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These adaptations The human body and the environment contain many micro- may protect them from normal body defense mechanisms and organisms cheap norvasc 10mg without a prescription high blood pressure medication valsartan, most of which live in a state of balance with the antimicrobial drugs generic 5mg norvasc amex blood pressure 8550. Drug-resistant bacterial strains can be human host and do not cause disease. Classifica- upset and infection occurs, characteristics of the infecting tions, normal microbial flora, and common pathogenic mi- microorganism(s) and the adequacy of host defense mech- croorganisms are described in the following sections. Conditions that impair defense mechanisms increase the incidence and severity of infections Classifications and impede recovery. In addition, use of antimicrobial drugs may lead to serious infections caused by drug-resistant micro- Bacteria are subclassified according to whether they are aer- organisms. Viruses are intracellular parasites that survive only in liv- ing tissues. They are officially classified according to their structures, but are more commonly described according to MICROORGANISMS AND INFECTIONS origin and the disorders or symptoms they produce. Human pathogens include adenoviruses, herpesviruses, and retro- In an infection, microorganisms initially attach to host cell re- viruses (see Chap. For example, Fungi are plant-like organisms that live as parasites on some bacteria have hair-like structures that attach them to living tissue or as saprophytes on decaying organic matter. Most microorganisms preferen- Approximately 50 species are pathogenic in humans (see tially attach themselves to particular body tissues. Detection of antigens uses The human body normally has areas that are sterile and areas features of culture and serology but reduces the time required that are colonized with microorganisms. Another technique to identify an organism in- body fluids and cavities, the lower respiratory tract (trachea, volves polymerase chain reaction (PCR), which can detect bronchi, lungs), much of the gastrointestinal (GI) and geni- whether DNA for a specific organism is present in a sample. Common Human Pathogens Normal skin flora includes staphylococci, streptococci, diphtheroids, and transient environmental organisms. The Common human pathogens are viruses, gram-positive entero- upper respiratory tract contains staphylococci, streptococci, cocci, streptococci and staphylococci, and gram-negative in- pneumococci, diphtheroids, and Hemophilus influenzae. The colon con- organisms are usually spread by direct contact with an infected tains Escherichia coli, Klebsiella, Enterobacter, Proteus, person or contaminated hands, food, water, or objects. Pseudomonas, Bacteroides, clostridia, lactobacilli, strepto- Opportunistic microorganisms are usually normal en- cocci, and staphylococci. Microorganisms that are part of the dogenous or environmental flora and nonpathogenic. They normal flora and nonpathogenic in one area of the body may become pathogens, however, in hosts whose defense mecha- be pathogenic in other parts of the body; for example, E. Opportunistic infections are likely to often cause urinary tract infections. Opportunistic bacterial infections, often tential pathogens to establish residence and proliferate. If the caused by drug-resistant microorganisms, are usually serious normal flora is suppressed by antimicrobial drug therapy, po- and may be life threatening. Viral An antibacterial drug may destroy the normal bacterial flora infections may cause fatal pneumonia in people with renal or without affecting the fungal organism. Much of the normal flora can cause disease under certain conditions, especially in Community-Acquired Versus elderly, debilitated, or immunosuppressed people. Normal Nosocomial Infections bowel flora also synthesizes vitamin K and vitamin B complex. Infections are often categorized as community acquired or hospital acquired (nosocomial). Because the microbial envi- Infectious Diseases ronments differ, the two types of infections often have dif- ferent etiologies and require different antimicrobial drugs. As Colonization involves the presence of normal microbial flora a general rule, community-acquired infections are less severe or transient environmental organisms that do not harm the and easier to treat. Infectious disease involves the presence of a pathogen vere and difficult to manage because they often result from plus clinical signs and symptoms indicative of an infection.

Os- BE purchase norvasc 2.5 mg visa blood pressure elevated, Redlund-Johnell I buy 5 mg norvasc overnight delivery hypertension history, Johnell O porosis: four-year results from a ran- teoporos Int 9:296–306 (2003) Prevalent vertebral deformities domized clinical trial. Galante J, Rostoker W, Ray RD predict increased mortality and in- crinol Metab 87:3609–3617 (1970) Physical properties of trabecu- creased fracture rate in both men and 21. Calcif Tis Res 5:236–246 women: a 10-year population-based MORE trial: multiple outcomes for 31. Gardner MJ, Flik KR, Mooar P, Lane study of 598 individuals from the raloxifene evaluation – breast cancer JM (2002) Improvement in the under- Swedish cohort in the European Ver- as a secondary end point: implications treatment of osteoporosis following tebral Osteoporosis Study. Gass R (2001) The early preclinical SN, van den Kroonenberg A, Court- once-yearly increases bone mineral diagnosis of osteoporosis measuring ney A, McMahon T (1996) Etiology density – implications for osteoporo- the pure trabecular bone density. Ensrud KE, Thompson DE, Cauley hoof J, Declerck K, Raus JN (2002) fenbuttel BH (2002) Intravenous JA, et al (2000) Prevalent vertebral The relationship among history of pamidronate compared with oral alen- deformities predict mortality and hos- falls, osteoporosis, and fractures in dronate for the treatment of post- pitalization in older women with low postmenopausal women. Fracture Intervention Trial Med Rehabil 83:903–906 60:315–319 Research Group. Holzer G, Majeska RJ, Lundy MW, 48:241–249 PJ, Abou-Samra AB (1999) Charac- Hartke JR, Einhorn TA (1999) terization of an element within the rat Parathyroid hormone enhances frac- parathyroid hormone/parathyroid hor- ture healing. Nakajima A, Shimoji N, Shiomi K, C, Garcia-Ocana A, Stewart AF M, Lane JM (2003) Six minute walk et al (2002) Mechanisms for the en- (2003) Short-term, high-dose parathy- test: a new powerful predictor of hancement of fracture healing in rats roid hormone-related protein as a functional dysfunction in osteoporotic treated with intermittent low-dose hu- skeletal anabolic agent for the treat- patients with and without vertebral man parathyroid hormone (1–34). J Bone Min Res J Bone Miner Res 17:2038–2047 J Clin Endocrinol Metab 88:569–575 (in press) 73. Lindsay R, Hart DM, Forrest C, Baird et al (2001) Effect of parathyroid hor- (1997) Peripheral QCT for the diag- C (1980) Prevention of spinal osteo- mone (1–34) on fractures and bone nosis of osteoporosis. Lindsay R, Silverman SL, Cooper C, Med 344:1434–1441 intermittent administration of parathy- Hanley DA, et al (2002) Risk of new 74. Neuner JM, Zimmer JK, Hamel MB roid hormone on fracture healing in vertebral fracture in the year follow- (2003) Diagnosis and treatment of os- ovariectomized rats. JAMA 17:285:320–323 teoporosis in patients with vertebral 23:1089–1094 62. Jalava T, Sarna S, Pylkkanen L, et al G, Braunstein E, Johnston CC (1997) Soc 51:483–491 (2003) Association between vertebral Effect of osteoarthritis in the lumbar 75. Nordin BE, Morris HA (1989) The fracture and increased mortality in os- spine and hip on bone mineral density calcium deficiency model for osteo- teoporotic patients. Jordan KM, Cooper C (2002) Epi- 7:564–569 Richards HK, Compston JE (2003) A demiology of osteoporosis Best Pract 63. Lofman O, Larsson L, Toss G (2000) prospective study of discordance in Res Clin Rheumatol 16:795–806 Bone mineral density in diagnosis of diagnosis of osteoporosis using spine 50. Kado DM, Duong T, Stone KL, En- osteoporosis: reference population, and proximal femur bone densitome- srud KE, et al (2003) Incident verte- definition of peak bone mass, and try. Osteoporos Int 14:13–18 bral fractures and mortality in older measured site determine prevalence. Osteo- J Clin Densitom 3:177–186 Urabe K, Sakai H, Iwamoto Y (2003) porosis Int 14:589–594 64. Looker AC, Johnston CC Jr, Wahner Expression of parathyroid hormone- 51. Kanis JA (2002) Diagnosis of osteo- HW, et al Prevalence of low femoral related peptide and insulin-like porosis and assessment of fracture bone density in older US women growth factor I during rat fracture risk. Luckey MM, Gilchrist N, Bone HG, (2000) Alendronate for the treatment (2001) The use of a surgical grade et al (2003) Therapeutic equivalence of osteoporosis in men. N Engl J Med calcium sulfate as a bone graft substi- of alendronate 35 milligrams once 343:604–610 tute: results of a multicenter trial. Osteoporosis prevention, diagnosis, Orthop 42–50 prevention of postmenopausal osteo- and therapy (2000) NIH Consensus 53. Obstet Gynecol 101:711–721 Statement 17:1–45 method of fall prevention in the el- 66. Orthop Nurs 17:27–29 (1996) Meta-analysis of how well (1997) Osteoclast activation: potent 54. Med- measures of bone density predict oc- inhibition by the bisphosphonate alen- ical prevention and treatment. Paganini-Hill A, Chao A, Ross RK, porosis: current modes of prevention Raspe H (1998) Health impact associ- Henderson BE (1991) Exercise and and treatment.

Example: cimetidine inhibits CYP 1A cheap norvasc 2.5mg otc hypertension headaches, 2C buy 5mg norvasc free shipping blood pressure chart for 80 year old woman, and 3A An interaction may occur between warfarin, a frequently drug-metabolizing enzymes in the liver and therefore used oral anticoagulant, and foods containing vitamin K. Be- interferes with the metabolism of many drugs (eg, ben- cause vitamin K antagonizes the action of warfarin, large zodiazepine antianxiety and hypnotic drugs, calcium amounts of spinach and other green leafy vegetables may off- channel blockers, tricyclic antidepressants, some anti- set the anticoagulant effects and predispose the person to dysrhythmics, beta blockers and antiseizure drugs, thromboembolic disorders. When these drugs are A third interaction occurs between tetracycline, an antibi- given concurrently with cimetidine, they are likely to otic, and dairy products, such as milk and cheese. Displacement of one drug from plasma protein-binding soluble, unabsorbable compound that is excreted in the feces. This increase occurs because the mole- Drug–Drug Interactions cules of the displaced drug, freed from their bound form, become pharmacologically active. The action of a drug may be increased or decreased by its in- Example: aspirin (an anti-inflammatory/analgesic/ teraction with another drug in the body. Most interactions antipyretic agent) + warfarin (an anticoagulant) → occur whenever the interacting drugs are present in the body; increased anticoagulant effect some, especially those affecting the absorption of oral drugs, occur when the interacting drugs are given at or near the Decreased Drug Effects same time. The basic cause of many drug–drug interactions Interactions in which drug effects are decreased are grouped is altered drug metabolism. Examples of such interactions are by the same enzymes may compete for enzyme binding sites as follows: and there may not be enough binding sites for two or more 1. Also, some drugs induce or inhibit the metabolism of given to antagonize the toxic effects of another drug. Protein binding is also the basis for some im- Example: naloxone (a narcotic antagonist) + mor- portant drug–drug interactions. A drug with a strong attrac- phine (a narcotic or opioid analgesic) → relief of opioid- tion to protein-binding sites may displace a less tightly bound induced respiratory depression. The displaced drug then becomes pharmacologically displace morphine molecules from their receptor sites on active, and the overall effect is the same as taking a larger nerve cells in the brain so that the morphine molecules dose of the displaced drug. Decreased intestinal absorption of oral drugs occurs when drugs combine to produce nonabsorbable com- Interactions that can increase the therapeutic or adverse ef- pounds. Additive effects occur when two drugs with similar (antacids) + oral tetracycline (an antibiotic) → binding pharmacologic actions are taken. Synergism or potentiation occurs when two drugs with tetracycline different sites or mechanisms of action produce greater 3. Activation of drug-metabolizing enzymes in the liver increases the metabolism rate of any drug metabo- lized primarily by that group of enzymes. Several drugs (eg, phenytoin, rifampin), ethanol, and cigarette How Can You Avoid This Medication Error? Beecher, a 76-year-old nursing home client, has just had a change in her antihypertension medications to felodipine 10 mg qd, (an anticoagulant) → decreased effects of warfarin a calcium channel blocker. Increased excretion occurs when urinary pH is changed her the tablet with a large glass of grapefruit juice and caution her and renal reabsorption is blocked. The sodium bicar- CHAPTER 2 BASIC CONCEPTS AND PROCESSES 19 bonate alkalinizes the urine, raising the number of bar- In general, people heavier than average need larger doses, pro- biturate ions in the renal filtrate. The ionized particles vided that their renal, hepatic, and cardiovascular functions are cannot pass easily through renal tubular membranes. Recommended doses for many drugs are listed in Therefore, less drug is reabsorbed into the blood and terms of grams or milligrams per kilogram of body weight. Genetic and Ethnic Characteristics Client-Related Variables Drugs are given to elicit certain responses that are relatively predictable for most drug recipients. When given the same Age drug in the same dose, however, some people experience in- adequate therapeutic effects, and others experience unusual The effects of age on drug action are most pronounced in or exaggerated effects, including increased toxicity. In children, drug action terindividual variations in drug response are often attributed depends largely on age and developmental stage. During to genetic or ethnic differences in drug pharmacokinetics or pregnancy, drugs cross the placenta and may harm the fetus. As a result, there is increased awareness Fetuses have no effective mechanisms for metabolizing or that genetic and ethnic characteristics are important factors eliminating drugs because their liver and kidney functions and that diverse groups must be included in clinical trials. For example, genes determine the types and Older infants (1 month to 1 year) reach approximately adult amounts of proteins produced in the body. When most drugs levels of protein binding and kidney function, but liver func- enter the body, they interact with proteins (eg, in plasma, tis- tion and the blood–brain barrier are still immature. Although the onset and enzymes in the liver and other organs) to be biotransformed duration of this period are unclear, a few studies have been and eliminated from the body.

Another study evaluated the rela- tionship of complication rates of carotid endarectomy to processes of care 50 The Healthcare Quality Book and reported findings similar to the original diabetes survey 10 mg norvasc heart attack cafe. Initial analy- sis showed that facilities with high complication rates likely had substan- dard processes of care buy 10mg norvasc visa arteria zigomatica. By repeating the study at the same location but at a different time, researchers found substantially different complication rates and concluded that the inability, in practice, to estimate complication rates at a high degree of precision is a fundamental difficulty for clinical policy making (Samsa et al. Physicians and administrators alike may challenge results they do not like on the grounds that they con- sider the data suspect because of collection errors or other inaccuracies. Patient socioeconomic status, age, gender, and ethnicity also influence physician profiles in medical prac- tice variation and analysis efforts (Franks and Fiscella 2002). Keys to Successful Implementation and Lessons Learned from Failures Despite the inherent appeal in improving quality, considerable limits and barriers to the successful implementation of quality improvement projects exist. These barriers are subject to or the result of variation in culture, infra- structure, and economic influences across an organization, and overcom- ing them requires a stable infrastructure, sustained funding, and the testing of sequential hypotheses as to how to improve care. Administrative and Physician Views Issues that must be addressed to implement quality improvements include organizational mind-set, administrative and physician worldviews, and patient knowledge and expectations. In one example in a primary care setting, screening for colorectal cancer improved steadily from 47 percent to 86 percent over a two-year period (Stroud, Felton, and Spreadbury 2003). This evolutionary change minimized the barriers of revolutionary change, especially physician and administrator push-back, as well as other personal issues that are difficult to identify and alter (Eisenberg 2002). Success in adjusting culture to embrace quality improvement requires a long view that is sympathetic to V ariation in Medical Practice and Implications for Quality 51 converting daily practice into an environment that adapts accordingly. Many decision makers expect immediate and significant results and are sensitive to short-term variation in results that might suggest the improvements are inappropriate or not cost effective. A monthly drop in screening rates, for example, could be viewed as an indication that the screening protocol is not working and should be modified or abandoned altogether to conserve scarce resources. Then again, the observed decrease could be random vari- ation and no cause for alarm or change (Wheeler 2000). Cultural tolerance to variation and change is a critical issue when considering successful fac- tors to implementing quality improvement efforts, and it can be addressed by systemic adjustments and educational and motivational interventions (Donabedian and Bashur 2003; Palmer, Donabedian, and Povar 1991). Physicians often think in terms of treating disease as it presents within each unique patient rather than in terms of population-based preventive care. As such, physician buy-in is critical to reducing undesired variation or creating new and successful clinical preventive services systems of care (Stroud, Felton, and Spreadbury 2003). The process includes training physi- cian champions and investing in them to serve as models, mentors, and motivators, and it reduces the risk of alienating the key participants in qual- ity improvement efforts. Patient Knowledge Patient education is equally subject to variation in quality of care. Increasingly patients are aware of the status of their healthcare providers in terms of national rankings, public revelations of quality successes (and failures), and participation in reimbursement schemes (e. Participation in public awareness efforts such as the CMS Public Domain program, which makes variation and processes of care measures available to the public (both consumers and researchers), is another opportunity to educate patients about a healthcare organization and its commitment to quality (CMS 2003b; Hibbard, Stockard, and Tisler 2003; Lamb et al. Organizational Mind-set Organizational infrastructure is an essential component in minimizing vari- ation, disseminating best practices, and supporting a research agenda asso- ciated with quality improvements. Electronic medical records (EMRs), computerized physician order entry systems, and clinical decision support 52 The Healthcare Quality Book tools may reduce errors, allow sharing of specific best practices across large organizations, and enable the widespread automated collection of data to support quality improvement research (Bates and Gawande 2003; Bero et al. Healthcare organizations therefore are addressing the challenge to articulate and implement a long- term strategy to employ EMR resources. Unfortunately, the economic implications of both short- and long-term infrastructure investments under- mine these efforts. Working in an environment that embraces short-term financial gain (in the form of either the quarterly report to stockholders or the report to the chairman of the board), physicians and hospital admin- istrators often face an outright disincentive to invest in an infrastructure that will improve compliance with best practices (Leatherman et al. Those same economic incentives may be effective in addressing vari- ation in healthcare by awarding financial bonuses to physicians and admin- istrators who meet quality targets or withholding bonuses from those who do not. This economic wake-up call makes it clear that future success within an organization is dependent on participating in quality improvement efforts, reducing undesirable variation in processes of care, and encourag- ing an environment conducive to quality research and improvement. The threshold for quality parameters is to meet or exceed 25 percent of the overall group performance from the previous year.