By F. Dudley. Vermont Technical College. 2018.

How will we ensure a healthy future for children like Luciano and the millions of others facing chronic diseases? This requires a new approach » The chronic disease threat can be overcome using existing knowledge by national leaders who are in a » The solutions are effective – and position to strengthen chronic disease highly cost-effective » Comprehensive and integrated prevention and control efforts purchase mentat 60 caps visa, and action at country level cheap mentat 60caps visa, led by governments order mentat 60 caps fast delivery, is the means to by the international public health achieve success community discount 60caps mentat fast delivery. Visual impairment and blind- ness purchase 60caps mentat amex, hearing impairment and deafness, oral diseases and genetic Projected gl o disorders are other chronic conditions that account for a substantial portion of the global burden of disease. Injuries * Chronic diseases include cardiovascular diseases, cancers, chronic respiratory disorders, diabetes, neuropsychiatric and sense organ disorders, musculoskeletal and oral disorders, digestive diseases, genito-urinary diseases, congenital abnormalities and skin diseases. These risk factors explain the vast majority of chronic disease deaths at all ages, in men and women, and in all parts of the world. Furthermore, chronic diseases – the gets and indicators to include chronic diseases major cause of adult illness and death and/or their risk factors; a selection of these in all regions of the world – have not countries is featured in Part Two. Health more broadly, including is addressed within the context of international chronic disease prevention, contributes health and development work even in least to poverty reduction and hence Goal 1 developed countries such as the United Republic 1 (Eradicate extreme poverty and hunger). Ten of the most common Notions that chronic dis- misunderstandings are pre- eases are a distant threat sented below. In reality, low and middle income countries are at the centre of both old and new public health challenges. While they con- tinue to deal with the problems of infectious diseases, they are in many cases experiencing a rapid upsurge in chronic disease risk factors and deaths, especially in urban settings. These risk levels foretell a devastating future burden of chronic diseases in these countries. The truth tion to his high blood pressure, nor to his drinking is that in all but the least and smoking habits. He then lost his ability to speak after two consecutive diseases, and everywhere strokes four years later. Roberto used to work as a public transport are more likely to die as agent, but now depends entirely on his family to survive. Moreover, chronic diseases cause substantial financial burden, and can push individuals and house- holds into poverty. People who are already poor are the most likely to suffer financially from chronic diseases, which often deepen poverty and damage long-term economic prospects. Much of the family’s Roberto is now trapped in his own body and always income is used to buy the special diapers that needs someone to feed him and see to his most basic Roberto needs. Noemia carries him in and out of the house so check-ups are free of charge but sometimes we he can take a breath of air from time to time. Noemia and four of her brothers and sisters also suffer But the burden is even greater: this family not from high blood pressure. We now know that almost half of chronic disease deaths occur prematurely, in people under 70 years of age. In low and middle income countries, middle- aged adults are especially vulnerable to chronic disease. People in these countries tend to develop disease at younger ages, suffer longer – often with preventable 10 years rose from 23% to 28% between 1995 complications – and die sooner than those and 2003. Health workers from a nearby medical centre spotted his weight problem last year during a routine community outreach activity. One year later, Malri’s health condition hasn’t changed for the better and neither has his excessive consumption of porridge and animal fat. His fruit and vegetable intake also remains seriously insufficient – “it is just too hard to find reasonably priced products during the dry season, so I can’t manage his diet,” his mother Fadhila complains. The community health workers who recently visited Malri for a follow-up also noticed that he was holding the same flat football as before – the word “Health” stamped on it couldn’t pass unnoticed. Malri’s neighbourhood is littered with sharp and rusted construction debris and the courtyard is too small for him to be able to play ball games. Fadhila, who is herself obese, believes that there are no risks attached to her son’s obesity and that his weight will naturally go down one day. In fact, Malri and Fadhila are at risk of developing a chronic disease as a result of their obesity. Children like Malri cannot choose the environment in which 13 they live nor what they eat.

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Virtual teams – such as specialists linked to gen- eral practitioners by telephone – are increasingly common in rural or remote settings cheap 60caps mentat free shipping. Ministries of health should work with ministries of education and professional societies to ensure that the health workforce is taught the right skills to prepare them adequately for chronic disease prevention and management buy mentat 60 caps low price. Continuing professional education allows the health workforce to develop skills after completion of training 60 caps mentat otc. Educational activities include courses 60caps mentat fast delivery, on-site follow-up and coaching order mentat 60caps, and regular assessments and feedback on progress. Medical, nursing and other health professional societies are valuable partners in the provision of continuing medical education. The stepwise » The private sector is a natural partner in chronic disease framework initiated by prevention and control governments can be best » Civil society plays a role that is implemented by working distinct from that of governments with some or all of the and the private sector, and adds private sector, civil soci- human and financial resources to a wide range of chronic disease ety and international or- prevention and control issues ganizations. This chapter » International organizations and outlines the ways in which donors have important roles to such cooperation can be play in the response to chronic disease put into practice. They offer all sectors new opportunities to work together in order to advance the greater public good. In order to be as effective as possible, they should work within the overall framework for prevention and control determined by the government (see previous chapter). Working in partnership ensures synergies, avoids overlapping and duplication of activities, and prevents unnecessary or wasteful competition. The partnership has recently released a strategic framework for are implemented with the full agreement of all action, and work is under way on parties. Developing and managing a successful partnership Transparent linkages are being requires an appropriate organizational structure. Possibilities for partnerships with pharmaceutical companies are also being explored (8). It to improve health in the Americas by reducing risk factors aims to create a dynamic inter- for chronic diseases. The main focus has been primary pre- national forum where health- vention of risk factors such as tobacco use, poor diet and care providers, researchers, physical inactivity. The research as well as clinical and network serves as a forum for advocacy, knowledge dis- public health information, thus semination and management, and technical support and as ensuring the high scientific an arena where directions, innovations and plans are made quality of the discussion (for for continuous improvement of chronic disease prevention more information see http:// initiatives in the Americas. Most adults spend a significant portion of their time in a work environment and are often surrounded by peers who may influence their behaviour and attitudes. Mobility India created the tems kept clean and tobacco- Millennium Building on Disability – the Mobility India free, assistive devices installed, Rehabilitation Research & Training Centre – as a model and physical activity promoted. The building is or if more resources are avail- friendly to all types of disabilities, and 40% of the staff able, employers can move on to have a disability. Braille signs; tile floors with varied surfaces to guide people with visual impairments; accessible bathrooms, switchboards, and washbasins; a lift with auditory sig- nals and an extra-sensitive door sensor; adequate and earmarked parking spaces; highly accessible hallways and workspaces with furniture kept in unchanged loca- tions; and contrasting colour schemes and natural light for people with low vision. The fact that Mobility India staff with personal experi- ence of disabilities and chronic conditions are working in an accessible building has created a productive environ- ment in which to work with confidence and dignity (9). The success of the Mectizan® (ivermectin) to prevent Mectizan® donation programme (see spotlight, onchocerciasis, or river blindness, in left) is one example of such a programme. In 1987, it decided to donate as much as is needed to every- one who needs it for as long as it takes to eliminate the disease worldwide. Mectizan® cannot restore lost sight but if it is taken early enough, it protects remaining vision. It kills the larvae responsible, and elimi- nates itching and damage to the eyes with just one dose per year, although infected people need to take Mectizan® for around 20 years. The Mectizan® donation programme has been a highly effective public health programme and serves as a possible model for tackling some future problems in international health. The private sector has a significant role to play in closing these gaps, as do public–private partnerships, which can invest strategically to accel- erate progress with regard to specific diseases. Current annual produc- Alternatives to insulin delivery tion of hearing aids provides approximately 33% of those technologies, such as nasal needed in high income countries, but less than 3% of those sprays, could reduce the need needed in low and middle income countries. Afford- reluctant to provide affordable hearing aids on a large able hearing aids (see spotlight, scale because of their perceived lack of a sustainable left) are another public health market, and the lack of infrastructure to provide them. Providing appropriate and affordable hearing aids and services worldwide would be a highly effective and cost- effective way to make a positive impact. Sustainable provision on a sufficiently large scale in low and middle income countries would also be crucial in terms of improv- ing equity and access. The guidelines state that public–private partnerships between the governments of developing countries and hearing aid manufacturers are necessary.

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Lung and breast cancers are only two examples mentat 60caps sale, because it is possible to recognise several entities within the same tumour type for many other cancers buy mentat 60 caps amex. Lung Cancer – Not One Disease: Histological (Tissue) and Molecular Subtypes of Lung Cancer discount 60 caps mentat visa. On the right side 60caps mentat otc, a pie chart showing the percentage distribution of molecular subsets of lung adenocarcinoma buy 60 caps mentat with amex. Personalisation Requires Humanisation of Medicine We don’t have the defnitive solution for all cancers yet, but it is very important for patients and patient organisations to understand a few issues. It will be very hard, for example, to start talking Medicine Task Force to patients about the evaluation of 255 genes that may be altered in a tumour that metastasises to the brain; we need to begin seeing through the eyes of our patients. So personalisation starts with an individual relationship on the part of the physician and the medical team who are taking care of the patient. Personalisation also depends on a multidisciplinary approach; we need a range of experts, because we need the medical oncologist, the surgeon and the expertise of the molecular pathologist, who should be part of the team in a more effective, integrated way than before. We don’t need the pathology report alone; we need to interact with all professionals, including nurses, who are dealing with the patient. This, to me, will create a lot of problems in terms of organisation of care and in terms of cost, but it is the only way to bring together knowledge on the biology and pathology of tumours for effective treatment in every single patient. We now understand that some genes contribute signifcantly to making us resistant to illness, while other genes may make us more susceptible to specifc diseases. In our chromosomes there are also instructions to make drugs work, or fail, or to produce side effects. Cancer occurs when the switches inside our genes that control cell growth do not work. For example, if a growth gene is supposed to be turned off, in cancer it is turned on. Knowing that oncogenes are the key, there can be no doubt that gene-based prevention and therapy will be crucial in winning the war on cancer. Now, things are changing and advances in technology and the results of the Human Genome Project* have enabled researchers to identify the molecular features of each single tumour. Researchers have found that there is a wide heterogeneity among apparently similar tumours. Each person has about 25 000 genes, which are stored in the nucleus, the vital centre of every cell. If an alteration occurs in the gene, the instructions on how to build the protein will be wrong and therefore the message will not be delivered correctly. This phenomenon means that the tumour can survive and reproduce itself mainly because this alteration is present. It is therefore intuitive that giving a drug that targets these specifc alterations is fundamental in fghting the war against cancer. To explain briefy, it means that we have to deeply analyse each tumour of every patient in order to identify those genetic characteristics that make the tumour able to survive. As a result, we can choose the appropriate drugs to target the specifc alterations. The clearest examples of this process are in melanoma, lung cancer and breast cancer. When oncologists identify these mutations in a patient’s tumour, they may observe that the lesion disappears a few weeks after treatment. Unfortunately, oncogene addiction is not the only process underlying carcinogenesis* and tumour growth. The tumour environment and so-called “epigenetic” alterations* play an important role in rendering the fght against cancer more and more challenging. Despite the enormous recent advances, a specifc alteration has not been identifed in all cancers. The hope is that the possibility of sequencing the full genome – which means every gene – will give us new insights and therefore new drugs for our patients. This means that a particular mutation is conferring susceptibility to that person to develop a particular type of cancer during his/her life. Mutations that are not germline are called somatic mutations*, which are acquired mutations and are found generally only in the tumour. The move from blockbuster or empirical medicine* towards personalised medicine is a stepwise process.

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Definition Clinical features This is the one of the two most common causes of Patients may present with asymptomatic proteinuria generic mentat 60 caps free shipping, nephrotic syndrome in non-diabetic adults (together or (in most cases) nephrotic syndrome cheap 60caps mentat with visa. The idiopathic form causes ∼20% usually with mild to moderate mesangial proliferation order mentat 60caps mastercard. Silver stains classically show ‘spikes’ where basement membrane has grown between subepithelial deposits cheap mentat 60 caps visa. Alternatively large plasma proteins may leak through the capillary wall cheap mentat 60 caps with visa, accumulate in the subendothelial space and compress the capillary Prognosis lumen. Some patients develop a rapidly progressive course loss of the function of that nephron. These may develop later in the course of drome in adults and the second most common cause the illness. Incidence/prevalence Causes ∼20% of cases of nephrotic syndrome in adults Macroscopy/microscopy and children. Increase in the mesangial matrix in glomeruli in a focal segmental pattern, with collapse of the adjacent capillary loop. It is thought to be part first, the disease may be missed on renal biopsy (and of a physiological response to glomerular hyperfiltra- hence a diagnosis of minimal change disease made). Steroid resistant cases action to the drug, with lymphocytes and eosinophils may respond to ciclosporin, and steroid-dependent infiltrating the interstitium causing tissue oedema. The cases may benefit from the addition of ciclosporin or tubular epithelium undergoes acute necrosis. High Patients with marked proteinuria, tubular atrophy, in- dose steroids may be given. Chronic renal failure may progress to end-stage renal disease and re- Acute Chronic quire renal replacement therapy. See also Renal Tubu- depletion, polyuria and immunodeficiency secondary lar Acidosis (see below). Water and r Phosphate transport defects: There are several types, anions such as aminoacids follow sodium. Osmotic di- usually X-linked, although occasional sporadic inher- uretics and carbonic anhydrase inhibitors act at this site. Treatment is with oral phosphate supple- condition characterised by glycosuria with normal ments with vitamin D or 1,25 dihydroxyvitamin D blood glucose. Thick ascending loop of Henle: Sodium is pumped Glycosuria is a normal response during pregnancy. The most important single defect is cystinuria, an concentration gradient within the medulla of the kid- autosomal recessive condition which predisposes to ney, which draws water out of the collecting duct and urinary stone formation (see page 270). Loop diuretics such as with high fluid intake and alkali ingestion, because the furosemide act from within the lumen of the ascending cystine is more soluble in alkaline conditions. There may be potassium results in high urinary sodium loss, dehydration, Chapter 6: Disorders of the kidney 253 secondary hyperaldosteronism and hypokalaemic dioxide). Even when bicarbonate levels fall to as low This results in a similar syndrome of sodium loss, de- as 10 mmol/L or below, the urine remains relatively hydration and hypercalciuria as Bartter type I; how- alkaline (pH ≥ 5. If untreated, persistent metabolic ever, hypokalaemia only occurs after treatment with acidosis leads to increased mobilisation of calcium sodium supplements. Once 3 collecting duct resulting in a hypokalaemic metabolic plasma bicarbonate levels fall to about 12–16 mmol/L, alkalosis. This The main problems occur due to the loss of other is under the influence of aldosterone which increases substances such as amino acids and phosphate. Spironolactone 2istreated with bicarbonate, thiazide diuretic and and amiloride affect this exchange and hence increase potassium bicarbonate or potassium-sparing diuret- urinary water and sodium loss. Fanconi syndrome is treated with large doses of diuretics, these cause potassium reabsorption and are vitamin D. This results in excessive water loss deficiency causes hyperkalaemia, which is associated in the urine. Hyper- Renal tubular acidosis kalaemia may be life-threatening and the underlying Definition disorder often shortens life expectancy. Under physiologi- Disorders of uric acid metabolism may cause renal dis- cal conditions, the kidneys help to maintain acid–base easeduetoachronicnephropathy,anacutenephropathy balance, together with the lungs (which remove carbon or through the formation of uric acid stones. Renal failure leads to raised uric acid levels Adult polycystic kidney disease is an autosomal dom- and in some cases there may have been another cause inant inherited condition characterised by gradual re- for their renal failure. It is thought that urate crys- placement of renal and occasionally other tissue by cysts.

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