tbuckley/cabot-search huggingface dataset:
Early integration of palliative care services with standard oncology care for patients with advanced cancer
Authors: Joseph A. Greer, Vicki A. Jackson, Diane E. Meier, Jennifer S. Temel
Journal: CA A Cancer Journal for Clinicians (2013)

Scientific advances in novel cancer therapeutics have led to remarkable changes in oncology practice and longer lives for patients diagnosed with incurable malignancies. However, the myriad options for treatment have established a culture of cancer care that has not been matched with a similar availability of efficacious supportive care interventions aimed at relieving debilitating symptoms due to progressive disease and treatment side effects. Accumulating data show that the introduction of palliative care services at the time of diagnosis of advanced cancer leads to meaningful improvement in the experiences of patients and family caregivers by emphasizing symptom management, quality of life, and treatment planning. In this review article, the rationale and evidence base for this model of early palliative care services integrated into standard oncology care are presented. In addition, the implications and limitations of the existing data to 1) elucidate the mechanisms by which early palliative care benefits patients and families; 2) guide the dissemination and application of this model in outpatient settings; and 3) inform health care policy regarding the delivery of high-quality, cost-effective, and comprehensive cancer care are discussed.
Prevalence of respiratory symptoms in migrant children to Italy: the results of SIDRIA‐2 study
Authors: E. Migliore, N. Pearce, M. Bugiani, G. Galletti, A. Biggeri, L. Bisanti, N. Caranci, V. Dell'Orco, M. De Sario, P. Sestini, S. Piffer, G. Viegi, F. Forastiere, C. Galassi, G. Ciccone
Journal: Allergy (2007)

Background: Epidemiological studies have documented large international variations in the prevalence of asthma, and ‘westernization’ seems to play an important role in the development of the disease. The aims of this study were to compare the prevalence of respiratory symptoms in migrant and nonmigrant children resident in Italy, and to examine the effect of length of time living in Italy. Methods: Data were collected in a large cross‐sectional study (SIDRIA‐2) performed in 12 Italian centres, using standardized parental questionnaires. For the 29 305 subjects included in the analysis (6–7 and 13–14 years old), information about place of birth and parental nationality was available. Results: There were 1012 children (3%) born outside of Italy, mainly in East Europe. Lifetime asthma and current wheeze were generally significantly less common among children born abroad than among children born in Italy (lifetime asthma: 5.4% and 9.7% respectively, P &lt; 0.001; current wheeze: 5.2% and 6.9%, respectively, P = 0.04). Lower risks for lifetime asthma (prevalence odds ratio, POR = 0.39; 95% CI: 0.23–0.66) and current wheeze (POR = 0.72; 95% CI: 0.47–1.10) were found for children who had lived in Italy &lt;5 years, while migrant children who had lived in Italy for 5 years or more had risks very similar to Italian children. Conclusions: Migrant children have a lower prevalence of asthma symptoms than children born in Italy. Prevalence increased with the number of years of living in Italy, suggesting that exposure to environmental factors may play an important role in the development of asthma in childhood.
Fetal Exposure to Diagnostic X Rays, and Leukemia and Other Malignant Diseases in Childhood
Authors: Dorothy D. Ford, J. C. S. Paterson, W. L. Treuting
Journal: JNCI Journal of the National Cancer Institute (1959)

A survey of the comparative incidence of exposure to antenatal irradiation in utero and of the occurrence of leukemia and other malignant diseases in later childhood is reported. The case material consisted of deaths, before the age of 10 years, from leukemia and other malignant diseases, in Louisiana during the 5-year period 1951–55. The control cases were deaths from other causes matched for age, sex, race, and place of death. Information concerning the incidence of irradiation (diagnostic X rays during the last trimester of pregnancy) was obtained from professional sources, either from the doctor who delivered the mother or from the institution in which the child was born. The incidence of X-ray exposure was found to be as follows: leukemia cases, 26.9 percent; malignant disease cases, 28.4 percent; and control cases, 18.3 percent. These findings are in substantial agreement with those of Stewart et al., in England. The findings lend emphasis to the need for minimizing exposure of the fetus to X rays, by careful determination of the indications for antenatal radiography and by attention to the technical procedures.
Abstract 8167: MiR-424 Promotes the Differentiation of Monocytes to Macrophages in Patients with Coronary Artery Disease, but Can Be Inhibited by Isoflavone In Vitro
Authors: Shao-Hua Li, Ji-Zheng Wang, Chang-Xin Wang, Lei Jia, Jing-Zhou Chen, Rutai Hui
Journal: Circulation (2011)

MiR-424 has been demonstrated to inhibit the expression of its target protein Nuclear factor I-A (NFI-A) in monocytes and promote the differentiation of monocytes to macrophages in hemopoiesis. This differentiation is also one of the pivotal steps in atherosclerosis. Whether miR-424 has a potential role in the atherosclerosis has been still unknown. Isoflavone has been proved to be an agonist of PPARγ and play anti-atherosclerotic roles by reducing the level of IL-6 and TNF-α in vitro . We assessed the hypothesis that miR-424 might participate the progression of atherosclerosis by inhibiting the expression of NFI-A in monocytes and promoting the differentiation of monocytes to macrophages. Isoflavone might reduce the level of miR-424 in ox-LDL stimulated monocytes to prevent the differentiation of monocytes to macrophages in vitro . Totally 50 subjects were enrolled and divided into three groups: acute myocardial infarction (AMI) group, unstable angina (UA) group and control group. The relative expressions of miR-424 and NFI-A in peripheral monocytes were determined. In vitro , monocytes from healthy subjects were cultured with ox-LDL or ox-LDL combined with isoflavone to clarify whether isoflavone could inhibit the expression of miR-424 in ox-LDL stimulated monocytes. The relative expression levels of miR-424 were significantly increased in UA (1.38±0.33 vs 1.00±0.21, P &lt;0.05) and AMI (3.69±0.92 vs 1.00±0.21, P &lt;0.001) groups as compared to controls. The expression of NFI-A was significantly reduced in UA group, even lower in patients with AMI (AMI: 0.17±0.03; UA: 0.62±0.03; Control: 1.00±0.09). In vitro , the relative level of miR-424 was significantly increased (5.22±0.75 vs 1.02±0.11, P &lt;0.001) in ox-LDL stimulated monocytes but obviously reduced (1.48±0.17 vs 5.22±0.75, P &lt;0.01) after isoflavone added. The levels of IL-6 (10.49±2.15 pg/ml vs 17.92±2.47 pg/ml, P &lt;0.01) and TNF-α (42.81±2.62 pg/ml vs 187.19±7.35 pg/ml, P &lt;0.001) were also significantly reduced in ox-LDL combined isoflavone group as compared to ox-LDL alone group. Conclusively, miR-424 promotes the progression of atherosclerosis by inhibiting the expression of NFI-A in monocytes. Isoflavone can inhibit the increased level of miR-424 in ox-LDL stimulated monocytes in vitro .
Abstract 2599: KDM3A tyrosine phosphorylation by Ack1 promotes tamoxifen-resistance in breast cancer
Authors: Kiran Mahajan, Sayantani Bandyopadhyay, Nupam Mahajan
Journal: Cancer Research (2014)

Abstract Hormone therapy with the selective estrogen-receptor modulator tamoxifen (TAM) provides palliative benefit for patients with breast cancer. However, estrogen receptor α (ER hereafter) positive breast tumors with high expression of HER2 receptor tyrosine kinase often develop significant resistance to tamoxifen therapy. Thus, precise understanding of activation of Estrogen (E2)-independent ER regulated gene transcription in tamoxifen-resistant breast tumors could open new therapeutic avenues to target drug-resistance and ameliorate poor prognosis. The non-receptor tyrosine kinase, Ack1 (also known as TNK2) has emerged as a major integrator of signaling from various receptor tyrosine kinases including HER2. Here we demonstrate that heregulin promoted ER activity at Estrogen Response Element (ERE) in the presence of tamoxifen, which was significantly downregulated upon Ack1 knockdown. We observed that Ack1 phosphorylated the ER co-activator, KDM3A, a H3K9 demethylase, at evolutionary conserved tyrosine 1114 in heregulin dependent manner in the presence of tamoxifen. KDM3A demethylates H3 mono- and dimethyl-K9 in vitro and in vivo. Heregulin mediated Ack1 activation resulted in significant decrease in the level of monomethyl-H3K9, while, monomethyl-H3K27 levels remained unchanged. Further, inhibition of Ack1 by small molecule inhibitor AIM-100 or Dasatinib resulted in significant increase in the level of monomethyl-H3K9. Therefore by its ability to regulate the activity of ER co-activator such as KDM3A, activated Ack1 may modulate ER target gene expression in the absence of estrogen and confer TAM-resistance to cancer cells. Thus, Ack1 inhibitors hold the potential as novel therapeutics to treat a subset of tamoxifen resistant breast cancers. Citation Format: Kiran Mahajan, Sayantani Bandyopadhyay, Nupam Mahajan. KDM3A tyrosine phosphorylation by Ack1 promotes tamoxifen-resistance in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2599. doi:10.1158/1538-7445.AM2014-2599
Textbook of Adverse Drug Reactions.
Authors: D. M. Davies
Journal: Annals of Internal Medicine (1981)

Adverse drug reactions represent a common problem for those of us who work in general internal medicine.Previous surveys have suggested that between 10 and 18% of patients admitted to general medical wards will suffer an adverse reaction to therapy prescribed while an inpatient.Thus, drug therapy is a main cause of iatrogenic illness.It is, therefore, important for doc- tors to have a reliable source of reference about adverse drug reactions.In order to test how far this work fulfilled the need, I used it for a period of a month to check on drug-related problems in patients referred to me.I used it also when writing a chapter on cardiovascular drug therapy in the elderly.By so doing, I was able to assess 17 of the 30 chapters, whose authors were mostly based in or had previously worked at Newcastle-upon-Tyne.For the most part the book satisfied my needs.It has an excellent index and is well referenced.I found it particularly helpful in the management of a patient with liver disease due to therapy for tuberculosis.Simi- larly, it was useful for another patient thought to have the neuroleptic malignant syndrome.Other 'success- es' included drug-induced convulsions, purpura and drug interactions with digoxin, as well as those between non-steroidal anti-inflammatory drugs and B- adrenoceptor antagonists or diuretics.The sections on antibiotic associated diarrhoea and renal dysfunction due to ACE inhibitors were well referenced, as were those on drug-induced hypotension.
Wrist actigraphy predicts outcome in patients with pulmonary hypertension
Authors: Silvia Ulrich, Manuel Fischler, Rudolf Speich, Konrad E. Bloch
Journal: European Respiratory Journal (2012)

Rationale:  Pulmonary hypertension (PH) impairs quality of life, exercise and survival. Simple measures to monitor the disease are needed. We tested whether actigraphy by a wrist-worn device in the patients home reflects disease severity in PH patients.   Methods:  We studied 23 outpatients with precapillary PH (15 females) in WHO functional classes II-IV. Evaluations comprised clinical examination and actigraphy during 2 weeks while patients pursued their usual life at home. Actigraphies were correlated with clinical data and mean pulmonary artery pressure (mPAP). Deaths, lung transplantations and pulmonary endarterectomy were recorded during 4 years.   Results:  Actigraphies revealed a mean±SD day-time with activity of 14:57±1:14 hours, activity counts were 146±125/min. Very severely impaired patients (mPAP 50±7 mmHg) rested more time immobile during nights (8:25±1:18h) and were less active during days (54±44 counts/min) compared to modestly impaired patients (mPAP 33±7 mmHg; night-time immobile 6:58±0:39h; day-time activity 229±148 counts/min, P   Conclusion:  A long nocturnal rest and reduced day-time activity recorded by actigraphy are associated with severe hemodynamic impairment and reduced survival in patients with PH. Therefore, wrist actigraphy performed during everyday life in the patient9s home holds promise as a simple tool for assessment of disease severity and prognosis in patients with PH.
Mental health bill will be subject to pre-legislative scrutiny
Authors: R. Dobson
Journal: BMJ (2003)

A revised mental health bill for England and Wales is to be brought forward as soon as possible and will be subject to pre-legislative scrutiny.

The government also plans to monitor the use of compulsion, an area of the draft bill published last year that proved highly controversial ( BMJ 2003;326: 406-7).

The bill, described as the first major overhaul relating to mental health since the 1950s, was said to …
Abstract P3-07-06: Survival benefit increases after breast conserving therapy compared to mastectomy when axillary node status is positive in early stage breast cancer: A registry based follow-up study of Norwegian women with screening and interval detected breast cancer pr
Authors: Olaf Johan Hartmann-Johnsen, Ellen Schlichting, Rolf Kaaresen, Jan Franz Nygaard
Journal: Cancer Research (2015)

Abstract BACKGROUND: Recent register studies on early stage breast cancer have shown better survival when women underwent breast-conserving treatment (BCT) compared to mastectomy (MTX). It is unclear if this is due to selection effects or to a systemic benefit of BCT compared to MTX. If there is a systemic benefit this could theoretically be more prominent in some subgroups of breast cancer. The aim of this study is to evaluate if there are any subgroups with early stage breast cancer that benefits more of BCT compared to MTX. METHOD: A cohort of 6.629 women aged 50-69 with primary operable breast cancer detected in the screening programme (on screening or between screening, interval cancer) were selected from January 1998 until December 2009 and followed up until end of 2010. Life tables for overall survival (OS) and breast cancer specific survival (BCSS) were calculated in surgery groups and stages. Corresponding Kaplan-Meier plots were stratified in T1N1M0 and Ductal Carcinoma. OS and BCSS were compared using Cox proportional hazard for estimating hazard ratio between BCT and MTX in crude and adjusted analysis. RESULTS: 5-years BCSS in T1N0M0 was 99% for both surgical cohorts (BCT and MTX). 5-years BCSS in T1N1M0 was 98% for women undergoing BCT and 91% for women undergoing MTX. Respectively, 10-years BCSS in T1N1M0 was 96% for women undergoing BCT and 83% for women undergoing MTX. In adjusted analysis, HR for breast cancer death for women with stage T1N1M0 undergoing MTX compared to BCT was 3.12 (95% CI: 1.71-5.72). Respectively, 3.67 (95% CI: 1.20-11.22) stratified on grade III and 4.89 (67 (95% CI: 1.25-19.01) stratified on hormone receptor negative disease. CONCLUSION: The benefit of BCT compared to MTX seems to increase with increasing severity of the breast cancer disease, positive nodal status (N1), grade III and hormone receptor negative disease. These finding indicate a systemic benefit of BCT compared to MTX. Citation Format: Olaf Johan Hartmann-Johnsen, Ellen Schlichting, Rolf Kaaresen, Jan Franz Nygaard. Survival benefit increases after breast conserving therapy compared to mastectomy when axillary node status is positive in early stage breast cancer: A registry based follow-up study of Norwegian women with screening and interval detected breast cancer pr [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-06.
Abstract 660: Engineering strategies to control stoichiometry, site of conjugation, serum stability and effector functions of antibody-drug conjugates
Authors: Nazzareno Dimasi, Ryan Fleming
Journal: Cancer Research (2014)

Abstract A promising approach to enhance the antitumor activity of antibodies and reduce the systemic toxicity of small molecule anti-cancer drugs is to covalently attach the small molecule to the antibody thus forming antibody drug conjugates (ADCs). Conventionally, ADCs are produced by chemical conjugation of drugs to antibodies through either lysine side chain amines or native cysteine sulfhydryl groups generated by reduction of interchain disulfide bonds. Both of these methods yield heterogeneous conjugates with complex biophysical properties. To limit these liabilities, we have designed, characterized, and validated antibody variants, which allow precise control of the site of conjugation and the drug load; such as two and/or four drugs per antibody can be site-specific conjugated. These engineered antibody variants can be efficiently and site-specifically conjugated with drug payloads at milligram and gram scales to yield homogenous ADC products. Engineered antibody variants described here retain antigen-binding affinities, FcRn binding, and have biochemical, biophysical and manufacturability properties similar to their non-engineered parent antibodies. Upon conjugation to highly cytotoxic drugs with anti-mitotic and/or DNA alkylating activities, the antibody variants have potent in vitro and in vivo anti-tumor activity. Furthermore, we describe ADCs vehicles that provide efficient scaffolds for site-specific conjugation of drugs while offering the opportunity to minimize off-target toxicities often observed with ADCs as a result of their binding to cells expressing Fc-gamma receptors. Finally, we show the impact of the identified sites for drug conjugation on the in vivo pharmacokinetic and safety profile of ADCs in rats. Our strategies for engineering ADCs with defined sites for conjugation, controlled drug loads, potentially decreased off-target toxicity, and optimal serum stability are broadly applicable to any full-length IgG or Fc-containing therapeutics as they involve the Fc constant domain of the antibody. Citation Format: Nazzareno Dimasi, Ryan Fleming. Engineering strategies to control stoichiometry, site of conjugation, serum stability and effector functions of antibody-drug conjugates. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 660. doi:10.1158/1538-7445.AM2014-660
Using a Novel Computer Technology for Tailoring Targeted and Chemotherapeutic Drug Schedules to the Individual Patient
Authors: Zvia Agur, Irit Ziv, Revital Shochat, Michael Wick, Craig Webb, David Hankins, Levon Arakelyan, David Sidransky
Journal: Clinical Cancer Research (2006)

Introduction: Over the last three decades, mathematical approaches have been employed in the attempt to improve the pharmaco-therapeutic rationale in oncology (e.g., Agur, Arnon, Schechter, 1988, 1992; Ubezio, Tagliabue, Schechter, Agur, 1994). To aid in tailoring drug treatments to individual patients, a predictive biosimulation technology was constructed, comprising computer-implemented mathematical models of physiological, pathological and pharmacological processes in a patient's body (denoted Virtual Cancer Patient, or VCP). The VCP was validated by accurately retrieving clinical outcomes in chemotherapy-treated breast cancer patients. Using this tool, in vivo effects of targeted drug therapy on tumor progression were predicted, such as the low efficacy of long-term monotherapy that inhibits the vascular endothelial growth factor (VEGF) receptor, and the higher prospects of a combined therapy, inhibiting both VEGF and the plateletderived growth factor (PDGF; Arakelyan, Vainstein, Agur, 2002a,b). The validated VCP served for identifying a new regimen involving a once weekly application of low docetaxel doses, which is expected to significantly improve efficacy/toxicity ratio in breast cancer patients. The aim of the present work was to test the efficacy of the suggested regimen in a mesenchymal chondrosarcoma (MCS) disease model, validated in xenografts, and to put forward improved regimens of chemotherapy and targeted drug combinations for a specific MCS patient. Materials & Methods: The validated disease model was calibrated by growth curves and histopathological results of untreated human tumor xenografts, derived from a lung metastasis of a MCS patient. The xenograft model was then scaled to a human MCS model, based on a gene expression analysis. Published data and in vitro proliferation assays of the patient's tumor cells served for modeling pharmacokinetics and
Costs Associated With the Primary Prevention of Type 2 Diabetes Mellitus in the Diabetes Prevention Program
Authors: William H Hernan, Michael Brandle, Ping Zhang, David F Williamson, Margaret J Matulik, Robert E Ratner, John M Lachin, Michael M Engelgau
Journal: Diabetes Care (2003)

OBJECTIVE—To describe the costs of the Diabetes Prevention Program (DPP) interventions to prevent or delay type 2 diabetes. RESEARCH DESIGN AND METHODS—We describe the direct medical costs, direct nonmedical costs, and indirect costs of the placebo, metformin, and intensive lifestyle interventions over the 3-year study period of the DPP. Resource use and cost are summarized from the perspective of a large health system and society. Research costs are excluded. RESULTS—The direct medical cost of laboratory tests to identify one subject with impaired glucose tolerance (IGT) was $139. Over 3 years, the direct medical costs of the interventions were $79 per participant in the placebo group, $2,542 in the metformin group, and $2,780 in the lifestyle group. The direct medical costs of care outside the DPP were $272 less per participant in the metformin group and $432 less in the lifestyle group compared with the placebo group. Direct nonmedical costs were $9 less per participant in the metformin group and $1,445 greater in the lifestyle group compared with the placebo group. Indirect costs were $230 greater per participant in the metformin group and $174 less in the lifestyle group compared with the placebo group. From the perspective of a health system, the cost of the metformin intervention relative to the placebo intervention was $2,191 per participant and the cost of the lifestyle intervention was $2,269 per participant over 3 years. From the perspective of society, the cost of the metformin intervention relative to the placebo intervention was $2,412 per participant and the cost of the lifestyle intervention was $3,540 per participant over 3 years. CONCLUSIONS—The metformin and lifestyle interventions are associated with modest incremental costs compared with the placebo intervention. The evaluation of costs relative to health benefits will determine the value of these interventions to health systems and society.