The New South Wales Sudden Cardiac Arrest Registry: A Data Linkage Cohort Study.

BACKGROUND: Sudden cardiac arrest (SCA) in young people aged 1 to 50 years often occurs with no presenting symptoms or risk factors prompting screening for cardiovascular disease prior to their cardiac arrest. Approximately 3,000 young Australians suffer from sudden cardiac death (SCD) each year, making this a major public health issue. However, there is significant variation in the way incidence is estimated resulting in discrepancy across reporting which impacts our ability to understand and prevent these devastating events. We describe the New South Wales (NSW) Sudden Cardiac Arrest Registry: a retrospective, data linkage study which will identify all SCAs in the young in NSW from 2009 through to June 2022. OBJECTIVE: To determine the incidence, demographic characteristics and causes of SCA in young people. We will develop an NSW-based registry that will contribute to a greater understanding of SCA including risk factors and outcomes. METHODS: The cohort will include all people who experience a SCA in the NSW community aged between 1 to 50 years. Cases will be identified using the following three datasets: the Out of Hospital Cardiac Arrest Register housed at NSW Ambulance, the NSW Emergency Department Data Collection, and the National Coronial Information System. Data from eight datasets will be collected, anonymised and linked for the entire cohort. Analysis will be undertaken and reported using descriptive statistics. CONCLUSIONS: The NSW SCA registry will be an important resource for the improved understanding of SCA and inform the widespread impacts it has on individuals, their families and society.

Post mortem genetic testing in young individuals: What clinical medical practitioners need to know.

Forensic medical practitioners are in a unique position as they observe the exact pathology of various diseases in thousands of autopsies performed each year. Most medico-legal autopsies reveal an underlying, natural disease as the cause of death. Such data, relayed to the various stakeholders in the public health sector (including clinical medical practitioners), contribute to determining the population health status as well as identifying and dealing with priority areas. One of the most important public health concerns in Africa is that of the continuous increase in cardiovascular diseases. An important particular subset of cardiovascular diseases in South Africa, is the sudden unexpected deaths in the young population. Research on these deaths has shown that post mortem genetic testing can detect an inherited cardiac arrhythmogenic disease as the cause of death in up to 40% of these cases.  The high heritability of cardiac disorders and the fact that it is often treatable, genetic analysis of such cases provides significant clinical benefit with regard to the diagnosis and treatment of family members at risk for the same disease. The societal benefits from clinicians receiving such evidence-based findings associated with the cause of a patient's sudden death, is currently underutilized in South Africa.

The added value of molecular-based diagnostics in the African forensic medical setting.

Sudden unexpected infant death (SUDI) is reported to be an extraordinarily high burden in sub-Saharan Africa, with the incidence rate in South Africa among the highest in the world. It is common for the cause of many such infant deaths to remain unexplained even after a full medico-legal death investigation, and then to be categorised as a sudden unexplained infant death (SUID). Fortunately, advances in molecular-based diagnostics allow researchers to identify numerous underlying inherited cardiac arrhythmogenic disorders in many SUDI cases, with a predominance of variants identified in the SCN5A gene. Such cardiac arrhythmogenic-related sudden deaths generally present with no structural alterations of the heart that are macroscopically identifiable at autopsy, therefore highlighting the importance of post mortem genetic testing. We report on a significant genetic finding that was made on a SUDI case in which the cause was ascribed to an acute bacterial pneumonia but it was still subjected to post mortem genetic testing of the SCN5A gene. The literature shows that many SUDI cases diagnosed with inherited cardiac arrhythmogenic disorders have demonstrated a viral prodrome within days of their death. It is therefore not uncommon for these cardiac disorders in infants to be mistaken for flu, viral upper respiratory tract infection or pneumonia, and without the incorporation of post mortem genetic testing, any other contributory causes of these deaths are often disregarded. This study highlights the need for research reporting on the genetics of inherited cardiac disorders in Africa.

Practical tips to using formalin-fixed paraffin-embedded tissue archives for molecular diagnostics in a South African setting.

Background: Formalin-fixed paraffin-embedded (FFPE) tissue archives in hospitals, biobanks, and others offer a vast collection of extensive, readily available specimens for molecular testing. Unfortunately, the use of tissue samples for molecular diagnostic applications is challenging; thus, the forensic pathology FFPE tissue archives in Africa have been a largely unexploited genetic resource, with the usability of DNA obtainable from these samples being unknown. Intervention: The study, conducted from January 2015 to August 2016, determined the usefulness of FFPE tissue as a reliable source of genetic material for successful post-mortem molecular applications and diagnostics. Formalin-fixed paraffin-embedded tissue samples were collected and archived from autopsies conducted over 13 years in the forensic medicine department of the University of Pretoria (Pretoria, South Africa). Deoxyribonucleic acid from FFPE tissue samples and control blood samples was amplified by high-resolution melt real-time polymerase chain reaction before sequencing. The procurement parameters and fixation times were compared with the quantity and quality of the extracted DNA and the efficiency of its subsequent molecular applications. Lessons learnt: This study has shown that FFPE samples are still usable in molecular forensics, despite inadequate sample preparation, and offer immense value to forensic molecular diagnostics. Recommendations: FFPE samples fixed in formalin for more than 24 h should still be used in molecular diagnostics or research, as long as the primer design targets amplicons not exceeding 300 base pairs.

Sudden Unexpected Death in Infancy [SUDI]: What the clinician, pathologist, coroner and researchers want to know.

The loss of an apparently healthy infant is confronting for any family, puzzling for a clinician and challenging for the pathologist charged with the task of demonstrating a cause for death. The term "cot death" evolved to "sudden infant death syndrome" [SIDS] and now "sudden unexpected death in infancy [SUDI]" as the epidemiology and pathology of infant death changed. Community interventions were successful in changing sleep practices for young babies. The current research focus is on understanding genetic predispositions to unexpected death in early childhood. Whilst much has been achieved in reducing the infant mortality rate from SUDI by between 50%, and 80% in some countries, over the last 30 years, there remain challenges for improving rates of accurate diagnosis and reaching out to more vulnerable families with clearly modifiable risk factors for SUDI. These challenges directly involve the clinician through taking a systematic and detailed history and better standardised death scene evaluations with specifically accredited assessors. Better knowledge regarding circumstances of SUDI cases will help Coroners and researchers provide answers for grieving families now, and in the future contribute to further reductions in the rate of SUDI in communities across the world.

Practical tips to using formalin-fixed paraffin-embedded tissue archives for molecular diagnostics in a South African setting

Background: Formalin-fixed paraffin-embedded (FFPE) tissue archives in hospitals, biobanks, and others offer a vast collection of extensive, readily available specimens for molecular testing. Unfortunately, the use of tissue samples for molecular diagnostic applications is challenging; thus, the forensic pathology FFPE tissue archives in Africa have been a largely unexploited genetic resource, with the usability of DNA obtainable from these samples being unknown.Intervention: The study, conducted from January 2015 to August 2016, determined the usefulness of FFPE tissue as a reliable source of genetic material for successful post-mortem molecular applications and diagnostics. Formalin-fixed paraffin-embedded tissue samples were collected and archived from autopsies conducted over 13 years in the forensic medicine department of the University of Pretoria (Pretoria, South Africa). Deoxyribonucleic acid from FFPE tissue samples and control blood samples was amplified by high-resolution melt real-time polymerase chain reaction before sequencing. The procurement parameters and fixation times were compared with the quantity and quality of the extracted DNA and the efficiency of its subsequent molecular applications.Lessons learnt: This study has shown that FFPE samples are still usable in molecular forensics, despite inadequate sample preparation, and offer immense value to forensic molecular diagnostics.Recommendations: FFPE samples fixed in formalin for more than 24 h should still be used in molecular diagnostics or research, as long as the primer design targets amplicons not exceeding 300 base pairs.

Feasibility of analysis of the SCN5A gene in paraffin embedded samples in sudden infant death cases at the Pretoria Medico-Legal Laboratory, South Africa.

To determine variations in the SCN5A gene linked to inherited cardiac arrhythmogenic disorders in sudden, unexplained infant death (SUID) cases examined at the Pretoria Medico-Legal Laboratory, South Africa. A retrospective study was conducted on SUID cases and controls, analyzing DNA extracted from archived formalin-fixed, paraffin-embedded (FFPE) myocardial tissue samples as well as blood samples. A total of 48 FFPE tissue samples (cases), 10 control FFPE tissue samples and nine control blood samples were included. DNA extracted from all samples was used to test for variations in the SCN5A gene by using high resolution melt (HRM) real-time PCR and sequencing. Genetic analysis showed 31 different single nucleotide variants in the entire study population (n = 67). Five previously reported variants of known pathogenic significance, and 14 variants of benign clinical significance, were identified. The study found 12 different variants in the cases that were not published in any database or literature and were considered novel. Of these novel variants, two were predicted as "probably damaging" with a high level of certainty (found in four case samples), one (identified in another case sample) was predicted to be "possibly damaging" with a 50% chance of being disease-causing, and nine were predicted to be benign. This study shows the significant added value of using genetic testing in determining the cause of death in South African SUID cases. Considering the high heritability of these arrhythmic disorders, post mortem genetic testing could play an important role in the understanding of the pathogenesis thereof and could also aid in the diagnosis and treatment of family members at risk, ultimately preventing similar future cases.

Self-inflicted explosive death by intra-oral detonation of a firecracker: a case report.

Self-inflicted explosive deaths due to detonation of fireworks are rare. In this case report, a peculiar case of an elderly male who discharged a firecracker inside his mouth, resulting in fatal blast induced craniofacial injuries, is described. There is paucity of published data describing fireworks-related suicidal and/or non-suicidal deaths. Even scantier data is present specifically describing fireworks-related blast induced neurotrauma and the mechanism(s) of injury involved in such cases. This case report emphasizes the severe damage that a commercially available explosive, the so-called "Gorilla Bomb", can cause, and raises questions about the relative ease of its acquisition.

Long QT syndrome and sudden unexpected infant death.

Long QT syndrome (LQTS) is an inheritable primary electric disease of the heart characterised by abnormally long QT intervals and a propensity to develop atrial and ventricular tachyarrhythmias. It is caused by an inherited channelopathy responsible for sudden cardiac death in individuals with structurally normal hearts. Long QT syndrome can present early in life, and some studies suggest that it may be associated with up to 20% of sudden unexplained infant death (SUID), particularly when associated with external stressors such as asphyxia, which is commonly seen in many infant death scenes. With an understanding of the genetic defects, it has now been possible to retrospectively analyse samples from infants who have presented to forensic pathology services with a history of unexplained sudden death, which may, in turn, enable the implementation of preventative treatment for siblings previously not known to have pathogenic genetic variations. In this viewpoint article, we will discuss SUID, LQTS and postmortem genetic analysis.

Venous air embolism: An under-recognised entity in blunt-force trauma and the importance of radiology.

Air embolism (AE) is considered a rare event and can be either iatrogenic or traumatic. Various post-mortem methods to detect AE exist, of which radiology is preferred. The presence of air in the heart can be demonstrated using special dissection techniques where the heart is opened under water or by needle puncture from a water-filled syringe. Three cases of blunt-force head injury are presented herein, with AE being diagnosed by conventional radiography using a Lodox Statscan® full-body digital X-ray machine in all cases. This case series demonstrates that AE due to blunt-force trauma to the head and sinuses might be under-recognised in the forensic post-mortem setting. It also highlights the importance of radiology in diagnosing AE post-mortem, especially where the results of post-mortem techniques might be unsatisfactory.

Managing the remains of fetuses and abandoned infants: A call to urgently review South African law and medicolegal practice.

This article reviews South African (SA) law and its impact on the medicolegal management of fetal remains emanating from elective and therapeutic termination of pregnancies, stillbirths and miscarriages and the remains of abandoned or exposed infants. It was found that remains are treated differently, some constituting medical waste while others have sufficient status in law to allow for burial. This approach results in some women or couples being denied a choice with regard to disposal via culturally relevant practices, and is insensitive to the fact that all remains ultimately constitute human remains. The article argues that SA law is in urgent need of reform, and turns to foreign law and forensic practice to shed light on possible alternative approaches that could assist with developing the SA position and thereby improve the practical management of fetal and infant remains in SA.

"Death at the wheel" due to tuberculosis of the myocardium: a case report.

According to the World Health Organization, an estimated 9 million people contracted tuberculosis (TB) with approximately 25% of TB cases being from Africa. TB was reported as the number one cause of natural death for the period 2011-2013 in South Africa. The first reported case of myocardial TB was in 1664 by Maurocordat and the first reported case of sudden cardiac death due to TB was made in 1977. We present a case report of myocardial TB in an apparently healthy, 35-year-old male who died suddenly while driving his car. The problems associated with the diagnosis of TB of the myocardium and an overview of the relevant literature is provided.

Evaluating current knowledge of legislation and practice of obstetricians and gynaecologists in the management of fetal remains in South Africa.

BACKGROUND: In the clinical setting, the main legislative provisions governing the management and 'disposal' of fetal remains in South Africa are the Choice on Termination of Pregnancy Act 92 of 1996 and the Births and Deaths Registration Act 51 of 1992. OBJECTIVES: To determine obstetricians' and gynaecologists' current knowledge of this legislation. Current practice with regard to certification of death and methods of disposal of fetal material was also reviewed. METHODS: A questionnaire-based study was conducted. The data collected included demographic details, qualifications, years of experience, working environment (public/private practice), responses to general questions reviewing knowledge of current legislation, and practical experience. RESULTS: Seventy-six questionnaires were returned, with practitioners from the private and public sectors nearly equally represented. It was found that there is a concerning gap in obstetricians' and gynaecologists' knowledge of the law, and that some practitioners are acting outside the scope of the law. The study further revealed that patients' needs are not properly accommodated under the current legislative provisions, because the law prevents certain remains from being respectfully managed. Conclusions. The study findings suggest that improved training of practitioners, together with possible law reform, are required to better serve the needs of patients.

Deaths from bee stings: a report of three cases from Pretoria, South Africa.

In South Africa bee stings are most commonly caused by either Apis mellifera capensis or A. mellifera scutellata, indigenous species which are notoriously aggressive when compared to European honey bees. According to Statistics South Africa, 109 deaths were documented for the period 2001-2011 as having been caused by hornets, wasps, and bees (ICD10-X26). This appears to be a small number but, as was reported in Australia, these statistics might be inaccurate due to either over- or underreporting of cases. We report 3 cases of fatalities due to bee stings, including one with postmortem features of diffuse intravascular coagulopathy. A brief overview of the venom of the honey bee, reactions following a bee sting and possible mechanisms of death are presented. Confirming the diagnosis in these cases may be very problematic for the forensic pathologist, as in many cases minimal history is available and both external and internal examination could fail to reveal any specific signs of bee sting or other obvious morphologic abnormalities. Thus, there is a need for reliable confirmatory or supportive diagnostic tests.

The prevalence of HIV in the sudden, unexplained and unexpected death population at the Pretoria Medico-Legal Laboratory.

PURPOSE: To determine the prevalence of HIV in the sudden, unexplained and unexpected (SUU) death population admitted to the Pretoria Medico-Legal Laboratory. METHODS: This study was conducted at the Pretoria Medico-Legal Laboratory. Blood samples were obtained from decedents who died suddenly and/or unexpectedly, during autopsy, by a forensic pathologist. Sample collection continued until 100 valid samples were analysed for HIV antibodies. The data collected included demographic details and case-related information. RESULTS AND CONCLUSION: SUU deaths accounted for 14% of all cases admitted to the Pretoria Medico-Legal Laboratory. The HIV prevalence in the SUU deaths was 43%, which is 17% higher than the general mortuary population in Pretoria (p = 0.0045). The majority of these deaths were due to respiratory disease processes, with 12 cases having HIV/TB co-infection.

The application of imaging technologies in the detection of trace evidence in forensic medical investigation.

In a country notorious for violent crime, it seems that South African medico-legal laboratories make minimal application of technology in the death investigation process and little attention is given to trace evidence. Non-destructive, non-invasive, portable and cost-effective tools are required. This study was conducted at the Pretoria Medico-Legal Laboratory. The surface area of the bodies and clothing of victims of fatal interpersonal violence were examined using a torch, magnifying lamp, portable digital microscope and alternate light source to gauge their potential for trace evidence detection. Most studies apply these and similar tools to inert surfaces, with few focusing on their application to human skin. There was a statistically significant difference in the detection of many of the evidence types between the naked-eye observation of the pathologists and the technologies. The different imaging technologies were compared as to their cost, evidence detection ability and ease of use. The most common evidence types discovered on the bodies and clothing of victims of fatal interpersonal violence, as well as the propensity of each tool to detect these, was evaluated in order to devise the best option for incorporation into the Pretoria Medico-Legal Laboratory routine. The digital microscope performed best overall followed by the magnifying lamp, torch and the Polilight(®). This study aimed to justify the investment of more time, effort and funding into trace evidence recovery in the South African mortuary environment.