Disease severity

In 1913, Goldberger demonstrated that pellagra was due to a dietary deficiency. Pellagra had been eadier described by Thiery, who had coined the term mal de la rosa for this disease. Several decades later, Elvehjem and co-workers isolated nicotinamide from a Hver extract and identified it as a peUagra-preventing factor (1). 

The typical U.S. daily diet contains 1.1—3.6 mg of vitamin B, most coming from meats and vegetables. Poor diets may provide less than half of these amounts and less than the RDA. Some populations require higher amounts persons with high protein intakes, pregnant and lactating women, users of oral contraceptives, alcohoHcs, users of dmgs which interfere with vitamin B function, and those afflicted with some diseases. Several reviews have examined the relationship of vitamin B and specific diseases in more detail (4,23). 

ROS, reactive oxygen species AHR, airway hyperresponsiveness MMP, matrix metalloprotease. Correlates with cough and chronic bronchitis. bNumber increases with disease severity. 

Those at risk of developing tuberculosis (eg, those with Hodgkin s disease, severe diabetes mellitus, leukemia, and other serious illnesses and those receiving corticosteroids or drug therapy for a malignancy)... 

The nitrates are used cautiously in patients witii severe hepatic or renal disease, severe head trauma, acute myocardial infarction (MI), hypotiiyroidism, and during pregnancy (Pregnancy Category C, except for amyl nitrate) or lactation. 

Compared with the standard health economic methodology applied in COI studies for other diseases (e.g. Keith and Shackleton 2006 Welte et al. 2000 Leidl et al. 1999 Henke et al. 1997 Xie et al. 1996), the quality of health economic analysis of HIV/AIDS is not always satisfactory as far as costs are concerned (Levy et al. 2006). Sometimes it is not clear whether researchers included both inpatient and outpatient medications in their analyses. Equally important, many of the early studies used costs and charges interchangeably data using charges may not accurately reflect true costs. Drummond and Davis (1988) also argued that there have been incorrect estimates of the survival times and costs in aU these early studies, since there were no explicit adjustments made for disease severity. 

An effective HE or cost-effectiveness analysis is designed to answer certain questions, such as Is the treatment effective What will it cost and How do the gains compare with the costs By combining answers to all of these questions, the technique helps decision makers weigh the factors, compare alternative treatments, and decide which treatments are most appropriate for specific situations. Typically, one chooses the option with the least cost per unit of measure gained the results are represented by the ratio of cost to effectiveness (C E). With this type of analysis, called a cost-effectiveness analysis (CEA), various disease end points that are affected by therapy (risk markers, disease severity, death) can be assessed by corresponding indexes of therapeutic outcome (mmHg blood pressure reduction, hospitalizations averted, life years saved, respectively). It is beyond the scope of this chapter to elaborate further on principles of cost-effectiveness analyses. A number of references are available for this purpose [11-13]. 

To be useful to those concerned with choices in the allocation of health and social care resources, the data for economic evaluations need to be timely, relevant, credible and accurate (Davies, 1998). As a minimum, the costs associated with the interventions should be estimated from activity data, which quantify resources used, and price or unit cost data. Often evidence from well-controlled prospective trials with high internal validity is required to establish whether differences in economic end points are directly attributable to the interventions. However, the economic evaluations of acetylcholinesterase inhibitors estimated costs from retrospective analysis of available datasets Qonsson et al, 1999b), analysis of published literature (e.g. Stewart et al, 1998) and expert opinion (e.g. O Brien et al, 1999 Neumann et al, 1999). This means that it is not clear whether differences in costs were due to the anticholinesterase inhibitors or to other factors such as availability of services in different areas, the living situation of the patient, or disease severity. 

Economic impact of Alzheimer s disease in the United Kingdom. Cost of care and disease severity for non-institutionalised patients with Alzheimer s disease. Br J Psychiatry 174, 51—5. 

Lentz MR, Westmoreland SV, Lee V, Ratal EM, Halpem EF, Gonzalez RG (2008) Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAlDS. Magn Reson Med 59(3) 475-484 Letendre SL, Lanier ER, McCutchan JA (1999) Cerebrospinal fluid beta chemokine concentrations in neurocognitively impaired individuals infected with human immunodeficiency virus type 1. J Infect Dis 180(2) 310-319... 

McCandless EE, Budde M, Lees JR, Dorsey D, Lyng E, Klein RS (2009) IL-IR signaling within the central nervous system regulates CXCL12 expression at the blood-brain barrier and disease severity during experimental autoimmune encephalomyehtis. J Immunol 183(l) 613-620 McEarland HE, Martin R (2007) Multiple sclerosis a complicated picture of autoimmunity. Nat Immunol 8 913-919... 

Schreiber K, Otura AB, Ryder LP, Madsen HO, Jorgensen OS, Svejgaard A, Sorensen PS (2002) Disease severity in Danish multiple sclerosis patients evaluated by MRI and three genetic... 

The incidence and severity of ROP both rise with decreasing birthweight and gestational age. Fielder et al. (1992) have shown that the incidence of ROP in infents of < 1700 g birthweight is about 50%, although only 5% had severe disease. Severe ROP results in vitreous haemorrhage from new vessel formation on the immature retina, retinal traction and eventually retinal detachment (Fig. 9.6). In the most severe cases, retinal detachment is complete, resulting in total blindness. Treatment with cryotherapy or laser has halved the incidence of retinal detachment. 

Enhanced TRPVl expression was demonstrated in IBD in man [17] and capsazepine was shown to attenuate disease severity in experimental colitis both in mice [145] and rats [146]. These findings confer a therapeutic potential for TRPVl antagonists in IBD and motility disorders [147, 148]. A related finding is the demonstration of increased TRPVl in the inflamed human oesophagus secondary to gastro-oesophageal reflux disorder [20]. 

Develop a specific evidence-based pharmacologic treatment plan for a patient with acute or chronic heart failure based on disease severity and symptoms. 

Blockers are contraindicated in patients with severe bradycardia (heart rate less than 50 beats per minute) or AV conduction defects in the absence of a pacemaker. (3-Blockers should be used with particular caution in combination with other agents that depress AV conduction (e.g., digoxin, verapamil, and diltiazem) because of increased risk for bradycardia and heart block. Relative contraindications include asthma, bronchospastic disease, severe depression, and peripheral vascular disease. (3,-Selective blockers are preferred in patients with asthma or chronic obstructive pulmonary... 

Asthma is also a significant economic burden in the United States, costing 12.7 billion in 1998 with direct medical expenditures accounting for 58% of the cost or approximately 7.4 billion.5 Hospital and emergency department care accounted for 45.1% of the direct medical expenditures, with prescription drugs and physician office visits accounting for 43.3% and 11.6%, respectively. Costs appear to increase with disease severity, and it has been suggested that fewer than 20% of asthma patients account for more than 80% of direct medical expenditures.5... 

In chronic asthma, classification of asthma severity is based on daytime and nighttime symptoms, physical activity, lung function (PEF or FEVfi, PEF variability, and reliever medication use. Because lung function is difficult to measure in preschool children (children 5 years of age or younger), it cannot be used to classify disease severity in this age group. Chronic asthma is classified as mild intermittent asthma, or mild, moderate or severe persistent asthma (Table 11-1). 

The intensity of pharmacologic therapy is based on the severity of the disease, and the least amount of medications necessary to meet the goals of asthma therapy should be used.1,3 Stepwise therapy for the treatment of chronic asthma based on disease severity is shown in Table 11—1. 

Use the patient s symptoms and pulmonary function tests to classify disease severity. 

Lastly, positive smoking status has been shown to have protective effects in UC, leading to reductions in disease severity. The opposite is true in CD, as smoking may lead to increases in symptoms or worsening of the disease.9... 

The pattern of inflammation in UC is continuous and confluent throughout the affected areas of the GI tract. The inflammation is also superficial and does not typically extend below the submucosal layer of the GI tract (Fig. 16-2). Ulceration or erosion of the GI mucosa may be present and varies with disease severity. The formation of crypt abscesses within the mucosal layers of the GI tract is characteristic of UC and may help to distinguish it from CD. Severe inflammation may also result in areas of hypertrophied GI mucosa, which may manifest as pseudopolyps within the colon.12 The inflammatory response may progress in severity, leading to mucosal friability and significant GI bleeding. 

Corticosteroids have potent anti-inflammatory properties and are used in active IBD to rapidly suppress inflammation. Corticosteroids have favorable effects in modulating several cell types involved in the inflammatory process.20,21 They may be administered systemically or delivered locally to the site of action by altering the drug formulation (Table 16-2). Because these drugs usually improve symptoms and disease severity rapidly, they should be restricted to short-term management of active disease. Long-term use of systemic corticosteroids is... 

Drug and dosing guidelines based on disease severity and location are presented in Table 16-4. 

Disease Severity and Location Active Disease Maintenance of Remission... 

Construct a drug treatment plan based on the disease severity and location. Identify potential contraindications or financial barriers to drug therapy. Inquire if the patient has an aversion to or inability to properly use certain drug formulations that you may wish to recommend, such as topical (rectal) products. 

The time frame the patient can expect improvement based on drug dose and disease severity... 

Findings on physical examination can assist in determining hydration status and disease severity. The presence of blood in... 

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