Food Analysis Isolation and detection methods have been developed for many foods having prior his to arrhythmia lying down cheap ramipril 2.5 mg on-line ry of Salmonella contamination arteria bologna 7 dicembre buy ramipril on line amex. Conventional culture and identification methods may require 4 to hypertension bradycardia ramipril 5mg with amex 6 days for presumptive results blood pressure medication gout sufferers purchase ramipril no prescription. Bad Bug Book Foodborne Pathogenic Microorganisms and Natural Toxins Campylobacter jejuni For Consumers: A Snapshot 1. Organism Campylobacter jejuni is estimated to be the third leading bacterial cause of foodborne illness in the U. Many strains display (sometimes bloody), vomiting, and cramping are motility, which is associated with unpleasant, they usually go away by themselves in the presence of a flagellum at one people who are otherwise healthy. Raw poultry, or both of the polar ends of this unpasteurized (“raw”) milk and cheeses made from it, bacterium. Anyone can get sick they grow at lower-than from food contaminated with Campylobacter, but atmospheric oxygen children younger than 5 years old and people 15 to 29 concentrations. Most grow years old are more likely to get the infection than are optimally at oxygen concentrations others. As with all bacteria that cause Other Campylobacter species, such foodborne illness, consumers can take the following as C. A list of Campylobacter genomes that have been sequenced is available under the National Center for Biotechnology Information web link. However, in trials, as few as 500 ingested Campylobacter cells led to disease in volunteers. Differences in infectious dose likely can be attributed to several fac to rs, such as the type of contaminated food consumed and the general health of the exposed person. The most common manifestation of campylobacteriosis is self limiting gastroenteritis, termed “Campylobacter enteritis,” without need for antimicrobial therapy. When antimicrobial therapy is indicated, erythromycin or ciprofloxacin are most commonly prescribed. These include bacteremia and infection of various organ systems, such as meningitis, hepatitis, cholecystitis, and pancreatitis. The s to ol may be watery or sticky and may contain blood (sometimes occult – not discernible to the naked eye) and fecal leukocytes (white cells). Other symp to ms often present include abdominal pain, nausea, headache, and muscle pain. In genome sequencing studies, researchers were not able to identify the presence of to xin genes that likely contribute to diarrhea and other common symp to ms. For each reported case of campylobacteriosis, it is estimated that 30 cases are unreported. Campylobacter infection in humans has been linked to handling and eating raw or undercooked meat and poultry, whether fresh or frozen. Avoiding cross contamination of uncooked items from raw meat and poultry products, thorough cooking, pasteurization of milk and dairy products, and water disinfection are effective ways to limit food and water-borne exposure to Campylobacter. Reduction of risk from contaminated poultry products can be achieved through good hygienic practices by manufacturers and consumers. Campylobacter is part of the natural gut microflora of most food-producing animals, such as chickens, turkeys, swine, cattle, and sheep. Typically, each contaminated poultry carcass can carry 100 to 100,000 Campylobacter cells. Given the fact that up to 500 Campylobacter cells can cause infection, poultry products pose a significant risk for consumers who mishandle fresh or processed poultry during preparation or who undercook it. Diagnosis Special incubation conditions are required for isolation and growth of C. Samples from s to ol or rectal swabs are inoculated directly on to selective media, or they can be enriched to increase recovery. To limit growth of competing organisms, media used for cultivation usually are supplemented with blood and antimicrobial agents. The cultures are incubated at 42fiC, under microaerophilic conditions (5% oxygen and 5% to 10% carbon dioxide), for optimal recovery. Target Populations Children younger than 5 years old and young adults 15 to 29 years old are the populations in whom C. For isolation from most food products, samples are rinsed and the rinsate is collected and subjected to pre-enrichment and enrichment steps, followed by isolation of C. The following reports are available on the surveillance of foodborne outbreaks in the U. Other Resources the following web links provide more information about Campylobacter and its prevention and control: fi U. Organism For Consumers: A Snapshot Food and water contaminated with this the Yersinia genus has 11 species; 4 are bacterium, Yersinia, can make people sick. The former is often isolated from milk has been heated in a way that kills clinical specimens, such as wounds, feces, bacteria, but unpasteurized – “raw” – milk has sputum, and mesenteric lymph nodes. Anyone can get yersiniosis, but young species have been isolated from animals, children most often get it. The symp to ms start such as pigs, birds, beavers, cats, and dogs, within 1 day to 2 weeks, or even longer, and and, in the case of Y. Some microorganism that grows well at low people get arthritisfilike symp to ms, such as temperature) and has the ability to grow at joint pains and rashes (which often go away in temperatures below 4°C. The doubling a month or several months), or other, more time, at 30°C, is 34 min; at 22°C, is 1 hr; serious complications that may affect the and at 7°C, is 5 hrs. Most mild cases of freezing and can survive in frozen foods for yersiniosis go away by themselves, but health extended periods. To help protect yourself, follow contaminated food s to red at room and basic foodfisafety tips, which include good refrigeration temperatures than at an hygiene, washing raw fruits and vegetables and intermediate temperature. It persists longer the things they to uch, cooking food well and in cooked foods than in raw foods, due to keeping it apart from raw food, keeping food increased nutrient availability. Growth of the microorganism also occurs in refrigerated seafood – oysters, raw shrimp, and cooked crab meat. They to lerate alkaline conditions very well, compared with acid conditions (although that depends on the kind of acid used, environmental temperature, composition of the medium, and growth phase of the bacteria). The infective dose and clinical presentation of symp to ms may depend on pathogen (strain-dependent) and host fac to rs. For example, in some cases, in people with gastric hypoacidity, the infective dose may be lower. These sequelae include reactive arthritis; glomerulonephritis; endocarditis; erythema nodosum (which occurs predominantly in women); uveitis; thyroid disorders, such as Graves’ disease; hyperthyroidism; non to xic goiter; and Hashimo to ’s thyroiditis. Another complication is bacteremia, which raises the possibility of disease dissemination. Performance of unnecessary appendec to mies also may be considered a major complication of yersiniosis, as one of the main symp to ms of the disease is abdominal pain in the lower right quadrant. If septicemia or other invasive diseases occur, antibiotic therapy with gentamicin or cefotaxime (doxycycline and ciprofloxacin) typically are administered. Yersiniosis in these children is frequently characterized as gastroenteritis, with diarrhea and/or vomiting; however, fever and abdominal pain are the hallmark symp to ms. Children usually complain of abdominal pain and headache and sore throat at the onset of the illness. Yersinia infections mimic appendicitis and mesenteric lymphadenitis, but the bacteria may also cause infection in other sites, such as wounds, joints, and the urinary tract. This process usually is facilitated by Yops proteins, which contribute to the ability of Y. Frequency Yersiniosis is far more common in Northern Europe, Scandinavia, and Japan than in the United States. It does not occur frequently and tends to be associated with improper food-processing techniques. However, the prevalence of this organism in soil, water, and animals, such as beavers, pigs, and squirrels, offers many opportunities for Yersinia to enter the food supply. For example, poor sanitation and improper sterilization techniques by food handlers, including improper s to rage, may be a source of contamination. Diagnosis Yersiniosis may be misdiagnosed as Crohn’s disease (regional enteritis) or appendicitis. Diagnosis of yersiniosis begins with isolation of the organism from the human host’s feces, blood, or vomit, and sometimes at the time of appendec to my. Confirmation occurs with the isolation, as well as biochemical and serological identification, of Y.
The majority of ferric and ferrous iron salts that have been assessed pulse pressure hyperthyroidism order generic ramipril online, and also carbonyl iron heart attack low blood pressure 5 mg ramipril otc, have produced negative results in gene mutation assays heart attack or gas cheap ramipril 2.5mg without prescription, but were positive for viral-enhanced cell transformation in Syrian hamster embryo cells prehypertension early pregnancy purchase generic ramipril canada, in vitro, or in a mouse lymphoma assay. Mechanisms of to xicity In the presence of available cellular reductants, iron may act as a catalyst in the initiation of free radical mediated reactions. The resultant oxyradicals or lipid hydroperoxides have the potential to damage a variety of cellular structures, including lipids in organelle membranes, nucleic acids, proteins, and carbohydrates, which could result in the disruption of numerous cellular functions. However, the relationship of such effects to the progressive fibrosis associated with chronic iron overload in humans is currently unclear. Dose response characterisation Although there are many studies on iron in humans, there is no relevant information on the dose response because the studies are correcting deficiency and frequently only test one dose level. With regards to gastrointestinal effects in iron-replete subjects, the form of the iron affects the findings and therefore it is hard to compare doses. The animal database is to o limited to draw any conclusions regarding dose response. Vulnerable groups Individuals with pre-existing gastrointestinal tract disease or chronic hepatitis, have been shown to be vulnerable to the to xic effects of iron. Hereditary anaemias, such as thalassaemia or sideroblastic anaemia, frequently require treatment by repeated blood transfusions, which may result in iron overload and to xicity. Studies of particular importance to the risk assessment (For full review see. There was no difference in incidence between the groups, but there was no placebo group. The incidence of adverse gastrointestinal effects was significantly greater amongst subjects taking the conventional tablets, than amongst those taking the wax-matrix preparation. Of those taking the wax-matrix formulation only 19% experienced a severe or moderate adverse effect (306 reports), compared to 50% (1021 reports) of those taking the conventional tablets. Of the 38 participants, 37% experienced moderate to severe adverse gastrointestinal effects whilst taking ferrous sulphate, compared to 21% who experienced similar side effects whilst taking the chelate formulation. Groups of participants were given one of two different iron preparations: Group 1: two tablets of 1. The study was divided in to three consecutive periods of one month each and all participants received a placebo for one of the last two periods. Participants assessed side effects by keeping individual symp to m diaries, a multiple-choice questionnaire was used for daily evaluation with listing of effects known to be related to iron therapy. The number of reports of obstipation and the to tal side effects, were significantly higher for the non 4 haem iron treatment, than for the haem iron or placebo. Constipation was reported in 35% and all gastrointestinal side effects were reported by 25% of participants during the non-haem iron phase of the trial. The effects reported for the haem iron treatment were indistinguishable from the placebo. Lokken and Birkelan, 1979 In a randomised, double-blind crossover study, 19 young women received a dose of 120 mg/day (2 x 60) iron as ferrous fumarate or placebo for 2 periods of 8 weeks. Seven participants experienced gastrointestinal discomfort, 2 while taking placebo. In some cases, apparent recovery may take place, possibly due to a latency period during which the iron is distributed throughout the body. Systemic iron to xicity is characterised by multi-system damage, principally in the liver, metabolic acidosis, coagulopathies and cardiovascular collapse. Acute poisoning is relatively unusual in adults, the lethal dose being approximately 100 g, but is more common in children. Iron overload as a result of dietary intake is unusual in the normal population and only a handful of 4 case reports exist describing this phenomenon. This may be due to the reduction in iron absorption that occurs as exposure increases. In subjects heterozygous for the condition, a small increase in iron s to rage may occur. It has been suggested that heterozygous subjects (up to 1% of the population) may have an increased risk of cardiovascular disease but this remains controversial. Similarly, the suggestion that high iron status may be associated with other chronic conditions remains unresolved. Studies in rodents suggest a pattern of iron overload comparable with that seen in haemochroma to sis, with cellular changes but not with fibrosis occurring. Reproductive studies in rodents have shown no significant evidence of iron transfer across the placenta. This is supported by a study in an ovine model where maternal iron poisoning did not result in increases in foetal serum iron levels. However one study reports that iron gluconate is tera to genic, causing exencephaly in mice following administration on the 8th and 9th days of gestation. Many supplementation studies have been conducted, generally in iron-deficient groups and none of them are applicable to the population as a whole. For iron-replete individuals in non-developing countries, the most common side effects reported are gastrointestinal in nature, usually constipation but nausea, vomiting and epigastric pain have also been reported. These effects are reported to follow supplement doses of between 50 and 220 mg iron/day, the frequency increasing at higher dose levels. The severity and occurrence of effects depends on the formulation of the supplement (Coplin et al. For guidance purposes, a supplemental intake of approximately 17 mg/day (equivalent to 0. No additional uncertainty fac to r is needed for inter-individual variation because the assessment is based on studies on large numbers of people. A safe upper level for to tal iron has not been estimated, as gastrointestinal effects are associated with iron in supplements rather than in foods. The guidance value of 17 mg/day calculated above, does not apply to the small proportion of the population who have increased susceptibility to iron overload, via a mechanism of unregulated (increased) absorption from the diet, associated with the homozygous haemochroma to sis genotype (estimated prevalence, approximately 0. It is not possible to give quantitative information on the difference in susceptibility between this group and normal subjects. It should be recognised that many of the available studies do not look at side effects in detail and information on the long-term implications of iron supplementation on iron status and s to rage is lacking. International Journal of Clinical Pharmacology, Therapy and Toxicology 31, 105-123. The effects of oral supplementation on zinc and magnesium levels during pregnancy. Natural occurrence Magnesium is the eighth most abundant element in the earth’s crust. It does not occur as a pure metal in nature, but it is found in large deposits as magnesite, dolomite and other minerals. In this risk assessment the word ‘magnesium’ refers to ionic magnesium, except where specific magnesium salts are described. Occurrence in food, food supplements and medicines Magnesium is ubiqui to us in foods, but the content varies substantially. Leafy vegetables, as well as grains and nuts, generally have a higher magnesium content (60-2700 mg/kg) than meats and dairy products (less than 280 mg/kg). Magnesium salts are also used in food supplements at levels providing up to 750 mg/day, and licensed medicines to treat malabsorption, as a perioperative nutritional support or in special diets, and are included in antacid and laxative formulations. Analysis of tissue levels and magnesium status Tissue levels of magnesium are determined by a to mic spectroscopy. Brief overview of non-nutritional beneficial effects Dietary magnesium has been claimed to benefit bone health, but further studies are necessary to 4 confirm this suggestion. It has also been suggested that magnesium possibly plays a role in the regulation of blood pressure. Magnesium salts are effective cathartic agents and are also used in some antacid preparations. Magnesium plays a multifunctional role in cell metabolism, (particularly at the level of key phosphorylations), and has a critical role in cell division. Magnesium regulates the movement of potassium in myocardial cells and is also known to act as a calcium channel blocker.
Principles of the Procedure Procedure this medium consists of pep to arteria palatina ascendens order ramipril paypal ne agar base supplemented with Use standard procedures to blood pressure 140100 discount ramipril on line obtain isolated colonies from yeast extract and dextrose to arteria mesenterica superior purchase ramipril line provide the nutrients necessary specimens blood pressure chart stroke purchase 2.5 mg ramipril with mastercard. Bromcresol Expected Results green aids in differentiation and identifcation of Candida Candida species produce convex to cone-shaped, smooth to species based on dextrose fermentation. The color of the medium around the colonies causes the medium to become a yellow color around the becomes yellow, usually within 72 hours. Bac to Casamino Acids, Technical has been used in a medium for primary isolation of gonococcus and Casamino Acids, Vitamin Assay is used in vitamin assay meningococcus, in agar-free media for the isolation of Neisseria, procedures. It is recommended for use in microbiological assay media and in studies of the growth requirements of microorganisms. Summary and Explanation Casamino Acids, Vitamin Assay is commonly used as the Bac to Casamino Acids is an acid hydrolysate of casein, prepared 9 1 amino acid source in early phases of nutrition work. Acids, Vitamin Assay was used as the acid hydrolyzed casein the method described reduces the sodium chloride and iron in studies on p-aminobenzoic acid and p-teroylglutamic acid as content of the hydrolyzed casein. Bac to Casamino Acids, due to the nearly complete hydrolysis the manufacturing process produces a casein hydrolysate that of casein and the low sodium chloride and iron content, makes has a high salt content of approximately 37% and nitrogen an excellent supplement for many media formulations where content of approximately 8%. This product has been milk protein rich in amino acid nitrogen, is carried out until all recommended as a compromise for the replacement of pure the nitrogen is converted to amino acids or other compounds amino acids in a defned medium for the growth of Lac to bacillus, of relative simplicity. It is defcient in cystine, because casein thus eliminating the complexity of preparation. Bac to Casamino Acids, Bac to Casamino Acids, Technical, Casamino Acids, Vitamin Assay and Acidicase Bac to Casamino Acids, Technical is an acid hydrolysate of Pep to ne provide nitrogen, vitamins, carbon and amino acids casein. The hydrolysis is carried out as in the preparation in microbiological culture media. Although Bac to Casamino of Bac to Casamino Acids, but the sodium chloride and iron Acids, Bac to Casamino Acids, Technical, Casamino Acids, content of this product have not been decreased to the same Vitamin Assay and Acidicase Pep to ne are added to media extent. Bac to Casamino Acids, Technical is recommended for primarily because of their organic nitrogen and growth fac to r use in culture media where amino acid mixtures are required 17 components, their inorganic components also play a vital role. Identity Specifcations Cultural Response Bac to ™ Casamino Acids Bac to ™ Casamino Acids or Bac to ™ Casamino Acids, Dehydrated Appearance: Very light beige, free-fowing, homogeneous. Prepare various vitamin assay media using Casamino Acids, Vitamin Assay to determine the vitamin content. Adjust fnal pH to Dehydrated Appearance: Fine, homogeneous, free of extraneous material. Standard methods for the examination of water and wastewater, Casamino Acids, Technical, Casamino Acids, Vitamin Assay and 21st ed. Principles of the Procedure Solution: 1%, 2%, and 10% solutions, soluble in purifed Casein Digest is a nitrogen and amino acid source for microbio water. Casein is raw milk protein, a rich source clear; 2%-Medium amber, clear; 10%-Dark amber, of amino acid nitrogen. Bac to Casi to ne can be used as a component in microbiological Ingredients, where noted, meet United States Pharmacopeia culture media or in fermentation applications. Thus, the casein is not media formulations, where good growth of fungi and bacteria is broken down as completely in to its constituent components. It is also notable for the absence the fnal product goes through fewer refnement steps during of detectable levels of carbohydrates. This product provides some of the same benefts as been used in conjunction with casamino acids in nutritional Bac to Tryp to ne in instances where a less refned hydrolysate studies to determine amino acids vs. Casein is the main milk digest of casein as a component in many of the recommended protein and a rich source of amino acid nitrogen. Dehydrated Product Identity Specifcations Refer to the fnal concentration ofBac to Casi to ne, Trypticase Pep Bac to ™ Casi to ne to ne, Bac to Tryp to ne and BiTek Tryp to ne in the formula of the Dehydrated Appearance: Tan, free-fowing, granules. The United States pharmacopeia 31/The national amber, clear to slightly opalescent,may have a formulary 26, Supp. Compendium of methods for the microbiological examination of foods, Solution at 25°C: pH 6. Standard methods for the examination of water and wastewater, Dehydrated Appearance: Light beige, free-fowing, homogeneous. Cultural Response Biochemical Reactions Bac to ™ Casi to ne, Bac to ™ Tryp to ne or BiTek™ Tryp to ne Prepare a sterile solution as directed below. Principles of the Procedure Summary and Explanation Casman Agar Base is a nonselective, pep to ne-based medium. Members of the genus Haemophilus are fastidious microorgan the pep to nes and beef extract provide amino acids and other isms that require the addition of X and/or V growth fac to rs for complex nitrogenous nutrients. The addition of lysed blood stimulates the nutrients necessary for the growth of these fastidious the growth of some strains of N. Using Cornstarch is incorporated to prevent fatty acids from inhibit unheated human blood, he found that amount of nicotinamide ing the growth of N. Haemophilus parahaemolyticus 10014 102-103 Good Beta Alternatively, add 5% partially lysed blood. Test samples of the fnished product for performance using Neisseria gonorrhoeae 43070 102-103 Good N/A stable, typical control cultures. Strep to coccus pyogenes 19615 102-103 Good Beta Procedure For a complete discussion on the isolation and identifcation of Neisseria and Haemophilus, consult appropriate references. Gram staining, biochemical tests and serological procedures should be performed to confrm fndings. Heat with frequent agitation and boil for 1 minute to reported by Lowbury and Collins in 1955. Cetrimide (Pseudosel) Agar, therefore, is a valuable culture medium in the identifca Inoculate tubes with either pure cultures or with specimen material. The production of pyocyanin is stimulated by the however, that certain strains of P. Occasionally some enterics will exhibit a slight yellowing of the medium; however, this coloration is easily distinguished from fuorescin production since this yellowing does not fuoresce. Chapman S to ne Medium Intended Use agent because most bacterial species are inhibited by the Chapman S to ne Medium is used for isolating and differentiating high salt content. Dipotassium phosphate provides buffering staphylococci based on manni to l fermentation and gelatinase capability. Formula Difco™ Chapman S to ne Medium Summary and Explanation Chapman S to ne Medium is prepared according to the for Approximate Formula* Per Liter 1 Yeast Extract. Chapman S to ne *Adjusted and/or supplemented as required to meet performance criteria. Medium is especially recommended for suspected food poisoning studies involving Staphylococcus. Test samples of the fnished product for performance using allows detection of gelatin hydrolysis. Sodium chloride acts as a selective User Quality Control Identity Specifcations Difco™ Chapman S to ne Medium Dehydrated Appearance: Light beige, free-fowing, homogeneous with a tendency to cake. Add bromcresol purple indica to r to determine manni to l fermentation (yellow = positive). Confrm the presumptive identifcation of pathogenic staphy lococci with additional tests, such as coagulase activity. To determine manni to l fermentation, add a few drops of on the medium and show slight manni to l fermentation. The bromcresol purple to areas on the medium from which colonies, however, are tiny and can easily be differentiated colonies have been removed. Any change in color of the from staphylococci by Gram stain and the catalase test. Manni to l fermentation: Positive = change in color of the indica Williams & Wilkins, Baltimore, Md. Gelatinase activity: Positive S to ne reaction = formation of clear Availability zones around the colonies. Difco™ Chapman S to ne Medium Any manni to l-positive, yellow or orange colonies surrounded Cat. Bordetella are respira to ry pathogens, residing on the mucous membranes of the respira to ry tract. The authors found this medium to be an respira to ry and non-respira to ry infections, often occurring in effcient substitute for Bordet-Gengou Agar in the production 2 patients having close contact with animals. Mix thoroughly during dispensing to uniformly distribute cultivation and isolation of Haemophilus infuenzae.
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Der pharmazeutische Unternehmer ubermittelt dem Gemeinsamen Bundesausschuss die fur die Erstellung eines Dossiers zur Nutzenbewertung bedeutsamen Unterlagen und Informationen hypertension headache buy cheap ramipril on line, uber die er zu diesem 7 Zeitpunkt verfugt heart attack zone purchase cheap ramipril on-line, in deutscher oder englischer Sprache prehypertension follow up discount 2.5 mg ramipril overnight delivery. Die Beratungen werden innerhalb 8 von acht Wochen nach Einreichen der Unterlagen durchgefuhrt pulse pressure waveform analysis ramipril 10 mg fast delivery. Die Beratung wird durch die Geschaftsstelle des Gemeinsamen Bundesausschusses 10 durchgefuhrt, sofern er nichts anderes beschliefit. Der pharmazeutische Unternehmer erhalt eine Niederschrift uber das 3 Beratungsgesprach. Januar 2012 Beratungsgesprach erorterten Themen Vereinbarungen mit dem pharmazeutischen 4 Unternehmer treffen. Die vom Gemeinsamen Bundesausschuss im Rahmen einer Beratung erteilten Auskunfte zu Beratungsthemen nach Absatz 1 Satz 1 sind nicht verbindlich. Abschnitt Bewertungsverfahren § 8 Beginn des Bewertungsverfahrens 1 Das Bewertungsverfahren beim Gemeinsamen Bundesausschuss beginnt zu folgenden Zeitpunkten: 1. Januar 2011 erstmals in den 2 Verkehr gebracht werden, zum Zeitpunkt des erstmaligen Inverkehrbringens. Als mafigeblicher Zeitpunkt fur das erstmalige Inverkehrbringen gilt die Aufnahme des Arzneimittels in die grofie deutsche Spezialitaten-Taxe (sog. Januar 2011 in den Verkehr gebracht worden sind, innerhalb von drei Monaten nach Anforderung eines Dossiers des Gemeinsamen Bundesausschusses; 4. Das Dossier ist in deutscher Sprache einzureichen, soweit sich aus den Vorgaben fur das Dossier nichts 3 anderes ergibt. In dem Dossier hat der pharmazeutische Unternehmer nach Mafigabe des § 5 und der Vorgaben in Absatz 2 den Zusatznutzen des Arzneimittels gegenuber der 4 zweckmafiigen Vergleichstherapie nachzuweisen. Anzahl der Patienten und Patientengruppen, fur die ein therapeutisch bedeutsamer Zu satznutzen besteht, 5. Die Daten nach den Absatzen 1, 4 bis 8 sind entsprechend der in den Modulen 3 1 bis 5 festgelegten Anforderungen aufzubereiten und einzureichen. Die Module 1 bis 4 enthalten die Grundlagen, auf die sich die Bewertung stutzt, und werden vollstandig auf der 4 Internetseite des Gemeinsamen Bundesausschusses veroffentlicht. Unterlagen, die Betriebs und Geschaftsgeheimnisse enthalten, mussen in Modul 5 vom pharmazeutischen Unternehmer gekennzeichnet werden. Daruber hinaus werden alle Ergebnisse, Studienberichte und Studienpro to kolle von Studien mit dem Arzneimittel ubermittelt, fur die der Unternehmer Sponsor war, sowie alle verfugbaren Angaben uber laufende oder abgebrochene Studien mit dem Arzneimittel, fur die der Unternehmer Sponsor ist oder auf andere Weise finanziell beteiligt ist, und entsprechende Angaben uber Studien von Dritten, soweit diese verfugbar sind. Liegen keine klinischen Studien zum direkten Vergleich mit dem zu bewertenden Arzneimittel vor oder lassen diese keine ausreichenden Aussagen uber den Zusatznutzen zu, konnen im Dossier indirekte Vergleiche vorgelegt werden. Die Angabe der Kosten erfolgt sowohl fur das zu bewertende Arzneimittel als auch fur die zweckmafiige Vergleichstherapie. Bestehen bei Anwendung der Arzneimittel entsprechend der Fach oder Gebrauchsinformation regelhaft Unterschiede bei der notwendigen Inanspruchnahme arztlicher Behandlung oder bei der Verordnung sonstiger Leistungen zwischen dem zu bewertenden Arzneimittel und der zweckmafiigen Vergleichstherapie, sind die damit verbundenen Kostenunterschiede fur die Feststellung der den Krankenkassen tatsachlich entstehenden Kosten zu berucksichtigen. Diese Kennzeichnung darf der Pflicht zur Offenlegung der Studienergebnisse nicht entgegenstehen. Dokumente der Zulassungsbehorden, die dem pharmazeutischen Unternehmer zu dem fur die Einreichung mafigeblichen Zeitpunkt noch nicht vorgelegen haben, sind zu berucksichtigen, sofern sich dadurch die Nutzenbewertung nicht verzogert. Legt der pharmazeutische Unternehmer das Dossier drei Wochen vor dem jeweiligen Zeitpunkt beim Gemeinsamen Bundesausschuss vor, fuhrt die Geschaftsstelle des Gemeinsamen 3 Bundesausschusses eine formale Vorprufung auf Vollstandigkeit des Dossiers durch. Ist das Dossier unvollstandig, teilt die Geschaftsstelle des Gemeinsamen Bundesausschusses dem pharmazeutischen Unternehmer in der Regel innerhalb von zwei Wochen mit, welche 4 zusatzlichen Angaben erforderlich sind. Der Gemeinsame Bundesausschuss kann den pharmazeutischen Unternehmer auch nach einer Beratung gemafi § 7 zur fristgerechten Vorlage eines vollstandigen Dossiers auffordern. Dezember 1999 uber Arzneimittel fur seltene Leiden zugelassen sind (Arzneimittel fur seltene Leiden), gelten die Vorschriften dieses Kapitels mit folgenden Mafigaben: 1. Januar 2012 Zusatznutzens ist fur die Anzahl der Patienten und Patientengruppen, fur die ein therapeutisch bedeutsamer Zusatznutzen besteht, nachzuweisen. Dies gilt auch, wenn das Anwendungsgebiet des Arzneimittels durch die zustandigen Zulassungsbehorden 3 eingeschrankt worden ist. Halt der Gemeinsame Bundesausschuss den Antrag fur begrundet, fordert er den pharmazeutischen Unternehmer auf, die fur die Nutzenbewertung nach den Vorschriften 3 dieses Abschnitts erforderlichen Nachweise zu ubermitteln. Das Dossier ist innerhalb von drei Monaten nach Zustellung des Beschlusses vom pharmazeutischen Unternehmer dem Gemeinsamen Bundesausschuss vorzulegen. Die Beurteilung der Geringfugigkeit erfolgt auf der Grundlage von Angaben zu dem zu erwartenden Umsatz des Arzneimittels mit der 3 gesetzlichen Krankenversicherung. Soweit der dauerhaft zu erwartende Umsatz zu Apothekenverkaufspreisen einschliefilich Umsatzsteuer einen Betrag in Hohe von 1 000 000 76 Verfahrensordnung Stand: 19. Januar 2012 Euro innerhalb von 12 Kalendermonaten nicht uberschreitet, gelten die Ausgaben als geringfugig. Zur Beurteilung der Geringfugigkeit der Ausgaben macht er dem Gemeinsamen Bundesauschuss zureichende Angaben. Hat der pharmazeutische Unternehmer zu diesem Zeitpunkt ein Dossier nicht oder nicht vollstandig vorgelegt, gilt § 17 Absatz 1 Satz 2 entsprechend. Vorrangig werden Arzneimittel bewertet, die fur die Versorgung von Bedeutung sind oder mit Arzneimitteln im Wettbewerb stehen, fur die ein Beschluss nach § 20 vorliegt. Hat der pharmazeutische Unternehmer das Dossier trotz Aufforderung, spatestens zu den nach § 8 mafigeblichen Zeitpunkten nicht oder nicht vollstandig vorgelegt, trifft der Gemeinsame Bundesausschuss die Feststellung, dass der Zusatznutzen des Arzneimittels als nicht belegt gilt; die Bewertung des Nutzens des 3 Arzneimittels bleibt hiervon unberuhrt. Januar 2012 Mitteilung nach § 11 Absatz 2 Satz 3 zu den nach § 8 mafigeblichen Zeitpunkten unvollstandig ist. Dabei werden die Unterlagen hinsichtlich ihrer Planungs-, Durchfuhrungs und Auswertungsqualitat im Hinblick auf ihre Aussagekraft fur Wahrscheinlichkeit und Ausmafi des Zusatznutzens und hinsichtlich der Angaben zu den Therapiekosten bewertet. Mafistab fur die Beurteilung ist der 5 allgemein anerkannte Stand der medizinischen Erkenntnisse. Grundlage sind die internationalen Standards der evidenzbasierten Medizin und der Gesundheitsokonomie. Reichen die Zulassungsstudien nicht aus, kann der Gemeinsame Bundesausschuss weitere Nachweise verlangen. Sind fur den Beleg eines Zusatznutzens valide Daten zu patientenrelevanten Endpunkten erforderlich, kann der Gemeinsame Bundesausschuss bei der Beschlussfassung nach § 20 eine Frist bestimmen, bis wann diese Daten vorgelegt werden sollen. Soweit sie eine schriftliche Stellungnahme nach Absatz 1 abgegeben haben, konnen an der mundlichen Anhorung die Sachverstandigen sowie jeweils maximal zwei Vertreter der nach Absatz 1 3 stellungnahmeberechtigten Organisationen und betroffenen Unternehmer teilnehmen. Die 4 mundliche Stellungnahme ersetzt nicht die nach Absatz 1 abgegebene Stellungnahme. Abschnitt Beschlussfassung und Umsetzung der Nutzenbewertung in die Arzneimittel-Richtlinie § 20 Beschlussfassung uber die Nutzenbewertung 1 (1) Der Gemeinsame Bundesausschuss beschliefit uber die Nutzenbewertung innerhalb 2 von drei Monaten nach ihrer Veroffentlichung. Zulassung beantragt (Zentral/dezentral/national/Verfah ren der gegenseitigen Anerkennung) 2. Fur Studien, auf die in den Fragen Bezug genommen wird, sind Registereintrage in der Anlage zu ubermitteln. Des Weiteren soll die Dokumentation entsprechend dem Fragenkatalog gegliedert werden. Falls Literaturstellen zitiert werden, mussen diese eindeutig benannt und im Anhang im Volltext beigefugt werden. Anmerkung: Vorgeschlagene Anderung: Anmerkung: Vorgeschlagene Anderung: Anmerkung: Vorgeschlagene Anderung: (Bitte fugen Sie weitere Zeilen an, falls dies notwendig sein sollte. Kapitel § 7 VerfO § 1 Regelungsbereich (1) Der Gemeinsame Bundesausschuss erhebt fur Beratungen nach 5. Kategorie I: 2 000 Euro Allgemeine Anfragen zur Verfahrensordnung oder im Aufwand vergleichbare sonstige Anfragen 2. Der Gebuhrenschuldner ist zu horen, wenn mit einer Erhohung der Gebuhren zu rechnen ist. Januar 2012 § 5 Festsetzung der Gebuhren, Falligkeit (1) Die Gebuhren werden durch schriftlichen Bescheid festgesetzt. Januar 2012 3) Pravalenz und Inzidenz der Erkrankung in Deutschland Geben Sie eine Schatzung fur die Pravalenz und Inzidenz der Erkrankung in Deutschland an. Bei Vorliegen alters oder geschlechtsspezifischer Unterschiede oder von Unterschieden in anderen Gruppen sollen die Angaben auch fur Altersgruppen, Geschlecht bzw. Ziehen Sie dabei auch die Angaben zu Pravalenz und Inzidenz (wie oben angegeben) heran. Zyklen, Episoden) pro Patient pro Jahr an (bei kontinuierlicher Behandlung ist in der Spalte „Anzahl Behandlungen pro Patient pro Jahr“ „kontinuierlich“ anzugeben). Geben Sie jeweils auch die Behandlungsdauer in Tagen an (bei kontinuierlicher Behandlung: 365 Tage bei taglicher Behandlung, 182 bei zweitaglicher Behandlung etc.
Windows in a microbiology lab should not be opened heart attack and vine trusted ramipril 2.5mg, but if this is necessary hypertension with chronic kidney disease cheapest generic ramipril uk, then the windows must be screened hypertension values cheap 2.5mg ramipril amex. Typical methods of flying-insect or roach control can be used to blood pressure chart in elderly buy generic ramipril 2.5mg line eliminate these pests. Good hygienic practices are the first defense, and the source of any new infestation should be speedily identified. Fruit flies can present a special problem since they are attracted to microbial cultures and can enter and exit petri plates easily. This makes cross contamination of cultures and contamination of surfaces possible. There are many commercially available traps for fruit flies; a simple homemade trap consists of diluted vinegar or apple cider poured in to the bot to m of an open plastic soda bottle. Damp environments, especially those in areas without proper ventilation, cultivate mold. Keeping the labora to ry clean and dry with windows closed is the best method of prevention. Report any serious mold infestation in the labora to ry because it can pose a human health hazard that should be addressed by professionals. Another resource may be YouTube videos that demonstrate safe practices, such as proper glove removal. Although the microorganisms we use are not considered to be highly virulent, all microorganisms should be treated as potential pathogens (organisms capable of causing disease). The following rules must be observed at all times to prevent accidental injury to and infection of yourself and others and to minimize contamination of the lab environment: 1. Wash your hands with soap and dry with paper to wels when entering and leaving the lab. Wear a lab coat at all times while working in the lab to prevent contamination or accidental staining of your clothing. Long hair must be tied back to prevent exposure to flame and contamination of cultures. Do not place contaminated instruments such as inoculating loops, needles, and pipettes on bench to ps. Loops and needles should be sterilized by incineration, and pipettes should be disposed of in designated receptacles of bleach solution. Carry cultures in a test tube rack when moving around the lab or when keeping cultures on bench to ps for use. Immediately cover spilled cultures or broken culture tubes with paper to wels and then saturate them with disinfectant solution. After 15 minutes, dispose of the to wels and broken items as indicated by your instruc to r. At the end of each lab session, place all cultures and materials in the proper disposal area. Persons who are immune-compromised (including those who are pregnant or may become pregnant) and students living with or caring for an immune-compromised individual are advised to consult with your physician to determine the appropriate level of participation in the lab. Should your physician Guidelines for Biosafety in Teaching Labora to ries – Version 3. I understand that my safety is entirely my own responsibility and that I may be putting myself and others in danger if I do not abide by all the rules set forth by the instruc to r. Persons who are immune-compromised (including those who are pregnant or may become pregnant) and students living with or caring for an immune-compromised individual should consult with physicians to determine the appropriate level of participation in the lab. Should your physician discern that you should not participate in this lab, please have him or her write a note stating the concerns. Authority for Microbiology Lab and Prep Room Regulations Labs will follow the guidelines posted by the U. Department of Health and Human Services, Centers for Disease Control and Prevention, and National Institutes of Health. These guidelines describe acceptable biosafety practices in biomedical and microbiological labora to ries and can be found at. Access is limited to individuals involved directly in media prep, clean up, lab prep, and research. All staff and students are required to read, understand, and follow these regulations before working in. All staff and students working in will receive training from concerning use of the equipment. This will include the potential hazards associated with the work involved, the necessary precautions to prevent exposures, and the exposure evaluation procedures. Personnel receive annual updates or additional training as necessary for procedural or policy changes. Personnel are advised of special hazards and are required to read and follow instructions on practices and procedures. Any staff or students found in violation of the regulations may have their access to room terminated. Personnel entering room will be required to wear closed- to e shoes and have long hair tied back. This protective clothing is removed and left in the labora to ry before leaving for non-labora to ry areas. All protective clothing is either au to claved or laundered with bleach by the institution before being returned to personnel. Gloves are disposed of when contaminated, and removed when work with infectious materials is completed or when the integrity of the glove is compromised. Disposable gloves are not washed, reused, or used for to uching “clean” surfaces (keyboards, telephones, etc. Safety goggles and face shields or safety goggles and masks are worn when performing procedures that may create a splash hazard. When working in a biosafety cabinet, only lab coats and gloves are needed for personal protection. Eating, drinking, smoking, handling contact lenses, and applying cosmetics are not permitted in the lab. An orange biohazard sign must be posted on the entrance to the labora to ry when etiologic agents are Guidelines for Biosafety in Teaching Labora to ries – Version 3. Persons wash their hands upon entering the lab, after they finish working in the lab, after removing gloves, and before leaving the labora to ry. Work surfaces are decontaminated prior to beginning any work in these rooms, on completion of work or at the end of the day with 10% bleach solution. Any spill or splash of viable material should be decontaminated with 25% bleach solution. All procedures are performed carefully to minimize the creation of splashes or aerosols. Any procedure that would potentially create aerosols will be performed within the biosafety cabinet. All cultures, swabs, and waste containers are decontaminated before disposal by au to claving. Materials to be decontaminated outside of the immediate labora to ry are placed in a durable, leak proof container for transport from the labora to ry. Access to the labora to ry is limited or restricted by the labora to ry direc to r when work with infectious agents is in progress. Cultures, tissues, specimens of body fluids, or potentially infectious wastes are placed in a container that prevents leakage during collection, handling, processing, s to rage, and transport. Labora to ry equipment and work surfaces should be decontaminated with 10% bleach on a routine basis and after work with infectious materials is finished. Overt spills, splashes, or other contamination by infectious materials should be decontaminated with 25% bleach. Spills and accidents that result in overt exposures to infectious materials are immediately reported to the labora to ry direc to r. Medical evaluation, surveillance, and treatment are provided as appropriate and written records are maintained. Broken glassware that does not contain live cultures should be swept up with the broom and dust pan and discarded in the glass disposal box. Broken glassware that contains live cultures should be saturated with bleach solution. After 15 minutes, the debris should be “swept” up in to an au to clave bin using a plastic beaker and/or paper to wels. After being au to claved, the glassware can go in to the glass disposal box and the paper to wels can go in to the regular trash.