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The X-ray shows a dilated fluid-filled oesophagus with no visible gastric air bubble discount forzest 20mg with mastercard. The oesophagus has now dilated and there has been spill-over of stagnant food into the lungs giving her the episodes of repeated respiratory infections generic forzest 20 mg. Such aspiration is most likely to affect the right lower lobe because of the more vertical right main bronchus, although the result of aspiration at night may depend on the position of the patient. It tends to be present for all foods, indicating a motility problem, and there may initially be some relief from the mechanical load as the oesophagus fills. The diagnosis can be made at this stage by a barium swallow showing the dilated oesopha- gus. Earlier it may require careful cine-radiology with a bolus of food impregnated with barium, or oesophageal motility studies using a catheter fitted with a number of pressure sensors to detect the abnormal motility of the oesophageal muscle. A similar condition can be produced by the protozoan parasite Trypanosoma cruzi (Chagas disease), but this is limited to South and Central America and would not be relevant to her stay in the north-west United States. Other common causes of dysphagia are benign oesophageal structures from acid reflux, malignant structures, external compression or an oesophageal pouch. Achalasia may be managed by muscle relaxants when mild, but often requires treatment to disrupt the lower oesophageal muscle by dilatation or surgery. In his abdomen the only abnormality is that his spleen is palpable 4 cm below the left costal margin. This is due to abnormal proliferation of red cell precursors derived from a single haematopoietic progenitor cell with the capacity for differentiation down red cell, white cell and platelet lines. As a result, there is an increase in haemoglobin, white cell count and platelet level. Patients may present with a throm- botic event or with symptoms due to increased blood viscosity such as headaches, tinni- tus and blurred vision. Severe pruritus is characteristic and is particularly related to warmth occurring on getting into a warm bed or bath. Conditions associated with generalized pruritus without a rash Obstructive jaundice due to bile salt retention Iron deficiency Lymphoma Carcinoma, especially bronchial Chronic renal failure, partially due to phosphate retention This patient should be referred to a haematology unit for investigation. It is important to exclude relative polycythaemia due to dehydration from diuretic and alcohol use. The red cell mass will be raised in polcythaemia rubra vera, but normal in relative polycythaemia. The erythropoietin level is low in polycythaemia rubra vera and high in secondary poly- cythaemia. The leucocyte alkaline phosphatase level is also raised in polycythaemia rubra vera. The patient should be venesected until the haematocrit is within the normal range. A var- iety of agents can be used to keep the haematocrit down: 32P, hydroxyurea and busulphan. The symptoms have been present for 2 months and have increased slightly over that time. He had noticed some skin lesions on the edge of the hairline and around his nostrils. Previously he had been well apart from an appendicec- tomy at the age of 17 years. Examination There is no deformity of the joints and no evidence of any acute inflammation. In the skin there are some slightly raised areas on the edge of the hairline posteriorly and at the ala nasae. The age is typical and sarcoidosis is more common in those of African-Caribbean origin. The blood results show a slightly raised calcium level which is related to vitamin D sensi- tivity in sarcoidosis where the granulomas hydroxylate 25-hydroxycholecalciferol to 1,25- dihydroxycholecalciferol. The skin lesions at the hairline and the nostrils are typical sites for sarcoid skin problems. The eye trouble 6 weeks earlier might also have been a manifesta- tion of sarcoidosis, which can cause both anterior and posterior uveitis. Tuberculosis can also cause hypercalcaemia although this is much less common than in sarcoid. Tumours, especially lymphoma, might give this X-ray appearance but would not explain the other findings. The arthralgia (pains with no evidence of acute inflammation or deformity on examination) can occur in sarcoid or tuberculosis but again they are commoner in sarcoid. The serum level of angiotensin-converting enzyme would be raised in over 80 per cent of cases of sarcoidosis but often in tuberculosis also; the granuloma cells secrete this enzyme.

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To Medicine Index reports jointly on General achieve these goals quality forzest 20 mg, more companies are using performance management systems Access to Medicine Management (gov- with access-linked targets and performance-linked incentives purchase forzest 20 mg without prescription. Stakeholder engage- ernance) and Market Infuence & ment to increase access to medicine is now commonplace and generally well organ- Compliance (compliance). The aim is ised, with some companies using secondment and volunteering programmes to to highlight where access to medicine help foster innovation. Companies have comprehensive compliance systems, yet misconduct continues Companies have comprehensive compliance systems for ensuring employees meet In this analysis, governance refers to: agreed standards of behaviour. Some companies are adopting innovative compli- ensuring oversight, enabling accounta- ance-management policies and practices, such as revolving-door policies to miti- bility and engaging with stakeholders gate risks related to conficts of interest. Yet, most companies continue to breach specifcally in relation to access-to-med- laws or codes relating to corruption and unethical marketing. Compliance refers to: greater risk of non-compliance in low- and middle-income countries, where regula- ensuring processes, operations and prac- tory systems are likely to be weaker. This underscores the need for strong enforce- tices meet standards, codes, regulations ment of compliance systems for companies operating in these jurisdictions. In the pharmaceu- actions, cases of misconduct have the When they are managed together,2 tical industry, this can cause the diver- potential to undermine a company s they create responsible and account- sion of public funds away from essential best eforts to improve access. Pro-access business models are more Access to Medicine Index reports Poor compliance is a particular cause common, but misconduct puts pro- jointly on General Access to Medicine for concern where regulatory frame- gress at risk Management (governance) and Market works and prosecutorial systems are In 2016, companies have increasingly Infuence & Compliance (compliance). The industry scores most integration of these areas of policy and treatment of customers and market highly when it comes to setting access management. Yet the industry s per- improve access formance in compliance is not keeping Having an access-to-medicine strat- Managing external relations pace. There is evidence that most com- egy increases a company s chances of Companies interact with diferent panies have continued to breach laws or making targeted, measurable and sus- stakeholders for diferent purposes: codes relating to marketing, which may tainable improvements to access to either to gather input from outside be undermining the success of their medicine. This includes setting specifc groups (via stakeholder engagement), access-to-medicine strategies in low- objectives relating to access to medi- to promote the company s positions and middle-income countries. To translate the strategy into pos- and interests (via lobbying) or to secure despite companies implementing more itive outcomes, companies need good market presence and penetration (via comprehensive compliance systems. The industry scores well in access management, but lags in compliance medicine, and a strategic approach to Where the Index measures management and compliance, companies perform best when it comes to stakeholder engagement. The industry scores well in management, but lags in compliance egies that support corporate aims and behaviour. Such misconduct can limit access to medicine, putting companies investments in access to Companies perform best when it comes to setting detailed access-to-medicine strategies. Such misconduct can limit access to medicine, to receive internal support among man- putting companies investments in access to medicine at risk. It ena- tive and qualitative targets that contrib- Access strategy based on the income bles the company to target middle-, ute to company-wide access goals. The pyramid lower-middle and low-income popu- three companies that still lack an over- Novartis has developed a best prac- lation segments, drawing on a portfo- all access strategy (AbbVie, Astellas, tice for reaching all socio-eco- lio of access models that Novartis has Daiichi Sankyo) do use a range of stand- nomic population segments through determined are scalable and replica- 47 Access to Medicine Index 2016 ble. These include sions are made according to income Incubator for social business ideas the Sustainable Development Goals level. This frame- new social business ideas, it brings social Using external benchmarking frame- work includes the approaches shown in innovators and partner organisations works enables companies to collaborate fgure 2. Where access strategies have Access strategies can follow the base-of-the-pyramid approach. This approach uses diferent tools a clear business rationale, companies to reach diferent income segments. While the long-term success of this approach is not yet proven, have a greater incentive to deliver on it does have advantages. It enables initiatives to be tailored to diferent levels of income, and income and expand them, increasing their long- levels can be used to indentify where other access barriers exist. These are usu- Pfzer s non-fnancial incentive and vol- 15,432 people and held 44 health camps ally run in partnership with stakehold- unteering programme focuses on provid- in India. Novo Nordisk will systematically ers and include an element of capac- ing high-quality, efcient health services review its contributions toward each of ity building and knowledge-transfer (i. Roche) have taken this step, with the remaining companies assigning exec- utive-level responsibility. Companies view employee s hands-on involvement as a source of quence, all companies regularly dis- insight cuss their access performances in board In total, 10 companies have an initiative that involves employees working directly with partner organisa- meetings. All companies now use performance management systems to track pro- gress toward access-related targets, which they set at both a company-wide Stakeholder and employee level. A few companies (AbbVie, Astellas AbbVie FutureFit and Boehringer Ingelheim) have yet to reward good access-related perfor- Bayer Volunteering Program mances, with either fnancial or non-f- nancial incentives.

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A patient information sheet (available in ten languages and Braille) is sent out to patients with their hospital appointment letter forzest 20mg visa, so that they are asked in advance of their appointment if they wish to donate their surplus tissue prior to surgery buy forzest 20mg lowest price. Importing bodily material from abroad (potentially any form of bodily material) 3. Global pharmaceutical companies, who have a significant number of collaborators overseas, may also choose to import tissue from collaborator countries because they find it useful to identify geographical patterns in disease similarities and differences. It is foreseen that the proposal for a revision of the Directive will be adopted in 2012. Some recent major campaigns in relation to blood and organs gametes are summarised in Box 3. As they progress, the camera focuses on one man, and the caption "severed artery, Monday 11:40am" appears. At the end of each advertisement, a voiceover asks viewers to "give blood, and you can save someones life. These include Adrian Turner, a former Olympic swimmer who had to have his spleen removed as a teenager and needed a blood transfusion. The website also focuses on those who still need blood, such as James Baffoe, a young man with sickle cell anaemia. In a video interview, he notes that "if I dont receive red cell exchanges, I would have a lot more crises; a lot more stays in hospitals, and I hate hospitals. The campaign uses several Welsh celebrities, including Colin Jackson and James Hook. For example, while disease-specific charities or research organisations may run campaigns for 443 certain types of bodily tissue to be donated for research, there are no overarching national campaigns to encourage patients to give unneeded tissue remaining after medical procedures for research purposes. Recognising the costs of donation (all forms of material and first-in-human trials) and non- financial tokens of gratitude (blood and organs) 3. Explicit payment for participation in first- in-human trials is, by contrast, routine (see paragraph 2. Examples of non-financial tokens of gratitude include inclusion in public memorials such as the service of thanks for people who have donated their body to medical research, held each year at Southwark Cathedral. These approaches may include 450 national memorials, local initiatives and personal follow-up to donor families. They could also include a system for the sale and purchase of organs or gametes, whether at non-market rates via a governmental organisation or in a fully-fledged free market. Israel has recently introduced such a scheme in respect of organ donation: citizens who commit to donating their own organs after death are promised priority in the queue 452 for an organ transplant, should they ever need one (see paragraph 2. However, because a reduced number of eggs is available to the egg sharer, she will have fewer frozen embryos, and therefore her cumulative pregnancy rate may be lower than if she had kept all the eggs for own use. There is some evidence to suggest that egg sharing is not an option 461 many women choose if other routes to pregnancy are available. Individuals may seek the help of an intermediary in such searches: for example a recently-established website offers to manage the recruitment of 471 egg donors for potential recipients. However, concerns have also been expressed that direct recruitment of donors in this way may potentially lead to the prohibition on financial reward for 473 donors being subverted in some cases. Initial conclusions suggest that significant drivers for people deciding to travel abroad for fertility treatment include a shortage of egg donors, the risk of long waiting times for treatment, and issues of cost. The process of cross-border fertility treatment may be prompted 478 by clinics, or taken wholly at the initiative of the individual. The preamble to the Declaration of Istanbul on Organ Trafficking and Transplant Tourism (Steering Committee of the Istanbul Summit), 2008, states, for example: "The legacy of transplantation must not be the impoverished victims of organ trafficking and transplant tourism 480 but rather a celebration of the gift of health by one individual to another". Recent media reports from Kosovo, India and South Africa appear to 482 confirm this. Ethical values often invoked in response to such concerns include: Altruism Autonomy Dignity Justice Maximising health and welfare Reciprocity Solidarity. This does not mean that they become redundant but rather that the way they are being used in particular circumstances needs to be made explicit and, where necessary, justified. It epitomises the opposite of theft and seizure by force, and in so doing it points to the desirability of material properly given rather than improperly taken. In donation, public and private are understood in many different ways, and it may be more helpful to think of public and private as being complementary and overlapping rather than as in opposition. We note how an awareness of these factors adds to the importance of seeking to find areas of mutual agreement and concern, where particular policies may be supported by diverse audiences for diverse reasons. These two aspects of the donation or volunteering of bodily material have generated a number of (sometimes competing) ethical concerns around consent, control, and ownership (See Box 4. Addressing the legitimate role of public and private bodies in responding to that shortage, the question becomes: how far should public and private bodies go in encouraging, or even incentivising, people to provide their bodily material or to volunteer for a trial? It will also consider the importance of considering the context in 485 which appeal is made to these values (see paragraph 4. The purpose of doing so is to highlight how controversies and disputes that arise in connection with the donation of bodily material are often not so much about the respective merits of particular values, but rather about the ethical dilemmas with which these values are associated, and the way in which values are invoked to make particular claims. Altruistic giving may be to strangers, or may take place within the context of family or other relationships. The widespread support for this model for donation is found both in the regulatory emphasis on voluntary and unpaid donation (see Box 2.

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