Ruxolitinib for Intermediate-2 Primary Myelofibrosis.

Ruxolitinib for Intermediate-2 Primary Myelofibrosis. Critical appraisal on the use of ruxolitinib for treatment in adult with intermediate-2 primary myelofibrosis. Introduction: Patients with primary myelofibrosis are prone to develop complicated infection due to defect in their humoral immunity. In addition, patients may develop complication such as portal hypertension, splenic infarction (which may lead to nausea, vomiting and shoulder discomfort), osteosclerosis, hypertrophic osteoarthropathy, occasionally periostitis, spinal cord compression, seizures, haemoptysis and gastrointestinal (GI) tract bleeding. (6, 7, 8, 9) In UK, Novartis holds the marketing authorisation for oral formulation. Ruxolitinib works by inhibiting Janus associated tyrosine kinase (JAK1 and JAK2) protein signalling. Ruxolitinib (Jakavi) is licensed for the treatment of disease related splenomegaly or symptoms in adult patients with primary myelofibrosis, post-polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis but not recommended by NICE.(10) The major adverse drug reaction associated with Jakavi, documented in the summary of product characterisation (SPC) at incidence greater than 10% are urinary tract infection, anaemia, thrombocytopenia, neutropenia, hypercholesterolemia, dizziness, headache, increase both alanine aminotransaminase and asparte aminotransferase, bruising , bleeding and increase blood pressure. Novartis also recorded other common side effect patient experienced incidence between 1-10% was weight gain, flatulence and herpes zoster, whiles tuberculosis incidence was 1%.(3) The following clinical study, COMFORT-I and COMFORT-II trails as well as primary peered review articles Verstovsek S, Masa RA, Gotlib J, et al and Harrison C, Kiladjian JJ, Al-Ali HK, et al published in The New England Journal of Medicine (NEJM) is used to address the questions below; Evidence recommendation for or against the use of ruxolitinib in Mrs MN treatment Pharmaceutical care plan and medication optimisation for Mrs MN. Creditability and quality of evidence The clinical trial from COMFORT-I was a multicentre (USA, Canada and Australia), phase III, randomised, double blind trial (large sample size, n=309) that compared patient treatment in primary myelofibrosis with ruxolitinib (n=155) to placebo (n=154). All patients enrolled in the trial had intermediate-2 risk or high risk of myelofibrosis, a palpable spleen length of at least 5cm and was 18years or above. Patients excluded were those with an absolute neutrophil count of 1x 109/L or less, platelet count less than 100x 109/L. Incyte pharmaceutical funded this trial.(5) The COMFORT-II trial, was a multicentre (Europe with UK inclusive), phase III, randomised, open label trial that compared ruxolitinib (146) with best available therapy n=73 (hydroxycarbamide, prednisone, opoetin, lenalidomide and thalidomide). The trial was funded by Novartis pharmaceuticals. (4) The primary outcome for both trails was the proportion of patients having a spleen volume reduction of 35% or more from baseline and assessed by MRI or CT scan. The primary efficacy outcome was measured at 24 weeks in CONFORT I and 48 weeks in COMFORT II. Also the COMFORT trail (50% of primary myelofibrosis PM) population of patients with different subtypes of myelofibrosis did not reflect the global prevalence (i.e. PM is 30 times more) data reported. In addition the trials were not powered to measure overall survival or to detect statistically significant differences between subgroups (that is sex, myelofibrosis subtype), IPSS risk category or JAK2 mutation status.(1,2,3,4,5) Patient background verse evidence: Mrs MN creatinine clearance (CrCl) is 60ml/ min (normal about 100-125ml/min). The UK guideline for identification, management and referral March 2006 show that, she has stage 2 mild degree of renal function. But from SPC it is unclear, how this will increase Mrs MN risk of taking ruxolitinib. I must point out that Mrs MN is overweight with a BMI of 28 and ruxolitinib common side effect is weight gain (1-10% incidence rate). Mrs MN is capable of carrying out light house or office work from her ECOG status 1. Again patient is taking clarithromycin prescribed by GP, for possible chest infection. Novartis pharmaceutical (Javaki SPC) advises to treat any infection prior to taking ruxolitinib. (3) Mrs MN presenting complain with symptoms of anorexia, lethargy, night sweats, fever and a productive cough is a suggestive of tuberculosis (TB) infection. She is returning from holiday where risk of getting TB infection is high. If Mrs MN is prescribed ruxolitinib, she has high chances of developing complicated TB. Base on the evolution of patient background and evidences, I will not recommend ruxolitinib treatment for Mrs MN. Since Mrs MN will be receiving treatment for tuberculosis (isoniazid/ rifampicin) for at least 6 months, there is significant interaction between isoniazid and clarithromycin. Isoniazid will increase the level or effect of clarithromycin by affecting hepatic or intestinal enzyme CYP3A4 metabolism. Hence clarithromycin dose be reduce when taking with isoniazid and monitor closely. (4, 5, 11) If opting for rifampicin TB treatment, rifampicin will decrease the level or effect of clarithromycin by affecting hepatic or intestinal enzyme CYP3A4 metabolism. Hence, increase the dose of clarithromycin for the duration of treating chest infection.(11) Also, Mrs MN should be advised to recognise signs of liver disorders to discontinue treatment and seek immediate medical attention if symptoms such as vomiting, nausea, malaise and jaundice develop. (11) References: Verstovsek S, Masa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trail of Ruxolitinib for Myelofibrosis. The New England Journal of Medicine.2012; 366(799): 807. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. The New England Journal of Medicine.2012; 366(787):98. JAKAVI, Summary of Product Characterisation. Novartis Pharmaceutical Ltd, http://www.medicines.org.uk/emc/medicine/26991. [Assessed on 07/02/2015] JAKAVI (ruxolitinib), COMFORT-II Clinical Study Fact Sheet. file:///F:/Appraisal%20Assignment/COMFORT-II-ClinicalTrial-fact-sheet.pdf. [Assessed on 08/02/2015]. .JAKAVI (ruxolitinib), COMFORT-I Clinical Study Fact Sheet. file:///F:/Appraisal%20Assignment/Jakavi.pdf. [Assessed on 08/02/2015] Heuck G. Zwei Falle von Leukemie mit eigenthumlichen Blutresp. Knockenmarksbefund. Arch Pathol Anat Physiol Virchows. 1879;(78)475-96. Barosi G. Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines. J Clin Oncol. 1999;17(9):2954-70.. Vallespà ­ T, Imbert M, Mecucci C, Preudhomme C, Fenaux P. Diagnosis, classification, and cytogenetics of myelodysplastic syndromes. Haematologica. Mar 1998;83(3):258-75. Jacobson RJ, Salo A, Fialkow PJ. Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis. Blood. 1978;51(2):189-94. NICE, Ruxolitinib for disease-related splenomegaly or symptoms in adults with myelofibrosis http://www.nice.org.uk/guidance/ta289/evidence . Assessed on 11/02/2015 BNF 68 September 2014 to March 2015. Joseph Appleton K0606850 Group 3Page 1

Essay --

I am mad. Wait, mad might not be the correct word. Perhaps I should have said angry, but does that truly evoke the complete image of my present emotional state? I think not. Exasperated, agitated, and resentful come to mind, but again, individually, they all fall short of expressing the complex set of emotions experienced when I feel I have been cheated or stolen from. What makes this even more emotionally demoralizing is the fact that those responsible for doing the cheating and stealing do not even recognize that is what they are doing. So who am I referring to, how are they cheating, and what have they stolen? They are the uninformed voters and they are cheating the system by having the same amount of control in election outcome as those who have taken the time to become involved and knowledgeable about the issues. But what are they stealing? In short my vote. Simply put, due to lack of interest, understanding, and participation in the electoral process, uninformed voters wh o should be awarding their support from a foundation of insight, preparation and knowledge are instead casting votes even they do not agree with. Ok, so what if a few people get confused and make a wrong vote, just how bad can it be? ‟According to political scientists Richard Lau and David Redlawsk in their book How Voters Decide, the authors find that, in the best case scenario of a choice of two candidates, approximately 70 percent of voters choose correctly†(Belt 643). Now take a minute to really think about the implications of that statement. In a best case scenario, 30 percent of the voter’s choice was for someone or something he or she did not even agree with but was too uninformed to know it. One might ask how could there possibly be this d... ...that regardless of which side of an issue one may support, award that support from a foundation of insight, preparation and knowledge. Somin in his book Democracy and Political Ignorance, and Their Ignorance is willful! states, ‟few will take the time and effort to assimilate more than a small amount of political information.† For this reason he states elsewhere in his book, we should be grateful that voter turnout is as low as it is, because increased turnout is often likely to increase the electoral effects of political ignorance by encouraging the unmotivated to vote (More Media 1). Realizing that all the time and effort I spend to discern the issues and candidates’ positions can be made futile by one uninformed voter, maybe our best hope is, come Election Day, the uniformed voter is so uninformed they will not be able to find the polling location.

A notion of liberty has been thoroughly

Through all the history of the humankind a notion of liberty has been thoroughly researched by the philosophers, politicians and economists. It was often proclaimed to be the most valuable thing a person can possess, but sometimes it was pronounced the greatest enemy of social and political stability. Till nowadays the dwellers of our planet can not agree on the same handling of this notion. It’s impossible to solve this problem in a short essay, so it should be seen as an attempt to compare different views on this notion.The editors of the Merriam-Webster Dictionary of Law (1996) explain freedom as an â€Å"enjoyment of the rights enjoyed by others in a society free of arbitrary or unreasonable limitation or interference†. The authors of the WordNet 2.0 presume that liberty is â€Å"personal freedom from servitude or confinement or oppression†. As we can note, the word liberty has different meanings by itself, and driven through the alembic of fancy of everyone who’s interested in the question multiplies the amount of explanations for the notion many times. This is the fact that often causes incomprehension and misunderstandings during discussing it.Liberty has always been highly appreciated by the creative people, such as writers, poets, painters and sculptors etc. For most of them it is an essential condition for the effective work and for the peace of spirit and mind. David Hume notes, that â€Å"†¦the arts and sciences could never flourish, but in a free government†¦Ã¢â‚¬  (1752) and many of the arist will completely agree with him, as freedom of thoughts and deeds is one of the most important things for them. It’s apparent that an artist cannot create anything of real value when his mind is shackled and when he is told what to do, think or dream about. The deprivation of liberty is often murderous for a creative person.But artists are not the only ones in need of freedom. Ordinary humans, the citizens of thei r countries also value the liberty highly. John J. Lalor says that it doesn’t take much effort to keep liberty within the bounds with the help of the self-respect, welfare and morality, even when it’s not limited legally. That sounds coherent, as the fact is known that the revolutions do not happen in societies where all of their members possess everything essential. People who have things they value do not rebel against the existing regime. The other way round, those who do not have anything to lose, are always ready to battle. This is the main reason for the dictatorial policy of the poor countries’ leaders.As you can see liberty is one of the vital things the government has to provide to its nation. But considering it, a dilemma appears, a question which was formulated by John Stuart Mill: â€Å"Ought we therefore to lay on no taxes, and, under whatever provocation, make no wars?†(1869). Sure enough it is problematic for the government and folk to reac h consensus on where the personal liberty has to give place to the civil duty. The cabinet gives people a right to choose their life-style, education and profession, but at the same time it makes them pay taxes, acquire some compulsory educational level, get the license for driving a car, and when the war comes all the men must go to protect their country from the invasion and occupation.As it was previously noted, not all the people agree on the meaning of the word liberty. Most think it is the right to do the things you want to do unless it doesn’t pinch the rights of the others. But some individuals presume that the liberty they possess gives them the right to do anything they desire, regardless of what other people think of their actions. Murray N. Rothbard asks: â€Å"What, for example, of â€Å"incitement to riot,† in which the speaker is held guilty of a crime for whipping up a mob, which then riots and commits various actions and crimes against person and prop erty?† Politicians, sociologists and social psychologist are still in search of an answer.It has always been a problem when the state is unable to provide its dweller with liberties declared. It often happens that if the person is not the member of the prevailing social, cultural or ethnical group his rights are strictly limited in spite of the existing laws designed to protect them. Bruce Smith in 1887 was sure that the effective majority had the right to do what it wanted to, and it was impossible for the individual to oppress its actions. More than hundred years passed but, ruefully, the situation hasn’t changed a lot.Liberty is not the stable thing that is presented you when you’re born and stays yours to the grave. You have to daily prove you’re worthy to possess it. At this point I agree totally with Bruce Smith who said: †Ã¢â‚¬ ¦ principle of individual freedom—which†¦ fired the most noble-minded of our ancestors to rebel against t he tyranny of those who won, or inherited, the rights of that conquest—is in imminent danger of being lost to us, at the very hour of its consummation.†Different people value liberty for various reasons. For some of them it’s a warranty that their kids won’t be forced to vote for the person they despise, or pray the gods they do not worship. Some see their liberty in a right to kill and be killed, some want to born as much children as they can handle. It depends on the person really. Anthony Lee Gregory, the American journalist and writer says that liberty is the right to carry any weapon of your choice. You can choose between living your life for yourself and devoting it to the other people’s benefit, between bringing love or hatred to the world around you. So, it’s your turn to choose how to use the liberty you possess.Works citedMackay, Thomas, ed. various authors. (1891). Plea for Liberty: An Argument Against Socialism and Socialistic Leg islation, ch2, 6, New York: D. Appleton and Company Smith, Bruce. (1887).   Liberty and Liberalism: A Protest Against the Growing Tendency toward Undue Interference by the State, with Individual Liberty, Private Enterprise and the Rights of Property, 14, London: Longmans, Green, and Co. Hume, David. (1987). Essays, Moral, Political, and Literary, Part 1, Essay 12, Of Civil Liberty, n.dLalor, John J. (1899). Cyclopedia of Political Science, Political Economy, and the Political History of the United States by the Best American and European Writers, License and Liberty, v.2, p. 266,   New York: Maynard, Merrill, and Co. John Stuart Mill. (1965). On Liberty, ch.2, p.43, London: Longman, Roberts & Green Murray N. Rothbard. (1978). For a New Liberty: The Libertarian Manifesto, ch.6, p.63, Collier Books, New York Merriam-Webster Dictionary of Law (1996), Freedom, Retrieved October 29, 2004 from the World Wide Web: https://www.merriam-webster.com/dictionary/freedom WordNet 2.0. (2003), Retrieved October 29, 2004 from the World Wide Web:   http://www.dictionary.com/browse/liberty Anthony Lee Gregory. (2002). What is liberty?, October 29, 2004 from the World Wide Web:   http://www.anthonygregory.com/whatisliberty.html

Notes On The Precious Jones - 1491 Words

Overview Clariecce Precious Jones, who simply goes by as Precious, is from Harlem, New York. She is the only child of Mary Johnson and Carl Jones. Precious lives in poverty, and suffers from physical, emotional, and sexual abuse from her parents. She also has two children by her father, and contacted HIV. Her first child has Down syndrome and lives with her grandmother, and her second child lives with her. Recently, Precious left her mother’s house, and is currently staying in a halfway until she is able to find permanent housing. Precious is 16-year old, but she is in middle school. Since Precious is too old to be in middle school, she was recommended to attend an alternative school. At the alternative school, Precious takes pre-GED classes, and then will take GED classes to earn her high school diploma. In Pre-GED classes she is learning to read and write. Precious enjoys writing, and in particular she likes poetry. Precious is very optimistic about her future, and wants to live a better life. Obstacles/Challenges Precious is faced with individual and institutional obstacles/challenges. Unfortunately, Precious deals with the ramifications of sexual, physical and emotional abuse. The abused she faced as a child led to illiteracy, H.I.V and low self-confidence. Eventually, Precious becomes homeless because she could no longer stand her hostile environment, and needed to get away from her mother. She now lives in a halfway house. Institutional challenges Precious facesShow MoreRelatedThe Counsel Of Heaven On Earth Essay1596 Words   |  7 Pages倀倀ODUCTION The Counsel of Heaven on Earth is a book written by Ian F. Jones on the topic of Christian counseling. Jones makes sure to let his readers know that this book is not meant to be a guide for Christian counseling; he in no way means to advocate a particular methodology, system, or school of thought. 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