Aims and objectives. The aim of the study was to investigate the phenomenon of Advance Care Planning and the use of Advance Care Directives in residential aged care facilities in Australia. The ...objectives were to:
•
investigate the implementation process of Advance Care Planning and the use of Advance Care Directives;
•
investigate the outcomes of Advance Care Planning and experiences of people involved in Advance Care Planning and Advance Care Directives, including residents, families and nursing staff.
Background. Benefits of Advance Care Planning for older residents are considerable given their degenerative health‐breakdown and minimal chance of recovery. To date, the use of Advance Care Planning and Advance Care Directives is limited and models of service delivery and processes are needed to enhance best practice with Advance Care Planning and positive outcomes for older Australians.
Design. Case study.
Methods. The study conducted using multiple sources of evidence to enrich understanding of the phenomenon of Advance Care Planning. The researcher engaged in data collection over six months involving participant observation, field notes, semi‐structured interviews and document analysis. The findings contribute to the limited knowledge of options currently available to older adults and their families in their decision‐making about end‐of‐life care options.
Permission to conduct the study. Prior to commencement of the data collection, ethics clearances from the University of Newcastle and the regional Area Health Service were achieved. Permission to access the residential aged care facilities to undertake the study was obtained from the relevant residential aged care facility ethics committees or designated authorities. The researcher undertook several strategies to ensure all the ethical principles were considered and adhered to while conducting the project.
Results. The research identified the components and factors involved in the Advance Care Planning process and in attaining desired outcomes. The conceptual framework developed elaborates how Advance Care Planning should be implemented and what may constitute successful implementation of Advance Care Planning in residential aged care facilities. The four main elements (input, throughput, output, feedback), and 20 sub‐elements were requisites for nurses to initiate and implement the Advance Care Planning.
Conclusion. The essential components for end‐of‐life care are identified in the implementation processes of Advance Care Planning in residential aged care facilities. The study contributes to greater awareness of the processes needed for ‘dying well’ and highlights the need to explore experiences of ‘successful dying’ and the way nurses contribute to these events.
Relevance to clinical practice. The case study identified four determinative requisites for successful implementation of Advance Care Planning in aged care facilities: the expert nurse, discussion, education and involvement of a multidisciplinary team. Nurses should take these factors into account and use person‐centred approach in formalised processes to encourage participation in plans for end‐of‐life care.
Aim
Atrioventricular septal defect (AVSD) is widely accepted as the most common type of congenital heart defect in trisomy 21. Most of these studies, however, were conducted in Caucasian communities. ...The few Asian studies that had been conducted on this subject yielded different results. In the largest study of its kind in Asia, we described the distribution of types of congenital heart defects associated with trisomy 21 in Singapore.
Methods
Five hundred and eighty‐eight patients with trisomy 21 born in 1996–2010, and confirmed by karyotyping, were included in the study. The diagnosis of congenital heart defects were made on echocardiography. Variables extracted for analysis were demographics (race and gender) and the types of congenital heart defects. Except for complex cyanotic heart defects, haemodynamically significant lesions were accounted for separately in cases where more than one type of congenital heart defect coexisted in a patient.
Results
Ventricular septal defect (VSD) (39.2%) was the most common congenital heart defect associated with trisomy 21 in our study, followed by patent ductus arteriosus (34.3%), secundum atrial septal defect (23.4%) and AVSD (15.6%). This study validates previous smaller Asian studies identifying VSD as the most common cardiac lesion associated with trisomy 21. A high proportion (25.0%) of trisomy 21 patients with tetralogy of Fallot also had AVSDs. Coarctation of the aorta was uncommon.
Conclusion
VSD was the most common congenital heart defect seen in trisomy 21 in our study. A high proportion (25.0%) of trisomy 21 patients with tetralogy of Fallot also had AVSDs.
In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady ...state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) (p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio (p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration (p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.
Purpose Ultrarapid drug metabolism of antidepressants has been associated with therapeutic failures. The CYP2C19*17 allele has been associated with higher levels of CYP2C19 gene transcription and ...increased rates of omeprazole and mephenytoin metabolism. The aim of this study was to compare the impact of the CYP2C19*17 allele on omeprazole single-dose kinetics with escitalopram exposure at steady state in volunteers genotyped as either CYP2C19*17/*17 or CYP2C19*1/*1. Methods Sixteen healthy volunteers participated in both study parts, five homozygous for CYP2C19*17 and 11 homozygous for CYP2C19*1. Individual pharmacokinetic parameters were determined after single-dose omeprazole of 40 mg and after 1 week on escitalopram 5 mg b.i.d. Results Escitalopram area under the concentration time curve from zero to 12 h (AUC₀₋₁₂h) was 21% lower in homozygous carriers of CYP2C19*17 compared with CYP2C19*1 (p = 0.08). There was a significant correlation between escitalopram exposure at steady state and the single-dose kinetics of omeprazole (Spearman correlation coefficient of 0.67; p = 0.006). Conclusion Based on our investigation using two different CYP2C19 substrates, we concluded that a clinically significant difference in escitalopram or omeprazole kinetics between the genotypes appears unlikely.
Background:
People with dementia have different care and support needs at their end of life compared to people with other life-limiting illnesses, and general palliative care models may not meet the ...needs of people with dementia and their carers and families. Some dementia-specific end-of-life care models have been implemented, and a summary of existing models was undertaken to inform development of a local model.
Aim:
To identify best-practice models of care for people in the advanced and end stages of dementia, and their families and carers.
Design:
A rapid review with narrative summary of peer-reviewed articles and grey literature was conducted.
Data sources:
Ten databases were searched for articles published between January 2000 and April 2022. Inclusion criteria were: all care settings; AND the model focuses on people with end-stage or advanced dementia; AND contained multiple components.
Results:
Nineteen articles or reports, describing twelve dementia-specific models of end-of-life care in a range of care settings were identified for inclusion in the review. There is strong evidence that the principles of best practice palliative care for people with advanced dementia are well known, but limited examples of translation of this knowledge into integrated models of care. The key issues that emerged from the findings were: referral and admission to care, integration of care, sustainability and evaluation.
Conclusions:
Findings can be used to inform development of improved end-of-life care pathways for people with dementia, but well-designed research studies are needed to evaluate the effectiveness of integrated models of care for this vulnerable population.
Abstract Background There is ongoing interest in the possible interaction of the serotonin-transporter-linked polymorphic region (5-HTTLPR) with environmental factors in determining Major Depressive ...Disorder (MDD). The current study contributes to this research area by comprehensively examining the interaction-effects and direct-effects of 5-HTTLPR and five environmental factors on MDD prevalence and course in a well-characterized longitudinal sample. Methods The sample consisted of 1625 patients with a CIDI-confirmed diagnosis of MDD and 1698 screened controls from the Netherlands. Four MDD outcomes were studied as dependent variables: one main MDD prevalence-outcome (all MDD), two more severe MDD prevalence-outcomes (suicidal and chronic MDD), and one MDD course outcome (chronic versus non-chronic MDD). Because SNP rs25531 modifies the effect of 5-HTTLPR, haplotypes of 5-HTTLPR and rs25531 were measured. For the four MDD outcome measures, we examined the direct effects of 5-HTTLPR/rs25531-haplotypes, five environmental factors (lifetime and recent stressful life-events, sexual abuse, low educational attainment, and childhood trauma) and their interaction in logistic regression models. Results The environmental factors had large and consistent effects on all four MDD outcomes, including course of MDD. The 5-HTTLPR/rs25531-haplotype had a suggestive effect on course of MDD, but not on presence of MDD. Gene-by-environment interaction was significant (<0.05) for one of the 20 tests performed, which is not more than expected by chance. Limitations Environmental factors were not assessed before the onset of MDD. Conclusions Environmental factors had a strong impact on the presence and course of MDD, but no evidence for gene-by-environment interaction was found.
Previous studies have suggested that pain in older people with dementia is often underestimated and undertreated in acute hospitals. Undermanaged pain negatively affects a person's recovery and ...prolongs hospital stays. However, the issues related to pain assessment and management by nurses for this group have not been fully understood. (1) To synthesize evidence about pain assessment and management for older people with dementia in hospital settings, and (2) to discuss implications for nurses and their practice. Integrative literature review. A systematic search of evidence-based research from six electronic databases (CINAHL, MEDLINE, ProQuest, Cochrane, JBI, and Scopus) was conducted for the period of 2006-2016. Following Cooper's integrative review framework and a systematic screening process, the articles included were analyzed and synthesized to identify the common issues and relationships. Fourteen empirical research articles were examined and synthesized. Two main categories were identified and include: the nursing practice of pain assessment in older patients with dementia is less than optimal, and the nursing practice of pain management for this group varies. The lack of initiation of pain assessment and use of pain assessment tools may contribute to the inadequate pain management by nurses. Whereas this review uncovered the extent and challenges related to pain assessment and management, previous studies were explorative and descriptive. The findings from the review provide nurses with an opportunity to establish empirical evidence that may improve nursing practice of pain assessment and management for older people with dementia in hospital settings.
Previously, cytochrome P450 3A7 (CYP3A7), which constitutes the major CYP enzyme in fetal livers, has been considered a fetus-specific enzyme. However, CYP3A7 mRNA has recently been shown to be ...expressed at significant levels in a subset of adult human livers, several of which carry the CYP3A7*1C allele that contains the proximal PXR/CAR element of CYP3A4. The objective of this study was to investigate CYP3A7 expression at the protein level by developing a CYP3A7-specific antibody to allow its quantification. Based on results from 59 adult human liver samples, we found significant CYP3A7 protein expression in approximately one in 10 adult livers amounting for 24-90 pmol/mg microsomal protein, thereby contributing 9-36% to total CYP3A levels in these livers. CYP3A7 protein was detected in five of seven livers carrying the CYP3A7*1C allele (two of which only had trace amounts), whereas an additional three livers expressing CYP3A7 were apparently homozygous for CYP3A7*1. The mean protein expression level of CYP3A7 was 42 pmol/mg within the group of livers expressing CYP3A7 and 4 pmol/mg in all liver samples. CYP3A7 expression was thus higher than that of the polymorphically expressed CYP3A5 in adult human livers, based on a comparison with a previous study using our CYP3A5 peptide-specific antibody. The relatively high level of CYP3A7 protein expression detected in a subset of adult livers may be relevant with respect to the metabolism of exogenous and endogenous substrates, such as retinoic acid and dehydroepiandrosterone.
CYP2C19 is an important enzyme for human drug metabolism, and it also participates in the metabolism of endogenous substrates, whereas the CYP2C18 enzyme is not expressed in human liver despite high ...mRNA expression. Mice transgenic for the human CYP2C18 and CYP2C19 genes were generated. Quantitative mRNA analysis showed CYP2C18 and CYP2C19 transcripts in liver, kidneys, and heart to be expressed in a sexually dimorphic manner, with male mice having 2- to 100-fold higher levels. Transcript levels in the small intestine were somewhat higher than liver but were similar in both sexes. Transgene mRNA expression was much lower in lung and brain and least in the heart. Immunoblotting using an antipeptide antiserum, reactive with human CYP2Cs and mouse CYP2C70, revealed increased immunoreactive protein in liver microsomes from heterozygous transgenic male mice and a concomitant increase in 5'-hydroxylation of R-omeprazole and S-mephenytoin intrinsic clearance, consistent with CYP2C19 overexpression. A CYP2C18-specific antiserum showed that this enzyme was not expressed in livers or kidneys from heterozygous transgenic mice, but the antiserum had high affinity for recombinant CYP2C18 expressed in COS-7 cells. It is concluded that 1) both the CYP2C18 and CYP2C19 genes are subject to sexually dimorphic regulation in murine liver, kidney, and heart; 2) the CYP2C18 protein is not expressed in murine liver or kidney despite high levels of the corresponding mRNA; and 3) this transgenic model may be suitable for studying sex-dependent regulation of the human CYP2C genes and possibly serve as an in vivo model for CYP2C19-dependent drug metabolism.
PDF
