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Legal Terms Asking to pay a lower price for a covered non-preferred drug is sometimes called asking for a "tiering exception. You cannot ask us to change the cost-sharing tier for any drug in Tier 5 (Specialty Drugs). For a faster decision, include this medical information from your doctor or other prescriber when you ask for the exception. Typically, our Drug List includes more than one drug for treating a particular condition. If an alternative drug would be just as effective as the drug you are requesting and would not cause more side effects or other health problems, we will generally not approve your request for an exception. We can say yes or no to your request If we approve your request for an exception, our approval usually is valid until the end of the plan year. This is true as long as your doctor continues to prescribe the drug for you and that drug continues to be safe and effective for treating your condition. If we say no to your request for an exception, you can ask for a review of our decision by making an appeal. The next section tells you how to ask for a coverage decision, including an exception. What to do if you have a problem or complaint (coverage decisions, appeals, complaints) Section 6. If your health requires a quick response, you must ask us to make a "fast coverage decision. For the details, go to Chapter 2, Section 1 and look for the section called, How to contact us when you are asking for a coverage decision about your Part D prescription drugs. Or if you are asking us to pay you back for a drug, go to the section called, Where to send a request that asks us to pay for our share of the cost for medical care or a drug you have received. You or your doctor or someone else who is acting on your behalf can ask for a coverage decision. Section 4 of this chapter tells how you can give written permission to someone else to act as your representative. If you want to ask us to pay you back for a drug, start by reading Chapter 7 of this booklet: Asking us to pay our share of a bill you have received for covered medical services or drugs. Chapter 7 describes the situations in which you may need to ask for reimbursement. It also tells how to send us the paperwork that asks us to pay you back for our share of the cost of a drug you have paid for. Or your doctor or other prescriber can tell us on the phone and follow up by faxing or mailing a written statement if necessary. If your health requires it, ask us to give you a "fast coverage decision" Legal Terms A "fast coverage decision" is called an "expedited coverage determination. What to do if you have a problem or complaint (coverage decisions, appeals, complaints) When we give you our decision, we will use the "standard" deadlines unless we have agreed to use the "fast" deadlines. To get a fast coverage decision, you must meet two requirements: o You can get a fast coverage decision only if you are asking for a drug you have not yet received. If your doctor or other prescriber tells us that your health requires a "fast coverage decision," we will automatically agree to give you a fast coverage decision. It tells how to file a "fast" complaint, which means you would get our answer to your complaint within 24 hours of receiving the complaint. For more information about the process for making complaints, see Section 10 of this chapter. Deadlines for a "fast" coverage decision If we are using the fast deadlines, we must give you our answer within 24 hours. Later in this section, we talk about this review organization and explain what happens at Appeal Level 2. Deadlines for a "standard" coverage decision about a drug you have not yet received If we are using the standard deadlines, we must give you our answer within 72 hours. If our answer is no to part or all of what you requested, we will send you a written statement that explains why we said no. Deadlines for a "standard" coverage decision about payment for a drug you have already bought We must give you our answer within 14 calendar days after we receive your request. If our answer is yes to part or all of what you requested, we are also required to make payment to you within 14 calendar days after we receive your request.

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  • Methotrexate
  • The amount swallowed
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Professionalism and Legal/Ethical Issues Knows the guidelines for obtaining informed consent for treatment including those for children and adolescents, third-party permission, and emergent situations. Knows appropriate prescriptive practices; knows appropriate use of opioids in terminally ill patients. Knows guidelines for reporting findings to proper authorities, such as social services, police medical society, or coroner. Recognizes and optimizes human and environmental factors such as workplace design, standardization, and processes. Understands and can apply principles of study design/flaws, such as bias and confounding, and methods to address these flaws; understands and can apply statistical principles. Understands use and interpretation of statistical principles and measures of association. Based on these additional data, it is most appropriate to conclude which of the following? Which of the following conclusions is most strongly justified based on this information/study? In determining the validity of the meta-analysis, which of the following is the most appropriate factor to consider? Compared with, which of the following is the relative risk for in ? Which of the following is the estimated odds ratio of in compared with ? Which of the following is the best estimate of the relative risk of for those with compared with those with ? Which of the following is the relative risk for 5 years following ? Which of the following is the attributable (excess) risk per patients for development of 5 years following ? Which of the following is the mean (or mode or standard deviation) in the sample shown in the graph? Assuming a normal (Gaussian) distribution, which of the following best represents the median for this group? According to these results, how many patients would need to be treated with the new drug to prevent mortality in one patient? Which of the following is the number needed to treat with instead of to prevent in one patient? Based on these data, which of the following best represents the number of patients that must be treated with to prevent one episode of ? The outcome of this study is statistically significant because of which of the following? Which of the following statistics is most likely to establish the difference among the of these groups? Makes decisions about patient care based on results of studies or other written materials. The Private Securities Litigation Reform Act of 1995 provides a safe-harbor for forward-looking statements. These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential," "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this presentation. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. To counter this, focus on first understanding the material and then being familiar with case scenarios that buttress these concepts (our focus today).

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This is done by inserting a catheter into the anal canal and taking pressure readings at intervals as the catheter is withdrawn. A liquid substance containing barium is inserted through the anus or, in case of a person with a colostomy, through the stoma. Birth Defects Babies may be born with a spinal defect (spina bifida) which could lead to problems of bowel and urinary control. If detected in its early stages, it is potentially the most curable of abdominal cancers. This is a lighted flexible tube several feet long that can be passed around loops and curves of the colon. This is because the important job of absorbing fluid, nutrients and vitamins is done by the small intestine. Less common reasons are injuries to the abdomen from motor vehicular accidents, industrial accidents, gun shot or stab wounds. A colostomy will be permanent if the anal sphincters must be removed or if they are not reliable. Anal sphincters will be removed if the disease (usually,but not always cancer) is invading or very close to anal tissue. When this type of surgery is needed, the bowel is diverted, a colostomy is made, but anal sphincters are not usually removed. The colostomy will be permanent if the anal sphincters cannot be surgically repaired. Anal sphincter function can be measured by a special test called anorectal manometry*. In many cases, the area of disease or injury of the bowel does not involve the anal sphincter. When this happens, it may be possible for the surgeon to remove the affected area and immediately rejoin the remaining healthy bowel. The surgeon may consider it necessary to allow this rejoined area (anastomosis) to heal for a period of time by diverting the passage of stool. A temporary colostomy is made upstream from the anastomosis allowing the bowel to heal satisfactorily. Some of the reasons for the temporary colostomy are infection, perforation or obstruction. In most cases of temporary colostomy, the continuity of the bowel can be reestablished by closure of the colostomy in several months. My rectum and anus have been removed, but occasionally I have the urge to move my bowels as before. Although the surgery has removed the diseased rectum and anus, there are still nerve endings that may signal the urgency to have a bowel movement. Sometimes this urgency feeling is called the "phantom" rectum, similar to the "phantom" limb that amputees experience. The colon remaining should be checked from time to time to assure that there is no recurrence of disease. Sometimes a check-up will help keep you informed on improvements in ostomy equipment and accessories. Should I get a note from my doctor so I do not have to wear my seat belt in the car? Persons with ascending or transverse colostomies should take medications in liquid or tablet form. I have a temporary loop colostomy and occasionally pass stool and mucus from the anus as well. The bowel that is disconnected and "resting" will continue to secret digestive fluids and mucus. As this builds up over time, the body will get the signal to pass it just as it did before the colostomy surgery. It is cut only half way through, leaving the intestine otherwise intact, but with two openings. Sometimes it is done to ensure a good blood supply to the stoma when the abdominal wall is thick. If a colostomy is necessary in the ascending colon, it will be on the right side and is called an ascending colostomy.

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Most vesiculobullous disorders are rare in children but need to be considered in chronic blistering conditions. Many are clinically indistinguishable from each other; skin biopsy, immunofluorescence, and electron microscopy are often necessary to make the definitive diagnosis. The usefulness of this algorithm is limited (without photographs) to categorizing potential diagnoses based on some broad clinical criteria. A more specific dermatology reference will often be necessary to confirm suspected diagnoses. Tiny papules, vesicles, or pustules are present on a blotchy erythematous macular base; the rash can be present on any surface except for the palms and soles. The onset generally is in the first few days of life (occasionally later), and remission is usually by 2 weeks. If microscopically examined, the lesions show an accumulation of eosinophils within the pilosebaceous apparatus. Cutaneous manifestations develop in the first 2 weeks of life, with red streaks and crops of vesicles or bullae developing on the trunk or in a characteristic linear distribution on the extremities. Evolution to verrucous lesions followed by characteristic pigmentation changes subsequently occurs, usually by 4 months of age. Areas occluded by heavy clothing or affected by sunburn are most commonly affected. This form of impetigo is much less common than the nonbullous form (crusted lesions). Small, fragile vesicles or pustules are noted at birth and can be present on any surface. The lesions rupture quickly, leaving a characteristic rim of scale and hyperpigmented macule that gradually fades. They are most likely to be found on the palms and soles and in the axillae and groin. Lesions associated with localized infections (involving only skin, eyes, and mouth) may be subtle, but diagnosis is critical because localized disease in these infants can progress to encephalitis or disseminated disease. Target lesions are well-demarcated round or oval macules with distinct "rings"-outermost erythema surrounding a whitish ring and then a central dusky blue/gray or blistered center; the typical size ranges from 1 to 3 cm. The disorder is characterized by a widespread eruption of large sausage-shaped bullae with a variable degree of pruritus. The inguinal region, lower trunk, buttocks, legs, and tops of the feet are most commonly affected, but the bullae may develop anywhere. Sometimes the bullae develop in an annular or rosette-like configuration surrounding a central crust ("cluster of jewels"). Onset in childhood is rare; there is an infantile subtype with a predilection for acral regions, and a childhood vulvar subtype. In the pemphigus vulgaris variant, painful oral lesions may precede cutaneous involvement by weeks or months. The palms, soles, and lateral aspects of the fingers and toes are most commonly affected. The characteristic exanthem of oval vesicles (when it occurs) affects primarily the hands and feet (occasionally includes elbows, knees, or buttocks) and develops after the oral lesions. Rarely, this combination of symptoms may herald a life-threatening illness, so it is essential to narrow the differential diagnosis with a careful history and physical. Causes of fever and rash include infections, vasculitides, and hypersensitivity disorders. Laboratory tests should be ordered according to the presumptive diagnosis based on the history and physical. Many rashes are pathognomonic for certain diseases (varicella), and testing may not be indicated. Past medical history should be reviewed, and a history of any prodromal or associated symptoms (abdominal pain, rash, headaches) obtained. Examination should include a general assessment of the patient to determine the severity of the illness, including vital signs and height of fever. Tachycardia and tachypnea in a patient with fever and rash may indicate sepsis, particularly if there is altered mental status.

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There are two parts to our coverage of Part D vaccinations: the first part of coverage is the cost of the vaccine medication itself. What you pay for your Part D prescription drugs Some vaccines are considered medical benefits. You can find out about your coverage of these vaccines by going to Chapter 4, Medical Benefits Chart (what is covered and what you pay). What you pay at the time you get the Part D vaccination can vary depending on the circumstances. For example: Sometimes when you get your vaccine, you will have to pay the entire cost for both the vaccine medication and for getting the vaccine. Other times, when you get the vaccine medication or the vaccine, you will pay only your share of the cost. To show how this works, here are three common ways you might get a Part D vaccine. Situation 1: You buy the Part D vaccine at the pharmacy and you get your vaccine at the network pharmacy. When you get the vaccination, you will pay for the entire cost of the vaccine and its administration. You can then ask our plan to pay our share of the cost by using the procedures that are described in Chapter 7 of this booklet (Asking us to pay our share of a bill you have received for covered medical services or drugs). You will be reimbursed the amount you paid less your normal coinsurance or copayment for the vaccine (including administration) less any difference between the amount the doctor charges and what we normally pay. What you pay for your Part D prescription drugs You will have to pay the pharmacy the amount of your coinsurance or copayment for the vaccine itself. When your doctor gives you the vaccine, you will pay the entire cost for this service. You can then ask our plan to pay our share of the cost by using the procedures described in Chapter 7 of this booklet. You will be reimbursed the amount charged by the doctor for administering the vaccine less any difference between the amount the doctor charges and what we normally pay. We recommend that you call us first at Member Services whenever you are planning to get a vaccination. We can tell you how to keep your own cost down by using providers and pharmacies in our network. If you are not able to use a network provider and pharmacy, we can tell you what you need to do to get payment from us for our share of the cost. Asking us to pay our share of a bill you have received for covered medical services or drugs Chapter 7. Other times, you may find that you have paid more than you expected under the coverage rules of the plan. In either case, you can ask our plan to pay you back (paying you back is often called "reimbursing" you). There may also be times when you get a bill from a provider for the full cost of medical care you have received. Here are examples of situations in which you may need to ask our plan to pay you back or to pay a bill you have received: 1. If you pay the entire amount yourself at the time you receive the care, you need to ask us to pay you back for our share of the cost. At times you may get a bill from the provider asking for payment that you think you do not owe. Send us this bill, along with documentation of any payments you have already made. Please note: While you can get your care from an out-of-network provider, the provider must be eligible to participate in Medicare. If the provider is not eligible to participate in Medicare, you will be responsible for the full cost of the services you receive. Asking us to pay our share of a bill you have received for covered medical services or drugs 2. When a network provider sends you a bill you think you should not pay Network providers should always bill the plan directly, and ask you only for your share of the cost.

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For women wanting reproductive autonomy, or those without a male partner, oocyte cryopreservation has become the standard method of preserving fertility. The poor outcomes of the past were related to several technical challenges inherent in freezing and thawing of oocytes, the largest human cells. Recent studies have found pregnancy rates with frozen eggs approaching those of fresh. Since the first experiments with ovarian transplantation in animals, steady advances have been made in human subjects. With fewer than 100 documented live births from transplanted ovarian tissue, the potential for reseeding testosterone deficiency is uncommon. Oligospermia and azoospermia rates range from 70% to 98% depending on the follow-up period. Spermatogenesis can recover at variable times, so long-term sperm testing is recommended. Sperm freezing For men, fertility preservation typically involves cryopreservation of ejaculated sperm. The testicle is very sensitive to even low doses of systemic chemotherapeutic agents. Additionally, cancer patients commonly present with reduced sperm counts secondary to their illness. Leydig function is typically unaffected, so Preserving fertility in children and adolescents Cure rates for childhood cancers exceed 80% for most types. Despite the larger ovarian reserve of most young patients going into treatment, subfertility and gonadal failure are possible after childhood exposure to chemotherapy, making future reproductive function a growing survivorship issue for these patients as they transition into adulthood. The Childhood Cancer Survivor Study, which compared patients exposed to chemo- therapy with randomly selected siblings, found a thirteenfold increase in the rate of ovarian failure in female cancer survivors. They typically lack knowledge about their own reproduction and existing technologies for assisting with fertility, but do eventually want children. There are no legal restrictions in Canada to the application of assisted reproductive technology in pediatric cases, so long as the reproductive material is reserved for the patient. For girls, challenges with vaginal procedures can often be addressed with the use of transabdominal pelvic ultrasound for monitoring of ovarian stimulation and general anesthesia for harvesting of eggs. Masturbation and exposure to pornography present ethical concerns, but for the most part is the only feasible approach. Obtaining appropriate consent is critical before employing invasive techniques such as testicular sperm retrieval and electroejaculation. In terms of reproductive health, transition to adulthood is poorly addressed by our medical system. Adequate management should include ovarian reserve surveillance, counseling on fertility and sexual health, and provision of egg and embryo 220 bc medical journal vol. All patients must be made aware of the fact that pregnancy is possible in the vast majority of cases, irrespective of gonadal function, through the use of egg and sperm donation technologies. In the event of premature ovarian failure, patients should be counseled on the use of hormone replacement. Fertility preservation for cancer patients · Breast cancer is the most common cancer in reproductive-age woman. Barriers to services Recent advances in cryopreservation are providing effective fertility preservation options for Canadians, yet barriers to services exist for cancer patients. A multidisciplinary approach to care and education of oncology professionals and patients on issues related to reproduction are both required. Presently, only Ontario and Quebec provide funding for egg, sperm, and embryo banking. Fertile Future, a national charity that is committed to making these treatments affordable for cancer patients, currently provides up to $3000 toward clinical costs for female patients and $350 for male patients. No area of our profession is more in need of public support and we will continue to lobby provincially and federally for these critical services. Fertility preservation for males usually involves freezing sperm, and for females involves ovarian reserve surveillance and freezing of embryos, oocytes, or ovarian tissue. Young patients with cancer should be referred to a fertility specialist with the ability to discuss and deliver these services. Dynamics and mechanisms of chemotherapy-induced follicular depletion in women of fertile age.

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Human health effects Although Staphylococcus aureus is a common member of the human microflora, it can produce disease through two different mechanisms. One is based on the ability of the organisms to multiply and spread widely in tissues, and the other is based on the ability of the organisms to produce extracellular enzymes and toxins. Infections based on the multiplication of the organisms are a significant problem in hospitals and other health care facilities. Multiplication in tissues can result in manifestations such as boils, skin sepsis, post-operative wound infections, enteric infections, septicaemia, endocarditis, osteomyelitis and pneumonia. The onset of clinical symptoms for these infections is relatively long, usually several days. Gastrointestinal disease (enterocolitis or food poisoning) is caused by a heat-stable staphylococcal enterotoxin and characterized by projectile vomiting, diarrhoea, fever, abdominal cramps, electrolyte imbalance and loss of fluids. Onset of disease in this case has a characteristic short incubation period of 1­8 h. The same applies to the toxic shock syndrome caused by toxic shock syndrome toxin-1. Source and occurrence Staphylococcus aureus is relatively widespread in the environment but is found mainly on the skin and mucous membranes of animals. The organism is a member of the normal microbial flora of the human skin and is found in the nasopharynx of 20­30% of adults at any one time. Staphylococci are occasionally detected in the gastrointestinal tract and can be detected in sewage. Staphylococcus aureus can be released by human contact into water environments such as swimming pools, spa pools and other recreational waters. Foods such as ham, poultry and potato and egg salads kept at room or higher temperature offer an ideal environment for the multiplication of S. The genus was created in 1988 to accommodate a group of chemically unique organisms characterized by a series of very long chain (68­76 carbons), highly unsaturated mycolic acids, meso-diaminopimelic acid and arabinogalactan, common to the genus Corynebacterium. Tsukamurella were reported in four cases of catheter-related bacteraemia and in individual cases including chronic lung infection, necrotizing tenosynovitis with subcutaneous abscesses, cutaneous and bone infections, meningitis and peritonitis. Significance in drinking-water Tsukamurella organisms have been detected in drinking-water supplies, but the significance is unclear. Vibrio cholerae is the only pathogenic species of significance from freshwater environments. While a number of serotypes can cause diarrhoea, only O1 and O139 currently cause the classical cholera symptoms in which a proportion of cases suffer fulminating and severe watery diarrhoea. The latter is distinguished by features such as the ability to produce a dialysable heat-labile haemolysin, active against sheep and goat red blood cells. The classical biotype is considered responsible for the first six cholera pandemics, while the El Tor biotype is responsible for the seventh pandemic that commenced in 1961. Other factors associated with infection are an adhesion factor and an attachment pilus. Not all strains of serotypes O1 or O139 possess the virulence factors, and they are rarely possessed by non-O1/O139 strains. Human health effects Cholera outbreaks continue to occur in many areas of the developing world. Symptoms are caused by heat-labile cholera enterotoxin carried by toxigenic strains of V. A large percentage of infected persons do not develop illness; about 60% of the classical and 75% of the El Tor group infections are asymptomatic. The initial symptoms of cholera are an increase in peristalses followed by loose, watery and mucus-flecked "rice-water" stools that may cause a patient to lose as much as 10­15 litres of liquid per day. Decreasing gastric acidity by administration of sodium bicarbonate reduces the infective dose of V. As many as 60% of untreated patients may die as a result of severe dehydration and loss of electrolytes, but well established diarrhoeal disease control programmes can reduce fatalities to less than 1%. Numbers associated with these aquatic organisms are often higher than in the water column.

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The period of validity of the International Vaccination Certificate for yellow fever is life time beginning 10 days after vaccination and immediately after revaccination. One dose of monovalent hepatitis A vaccine administered at any time before departure can provide adequate protection for most healthy people aged 40 years. For adults aged >40 years, immunocompromised people, and people with chronic liver disease or other chronic medical conditions planning to depart to an area in <2 weeks should receive the initial dose of vaccine along with immunoglobulin in dose of 0. Since immune globulin provides protection for only 3­5 months, it should be given immediately before departure and would provide protection for only 3­5 months. In countries or areas belonging to categories 2­4, pre-exposure immunization against rabies is recommended for travelers. Modern rabies vaccinescell-culture or embryonated egg origin are safer and more effective. Pre-exposure immunization should be considered for: (i) travelers intending to live or work in areas where rabies is enzootic and rabies control programs for domestic animals are inadequate; (ii) travel to area where adequate and safe postexposure management is not available; (iii) travelers with extensive outdoor exposure in rural areas-such as might occur while running, bicycling, hiking, camping, etc. A course of two intramuscular injections of modern vaccines of cell-culture vaccine should be administered in schedule of one on each of days 0 and 14, and 7 and 14 Days. The risk varies according to season, destination, duration of travel, and activities. Typhoid Fever Vaccine should be recommended to those traveling to destinations where the risk of typhoid fever is high, especially individuals staying in endemic areas for >1 month and/or in locations where antibiotic resistant strains of Salmonella typhi are prevalent. Travelers should be informed that typhoid immunization is not 100% effective and other hygienic measure should be undertaken. Cholera Cholera vaccination is not required as a condition of entry to any country. The vaccine should be considered for travelers visiting endemic areas and who are at high risk. Whenever to be used the first dose should be administered at least 2 weeks before the departure and for the effective protection, ideally the full course of two doses should be completed before departure. In general, the vaccine response rate in these patients is diminished and they may be more likely to have adverse effects from vaccines containing live attenuated virus. Overall considerations for vaccine recommendations, such as destination and the likely risk of exposure to disease, are the same for immunocompromised travelers as for other travelers. The risk of a severe outcome from a vaccine-preventable disease must be weighed against potential adverse events from administering a live vaccine to an immunocompromised patient. In some complex cases when travelers cannot tolerate recommended immunizations or prophylaxis, the traveler should consider changing the itinerary, altering the activities planned during travel, or deferring the trip. Patients receiving other immunosuppressive drugs should be advised on a case-by-case basis depending on the degree of immune suppression as judged by the prescribing physician. Asplenic patients and persons with terminal complement deficiencies are susceptible to overwhelming sepsis with encapsulated bacterial pathogens. These groups of people should be immunized with the meningococcal A/C/Y/W-135 conjugate vaccine. As vaccine response may be suboptimal, such vaccinees are candidates for serologic testing 1 month after vaccination. Travelers with severe immune compromise should not be vaccinated with yellow fever vaccine and should be strongly discouraged from travel to destinations that put them at risk for yellow fever. The benefits of vaccinating pregnant women usually outweigh potential risks when the likelihood of disease exposure is high, infection would pose a risk to the mother or fetus, and the vaccine is unlikely to cause harm. Pregnant travelers may visit areas of the world where diseases eliminated by routine vaccination in their native country are still endemic, and therefore may require immunizations before travel. If the pregnant traveler is at risk for influenza on this trip (high season), she should be advised to be vaccinated with inactivated whole virus or subunit influenza vaccine. However, in addition to these two languages the certificate may also be completed in another language on the same document. As a proof of yellow fever vaccination, traveler must carry the original International Certificate of Vaccination. Knowledge, attitudes and practices in travel-related infectious diseases: the European airport survey. Update: Prevention of hepatitis A after exposure to hepatitis A virus and in international travellers.

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Disease may result from the ingestion of the organisms or toxins produced by the organisms. Drinking-water has not been identified as a source of infection of pathogenic Bacillus spp. The organism is acid tolerant and survives in water for prolonged periods in the absence of nutrients. Human health effects Burkholderia pseudomallei can cause the disease melioidosis, which is endemic in northern Australia and other tropical regions. In some of these areas, melioidosis is the most common cause of community-acquired pneumonia. Many patients present with milder forms of pneumonia, which respond well to appropriate antibiotics, but some may present with a severe septicaemic pneumonia. Other symptoms include skin abscesses or ulcers, abscesses in internal organs and unusual neurological illnesses, such as brainstem encephalitis and acute paraplegia. Although melioidosis can occur in healthy children and adults, it occurs mainly in people whose defence mechanisms against infection 226 11. Source and occurrence the organism occurs predominantly in tropical regions, typically in soil or surfaceaccumulated muddy water, from where it may reach raw water sources and also drinking-water supplies. The number of organisms in drinking-water that would constitute a significant risk of infection is not known. Routes of exposure Most infections appear to be through contact of skin cuts or abrasions with contaminated water. Infection may also occur via other routes, particularly through inhalation or ingestion. Significance in drinking-water In two Australian outbreaks of melioidosis, indistinguishable isolates of B. The detection of the organisms in one drinking-water supply followed replacement of water pipes and chlorination failure, while the second supply was unchlorinated. Campylobacter jejuni is the most frequently isolated species from patients with acute diarrhoeal disease, whereas C. Two closely related genera, Helicobacter and Archobacter, include species previously classified as Campylobacter spp. Wild and domestic animals, especially poultry, wild birds and cattle, are important reservoirs. Food, including meat and unpasteurized milk, are important sources of Campylobacter infections. The occurrence of the organisms in surface waters has proved to be strongly dependent on rainfall, water temperature and the presence of waterfowl. Routes of exposure Most Campylobacter infections are reported as sporadic in nature, with food considered a common source of infection. Meat, particularly poultry products, and unpasteurized milk are important sources of infection. Contaminated drinking-water supplies have been identified as a source of outbreaks. The number of cases in these outbreaks ranged from a few to several thousand, with sources including unchlorinated or inadequately chlorinated surface water supplies and faecal contamination of water storage reservoirs by wild birds. Waterborne transmission has been confirmed by the isolation of the same strains from patients and drinking-water they had consumed. Routes of exposure Infection is associated with person-to-person transmission, contact with animals, food and consumption of contaminated water. Person-to-person transmissions are particularly prevalent in communities where there is close contact between individuals, such as nursing homes and day care centres. The outbreak took place in May 2000 and led to 7 deaths and more than 2300 illnesses. The drinking-water supply was contaminated by rainwater runoff containing cattle excreta. Human health effects Helicobacter pylori is found in the stomach; although most infections are asymptomatic, the organism is associated with chronic gastritis, which may lead to complications such as peptic and duodenal ulcer disease and gastric cancer. The infections are more prevalent in developing countries and are associated with overcrowded living conditions.

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The 1993 Guidelines did not establish a guideline value for monochloroacetic acid, as available toxicity data were considered insufficient. There is limited evidence of carcinogenicity in male rats, with high doses increasing the occurrence of neoplastic nodules in the liver. In the first edition of the Guidelines for Drinking-water Quality, published in 1984, no guideline value for chlorobenzene was recommended after a detailed evaluation of the compound. Following consideration of the calculated toxicological limit for drinking-water of 0. Food is the dominant source of nickel exposure in the non-smoking, non-occupationally exposed population; water is generally a minor contributor to the total daily oral intake. However, where there is heavy pollution or use of certain types of kettles, of nonresistant material in wells or of water that has come into contact with nickel- or chromium-plated taps, the nickel contribution from water may be significant. In special cases of release from natural or industrial nickel deposits in the ground, the nickel concentrations in drinking-water may be even higher. However, there is a lack of evidence of a carcinogenic risk from oral exposure to nickel. Dose-related increases in perinatal mortality were observed in a carefully conducted two-generation study in rats, but variations in response between successive litters make it difficult to draw firm conclusions from this study. In the first edition of the Guidelines for Drinking-water Quality, published in 1984, it was concluded that the toxicological data available indicate that a guideline value for nickel in drinking-water was not required. This guideline value was maintained in the addendum to the Guidelines published in 1998 because, on the basis of the available data, it was considered to provide sufficient protection for individuals who are sensitive to nickel. However, the guideline value was designated as provisional owing to uncertainties about the effect level for perinatal mortality. Nitrate is used mainly in inorganic fertilizers, and sodium nitrite is used as a food preservative, especially in cured meats. The nitrate concentration in groundwater and surface water is normally low but can reach high levels as a result of leaching or runoff from agricultural land or contamination from human or animal wastes as a consequence of the oxidation of ammonia and similar sources. Chloramination may give rise to the formation of nitrite within the distribution system if the formation of chloramine is not sufficiently controlled. The formation of nitrite is as a consequence of microbial activity and may be intermittent. Guideline value for nitrate Guideline value / Provisional guideline value for nitrite 50 mg/litre to protect against methaemoglobinaemia in bottle-fed infants (short-term exposure) 3 mg/litre · exposure) for methaemoglobinaemia in infants (short-term (provisional) (long-term exposure) · 0. The occurrence of nitrite in distribution as a consequence of chloramine use will be intermittent, and average exposures over time should not exceed the provisional guideline value. Guideline value for combined nitrate plus nitrite Occurrence the sum of the ratios of the concentrations of each to its guideline value should not exceed 1. In most countries, nitrate levels in drinking-water derived from surface water do not exceed 10 mg/litre, although nitrate levels in well water often exceed 50 mg/litre; nitrite levels are normally lower, less than a few milligrams per litre. Methaemoglobinaemia is therefore the most important consideration, and the guideline derived for protection against methaemoglobinaemia would be the most appropriate under these circumstances, allowing for any nitrate that may also be present. All water systems that practise chloramination should closely and regularly monitor their systems to verify disinfectant levels, microbiological quality and nitrite levels. Methaemoglobinaemia in infants also appears to be associated with simultaneous exposure to microbial contaminants. The reduced oxygen transport becomes clinically manifest when metHb concentrations reach 10% or more of normal Hb concentrations; the condition, called methaemoglobinaemia, causes cyanosis and, at higher concentrations, asphyxia. The Hb of young infants is more susceptible to metHb formation than that of older children and adults; this is believed to be the result of the large proportion of fetal 418 12. In addition, there is a deficiency in infants of metHb reductase, the enzyme responsible for the reduction of metHb to Hb. The reduction of nitrate to nitrite by gastric bacteria is also higher in infants because of low gastric acidity. The level of nitrate in breast milk is relatively low; when bottle-fed, however, these young infants are at risk because of the potential for exposure to nitrate/nitrite in drinking-water and the relatively high intake of water in relation to body weight. The higher reduction of nitrate to nitrite in young infants is not very well quantified, but it appears that gastrointestinal infections exacerbate the conversion from nitrate to nitrite. The weight of evidence is strongly against there being an association between nitrite and nitrate exposure in humans and the risk of cancer.

References:

  • https://www.thoracic.org/patients/patient-resources/resources/cteph.pdf
  • https://www.worldgastroenterology.org/UserFiles/image/WGOF/WGOF_180220_WDHD2017_WGOHandbook_FINAL.pdf
  • http://www.sdkrashen.com/content/books/sl_acquisition_and_learning.pdf
  • http://www.ehealthnews.eu/images/stories/pdf/bigdata_report_en.pdf
  • https://cdn.elitecme.com/advance/downloads/2011/020711/obstructive_sleep_apnea_patient_education_collection.pdf
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