Encephalopathy screening

Population PK screening in Phase II and Phase III is useful in assessing the impact of altered hepatic function (as a covariate) in PKs, if those patients are not excluded from Phase II and III trials, and if there is sufficient PK information collected about the patients to characterize them reasonably well. If a population PK approach is used, patients in Phase II and III studies are assessed for encephalopathy, ascites, serum bilirubin, serum albumin, and prothrombin time (which are components of the Child-Pugh score) or a similar group of measures of hepatic function. The population PK study, then, would include the following features ... 

Albumin (human) Epoetin alfa contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. No cases of transmission of viral diseases or Creutzfeldt-Jakob disease have ever been identified for albumin. Anemia Not intended for CRF patients who require correction of severe anemia epoetin alfa may obviate the need for maintenance transfusions but is not a substitute for emergency transfusion. Not indicated for treatment of anemia in HIV-infected patients or cancer patients due to other factors such as iron or folate deficiencies, hemolysis, or Gl bleeding, which should be managed appropriately. Hypertension Up to 80% of patients with CRF have a history of hypertension. Do not treat patients with uncontrolled hypertension monitor blood pressure adequately before initiation of therapy. Hypertensive encephalopathy and seizures have occurred in patients with CRF treated with epoetin. 

A 6-year-old boy sustained pelvic injuries and a femoral fracture. The first anesthetic he received consisted of thiopental, suxamethonium, isoflurane, and nitrous oxide. He also received two units of blood. He subsequently underwent four halothane anesthetics over 6 weeks for dilatation of a urethral stricture. Two days after the last anesthetic he was noted to be jaundiced. He had a negative viral screen but was positive for antitrifluoroacetyl IgG antibodies. He developed fulminant hepatic failure with grade 2 hepatic encephalopathy and underwent an auxiliary Uver transplantation 24 days after his last exposure to halothane. He died of septicemia 18 days later. Both at autopsy and on a previous hepatobiliary scan he was noted to have had extensive native Uver regeneration. 

Neuropsychiatric rating scales provide specific information such as the rate of change and severity of cognitive decline or improvement. They are useful in situations in which repeated measurements of a patient s mental status are needed because they allow the clinician to determine response to an intervention (e.g., medication) in a more systematic manner. In addition, some cognitive function measures are useful screens for Alzheimer s and other dementias, cerebral infarction, and encephalitis or encephalopathies. A number of cognitive... 

A thorough nutrition-focused history and physical examination is the most valuable means of screening patients for vitamin deficiency or toxicity (Table 135-9). It is uncommon to see a single vitamin deficiency usually multiple vitamin deficiencies occur with general malnutrition. Single vitamin deficiencies do occur, however. Thiamine deficiency may result in lactic acidosis and encephalopathy, whereas pernicious anemia due to vitamin B12 deficiency has been reported with increasing frequency, especially in the elderly. Recently, the incidence of vitamin D deficiency has increased in children. Laboratory assessment may be useful to confirm the clinical suspicion of a deficiency state. The first indication of a deficiency is usually a fall in circulating serum concentrations of the vitamin or its coenzyme. 

Karp inski FE, Rieders F, Girsh LS Calcium disodium versenate in the therapy of lead encephalopathy. J Pediatr 42 687-699, 1953 Kirkconnell SC, Hicks LE Residual effects of lead poisoning on Denver Developmental Screening Test scores. J Abnorm Child Psychol 8 257-267, 1980 Kotok D Development of children with elevated blood lead levels a controlled study. J Pediatr 80 57-61, 1972... 

These biochemical and antiviral screening studies (10,12-16) suggest that FEAU should be more selective in its antiviral activity and thus offer less host toxicity. In vivo experiments in mice (10.13) show that both FMAU and FEAU are relatively nontoxic. However, FMAU is very nenrotoxic in dogs (lethal dose 2.5 mg/kg/day, i.v. x S), while preliminary studies on FEAU in dogs at 50 mg/kg/day x 10 show no encephalopathy (lethal dose 100 mg/kg/day x 10). As mentioned previously, FMAU exhibited dose-limiting CNS toxicity in patients with advanced cancer (2) at an intravenous dose of 0.8 mg/kg/day x 5. The toxicity of FEAU in humans is not known. 

Thanks to broad screening and increased awareness of lead poisoning and its causes, in only a small fraction of a percent of cases of lead poisoning—those with extremely high levels of lead (over 80—150 micrograms per deciliter)—does a child go into convulsions or a coma. Although this condition of lead encephalopathy, untreated, usually leads to death, since the 1950s medical treatment with chelation therapy has reduced the mortality rate to 1-2% in even these extremely rare cases. ... 

Sachs, 1974) indicated that the incidence of high lead exposure appeared to be falling. This was due to such factors as the changes in the population of the children being screened, increased awareness about lead neurotoxicity, and slum clearance programmes. Death from lead poisoning is now almost zero and encephalopathy is rare. This in turn has focussed attention on the subclinical effects of lead toxicity. 

In light of the difficulties in diagnosing subclinical forms of thiamine deficiency, all patients deemed at risk of encephalopathy should be screened for such possibility. However, there is no clear indicator for laboratory tests or criteria for preclinical thiamine deficiency diagnosis. Decreased TDP levels in blood of alcoholics correlated modestly with worsening of their memory performance (Table 33.2). This may result from large variations in individual susceptibility to low TDP levels. In addition, only 0.5% of the body s whole store of TDP is present in the blood and blood TDP may thus not reflect well its content in the brain and other tissues (Pitel et al. 2011). 

Hospitalized or screened children 100-150+ pg/dl PbB Developing brain injury (CNS) Acute/chronic encephalopathy with high mortality before chelation use Chisolm and Harrison (1956), NAS/ NRC(1972, 1980, 1993), USCDC (1978)... 

MacGregor, I. R. Screening assays for transmissible spongiform encephalopathies. Vox Sang (Suppl. 2) 3-6, 2004. 

---