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By H. Asam. Thunderbird School of Global Management. 2018.

To maintain participants’ genetic privacy buy toradol 10mg mastercard best treatment for pain from shingles, researchers will de-identify both saliva samples and health assessment questionnaires toradol 10 mg on line joint pain treatment in ayurveda, encrypt the data, and store it in a secure database. In addition, researchers plan to use genetic variations identified in the study to improve their understanding of the genetics underlying diseases and the application of this genetic information for preventing, diagnosing, and treating diseases. Affymetrix will perform the genome scans, while Navigenics (now acquired by Life Technologies) will interpret the results and offer guidance on steps individuals can take to try to decrease health risks based on their personal genetic information. Personalized Predictive Medicine There has been an increasing emphasis on preventive medicine during the past decade and now predictive medicine is gaining popularity as an approach to improve healthcare in the future. Predictive medicine involves prediction of risk of disease in an individual and its personalized management. It is sometimes referred to as preemptive approach as it involves treat- ment before the disease develops. By the time most diseases are diagnosed, some damage is already done and in some situations it is irreparable. Moreover, chances cure of diseases such cancer would be anticipated to improve with this approach. Advances in molecular diagnostics, proteomics, and metabolomics are facilitating the development of tests for predictive medicine. The concept of predictive medi- cine is extended further to predict response of the disease to a particular therapeutic. A significant reduction in disease-related mortality as well as a reduction in costs can be expected if prevention and screening are focused on individuals at risk. In the pharmaceutical industry, predictive modeling of disease can be used to test efficacy of drugs before developing them. The following definition proposed: ‘Connected Health encompasses terms such as wireless, digi- tal, electronic, mobile, and tele-health and refers to a conceptual model for health management where devices, services or interventions are designed around the patient’s needs, and health related data is shared, in such a way that the patient can receive care in the most proactive and efficient manner possible’ (Caulfield and Donnelly 2013 ). Technological advances have made determination of genetic predisposition to disease possible and have gained wide use in medicine of developing personalized medicine. There is growing inter- est in the application of these genetic tests in predicting risk for complex genetic diseases as direct-to-consumer tests are increasingly becoming available and afford- able. Evolution of Medicine as a Driver for Personalized Therapy Markets There are no revolutions in medicine but evolution. This process has already been set in motion by the advent of the genomic era and will continue. Pharmacogenetics is increasingly driven by industrial researchers, partly because of their ready access to clinical trial data on which phar- macogenetic research can be carried out. The future generation of physicians in training should be learning about personalized medicine at their formative stage and the current restrictions about the participation of the commercial sector in this effort needs to be relaxed. The industry can maintain its lead in the use of modern communication tools, such as the Internet, to allow patients to provide samples for future research yet retain control of them in the light of future developments. Both industry and aca- demic researchers have a common goal in that both want to bring innovative solu- tions into clinical practice to improve health care. Universal Free E-Book Store Opportunities and Challenges of Personalized Medicine 701 Presymptomatic treatment Integrated healthcare Personalized medicine 2010-2015 Automated systems Rational therapies Bioinformatics Genetic screening Evolving medicine 2005-2010 Pharmacoproteomics Pharmacogenomics Pharmacogenetics Medicine in 2000-2005 beginning of 21st Molecular diagnostics century Empirical treatments © Jain PharmaBiotech Fig. Currently there are some reservations about the value of genetic testing in prediction of disease as there are multiple factors involved. It is currently being debated if it is worthwhile to continue with the multi-million dollar genomewide studies or to decode the entire genomes of individual patients. Although genomewide association studies have worked better and faster than expected, they have not explained as much of the genetic component of many Universal Free E-Book Store 702 24 Future of Personalized Medicine diseases and conditions as was anticipated, and suggestion has been made to turn more sharply toward the study of rare variants (Goldstein et al.

Hypokalemia and thrombocytosis can occur upon conversion of severe megaloblastic anemia to normal erythropoiesis with cyanocobalamin therapy toradol 10 mg online kingston hospital pain treatment center. Most folate is absorbed in the proximal portions of the small intestine and is transported to tissues bound to a plasma-binding protein buy generic toradol 10 mg line pain management utica. Folic acid requires reduction by dihydrofolate reductase to the active metabolite methyltetrahydrofolate. The cofactors of folic acid provide single carbon groups for transfer to various acceptors and are essential for the biosynthesis of purines and the pyrimidine deoxythymidylate. Catabolism and excretion of vitamin B9 is more rapid than that of vitamin B12; hepatic reserves are sufficient for only 1–3 months. Folic acid is used to correct dietary insufficiency (commonly observed in the elderly), as a supplement during pregnancy to decrease the risk of neural tube defects, during lactation, and in cases of rapid cell turnover, such as hemolytic anemia. Leucovorin may be used to reverse the effects of the folate antagonists (see Chapter 12) methotrexate, pyrimethamine, and trimethoprim. Hydroxyurea has been shown effective in reducing painful episodes by about 50%; the necessity of blood transfusions was also shown to be reduced. Hydroxyurea increases the production of fetal hemoglobin, which makes red cells resistant to sickling and reduces the expression of ad- hesion molecules such as L-selectin. The actions of pentoxifylline include increased erythrocyte flexibility and decreased blood viscosity. Myeloid growth factors are glycoproteins produced by many cells including fibroblasts, endo- thelial cells, macrophages, and immune cells that act to stimulate proliferation and differen- tiation of one or more myeloid lineage. Sargramostim is a recombinant protein essentially identical to the native protein. Its princi- pal action is to stimulate myelopoiesis in granulocyte–macrophage pathways as well as megakaryocytic and erythroid progenitor cells. Clinical uses (1) Reduce the duration of neutropenia and incidence of infection in patients receiving myelosuppressive chemotherapy or bone marrow transplantation (2) Mobilize peripheral blood progenitor cells prior to collection (3) For bone marrow graft failure c. Filgrastim is a recombinant protein that stimulates bone marrow production of neutrophils without increasing the number of basophils, eosinophils, or monocytes. Pegfilgrastin is filgrastin with a polypropylene glycol molecule added to the N-terminus. Its clinical uses are similar to those of sargramostim: reduction in the duration of neutrope- nia in patients on anticancer regimens and for patients with chronic severe neutropenia. It is used clinically to prevent severe chemotherapy-induced thrombocytopenia and to reduce the need for platelet transfusions following myelosuppressive chemotherapy for nonmyeloid malignancies. Commercial heparin contains 8–15 repeats of d-glycosamine-l-iduronic acid and d-glucosamine-d-glucu- ronic acid. Commercial preparations are derived from bovine lung or porcine intes- tinal extracts. The clotting factor is inactivated, and intact heparin is released and recycled in a catalytic man- ner. Pharmacologic properties (1) Heparin must be given parenterally (by slow infusion or deep subcutaneous injec- tion); it is not injected intramuscularly because of the potential for hematoma formation. The principal advantage of the low- molecular-weight heparins is a greater pharmacokinetic predictability that allows once- or twice-a-day subcutaneous dosing without the need for monitoring. Therapeutic uses (1) Heparin provides preoperative prophylaxis against deep vein thrombosis. Adverse effects (1) Bleeding is a common adverse effect, especially in older women. Chapter 7 Drugs Used in Anemia and Disorders of Hemostasis 181 (3) Heparin can cause hypersensitivity reactions, including chills, fever, urticaria, and anaphylaxis.

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The most common sites of involvement correspond to injection sites: the upper and lower extremities buy toradol 10mg on line pain treatment center baton rouge louisiana, the groin and antecubital fossa purchase toradol 10 mg mastercard back pain after treatment for uti, with the microbiology being monomicrobial or polymicrobial, involving S. Neutropenia is frequently associated with mucosal disruption, and the indigenous colonizing florae are responsible for most infections. Pathogens causing initial infections are usually bacterial, including both gram-positive and gram-negative organisms. Pathogens causing subsequent infections are usually antibiotic-resistant bacteria, yeast, or fungi. Acute disseminated candidiasis in neutropenic host can have an erythematous or hemorrhagic palpable rash, which is consistent with small vessel vasculitis (75). Primary cutaneous zygomycosis is seen with disruption of skin in immunocompromised patients and patients with burns or severe soft tissue trauma. It starts as erythema and induration of the skin at a puncture site and progresses to necrosis. In neutropenic patient’s local necrosis, tissue infarction, vessel invasion, and dissemination can occur (76,77). Patients with cellular immune deficiency are at increased risk of infection with Mycobacterium, which can manifest as cellulitis, painless nodules, necrotic ulcers, and abscesses. Histologically, consist of circum- scribed, lobular proliferation of capillaries lined with prominent large endothelial cells. Cutaneous Cryptococcus infection can appear as papules, nodules, pustules, or necrotic ulcers. Cutaneous manifestation of acute disseminated histoplasmosis are rare, and they appear as nonspecific maculopapular eruptions that may become hemorrhagic. Varicella zoster virus can cause dissemination complicated by secondary bacterial and fungal super infection. Skin and soft tissue infection can rarely be infected by parasites (Strongyloides stercoralis, Sarcoptes scabiei, Acanthamoeba sp. Biopsy and culture of suspicious lesions frequently are necessary to diagnose these pathogens. Ecthyma Gangrenosum Ecthyma gangrenosum is the classic skin lesion associated with P. Neutropenic patients with overwhelming septicemia develop a patchy dermal and subcuta- neous necrosis. The characteristic skin lesion starts with erythematous macular eruptions that become bullous with central ulceration and necrosis. These are usually multiple occurring in different stages of development, which may concentrate on the extremities or the head and neck. Ecthyma gangrenosum is a cutaneous vasculitis caused by bacterial invasion of the media and adventitia of the vessel wall. Diagnosis of the etiological agent may occur with biopsy of the lesion being cultured or isolated from blood cultures. Implicated pathogen is usually the patient’s endogenous flora of patient’s skin, mucous membranes, or hollow viscera. Polymicrobial infections are often seen in clean-contaminated, contaminated or dirty wounds. Acute onset within 24 to 48 hours postoperatively or after trauma with systemic manifestation are usually due to Streptococcus and Clostridium sp. Antibiotic therapy can be guided by findings of Gram stain and wound cultures (13,39). It primarily affects neonates and young children; although adults with underlying diseases are also susceptible.

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Control Sample that is chemically & physically similar to unknown specimen & is tested in exactly the same manner discount toradol 10 mg on line pain treatment center colorado springs co. Internal monitoring systems Electronic quality 10 mg toradol acute chest pain treatment guidelines, internal, or procedural controls that are built into test system. If it occurs more than once in 20 successive runs, investigation must be carried out. Indicated by trend or shift on Levey-Jennings chart, or violation of 22S, 41S, or 10×Westgard rules (see following). If control is still out, look for & correct any problems, then Consider reagents (low, outdated, improperly stored, contaminated, run control. Evaluate all patient results in rejected run & since last run Ensure accuracy of reported results. Programmed into analyzer’s computer for use in calculating concentration of unknowns. Calibration verification Testing materials of known concentrations (calibrators, controls, proficiency testing samples, patient speci- mens with known values) to ensure accuracy of results throughout reportable range. Required every 6 months, when lot # of reagents changes, following preventive mainte- nance or repair, & when controls are out of range. Lab tests samples of known values (controls, calibrators, proficiency samples, previously tested patient speci- mens) to see how close results are to known value. How close results are when same Lab repeatedly tests same samples (on same day & sample is tested multiple times. Reportable range Range of values over which lab can verify accuracy Lab tests samples with known values at highest & of test system. Can vary for different If manufacturer’s or published reference ranges are patient populations (age, gender, race). Established used, lab must test specimens from normal subjects to by testing minimum of 120 healthy subjects & de- verify ranges. Analytical specificity Ability of method to measure only analyte it’s sup- Determined by manufacturer. Requires a minimum of 40 patient samples representing wide range of concen- trations. Reference values (existing method) are plotted onxaxis, values from new method onyaxis. Preventive maintenance Schedule of maintenance to keep equipment in peak operating condition. Maintenance must be documented & must follow manufacturer’s specifications & frequencies. Function checks Procedures specified by manufacturer to evaluate critical operating characteristics of test system, e. Must be within manufacturer’s established limits before patient testing is conducted. When limit is exceeded, must determine if due to medical change in patient or lab error. Critical values Test results that indicate a potentially life-threatening situation. Person receiving critical values must record & read back patient’s name & critical values. Pertinent literature references collection, labeling, storage, preservation, transporta- 13. System for entering results in patient record & report- tion, processing, referral & criteria for specimen ac- ing (including protocol for critical values) ceptability & rejection 14. Procedures for microscopic examinations, including detection of inadequately prepared slides 3.

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Their diet is rich in vegetables and soy foods purchase toradol 10 mg on-line fort collins pain treatment center, grains order toradol 10mg mastercard pain medication for dogs dosage, beans, small amounts of fruit, and minimal dairy products. The elders remain functionally healthy into their eighties, nineties, and one hundreds. On the oth- er hand, the younger generations of Okinawans in the same geo- graphic locations with the same genes are experiencing dramatic increases in obesity, diabetes, and cardiovascular diseases that can be directly traced to their consumption of highly processed and fast foods as a direct result of Western influence in the area. The sad part is that the Okinawan elders are dying out, and the younger Okinawan generations adopting the Western diet are dying young—many times before their long-living parents. American Diet Meat, poultry, eggs 3% 29% Calcium-rich foods 2% (dairy, seaweed) 23% (dairy) Vegetables 34% 16% Fruit 6% 20% Flavonoid foods (soy) 12% < 1% Grains 32% 11% Omega 3 foods 11% (fish) < 1% (fish) Note: Percentages by weight of a particular food. The Okinawa Program: How the World’s Longest-Lived People Achieve Everlasting Health— And How You Can Too. Each successful aging culture, in its geographic location, has foods that are high in antioxidant properties and rich in beneficial phytonutrients. For example, the Okinawans used to eat a lot of imo or sweet potato; it was the only thing that would grow dur- ing some very harsh times. As it turns out, imo has an excellent glycemic response (slow blood sugar absorption) and is very high in beta-carotene. They eat lots of antioxidant rich vegetables and a 10 high quantity of soy products rich in isoflavones. The long liv- ing Sardinians in Italy might use more tomato products contain- ing lycopene, fava beans rich in protein and fiber, milk and cheese containing the anti-inflammatory substance arzanol from goats grazing on the dwarf curry plant, or resveratrol in their homemade 11 red wine. Both cultures are getting powerful antioxidants and phytochemicals from their “local” foods that provide protection against chronic disease. That’s where the magic is: in the plants (or some animal products that eat the protective plant compounds). Also, it is the unique compound sur- rounded by known and unknown synergistic plant compounds, not the isolated substance, that creates the enhanced health benefits. That means that eating the whole food is far and away more effec- tive than simply popping a supplement extracted from some exotic super-food. The take-home point: a healthy diet is comprised of a variety of unrefined, local plant and vegetable foods and may or may not contain small amounts of animal foods. The Importance of Studying Modern Day Blue Zone Cultures While I think it is interesting and educational to study the dif- ferent dietary patterns from which we evolved (Simian, Paleolithic, Neolithic), I think it is considerably more important and urgent to study modern-day healthy aging population’s (Blue Zone) dietary (and lifestyle) patterns. These modern-day cultures have the same genetics as our evolutionary ancestors, but because they are living relatively free from chronic diseases and remain highly functional into their eighties, nineties, and one hundreds, the environment with which they “bathe” their genes—which includes the foods they eat, the physical activity they get, and their social interac- tions and mind-set—are critically important to learn from so we can solve our current healthcare crisis. If we wipe out chronic dis- eases, or delay them significantly, like many of these healthy aging cultures do, then we are going to go a long way in solving the U. They are living laboratories that can give us simple, doable solutions to our healthcare crisis. As mentioned in Chapter 6, my favorite books on this subject are The Blue Zone (2008), The Okinawa Program (2001), The Okinawa Diet Plan (2004), and Healthy at 100 (2007). This by itself would wipe out a large portion of chronic diseases—your grocery store would prob- ably be a fraction of its size if only whole, unprocessed foods were available (fruit, vegetables, beans, whole grains, nuts, seeds, eggs, fish, poultry, and meat; dairy products are not whole foods, in my opinion). Even if you did the opposite of what I recommend with re- gard to portions of food groups (more than half your food intake as vegetables and more than 90 percent plant foods), but still ate only whole unprocessed foods, the average American would do consid- erably better.

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