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Case series3, 12-14 have reported lower mortality among patients diagnosed with TTP who had severe ADAMTS13 deficiency Table 4 ; . In the two studies3, 13 that distinguished patients who had idiopathic TTP from patients who had potential etiologies and associated conditions that could have contributed to their illness, the mortality rates were less in the patients with idiopathic TTP. These reports suggested that the high rates of mortality among patients who did not have severe ADAMTS13 deficiency may have been caused by other serious conditions, such as systemic infections. Among the four case series reporting mortality in patients with severe ADAMTS13 deficiency, 3, 12-14 overall mortality was 13% Table 4 ; . Among the 3 case series reporting relapses in patients with severe ADAMTS13 deficiency, the frequencies of relapse were 10 of 44 23% ; , 15 6 of 16 38% ; , 13 and 7 of 16 patients 44% ; 3 Table 4 ; . Zheng et al13 have reported a further distinction among patients with severe ADAMTS13 deficiency, between patients who had no demonstrable inhibitor at presentation and those patients who had a high titer of inhibitory activity. In patients with no demonstrable and
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Nine clearance Table 1 ; . Several volunteers had stable, preexisting medical conditions, including hypertension, hypothyroidism on hormone replacement, or non-insulin dependent diabetes. One 78-year-old male subject 17 ; had premature ventricular contractions on the screening electrocardiograph and was evaluated by 12-h continuous ambulatory electrocardiographic monitoring unifocal, 5 premature ventricular contractions per h ; prior to study entry. Intercurrent illness presumed unrelated to the study drug developed in several volunteers. One female subject 12 ; developed an acute purulent bronchitis on day 16 of the study that was associated with premature ventricular contractions. She was treated with oral antimicrobial agents. Another female subject 3 ; developed a lower urinary tract infection during the study, and she was treated with oral antimicrobial agents. A 78-year-old male subject 17 ; developed bleeding from prostatic varices on day 17 of the study after playing tennis. This condition resolved spontaneously. There were no recognized exacerbations of preexisting medical conditions. Adverse events and laboratory monitoring. Possible adverse drug effects were common but generally mild Table 2 ; . One 59-year-old female subject, who did not eat breakfast after the initial drug dose, developed severe nausea and vomiting after ingesting the first tablet. This condition lasted for 4 h more and necessitated the intravenous administration of fluids. This patient did not continue the study. Nine of the remaining 18 subjects reported mild, short-lived CNS symptoms, primarily anxiety or nervousness. Three persons reported gastrointestinal GI ; symptoms, one case of which occurred 5 days after the last dose and was presumed unrelated to the study. No age-related increases in the frequency of side effects were noted. In fact, a smaller portion of the oldest age group one of six ; compared with the youngest group five of seven ; reported CNS or GI complaints during drug administration. Analysis of pre- and poststudy values for serum electrolytes, renal and hepatic functions, complete blood counts, triglycerides, and cholesterol and routine urinalysis showed no clinically important changes over the course of this study. The mean poststudy triglyceride level 85.3 ; was significantly lower than the prestudy level 133.6 ; , probably because poststudy samples were drawn when the subjects were in the fasting state whereas the prestudy samples were taken randomly. A significant difference in hemoglobin values prestudy, 13.9 mg dl; poststudy, 13.3 mg dl ; and in erythrocyte count 4.5 x 106 mm3 and 4.3 x 106 mm3 for prestudy and poststudy, respectively ; was likely related to the phlebotomy of approximately 300 ml over the study period. Subject 17 began the study with an elevated absolute eosinophil count 492 mm3 ; , which increased to 924 mm3 at the end of the study. Electrocardiographic tracings taken before and again at the end of the dosing period showed no significant differences in PR, QRS, or QT intervals. Three subjects had apparently new poststudy electrocardiographic findings. One showed a persistent sinus arrhythmia, another developed minor left axis deviation, and the third had unifocal premature ventricular contractions. This last person subject 12 ; developed intercurrent bronchitis, and the ventricular arrhythmia resolved with resolution of the illness. Pharmacokinetics. The single- and multiple-dose pharmacokinetic parameters for the three groups are shown in Table 3. The values for any specific parameter did not differ markedly among the three groups Table 3 ; . Similarly, the and
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Traditionally, imaging was considered important solely as a means of excluding treatable causes of dementia. These conditions account for a small proportion of all causes of dementia with far more common causes being AD, VaD, DLB, and FTD [54]. Neuroimaging is now the most important ancillary investigation in the workup of dementia to aid in differential diagnosis and management decisions. Computed tomography Computed tomography CT ; is mostly used to exclude other illnesses that are potentially amenable to surgical ; treatment, e.g. tumours, haematomata, and hydrocephalus. The yield of such a procedure has been debated but probably lies somewhere between 1% and 10% and may even be lower [55, 56] II ; . Farina et al. performed CT in 513 patients referred to a memory clinic of whom 362 were found demented [57] II ; . In them 7.2% ; a potential reversible cause of dementia was detected. However, in none of the cases did CT reveal findings that had not been discovered clinically. Foster et al. carried out a systematic review on the use of CT scanning in dementia [58]. Comparing costs and outcome they concluded that scanning each patient under 65 years and treating only subdural haematomas would be the most cost-effective approach. Recently, Condefer [59] showed that in a memory clinic setting, routine CT impacted on diagnosis in 12% of cases and on management in 11% II ; , mainly because of the identification of vascular changes. Because Gifford et al. [60] showed that there is considerable uncertainty in the evidence underlying clinical prediction rules to identify which patients with dementia should undergo neuroimaging and application of these rules may miss patients with potentially reversible causes of dementia, it is generally felt that a structural imaging investigation in the evaluation of a patient suspected of dementia should be performed routinely. Magnetic resonance imaging Magnetic resonance imaging MRI ; may be used for the same reason as CT but has the ability to increase specificity to an already quite high sensitivity of the clinical diagnosis. Hippocampal atrophy in AD. Hippocampal atrophy is an early and specific marker of the AD process [6165] and
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Brown, AB, and Garber, AM. 1998 ; . The cost-effectiveness of three new technologies to enhance Pap testing. Chicago, Illinois: Blue Cross & Blue Shield Association Technology Evaluation Center. 3 ; Brown, AD, and Garber, AM Cost-effectiveness of 3 methods to enhance the sensitivity of papanicolaou testing. JAMA 281: 347-353, 1999 and 282: 1420, 1999. ; McCrory, DC, Matchar, DB, Bastian, L, Datta, S, Hasselblad, V, Hickey, J, Myers, E, Nanda, K. Evidence Report Technology Assessment: Evaluation of Cervical Cytology, Rockville, Maryland Agency for Health Care Policy and Research, 1999. 5 ; Nanda, K, McCrory, DC, Myers, ER, Bastian, LA, Hasselblad, V, HickeyJD, Matchar, DB. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities. A systematic review. Ann Int Med. 132: 810-819, 2000. ; Payne, N, Chilcott, J, & McGoogan, E. 2000 ; . Liquid-based cytology in cervical screening. A report by the School of Health and Related Research ScHARR ; , the University of Sheffield, for the NCCHTA on behalf of NICE, Sheffield, : ScHARR, University of Sheffield. 7 ; Broadstock, M. Effectiveness and cost-effectiveness of automated and semiautomated cervical screening devices: a systematic review. NZHTA report. Vol.3. Christchurch, New Zealand: Clearing House for Health Outcomes and Health Technology Assessment, 2000. 8 ; Hutchinson, ML, Berger, B.Clinical and Cost Implications of New Technologies for Cervical Cancer Screening: The Impact of Test Sensitivity. J Manag care 6: 766-780, 2000. ; Montz, FJ, Farber, FL, Bristow, RE, Cornelison, T. Impact of Increasing Papanicolaou Test Sensitvity and Compliance: A Modeled Cost and Outcomes Analaysis. Obstet Gynecol 9: 781-788, 2001. ; Melamed, MR, Hutchinson, ML, Kaufman, EA, Schechter, CB. Evaluation of Costs and benefits of Advances in Cytologic Technology. IAC Task Force Summary. Acta Cytol 42: 6975, 1998. ; Laupacis, A, Feeny, D, Detssky, AS, Tugwell, PX. How attractive does a new technology have to be to warrant adoption and utilization? tentative guidelines for using clinical and economic evaluations. Can Med Assoc J 146: 473-481, 1992. ; Brown, A, Raab, S, Suba, EJ, Wright, GK. Cost-effectiveness Studies on Cervical Cancer. Acta Cytol 45: 509-514, 2001. ; Solomon, D, Schiffman, M, Tarone, R. Comparison of Three management Strategies for Patients with Atypical Squamous Cells of Undetermined Significance: Baseline Results from a Randomized trial. J Natl Cancer Inst 93: 293-299. 2001. ; Berenstein, SJ, Sanchez-Ramios, L, Nduhisi, B. Liquid-based cervical cytologic smear study and conventional Papanicolaou smears: A metaanalysis of prospective studies comparing cytologic diagnosis and sample adequacy. J Obstet Gynecol 185: 308-317, 2001.
1. Not all dose forms are listed. Higher doses, not generally or widely used in children, are not represented. 2. BG indicates that the drug is a "branded generic, " a medicine that is generic but given a special name by its maker for marketing purposes. 3. As typically prescribed but dosing varies with these drugs. 4. Monthly costs reflect national average retail prices for December 2005, rounded to the nearest dollar. Information derived by Consumer Reports Best Buy Drugs from data provided by Wolters Kluwer Health, Pharmaceutical Audit Suite and
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