Beyond monogenetic rare variants: tackling the low rate of genetic diagnoses in predominantly antibody deficiency

Predominantly antibody deficiency (PAD) is the most prevalent form of primary immunodeficiency, and is characterized by broad clinical, immunological and genetic heterogeneity. Utilizing the current gold standard of whole exome sequencing for diagnosis, pathogenic gene variants are only identified in less than 20% of patients. While elucidation of the causal genes underlying PAD has provided many insights into the cellular and molecular mechanisms underpinning disease pathogenesis, many other genes may remain as yet undefined to enable definitive diagnosis, prognostic monitoring and targeted therapy of patients. Considering that many patients display a relatively late onset of disease presentation in their 2^nd or 3^rd decade of life, it is questionable whether a single genetic lesion underlies disease in all patients. Potentially, combined effects of other gene variants and/or non-genetic factors, including specific infections can drive disease presentation. In this review, we define (1) the clinical and immunological variability of PAD, (2) consider how genetic defects identified in PAD have given insight into B-cell immunobiology, (3) address recent technological advances in genomics and the challenges associated with identifying causal variants, and (4) discuss how functional validation of variants of unknown significance could potentially be translated into increased diagnostic rates, improved prognostic monitoring and personalized medicine for PAD patients. A multidisciplinary approach will be the key to curtailing the early mortality and high morbidity rates in this immune disorder.     

Alternatives to sharing COVID-19 data with law enforcement: Recommendations for stakeholders

During the COVID-19 pandemic, in some jurisdictions, police have become involved in enforcing coronavirus-related measures. Relatedly, several North American jurisdictions have established COVID-19 data sharing protocols with law enforcement. Research across a range of fields has demonstrated that involving police in matters of public health disproportionately impacts the most vulnerable and does more harm than good. This is reflected in the consensus against COVID-19 criminalization that has emerged among civil society organizations focused on HIV, human rights, and harm reduction. The European Data Protection Board has also released guidelines against re-uses of COVID-19 data for law enforcement purposes. This article offers an overview of the harms of criminalizing illnesses and strategies for health stakeholders to seek alternatives to sharing COVID-19 data with police agencies while facilitating interoperability with healthcare first responders. It also presents case studies from two North American jurisdictions – Ontario and Minnesota – that have established routine COVID-19 data sharing with police. We recommended seven alternatives, including designating COVID-19 data as sensitive and implementing segmented interoperability with first responder agencies. These guidelines can help ensure that health information technology platforms do not become vehicles for the criminalization of COVID-19, and that health data stay within the health system.     

Bronchoscopy in severe childhood asthma: Irresponsible or irreplaceable?

For children with severe asthma, guideline‐based management focuses on the escalation of anti‐inflammatory and bronchodilatory medications while addressing comorbid conditions. Bronchoscopy, in this context, has been relegated to ruling out asthma mimickers. More recently, however, there have been questions surrounding the clinical utility of bronchoscopy in severe childhood asthma. In this solicited lecture summary, we discuss the past, present, and potential future applications of bronchoscopy in severe childhood asthma.     

Detection of highly pathogenic avian influenza in Sekong Province Lao PDR 2018—Potential for improved surveillance and management in endemic regions

Significant global efforts have been directed towards understanding the epidemiology of highly pathogenic avian influenza (HPAI) across poultry production systems and in wild‐bird reservoirs, yet understanding of disease dynamics in the village poultry setting remains limited. This article provides a detailed account of the first laboratory‐confirmed outbreak of HPAI in the south‐eastern provinces of Lao PDR, which occurred in a village in Sekong Province in October 2018. Perspectives from an anthropologist conducting fieldwork at the time of the outbreak, clinical and epidemiological observations by an Australian veterinarian are combined with laboratory characterization and sequencing of the virus to provide insights about disease dynamics, biosecurity, outbreak response and impediments to disease surveillance. Market‐purchased chickens were considered the likely source of the outbreak. Observations highlighted the significance of a‐lack‐of pathognomonic clinical signs and commonness of high‐mortality poultry disease with consequent importance of laboratory diagnosis. Sample submission and testing was found to be efficient, despite the village being far from the national veterinary diagnostic laboratory. Extensively raised poultry play key roles in ritual, livelihoods and nutrition of rural Lao PDR people. Unfortunately, mass mortality of chickens due to diseases such as HPAI and Newcastle disease (ND) imposes a significant burden on smallholders in Lao PDR, as in most other SE Asian countries. We observed that high mortality of chickens is perceived by locals as a new ‘normal’ in raising poultry; this sense of it being ‘normal’ is a disincentive to reporting of mortality events. Establishing effective people‐centred disease‐surveillance approaches with local benefit, improving market‐biosecurity and veterinary‐service support to control vaccine‐preventable poultry diseases could all reduce mass‐mortality event frequency, improve veterinary–producer relationships and increase the likelihood that mortality events are reported. Priority in each of these aspects should be on working with smallholders and local traders, appreciating and respecting their perspectives and local knowledge.     

Factors influencing attendance at cardiac rehabilitation among coronary heart disease patients.

OBJECTIVE: The current study examined predictors of, and reasons for, non-attendance at cardiac rehabilitation (CR) among coronary heart disease patients. METHODS: Measures of demographics, surgical procedures, cardiac risk factors, cardiac damage, and psychological variables (depression, trauma, anxiety and alexithymia) were obtained at baseline in 85 coronary heart disease patients, of whom 34 (40%) attended CR. Patients not attending CR reported reasons for their non-attendance. RESULTS: Men who had a sedentary lifestyle or were obese were significantly more likely to attend CR. Women were significantly more likely to attend CR if they had a partner. Patients reported numerous personal reasons for their non-attendance, some of which reflect a dislike of a group format. CONCLUSION: The results suggest the presence of obstacles to attendance and completion of CR that may differ for men and women. Innovative approaches are needed to encourage participation, including the development and evaluation of alternative formats of CR.     

General practitioners' promotion of healthy life styles: what patients think

Abstract: The study examined the prevalence of cigarette smoking, alcohol consumption, exercising to keep fit and dieting to lose weight among general practice patients, and patients' perceptions of the role of the general practitioner in advising about life style. A cross-sectional survey using a self-administered questionnaire was completed by 13 017 patients aged 18 to 70 years who were attending one of 119 general practitioners from 40 group practices in metropolitan Sydney over a six- to eight-week period. More women than men reported dieting to lose weight, just over half of the men and women were exercising regularly to keep fit, 35 per cent of men and 29 per cent of women reported smoking, and 12 per cent of men and 10 per cent of women were drinking alcohol at levels considered hazardous or harmful. More young people were smoking, drinking hazardously or harmfully, dieting to lose weight and exercising than the older age groups, and their smoking rates exceeded those of the general population. Most patients reported that general practitioners should be interested in their life-style behaviours, particularly smoking. Substantially fewer patients (particularly women who drank excessively) reported receiving advice about their habits. General practitioners were more likely to give advice when smoking and drinking levels were very high. There were discrepancies between patients' expectations of the doctor's role in promoting healthy life styles, and their likelihood of receiving advice. Doctors could reduce the diseases associated with unhealthy practices. Developments in medical training in the 1990s may extend the way they engage in advising on issues of life style.     

Nonfatal firearm misuse: licence status of perpetrators and legality of the firearms

Abstract: The primary aim of this study was to identify the licence status of those involved in incidents of nonfatal firearm-related misuse and to determine the involvement of legal firearms in such incidents. Firearm-related attempted suicides were excluded. The study also sought to identify the types of firearms most likely to be misused. Over a three-month period in early 1994, all nonfatal firearm-related incidents reported in any New Zealand newspaper were identified by a commercial clipping bureau. Data pertaining to the licence status and the legality of the firearm involved in these incidents were obtained from the police who completed a standardised questionnaire under the Official Information Act (1982). Over the study period, 78 incidents yielded information on 97 perpetrators and 100 firearms. Of the 97 perpetrators, 66 per cent were unlicensed, 20 per cent were licensed, the licence status of 8 per cent of the perpetrators was unknown and the remaining 7 per cent were using air guns, and therefore a licence was not required. Half of the perpetrators involved in domestic disputes were licensed. Of the 100 firearms, 44 per cent were classified as 'legal firearms' and 56 per cent were classified as 'illegal firearms'. These findings suggest that strategies aimed at reducing or preventing injury due to firearm misuse must focus on both licensed and unlicensed individuals and both legal and illegal firearms.