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Muscle Relaxants The neuromuscular blocking agents are divided into depolarizing (succinylcholine) and non-depolarizing (vecuronium order 0.2mg tamsulosin fast delivery androgen hormone questions, pancuronium) categories tamsulosin 0.2 mg otc androgen hormone qui. Acute anaphylactic reactions present as sudden onset hypotension generic tamsulosin 0.4 mg prostate location in body, shock discount tamsulosin 0.2mg otc prostate jewelry, or acute bronchoconstriction with difficulty in ventilation by the anesthesiologist. Generalized urticaria may or may not be reported but flushing or angioedema may be observed on the face. The neuromuscular blocking agents may cause an IgE mediated reaction or induce mast cell activation independent of IgE antibodies. Improvements in synthesis have resulted in agents with little ability to activate mast cells. In some cases, very rapid infusion of the agent causes an immediate reaction, whereas administration over 30 60 seconds does not. The incidence of immediate generalized reactions during general anesthesia ranges from about 1:5000 to 1:20,000 ( 198). The non-depolarizing neuromuscular blocking agents have tertiary and quaternary ammonium groups that are considered to be the antigenic sites for IgE. The lowest dilution (10 ) is used for intradermal testing if the prick test is positive. If the -1 first intradermal skin test is negative, continue with step-wise skin testing until the 10 dilution is used. Skin testing will identify cross-reactive agents, but some patients have immediate cutaneous reactivity to a single agent. Anesthetic agents such as benzodiazepines, thiopental, and propofol rarely are proven to be causative, but adverse reactions have been reported to all of them. The hypnotic agent ketamine, which has sympathetic stimulating actions, caused acute severe pulmonary edema in an 8-year-old child ( 200). Latex allergy, antibiotics, and protamine are in the differential diagnosis of allergic reactions. Part C: Immunologic Reactions to High-Molecular-Weight Therapeutic Agents Leslie C. This recognition can result in sensitization and hypersensitivity reactions on subsequent exposure. Therapeutic agents that are proteins, either of human or nonhuman origin, greater than 3 to 5 kDa, can be recognized by the human immunologic system and can cause sensitization and hypersensitivity reactions. Because these proteins are complete antigens, they can be used as skin testing reagents or as antigens in in vitro assays. Nonhuman protein enzymes like chymopapain and streptokinase have been reported to cause anaphylaxis and other milder hypersensitivity reactions ( 3). Human recombinant proteins are less likely than nonhuman proteins to result in hypersensitivity reactions, but they do occur ( 5). A likely explanation for this somewhat unexpected occurrence is that they are caused by B-cell recognition of alteration in tertiary or quaternary structure because the primary amino acid sequence, recognized by T cells, is an exact copy of the endogenously produced human protein ( 6). Insulin was the first recombinant human protein to which hypersensitivity reactions were reported ( 1). Initially, most of the patients who were reported to be allergic to human recombinant insulin had actually been sensitized to porcine or bovine insulin. In most patients, the antiinsulin antibody appears to be directed against a determinant present in all commercially available insulins ( 12). There has even been a report of systemic allergy to endogenous insulin during therapy with recombinant insulin ( 13). About 40% of patients receiving porcine insulin develop clinically insignificant immediate wheal-and-flare skin test reactivity to insulin. It has been suggested that the presence of antiinsulin IgG antibodies may serve as blocking antibodies and prevent allergic reactions in patients with antiinsulin IgE antibodies. Immunologic insulin resistance that is due to antiinsulin IgG antibodies may follow or occur simultaneously with IgE-mediated insulin allergy ( 10). The most common, clinically important, immunologic reactions to insulin are local and systemic allergic reactions and insulin resistance. Local allergic reactions are not uncommon and usually appear within the first 1 to 4 weeks of treatment. They are usually mild and consist of erythema, induration, burning, and pruritus at the injection site. They may occur immediately (15 to 30 minutes) after the injection or may be delayed for 4 hours or more. Some patients have a biphasic IgE reaction in which the initial local reaction resolves within an hour or so and is followed by a delayed indurated lesion 4 to 6 hours later that persists for 24 hours (14). These local allergic reactions almost always disappear in 3 to 4 weeks with continued insulin administration. In fact, stopping treatment because of local reactions may increase the risk for a systemic allergic reaction when insulin therapy is resumed. Treatment of local reactions, if necessary at all, involves the administration of antihistamines for several weeks for symptomatic relief until the reaction disappears. Systemic allergic reactions to insulin are IgE mediated and are characterized by urticaria, angioedema, bronchospasm, and hypotension. Most commonly, these patients have a history of interruption in insulin treatment. Systemic reactions occur most frequently within 12 days of resumption of insulin therapy and are often preceded by the development of progressively larger local reactions. It is most common to have a large urticarial lesion at the site of insulin injection. Immunologic insulin resistance is even more rare than insulin allergy and is related to the development of anti-insulin IgG antibodies of sufficient titer and affinity to inactivate large amounts of exogenously administered insulin (in excess of 200 units daily). It occurs most commonly in patients older than 40 years of age and usually appears during the first year of insulin treatment. This is effective in about 75% of patients, and improvement is expected during the first 2 weeks of treatment. The dose of prednisone is decreased gradually once a response has occurred, but many patients may require small doses, such as 20 mg on alternate days, for up to 6 to 12 months (5). Diagnostic Testing About half of patients receiving porcine insulin have positive skin tests to insulin. However, skin testing is of value in selection of the least allergenic insulin (porcine, human) to be used for desensitization. Management of Patients with Systemic Insulin Allergy After a systemic allergic reaction to insulin, and presuming insulin treatment is necessary, insulin should not be discontinued if the last dose of insulin has been given within 24 hours. The next dose should be reduced to about one third to one tenth of the dose that produced the reaction, depending on the severity of the initial reaction. Subsequently, insulin can be increased slowly by 2 to 5 units per injection until a therapeutic dose is achieved ( 15). If more than 24 hours has elapsed since the systemic allergic reaction to insulin, desensitization may be attempted cautiously if insulin is absolutely indicated. Insulin desensitization schedule When no emergency exists, slow desensitization over several days is appropriate. The schedule may require modifications if large local or systemic reactions occur. In addition to being prepared to treat anaphylaxis, the physician must also be prepared to treat hypoglycemia, which may complicate the frequent doses of insulin required for desensitization. Desensitization is usually successful and is associated with a decline in both specific IgE insulin-binding levels, and skin tests may actually become negative (17). This latter application has increased significantly with the increased use of cardiopulmonary bypass procedures, cardiac catheterization, hemodialysis, and leukopheresis.

Manuscript with no numbers on the pages of the book Physical Description for Individual Manuscripts (optional) General Rules for Physical Description Give the total number of containers holding the manuscript and/or the total number of linear feet of shelf space the manuscript occupies Follow with the type of container or the words linear feet discount tamsulosin 0.2mg without a prescription prostate cancer 5k pittsburgh. Typical words used include: color black & white positive negative 650 Citing Medicine 4 x 6 in generic 0.2mg tamsulosin prostate cancer 710. Manuscript in a microform Availability for Individual Manuscripts (optional) General Rules for Availability Enter the phrase "Located at" followed by a colon and a space Give the name of the library or archive cheap 0.2 mg tamsulosin with amex prostate cancer journey, preceded by any subsidiary division(s) trusted tamsulosin 0.2mg prostate and ed, and followed with a comma and a space. Bibliotyeka, Rossiiskaia Akademiia Meditsinskikh Nauk [Library, Russian Academy of Medical Sciences] or Manuscripts 651 [Library, Russian Academy of Medical Sciences] Translate names of organizations in character-based languages such as Chinese and Japanese. If you choose an angelicized form for a city name or choose a country code, use that same form or code throughout all references. Manuscript with information on availability 652 Citing Medicine Language for Individual Manuscripts (required) General Rules for Language Give the language of the manuscript if other than English Capitalize the language name Follow the language name with a period Examples for Language 12. Manuscript with title in a language other than English with optional translation Notes for Individual Manuscripts (optional) General Rules for Notes Notes is a collective term for any type of useful information given after the citation itself Complete sentences are not required Be brief Specific Rules for Notes Information about any restrictions on use Other types of material to include in notes Box 32 Information about any restrictions on use A library or other archive may place a variety of restrictions on the use of manuscripts, or the donors of the manuscripts may restrict use. No part of this manuscript may be quoted without the written permission of the Director of the Schlesinger Library and Helen Brooke Taussig, M. Box 33 Other types of material to include in notes Notes is a collective term for any useful information given after the citation itself. Examples include: If the manuscript was translated, provide the name of the original document Heister, Lorenz. Apparently written by a military doctor providing a concise history of the origins and progress of an epidemic of measles and scarlet fever that swept through the city of Queretaro, Mexico, during the summer and early fall of 1825. Manuscript with supplemental note included Examples of Citations to Individual Manuscripts 1. Manuscript author name or secondary author name with designations of rank within a family Heister, Lorenz. The basic sciences: their relationship to the control and regulation of the healing arts. Manuscript with no authors found Arzneybuchlein von mancherley bewarthen und erfahrnen Arzneyen, fur allerley Zufalle und Krankheiten des menschlichen Leibs dienstlich. Descripcion y plan curativo de la epidemia que ha reinado en Queretaro desde fines de junio de este presente ano, hasta la fecha en que esto se escribia [Description and treatment plan for the epidemic that occurred in Queretaro in June of this year, until the date of this writing]. Arzneybuchlein von mancherley bewarthen und erfahrnen Arzneyen, fur allerley Zufalle und Krankheiten des menschlichen Leibs dienstlich. Manuscript with title in a language other than English with optional translation De la grippe et de son traitement par le sulfate de quinine: 2 e partie. Manuscript with translators and other secondary authors Berengario da Carpi, Jacopo. Manuel des operations de chirurgerie par monsieur De Puys premier medicine du Royal Hopital de la Marine de Rochefort [Surgical operations manual of Monsieur De Puy, chief of medicine of the Royal Hospital de la Marine de Rochefort]. Manuscript date with month or month and day provided Kansas Legislative Council, Research Department. Relations of the war to medical science: the annual address delivered before the Westchester Co. Descripcion y plan curativo de la epidemia que ha reinado en Queretaro desde fines de junio de este presente ano, hasta la fecha en que esto se escribia [Description and treatment plan for the epidemic that occurred in Queretaro from the end of June of this year, until the date of this writing]. Apparently written by a military doctor providing a concise history of the origins and progress of an epidemic of 660 Citing Medicine measles and scarlet fever that swept through the city of Queretaro, Mexico, during the summer and early fall of 1825. Chabert came to Paris where he taught at and, in 1780, took over the Royal Veterinary School. In two sections: the first is mainly Greek Orthodox Christian prayers for clergy members for the benefit of sick laypersons in their care; the second half contains recipes for medicines and directions for therapies, also written for clergy. Original manuscript of the printed article found in the Indian Medical Gazette, June 1920. Sample Citation and Introduction to Citing Manuscript Collections The general format for a reference to a manuscript collection, including punctuation: Examples of Citations to Manuscript Collections A manuscript refers to any type of work, either handwritten or typewritten, that is not published. Titles for collections of manuscripts are unusual in that they are assigned by the library or other Manuscripts 661 archive housing the collection. Although they are thus constructed titles, they are not placed in square brackets as are constructed titles for books. If a manuscript collection is not available in any public archive, most authorities recommend placing references to it within the running text, not as a formal end reference. Place the source information in parentheses, using a term or terms to indicate clearly that the citation is not represented in the reference list. For example: material gathered from a collection of papers of Harold Jones (private collection; unreferenced, see "Notes") that The rules below apply when a manuscript collection is included in a reference list rather than within the text as described above. Note that most of the examples for citations provided in this chapter are taken from the Modern Manuscripts Collection of the National Library of Medicine. Citation Rules with Examples for Manuscript Collections Components/elements are listed in the order they should appear in a reference. Box 35 Other surname rules Keep prefixes in surnames Lama Al Bassit becomes Al Bassit, Lama Jiddeke M. Box 42 No author can be found If no person or organization can be found as the author but a compiler is present, begin the reference with the name of the compiler. Follow the same rules as used for author names, but end the list of names with a comma and the word compiler. Manuscripts 667 If no person or organization can be identified as the author or compiler and no translators are given, begin the reference with the title of the manuscript collection. Box 47 Names for cities and countries not in English Use the English form for names of cities and countries whenever possible. Manuscript collection with items not in English Type of Medium for Manuscript Collections (required) General Rules for Type of Medium Indicate the specific type of medium (microfilm, microfiche, etc. Manuscript collection in microform Secondary Author for Manuscript Collections (optional) General Rules for Secondary Author A secondary author modifies the work of the author. Box 52 Secondary author performing more than one role If the same secondary author performs more than one role: List all the roles in the order they are given Separate the roles by "and" End secondary author information with a period Example: Jones, Albert B. Box 53 Non-English names for secondary authors Translate the word found for editor, translator, illustrator, or other secondary author into English whenever possible. Manuscript collection with author and compiler Date for Manuscript Collections (required) General Rules for Date Give the date range of the items in the collection Enter the earliest date of the items in the collection, a hyphen, and the latest date of the items. Manuscript collection with dates estimated Extent (Pagination) for Manuscript Collections (optional) General Rules for Pagination Give the total number of the items in the collection End with a semicolon and a space if Physical Description is provided; end with a period if there is no physical description Specific Rules for Pagination Collection bound in volumes Number of items unknown Box 58 Collection bound in volumes A collection of manuscripts may be bound in volumes rather than being placed in boxes or other containers. When this occurs: Express extent as the number of volumes Abbreviate volume to vol. Box 59 Number of items unknown A collection may be so large that an exact count of the number of items in it has not been made. Manuscript collection with extent estimated Physical Description for Manuscript Collections (optional) General Rules for Physical Description Give the total number of containers holding the collection and/or the total number of linear feet of shelf space the collection occupies Follow with the type of container or the words linear feet, such as 3 boxes or 10 linear feet End with a period Give information on the total number and physical characteristics of the items in the collection if they reside in a microform, such as 26 microfiche: black & white, 4 x 6 in. Typical words used include: color black & white positive negative Manuscripts 679 4 x 6 in. Box 61 More than one type of medium If a manuscript collection is in a microform such as microfilm or microfiche, place the name of the type of microform after the title in square brackets Alchemy collection [microfilm]. Manuscript collection with physical description Availability for Manuscript Collections (required) General Rules for Availability Enter the phrase "Located at" followed by a colon and a space Give the name of the library or archive, preceded by any subsidiary division(s), and followed by a comma and a space. Bibliotyeka, Rossiiskaia Akademiia Meditsinskikh Nauk [Library, Russian Academy of Medical Sciences] or [Library, Russian Academy of Medical Sciences] Translate names of organizations in character-based languages such as Chinese and Japanese. Manuscript collection with availability Language for Manuscript Collections (required) General Rules for Language Give the language of the collection if not English Capitalize the language name Follow the language name with a period Specific Rules for Language Collections with items in more than one language Box 62 Collections with items in more than one language If the items in the collection appear in more than one language, give all languages found, separating them by a comma and a space Examples: von Diringshofen, Heinz. Box 66 Collections with restrictions on use A library or other archive may place a variety of restrictions on the use of manuscript collections, or the donors of the manuscripts may restrict use. Gertrude Henle required to quote, cite, paraphrase, or publish any of the unpublished material during her lifetime. Box 67 Other types of material to include in notes Notes is a collective term for any type of useful information given after the citation itself.

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Fre- quently 0.4 mg tamsulosin for sale prostate cancer diet plan, it is hard to express the rules for the system and also the translation of implicit knowledge into explicit rules would lead to loss and distortion of infor- mation content [3] buy discount tamsulosin 0.4mg online prostate 3 times normal size. On the other hand buy 0.4 mg tamsulosin otc prostate with grief, the tree structure of rule-based relation- ships becomes too complex if new levels of knowledge are added purchase 0.2mg tamsulosin prostate oncology johnson. For example, there are many types of hepatitis B and if the system described before has to de- cide between these types, it will be difficult to implement it. A problem that must be taken into consideration is linked to the fact that inferences are done based on the informa- tion contained in a sample, which is only a part of the whole population. The probabil- ity plays an important role, being used to define the quality of an affirmation, to measure the uncertainty or to describe the chance for an event to happen. In this area, the most frequently used method is the Bayes s theorem, which sets a probabilistic value for each considered output (disease, if the system is applied in medical diagnosis). Bayesian networks have an important area of applicability in the entire field of artificial intelligence, setting a posterior probability when prior probability is known [4]. The analysis starts with the prior probabilities (preceding the experience) for the interesting events. Then it is used a supplementary information from a sample, a test, a report or from other sources, information that affects the prob- ability of the events. The prior probability will be revised using this new informa- tion and the result will be the posterior probability (after the experience and based on the experience). It is very useful to have an expert system that can predict, using symptoms and laboratory test results, what type and what form of hepatitis B is present for a new patient. It needs a database with symptoms for a number of patients ( - statistical population) that have associated a final diagnosis set. In this application was used a database with over 150 patients with hepatitis B virus infection. Medical Predictions System Bayes s theorem is a formula with conditioned probabilities. If it is applied in medical diagnosis, its form is: p( S | Dk ) p( Dk ) p( Dk | S ) = (1) p( S ) where Dk is a disease and S a set of symptoms. Using the theorem it can be calcu- lated, for a patient, the probability of appearance for each disease Dk when the set of symptoms S is present. This formula will be applied for each evolutional type and each form of hepatitis B disease, offering for each one a plausibility score. Such an expert system could be successfully used if it is developed for mutual exclusive diseases and independent symptoms. But sometimes these restrictions cannot be accomplished because there are situations when some symptoms have the same cause (being connected) and a patient can suffer of more than one dis- ease. It was also observed that Bayes s theorem needs an excessive calculation time if statistical population is very large. In order to avoid these problems, two other statistical algorithms were implemented: Aitken s formula and Logistic model. Aitken s formula [5] is an alternative for equation (3) (which is the most time con- sumer in Bayes s theorem). Medical Predictions System p( E ) p( E ) o( E ) = = (10) p( E ) 1 p( E ) and conditioned anti-probability: p( E | F ) o( E | F ) = (11) p( E | F ) From (10) and (11), where E and F are two events, can be written equations (12) and (13): o( E ) p( E ) = (12) 1 + o( E ) o( E | F ) p( E | F ) = (13) 1 + o( E | F ) It is easier to calculate o(E|F) than p(E|F). B Artificial Neural Networks There are a lot of cases when is not possible to implement human intelligence with expert systems. The initial idea was that in order to reproduce human intelligence, it would be necessary to build systems with a similar architecture [6]. Artificial neural networks are developed based on brain structure, representing a simplified mathematical model of central nervous system. They are made by artificial neurons, which implement the essence of biologi- cal neuron. In this system, artificial neural networks are used in order to make some predic- tions regarding the treatment response for a patient infected with hepatitis C virus. Hepatitis C is a serious and frequent disease and its evolution has to be carefully overseen during the treatment. Even the efficiency of the hepatitis C treatment improves continuously, the burden of this infection will remain a major issue for the next several decades. The system offers for each evaluated biological indicator predictions regarding the next 12 months evolution, indicating its growing tendency, its stabilizing or de- creasing tendency. It was developed using feed-forward neural networks with back-propagation learning algorithm. Each neural network has a layer of 10 hidden neurons, a single output unit and a variable number of inputs. For each of the four biological indicators that have been studied, there are four layers of neural networks. The advantage of this architecture is that the input data are processed separate for each biological indicator. The disadvantage is that the errors are propagated through the system because the results of the networks from the first level (to- gether with their errors) are used in the following levels. It develops a multifunctional database and imple- ments an expert system used in order to diagnose different types of hepatitis and to realize some predictions regarding the evolution of the patient and the response to the treatment. The system uses two major components (an inference machine and an architecture of neural networks) that operate on the multifunctional data- base (Fig. It has an interdisciplinary character and fulfils the requirements of a system used in medical diagnosis and prediction. The user has to set the values of the markers that determine which is the hepatitis type. If the human expert needs more predictions regarding the diagnosis, than he can use the other two branches of the application. After that, he will choose one of the three implemented algorithms (Bayes s theorem, Aitken s formula, or Logistic model) and the plausibility scores for each evolutional type and grade of hepatitis B are calculated (as can be seen in the right part of Fig. These statistical algorithms are using a part of the multifunctional database: 165 patients infected with hepatitis B virus. The data which describe medical status of these patients were collected from Clinical Hospital of Infectious Diseases No. It is also necessary to introduce the values of the biological indicators before the treatment. The system will predict the evolution of the biological indicators depending on the treatment. Looking at the predicted tendency of the biological indicators during the treatment, a physician can estimate if the patient will respond to a treatment or not. All these are stored in another part of multifunctional database, which con- tain almost 200 patients infected with hepatitis C virus. These real data were col- lected from Country Clinical Emergency Hospital, Timisoara. Conclusions This paper tried to evidence some important aspects connected to medical deci- sion making. First of all, logical inference is used to decide what type of hepatitis virus is present for a new patient. After that, the sec- ond part of the system will be used to see what will be the type and the grade of hepatitis B (if the patient is infected with hepatitis B virus). The third part of the system is made for the patients infected with hepatitis C virus and it predicts the biological parameters evolution during the treatment using artificial neural net- works. The hepatitis is a serious disease, its treatment is expensive and severe side effects can appear very often. Therefore, it is important to set a correct diagnosis and to identify those patients who most probably can react to the treatment, so that the others can be protected from a treatment with no benefits. Zurada: Introduction to Artificial Neural Systems, West Publishing Company, United States of America, 1992 [4] D. Niedermayer: An Introduction to Bayesian Networks and their Contem- porary Applications, www.

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It contributes to meeting ease burden or prevalence, as well as the state company is not a signatory of the United Nations the London Declaration targets by 2020, includ- of public fnancing systems. This makes it the newest pharma- ceutical company to engage in non-exclusive vol- Rises four places. With four donation programmes, AbbVie does not have disease-specifc registra- Abbvie has the second largest number of struc- tion targets and does not publish products reg- Does not publish its policy positions on trade tured donation programmes. As a result, it is positions regarding the Doha Declaration on the Expands product donation activity. AbbVie launched a new donation programme, its products based on the need for access. Its ter a few of its recently launched products in all new programme aims to improve the survival corresponding priority countries (disease-spe- No change in rank. AbbVie performs above rates of premature babies in Honduras, India, cifc sub-sets of countries with a particular need average when it comes to strengthening phar- Jamaica, and Paraguay. However, most macovigilance systems and disclosed one of of these products were frst marketed 15 20 the strongest commitments to reporting sus- Clear commitment to product donations. Its performance in AbbVie has made a public commitment to sup- products launched since 2014 in only a few pri- other areas, however, is comparatively weak. AbbVie has glob- AbbVie also commits to adhering to a strict ally consistent guidelines for issuing drug recalls Among the leaders in strengthening pharma- Global Product Donations Policy, which aligns in all countries relevant to the Index where its covigilance systems. AbbVie has not recalled safety data with authorities upon request and a product for a relevant disease in a country in updates safety labels in countries in scope. AbbVie s scope during the period of analysis but states company has a number of initiatives to build Global Product Donations Policy requires dona- that product recalls would be made public via its local pharmacovigilance capacity, focusing on tion partners to regularly report on whether company website. AbbVie screens potential partners to ensure they have Widespread pricing monitoring and track- Strong information sharing to improve supply implemented and abide by appropriate policies ing. In certain markets, it also frmed cases in a timely manner, and shares audits of its donation partners. While the Makes ad hoc donations for disaster relief and Limited adaptations of its brochures and pack- company shares information, it does not under- in emergencies. AbbVie partners relatively rarely it takes literacy, environmental, demographic or with local research organisations. Rises 9 places due to improved engagement in Limited evidence of mitigating confict of inter- licensing. AbbVie moves up from 17th position est in capacity building outside the value chain. It did not report any eforts to build AbbVie has agreed access-oriented licences local manufacturing capacity during the period for both paediatric and adult formulations of of analysis. It now publishes the statuses of its patents, but has yet compliance systems, but drops across other areas of meas- to agree a non-exclusive voluntary licence for one of its pat- urement. In addi- second-line treatment for diabetes) to permit cerns for non-communicable diseases more tion to its pricing strategy for human insulin, generic medicine manufacturers to produce bio- broadly. Novo Nordisk can leverage its exper- Novo Nordisk can implement new measures to similars. This can help address issues of aforda- tise in diabetes to support public and/or pri- support sustainable and afordable access to bility and supply. Considering the complexity of vate partners in strengthening care for diferent new diabetes treatments (including insulin ana- biosimilar production, the company can consider non-communicable diseases. Novo Nordisk can apply its exist- ing activities and target local needs and skills mitments to prioritise those markets where the ing model of engaging with health care profes- gaps more strategically (e. The company can also the needs of patients in low- and middle-income share information with local stakeholders to help Consider a company-wide approach to volun- countries. This includes ensuring specifc access strengthen supply chains and pharmacovigilance tary licensing. Novo Nordisk can consider terms plans are in place for candidates currently in the systems. Novo 0 Nordisk has sales in 79 countries in scope, and 2011 2012 2013 2014 2015 over 20% of its sales come from emerging and Rest of world China Japan/Korea Europe frontier markets. It has a small The company is developing four medicines, all in pipeline of four R&D projects that address the phase I clinical trials. Its rele- basal insulin analogue for once-weekly dosing, 11 vant portfolio and pipeline focus exclusively on an appetite-regulating hormone peptide tyrosine diabetes. The latter has progressed from discovery stage Nine of its 11 medicines are insulins, including to phase I trials since 2014. In 2015, its insulin degludec (Tresiba ) was approved for The company s focus is on diabetes. Its remaining two products are geting high-priority product gaps with low com- Novo Nordisk s medicines all target diabetes: nine liraglutide (Victoza ), a glucagon-like peptide-1 mercial incentive, for diseases that disproportio- out of 11 are insulins and insulin analogues. It is developing a Novo Nordisk is not currently adapting any products to meet the needs of daily oral insulin tablet that will not require refrigeration, potentially improv- people living in low- or middle-income countries. A leader, due to a strong strategy and sys- Goes beyond sales-linked incentives; has broad tems. It rewards relatively high proportion of Novo Nordisk s R&D access strategy, good performance management its sales agents for more than just sales, using investments are relevant to the Index. It pub- systems and an innovative initiative in govern- product availability and stock maintenance as lishes its investments into diabetes and obesity ance and stakeholder engagement. Access is integrated into corporate strategy, keting activities in countries in scope. Globally, the com- No commitment to access-oriented R&D part- pany aims to reach 40mn people with diabetes Relatively high transparency regarding lobby- nerships. Novo Nordisk is transparent about its lobby- ensuring access-oriented terms are system- annual strategic planning process. Novo Nordisk plans its Novo Nordisk uses two performance manage- audits based on an independent risk assessment, Takes measures to ensure clinical trials are ment systems to monitor and measure progress to ensure certain units are visited every year and conducted ethically. Two to cies in place and takes measures to ensure its Scorecard, used for tracking the company s three external audits of selected high-risk third in-house and outsourced clinical trials are con- goals, and the second is its People Performance parties are performed annually. The Well-defned strategic stakeholder engage- Novo Nordisk has not been the subject of any company upholds high standards of clinical trial ment. Novo Nordisk has a strategic approach settlements for criminal, civil or regulatory data transparency, including providing scien- to stakeholder engagement. The process is infractions relating to unethical marketing or tifc researchers access to patient-level data well defned, making it easier for subsidiaries to corruption anywhere in the world during the upon request. Cities Changing Novo Nordisk has an enforcement process in Diabetes is a cross-disciplinary and cross-sector place, including disciplinary measures. Novo Nordisk is committed to systematically review- Drops in R&D, with a smaller pipeline for the Same products with equitable pricing. Novo Nordisk s performance fell, largely Nordisk has equitable pricing strategies for the Development Goals, focusing on health and due to a decrease in the size of its adaptive pipe- same human insulin products as in 2014. One ity countries (disease-specifc sub-sets of coun- Top performer in market infuence and com- of Novo Nordisk s strategic aims is to build and tries with a particular need for access to relevant pliance. Novo Nordisk is 2nd once again, with maintain a leading position in emerging mar- products).

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