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By I. Fabio. Aquinas College.

They often examine the short-term effects of drugs that in practice are used for much longer periods of time cheap 100 caps gasex mastercard chronic gastritis food allergy. Finally discount gasex 100caps with visa gastritis tips, efficacy studies tend to use objective measures of effects that do not capture all of the benefits and harms of a drug or do not reflect the outcomes that are most important to patients and their families purchase 100 caps gasex mastercard gastritis snacks. An evidence report also highlights studies that reflect actual clinical effectiveness in unselected patients and community practice settings. Effectiveness studies conducted in primary care or office-based settings use less stringent eligibility criteria, assess health outcomes, and have longer follow-up periods than most efficacy studies. The results of effectiveness studies are more applicable to the “average” patient than results from highly selected populations in efficacy studies. Examples of effectiveness outcomes include quality of life, hospitalizations, and the ability to work or function in social activities. These outcomes are more important to patients, family, and care providers than surrogate or intermediate measures such as scores based on psychometric scales. Beta blockers Page 9 of 122 Final Report Update 4 Drug Effectiveness Review Project Efficacy and effectiveness studies overlap. For example, a study might use very narrow inclusion criteria like an efficacy study, but, like an effectiveness study, might examine flexible dosing regimens, have a long follow-up period, and measure quality of life and functional outcomes. For this report we sought evidence about outcomes that are important to patients and would normally be considered appropriate for an effectiveness study. However, many of the studies that reported these outcomes were short-term and used strict inclusion criteria to select eligible patients. For these reasons, it is neither possible nor desirable to exclude evidence based on these characteristics. Labeling each study as an efficacy or effectiveness study, while convenient, is of limited value; it is more useful to consider whether the patient population, interventions, time frame, and outcomes are relevant to one’s practice, or, in the clinical setting, how relevant they are to a particular patient. Studies across the continuum from efficacy to effectiveness can be useful in comparing the clinical value of different drugs. Effectiveness studies are more applicable to practice, but efficacy studies are a useful scientific standard to determine whether the characteristics of different drugs are related to their effects on disease. An evidence report reviews the efficacy data thoroughly to ensure that decision-makers can assess the scope, quality, and relevance of the available data. This thoroughness is not intended to obscure the fact that efficacy data, no matter how much there is of it, may have limited applicability to practice. Clinicians can judge the relevance of the study results to their practice and should note where there are gaps in the available scientific information. Unfortunately, for many drugs, there are few or no effectiveness studies and many efficacy studies. As a result, clinicians must make decisions about treatment for many patients who would not have been included in controlled trials and for whom the effectiveness and tolerability of the different drugs are uncertain. An evidence report indicates whether or not there is evidence that drugs differ in their effects in various subgroups of patients, but it does not attempt to set a standard for how results of controlled trials should be applied to patients who would not have been eligible for them. With or without an evidence report, these are decisions that must be informed by clinical judgment. In the context of developing recommendations for practice, evidence reports are useful because they define the strengths and limits of the evidence, clarifying whether assertions about the value of the intervention are based on strong evidence from clinical studies. Judgment, reasoning, and applying one’s values under conditions of uncertainty must also play a role in decision making. Users of an evidence report must also keep in mind that not proven does not mean proven not; that is, if the evidence supporting an assertion is insufficient, it does not mean the assertion is not true. The quality of the evidence on effectiveness is a key component, but not the only component, in making decisions about clinical policies. Additional criteria include acceptability to physicians or patients, the potential for unrecognized harms, the applicability of the evidence to practice, and consideration of equity and justice. Scope and Key Questions The participating organizations of the Drug Effectiveness Review Project are responsible for ensuring that the scope of the review reflects the populations, drugs, and outcome measures of interest to their constituencies. Initially, the Oregon Evidence-based Practice Center wrote preliminary key questions, identifying the populations, interventions, and outcomes of interest, Beta blockers Page 10 of 122 Final Report Update 4 Drug Effectiveness Review Project and based on these, the eligibility criteria for studies. These were reviewed, revised, and approved by representatives of organizations participating in the Drug Effectiveness Review Project. The participating organizations approved the following key questions to guide this review. For adult patients with hypertension, angina, coronary artery bypass graft, recent myocardial infarction, heart failure, atrial arrhythmia, migraine or bleeding esophageal varices, do beta blocker drugs differ in effectiveness/efficacy? For adult patients with hypertension, angina, coronary artery bypass graft, recent myocardial infarction, heart failure, atrial arrhythmia, migraine prophylaxis or bleeding esophageal varices, do beta blocker drugs differ in harms? Are there subgroups of patients based on demographics (age, racial groups, gender), other medications (drug-drug interactions), or co- morbidities (drug-disease interactions) for which one beta blocker is more effective or associated with fewer adverse effects? This review includes beta blockers that are available in the United States in an oral form and are indicated for hypertension. We excluded esmolol, an ultra-short acting beta blocker available only in intravenous form. Esmolol is used primarily as an antiarrhythmic drug for intraoperative and other acute arrhythmias. We also excluded sotalol, a nonselective beta blocker with Class III antiarrhythmic activity that is used exclusively for arrhythmias. Beta blockers that are unavailable in the United States are bopindolol, bucindolol, medroxalol, and oxprenolol. METHODS To identify relevant citations, we searched Ovid MEDLINE (1966 to January Week 4 2009), the Cochrane Database of Systematic Reviews (Second Quarter 2008), Database of Abstracts of Reviews of Effects (Third Quarter 2008) and the Cochrane Central Register of Controlled Trials (Third Quarter 2008), using terms for included drugs, indications, and study designs (see Appendix B for complete search strategies). In addition, pharmaceutical manufacturers were invited to submit dossiers, including citations, using a protocol issued by the Center for Evidence-based Policy (available at: http://www. Study Selection One reviewer assessed all citations and selected full articles for inclusion, with consultation from a second reviewer where necessary. We included English-language reports of studies of the patient populations and efficacy outcomes listed in Table 3. For studies of hypertension, we excluded studies in which blood Beta blockers Page 11 of 122 Final Report Update 4 Drug Effectiveness Review Project pressure lowering was the only endpoint; most of these studies sought to identify equivalent doses of beta blockers rather than differences in clinical effectiveness. Instead, we sought evidence of long-term effects on mortality, cardiovascular events, and quality of life. We only included studies in stable angina patients with duration of 2 months or longer. We only included studies of long-term treatment in post-coronary artery bypass graft patients, excluding studies of the short-term use of beta blockers to suppress atrial arrhythmias. With regard to placebo- controlled trials of recent myocardial infarction or heart failure, we only included studies with sample sizes of 100 patients or more. Cardiovascular events (stroke, myocardial infarction, or development of heart failure) Hypertension 3. End-stage renal disease (including dialysis or need for transplantation) or clinically significant and permanent deterioration of renal function (increase in serum creatinine or decrease in creatinine clearance) 4.

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For example discount gasex 100caps with visa chronic gastritis foods to eat, a study might use very narrow inclusion criteria like an efficacy study purchase genuine gasex line gastritis attack diet, but purchase gasex with amex gastritis pain treatment, like an effectiveness study, might examine flexible dosing regimens, have a long follow-up period, and measure quality of life and functional outcomes. For this report we sought evidence about outcomes that are important to patients and would normally be considered appropriate for an effectiveness study. However, many of the studies that reported these outcomes were short-term and used strict inclusion criteria to select eligible patients. For these reasons, it is neither possible nor desirable to exclude evidence based on these characteristics. Labeling each study as an efficacy or effectiveness study, while convenient, is of limited value; it is more useful to consider whether the patient population, interventions, time frame, and outcomes are relevant to one’s practice, or, in the clinical setting, how relevant they are to a particular patient. Studies across the continuum from efficacy to effectiveness can be useful in comparing the clinical value of different drugs. Effectiveness studies are more applicable to practice, but efficacy studies are a useful scientific standard to determine whether the characteristics of different drugs are related to their effects on disease. An evidence report reviews the efficacy data thoroughly to ensure that decision-makers can assess the scope, quality, and relevance of the available data. This thoroughness is not intended to obscure the fact that efficacy data, no matter how much there is of it, may have limited applicability to practice. Clinicians can judge the relevance of the study results to their practice and should note where there are gaps in the available scientific information. Unfortunately, for many drugs, there are few or no effectiveness studies and many efficacy studies. As a result, clinicians must make decisions about treatment for many patients who would not have been included in controlled trials and for whom the effectiveness and tolerability of the different drugs are uncertain. An evidence report indicates whether or not there is evidence that drugs differ in their effects in various subgroups of patients, but it does not attempt to set a standard for how results of controlled trials should be applied to patients who would not have been eligible for them. With or without an evidence report, these are decisions that must be informed by clinical judgment. In the context of developing recommendations for practice, evidence reports are useful because they define the strengths and limits of the evidence, clarifying whether assertions about the value of the intervention are based on strong evidence from clinical studies. Judgment, reasoning, and applying one’s values under conditions of uncertainty must also play a role in decision making. Users of an evidence report must also Controller medications for asthma 19 of 369 Final Update 1 Report Drug Effectiveness Review Project keep in mind that not proven does not mean proven not; that is, if the evidence supporting an assertion is insufficient, it does not mean the assertion is not true. The quality of the evidence on effectiveness is a key component, but not the only component, in making decisions about clinical policies. Additional criteria include acceptability to physicians or patients, the potential for unrecognized harms, the applicability of the evidence to practice, and consideration of equity and justice. Scope and Key Questions The purpose of this review is to assist healthcare providers, researchers and policy makers in making clinical decisions, creating formularies, and developing policies regarding long-term asthma control medications based on the most current available literature. We compare the efficacy, effectiveness, and tolerability of controller medications used in the treatment of persistent asthma as well as look for subgroups that may differ in these areas. The Research Triangle Institute International-University of North Carolina Evidence-based Practice Center (RTI-UNC EPC) wrote preliminary key questions, identifying the populations, interventions, and outcomes of interest, and based on these, the eligibility criteria for studies. These were reviewed and revised by representatives of organizations participating in the Drug Effectiveness Review Project (DERP) along with the RTI-UNC EPC, after considering comments received from the public which derived from a draft version posted to the DERP web site. The participating organizations of DERP are responsible for ensuring that the scope of the review reflects the populations, drugs, and outcome measures of interest to both clinicians and patients. The participating organizations approved the following key questions to guide this review: 1. What is the comparative efficacy and effectiveness of controller medications used to treat outpatients with persistent asthma? What is the comparative tolerability and frequency of adverse events for controller medications used to treat outpatients with persistent asthma? Are there subgroups of these patients based on demographics (age, racial groups, gender), asthma severity, comorbidities (drug-disease interactions, including obesity), other medications (drug-drug interactions), smoking status, genetics, or pregnancy for which asthma controller medications differ in efficacy, effectiveness, or frequency of adverse events? Inclusion Criteria This review includes pediatric or adult outpatients with persistent asthma being treated with any of the following agents: inhaled corticosteroids (beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone propionate, triamcinolone, mometasone), Long-Acting Beta-2 Agonists (formoterol, arformoterol, salmeterol), leukotriene modifiers (montelukast, zafirlukast, zileuton), anti-IgE therapy (omalizumab), combination products (fluticasone propionate/salmeterol xinafoate, budesonide/formoterol), or tiotropium. For efficacy and effectiveness outcomes of interest we included randomized controlled trials of at least 6 weeks duration and a sample size of at least 40 which evaluate control of symptoms, functional capacity and quality of life, urgent Controller medications for asthma 20 of 369 Final Update 1 Report Drug Effectiveness Review Project care services, adherence, hospitalization, or mortality. For adverse events outcomes, we also included observational studies of at least 6 months duration and a sample size of at least 100 (Table 4). Further details related to inclusion criteria are provided below in the Methods section under Study Selection. Boxed warnings associated with these products are provided in Appendix 1 C. Dosing equivalency of the agents was based on the 2007 NAEPP Expert Panel publication. A comparison of labeled and delivered doses for inhalers is provided in Appendix D. Outcome measures and study eligibility criteria Outcome Outcome measures Study eligibility criteria • Asthma control - Asthma exacerbations • Randomized controlled clinical trials - Days/nights frequency of symptoms of at least 6 weeks duration and n ≥ - Frequency of rescue medication use 40 or quality systematic reviews - Courses of oral steroids • Quality of life • When sufficient evidence was not Efficacy / • Ability to participate in work, school, sports, or available for head-to-head trials within Effectiveness physical activity a specific diagnostic group we • Adherence evaluated placebo-controlled trials • Emergency department / urgent medical care visits • Hospitalization • Mortality • Overall adverse events reported • Randomized controlled clinical trials • Withdrawals due to adverse events of at least 6 weeks duration and n ≥ • Serious adverse events 40 • Specific adverse events including: - Growth • Observational studies of at least 6 Adverse - Bone mineral density months duration and n ≥ 100 Events/Safety - Osteoporosis/fractures - Ocular toxicity • When sufficient evidence was not - Suppression of HPA axis available for head-to-head trials within - Anaphylaxis a specific diagnostic group, we - Death evaluated placebo-controlled trials METHODS Literature Search ® To identify relevant citations, we searched MEDLINE , the Cochrane Database of Systematic ® ® Reviews , the Cochrane Central Register of Controlled Trials , and the International Pharmaceutical Abstracts (through September 2010), using terms for included drugs, indications, and study designs (see Appendix E for complete search strategies). We limited the electronic searches to “human” and “English language. In addition, we searched the FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER), the Canadian Agency for Drugs and Technology in Health, Controller medications for asthma 21 of 369 Final Update 1 Report Drug Effectiveness Review Project and the National Institute for Health and Clinical Excellence web sites for medical and statistical reviews, and technology assessments. Finally, we searched dossiers submitted by pharmaceutical companies for the current review. All citations were imported into an electronic database ® (Endnote v. Study Selection All citations were reviewed for inclusion using the criteria shown in Table 5. Two reviewers independently assessed titles and abstracts, where available, of citations identified from literature searches. If both reviewers agreed that the trial did not meet eligibility criteria, it was excluded. Full-text articles of potentially relevant citations were retrieved and again were assessed for inclusion by two reviewers. Results published only in abstract form and unpublished data were not included unless adequate details were available for quality assessment. Study inclusion criteria Populations • Adult or pediatric outpatients with persistent asthma 1 • Persistent asthma is defined using the NAEPP classification (see Table 1) Interventions/Treatments Inhaled corticosteroids: • Beclomethasone • Budesonide • Ciclesonide • Flunisolide • Fluticasone propionate • Triamcinolone • Mometasone Long-Acting Beta-2 Agonists (LABAs) • Formoterol • Arformoterol • Salmeterol Leukotriene modifiers • Montelukast • Zafirlukast • Zileuton Anti-IgE therapy • Omalizumab Combination products • Fluticasone propionate/Salmeterol xinafoate • Budesonide/formoterol Long-Acting Anticholinergics • Tiotropium Efficacy and effectiveness outcomes • Control of symptoms (e. Study inclusion criteria work/school/sports/physical activity, activity limitation, improved sleep/sleep disruption) • Urgent care services (Emergency department visits/urgent medical care visits) • Adherence • Hospitalization • Mortality Adverse events/safety outcomes • Overall adverse events • Withdrawals due to adverse events • Serious adverse events (e. Results from well-conducted, systematic reviews and head-to-head trials provide the strongest evidence to compare drugs with respect to effectiveness, efficacy, and adverse events; head-to-head trials were defined as those comparing one included treatment of interest (those listed in Table 5) with another treatment of interest. If sufficient evidence was available from head-to-head trials we did not examine placebo-controlled trials for general efficacy/effectiveness. If no head-to-head evidence was published, as was the case for omalizumab, we reviewed placebo-controlled trials. We did not include studies that compare step-down therapy for people with stable asthma, different doses of the same medication, or different delivery devices with the same medication unless there was another eligible comparator arm. We did not include studies evaluating adjustable dosing strategies.

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A double-blind comparison between a new multidose powder inhaler (Turbuhaler) and metered dose inhaler in children with asthma generic gasex 100caps with visa gastritis onions. Hultqvist C purchase gasex american express gastritis diet ?, Ahlstrom H discount 100 caps gasex with amex chronic gastritis gas, Kjellman NI, Malmqvist LA, Svenonius E. A 5 comparison between bricanyl turbuhaler and bricanyl dose aerosol (MDI) in children with asthma. Hypokalemia and salbutamol 6-DESIGN therapy in asthma. Supraventricular tachycardia after 6-DESIGN fenoterol inhalation: report of two cases. The effects of ipratropium bromide and 1 salbutamol on the isolated hyperinflation during symptomfree periods in asthmatic children. Asthma specific quality 6 of life scale in a study of salmeterol hydroxynaphthoate. Levalbuterol inhibits human airway 6-DESIGN smooth muscle cell proliferation: therapeutic implications in the management of asthma. Comparative dose-response 6 study of three anticholinergic agents and fenoterol using a metered dose inhaler in patients with chronic obstructive pulmonary disease. Quick-relief medications for asthma Page 94 of 113 Final Report Update 1 Drug Effectiveness Review Project Citation Exclusion Code Ikeda A, Nishimura K, Koyama H, et al. Comparison of the 6-POWDER bronchodilator effects of salbutamol delivered via a metered-dose inhaler with spacer, a dry-powder inhaler, and a jet nebulizer in patients with chronic obstructive pulmonary disease. Imhof E, Elsasser S, Karrer W, Grossenbacher M, Emmons R, 6 Perruchoud AP. Comparison of bronchodilator effects of fenoterol/ipratropium bromide and salbutamol in patients with chronic obstructive lung disease. SHORT Turbuhaler as reliever medication compared with terbutaline in moderate asthma. Terbutaline via pressurised metered 6-POWDER dose inhaled (P-MDI) and Turbuhaler in highly reactive asthmatic patients. A comparative trial of atrovent and 6 ventolin in chronic bronchitis. Broncholytic effect of salbutamol, 1 ventolin and berotec aerosols in bronchial asthma. Bronchodilator 2 intake and plasma levels on admission for severe acute asthma. Exacerbations of 5 asthma in patients on salmeterol. Comparison of albuterol and 6 isoproterenol aerosols in bronchial asthma. The debate on S-enantiomers of beta-agonists: tempest in a 5 teapot or gathering storm? Subsensitivity of beta 3 responses during therapy with a long-acting beta-2 preparation. Objective and 3 subjective tremor responses to oral beta 2 agents on first exposure. Relative bronchodilatory responsiveness attributable 6 to sympathetic and parasympathetic activity in bronchial asthma. Clinical experience with terbutaline sulphate and 6 ipratropium bromide in bronchial asthma. Quick-relief medications for asthma Page 95 of 113 Final Report Update 1 Drug Effectiveness Review Project Citation Exclusion Code Jiro M, et al. Evaluation of the Clinical Efficacy of Berotec Tablet 1 (Fenoterol Hydrobromide) in Patients with Bronchial Asthma. Turbuhaler (R): a new device for dry powder 6-POWDER terbutaline inhalation. A comparison of fenoterol (Berotec) and salbutamol (Ventolin. Juniper EF, Johnston PR, Borkhoff CM, Guyatt GH, Boulet LP, Haukioja 6-LONG VS. Quality of life in asthma clinical trials: comparison of salmeterol and salbutamol. SHORT quality of life in adults during an acute asthma exacerbation. SHORT formoterol have less systemic effects in asthmatic children 6-11 years- old than cumulative high doses of inhaled terbutaline. Kaplan AE, Stanbrook M, Travers A, Schiebel N, Rowe BH. Non- 5 selective beta agonists versus beta -agonists for acute asthma. Fenoterol by metered dose inhaler and delay of 5 steroid therapy. A multi-clinic double-blind trial of salbutamol in bronchial 3 asthma. Risk versus benefit considerations for the beta(2)-agonists. What is new with the beta -agonists: issues in the2 6 management of asthma. SHORT albuterol aerosol as maintenance therapy for asthma in adolescent and adult patients. SHORT salmeterol in asthmatic patients with 24-hour spirometry and Holter monitoring. Albuterol treatment for 6-POWDER children with asthma: a comparison of inhaled powder and aerosol. Kemp JP, Hill MR, Vaughan LM, Meltzer EO, Welch MJ, Ostrom NK. Clinical trial of metaproterenol aerosol in bronchial asthma. Quick-relief medications for asthma Page 96 of 113 Final Report Update 1 Drug Effectiveness Review Project Citation Exclusion Code Kesten S, Chapman KR, Broder I, et al. SHORT twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma. Effects of salmeterol on arterial blood gases in 6-LONG VS. SHORT patients with stable chronic obstructive pulmonary disease: Comparison with albuterol and ipratropium. Fenoterol inhalation powder and aerosol in the treatment of 6-POWDER asthma. Klusova EV, Semenovich NI, Polivanov EG, Pashkova TL. Berotek 1 treatment of bronchial asthma in combination with ischemic heart disease. A comparison of the effects of subcutaneous orciprenaline, 3 salbutamol and terbutaline in asthmatic children.

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This can occur when molecules are bound to the surface of the RBC cheap 100 caps gasex otc gastritis diet queen, leading to immunologic clearance; when microorganism- produced toxins damage the RBC membrane buy generic gasex 100caps gastritis definition wikipedia, leading to hemolysis; when previous crypt-antigens are exposed cheap 100caps gasex with amex gastritis diet plan foods, leading to accelerated removal; when microorganism-produced toxins alter RBC antigens to a different phenotype, or when microorganism suppression of erythropoiesis occurs due to specific binding to RBC precursors. Learning Objective There is rossetting of parasitized cells, with nonparasitized cells ● To understand the variety of infectious agents that affect leading to complement activation on the uninfected RBCs and RBCs directly or indirectly. Several uninfected RBCs are removed from the circulation for each parasite infected RBC, thus magnifying the extent of hemolysis. The osmotic fragility of Introduction nonparasitized cells is increased. Infected RBCs also develop some This chapter reviews the obvious infections in which microorgan- modified receptors binding to endothelial proteins, platelet glycopro- isms specifically enter the RBC and also addresses infectious teins, thrombospondin, intracellular adhesion molecule 1, and some situations in which the RBC may be altered or damaged secondarily vascular adhesion molecules. Litchman1 lists 39 infectious agents that cause hemolytic Infected cells also have a highly irregular surface and there is anemia. Some organisms invade the RBC and others damage the activation of hepatosplenic macrophages that increases RBC clear- RBC, causing premature clearance; cause hemolytic anemia from ance. There are changes on the surface of both parasitized and the hemolysins that they produce or by stimulating an immune nonparasitized RBCs that increase RBC recognition and thus response due to alterations of the RBC surface; stimulate antibodies phagocytosis. The loss of RBC deformity in the parasitized cells to RBC antigens; or deposit immune complexes, causing increased leads to shortened RBC survival. Because this discussion focuses on the RBC, the other IgG and complement on the RBC surface, which also increases diseases are not discussed in detail. RBCs as primary targets of infection (Table 1) Role of the Fy (Duffy) blood group antigens in malaria. Duffy Malaria antibodies are commonly encountered in routine blood banking Upon infection, malaria parasites multiply in hepatocytes and the and transfusion medicine. The Duffy system is composed of 6 engorged cells rupture, releasing merozoites into the circulation. This is a multistep process involving several different and disruption of chemokine gradients. Plasmodium falciparum, the most serious form of for P. In the absence of the malaria, uses multiple ligands, one of which involves the glyco- Duffy molecule, the parasites are not able to establish a junction phorins (GPs) A, B, and C. Therefore, individuals with the Duffy null phenotype receptor containing the Duffy antigen receptor for chemokines Fy(a,b) in which DARC is absent from RBCs, are resistant to (DARC). Low rates of parasitemia may have little frequency varies in different populations and, not surprisingly effect on causing anemia, whereas high rates in which 10% of the Fy(a,b) phenotype is very common, approaching 100% in RBCs are parasitized may cause significant hemolysis. Within the RBC, the parasites multiply, ultimately bursting the RBC Role of ABO blood group antigens in malaria. One of the and releasing more merozoites to invade other RBCs. The bursting adhesion domains, called Duffy-binding ligand, binds primarily to and release of parasite products coincides with the occurrence of the area on the RBC surface that contains the oligosaccharides of the symptoms of malaria. However, the degree of anemia may also be A and B blood group system. Whereas the Duffy blood group is greater than that suggested by the number of parasitized RBCs. Infectious agents with RBCs as targets Babesiosis RBCs as primary targets of infection Babesiosis is a tick-borne disease that is transmitted to humans Malaria by the bite of an infected tick, the host of which is usually the Fy (Duffy) blood group antigens deer mouse. The Babesia species are intraerythrocytic protozo- ABO blood group antigens ans that primarily infect wild and domestic animals, but occasion- Knops blood group ally infect humans. The most common human infecting species, Gerbich blood group especially in the United States, is Babesia microti. Babesia Babesiosis divergens occurs mostly in asplenic patients and often involves Bartonellosis (Oroya fever) severe hemolysis and a fulminant course. RBCs as secondary targets in infection What little is known about the interaction of Babesia with RBCs Alterations of the RBCs causing immunologic clearance 9 10 is from studies of Babesia bovis and B. The specific receptor on the human RBC Enzymatic exposure of previously cryptic antigens: polyagglutination for the B. The merozygotes attach to the RBC and invaginate the Other toxins membrane to form a vacuole, causing the RBC to be more rigid. Inhibition of RBC production This is due partly to the presence of the abnormal nondeformable Parvovirus B-19 parasite within the RBC, but also there is some alteration of the EBV RBC skeleton and membrane due to parasite-produced proteins. Acquired RBC antigens due to infectious agents Budding occurs, but the mode of exit of the parasite from the Acquired B antigen RBC is not known on a molecular level. However, because budding is asynchronous, massive hemolysis is unusual. The parasite delivers proteins that associate with the underside of the RBC P. These “sticky knobs” that bind A antigens on uninfected RBCs and poorly understood factors contribute to an adhesive effect of the rosettes of infected and uninfected RBCs. Rosetting is associated RBC and parasitized RBCs become abnormally adhesive, including with severe disease by clogging the microvasculature of key organs, to vascular endothelial cells. The exact role of surface adhesion especially the brain, leading to cerebral malaria. Nonparasitized molecules is not clear, but in the aggregate, these membrane RBCs are removed from the circulation along with parasitized abnormalities result in accelerated RBC splenic clearance. RBC RBCs by adherence to the vascular endothelium or to other RBCs. The accumulation distribution of ABO blood groups is highly statistically significantly of parasitized RBCs in the microvasculature leads to severe clinical different between individuals with severe versus mild malaria. Symptoms may be mild to severe, necessitating in malaria: Duffy involvement in parasite attachment to the RBC RBC transfusion or even exchange transfusion. Usually, 1%–10% surface and ABO with the subsequent pathophysiology of RBC of RBCs are parasitized, although this may be up to 80% in asplenic adhesion and thus the severity of the disease. Babesiosis is fatal in 6%–9% of reported patients, although may reach 42% in asplenic patients (12). The Knops system antigens are located on the Babesia infections are one of the major current issues in transfusion DR1 complement control protein. However, infected RBCs do not form deaths cannot be determined from the literature. Individuals with low expres- In 1865, a medical student named Carrion inoculated himself with sion of CD 35 show reduced rosetting when parasitized with P. Carrion developed a fatal hemolytic anemia that became known as bartonellosis or Oroya fever, caused Gerbich blood group. The Gerbich antigens are on GPC and by the agent Bartonella bacilliformis. Because GPs are involved with malaria adhesion, RBCs of the humans by the bite of the sandfly. After the bite, RBCs become Gerbich-negative phenotype are partially resistant to malaria infected with B.

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