationally in adult patients with cancer, and enrollment rates increased after the introduction of a clinical trial initiative.
10P Characterization of chromosomal region 18q in NSCLC KRAS mutant tumors
Authors: S. Clavé, L. Pijuan, D. Casadevall, G. Piquer, F. Rojo, E. Carcereny, Á. Taus, E. Arriola, B. Bellosillo, M. Salido
Journal: Journal of Thoracic Oncology (2016)
Healthcare services in police custody in England and Wales
Authors: Andrew Forrester, Lucia Valmaggia, Pamela J Taylor
Journal: BMJ (2016)

Recent government U turn leaves police healthcare adrift from the NHS

In December 2015, the UK government announced that planned changes to the commissioning of healthcare for people held in police custody in England and Wales would not proceed. These changes had been well considered (having been in planning since a key report by Lord Bradley in 20091), set out formally, and described as one route to securing excellence.2 The government announcement, however, means that the commissioning of these specialist health services will remain with police and crime commissioners instead of being transferred to the National Health Service. This sets police healthcare apart from all other healthcare services, including those that are provided in other parts of the criminal justice pathway. 

The decision represents a missed opportunity. It will prevent much needed service development and could set back current healthcare delivery. It represents a policy reversal that …
The Natural History of Borderline Isolated Systolic Hypertension
Authors: Alex Sagie, Martin G. Larson, Daniel Levy
Journal: New England Journal of Medicine (1993)

Patients with isolated systolic hypertension are at increased risk for cardiovascular disorders. We attempted to determine whether those with borderline isolated systolic hypertension (defined as a systolic blood pressure of 140 to 159 mm Hg and a diastolic blood pressure below 90 mm Hg) have a greater risk of progression to definite (more severe) hypertension and of major morbid or fatal events than people with normal blood pressure (< 140/90 mm Hg).A total of 2767 of the original participants in the Framingham Heart Study were monitored with biennial examinations for up to 34 years for the development of definite hypertension (defined as a systolic blood pressure of > or = 160 mm Hg, a diastolic blood pressure of > or = 90 mm Hg, or the initiation of antihypertensive therapy) and for major cardiovascular events.Borderline isolated systolic hypertension was the most common type of untreated hypertension among adults over the age of 60. After 20 years of follow-up, 80 percent of those with borderline isolated systolic hypertension had progression to definite hypertension, as compared with 45 percent of the normotensive participants (P < 0.001). After adjustment for age, sex, and risk factors for cardiovascular disease, participants with borderline isolated systolic hypertension had an excess long-term risk of cardiovascular disease (hazard ratio, 1.47; 95 percent confidence interval, 1.24 to 1.74) and death from cardiovascular disease (hazard ratio, 1.57; 95 percent confidence interval, 1.24 to 2.00), as compared with normotensive participants. In an analysis of pooled data from biennial examinations to study short-term sequelae, subjects with borderline isolated systolic hypertension had an increased risk of progression to definite hypertension (odds ratio, 3.84; 95 percent confidence interval, 3.35 to 4.41) and of cardiovascular disease (odds ratio, 1.39; 95 percent confidence interval, 1.06 to 1.82).In both the short term and the long term, subjects with borderline isolated systolic hypertension are at increased risk of progression to definite hypertension and the development of cardiovascular disease.
Identifying a role for WT1 in pediatric leukemia.
Authors: M. M. Moazam, K. Eisermann, G. Fraizer, S. J. Kuerbitz
Journal: Journal of Clinical Oncology (2010)

e20005 Background: Leukemia is the most common malignancy in the pediatric age group. To understand the molecular basis of leukemogenesis we examined gene expression patterns. One of the genes expressed in leukemia is the Wilms tumor gene (WT1), which has been shown to be variably expressed based on the type and subtype of leukemia. A mechanistic role as a transcriptional regulator for WT1 in leukemogenesis has not been established. Another gene expressed in leukemia is the vascular endothelial growth factor (VEGF). A high serum VEGF level during induction therapy is associated with poor event free survival in pediatric acute lymphoblastic leukemia (ALL). Previous studies identified potential WT1 binding sites on the VEGF-A gene promoter and demonstrated that WT1 transcriptionally regulated VEGF expression in kidney and prostate cell lines. Methods: 1) To determine the relationship of VEGF and WT1 in pediatric leukemias, their expression was quantified in 16 pediatric ALL samples and normalized to six normal bone marrow samples using quantitative real time PCR (QRT-PCR). 2) Thus, we hypothesized that WT1 negatively regulates VEGF expression in pediatric leukemia. To test this hypothesis, MOLT-4 (T-cell ALL) cells were electroporated with a GFP-tagged WT1 expression construct and VEGF levels were quantified by QRT-PCR. 3) To determine whether WT1 transcriptionally represses the VEGF promoter, a luciferase reporter assay was performed in cells co-transfected with GFP-WT1. The 1012bp VEGF promoter region tested contains 5 potential WT1 binding sites. Results: 1) An inverse relationship was observed between WT1 and VEGF expression in 12 of 16 ALL samples. WT1 negatively regulates VEGF expression in pediatric leukemia. 2) VEGF mRNA levels were repressed in WT1 transfected MOLT-4 compared to untransfected cells. 3) Consistent with our expression studies, we found that WT1repressedthe VEGF promoter. Conclusions: These data support the notion that in pediatric ALL WT1 plays a protective role by repressing VEGF expression. A better understanding of pediatric leukemogenesis and the role of WT1 is needed. The identification of WT1 target genes will help illuminate this poorly understood disease and may identify novel therapeutic targets. No significant financial relationships to disclose.
Why are patients lost to follow-up in a gynecologic oncology clinic?
Authors: V. C. Garcia, A. M. Manalo, J. B. Toral, M. L. Siasu
Journal: Journal of Clinical Oncology (2009)

e17571 Background: The aim of this study is to investigate why patients are lost to follow-up in a gynecologic oncology clinic. Methods: Patients who had been lost to follow up previously, and eventually followed up between April and August 2007 were given a consent form and questionnaire to answer. An approximately equal number of patients who were not lost to follow-up were given the same questionnaire as controls. The first part of the questionnaire included the age, marital status, location, diagnosis/type of gynecologic cancer, type of intervention, educational attainment, occupation and monthly income. The second part asked directly the reason why they were lost to follow-up. Data were recorded in a computerized database via Microsoft Excel. Descriptive statistics were presented in mean, median, standard deviation, minimum, maximum and frequencies. Differences between patients who failed to follow-up (LF) and their controls (NLF) with respect to demographics, disease and treatment characteristics were assessed by an x 2 test or independent t test, depending on the variable. SPSS version 15 was used to perform all analyses. A p &lt; 0.05 was considered significant. Results: There were 50 patients who were not lost and 52 patients who were lost to follow-up. The demographic characteristics between these two groups; i.e., age, marital status, location, diagnosis/type of gynecologic cancer, type of intervention, educational attainment, occupation, and monthly income of patients were all not statistically significant. The most common reason why patients were lost to follow-up was they had no money. Other reasons included: symptoms became better or problems resolved, the follow up was at an inconvenient time and I had family commitment. Conclusions: Patients expressed that the main reason for not following-up was the lack of funds. The majority in these respondents lived below the minimum salary wages. No significant financial relationships to disclose.
Defect of Receptor–Cyclase Coupling Protein in Pseudohypoparathyroidism
Authors: Zvi Farfel, Arnold S. Brickman, Harvey R. Kaslow, Virginia M. Brothers, Henry R. Bourne
Journal: New England Journal of Medicine (1980)

Hormone-sensitive adenylate cyclase contains a recently discovered protein component that is required for stimulation of cyclic AMP synthesis by hormones and guanine nucleotides; the component presumably couples the membrane receptor to the cyclase. We studied this protein (termed "N") in erythrocyte membranes of patients with pseudohypoparathyroidism, using assays of the protein's biochemical activity and of its susceptibility to radiolabeling in the presence of [32P]NAD and cholera toxin. By both assays, the protein's activity was reduced by 40 to 50 per cent in erythrocytes of five of 10 patients with Type I pseudohypoparathyroidism as compared with those of normal and hypoparathyroid subjects and one patient with Type II pseudohypoparathyroidism. If activity of the N protein is reduced in other tissues, this deficiency could cause the resistance of target organs in pseudohypoparathyroidism to parathyroid hormone and other hormones that work via cyclic AMP. Erythrocytes of five patients with Type I pseudohypoparathyroidism, all in one family, showed no defect in activity of the N protein; the biochemical defect of this family remains undefined.
Abstract 1603: High purity isolation of circulating tumor cells for next-generation sequencing
Authors: Nur Lina Mohd Salleh, Yi Fang Lee, Mei Hui Tan, Michelle A. Rosario, Ross A. Soo, Ali Asgar Bhagat, Richie Chuan Teck Soong
Journal: Cancer Research (2015)

Abstract Background: Being able to capture circulating tumor cells (CTCs) and characterize them at a molecular level promises novel insights into the mechanisms that drive metastasis, tumor recurrence and drug resistance. However, next generation sequencing (NGS) of CTCs has been challenged by antibody-enrichment bias, low CTC purity and nucleic acid yields commonly derived from existing technologies. Here, we describe the results of a new label-free protocol for CTC enrichment and NGS analysis. Methods: The lung adenocarcinoma cell line, NCI-H1975, with EGFR T790M and L858R mutations, and colorectal cancer cell line HCT-116, with KRAS G13D mutation, were fluorescently labelled and spiked in concentrations of 250, 50, 10 and 0 cells per 7.5 mL healthy volunteer blood in duplicate. CTCs were enriched using a modified protocol of the label-free spiral microfluidics-based ClearCell® FX system. DNA was extracted by QIAamp Micro kit and sequenced using the Ion AmpliSeq Cancer Hotspot Panel and Ion Torrent PGM system. Results: Imaging analysis indicated that CTCs were efficiently enriched (40-70% recovery) with extremely low leukocyte background (650-1300 cells). Despite a low DNA quantity (&amp;lt;5ng), an average depth of 6897 reads and 97% coverage was achieved in NGS analysis. Expected mutations were detectable in samples down to 10 spiked tumor cells (0.5% CTC purity). Analysis of CTCs from clinical samples is currently on-going. Conclusion: The new protocol generated sufficient label-free CTC purity for NGS analysis, overcoming current limitations in the field, and facilitating discovery and clinical application. Citation Format: Nur Lina Mohd Salleh, Yi Fang Lee, Mei Hui Tan, Michelle A. Rosario, Ross A. Soo, Ali Asgar Bhagat, Richie Chuan Teck Soong. High purity isolation of circulating tumor cells for next-generation sequencing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1603. doi:10.1158/1538-7445.AM2015-1603
Immunologic Control of the Ascites Form of Murine Adenocarcinoma 755. I. Protection With Syngeneic Immune Serum or Lymphoid Cells 2
Authors: Darrow E. Haagensen, Gary Roloson, Jeffrey J. Collins, Samuel A. Wells, Dani P. Bolognesi, Hans J. Hansen
Journal: JNCI Journal of the National Cancer Institute (1978)

The ascites form of the mouse mammary adenocarcinoma 755 (AD755a) that originally arose in a C57BL mouse was used as a model system for the study of the induction of specific tumor immunity. Syngeneic C57BL/6J mice could be immunized against ip challenge with greater than 104 times the dose of AD755a cells necessary to kill 100% of mice by sc inoculation of the cells. The mice were resistant to further challenges for at least 3 months after immunization. Mice hyperimmunized by repeated sc and ip injections of AD755a cells served as donors of immune serum and lymphoid cells, each of which could transfer specific tumor immunity to nonimmunized mice. Protection with immune serum could be transferred with minute quantities of serum (as little as 5 μl) and appeared to have mouse strain specificity. Furthermore, protection against two other mouse tumors, both of which also arose as mammary carcinomas (Ehrlich ascites carcinoma and sarcoma 180), could be achieved by this procedure. Although transfer of protection could be obtained with immune splenocytes and mesenteric lymph node lymphocytes, it could not be obtained with thymocytes. Preliminary results suggested that the protective factor in immune serum was contained in the IgG fraction and had an effective half-life in vivo of greater than or equal to 4.5 days. Initial in vitro and in vivo experiments also indicated that the immune serum led to rosette formation between normal mouse lymphoid cells and the AD755a tumor cells, and these observations were discussed in terms of the possible mechanism(s) of serum-transferred protection.
Cholecystography in the Presence of Liver Disease
Authors: A. David Etess, Bernard Straus
Journal: New England Journal of Medicine (1953)

SYMPTOMS simulating biliary-tract disease may arise in the course of acute or chronic liver disease. Diseases of the liver that produce pain in the right upper quadrant and otherwise mimic affections of the gall bladder or bile ducts include acute hepatitis, portal cirrhosis, acute or chronic passive congestion of the liver and hepatoma. Although the differential diagnosis between jaundice due to parenchymal liver damage and that due to biliary obstruction presents the problem in its most familiar and manifest form, the distinction in patients without jaundice is a problem frequently encountered in clinical medicine. Moreover, disease of the biliary tract . . .
P261 Chemoprophylaxis for LTBI following mass screening in the workplace: unexpected outcomes in the over 35s
Authors: Y Abunga, M Day, J Williams, JP Mamo, SO Brij
Journal: Thorax (2015)

<h3>Introduction</h3> In 2014, over 500 workers in a local factory were screened for TB. 3 cases of active pulmonary TB were identified and seen in the next weekly TB Clinic. 128 workers were identified for further assessment by the local TB Service, of whom 100 were found to be IGRA-reactive. This was declared a major incident and a TB Action Group was set up to facilitate additional out-of-hours TB clinics. <h3>Methods</h3> The local CCG commissioned the additional TB clinics at standard respiratory out-patient tariff: approximately 35 workers were to be assessed by 5 TB clinicians in 2 weekly sessions (18:00–21:00 – 20 min slots) for the first 2 weeks, so that by week 3, all workers would be assessed. As in the weekly TB Clinic, the TB Pharmacy Team would be present to dispense TB medication with drug information leaflets and contact details. Chemoprophylaxis for LTBI was offered to all workers with reactive IGRA and no evidence of active TB independent of their age despite NICE guidance. <h3>Results</h3> Of the 100 workers with reactive IGRA: 18 did not attend; 82 were offered chemoprophylaxis of whom 15 declined treatment; 67 started chemoprophylaxis of whom only 33 completed 3 months treatment with rifampicin and isoniazid. The rate of completion of chemoprophylaxis in the eligible group was 9/35 (25.7%) compared to 24/47 (51.1%) in the over 35 year olds. There was a transient rise in liver enzymes in 1 worker aged over 35 but otherwise there were no other significant side-effects. <h3>Discussion</h3> It is difficult to deny chemoprophylaxis for LTBI infection on the basis of age in a large screening event such as this when the average age is 40 (range 17–63) and the oldest member of the cohort tolerated chemoprophylaxis without significant side-effects. The reasons for reluctance to continue chemoprophylaxis in this cohort are poorly understood although lifestyle issues such as reducing alcohol consumption were perceived to be barriers to successful completion of treatment. <h3>Conclusion</h3> Chemoprophylaxis for LTBI in this cohort was not tolerated in the eligible population. When undertaking mass screening, it is important to ensure that non-standard treatment is funded, if this is to be offered. Treatment of the over 35s significantly increased the workload and cost of this cohort, although uptake of chemoprophylaxis and successful completion was twice that of the workers aged 35 or less.
Genetic and Environmental Influences on Premature Death in Adult Adoptees
Authors: T I Sørensen, G G Nielsen, P K Andersen, T W Teasdale
Journal: New England Journal of Medicine (1988)

To assess genetic and environmental influences on adult mortality, we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them. We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70. We compared these risks with the adoptees' risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70. The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 1.71 (95 percent confidence interval, 1.14 to 2.57) for all causes, 1.98 (1.25 to 3.12) for natural causes, 5.81 (2.47 to 13.7) for infections, 4.52 (1.32 to 15.4) for cardiovascular and cerebrovascular causes, and 1.19 (0.16 to 8.99) for cancers. The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes, natural causes, and infections, 3.02 (0.72 to 12.8) for vascular causes, and 5.16 (1.20 to 22.2) for cancers. A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70. We conclude that premature death in adults has a strong genetic background — especially death due to infections and vascular causes. In contrast, death from cancer, and possibly also from vascular causes, appears to be influenced by the family environment. (N Engl J Med 1988; 318:727–32.)
Case 27-1980
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Raymond D. Adams, Richard S. K. Young, David L. Gang
Journal: New England Journal of Medicine (1980)

Presentation of Case First admission. An 11-year-old boy was admitted to the hospital because of a mediastinal mass.He was well until six weeks earlier, when a nasal voice and cervical lymphadenopathy were observed. One week before admission the cervical lymphadenopathy increased, and a dry cough developed, with intermittent wheezing and dyspnea. An x-ray film of the chest showed a mediastinal mass and a pleural effusion.The temperature was 36.9°C, the pulse 84, and the respirations 22. The blood pressure was 110/80 mm Hg.On examination he appeared well except for marked respiratory stridor in the supine position. Firm, . . .
Chloroqine Treatment of Severe Malaria in Children
Authors: Nicholas J. White, Kirk D. Miller, Frederick C. Churchill, Carol Berry, Judith Brown, Sharyon B. Williams, Brian M. Greenwood
Journal: New England Journal of Medicine (1988)

Although empirical regimens of parenteral chloroquine have been used extensively to treat severe malaria for 40 years, recent recommendations state that parenteral chloroquine should no longer be used because of potential toxicity. We studied prospectively the pharmacokinetics and toxicity of seven chloroquine regimens in 58 Gambian children with severe chloroquine-sensitive falciparum malaria. In all regimens the total cumulative dose was 25 mg of chloroquine base per kilogram of body weight. Chloroquine was rapidly absorbed after either intramuscular or subcutaneous administration (5 mg of base per kilogram every 12 hours), producing high peak blood concentrations but transient hypotension in 5 of 18 patients (28 percent). Intermittent intravenous infusion (5 mg of base per kilogram over 4 hours, repeated every 12 hours) also produced wide fluctuations in chloroquine levels, suggesting incomplete distribution from a small central compartment. Continuous infusion (0.83 mg of base per kilogram per hour for 30 hours) and smaller, more frequent intramuscular or subcutaneous injections of chloroquine (3.5 mg of base per kilogram every 6 hours) produced smoother blood-concentration profiles with lower early peak levels and no adverse cardiovascular or neurologic effects. Chloroquine given by nasogastric tube (initial dose, 10 mg of base per kilogram) was absorbed well, even in comatose children. We conclude that simple alterations in dosage and frequency of administration can give parenteral chloroquine an acceptable therapeutic ratio and reinstate it as the treatment of choice for severe malaria in areas where chloroquine resistance is not a major problem.