Non-responders

Flink HJ, Hansen BE, Heathcote EJ, Feinman SV, Simsek H, Karayalcin S, Mach T, Leemans WF, de Man RA, Verhey E, Schalm SW, Janssen HL (2006a) Successful treatment with pegjnter-feron alfa-2b of HBeAg-positive HBV non-responders to standard interferon or lamivudine. 

Course of Virus Load / Hours, Drug naive patients vs. Non responders BiLN 2061 ZW 200mg... 

Previously vaccinated Known responder Known non-responder Antibody response unknown No treatment HBIG x 1 and initiate HB revaccination or HBIG x 2 Test exposed person for anti-HBs (1) if adequate, no treatment (2) if inadequate, HBIG x 1 and vaccine booster No treatment No treatment No treatment No treatment If known high-risk source, treat as if source were HBsAg-positive Test exposed person for anti-HBs (1) if adequate, no treatment (2) if inadequate, vaccine booster and recheck titer in 1-2 months... 

Venlafaxine extended release, in doses of 75 to 225 mg/day, improves social anxiety, performance, and avoidance behavior with a reduction in disability.61 Treatment with venlafaxine results in response rates similar to those seen with paroxetine.60 Venlafaxine may be effective in SSRI non-responders.62 As with SSRIs, doses should be tapered slowly when discontinuing therapy. Tolerability is similar to that observed in depression trials with venlafaxine extended release. Common side effects are anorexia, dry mouth, nausea, insomnia, and sexual dysfunction. 

Evaluate patient response and devise alternative treatment regimens for non-responding... 

Stress-induced adrenal insufficiency complicates 9% to 24% of septic patients and is associated with increased mortality. Adrenal-insuffident patients are identified by a adrenocorticotropic hormone (ACTH) stimulation test. Patients are given 250 meg ACTH and a cortisol level is checked within 30 to 60 minutes. Responders are defined as a greater than 9-mcg/dL increase in cortisol and non-responders as a less than 9-mcg/dL increase in cortisol. Septic shock patients refractory to resuscitation and vasopressors, and with adrenal insufifidency (non-responders to the ACTH test) should be administered intravenous hydrocortisone 200 to 300 mg per day in three divided doses for 7 days.24,44... 

Shaikh etal. (1996) DRD3 (S9G) Clozapine sis genotype more frequent among non-responders. Schizophrenia Caucasian... 

In their next study, Mayberg and her colleagues scanned the brains of depressed patients who had responded positively to treatment for depression in a clinical trial of Prozac. The patients were scanned twice, once before the treatment had begun and once again after six weeks of treatment. About half of the patients responded positively to the treatment by showing at least a 50 per cent reduction in their symptoms the other half did not improve that much and were classified as non-responders. For the responders, but not for the non-responders, treatment of depression produced changes in brain activation in exactly the same areas in which normal sadness had produced changes, but in the opposite direction. In other words, successful treatment decreased brain activity in areas where sadness produces increased activity, and it increased brain activity in areas where sadness decreases it. 

Pattern Genotype Drug Responders Non-responders Odds ratio... 

Fig. 6.2 Hypothetical example of bimodal distribution according to a marker that indicates non-responder" or responder status. Note that in both cases a distribution is present, with overlaps, thus, the categorization into responders or non-responders based on the marker must be understood to convey only the probability to belong to one or the other group.

Both interindividual variations (responders and non-responders) and variable intraindividual temporal efficacy (short-term responders) for HbF expression may reflect the inherited differences in the metabolic pathways of the drug, in their targets, or in their adaptative mechanisms. These aspects remain to be clarified. 

The second IND vaccine, C-85, has been tested but not licensed for humans. It is prepared by formalin-inactivation of the TC-83 strain (see above). The vaccine is not used for the primary immunization, but rather to boost non-responders to TC-83. The required regimen for this vaccine is to administer 0.5 mL subcutaneously at two to four week intervals for up to three inoculations or until an antibody response is measured. Booster shots are required for the C-84 vaccine, and it does not protect rodents from an aerosol challenge. 

Babiloni, C., Cassetta, E., Dal Forno, G., et al. (2006) DonepezU effects on sources of cortical rhythms in mild Alzheimer s disease responders vs non-responders. Neuroimage, 31, 1650-1665. 

Before this molecular basis for differing response to drugs was understood, ultra-rapid metabolizers would have been thought of as non-responders to the drug - or accused, falsely, of failing to take their medication properly. 

Bourbeau, 1998 Budesonide 1.6 mg/d 6 months n = 19 No effect on lung function, quality of life, symptoms, or exercise capacity (only non-responder to oral steroids) No benefit... 

Burge PS, Calverly PMA, Daniels JE. The acute effect of oral prednisolone in patients with COPD in the ISOLDE trial responders and non-responders . Am J Respir Crit Care Med 1996 153 A126. 

Abdelmageed E, Fayed M, Sharaf M. Letrozole induction of ovulation in clomiphene citrate resistant polycystic ovary syndrome responders and non-responders. Middle East Fertility Soc J 2004 9 2. 

Probably the second most common data type is binary. Examples of binary data include cured/not cured, responder/non-responder, died/survived. Here the measure is based on a dichotomy. 

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