Pregnancy Following Heart Transplantation: A Single Centre Case Series and Review of the Literature.

BACKGROUND: Maternal and fetal outcomes of pregnancy amongst cardiac transplant recipients are limited in the current literature. METHODS: We describe five pregnancies in three cardiac transplant recipients managed between a tertiary centre for obstetric medicine and an associated state-wide transplant centre between 2014-2018, and provide a narrative review of the literature. RESULTS: Pre-conception counselling was undertaken. There were no recent rejection episodes and all women demonstrated good baseline cardiac function. Median maternal age was 27 years (range 23-38 yrs.). Median time from transplantation to pregnancy was 5 years (range 2-14 yrs.). All women were managed with modified immunosuppressant regimens and multidisciplinary care. Cardiac function, tacrolimus levels and renal function were closely monitored with frequent monitoring for common complications of pregnancy. There were no maternal or fetal deaths. There was no evidence of graft rejection and no deterioration in cardiac function. Tacrolimus doses were increased to maintain therapeutic targets. Gestational diabetes occurred in three women and cholestasis of pregnancy occurred in one. Each infant was delivered by vaginal delivery. One mother had postpartum haemorrhage in both pregnancies. Pre-eclampsia did not occur. Median gestation at delivery was 37 weeks (range 35+4-40+5 days) with two preterm deliveries. One (1) infant was born with low birth weight. One (1) infant had jaundice requiring phototherapy. All infants were breastfed. CONCLUSION: Pregnancy in transplant recipients confers risk to the mother and fetus. Pre-conception counselling, immunosuppressant tailoring and regular monitoring are paramount to avoid rejection and possible teratogenic complications. Favourable pregnancy outcomes are achievable with specialist multidisciplinary care.

Dilated Cardiomyopathy in Pregnancy: Outcomes From an Australian Tertiary Centre for Maternal Medicine and Review of the Current Literature.

BACKGROUND: Peripartum cardiomyopathy is associated with significant risks of decline in left ventricular function and adverse maternal and fetal outcome in subsequent pregnancy. The risks of pregnancy in women with dilated cardiomyopathy are unclear. We aimed to assess the outcome of pregnancy in women with dilated cardiomyopathy seen at our institution and to review the literature on this subject. METHODS: A retrospective audit of the outcomes of 14 pregnancies to 12 women with dilated cardiomyopathy. RESULTS: There were no cardiac events and no woman had a decline in left ventricular function during pregnancy. There was a high rate of prematurity and adverse fetal outcome related to this, including four neonatal deaths. CONCLUSION: Maternal outcomes in this small series were satisfactory though only three women had moderate-severe left ventricular dysfunction at baseline. There was a high rate of premature delivery and adverse neonatal outcome.

Development and evaluation of a primary care interprofessional education intervention to support people with dementia.

International policy documents emphasize the need to develop interprofessional education (IPE) to support collaborative dementia care in the community. The aim of this short report is to describe the development and pilot evaluation of an interprofessional dementia education workshop for primary care healthcare professionals. A three-hour workshop was iteratively developed through consultation with an expert reference group and people with dementia. The workshop was piloted with three separate primary care teams. A total of fifty-four primary care based healthcare staff who represented fourteen different health care roles in primary care participated in the pilot evaluation. The pilot workshops were evaluated using a mixed method approach which included post-workshop questionnaires for participants (n= 54)and a post-workshop focus group (n=8) with the program design team and workshop facilitators. The results of the pilot phase indicated that the workshop was useful and feasible. The workshop improved participants' self-reported knowledge, understanding and confidence to support people with dementia and their families.Areas for improvement were identified and will be used to inform improvements to the workshop content and delivery in advance of a national roll-out. Future evaluations of the implementation of this interprofessional educational workshop will focus on its impact on healthcare professional behavior and outcomes for the person with dementia and their families.

The development and evaluation of peer-facilitated dementia workshops in general practice.

BACKGROUND: Rising dementia prevalence rates, combined with the policy objectives of integrated care in the community, means that general practitioners (GPs) are playing an increasing and pivotal role in dementia care. However, GPs are challenged by dementia care and have identified it as an area of learning need. We describe the development, roll-out and evaluation of peer-facilitated workshops for GPs, as part of a national programme to support GPs in their delivery of dementia care. METHOD: Informed by a triangulated educational needs analysis, small-group case-based workshops were designed. Five GPs were trained as facilitators and delivered workshops in GP practices within their own locality. A mixed-methods evaluation was undertaken, incorporating participant completion of post-workshop questionnaires along with the collection and analysis of qualitative data obtained from a focus group with workshop facilitators. RESULTS: 104 GPs attended 39 workshops (median attendance number 3, range 2-9). The majority of participants reported an improvement in their knowledge and confidence in dementia care. In particular, participants felt that workshop content was relevant and they liked peer-facilitation within their own practices. Facilitators emphasised the importance of skilful facilitation of sensitive topics and described the tension between being regarded as a facilitator and a subject expert. CONCLUSIONS: The findings of this study indicate that practice-based, peer-facilitated, small-group workshops improve self-reported knowledge and confidence in dementia care and are well-received by GPs. Findings further suggest that similar educational approaches may be effective in supporting GPs in other areas of complex chronic care in general practice.

"We're certainly not in our comfort zone": a qualitative study of GPs' dementia-care educational needs.

BACKGROUND: Rising dementia prevalence rates rise combined with the policy objective of enabling people with dementia to remain living at home, means that there will be a growing demand for dementia care in the community setting. However, GPs are challenged by dementia care and have identified it as an area in which further training is needed. Previous studies of GPs dementia care educational needs have explored the views of GPs alone, without taking the perspectives of people with dementia and family carers into account. The aim of the study was to explore GPs' dementia care educational needs, as viewed from multiple perspectives, in order to inform the design and delivery of an educational programme for GPs. METHODS: A qualitative study of GPs, people with dementia and family carers in a community setting was undertaken. Face-to-face interviews were performed with GPs, people with dementia and with family carers. Interviews were audio-recorded, transcribed verbatim and thematically analysed. RESULTS: Thirty-one people were interviewed, consisting of fourteen GPs, twelve family carers and five people with dementia. GPs expressed a wish for further education, preferentially through small group workshops. Five distinct educational needs emerged from the interviews, namely, diagnosis, disclosure, signposting of local services, counselling and the management of behavioural and psychological symptoms (BPSD). While GPs focused on diagnosis, disclosure and BPSD in particular, people with dementia and family carers emphasised the need for GPs to engage in counselling and signposting of local services. CONCLUSIONS: The triangulation of data from multiple relevant sources revealed a broader range of GPs' educational needs, incorporating both medical and social aspects of dementia care. The findings of this study will inform the content and delivery of a dementia educational programme for GPs that is practice-relevant, by ensuring that the curriculum meets the needs of GPs, patients and their families.

Pregnancy in patients with the Fontan operation.

Improved survival rates for patients with a Fontan circulation has allowed more women with this complex cardiac physiology to contemplate pregnancy. However, pregnancy in women with a Fontan circulation is associated with a high risk of adverse maternal and foetal outcomes, high rates of miscarriage, and preterm delivery. Factors associated with a successful pregnancy outcome are younger age, normal body weight, absence of significant functional limitation, no Fontan-related complications, and well-functioning single ventricle physiology. Appropriate care with timely preconception counselling and regular, frequent clinical reviews by a multidisciplinary team based at a tertiary centre improves the chance of a successful pregnancy. Empowerment of patients with education on their specific congenital cardiac condition and its projected trajectory helps them make informed choices regarding their health, reproductive choices, and assists them to achieve their life goals.

Pregnancy in women with Fontan is feasible but associated with a high risk of adverse maternal/foetal outcomes. Younger age, normal body weight, absence of significant functional limitation, and no Fontan-related complications are favourable factors. Timely preconception counselling and regular clinical reviews in a tertiary centre with an MDT improves pregnancy outcomes. Empowerment of patients with education helps them make informed choices on health, family planning, and the future.

Cardiovascular Magnetic Resonance from Fetal to Adult Life-Indications and Challenges: A State-of-the-Art Review.

Cardiovascular magnetic resonance (CMR) imaging offers a comprehensive, non-invasive, and radiation-free imaging modality, which provides a highly accurate and reproducible assessment of cardiac morphology and functions across a wide spectrum of cardiac conditions spanning from fetal to adult life. It minimises risks to the patient, particularly the risks associated with exposure to ionising radiation and the risk of complications from more invasive haemodynamic assessments. CMR utilises high spatial resolution and provides a detailed assessment of intracardiac and extracardiac anatomy, ventricular and valvular function, and flow haemodynamic and tissue characterisation, which aid in the diagnosis, and, hence, with the management of patients with cardiac disease. This article aims to discuss the role of CMR and the indications for its use throughout the different stages of life, from fetal to adult life.

Effects of perilipin 2 antisense oligonucleotide treatment on hepatic lipid metabolism and gene expression.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. We previously showed that Perilipin 2 (Plin2), a member of lipid droplet protein family, is markedly increased in fatty liver, and its reduction in the liver of diet-induced obese mice by antisense oligonucleotide (ASO) decreased steatosis and enhanced insulin sensitivity. Plin2-ASO treatment markedly suppressed lipogenic gene expression. To gain a better understanding of the biological role of Plin2 in liver, we performed microarray analysis to determine genes differentially regulated by Plin2-ASO compared with a control (scrambled) oligonucleotide (Cont). Male C57BL/6J mice on a high-fat diet were treated with Plin2- or Cont-ASO for 4 wk. Plin2-ASO decreased hepatic triglycerides, and this was associated with changes in expression of 1,363 genes. We analyzed the data for functional clustering and validated the expression of representative genes using real-time PCR. On the high-fat diet, Plin2-ASO decreased the expression of enzymes involved in fatty acid metabolism (acsl1, lipe) and steroid metabolism (hmgcr, hsd3b5, hsd17b2), suggesting that Plin2 affects hepatic lipid metabolism at the transcriptional level. Plin2-ASO also increased the expression of genes involved in regulation of hepatocyte proliferation (afp, H19), mitosis (ccna2, incenp, sgol1), and extracellular matrix (col1a1, col3a1, mmp8). Plin2-ASO had similar effects on gene expression in chow-fed mice. Together, these results indicate that Plin2 has diverse metabolic and structural roles in the liver, and its downregulation promotes hepatic fibrosis and proliferation.

How a 7-Week Food Literacy Cooking Program Affects Cooking Confidence and Mental Health: Findings of a Quasi-Experimental Controlled Intervention Trial.

Obesity and mental health disorders are rising simultaneously with shifting dietary behavior away from home cooking, toward typically nutrition-poor and energy-dense convenience meals. Food literacy strongly influences nutrition choices. Community-based cooking interventions target barriers to healthy eating and facilitate development of food literacy skills, thereby potentially increasing preparation of home-cooked meals and positively influencing health. This study of 657 healthy Australian adults explored the efficacy of a 7-week cooking program in improving cooking confidence, whether this transferred to behavior surrounding food, and/or affected mental health. Significant post-program improvements in cooking confidence and satisfaction (all p < 0.001, η p 2 1.12 large), ability to change eating habits (p < 0.001) and overcome lifestyle barriers (p = 0.005) were observed for the intervention group but not control. Participation also improved mental and general health (all p < 0.05, η p 2 0.02 small). No changes were observed for acquisition and consumption of food, or nutrition knowledge in either group. This 7-week cooking program built cooking confidence and improved general and mental health but did not change dietary behavior. To further improve nutrition related behaviors associated with better mental health, more effort is needed to recruit those with below-average nutrition knowledge and interest in cooking.

Rapid identification of protein biomarkers of Escherichia coli O157:H7 by matrix-assisted laser desorption ionization-time-of-flight-time-of-flight mass spectrometry and top-down proteomics.

Six protein biomarkers from two strains of Escherichia coli O157:H7 and one non-O157:H7, nonpathogenic strain of E. coli have been identified by matrix-assisted laser desorption ionization time-of-flight-time-of-flight tandem mass spectrometry (MALDI-TOF-TOF-MS/MS) and top-down proteomics. Proteins were extracted from bacterial cell lysates, ionized by MALDI, and analyzed by MS/MS. Protein biomarker ions were identified from their sequence-specific fragment ions by comparison to a database of in silico fragment ions derived from bacterial protein sequences. Web-based software, developed in-house, was used to rapidly compare the mass-to-charge (m/z) of MS/MS fragment ions to the m/z of in silico fragment ions derived from hundreds of bacterial protein sequences. A peak matching algorithm and a p-value algorithm were used to independently score and rank identifications on the basis of the number of MS/MS-in silico matches. The six proteins identified were the acid stress chaperone-like proteins, HdeA and HdeB; the cold shock protein, CspC; the YbgS (or homeobox protein); the putative stress-response protein YjbJ (or CsbD family protein); and a protein of unknown function, YahO. HdeA, HdeB, YbgS, and YahO proteins were found to be modified post-translationally with removal of an N-terminal signal peptide. Gene sequencing of hdeA, hdeB, cspC, ybgS, yahO, and yjbJ for 11 strains of E. coli O157:H7 and 7 strains of the "near-neighbor" serotype O55:H7 revealed a high degree sequence homology between these two serotypes. Although it was not possible to distinguish O157:H7 from O55:H7 from these six biomarkers, it was possible to distinguish E. coli O157:H7 from a nonpathogenic E. coli by top-down proteomics of the YahO and YbgS. In the case of the YahO protein, a single amino acid residue substitution in its sequence (resulting in a molecular weight difference of only 1 Da) was sufficient to distinguish E. coli O157:H7 from a non-O157:H7, nonpathogenic E. coli by MALDI-TOF-TOF-MS/MS, whereas this would be difficult to distinguish by MALDI-TOF-MS. Finally, a protein biomarker ion at m/z approximately 9060 observed in the MS spectra of non-O157:H7 E. coli strains but absent from MS spectra of E. coli O157:H7 strains was identified by top-down analysis to be the HdeB acid stress chaperone-like protein consistent with previous identifications by gene sequencing and bottom-up proteomics.

Web-based software for rapid top-down proteomic identification of protein biomarkers, with implications for bacterial identification.

We have developed web-based software for the rapid identification of protein biomarkers of bacterial microorganisms. Proteins from bacterial cell lysates were ionized by matrix-assisted laser desorption ionization (MALDI), mass isolated, and fragmented using a tandem time of flight (TOF-TOF) mass spectrometer. The sequence-specific fragment ions generated were compared to a database of in silico fragment ions derived from bacterial protein sequences whose molecular weights are the same as the nominal molecular weights of the protein biomarkers. A simple peak-matching and scoring algorithm was developed to compare tandem mass spectrometry (MS-MS) fragment ions to in silico fragment ions. In addition, a probability-based significance-testing algorithm (P value), developed previously by other researchers, was incorporated into the software for the purpose of comparison. The speed and accuracy of the software were tested by identification of 10 protein biomarkers from three Campylobacter strains that had been identified previously by bottom-up proteomics techniques. Protein biomarkers were identified using (i) their peak-matching scores and/or P values from a comparison of MS-MS fragment ions with all possible in silico N and C terminus fragment ions (i.e., ions a, b, b-18, y, y-17, and y-18), (ii) their peak-matching scores and/or P values from a comparison of MS-MS fragment ions to residue-specific in silico fragment ions (i.e., in silico fragment ions resulting from polypeptide backbone fragmentation adjacent to specific residues [aspartic acid, glutamic acid, proline, etc.]), and (iii) fragment ion error analysis, which distinguished the systematic fragment ion error of a correct identification (caused by calibration drift of the second TOF mass analyzer) from the random fragment ion error of an incorrect identification.

The development and evaluation of an online dementia resource for primary care based health professionals.

BACKGROUND: Primary care based health professionals struggle with many aspects of dementia care. General practitioners (GPs) find providing post-diagnosis information on services and supports particularly challenging. Likewise, people with dementia and their family caregivers feel they need more support from their GPs in this post-diagnosis period. OBJECTIVE: This study aimed to develop and evaluate an online educational resource for primary care health professionals that included a dementia specific services and supports directory. METHOD: A previously conducted educational needs analysis informed the content of the resource. This content was further developed by a review of the literature and through consultation with an expert reference group and a stakeholder group. A mixed method approach was taken to the evaluation of the online resource which included analysis of the website traffic, qualitative feedback from stakeholders and evaluation by general practitioners. RESULTS: The online resource www.dementiapathways.ie was developed. Initial qualitative feedback obtained from potential end-users was positive. Data analysis was performed on over 4000 people who accessed the site. Finally, the online resource was demonstrated to 190 general practitioners in 36 workshops. All of the general practitioners surveyed felt that dementipathways.ie would be a useful resource for them. Several potential barriers to the successful development and implementation of a services and supports directory were identified. CONCLUSION: This study provides a prototype for the development of an online dementia educational resource and demonstrates the value of a dementia-specific services and supports directory for primary care based health professionals.

Development of performance indicators for systems of urgent and emergency care in the Republic of Ireland: Systematic review and consensus development exercise.

Objectives: To develop a set of performance indicators to monitor the performance of emergency and urgent care systems in the Republic of Ireland. Design: This study comprised of an update of a previously performed systematic review and a formal consensus development exercise. Results: Initial literature searches yielded 2339 article titles.  After further searches, sixty items were identified for full-text review. Following this review, fifty-seven were excluded. Three articles were identified for inclusion in the systematic review. These papers produced 42 unique indicators for consideration during the consensus development exercise. In total, 17 indicators had a median of greater than 7 following the meeting and met our pre-specified criterion for acceptable consensus. Discussion: Using this systematic review and nominal group consensus development exercise, we have identified a set of 17 indicators, which a consensus of different experts regard as potentially good measures of the performance of urgent and emergency care systems in Ireland.