Pharmacogenetics of antipsychotic adverse effects: Case studies and a literature review for clinicians

There is a growing body of literature supporting the contribution of genetic variability to the mechanisms responsible for the adverse effects of antipsychotic medications particularly movement disorders and weight gain. Despite the current gap between research studies and the practical tools available to the clinician to identify such risks, it is hoped that in the foreseeable future, pharmacogenetics will become a critical aid to guide the development of personalized therapeutic regimes with fewer adverse effects. We provide a summary of two cases that are examples of using cytochrome P450 pharmacogenetics in an attempt to guide treatment in the context of recent literature concerning the role of pharmacogenetics in the manifestation of adverse effects of antipsychotic therapies. These examples and the review of recent literature on pharmacogenetics of antipsychotic adverse effects illustrate the potential for applying the principles of predictive, preventive, and personalized medicine to the therapy of psychotic disorders.     

Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

Social networks of residents in supportive housing

One goal of supportive housing is to enlarge and improve the functioning of the social support networks of residents. The networks of a convenience sample of 42 residents were assessed using scales developed by Barrera. The size of the networks (11.5) was no larger than that reported for similar clients living in other types of community settings but the composition differed. Staff and co-residents appear to partially replace rather than add to family and friends. This is of concern because friends are uniquely important determinants of satisfaction. An association between perceived need for support and network size was also found. These findings suggest some positive influences but also raise questions about unintended negative consequences of living in artificially constructed social environments.When this project was undertaken, Dr. Goering, Janet Durbin, Bill Lancee and Taras Babiak were all members of the Social and Community Psychiatry Section, Clarke Institute. Robert Foster was Executive Director of Regeneration House, Inc., where Susan Boyles is Assistant Executive Director.     

Causes of blindness in children attending four schools for the blind in Thailand and the Philippines

Using WHO definitions of visual loss and a standardised methodology, 256 children were examined in schools for the blind in Thailand (1 school) and the Philippines (3 schools). 244 (95%) were blind (BL) or severely visually impaired (SVI). Causes of SVI and blindness were classified anatomically and aetiologically, and avoidable causes identified. Causes of visual loss in Khon Kaen, Thailand (n = 65) and Manila, Philippines, (n = 113) were similar, with conditions of the whole globe accounting for 27.7 and 27.4% of SVI/BL; retinal disease 29.2 and 23.0%; cataract 16.9 and 16.8%; corneal disease 12.3 and 13.4%; and optic nerve disease and glaucoma 6.2 and 8.8%. Perinatal factors accounted for 20.0 and 23.0% of SVI/BL; hereditary disease 13.8 and 17.7%; and 12.3 and 15.0% was due to events occurring during childhood. The underlying aetiology could not be determined in 50.8 and 41.6% of cases, respectively. In the two schools together twenty six children (15%) were blind from retinopathy of prematurity (ROP) and 16 (9%) from corneal scarring attributed to Vitamin A deficiency. 103 of 178 (58%) children had avoidable causes of visual loss. In the Filipino towns of Baguio and Davao (n = 66), the causes of visual loss were different from those in Khon Kaen and Manila, with 54.8 and 42.9% of SVI/BL being due to corneal disease, and only 3.2 and 8.5% to retinal disease. Childhood factors were more important (61.3 and 57.1%) than hereditary (9.7 and 17.1%) or perinatal factors (0 and 2.9%). Thirty one children (47%) had SVI/BL attributed to Vitamin A deficiency. No child was blind from ROP. 42 of 66 (64%) of children had avoidable causes of blindness. Overall 60% of children with SVI/BL had avoidable causes of visual loss in these 4 schools. Approximately half could have been prevented by primary health and eye care services and half could have been managed by surgical ophthalmological procedures. The causes of blindness identified in this blind school study suggest that the major causes are different for schools serving rural populations compared to those serving urban communities. Different control strategies are required for the different situations.     

Nurses using physical restraints: Are the accused also the victims? – A study using focus group interviews

Background  

To date, the literature has provided an abundance of evidence on the adverse outcomes of restraint use on patients. Reportedly, nurses are often the personnel who initiate restraint use and attribute its use to ensuring the safety of the restrained and the others. A clinical trial using staff education and administrative input as the key components of a restraint reduction program was conducted in a rehabilitation setting to examine whether there were any significant differences in the prevalence of restraint use pre- and post-intervention. Subsequent to the implementation of the intervention program, focus group interviews were conducted to determine the perspective of the nursing staff on the use of restraints and their opinions of appropriate means to reduce their use.     

Correlates of well-being in mothers of children and adolescents with cystic fibrosis

Fifty mothers and 44 well siblings of children and adolescents with cystic fibrosis (CF) participated in this study to identify correlates of maternal well-being. Participants completed postal questionnaires which assessed maternal well-being, problems experienced surrounding the illness and treatment and the nature of the sibling relationship. Due to the demanding nature of treatment and the fact that CF is both genetic and incurable at present we anticipate mothers of these children will experience higher levels of stress and consequently poorer well-being than the normal population. In addition, illness severity, problems with adherence to treatment, child communication, maternal support and the sibling relationship are expected to relate to maternal well-being. Mothers in this sample did not rate their well-being as any different to the normal population. Results suggest that mothers are likely to rate their own well-being as poor when they report more frequent problems surrounding the illness and treatment and well children rate their sibling relationship as having frequent disagreements and aggression. This study highlights factors that are related to maternal well-being in families where one child has CF. These mothers as a group do not appear to be experiencing more stress in their daily lives than the normal population but certain illness and family variables are related to their well-being when examining the mothers on certain dimensions.     

Abnormal Digital Pressure Measurements in Diabetic Neuropathic Foot Ulceration

The diabetic neuropathic ulcer is typically slow to heal and recurrent. Macrovascular insufficiency is usually excluded as foot pulses are present and ankle:brachial pressure ratios are not decreased. These assessments cannot however exclude more distal vascular disease. Digital pressure measurements enable a reliable assessment of the distal peripheral vascular status to be made. The aim of this study was therefore to use toe pressures to assess the contribution of distal ischaemia in the pathogenesis of the neuropathic ulcer. Sixteen diabetic patients with recurrent neuropathic foot ulceration had their toe pressures compared to 10 neuropathic patients without a history of foot ulceration, 10 diabetic control subjects, and 11 normal subjects. Four non-diabetic patients with neuropathy and foot ulceration were also assessed. All subjects had ankle:brachial pressure indices ≧ 1. Toe pressure was assessed using laser Doppler flowmetry to record the return of skin blood flow. The toe:brachial pressure index (TBI) was then calculated. The diabetic patients with a history of recurrent neuropathic ulceration, had the lowest mean TBI, 0.63 ± 0.14 (SD), compared to the non-ulcerated diabetic neuropathy patients, the diabetic control subjects, and the normal subjects. 0.84 ± 0.11, 0.82 ± 0.1, and 0.81 ± 0.07, p < 0.01, respectively. Three of the four non-diabetic patients with neuropathic foot ulceration also had an abnormally low TBI. Reduced toe pressure measurements are thus found to be associated with neuropathic foot ulceration. The contribution of distal ischaemia in the pathogenesis of the diabetic neuropathic foot ulcer needs to be evaluated. One hundred and eight non-insulin-dependent diabetic patients who had been tested for autonomic dysfunction in 1984/85 were re-evaluated 5 years later. Autonomic function was assessed by means of four cardiovascular tests (heart rate variation during deep breathing and standing, and blood pressure variation after standing and sustained handgrip). Eighteen subjects were lost to follow-up; in the 90 patients who completed the study, both the deep breathing and the handgrip test significantly worsened (respectively from 13.7 ± 7.8 to 11.6 ± 6.3 beats min^?1 p < 0.01, and from 16.9 ± 8.2 to 12.7 ± 7.1 mmHg, p < 0.001), whereas both the 30:15 ratio and the variation of blood pressure on standing did not change. The impairment of a comprehensive evaluation score (from 2.5 ± 1.7 to 3.0 ± 1.5; p < 0.05) also confirmed the gradual deterioration of autonomic function over the study period.