Carnitine palmitoyltransferase 1A (CPT1A) P479L prevalence in live newborns in Yukon,Northwest Territories,and Nunavut

Carnitine palmitoyltransferase 1A (CPT1A), encoded by the gene CPT1A, is the hepatic isoform of CPT1 and is a major regulatory point in long-chain fatty acid oxidation. CPT1A deficiency confers risk for hypoketotic hypoglycaemia, hepatic encephalopathy, seizures, and sudden unexpected death in infancy (SUDI). It remains controversial whether the CPT1A gene variant, c.1436C>T (p.P479L), identified in Inuit, First Nations, and Alaska Native infants, causes susceptibility to decompensation, in particular during times of fever and intercurrent illness. Although newborn screening for the P479L variant occurs in some jurisdictions, background knowledge about the presence of the variant in Canadian Aboriginal populations is lacking. In an effort to understand the population implications of the variant in northern Canada, overall frequencies of the variant were assessed. Further studies are underway to determine associated risk. Ethics approval was obtained from university REBs, local research institutes, and with consultation with territorial Aboriginal groups. Newborn screening blood spots from all infants born in 2006 in the three territories were genotyped for the p.P479L variant. p.P479L (c.1436C>T) allele frequencies in the three territories were 0.02, 0.08, and 0.77 in Yukon (n = 325), Northwest Territories (n = 564), and Nunavut (n = 695), respectively. Homozygosity rates were 0%, 3%, and 64%. Aboriginal status was available only in NWT, with allele frequencies of 0.04, 0.44, 0.00, and 0.01 for First Nations, Inuvialuit/Inuit, Métis, and non-Aboriginal populations. Although individual blood spots were not identified for Aboriginal ethnicity in Nunavut infants, ~ 90% of infants in Nunavut are born to Inuit women. The allele frequency and rate of homozygosity for the CPT1A P479L variant were high in Inuit and Inuvialuit who reside in northern coastal regions. The variant is present at a low frequency in First Nations populations, who reside in areas less coastal than the Inuit or Inuvialuit in the two western territories. The significance of the population and geographic distribution remains unclear, but the high population frequencies of the variant suggest a historically low penetrance for adverse outcomes. Further evidence is needed to determine if there is an increased risk for infant mortality and morbidity and whether newborn screening will be indicated on a population basis.     

Formative evaluation of a telemedicine model for delivering clinical neurophysiology services part I: Utility,technical performance and service provider perspective

Background

Formative evaluation is conducted in the early stages of system implementation to assess how it works in practice and to identify opportunities for improving technical and process performance. A formative evaluation of a teleneurophysiology service was conducted to examine its technical and sociological dimensions.

Methods

A teleneurophysiology service providing routine EEG investigation was established. Service use, technical performance and satisfaction of clinical neurophysiology personnel were assessed qualitatively and quantitatively. These were contrasted with a previously reported analysis of the need for teleneurophysiology, and examination of expectation and satisfaction with clinical neurophysiology services in Ireland. A preliminary cost-benefit analysis was also conducted.

Results

Over the course of 40 clinical sessions during 20 weeks, 142 EEG investigations were recorded and stored on a file server at a satellite centre which was 130 miles away from the host clinical neurophysiology department. Using a virtual private network, the EEGs were accessed by a consultant neurophysiologist at the host centre for interpretation. The model resulted in a 5-fold increase in access to EEG services as well as reducing average waiting times for investigation by a half. Technically the model worked well, although a temporary loss of virtual private network connectivity highlighted the need for clarity in terms of responsibility for troubleshooting and repair of equipment problems. Referral quality, communication between host and satellite centres, quality of EEG recordings, and ease of EEG review and reporting indicated that appropriate organisational processes were adopted by the service. Compared to traditional CN service delivery, the teleneurophysiology model resulted in a comparable unit cost per EEG.

Conclusion

Observations suggest that when traditional organisational boundaries are crossed challenges associated with the social dimension of service delivery may be amplified. Teleneurophysiology requires a governance and management that recognises its socio-technical nature.

     

Cardiac rehabilitation uptake following myocardial infarction: cross-sectional study in primary care

Background

Policies suggest that primary care should be more involved in delivering cardiac rehabilitation. However, there is a lack of information about what is known in primary care regarding patients’ invitation or attendance.

Aim

To determine, within primary care, how many patients are invited to and attend rehabilitation after myocardial infarction (MI), examine sociodemographic factors related to invitation, and compare quality of life between those who do and do not attend.

Design of study

Review of primary care paper and computer records; cross-sectional questionnaire.

Setting

Northern Ireland general practices (38); stratified sample, based on practice size and health board area.

Method

Patients, identified from primary care records, 12–16?weeks after a confirmed diagnosis of MI, were posted questionnaires, including a validated MacNew post-MI quality-of-life questionnaire. Practices returned anonymised data for non-responders.

Results

Information about rehabilitation was available for 332 of the 432 patients identified (76.9%): 162 (37.5%) returned questionnaires. Of the total sample, 54.4% (235/432) were invited and 37.0% (160/432) attended; of those invited, 68.1% (160/235) attended. Invited patients were younger than those not invited (mean age 63?years [standard deviation ﹛SD﹜ 16] versus 68.5?years [SD 16]); mean difference 5.5?years (95% confidence interval [CI] = 1.7 to 9.3). Among questionnaire responders, those who attended were younger and reported better emotional, physical, and social functioning than non-attenders (P = 0.01; mean differences 0.44 (95% CI = 0.11 to 0.77), 0.48 (95% CI = 0.10 to 0.85) and 0.54 (95% CI = 0.15 to 0.94) respectively).

Conclusion

Innovative strategies are needed to improve cardiac rehabilitation uptake, integration of hospital and primary care services, and healthcare professionals’ awareness of patients’ potential for health gain after MI.     

3D prostate model formation from non-parallel 2D ultrasound biopsy images

Biopsy of the prostate using 2D transrectal ultrasound (TRUS) guidance is the current gold standard for diagnosis of prostate cancer; however, the current procedure is limited by using 2D biopsy tools to target 3D biopsy locations. We propose a technique for patient-specific 3D prostate model reconstruction from a sparse collection of non-parallel 2D TRUS biopsy images. Our method conforms to the restrictions of current TRUS biopsy equipment and could be efficiently incorporated into current clinical biopsy procedures for needle guidance without the need for expensive hardware additions. In this paper, the model reconstruction technique is evaluated using simulated biopsy images from 3D TRUS prostate images of 10 biopsy patients. All reconstructed models are compared to their corresponding 3D manually segmented prostate models for evaluation of prostate volume accuracy and surface errors (both regional and global). The number of 2D TRUS biopsy images used for prostate modeling was varied to determine the optimal number of images necessary for accurate prostate surface estimation.     

Case managers' roles and functions: Commission for Case Manager Certification's 2004 Research, Part I

The Commission for Case Manager Certification (CCMC) conducted its third case managers' role and functions study in 2004. The purpose of this research was to validate the currency and relevancy of the certified case manager examination. The results of this study are shared in 2 parts of an article. Part I discusses the process the CCMC used for the development of the Case Manager's Role and Functions Survey Instrument (CMRFSI). The research leads to the identification of 6 new essential functions and 6 new knowledge areas, which describe case management practice. These findings were based on the survey of a large national sample of practicing case managers. Part II continues the analysis of the survey results and focuses on identifying the empirical activity and knowledge domains of case management practice, using factor analysis. It also discusses the similarities and differences found among various subgroups of case managers who were compared on the basis of certain demographic variables. In addition, it summarizes future changes in the field of case management as perceived by those who participated in the study.     

Genotyping of enteroaggregative Escherichia coli and identification of target genes for the detection of both typical and atypical strains

Enteroaggregative Escherichia coli (EAggEC) is an important cause of diarrhea worldwide, and there is a need for better detection methods in diagnostic laboratories. The aims of this study were i) to characterize strains of EAggEC by assigning each isolate a genotypic profile and (ii) to determine target genes for the detection of both typical and atypical EAggEC. The heterogeneity of the EAggEC group makes selection of a single target gene difficult. The plasmid-encoded genes, aat, aggR, and aap, are all appropriate targets for the detection of typical EAggEC. Of the chromosomally encoded genes, aaiA would be the most suitable target gene to identify typical and atypical EAggEC. The astA gene, encoding the enteroaggregative heat stable toxin, although not specific for EAggEC, may be used effectively in combination with other specific EAggEC genes. A polymerase chain reaction test based on the detection of characteristic EAggEC virulence genes, such as aat, astA, and aaiA, would improve EAggEC diagnosis.     

Childhood obesity: determinants, prevention, and treatment

The prevalence of child and adolescent obesity has increased dramatically in the last 20 years and has led to a rise in cardiovascular-related comorbidities, including type 2 diabetes, in children and youth. The American Heart Association (AHA) issued a scientific statement with available evidence and guidance for health professionals involved in the prevention and management of childhood obesity. The scientific statement was ranked as 1 of the Top 10 Research Advances of 2005 by the AHA. This article builds on the scientific statement, presents multilevel determinants, and emphasizes individual and population-based approaches to prevention. Treatment of child and youth obesity, along with the implications for nurses and other health professionals, is also included.     

The training and education of nurses working in stroke care

The National Clinical Guidelines for Stroke (2004) recommend that patients are cared for by staff who have expertise in stroke rehabilitation and access to relevant educational programmes. However, they provide only limited information as to the content and delivery of such programmes and recommend that such decisions are made at a local level. This must inevitably lead to the duplication of efforts and variations in standards and content across national services. This literature review hopes to identify how the content and delivery of educational programmes for nurses on stroke units meet the needs of their role, impact on their practice and influence patient outcomes. It is expected that the findings will be valuable in the development of ongoing training programmes and may contribute to a cohesive approach at national level.     

Identification of a novel HLA B*57 restricted cytotoxic T-lymphocyte epitope within HIV-1 rev

HLA-B5701 and its related allele B5703 have been shown to be strongly associated with slow HIV-1 disease progression. To elucidate the effect of these alleles fully on disease progression it is essential to identify key HIV-1 epitopes that are restricted by these alleles. Here we describe the identification of a novel HLA-B5701, B5703 restricted epitope within HIV-1 rev, which accounted for up to 25 and 40% of the total cytotoxic T-lymphocyte responses in two patients.     

A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy

BACKGROUND: Long-term antiretroviral therapy, while dramatically reducing HIV-related morbidity and mortality, is associated with metabolic and morphological changes. Peripheral fat loss, lipoatrophy, appears most associated with prolonged therapy with thymidine nucleoside analogues. METHODS: A randomized, open-label, comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate (DF) or abacavir in 105 individuals on successful antiretroviral therapy with clinically evident moderate to severe lipoatrophy. RESULTS: Individuals were randomized to tenofovir DF (52) or abacavir (53). The switch was well tolerated and the majority of patients completed 48 weeks of study. One individual in the tenofovir DF group and three in the abacavir group discontinued due to drug-related adverse events. Both groups similarly maintained virological control. Limb fat mass increased similarly in both groups: mean increases by week 48 of 329 and 483 g in tenofovir DF and abacavir groups, respectively [mean 95% confidence interval for difference, -154.3 (range -492.8 to 184.3)]. This change from baseline was statistically significant in both groups (tenofovir DF, P = 0.01; abacavir, P = 0.0001). Mean total cholesterol, low density lipoprotein cholesterol and triglycerides improved modestly with switching to tenofovir DF but were unchanged with abacavir. The changes in these parameters were significantly greater in the tenofovir DF arm relative to abacavir. CONCLUSIONS: Switching from a thymidine nucleoside analogue to either tenofovir DF or abacavir leads to significant improvement in limb fat mass over 48 weeks. Tenofovir DF may have modest advantages over abacavir for changes in lipids. Peripheral lipoatrophy, when clinically apparent, resolves slowly following treatment switching.