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In lung and heart-lung transplant recipients order cymbalta 40mg mastercard, the types of disease presentation include bronchial anastomosis dehiscence buy cymbalta 20mg without a prescription, vascular anastomosis erosion buy discount cymbalta 30 mg on-line, bronchitis, tracheobronchitis, invasive lung disease, aspergilloma, empyema, disseminated disease, endobronchial stent obstruction, and mucoid bronchial impaction. Retransplantation is also an independent risk factor (103,104), although aspergillosis may happen in low-risk Infections in Organ Transplants in Critical Care 395 patients if an overload exposure has occurred (39). Aspergillus may appear late after transplantation, mainly in patients with a neoplastic disease (106). Although the lung is the primary site of infection, other presentations have also been described (surgical wound, primary cutaneous infection, infection of a biloma, endocarditis, endophthalmitis, etc. Voriconazole is the mainstay of therapy; although combined therapy may be indicated in especially severe cases (108). These fungi now account for *25% of all non-Aspergillus mould infections in organ transplant recipients (109). We found that 46% of Scedosporium infections in organ transplant recipients were disseminated, and patients may occasionally present with shock and sepsis-like syndrome (110). Overall, mortality rate for Scedosporium infections in transplant recipients in our study was 58%. When adjusted for disseminated infection, voriconazole as compared with amphotericin B was associated with a lower mortality rate that approached statistical significance (p ¼ 0. Before prophylaxis, incidence was around 5%, although it has been described to reach up to 80% in lung transplant recipients. Clinical presentation was acute (less than 48 hours) with fever (89%), shortness of breath (84%), dry cough (74%), and hypoxia (63%). Week-end prophylaxis (1 double- strength tablet, 160/800 mg, every 12 hours on Saturdays and Sundays) has shown practically universal efficacy, also eliminating the risk for Listeria infections and most cases of Nocardia infections (95,112). However, the disease is uncommon and appears a median of 24 months after transplantation (1 month to 17 years). An immune reconstitution syndrome-like entity may occur in organ transplant recipients with C. Immunomodulatory agents may have a role as adjunctive therapy in such cases (114). It has been reported in lung transplant recipients and the diagnosis requires histological confirmation, since the recovery of Candida may represent colonization. In these patients, infection with Candida may be associated with very severe complications such as the necrosis of bronchial anastomoses (116–119). Nevertheless, it may be helpful to evaluate the efficiency of ongoing treatment methods in these patients (120). The respiratory viruses, particularly respiratory syncytial virus, influenza, parainfluenza, adenovirus, and picornavirus, are increasingly recognized as significant pathogens in these populations. Adenovirus may also cause pneumonia, occasionally with dysfunction of the allograft (123). Respiratory syncytial virus and influenza have been found to be the most common of the respiratory viruses causing severe infections in transplant recipients (124–130). New antiviral medications may bring improved outcomes of picornavirus infections in this population. Finally, a new virus, the human metapneumovirus, has recently been described and may be a significant respiratory pathogen in immunocompromised transplant recipients, particularly lung recipients. In this population, human metapneumovirus is a leading cause of acute respiratory tract illness. Respiratory viruses may be associated with high morbidity, particularly in lung transplant recipients and may appear as “culture-negative” pneumonia. Advances in prevention, particularly with regard to infection control practices, and to a lesser extent treatment have had a substantial impact on the frequency and outcomes of this infection. Considering the high mortality that some of these pathogens condition, the prompt detection of the etiology is of the utmost importance. As with other critical patients, differentiating pneumonia from other etiologies of pulmonary infiltrates can be extremely difficult. It is important to bear in mind that some drugs, such as sirolimus, may cause pulmonary infiltrates (134). The presentation ranges from insidious to fulminant, and usually there is a rapid response to sirolimus withdrawal. Chest X rays predominantly show alveolar or interstitial infiltrates of variable extension. The differential diagnosis of a lung nodule in a normal host includes many malignant and benign processes. However, in immunosuppressed patients the most common causes are potentially life-threatening opportunistic infections that may be treated and prevented. Aspergillus infection was detected early after transplantation (median 38 days, range 23–158), whereas N. Patients with Aspergillus were, overall, more symptomatic and were the only ones in our series to present neurological manifestations and hemoptysis. For this reason, fast diagnostic procedures that guide antimicrobial treatment are necessary. Etiological diagnosis may be performed by using different techniques, so this requires careful tailoring to each single patient. Once pneumonia is identified, blood cultures, respiratory samples for culture of bacteria, mycobacteria, fungi, and viruses and urine for Legionella and S. Infections in Organ Transplants in Critical Care 397 The only complications were a minor pneumothorax after a transbronchial biopsy and minor hemoptysis after a transthoracic needle aspiration. Direct microscopic examination of the respiratory samples (Gram stain, potassium hydroxide, or cotton blue preparations) were positive in 3/5 cases of aspergillosis and in 3/4 cases of nocardiosis (101). The selection of the empirical therapy will be guided by the characteristics of the patient and the clinical situation. Postsurgical Infections Complications in the proximity of the surgical area must always be investigated. Surgical problems leading to devitalized tissue, anastomotic disruption, or fluid collections markedly predispose the patient to potentially lethal infection. Liver transplant recipients are at risk for portal vein thrombosis, hepatic vein occlusion, hepatic artery thrombosis, and biliary stricture formation and leaks. Heart transplant recipients are at risk for mediastinitis and infection at the aortic suture line, with resultant mycotic aneurysm, and lung transplantation recipients are at risk for disruption of the bronchial anastomosis. In intestinal transplant recipients, abdominal wall closure with mesh should be avoided because of the high rate of infectious complications (139). Occasionally, the complications will appear after the performance of some procedure such as a liver biopsy or a cholangiography. Most common microorganisms include Enterobacteriaceae bacilli, enterococci, anaerobes, and Candida. Biliary anastomosis leaks may result in peritonitis or perihepatic collections, cholangitis, or liver abscesses (144–146). Recent data suggest that duct-to-duct biliary anastomosis stented with a T tube tends to be associated with more postoperative complications (147). A percutaneous aspirate with culture of the fluid is required to confirm infection. In one series, median time from transplant to hepatic abscess was 386 days (range 25–4198). Clinical presentation of hepatic abscess was similar to that described in nonimmunosuppressed patients. Occasionally, the only manifestations are unexplained fever and relapsing subacute bacteremia. Prolonged antibiotic therapy, drainage, and even retransplantation may be required to improve the outcome in these patients. However, sterile fluid collections are exceedingly common after liver transplantation, so an aspirate is necessary to establish infection. Mediastinitis In heart and lung transplant recipients, the possibility of mediastinitis (2–9%) should be considered. Inflammatory signs in the sternal wound, sternal dehiscence, and purulent drainage may appear later.

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Nutrition transition that is currently underway in Asian countries such as India is characterized by moving away from the traditional diets that are high in carbohydrates and low in fat buy 30mg cymbalta mastercard, to a modern diet which has higher contribution of energy from fats and lower 74 contribution of energy from complex carbohydrates buy discount cymbalta 20 mg on-line. An analysis carried out by Deaton et al has shown that there has been a sustained decline in per- 75 capita calorie consumption during the last twenty five years cymbalta 20mg. The decline of per-capita consumption largely applies to proteins, carbohydrates and many other essential nutrients with the sole exception of fat consumption which has increased steadily in both urban and rural areas. Even though the calorie consumption is declining, the nutritional status of the population appears to have improved as evident from the population anthropometric data. Similarly, between 1975-79 and 2004-05, there have been reductions of around fifty percent in the prevalence of severe under nutrition, among children as well 76 Table: Time trends in per capita intake of nutrients in rural and urban India Energy Carbohydrates* Protein Fats Years (Kcal/person/day) (gm/person/day) (gml/person/day) (gm/person/day) Rural Urban Rural Urban Rural Urban Rural Urban 1972-73 2266 2107 450 390 62 56 24 36 1983-84 2221 2089 433 377 62 57 27 37 1993-94 2153 2071 407 366 60. An upward trend has been observed in the height and weight of urban middle and upper class 77 children. Close to half of all Indian children are underweight, about half suffer from anemia and India is among the most “undernourished” countries in the world. However, for comparable levels of under-nutrition, adverse outcomes may be different among different populations. Therefore, a 63 uniform definition of under-nutrition may overestimate the burden of childhood under-nutrition 78 in South Asia. Several studies have demonstrated the inverse relationship of low birth weight and under nutrition during early childhood to diabetes and cardiovascular diseases. For example, among fats, trans-fats and saturated fatty acids add to higher risk for coronary heart diseases. Although the exact data on consumption of these different types of oils/fats at the individual and household level is missing, national aggregates on consumption statistics show a high consumption of unhealthy oils in India. The share of raw oil, refined oil and vanaspati oil (hydrogenated oils) in the total edible oil market is estimated at 35%, 55% and 10% respectively. Trans-fats, present in the popular vanaspati is widely used in the commercial food industry including sweets due to higher shelf life of products. Fats/oils high in saturated fats such as butter/ghee, lard, coconut oil, palm oil etc accelerate the process of atherosclerosis. Dietary use of coconut oil is confined to southern states such as Kerala and Tamil Nadu, whereas, Palm oil is widely used and India is the second largest market for Palm oil in the world. The edible oil import statistics for the year 2007-08 shows that Palm 80 oil accounts for 85% of the edible oil imports. The poor and the food industry use more Palm oil, due to its cost advantage over healthy oils such as sunflower oil, soya oil, groundnut oil, mustard oil, safflower oil and rice bran oil which are high in poly unsaturated and monounsaturated fatty acids. Re-heating and re-cooking vegetable oil is often practiced at both households and commercial food vendor level. These practices alter the healthy profile of fatty acids in the vegetable oils, increases the content of trans-fats and release free-radicals that increases the risk of both coronary heart diseases and cancers. It is reported that a large proportion 64 of those surveyed used vegetable oils (83%) for cooking meals. However these figures do not match with the national consumption statistics due to weakness in the methodology of assessing consumption. Adequate consumption of fruits and vegetables (5 or more servings per one typical day) is reported to be higher in urban areas than rural population 13 (27% vs. Insufficient intake of fruits (less than five servings a day) was higher in low income groups as compared to the high income groups (lowest quartile: 84. The sharp rise in price of fruits and vegetables as compared to oils and fats has resulted in a negative impact on the consumption pattern among poor. The poor tend to reduce the consumption of vegetables and fruits that are healthy while the consumption of cheaper saturated 82 oils tends to remain the same. Nearly 10-15 per cent of the grains and 25 per cent of the fruit and vegetables in India perish each year due to lack of warehouse infrastructure in the rural 83 areas. Agricultural polices and better rural storage and transportation is critical to ensuring adequate supply and affordability of such healthy foods to the masses. A study in the areas of Delhi, Mumbai and Trivandrum, most diets consumed were of traditional regional food items and could be categorized as the Delhi, the “fruit and dairy” dietary pattern which was positively associated with abdominal adiposity and hypertension, Trivandrum, the “pulses and rice” pattern was inversely related to diabetes] and the “snacks and sweets” pattern was positively associated with abdominal adiposity and in Mumbai, the “fruit and vegetable” pattern was inversely associated with hypertension and the “snack and meat” pattern appeared to 84 be positively associated with abdominal adiposity. Physical Activity Physical activity is a key determinant of energy expenditure, and thus is fundamental to energy balance and weight control. A physically active life reduces the risk of coronary heart disease, 85 type 2 diabetes, stroke, colon cancer and breast cancer. Thirty minutes of moderate-intensity physical activity 5 days per week is the minimum recommended to level of physical activity. However, rapid changes in urbanization and associated mechanization and sedentary jobs increase the level of physical inactivity in the population. Due to methodological difficulties, reliable estimates of physical activity of individuals in relation to various domains of life at community level have been scanty. The World Health Survey which used standardized questionnaires reported that, overall in India, 29% of the 65 population were having inadequate physical activity (in all domains of life) particularly in the 13 older age groups. A quarter of men (24%) and one-third of women (34%) of women report inadequate physical activity (defined as 1-149 minutes of activity in the seven days preceding the survey). The proportion of respondents with inadequate physical activity is 39% in urban and 27% in rural areas. Obesity and Overweight Physical inactivity and inappropriate nutrition are directly reflected in the growing burden of overweight in the Indian population predominantly in the urban areas. Studies among urban school children have also reported a rising trend in overweight and obesity (72, 73). The World Health Survey also supports these findings which reported that a quarter of the men (24%) and women (29%) were below the standard body mass index 2 13 weight of 18. Several small but well designed community studies report the prevalence of central obesity as high as 72% in urban men and 40% in urban women as against a lower rural 89 prevalence of 55% in men and 36% in women. Central obesity is an important risk factor for 90 diabetes and appears to better predict the risk of diabetes among Asian Indians. India is in epidemiological, nutrition, socio-economic and lifestyle transition, all contributing to problem of obesity. India is following a trend of other developing countries that are steadily becoming more obese. Indians are genetically susceptible to weight accumulation especially around the waist. India has controlled the problem of severe under-nutrition to a substantial extent, but is now facing a rising epidemic of obesity. This epidemic is assuming serious proportions in cities and is 92 affecting young adults and children. Recent trends in Indian population indicate a rise in obesity both in children as well as adults. Almost 38-65% of adult urban Indians in Delhi fulfill the 93 criteria for either overweight/obesity or abdominal obesity. India shows that children aged 4 and 8 years who were born small and later showed accelerated growth had a propensity to abdominal obesity. In 1995, there were an estimated 200 million obese adults worldwide but as of 2000, the number of obese adults has increased to over 300 million. In developing countries it is estimated that over 115 million people suffer from obesity-related problems. Obesity is a complex condition, one with serious social and psychological dimensions, that affects virtually all age and socioeconomic groups. In the analyses carried out for World Health Report 2002, approximately 58% of diabetes and 21% of heart disorders and 8-42% of certain cancers globally were attributable to excess weight. While a third of Indian population still falls below the poverty line, there has been a steady growth of the relatively affluent urban middle class now estimated to number over 200 million. The prevalence of 94 abdominal obesity is 29 per cent among middle-class men and 46 per cent among women. Obesity is positively associated to many chronic disorders such as hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, pregnancy, bone metabolism and certain 96,97 cancers. Obesity Hypertension and Cardiovascular Diseases Adipose tissue has a central role in lipid and glucose metabolism and produces a large number of hormones and cytokines, e. These are closely associated with abdominal obesity and can often be controlled by dietary changes and weight reduction. Obesity and Pregnancy Overweight and obesity during pregnancy raises the risk of gestational diabetes and complications during delivery. Lifestyle factors like physical activity may ameliorate many of 101 these risks through its beneficial effects on the glucose homeostasis. As obesity is associated with chronic inflammation, excessive fat accumulation is detrimental to bone mass.

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