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Streamfow immediately downstream from Buford Dam is generated only by water released from Lake Sidney Summary Statistics Lanier (Lake Lanier) medications hypertension discount oxcarbazepine online visa. Because Lake Lanier is so large osteoporosis treatment buy oxcarbazepine 300mg on line, the water released does not refect s to treatment 911 buy oxcarbazepine with a mastercard rmfow in a manner Summary statistics were computed for E medications 512 order oxcarbazepine 600 mg mastercard. Rainfall data were of limited in this report as non-exceedance probabilities (1-exceedance use in assigning a s to rmfow event to samples collected from probability). Rainfall runoff relations are complex because of the interactions Regression Analysis–Theory among rainfall amounts and intensity, antecedent rainfall period, degree of urbanization in tributary watersheds, and Regression analysis is a statistical method for identifying areal extent of rainfall. These interactions can be especially and modeling the relations between two or more variables troublesome during small, isolated thunders to rms that may be (Montgomery and others, 2006, p. As in most statistical confned to specifc watersheds such as those tributary to the methods, regression analysis attempts to estimate an unknown Chattahoochee River upstream from both sites. In addition, and immeasurable parameter in a population with a subset or turbidity and Escherichia coli (E. The subsample (or sample), were frequently masked when s to rm runoff from small s to rms if random and unbiased, is assumed to mirror the statistical was diluted by high volumes of water released by Buford Dam properties of the population. Commonly, regres Ward’s method (Romesburg, 1984; Mirkin, 2005) with sion analysis is used to fulfll three objectives: (1) identify E. Table 3 lists these groups and streamfow measurements so that long-term trends in turbidity Appendix 2 65 can be assessed apart from trends in streamfow); or (3) predict variables, commonly called indica to r or dummy variables, the value of one measurement given the value of another are typically binary, having values of 0 or 1, although any measurement. A regression model does not infer a cause and arbitrary integer could be used (Montgomery and others, 2006, effect relation between variables. Using indica to r variables in a regression analysis can help to confrm a cause and effect relation, it cannot be the enables the researcher to simplify data analysis and develop only basis for inferring that relation (Montgomery and others, an equation with more predictive power and greater robust 2006, p. A variable commonly called the explana to ry, indepen stream turbidity, to tal 72-hour rainfall, antecedent rainfall, dent, or X variable is the set of measurements used to predict stream temperature, and streamfow measurements at the the mean response in another variable, commonly called Norcross and Atlanta sites and qualitative computations of the response, dependent, or Y variable (Helsel and Hirsch, season, streamfow event, and six streamfow conditions. Explana to ry variables can be qualitative to represent Several data transformations of E. Parsimony is maintained variable) are not minimized because it is assumed that this when explana to ry variables are frst transformed before adding variable is measured without error (Montgomery and others, more explana to ry variables to the regression analysis (Mont 2006). The R indicates the proportion of variability Nevertheless, Montgomery and others (2006, p. The term regression equation is used to identify tions are true: (1) the variables used for the response and different sets of explana to ry variables that are used to estimate explana to ry data have similar joint normal distributions about the intercept (fi), slope (fi), and the mean response in a0 1 the conditional mean of the regression (determined by statisti regression analysis. Also, the term linear regression means that cally signifcant correlation) and (2) the value of the explana the response or Y-variable is a linear function of the regres to ry variable is independent and random without association sion coeffcients (fi, fi) rather than the linearity of the data0 1 with the fi, fi or conditional variance of the regression. This is important in extending a hydrologic give the observed response or when residuals are so large that record or imputing missing data because the variance structure some unknown explana to ry variable is affecting the response of the actual data is imparted to the estimated data. For this report, regression analysis was divided in to parameters (fi and fi) are linear, and the errors are normally0 1 four phases: (1) explora to ry analysis and data reduction, distributed. The most common binomial distribution used to In addition, sample dates were transformed to produce develop a regression model with binary data is the logistic new variables that described seasons, Julian day, months, distribution. The logistic regression model, which uses the and monthly and annual periodicity using sine and cosine logistic distribution, produces a conditional mean of the functions. The leaps and bounds function is an iterative process 1 that shuffes and combines explana to ry variables in to various Conditionalmean of Y,given X =(fix)= 1+exp fi +fi X permutation sets and regresses the response variable against (0 1 1) those sets of explana to ry variables. The function then sorts (2–8) each subset of explana to ry variables in to ascending order where starting with the subset with the lowest number of variables and Y = response variable lowest C statistic for that group of variables. The C statisticp p fi = Yfiintercept parameter (Mallow’s C statistic, Montgomery and others, 2006, p. The C statistic balances the needp is approached asymp to tically and must be transformed to 2 to maximize the R with the need to minimize the regression create a linear equation and to develop a linear regression mean square error (Montgomery and others, 2006, p. In order to create a this initial leaps and bounds procedure was completed linear equation from equation 2–8, a logit transformation is on all Norcross and Atlanta data to identify the “best” one performed and shown as equation 2–9. Simple linear regression analyses were completed on full datasets from the Norcross and Atlanta sites fi fi fi g =lnfi x fi=fi +fi X (2–9) using E. The primary purpose of this initial regression where was to identify highly infuential or highly leveraged values gx = logit transformation (outliers) in the dataset. Data with the logit transformation gives gx many of the properties of a high leverage and infuence can exert a strong, negative linear regression (such as linearity in fi and fi). The logistic0 1 infuence on the regression equations and bias the predicted regression is ft to a binary dataset by maximum-likelihood response variable (Helsel and Hirsch, 1992; Montgomery estimation using statistical computer software (Hosmer and and others, 2006, p. Outliers may represent a measurement error leverage and infuence (outliers) for each value in the dataset; or other anomaly in one or more explana to ry variables. One diagnostic value from the analysis of or a studentized residual with an absolute value greater than variance, the F-value and its associated p-value, indicates the 1. Associated with the F-value for each regression where analysis is a p-value, which indicates the probability of a p = number of parameters in regression equation higher F-value and thus the probability or chance that there n = number of samples used in the regression is no linear relation between the response and explana to ry Regression analysis using this new dataset was completed variables. In this report, computed p-values that are less than to determine if removing outliers improved the regression statis 0. Using this new equation, additional variables were added response variable and explana to ry variables (Montgomery and to the leaps and bounds results to determine other characteristics others, 2006, p. Only those regression analyses having that accounted for a statistically signifcant amount of the vari a p-value less than 0. In addition, a logistic regression model Another diagnostic value that is typically presented with was developed to predict the probability of E. Environmental Protection Agency for the intercept and each explana to ry variable added to the beach criterion at a specifc turbidity measurement. If the t-value calculated by the regression analysis shows that the computed p-value for the variable is Evaluating the Regression Equation less than 0. Typically, when computed t-values result in a p-value predict a response with minimal errors. Including such a variable by defnition) that consists of measurement errors in the in the equation may increase the variance around the intercept response variable and regression errors (bias). The to tal error and may be detrimental when statistically comparing the in any regression can never be less than the measurement regression equation at some later date. Furthermore, if statistical an interaction term to the regression causes the p-value of an inference (hypothesis testing) is used to compare or validate explana to ry variable to exceed 0. Common measures, and those used for this report, Figures showing diagnostic graphs for the regression for evaluating the regression analysis include identifying: analyses considered but not chosen for the Norcross and (1) the statistical signifcance of the regression (is the Atlanta predictive models are presented in appendixes 5 and 6, slope statistically different from zerofi These plots show the normality and variance Appendix 2 69 character of the regression residuals, which are important interval at which au to correlation no longer exists could be measures of robustness in the regression. In the frst graph used to subset the original dataset or the dataset could be (labeled A), the measured E. For this report, however, the au to correlation this type of graph can show linear or mono to nic trends in the analyses were informational only because the regression residuals that may result from nonconstant variance. In the analyses did not incorporate a time series component and third graph (labeled C), quantile-quantile plots of the residuals were not intended to forecast E. Unwanted nonlinear regression, such as logistic regression (Harrell, correlation includes correlation among explana to ry variables 2001, p. For each two or more explana to ry variables in a regression equation plausible equation identifed by the leaps and bound procedure (Montgomery and others, 2006, p. Regression equations chosen as the “best” for each site In addition to multicollinearity, serial correlation may were considered estimation or calibration equations. The estima exist in a dataset when samples are collected sequentially tion equations were used with a validation dataset (sometimes within a short time period. This correlation, called au to called a confrmation dataset) to determine how well the correlation, is determined in two ways in this report: (1) by equation predicts values of the response variable. In this report, the Durban-Watson statistic (Montgomery and others, 2006, the validation dataset consisted of data collected at the Norcross p. This function creates temporary copies residuals and used to determine how well predicted E. In other words, residuals for a given sample plots were constructed showing the relation of prediction were compared sequentially to the regression residuals in residuals to the predicted E. Comparisons Between Escherichia coli and Fecal Coliform Bacteria Density the Escherichia coli (E.
Brief overview of claimed non-nutritional beneficial effects It has been claimed that vitamin C protects against the common cold medicine xifaxan oxcarbazepine 300mg without a prescription. Beneficial effects on conditions such as cancer treatment naive definition cheap oxcarbazepine 600mg visa, vascular disease treatment dynamics florham park cheap oxcarbazepine 150mg with visa, cataracts medicine 75 purchase oxcarbazepine overnight, diabetes, asthma, arthritis, Parkinson’s disease, autism and depression have also been suggested. Vitamin C is involved in the synthesis of collagen, neurotransmitters and carnitine; it is an enzyme co-fac to r and also increases the gastrointestinal absorption of non-haem iron. Deficiency Vitamin C deficiency in humans leads to the clinical syndrome of scurvy. In later stages scurvy is characterised by anaemia, bleeding from the gums, petechial and sheet haemorrhages, and delayed wound healing. Absorption and bioavailability Gastrointestinal absorption of vitamin C is efficient and occurs in the small intestine via a saturable active transport mechanism. Absorption efficiency of low oral doses of vitamin C (4 – 64 mg) may be as high as 98%, but decreases with increasing doses of the vitamin. Distribution and metabolism Ascorbic acid is widely distributed in all tissues of the body, with higher levels found in the adrenal glands, pituitary and retina, and lower levels in kidney and muscle tissue. Vitamin C is oxidised to dehydroascorbic acid, which is hydrolysed to dike to gulonic acid and then oxidised to oxalic and threonic acid. Excretion Unmetabolised vitamin C and vitamin C metabolites, such as oxalate, are largely excreted in the urine. Toxicity Human data Gastrointestinal effects are the most common adverse clinical events associated with acute, high doses of vitamin C given over a short period of time. Adverse effects related to the urinary route of excretion have been claimed, including renal s to nes, renal tubular disease and oxaluria. It has been suggested that vitamin C consumption may increase oxalate excretion and cause the formation of urinary s to nes, and subjects with a predisposition to the formation of kidney s to nes may be more sensitive to increases in urinary oxalate associated with vitamin C. However, studies in humans have not revealed a substantial increase in urinary oxalate after high intakes of vitamin C, and the moderate increases reported may be an experimental artefact (see later). Vitamin C increases iron uptake from the gut and it is possible that this may be important in subjects with conditions such as haemochroma to sis or in subjects heterozygous for this condition. However, when doses of vitamin C of 2000 mg/day were given to healthy volunteers for 20 months or more, no effects on iron status were found. Supplementation trials Vitamin C was administered (in combination with other vitamins and minerals) at doses of up to 1000 mg/day for up to 5 years in two supplementation trials with good compliance and no reported adverse effects. Reduced vitamin B12 levels in 3 (of 90) individuals consuming more than 1000 mg/day over a minimum of 3 years were reported in an earlier trial, although the relevance of these observations has been questioned. Animal data Vitamin C has low to xicity when large doses are given over a short period of time. High doses of vitamin C are associated with decreased growth rates in guinea pigs (50 mg/day), increased cholesterol levels in rats (150 mg/kg bw/day) and interference with trace element metabolism in chicks. A conditioned increase in vitamin C requirements has been reported in guinea pigs. Some positive in vitro mutagenicity tests have been reported, although results are generally mixed. However, the positive results tended to occur when vitamin C was tested in the presence of copper. Vulnerable groups Individuals unable to regulate iron absorption due to haemochroma to sis or thalassaemia may be vulnerable to any enhanced iron absorption caused by vitamin C. Although clear and substantial rises in urinary oxalate excretion have not been demonstrated during increased vitamin C intake, it remains possible that individuals with risk fac to rs such as uricosuria will be more sensitive. Adverse effects attributed to vitamin C may be due to increased sensitivity to oxidant stress, because vitamin C can be pro-oxidant at very high concentrations. Dose-response characterisation the dose-response is unclear, as many studies have used only one dose level. However, where found, adverse effects are generally reported at levels in excess of 1000 mg vitamin C/day. Genetic variations Polymorphisms in hap to globin and transferrin have been reported to be associated with altered metabolism of vitamin C. Certain conditions may increase sensitivity to the adverse effects associated with this compound. Cameron and Campbell, 1974 In a stepped study, healthy human volunteers were given vitamin C with the dose increasing each week by 1000 mg. Abdominal distention, flatulence, diarrhoea and transient colic were described as ‘fairly frequent’ effects at supplemental dose levels of 3000-4000 mg daily. Nine subjects continued in the study, taking these doses of vitamin C for 24 months. Although vitamin C enhances absorption of non-haem iron, no increase in serum ferritin levels was found, despite wide variation in initial iron status between the volunteers. The authors concluded that supplemental vitamin C had a negligible effect on iron s to res. Vitamin C supplementation continued for a further 20 months in 4 iron-deficient and 4 iron-replete subjects. No effect of vitamin C on body iron reserves (as measured by serum ferritin levels) was apparent and no intestinal adaptation to the enhancing effect of the vitamin had occurred. No adverse effects were reported in this study of large supplemental doses of vitamin C but the authors noted that the study did not exclude possible adverse effects in individuals who are heterozygous for the haemochroma to sis gene (approximately 10% of the population). The study involved small numbers of participants with variable iron status and was not blinded, though compliance was checked. The patients were interviewed about side effects after 2 weeks and 4 weeks of treatment. Out of the 10 patients receiving the active supplement, one reported slight facial erythema at week 2, which subsequently subsided during continued treatment, one reported passing urine with a peculiar smell. Three of the 10 patients receiving the placebo reported an increased number of headaches. The increase in urinary oxalate was statistically significant at doses of administered vitamin C of 500 mg or more. The authors estimated that there was a 6-13 mg/day increase in urinary oxalate excretion per 1000 mg/day administered ascorbic acid, and concluded that vitamin C supplementation was associated with an increased risk of calcium oxalate renal s to nes. Twenty-four-hour urine samples were preserved by adding hydrochloric acid to reduce the pH to 2 and frozen. Ascorbate appeared to be converted non enzymatically in to oxalate during analysis, confounding the analytical measurement. This may explain the previously published results in other studies, where oxalate excretion was affected by ascorbate consumption. A moderate, dose-dependent increase in urinary oxalate was found in the volunteers. However, a clear trend was not apparent when the non-enzymatic ascorbate- to -oxalate conversion was taken in to account. Subjects were advised to take the vitamin C tablets at mealtimes to minimise potential adverse gastrointestinal effects. However, two out of 15 volunteers experienced diarrhoea when consuming 10,000 mg supplemental vitamin C/day and were unable to continue taking this level. At vitamin C intakes of 1000 mg/day there were statistically significant increases in urinary oxalate excretion (though this was still within physiological limits) and uric acid excretion. In the preserved samples there was no significant increase in oxalate excretion at any stage of the pro to col. Excretion of ascorbic acid increased when vitamin C ingestion commenced but levels stabilised after 24 hours suggesting saturation of the metabolic pool. While transient and statistically significant changes 104 Expert Group on Vitamins and Minerals 2003 1 occurred in some of the biochemical risk fac to rs, it was concluded that large doses of vitamin C did not affect the principal risk fac to rs associated with calcium oxalate kidney s to ne formation. A significant increase in flow-mediated dilation of the brachial artery was observed, compared to controls, following the single dose of 2000 mg vitamin C. This improvement was sustained after the 30-day supplementation period with 500 mg/day vitamin C. Amongst the users of vitamin C supplements, supplemental intake ranged from 100 mg/day to 5000 mg/day; the mean was calculated to be 745 mg/day. High oral doses of vitamin C are associated with gastrointestinal effects, generally at doses of several grams, but have also been reported at doses of 1000 mg (1 g). Controlled studies do not support anecdotal reports of other possible adverse effects, such as infertility. Earlier suspicions of potential adverse effects, such as destruction of vitamin B12, have not been confirmed following subsequent developments in analytical techniques. Some reported increases in urinary oxalate might be attributable to experimental artefact (Auer et al.
Tese host strains are defcient in Ion and OmpT proteases nail treatment discount 150 mg oxcarbazepine amex, which is responsible for increased protein stability medications for rheumatoid arthritis 600 mg oxcarbazepine. Tus novel technological advancements are expression host are discussed in the previous section on selection of unceasingly being prepared to medications gerd discount 150 mg oxcarbazepine free shipping advance the E treatment for gout discount oxcarbazepine uk. In this method, the plasmid copy number is relatively modifcations are some of them. Due to the presence of rare codons low at lower temperatures and increased when the temperature is translational errors occur which result in mutation and production of elevated. Tus, while expressing recombinant proteins in genetics and also by cultivation condition such as growth rates, media E. Such an ideal expression system should have a consensus Tere are number of other parameters which can be taken in to promoter. Efcient transcription termina to r will minimize the drain of account while trouble shooting the recombinant protein production in cellular energy and will reduce the metabolic burden for the host. Optical density during induction, inducer concentration, post transcription termina to r should be able to form secondary structure induction time, usage of efective termina to r codons is some of the at 3’ end to improve the stability and protein yield. Appropriate host strategies which can be implemented to enhance the desired protein selection will favor the protein yield and enhance the stability of production. Every protein poses a new problem, high level Challenges in T erapeutic Protein Production in E. Extended through bacterial expression systems: a review of the existing biotechnology strategies. SaAfida F, Uzan M, Odaert B, Bontems F (2006) Expression of highly to xic evaluation of the advantages and limitations of frequently used expression genes in E. Proc Natl Acad evolution of AraC for improved compatibility of arabinose and lac to se-inducible Sci U S A 82: 1074-1078. Adhya S, Gottesman M (1982) Promoter occlusion: transcription through a promoter may inhibit its activity. Vimberg V, Tats A, Remm M, Tenson T (2007) Translation initiation region sequence preferences in Escherichia coli. Nishihara T, Iwabuchi T, Nohno T (1994) A T7 promoter vec to r with a transcriptional termina to r for stringent expression of foreign genes. Medium-scale structural genomics: strategies for protein expression and crystallization. CA©sar SAfinchez J, PadrAfin G, Santana H, Herrera L (1998) Elimination J Mol Biol 284: 579-590. Department of Microbiology, School of Life Sciences, Sikkim University, Gang to k, Sikkim, India. Department of Microbial Biotechnology, Punjab University, Chandigarh, Punjab, India. State Institute of Rural Development, Government of Sikkim, Gang to k, Sikkim, India. Author’s Contribution: 1*: Designed the manuscript as well as supervised the study; # 1; Performed the experiment; analyze the data and prepared the manuscript; # @ @ 1,1,2,: Analyzed the data and prepared the manuscript; $ 1; Helped in the sample collection, survey and lab experiments. Merely a few community-based studies on the prevalence of antibiotic resistance in commensal bacteria have been conducted so far in Southeast Asia and other parts of India. Northeastern India is still untapped regarding the surveillance of antibiotic-resistant genes and prevalence in commensal bacteria. In the present work, the prevalence of antibiotic resistance in commensal Escherichia coli was investigated along with the associated demographic fac to rs in pre-school and school going children in rural areas of Sikkim. A structured questionnaire was designed to study the fac to rs associated with carriage of antibiotic resistance in commensal E. Descriptive statistics analysis and a logistic regression model were used to identify the effect of external fac to rs on antibiotic resistance pattern. High prevalence of resistance was found against commonly used antibiotics ampicillin (92%), ceftazidime (90%), cefoxitin (88%), strep to mycin (40%) and tetracycline (36%) among the samples examined in our present study. Fifty-two percent of the isolates were resistant to the combination of penicillin and quinolone group of antibiotics. Children living in nuclear families showed higher incidence of resistance to ampicillin (63. A close association between different demographic fac to rs and the pattern of carriage of antibiotic-resistant isolates was observed suggesting a concern over misuse of antibiotics and warrants a future threat of emerging multidrug resistant isolates. Introduction During the last decade, an alarming worldwide increase in the incidence of community acquired infections with bacteria resistant to multiple antibiotics of common use has been observed [1]. Use of antibiotics plays a crucial role in the development of antibiotic resistance [2]. All over the world, development of resistance to antibiotics is on the rise amongst pathogenic bacteria [3]. However, to counter the situation, very few new antibiotics have come in to use in the last three decades [4]. Rising resistance to antimicrobials in pathogens is a worldwide problem and is particularly serious in developing countries, where alternative antimicrobials are often not available or to o expensive [5]. Inappropriate use of antimicrobials is considered to be one of the main fac to rs responsible for the high prevalence of antibiotic resistance in developing countries [5]. Increased antibiotic resistance in pathogens leads to increased mortality and morbidity, enhanced transmission of antibiotic-resistant bacteria and increased health costs [6]. A large number of commensal bacteria colonize the gastrointestinal tract of mammals [7]. The commensal bacteria reside in the gut without being eliminated, they play an important role in human nutrition and health, by promoting nutrient supply, preventing pathogen colonization, shaping and more importantly maintaining the homeostasis of the intestinal immune system [6]. In community settings, young children tend to be the 3 most exposed to antibiotics and several studies have revealed that younger children have the highest risk of carrying antibiotic resistant commensal bacteria [9][8][10]. Escherichia coli is a member of the Enterobacteriaceae family, the enteric bacteria, which are facultative anaerobic Gram-negative bacteria, commonly found in the intestinal tract of warm-blooded animals including humans [7]. Escherichia coli, a near ubiqui to us colonizer of the gastrointestinal tract in children and adults has often been used in studies of the incidence of antibiotic resistance in commensal bacteria [11]. In recent years, the potential role of the commensal microbiota for the emergence and spread of antimicrobial resistance in pathogens has been universally acknowledged [12]. India is among the nations with the highest burden of bacterial infections and the crude mortality from the infectious diseases (In India 417 per 100,000 persons dies due to bacterial infections) [14]. In 2010, India was the world’s largest consumer of antibiotics 9 for human health with 12. The emergence of antimicrobial resistance is not only limited to the older and more frequently used classes of drugs but there has also been a rapid increase in the emergence of resistance to the newer and more expensive drugs, like carbapenem [14]. Limited research has been done with regards to prevalence of antibiotic resistance in E. However, none of these studies were done in the north eastern population, hence there is no data suggesting the prevalence of antibiotic resistance in this area. In the few studies conducted, the wide variation has been demonstrated in resistance pattern of E. To evaluate the correlation between increasing antibiotic use and the emergence of antibiotic-resistant pathogens, community-based surveillance could be of great use. The aim of the present study was to investigate the prevalence of antibiotic resistance in commensal E. Materials and Methods Site and study duration the selected study area was Sikkim state of India and the study was conducted during July 2015 to June 2017. Sikkim is a northeastern state of India surrounded by Tibetan Plateaus in North, Chumbi Valley of Tibet as well as Bhutan kingdom in East. South is surrounded by Darjeeling district of West Bengal and the West by the Kingdom of Nepal [18]. The land of Sikkim is divided in to lower hills (Altitude 270 to 1500 meters), middle hills (Altitude 1500 to 2000 meters) and higher hills (Altitude 5 2000 to 3000 meters) based on the geographical parameter. Sikkim has an Alpine zone (Altitude above 3900 meters with vegetation) and Snowbound Land (Very high mountains without vegetation up to 8580 meters) [18]. Survey Sikkim has a to tal of 451 villages with a population of 4,55,962 as per census 2011[20]. The survey was carried out in randomly selected 150 villages of Sikkim at different altitude with a to tal average population of children was 4500. The study design and the demographic details of respondent were summarized in Fig 1 and Fig 2. The healthy children from age 1-14 years were included in this study (Healthy: children who are metabolically active without any symp to matic diseases especially gastrointestinal abnormalities like diarrhea, vomiting, abdominal cramps, nausea at the time of survey; Unhealthy: Children with gastrointestinal abnormalities at the time of survey).
Syndromes
- Blood tests, including blood sugar, CBC, ESR, Lyme test
- Severe brain damage
- Unsteadiness
- Fever
- Mental status changes
- Weak, uncoordinated speech sounds
Eine solche grundsatzliche Bedeutung liegt in der Regel in Fragen mit sek to treatment of schizophrenia generic oxcarbazepine 600 mg with mastercard renubergreifender Versorgungsrelevanz symptoms 0f high blood pressure buy oxcarbazepine 150mg low cost. Die Erstellung und Berucksichtigung der vom Bundesministerium fur Gesundheit nach § 139b Abs medicine escitalopram discount 300 mg oxcarbazepine with visa. Er muss a) den Auftragsgegenstand hinreichend genau bestimmen shinee symptoms buy oxcarbazepine 300 mg without prescription, b) den Aufgabenbereich nach § 139a Abs. Letzteres ist insbesondere dann der Fall, a) wenn noch kein Antrag nach § 135 Abs. Die Dauer der Antragsprufung soll 3 3 Monate nach seinem Eingang nicht uberschreiten. In Abstimmung mit dem Institut fur Qualitat und Wirtschaftlichkeit im Gesundheitswesen kann das Plenum Auftrage ruhen lassen, andern oder zurucknehmen. Aufierdem kann der Auftrag Unterlagen angeben, die neben den vom Institut recherchierten Beurteilungsgrundlagen zu 3 berucksichtigen sind. Die Formulierung des Auftrages und die Festlegung der Termine zur Abgabe der Auftragsleistung erfolgen im Benehmen mit dem Institut. Januar 2012 § 20 Auftragspflichten Mit dem Auftrag ist das Institut fur Qualitat und Wirtschaftlichkeit im Gesundheitswesen zu verpflichten, a) die Verfahrensordnung zu beachten, b) in regelmafiigen Abstanden uber den Stand der Bearbeitung zu berichten, c) den Gremien des Gemeinsamen Bundesausschusses fur Ruckfragen und Erlauterungen auch wahrend der Bearbeitung des Auftrages zur Verfugung zu stehen und d) die durch die Geschaftsordnung des Gemeinsamen Bundesausschusses bestimmte Vertraulichkeit der Beratungen und Beratungsunterlagen zu beachten. Diese sind auf Wunsch des Instituts fur Qualitat und Wirtschaftlichkeit im Gesundheitswesen vertraulich zu behandeln. Abschnitt Offenlegungspflichten § 23 Verpflichtete 1 (1) Sachverstandige, die den Gemeinsamen Bundesausschuss oder seine Untergliederungen mundlich oder schriftlich beraten sollen, haben nach Mafigabe dieses Abschnitts Tatsachen offen zu legen, die ihre Unabhangigkeit bei dem jeweiligen 2 Beratungsgegenstand potenziell beeinflussen. Die oder der Ausgeschlossene darf bei der weiteren Beratung und der Beschlussfassung nicht zugegen sein. Januar 2012 § 24 Offenlegung (1) Inhalt und Umfang der Offenlegungspflicht bestimmen sich nach Anlage I (Selbsterklarungsformular). Das Gremium sucht bei unklaren oder unstimmigen Angaben um erganzende Ausfuhrungen nach. In die Sitzungsniederschrift ist nur anzugeben, dass eine Offenlegungserklarung abgegeben wurde. Eine Bewertung in diesem Sinne findet insbesondere statt bei Erlass der Richtlinien nach den folgenden Nummern des § 92 Abs. Januar 2012 die zu prufende Methode in ihrer Art, die zu prufenden Indikationen und indikationsbezogenen Zielsetzungen beschreiben, die Rechtsgrundlagen der beantragten Entscheidung angeben und soll eine substantiierte Begrundung enthalten. Angaben uber die spezielle Zielpopulation, zu Versorgungsaspekten von Alter, biologischem und sozialem Geschlecht sowie lebenslagenspezifischen Besonderheiten und die erforderlichen organisa to rischen Rahmenbedingungen der zu uberprufenden 3 Methode konnen erforderlich sein. In der Begrundung sind aufierdem Angaben zur Relevanz und Dringlichkeit der beantragten Prufung zu machen, auf die eine Priorisierung gemafi § 5 gestutzt werden kann. Soweit erforderlich konnen auch die zu beratenden Indikationen gemafi Satz 1 sortiert oder in begrundeten Ausnahmefallen erweitert, beschrankt oder zusammengefasst werden. Zur Abgabe der Stellungnahmen einschliefilich der Belegunterlagen ist durch den Unterausschuss eine angemessene Frist zu setzen, die einen Monat nicht unterschreiten soll. Abschnitt Bewertungsverfahren § 7 Grundzuge des Verfahrens (1) Das Bewertungsverfahren untergliedert sich in a) die sek to renubergreifende und damit einheitliche Bewertung des Nutzens und der medizinischen Notwendigkeit sowie b) die sek to rspezifische Bewertung der Wirtschaftlichkeit und Notwendigkeit im Versorgungskontext. Januar 2012 der Verfahrensordnung geregelten methodischen Anforderungen ist durch die Besetzung der themenbezogenen Arbeitsgruppe oder durch die Geschaftsfuhrung zu gewahrleisten. Soweit die Stellungnahmen eine in Auftrag gegebene Fragestellung betreffen, sind sie der Auftragnehmerin oder dem Auftragnehmer zuzuleiten. Soweit das Bewertungsverfahren noch nicht durch eine Veroffentlichung gemafi § 6 Abs. Januar 2012 b) Diagnosestudien, die die Aussagekraft der diagnostischen Mafinahmen in einem Fruherkennungs-Setting nachweisen und Ruckschlusse auf den Nutzen bei ihrer Anwendung zulassen, c) Studien zur Effektivitat einer Fruherkennungsuntersuchung bezuglich patientenrelevanter Outcomeparameter und d) Unterlagen dazu, ob die in Studien gezeigte Aussagekraft und Qualitat auch bei flachendeckendem Einsatz gewahrleistet werden kann. Bundesarztregister, Krankenhausadressbuch, Landeskrankenhausplane der Lander, Register anderer, spezifischer Leistungserbringer), d) notwendigen Organisation der gesamten Screeningkette, einschliefilich der Behandlung, und e) Struktur der Behandlung. Die Uberprufung des Nutzens einer Methode erfolgt insbesondere auf der Basis von Unterlagen a) zum Nachweis der Wirksamkeit bei den beanspruchten Indikationen, b) zum Nachweis der therapeutischen Konsequenz einer diagnostischen Methode, c) zur Abwagung des Nutzens gegen die Risiken, d) zur Bewertung der erwunschten und unerwunschten Folgen (outcomes) und e) zum Nutzen im Vergleich zu anderen Methoden gleicher Zielsetzung. Die Uberprufung der medizinischen Notwendigkeit einer Methode erfolgt insbesondere auf der Basis von Unterlagen a) zur Relevanz der medizinischen Problematik, b) zum Spontanverlauf der Erkrankung und c) zu diagnostischen oder therapeutischen Alternativen. Die Uberprufung der Wirtschaftlichkeit einer Methode erfolgt insbesondere auf der Basis von Unterlagen zur a) Kostenschatzung zur Anwendung beim einzelnen Patienten oder Versicherten, b) Kosten-Nutzen-Abwagung in Bezug auf den einzelnen Patienten oder Versicherten, c) Kosten-Nutzen-Abwagung in Bezug auf die Gesamtheit der Versicherten, auch Folgekosten-Abschatzung, und d) Kosten-Nutzen-Abwagung im Vergleich zu anderen Methoden. Januar 2012 V Assoziationsbeobachtungen, pathophysiologische Uberlegungen, deskriptive Darstellungen, Einzelfallberichte, u. Im Einklang mit allgemein anerkannten Empfehlungen bewertet er die Planungs-, Durchfuhrungs und Auswertungsqualitat der Unterlagen, die Konsistenz der Ergebnisse und die Ubertragbarkeit der Studienergebnisse auf den Versorgungskontext. Mortalitat, Morbiditat, Lebensqualitat), Versorgungsaspekte von Alter, biologischem und sozialem Geschlecht sowie lebenslagenspezifischen Besonderheiten, besondere Belange behinderter und chronisch kranker Menschen und die eingesetzten Mafinahmen zur Vermeidung von verzerrten Studienergebnissen berucksichtigt werden. Abschnitt Entscheidungsfindung § 12 Entscheidungsgrundlagen 1 (1) Die Anerkennung einer Untersuchungs oder Behandlungsmethode nach § 135 Abs. Januar 2012 allgemein anerkannten Standes der medizinischen Erkenntnisse nicht erforderlich ist, erlasst das Plenum eine entsprechende Richtlinie; die Durchfuhrung klinischer Studien sowie die Behandlung im besonderen Einzelfall gemafi § 13 Abs. Bei seltenen Erkrankungen, bei Methoden ohne vorhandene Alternative oder aus anderen Grunden kann es unmoglich oder unangemessen sein, Studien dieser Evidenzstufe durchzufuhren oder zu fordern. Die Anerkennung des medizinischen Nutzens einer Methode auf Grundlage von Unterlagen einer niedrigeren Evidenzstufe bedarf jedoch auch unter Berucksichtigung der jeweiligen medizinischen Notwendigkeit zum Schutz der Patientinnen und Patienten umso mehr einer Begrundung, je weiter von der Evidenzstufe I abgewichen 6 wird. Dafur ist der potentielle Nutzen einer Methode, insbesondere gegen die Risiken der Anwendung bei Patientinnen oder Patienten abzuwagen, die mit einem Wirksamkeitsnachweis geringerer Aussagekraft einhergehen. Mafistab ist dabei auch die von der Anwendung der Methode bereits erzielte oder erhoffte Verbesserung der Versorgung durch die Gesetzliche Krankenversicherung unter Berucksichtigung der mit der Erkrankung verbundenen Einschrankung der Lebensqualitat und den besonderen Anforderungen an die Versorgung spezifischer Patientengruppen unter Berucksichtigung der Versorgungsaspekte von Alter, biologischem und sozialem Geschlecht sowie der lebenslagenspezifischen Besonderheiten. Kapitels durch Beschluss uber das Ergebnis des Bewertungsverfahrens oder uber seine Aussetzung. Januar 2012 1 (4) Der Gemeinsame Bundesausschuss kann bei Methoden, bei denen noch keine ausreichende Evidenz vorliegt, aber zu erwarten ist, dass solche Studien in naher Zukunft vorgelegt werden konnen, Beschlusse mit der Mafigabe treffen, dass bei Untersuchungs und Behandlungsmethoden in der ambulanten vertragsarztlichen Versorgung gemafi § 135 Abs. Die Beschlussfassung soll mit Anforderungen an die Strukturqualitat, Prozessqualitat und/oder an die Ergebnisqualitat der Leistungserbringung gemafi § 137 Abs. Der Gemeinsame Bundesausschuss kann die Beratungen auch vor Ablauf der festgelegten Frist wieder aufnehmen; dies gilt insbesondere, wenn die fur die Entscheidung erforderlichen Erkenntnisse bereits zu einem fruheren Zeitpunkt vorliegen oder wenn erkennbar ist, dass auch bis zum Ablauf der Frist keine erhebliche Anderung des Kenntnisstandes erreicht werden wird. Kapitels, d) der Abwagungsprozess nach § 13 sowie e) der Beschluss und tragende Grunde. Abweichende Beschlussentwurfe werden zusammen mit ihrer Begrundung in die zusammenfassende Dokumentation aufgenommen. Hierzu sollten auch Angaben fur die Abgrenzung zu ahnlichen, aber von der Vorlage nicht 3 umfassten Leistungen oder Indikationen gemacht werden. Zuvor fordert der zustandige Unterausschuss die vorlegende Organisation nach § 2 zur Erganzung oder Prazisierung ihrer Vorlage innerhalb einer angemessenen Frist auf. Januar 2012 § 4 Priorisierung Die Reihenfolge, in der die nach § 2 zur Beratung anstehenden Vorlagen zu beraten sind, legt der zustandige Unterausschuss unter Berucksichtigung der Relevanz einer ambulanten Erbringung der zur Beratung stehenden Leistungen und Behandlungen im Krankenhaus im Vergleich zur Erbringung allein in Vertragsarztpraxen fest; dem Plenum ist die aus der Festlegung entstehende Bearbeitungsliste vorzulegen. Januar 2012 (2) Wenn eine Bewertung des Nutzens und der medizinischen Notwendigkeit nicht vorliegt oder begrundete Zweifel bestehen, dass diese noch dem allgemein anerkannten Stand der medizinischen Erkenntnisse entspricht, kann das Plenum eine sek to renubergreifende Bewertung nach dem 2. Dabei sind die Besonderheiten der ambulanten Leistungserbringung im Krankenhaus zu berucksichtigen. Abschnitt Regelungsbereich und allgemeine Vorschriften § 1 Regelungsbereich (1) Dieser Abschnitt regelt die Verfahren 1. Abschnitt Bewertung des therapeutischen Nutzens, der medizinischen Notwendigkeit und der Wirtschaftlichkeit von Arzneimitteln 1. Titel Regelungsbereich und Grundzuge des Verfahrens § 3 Anwendungsbereich 1 (1) Dieser Abschnitt regelt das Verfahren fur Richtlinienbeschlusse nach § 92 Abs. Der Gemeinsame Bundesausschuss kann dabei die Verordnung von Arzneimitteln einschranken oder ausschliefien, wenn die Unzweckmafiigkeit erwiesen ist oder eine andere, wirtschaftlichere Behandlungsmoglichkeit mit vergleichbarem 5 diagnostischen oder therapeutischen Nutzen verfugbar ist. In Therapiehinweisen konnen Empfehlungen zur wirtschaftlichen Verordnungsweise von Arzneimitteln gegeben werden. Titel Bewertung des therapeutischen Nutzens § 6 Therapeutischer Nutzen (1) Die Bewertung des therapeutischen Nutzens eines Arzneimittels erfolgt auf der Grundlage von Unterlagen entweder zum Ausmafi des therapeutischen Nutzens des Arzneimittels bei einer bestimmten Indikation oder durch Vergleich mit anderen Arzneimitteln oder Behandlungsformen unter Berucksichtigung des therapeutischen Zusatznutzens fur die Patientinnen oder Patienten. Vorrangig sind randomisierte, kontrollierte, klinische Studien, insbesondere direkte Vergleichsstudien mit anderen Arzneimitteln oder Behandlungsformen, zu berucksichtigen. Titel Bewertung der medizinischen Notwendigkeit und Wirtschaftlichkeit § 9 Medizinische Notwendigkeit Die Bewertung der medizinischen Notwendigkeit erfolgt im Hinblick darauf, ob 1. Bestehen bei Anwendung der Arzneimittel entsprechend der Fach oder Gebrauchsinformation regelhaft Unterschiede bei der notwendigen Inanspruchnahme arztlicher Behandlung oder bei der Verordnung sonstiger Leistungen, sind die damit verbundenen Kostenunterschiede zu berucksichtigen. Titel Umsetzung des Ergebnisses der Nutzenbewertung in die Arzneimittel Richtlinie § 11 Ergebnis der Bewertung 1 (1) Ergibt die Bewertung, dass ein Arzneimittel im Vergleich zu anderen Arzneimitteln oder Behandlungsmoglichkeiten therapierelevant unterlegen ist oder sein kann, ist zu prufen, ob die Verordnung des Arzneimittels wegen Unzweckmafiigkeit gemafi § 92 Abs. Das Nahere zur Bewertung der Unzweckmafiigkeit eines Arzneimittels regeln die §§ 12 und 13.
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