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By R. Leon. Pittsburg State University.

The importance of this issue will escalate over time as the Knowledge Network and its linked molecular-based taxonomy evolve into a system whose sheer complexity greatly exceeds current approaches to disease classification 200 mg ketoconazole free shipping antifungal bacteria. One concern is that the infusion of large molecular datasets into clinical records will reinforce a tendency many perceive as already crediting genetic and other molecular findings with more weight than they deserve 200 mg ketoconazole with visa fungus gnat nepenthes. In extreme cases 200 mg ketoconazole with amex antifungal bar soap, this cultural bias has enabled the promoting and marketing of omic tests with no clinical value whatsoever (Kolata 2011) 200 mg ketoconazole for sale fungus gnats pesticide. In other cases genetic or omic tests with real value in specific contexts may be over-interpreted and thereby occlude consideration of other relevant clinical data. To develop the Knowledge Network of Disease and the New Taxonomy that will be derived from it, health-care providers will need to develop much greater literacy in the interpretation and application of molecular data. To meet these challenges, health-care providers will require both decision-support systems and new training paradigms. Whenever possible, such decision-support systems should enable shared decision-making by patients and their care-givers. In order to prepare physicians for the use of a comprehensive, dynamically changing disease- Knowledge Network, biomedical education will need to adjust. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 61 (2011) recently proposed that graduate and medical-life-sciences curricula would significantly benefit from a major shift away from the current discipline-specific model to a vertically integrated nodes-and-connections framework. It also would give future physicians a more holistic view of biological processes, which reflects what will be required to fulfill the promises of genomics and personalized medicine (Ashley et al. In this teaching model a given topic for example, gene expression would be taught in a vertically integrated fashion, with essential information all the way from the atomic to the whole-organism scale discussed. Adjusting teaching strategies to reflect the biological reality of the material has the potential to create significant synergies. Students may retain more knowledge of basic science when this information is directly connected to medicine. The enhanced ability to use the New Taxonomy in medical practice and research would reinforce the student s conception of biology. Although it is beyond the scope of this report to suggest detailed reforms of the medical-school curriculum, the Committee would like to emphasize that full realization of the power of the Knowledge Network of Disease and the New Taxonomy derived from it would almost certainly require a major shift in educational strategy. The multicolored bars in the nodes and connections course represent fundamental principles and essential facts about each key process integrated across scales. Although not based on specific patients, these scenarios reflect current medical practice and are typical of thousands of real 8 people who visit American clinics every day. Patient 1 an otherwise healthy woman with breast cancer is a direct beneficiary of the stunning advances in science and medicine that have occurred during recent decades. Her physician knows the molecular details of the pathological processes that threaten her life and has at her command therapies that directly target the aberrant molecular events occurring in Patient 1 s cells. The safety and efficacy of these therapies have been confirmed by randomized clinical trials involving other patients well matched with Patient 1 in the molecular details of their disease. Contemporary medicine has little to offer him beyond a long-available diagnosis and treatment plan. After 50 years of intensive study, substantial headway has been made in the scientific understanding of diabetes. Unlike many children who have a sudden onset of diabetes early in life, we know that Patient 2 has high levels of circulating insulin. His blood sugar remains abnormally high even as his cells receive a strong signal to take the sugar up and metabolize it. The insidiously toxic effects of high levels of circulating sugar threaten the health of Patient 2 s blood vessels. Responses to drug treatments, which have changed little for decades, are highly variable. Similarly, changes in exercise habits and diet help some patients more than others. There is a high likelihood that Patient 2 faces a future of escalating medical interventions, declining health, and increasing disability. The human, social, and economic costs associated with patients such as Patient 2 are daunting and 8 In 2010, approximately 1. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 64 distressingly typical of those seen for patients with chronic diseases throughout our aging population. The Committee s assigned task was to explore the feasibility and need, and develop a potential framework, for creating a New Taxonomy of human diseases based on molecular biology. Moreover, the Committee clearly recognized that developing and implementing a Knowledge Network of Disease has the unique potential to go far beyond classification of disease to act as a catalyst that would help to revolutionize the way research is done and patients are treated. Patient 1 has a high likelihood of overcoming her life-threatening disease and going on to live a long, healthy, and productive life. These prospects are a direct result of a new ability to recognize, based on molecular analyses, the precise type of breast cancer she has and to target a rational therapy to her disease. The Committee believes that the best prospects for creating a similarly bright future for Patient 2 lies in achieving a similarly precise understanding of his disease by creating a Knowledge Network of Disease and an associated New Taxonomy. Both these points suggested that we could best address our charge by framing the new-taxonomy challenge broadly. Many of the conclusions and recommendations could apply, as well, to other challenges in translational research such as evaluating and refining existing treatments and developing new ones. However, disease classification is inextricably linked to all progress in medicine, and the Committee took the view that an ambitious initiative to address this challenge and particularly to modernize the discovery model for the needed research is an excellent place to start. The Committee thinks that the key to success lies in building new relationships that must span the whole spectrum of research and patient-care activities that comprise American medicine. Our recommendations seek to empower stakeholder communities by providing them with informational resources the Information Commons, the Knowledge Network, and the New Taxonomy itself that would transform the way they work and make decisions. At the core of the Committee s optimism is a conviction that dramatic advances in biological knowledge can be coupled more effectively than they are now to the goal of improving the health outcomes of individual patients. Biology has flourished in the 50+ years since the discovery of the molecular basis of inheritance. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 65 Genome Project, genetics is in a golden age of discovery. Sequence similarity between genes studied in fruit flies and those studied in humans allows nearly instant recognition of the potential medical relevance of the most basic advances in biochemistry and cell biology. Increasingly, this process also works in reverse: unusual human patients call attention to molecules and biochemical pathways whose importance in basic biology had been overlooked or was otherwise inaccessible. Indeed, there are already many areas of basic biology in which human studies are leading the way to deep new insights into the way organisms work. For the simple reason that one can ask a research subject what she sees when looking at a pattern of light instead of having to develop a crude behavioral test to find out whether she sees anything at all we know far more about the molecular details of light reception in humans than we could ever have learned from studying mice. Particularly as biomedical research puts an increasing emphasis on unraveling the molecular underpinnings of behavior, the advantages of starting research studies with humans, rather than model organisms, are likely to grow. Experience tells us that translation of intensifying knowledge of basic biology into clinical advances is a daunting task. Furthermore, the Committee shares the sense that basic biology is at an inflection point in which there is every reason to expect increasing payoffs from the large investments in basic science that have brought us to this point. However, the grand challenge of coupling basic science more effectively to medicine will require a rethinking of current practices on a scale commensurate with the challenge. The Committee regards the initiative it proposes to develop the tripartite Information Commons, Knowledge Network, and New Taxonomy, as having the potential to rise to this level. Information technology is the key contributor to the technological convergence the Committee perceives.

What is central to stress management is the atten- This chapter will tion we give ourselves in the present moment generic 200 mg ketoconazole with visa fungus eye eq. Do we pay attention to each bite of our breakfast ketoconazole 200mg line black fungus definition, or do we hurry it down with gulps of coffee while scanning our emails generic ketoconazole 200 mg free shipping fungus vs eczema, half-listening to the radio in the background? Case Do we carefully listen to our patient s complaints cheap ketoconazole 200mg online fungus yellow mulch, or are we A third-year resident has suffered from anxiety throughout mostly focused on getting through the patient list in time their medical training. But competent than their peers has made the anxiety particularly mindfulness is not something foreign; it s a capacity we often acute. It is both the ability to focus on this text as we read it, and purging as a way to cope with stress. The resident hides the aspect of mind that notices when our attention has drifted this behaviour from others, as they consider the anxiety away. Mindfulness is not thinking: it s more like the awareness and bulimia a further sign of inadequacy. Deepening our resident does enter an introductory six-week mindfulness mindfulness through practise is a way of inoculating ourselves program offered by the medical school. Introduction The relaxation response The road to independent medical practice is long, demanding We can t avoid stress: stress is triggered by change, and life and fraught with stress. When residents eventually largely determines how much they enjoy this period of their fnish their training, new challenges will come. Many manage the inevitable stress of their residency can prepare for an exam by studying, we can prepare for years by focusing on the light at the end of the tunnel, thus the inevitable presence of stress by practising being present. A considerable body of ceptance the workload increases: Oh well, it will be different research demonstrates that mindfulness techniques produces in residency; I ll be making money and can fnally focus on my a relaxation response that has the opposite effect of the stress real vocation. Postponing certain choices today for the promises of tomor- row often makes sense. If we don t crack the books until the Refection: Practising mindfulness in daily life week before our fellowship exams, well, we know how that Allow yourself a few mindful breaths in the will turn out. But, while planning for the future is helpful, liv- morning before you get out of bed. Planning for the Try preparing and eating your breakfast quietly, future means orienting our actions so that they contribute to a without distraction, once a week. Managing stress with mindfulness Let the world wake you up: when you notice a This habit of living for tomorrow is a fawed coping strategy: it phone ring, a door slam, and so on, take a is based on the false premise that tomorrow is more real than moment to sense where you are and how you today. Cultivating mindful- weeks to delay, and eventually eliminate, the binging ness through regular formal practise extends the habit of episodes. The resident also begins to question these nega- being present into our daily activities. Try this for the next tive self-judgments and seeks counselling for the eating few breaths. The resident discloses abdomen moving in and out with each breath and stay with these challenges and fears to a close friend and feels less that sensation. Before long your mind will likely drift off into isolated and less anxious about life in general. The resident thoughts about this experience, or about something completely plans to continue with regular meditation. When you notice that your mind has drifted into thinking, let go of the thoughts and come back to the sense of breathing. It s simple and yet Self-acceptance diffcult to stay present: it takes discipline to train our minds As we become mindful of uncomfortable feelings and the to simply be in the moment when our tendency is to want to habitual patterns they trigger, we may become self-critical: control it. Such activities might take the edge off ing of our quirks and foibles, we also naturally become more our anxiety momentarily, but when anxiety has the upper hand accepting of others. In medical practice there is no greater in our lives the activities that are motivated by anxiety become kindness we can offer our patients than our attention and deeply entrenched habits. Key references In a state of mindfulness we allow ourselves to feel whatever Hassed C, de Lisle S, Sullivan G, Pier C. Whether we are feeling overwhelmed by anger the health of medical students: outcomes of an integrated or lost in boredom we simply allow ourselves to be aware of mindfulness and lifestyle program. Wherever You Go, There You Are: Mindfulness of thoughts and feelings may food through us, our patience Meditation in Everyday Life. New York: Oxford can learn to stay present with our feelings and let go of the University Press. Case A journal of the grieving process A second-year resident began their cardiology rotation two Dr. She was distressed by the loss of two young patients, ful week with more than the usual number of admissions. She began to write intermittently in a journal, old architect to the coronary care unit with the diagnosis describing her thoughts and interpretations of these dif- of a second myocardial infarction. She purposefully wrote without much fore- well until shortly before his 49th birthday, when he began thought, letting the words fow, letting her feelings bubble to experience anginal pain. His recovery proceeded without com- plication, and he returned to work within approximately She described the rooms where Jason and Steven had died three months. The resident feels threatened and uncertain about how to proceed, given the patient s apathy. During cardiology She recalled how she had bought a large bouquet of helium rounds with the staff cardiologist, various medical data balloons on her way home from work the day after Jason are reviewed and a vigorous debate ensues among team died. She was coming home to her two-year-old daughter, members regarding the appropriate thrombolytic therapy and to her son, who was Jason s age. The resident realizes during the course of to her own children some emblem of joyfulness and hope, daily assessments and interactions with the patient that, as and something that pointed toward heaven. This process The following week, overtired but determined, the resident allowed her to refect on her responses and to consider her fnally breaks through. The resident ends up asking the personal reasons for feeling so overwhelmed at the time. She also began to speak with Introduction a more experienced colleague about how she was handling Medical practice has always been grounded in life s intersubjec- things. He spoke of his anger practitioners, we learn to identify and interpret our emotional and resentment of being afficted with a life-threatening responses to patients and in doing so are able to make sense illness so early in his productive years. He did not want of their life journeys and grant what is called for and called people s sympathy, nor did he want to be a burden to forth in facing ill and vulnerable patients (Charon 2006). The resident learns The textbox gives an example of how keeping a journal can the therapeutic value of talking with a patient about his assist in this emotional process. Summary Writing in a journal can help us to bridge professional and Key references personal gaps. A model for empathy, close reading allows physicians to do what medical sociolo- refection, profession, and trust. New England Journal it affecting one s own life and to fnd in that effect a certain of Medicine. By chronicling our experi- ences as physicians, we learn the value of telling and retelling, of gaining understanding, and of respecting and learning from the many authentic stories we share. Many people activity into one s lifestyle, and do not appreciate that the multiple health benefts of regular discuss the importance of modelling being physically ac- physical activity enhanced cardio-respiratory and musculo- tive to colleagues, students and the medical community. It is not necessary to become an athlete to enjoy breathless than before when climbing stairs. The benefts of cally active throughout their teens, as an undergraduate sustained, moderate-intensity aerobic activity are protean and medical student, the resident realizes that over the and go well beyond improving cardiovascular health. Regular four years of the postgraduate program they have become physical activity can be a time for recreation in the fullest increasingly sedentary.

In the context of living kidney donations discount ketoconazole 200mg with mastercard antifungal skin cream, the illegal nature of most of those operations on which data are available makes any kind of meaningful comparison exceedingly difficult ketoconazole 200mg fungi definition yahoo answers. One carried out in Sweden among 262 students found that the offer of a small financial incentive ($7) had neither a positive nor a negative effect 591 overall on determining whether potential blood donors actually donated generic 200 mg ketoconazole free shipping fungus habitat. Nor did the alternative option of donating the money to charity increase donation rates discount ketoconazole 200mg fast delivery antifungal gold bond. A Swiss study (involving over 11,000 participants) similarly found that the offer of a free cholesterol test had no 592 effect on donation rates. A second Swiss study of 10,000 previous blood donors showed a five per cent higher donation rate in those offered a free lottery ticket (estimated face value $4. It was noted that the increase in donations among those offered a lottery ticket derived from those with a low rate of past donations, with no effect (positive or negative) on those with a past high rate. These results were replicated in a small-scale field experiment of four pairs of blood drives, where one drive from each pair offered potential donors a gift card ($5 in two drives and $20 in the other two), while no incentive was offered to the paired controls. Both turnout and the amount of blood collected at the drives offering the incentives were increased, with larger effects noted in connection with 595 the greater incentive. This contrasts with the findings of studies that only ask people about their intentions (as opposed to measuring their actual behaviour), which appear to support concerns 596 about the possibility of crowding out. The same distinction between intention and actual behaviour is demonstrated by the failure in the Swiss studies to recruit additional donors by offering a free cholesterol test, since surveys of intention regularly suggest such an offer would 597 be effective. On the other hand, studies from Iran (which do not, of course, derive from the kind of controlled experiment or observational study included within our review) note how the 590 Iran is the only country that permits financial reward to be offered to living kidney donors. A significant majority of respondents thought that direct payments of any size were unethical and would not influence their own decision to donate, while a donation to charity in return for bodily donation was viewed much more positively. As we note above, the lack of response to the offer of a donation to charity in the Swedish study on blood suggests that such offers do not seem necessarily to influence actual behaviour. However, the fact that many people expressed a theoretical liking for and approval of such a suggestion (coupled with dislike of the notion of direct financial payment in return for bodily donation) might be seen as a further endorsement of the ideal of a system based on altruism and concern for others, regardless of what decision that individual would personally make in practice. The more intrusive and restrictive the policy on individual choice and liberty, the greater the justification required for the public health policy, in terms both of the possible benefits, and of the strength of the evidence that such benefits will indeed eventuate. See also: Bagheri A (2006) Compensated kidney donation: an ethical review of the Iranian model Kennedy Institute of Ethics Journal 16: 269-82. As an Intervention Ladder, with rung 1 starting at the bottom, the six rungs will thus look like this: 168 H u m a n b o d i e s : d o n a t i o n f o r m e d i c i n e a n d r e s e a r c h 6. The specific question here is whether offering incentives to donate might raise additional concerns in any of these areas. Given that one of the key concerns around any forms of non-altruistic-focused intervention is the risk of material being mis-valued, we distinguish between these two approaches through rungs 5 and 6 on the Intervention Ladder. It will also be less relevant in considering issues around the ongoing post-donation role or interest of the donor in connection with the use of the material. Injury to the body can no longer literally injure the (deceased) person, and what is at issue is the extent to which family, kin and others who knew the person continue to associate the person with the body, so its treatment is significant as a metaphor or sign of their relationship with the person now departed. In particular, we suggest that the degree of detail required when providing information about the proposed procedure will differ significantly, and that it should be possible for a person to provide legal authority for donation after death on the basis of quite minimal information, if this is sufficient for them to be clear about their own wishes. Where stocks do run low (for example because of bad weather leading to cancelled donor sessions), urgent appeals for 607 donors are generally effective in bringing supplies back up to safe levels. That current system relies on good publicity and awareness among the general public as to the constant need for blood (see Box 3. Such a consideration would suggest that any changes in policy regarding blood donation should be subject to particular scrutiny as to their impact on wider communal values. We also note that suggestions have been put forward for example, by a Member of the Scottish Parliament that employers should permit their staff to 608 have paid time off in order to donate blood. Such a suggestion would fall into the third rung on our Intervention Ladder it would constitute an altruist-focused intervention seeking to remove a barrier (possible lost earnings or requirement to make up lost working time, depending on the employer) that might otherwise be hindering people from deciding to donate. We do not consider that there would be ethical concerns about such a change; we would, however, suggest that evidence (for example through carefully monitored pilot schemes) would be helpful in determining its likely efficacy before such a change should be recommended more widely. We consider that the life-saving nature of the need for organs is such that it is reasonable to consider new approaches to increasing supply (see paragraph 5. In terms of the professional responsibilities of the health professionals who would be involved in an incentivised system, we note the opposition of the British Transplantation Society (whose membership includes the many different professions involved in transplantation) to the 611 introduction of any financial incentives for donation. See also: House of Commons Library (2009) The Islamic Republic of Iran: an introduction (London: House of Commons Library). International Forum for Transplant Ethics The Lancet 351: 1950-2) argue that the burden of proof should be the other way round, falling on those who resist payment. Possible ways of achieving this would include through legally binding 615 Directions or through the Code of Practice issued under the Human Tissue Act. As such, we do not think such a payment would challenge the current consensus in any ethically significant way. Given these concerns, coupled with a lack of evidence as to the likely effectiveness of such an intervention, we do not think it should be pursued. Moreover, while those who are neutral about donation after death might be swayed by such an incentive, it seems unlikely that a person actively opposed to the use of their bodily material after death (for example because of concerns about the integrity of the body) would be tempted to act against those beliefs. Donors cannot be physically harmed and are highly unlikely to have signified their willingness to donate in these circumstances if they had strong objections. While there is no direct evidence as to how effective or popular such a system would be, the fact that a very similar system exists for covering cremation costs of those who donate their bodies to medical science (which appears to be regarded by both professionals and families as an appropriate acknowledgment of the persons 617 gift), suggests that the extension of such a scheme to organ donors would not be detrimental either to professional values or the common good. Another study, published subsequently, concluded by contrast that opt-out systems are associated with relatively higher rates of deceased donation but also with relatively lower rates 619 of living donation. We are also aware of research modelling the possible effects on organ 620 supply of an opt-out system, based on differing levels of individual and family opt-out. We note that, while such models demonstrate a potential increase in the number of available organs (and hence lives saved) on the basis of particular assumptions about numbers opting out, such assumptions clearly remain to be tested. First we suggest that initial assumptions as to the numbers of additional organs that might be obtained in such a way should be modest, if families 621 do indeed continue to feel genuinely free to express any objections they feel. Indeed, if families in such cases felt coerced in any way, then this would potentially render their role meaningless. Similarly, if families felt relieved from the requirement actively to make the decision, this too might lead to fewer refusals. We are therefore hesitant to rely on research reporting on how people say they would respond to the introduction of a soft opt-out system including all the protections described above. We note, however, that the Welsh Assembly has expressed a 623 clear intention to introduce such a scheme in Wales. Such an approach would seek to avoid the risk that people feel coerced into making a decision, but would also enable those who are genuinely unsure at the time of answering the question to indicate that they are happy to delegate their decision to their family, and that they are not actively opposed. The Government will examine thoroughly the detail of the Bill when it is introduced to the National Assembly. The possibility of explicit refusal can only strengthen the significance of approval: at the same time it allows for strength of personal feeling to be expressed in both directions (approval and disapproval). The importance of this cannot be overemphasised when the subject matter is bodily material. In such cases, we endorse the current position that the option of refusal should rest with familial associates of the deceased. The clear aim should be to ensure that the donor is in the same financial position as a result of their donation, as they would have been if they had not donated. Where such costs or losses are incurred as a direct result of donation, they should be met in full.

This could can rigorously monitor and evaluate the drug Improve clinical trial transparency ketoconazole 200 mg without prescription antifungal iv. Gilead lags help address the increasing burden of these con- donation programme it has initiated in Georgia buy generic ketoconazole 200 mg fungus cream, behind the industry in this area generic 200mg ketoconazole amex zeasorb af antifungal drying gel. The company can also introduce a mech- including more high-prevalence middle income socio-economic factors in its inter-country equi- anism for sharing anonymised patient-level data countries in the terms of its hepatitis C licens- table pricing strategies buy 200mg ketoconazole visa antifungal pills for ringworm, to help ensure products with third parties. Gilead Ethics, Gilead discloses the details of its policy only company in the industry that does not have falls three places, despite having a range of for managing conficts of interest. It does not publish information No breaches of laws or codes of conduct gov- level data on request. As in 2014, Gilead has not been the subject of any settlements for Does not share intellectual property. It has a centralised employees must undergo training in this respect Gilead drops six places, but remains among the performance management system with quar- and understand all the various elements of the leaders. Low transparency on stakeholder engagement Business Partner Compliance Pocket Guide, It is less transparent than in 2014 about its vol- strategy and activities. Gilead has a clear stake- which addresses a range of interactions with umes of sales, which means there is little evi- holder engagement strategy, but does not pro- physicians and government ofcials. Gilead dence for the implementation of its pricing vide information regarding the stakeholder ofers compliance training, featuring case-based strategies. Its inter-country equitable pricing engagement activities of its branch organisa- scenarios, to business partners across multi- strategies only consider a few socio-economic tions. Gilead s relevant pipeline is smaller than ister half (50%) of its newest products in a few strong compliance system, including guidance the industry average, and it falls below indus- priority countries (disease-specifc sub-sets and contractual obligations to contractors. In an try standards for clinical trial conduct and clinical of countries with a particular need for access innovative move, the company has developed a data transparency. Gilead has an ethical marketing ted to conducting R&D for resource-limited set- Monitors prices and provides pricing guidelines code that also applies to third parties, but it has tings. For its hepatitis C prod- marketing activities and payments in countries ucts, the company sets pricing guidance for its within scope. The company is not a signatory to Poor measures to ensure clinical trials are con- sales agents via transfer prices. Despite having policies in place to ensure ethical clinical trial conduct, Gilead Consistent recall guidelines. Gilead has glob- Publicly discloses policy positions and con- does not provide evidence that it monitors clin- ally consistent guidelines for issuing drug recalls fict of interest policy. Gilead publishes its policy ical trial conduct or takes disciplinary action in all countries relevant to the Index where its positions related to access, in particular those when ethical violations occur. Gilead has not recalled 110 Access to Medicine Index 2016 a product for a relevant disease in a country in all of its hepatitis C portfolio. Notably, it did so Monitoring mainly the responsibility of part- scope during the period of analysis. Gilead contractually requires that donation it does make recall information publicly available. The com- fovir disoproxil fumarate and efavirenz/emtric- environmental conditions, demographic or cul- pany builds manufacturing capacity in coun- itabine/tenofovir disoproxil fumarate each year tural needs. In April 2015, Gilead launched an with equitable pricing strategies that target the capacity. Gilead makes a general commitment innovative donation programme with the goal of majority of priority countries (disease-specifc to building manufacturing capacity in relevant eliminating hepatitis C virus in Georgia. In the period of analysis, the com- gramme includes universal screening and treat- to relevant products). Together, these strategies pany undertook a number of technology trans- ment, prevention and surveillance. Gilead now has more products with equitable will provide 20,000 free courses of sofosbuvir/ pricing strategies than in 2014. Gilead routinely updates safety Best practice: high transparency of products labels for its products in countries in scope. The company discloses one relevant initiative HiV- Maintains top rank in Patents & Licensing. Gilead did not dis- close any relevant activities to build R&D capac- Continuing engagement in voluntary licens- ity or strengthen supply chains in countries in ing. It main- Best practice: licensing all on-patent prod- tains its long-term donation programmes for vis- ucts in scope for high-burden diseases. Once again, it was not found to have breached to more products than in 2014, only half target high-burden laws or regulations. It is building pharmacovigilance capacity, mainly in Latin management, and its approach to transparency in market- America. A structured approach would AbbVie can further develop its access AbbVie can strengthen its identifcation and tar- entail setting clear registration targets within a approaches into a strategy and clearly align it geting of local skills gaps in low- and middle-in- fxed timeframe, tied to decision-making crite- with its corporate strategy. This can help AbbVie ensure new products wider availability of high-need products for pop- ing (for example, to increase local R&D capac- are brought to markets in low- and middle-in- ulations in need. The company can also demonstrate that it come countries as soon as possible upon leav- cally using more equitable pricing and reponsible has a clear process in place for mitigating con- ing the pipeline. AbbVie can expand more high-need countries such as China and the geographic scope of licences agreed for for- Indonesia: combination ombitasvir/paritaprevir/ mulations of ritonavir (Kaletra ) in its licens- ritonavir (Technivie ) and dasabuvir/ombitas- ing activities. Rest of world Japan Europe North America *AbbVie Inc became an independent company on 1 January 2013. The company has gained fve market AbbVie s R&D projects have progressed along Communicable Multiple categories approvals since 2014: including, in Q4 2014, the pipeline. It has several features intended to development, plus atrasentan for diabetic nephropathy. Commitment to R&D partnerships, but no Drops two places due to a lack of improvement policy. AbbVie discloses a list of trade associa- compounds for screening and technical exper- all areas of measurement. It is not transparent tions from around the world in which one of its tise to outside partners. However, it does not regarding its access targets, the performance of employees is a board member. Nevertheless, it report an ofcial policy of ensuring access-ori- its access activities and its stakeholder engage- does not publish its policy positions on topics ented measures are systematically included in its ment selection process. Takes strategic approaches to access but these Takes measures to ensure ethical clinical trial do not align with business strategy. However, AbbVie has not specifed how marketing or corruption anywhere in the world High transparency around clinical trials. AbbVie these components are connected, nor how they during the period of analysis. Has a centralised performance management AbbVie has strong procedures for holding all AbbVie manages requests for data in-house. AbbVie has assigned board- employees and business partners accountable Rejections based on scientifc merit are for- level responsibility for access issues and has for their behaviour. It does not disclose specifc access-related to and including termination of employment. The company has an Has stakeholder engagement strategy, but auditing system, but does not provide details Drops 8 places due to relatively poor pric- is not transparent. AbbVie has a stakeholder about its processes and whether these include ing and registration performance. However, AbbVie does ers when it comes to rapidly registering new not publish details of the stakeholder groups it Drops two places but maintains strong perfor- products in high-burden countries, or to adapt- engages with, nor its process for selecting who mance.

Percentage of responses from all respondents to Doctors should only prescribe antibiotics when needed by country surveyed 200mg ketoconazole fungus gnats garlic. Percentage of responses from all respondents to Pharmaceutical companies should develop new antibiotics by country income classification generic ketoconazole 200 mg online antifungal uti. It is also important to note that 57% agree that There is not much people like me can do to stop antibiotic resistance with only 18% disagreeing with this statement order 200 mg ketoconazole overnight delivery fungus gnats lifespan, and therefore indicating that they believe they do have a part to play purchase 200mg ketoconazole with amex fungal rash on face. Percentage of responses from all respondents to statements surrounding attitudes towards antibiotic resistance. There are some significant variations in the findings between the countries surveyed and socio-demographic groups in relation to some of these statements, which are explored further below. In contrast, only 33% of respondents in Serbia and 27% of respondents in Barbados agree that antibiotic resistance is one of the biggest problems in the world, with more than one quarter in each country disagreeing and almost half neither agreeing nor disagreeing with this statement. Percentage of responses from all respondents to Antibiotic resistance is one of the biggest problems the world faces by country surveyed. More than one third of respondents in the Russian Federation (36%), Serbia (35%) and South Africa (36%) are also uncertain. In contrast, 89% of respondents in Sudan agree that experts will solve the problem, as well as 81% of Nigerian respondents. Percentage of responses from all respondents to Medical experts will solve the problem of antibiotic resistance before it becomes too serious by country surveyed. Percentage of responses from all respondents to I am not at risk of getting an antibiotic-resistant infection, as long as I take my antibiotics correctly by country income classification. The majority of respondents (62%) think that antibiotics are widely used in agriculture in their country. Respondents in Serbia (53%), Indonesia (52%) and Barbados (40%) are least likely to agree with this statement. Percentage of responses from all respondents to Do you think antibiotics are widely used in agriculture in your country? These findings can both help shape future public awareness efforts and aid evaluation of the impact of these efforts. Although antibiotic resistance occurs naturally, overuse and misuse of antibiotics in humans and animals is accelerating the process. For this reason, it is critical that people understand the problem, and the way in which they can change their behaviour. They show that although people recognize the problem, they do not fully understand what causes it, or what they can do about it. Antibiotic use The results of the survey questions on antibiotic use demonstrate how frequently antibiotics are taken, with a considerable majority of respondents (65%) across the 12 countries reporting having taken them within the past six months. This rises to 76% in Egypt, the country with the highest number of respondents reporting having taken antibiotics in the past six months, including 54% having taken them within the past month. Even in Barbados the country in which respondents reported the lowest use in the past six months the number stands at 35%. This prevalence is highly relevant to public campaigns on antibiotic resistance both because high levels of use contribute to the problem, and because it demonstrates just how many people it could impact in a short time frame if the antibiotics they are taking become increasingly ineffective. The results of the survey questions on how people obtained antibiotics and whether they got advice on how to take them show that a sizeable majority of respondents across the countries surveyed state that they got their last course of antibiotics, or a prescription for them, from a doctor or nurse (81%), and that they received advice from a medical professional on how to take them (86%). These factors indicate that the antibiotics are more likely to be taken to treat an appropriate condition and in the appropriate fashion, both of which are important in the context of tackling antibiotic resistance. Respondents were asked to indicate whether they thought the statement It s okay to use antibiotics that were given to a friend or family member, as long as they were used to treat the same illness was true or false. Although it is in fact a false statement, one quarter (25%) of respondents across the 12 countries included in the survey believe that this statement is true, though there is considerable variation in the findings between countries. While only 10% of respondents in Barbados think the statement is true, this rises to 37% in Nigeria. Across the 12 countries surveyed, respondents in rural areas, those with lower levels of education and those in lower income countries are more likely to think that this statement is true. Further investigations are needed in order to check if there is a link between broader issues around access to health care and medicine, and the affordability of antibiotics and other drugs for these groups. There is even more evidence of misunderstanding around the second statement shown to respondents: It s okay to buy the same antibiotics, or request these from a doctor, if you re sick and they helped you get better when you had the same symptoms before. Across the 12 countries included in the survey, 43% think this false statement is in fact true. However, close to one third (32%) of respondents surveyed across the 12 countries believe that they should stop taking the antibiotics when they feel better, and this rises to 62% in Sudan. Younger respondents and those in rural areas across the 12 countries, as well as those in lower income countries, are more likely to think they should stop taking antibiotics when they feel better. Understanding which conditions can be treated with antibiotics is also important, as the use of antibiotics for conditions which are not in fact treatable with these medicines is another contributor to misuse, and therefore to the development of resistance. Respondents were asked to indicate which of a list of medical conditions could be treated with antibiotics the list included both conditions that can and cannot be treated with antibiotics. Antibiotics are used to treat bacterial infections, whereas colds and flu are caused by viruses and therefore are not treatable with antibiotics. Further to this, we see that in Sudan, Egypt and India, three quarters or more of respondents think colds and flu can be treated with antibiotics. Younger respondents and those with lower levels of education are also more likely to think antibiotics should be taken for colds and flu. In combination, these survey findings related to the appropriate use of antibiotics suggest that action which effectively builds understanding of how and when to take antibiotics and what they should be used for particularly targeting groups among whom misunderstandings seem to be most prevalent is critical. The survey explored levels of awareness and understanding by asking respondents whether they had heard of a series of commonly used terms relating to the issue. The results show high levels of familiarity (more than two thirds of respondents) with three of the terms: antibiotic resistance, drug resistance and antibiotic-resistant bacteria. Levels of awareness of the terms is not uniform across the countries surveyed however for example, while 89% of respondents in Mexico are aware of the term antibiotic resistance, only 21% of those in Egypt are. Those who were aware of any or all of the terms were asked where they had heard the term. It is, of course, important that the public is not only aware of the issue, but also understands it. The survey sought to establish levels of understanding by asking respondents to indicate whether a series of statements around antibiotic use were true or false. Similarly to the survey findings related to appropriate antibiotic use, the results suggest that there are high levels of misunderstanding in this area. While large proportions of respondents correctly identify some statements, even larger numbers incorrectly identify others. For example, more than three quarters (76%) of respondents believe that antibiotic resistance occurs when their body becomes resistant to antibiotics. Encouragingly, the majority of respondents in all cases agreed that the actions could help, with numbers rising to 91% across the 12 countries in relation to People should wash their hands regularly. However, when respondents were then asked whether or not they agreed with a series of statements on the scale of the problem of antibiotic resistance, the results reveal some misconceptions and misunderstandings. Notable is the fact that 63% of respondents believe they are not at risk of an antibiotic-resistant infection, as long as they take their antibiotics correctly, which is not in fact the case. Antibiotic-resistant bacteria can spread from person to person, with the potential to affect anyone, of any age, in any country. The findings show considerable variation between countries 89% of those surveyed in Sudan and 81% in Nigeria believe that taking antibiotics correctly protects them from risk, compared to 27% in Barbados. Also notable is the fact that 57% agree with the statement: There is not much people like me can do to stop antibiotic resistance. This is concerning, as addressing the problem of antibiotic resistance in fact requires action from everyone, from members of the public and policy makers, to health and agricultural professionals.

Most of them were resistant to ampicillin buy 200 mg ketoconazole fast delivery fungus that looks like carrot, chloramphenicol buy 200 mg ketoconazole fungus gnats bunnings, streptomycin 200mg ketoconazole free shipping fungal disease definition, tetracycline and trimethoprim/sulfamethoxazole cheap 200mg ketoconazole visa fungus kills ants. Fecal leukocytes were identified under a high power microscope by wet mounting of methylene blue staining method. Those cells clearly identified with either round nucleus or as polymorphonuclear were noted and degenerated cells that could not be clearly identified were ignored. The bacterial pathogens and protozoal pathogens were identified by standard methods. Fecal leukocytes were present 114 Bibliography of Research Findings on Gastrointestinal Diseases in Myanmar in 31. The association between the presence of fecal leukocytes and isolated pathogens from the stools was analyzed. It was found that fecal leukocytes were seen in stools which are associated with shigella (25%), Shigella and Entamoeba histolytica 971. A total of 1805 isolates 115 Bibliography of Research Findings on Gastrointestinal Diseases in Myanmar of E. It was serotyped by using O antisera using test tube terial dilution technique and observed that 93 isolates showed agglutination. The ingredients (24 plants) present in it were selected singly and tested for their antibacterial activities. A total of 35 strains of bacteria (Escherichia coli=11; Staphylococcus aureus=3; Salmonella species=7; Shigella species=4; Vibrio cholerae=7 and one species each of Bacillus subtilis, Pseudomonas aeruginosa and Proteus morganil) were chosen for testing. Among the 23 plants tested, they were found to be active on one, two or more of the bacteria tested with different patterns 328 Mar Mar Nyein; T. It was also noted that Salmonella and Plesiomonas isolation rates were higher in the control group. Antibiotic susceptibility test revealed that these shigellae were resistant to ampicillin (84 per cent), chloramphenicol (76 per cent). From the above cases, 272 cases were also performed for the isolation of other aetiologic agents and observed that Shigella isolated from 3 cases; Vibrio species were isolated from 2 cases; and Plesiomonas shigelloides was isolated from 3 cases respectively. Adherence cell assay was done by using Lab Tek chamber slides seeded with Hep- 2 cells. Thus a study was conducted on 2522 Escherichia coil isolates from 501 diarrhoeal cases and 374 control cases from the Intakaw survey. Enterotoxigenic stains were isolated from 91 cases of diarrhoea ad from 29 control cases. A total of 923 cases of diarrhoea and 932 cases of control were included in this study. They were Vibrio cholerae O1 (21 cases) and Vibrio cholerae O139 (136 cases) from diarrhoea case attending the Infectious disease Hospital during 29-9-98 to 29-10-98. Salmonella typhi (38cases) and Escheriachia coli (15 cases) from cases with high fever for more than five days admitted to Yangon Children s Hospital during 27-8-98 to 17-8-2000. Biopsy findings of gastric ulcers and, operative findings st of some of the cases were recorded. It was a prospective study of 6 months-period from 1 th April 1994 to 30 September 1994. There were 35 patients with radiologically diagnosed ulcer, 11 cases have gastric and 24 cases have duodenal ulcers. Gastric ulcers are more commonly found at the distal 119 Bibliography of Research Findings on Gastrointestinal Diseases in Myanmar part the stomach. The diagnostic radiographic features of duodenal, and both benign and malignant gastric ulcers are studied and discussed in detail. Ten patients treated with sclerotherapy alone and 20 patients treated with propranolol alone. Elective sclerotherapy was performed by using absolute alcohol injection 2 weekly, after that 3 weekly till up to 3 months. Patients treated with propranolol bled significantly less, experienced less bleeding episode per patients (7 vs 28; p<0. Propranolol is cheap, easily available and thus, may prove beneficial and superior to injection sclerotherapy in preventing of upper gastrointestinal bleeding in cirrhotic patients. This study was also carried out to observe the effectiveness of metronidazole on them. The stool samples were collected from diarrhoeal unit of Yangon Children Hospital. If they were present in the stool, the patient was treated with metronidazole and the stool was rechecked again. Intragastric injection of both the argete and unlabelled toxin produced a significant increase of fluid targeted n i ratio over the controls indicating that the biological activity was not lost during radioiodination. In vivo uptake studies of the argete toxin by different parts of the intestine namely duodenum, jejunum and ileum indicated that the uptake by duodenum was highest and the uptake was found to decrease gradually in other parts of the intestine, jejunum and ileum, respectively. The uptake of the argete toxin by subcellular particles of intestinal cells indicated that the toxin uptake was maximum in mitochondrial-lysosomal fraction probably confirming our previous report on lysosomal involvement in the digestion of toxin. The results also seem to be consistent with the short-lived physiologic hypersecretory action of the toxin. Random samples of 396 stool samples from 238 males and 158 females with their ages ranged from one month to ten years old were included in this study. Simultaneously, a set of questions was prepared to ascertain stool characteristics and the duration and motion of diarrhoea of children. Cryptosporidium oocysts were stained by the method of Kinyoun s acid modified Haley and Standard 1973. Socio-economic status, and severity of diarrhoeal diseases, in children under five years of age. The study was a cross sectional survey and standard structured interview schedule was employed. A total of 270 mothers from children with severe, moderate, and mild diarrhoea were interviewed. A high socio- maternal knowledge and attitude but relatively low practices related to diarrhoea were encountered. The study concluded that communication and education for health programmes integrated localized programmes as well as multi- media approach. Defective gastric acid secretion predisposes to abnormal small intestinal bacterial overgrowth and recurrent enteric infection, both conditions may lead to the development of persistent diarrhoea and malabsorption, resulting in malnutrition and growth, failure; and excessive g astric acid secretion may lead to peptic ulceration. Generally, it is measured by aspirating stomach contents with a nasogastric tube after administration gastric stimulant such as pentagastrin. The samples are titrated to neutrality to determine their acid content A simple, non invasive procedure which may be useful a test for gastric acid secretion was developed by Sack and - his coworker in 1985. It is based on the reaction of ingested magnesium metal with gastric acid to produce hydrogen gas, which is detected in exhaled air and belches. Another new, non- 121 Bibliography of Research Findings on Gastrointestinal Diseases in Myanmar invasive test of gastric acid secretion was developed for ideal field studies in the developing world, where chronic diarrhoea and undernutrition are common. The test relies on the capacity of the kidney to retain hydrogen ion during acid secretion, leading to a post-prandial urinary alkaline tide. This research is aimed to study the comparison between the basal and stimulated gastric acid secretion and invasive and non-invasive test for gastric acid analysis in Myanmar adults. Thirty apparently healthy Myanmar male volunteers (25-45) years participated in this study. After overnight fasting, they ingested 150mg of magnesium metal suspended in 3ml of glucose syrup and 100rn1 of 7% ethanol on the first day and alcohol without magnesium on second day. Another 11 samples of gastric juice and breath hydrogen were collected after meal for 180 minutes at 15-minute intervals. Acid contents of gastric juice and urine were determined by traditional titration method.

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