The SCN5A gene is implicated in many arrhythmogenic and cardiomyopathic processes. We identified a novel SCN5A variant in a family with significant segregation in individuals affected with progressive sinus and atrioventricular nodal disease, atrial arrhythmia, dilated cardiomyopathy, and early sudden cardiac arrest.

A patient pedigree was created following the clinical evaluation of three affected individuals, two monozygotic twins and a paternal half-brother, which lead to the evaluation of a paternal half-sister (four siblings with the same father and three mothers) all of whom experienced varying degrees of atrial arrhythmias, conduction disease, and dilated cardiomyopathy in addition to a paternal history of unexplained death in his 50s with similar autopsy findings. The index male underwent sequencing of 58 genes associated with cardiomyopathies. Sanger sequencing was used to provide data for bases with insufficient coverage and for bases in some known regions of genomic segmental duplications. All clinically significant and novel variants were confirmed by independent Sanger sequencing.

All relatives tested were shown to have the same SCN5A variant of unknown significance (p. Asp197His) and the monozygotic twins shared a co-occurring NEXN (p. Glu575*). Segregation analysis demonstrates likely pathogenic trait for the SCN5A variant with an additional possible role for the NEXN variant in combination.

There is compelling clinical evidence suggesting that the SCN5A variant p. Asp197His may be re-classified as likely pathogenic based on the segregation analysis of our family of interest. Molecular mechanism studies are pending.

This presentation will enable the learner to:

1. 1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2. 2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management

Older adults presenting with mild cognitive impairment (MCI) have a higher risk of developing dementia and also demonstrate impairments in social cognition. This study sought to establish whether in people with MCI, poorer theory of mind (ToM) was associated with volumetric changes in the amygdala and hippocampus, as well as early changes in behaviour.

One hundred and fourteen people with MCI and fifty-two older adult controls completed the Reading the Mind in the Eyes Test (RMET), while close informants (e.g., spouse/family member/friend/carer) described any current behavioural changes using the Revised Cambridge Behavioural Inventory (CBI-R). A subsample of participants completed structural magnetic resonance imaging (MRI).

The MCI group showed poorer performance on all neuropsychological tests administered, and moderate reductions on the RMET compared to the control group (d = .44), with greater reduction observed in those with amnestic compared to non-amnestic MCI (p = .03). While a robust correlation was identified between poorer RMET performance and smaller hippocampal volume in the control group (ρ = .53, p = .01), this relationship was not apparent in the MCI group (ρ = .21, p = .11). In the MCI group, poorer RMET performance was associated with poorer everyday skills (ρ = −.26, p = .01) assessed by the CBI-R.

Our findings cross-validate previous reports that social cognitive deficits in ToM are a feature of MCI and also suggest that disruptions to broader neural networks are likely to be implicated. Furthermore, ToM deficits in MCI are associated with a decline in everyday skills such as writing or paying bills.

The objective of this study was to systematically assess the literature regarding postnatal healthcare utilization and barriers/facilitators of healthcare in neonatal abstinence syndrome (NAS) children.

A systematic search was performed in PubMed, Cochrane Database of Systematic Reviews, PsychINFO, CINAHL, and Web of Science to identify peer-reviewed research. Eligible studies were peer-reviewed articles reporting on broad aspects of primary and specialty healthcare utilization and access in NAS children. Three investigators independently reviewed all articles and extracted data. Study bias was assessed using the Newcastle-Ottawa Assessment Scale and the National Institute of Health Study Quality Assessment Tool.

This review identified 14 articles that met criteria. NAS children have poorer outpatient appointment adherence and have a higher rate of being lost to follow-up. These children have overall poorer health indicated by a significantly higher risk of ER visits, hospital readmission, and early childhood mortality compared with non-NAS infants. Intensive multidisciplinary support provided through outpatient weaning programs facilitate healthcare utilization and could serve as a model that could be applied to other healthcare fields to improve the health among this population.

This review investigated the difficulties in accessing outpatient care as well as the utilization of such care for neonatal abstinence syndrome infants. NAS infants tend to have decreased access to, and utilization of outpatient healthcare following hospital birth discharge. Outpatient weaning programs have proven to be effective; however, these programs require intensive resources and care coordination that has yet to be implemented into other healthcare areas for NAS children.

Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.

Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.

Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.

This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.

Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.

We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.

16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).

PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.

A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.

A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.

Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.

The term “golden hour” describes the first 60 minutes after patients sustain injury. In resource-available settings, rapid transport to trauma centers within this time period is standard-of-care. We compared transport times of injured civilians in modern conflict zones to assess the degree to which injured civilians are transported within the golden hour in these environments.

We evaluated PubMed, Ovid, and Web of Science databases for manuscripts describing transport time after trauma among civilian victims of trauma from January 1990 to November 2017.

The initial database search identified 2704 abstracts. Twenty-nine studies met inclusion and exclusion criteria. Conflicts in Yugoslavia/Bosnia/Herzegovina, Syria, Afghanistan, Iraq, Israel, Cambodia, Somalia, Georgia, Lebanon, Nigeria, Democratic Republic of Congo, and Turkey were represented, describing 47 273 patients. Only 7 (24%) manuscripts described transport times under 1 hour. Transport typically required several hours to days.

Anticipated transport times have important implications for field triage of injured persons in civilian conflict settings because existing overburdened civilian health care systems may become further overwhelmed if in-hospital health capacity is unable to keep pace with inflow of the severely wounded.