The mental health of Australians bereaved during the first two years of the COVID-19 pandemic: a latent class analysis.

BACKGROUND: The COVID-19 pandemic disrupted many areas of life, including culturally accepted practices at end-of-life care, funeral rites, and access to social, community, and professional support. This survey investigated the mental health outcomes of Australians bereaved during this time to determine how these factors might have impacted bereavement outcomes. METHODS: An online survey indexing pandemic and bereavement experiences, levels of grief, depression, anxiety, and health, work, and social impairment. Latent class analysis (LCA) was used to identify groups of individuals who shared similar symptom patterns. Multinomial regressions identified pandemic-related, loss-related, and sociodemographic correlates of class membership. RESULTS: 1911 Australian adults completed the survey. The LCA identified four classes: low symptoms (46.8%), grief (17.3%), depression/anxiety (17.7%), and grief/depression/anxiety (18.2%). The latter group reported the highest levels of health, work, and social impairment. The death of a child or partner and an inability to care for the deceased due to COVID-19 public health measures were correlated with grief symptoms (with or without depression and anxiety). Preparedness for the person's death and levels of pandemic-related loneliness and social isolation differentiated all four classes. Unemployment was associated with depression/anxiety (with or without grief). CONCLUSIONS: COVID-19 had profound impacts for the way we lived and died, with effects that are likely to ricochet through society into the foreseeable future. These lessons learned must inform policymakers and healthcare professionals to improve bereavement care and ensure preparedness during and following future predicted pandemics to prevent negative impacts.

Adverse drug event-related hospitalisation in persons with neurodevelopmental disorders: a state-wide retrospective cohort study.

BACKGROUND: Little is known about the sociodemographic and clinical characteristics of adverse drug events (ADEs) in patients with neurodevelopmental disorders (NDD). OBJECTIVE: The objective of this study was to describe and compare the demographic details of people with and without NDD hospitalised due to ADEs. METHODS: The all-inclusive New South Wales Admitted Patient Data Collection from 2001 to 2014 was employed to identify ADE-related hospitalisations in patients with NDD using the International Classification of Diseases 10th revision Australian modification codes. We derived case sets specific to different clinical groups and patient characteristics and compared proportional differences between patients with and without intellectual disability using chi squared tests. RESULTS: A total of 2173 patients with NDD were admitted for acute care of ADEs, accounting for 0.7% of all ADE-related hospitalisations. Hospitalised ADEs among patients with NDD increased by twofold over the 14-year study period. Psychotropic medications and opioid analgesic medications were leading causes of ADE-related hospitalisations in patients with NDD. Compared with their counterparts, patients with NDD were younger, experienced more socio-economic disadvantage and less private insurance coverage, suffered with less severe but different co-morbid clinical conditions and incurred more challenges in the acute hospital care setting. CONCLUSION: Although the pattern of ADE-related hospitalisations in patients with NDD differed from that in patients without NDD, there is a lack of targeted healthcare programmes to meet their special needs. This study suggests the need for countermeasures in primary healthcare settings to reduce the burden of ADEs in this vulnerable group.

'Aussie Normals': an a priori study to develop reference intervals in a healthy Australian population using the Beckman Coulter LH 750 Haematology Analyser as candidates for harmonised values.

Reference limits or intervals are important benchmarks or tools that help the clinician to distinguish between a result that is most likely to lie within a 'healthy' or diseased category. It has been suggested that a review of haematology reference intervals is long overdue. In this study we report on our findings for analytes routinely measured in a complete blood count (CBC) performed on the Beckman Coulter LH 750 analyser and an additional comparative study using the Beckman Coulter LH 750, the Sysmex XN and Abbott Sapphire. The results from the comparative study indicate that bias would not prevent harmonisation of reference intervals for these common haematology parameters. The results offered by the Aussie Normals study represent good candidates as the basis for harmonisation reference intervals.

'Aussie normals': an a priori study to develop clinical chemistry reference intervals in a healthy Australian population.

Development of reference intervals is difficult, time consuming, expensive and beyond the scope of most laboratories. The Aussie Normals study is a direct a priori study to determine reference intervals in healthy Australian adults. All volunteers completed a health and lifestyle questionnaire and exclusion was based on conditions such as pregnancy, diabetes, renal or cardiovascular disease. Up to 91 biochemical analyses were undertaken on a variety of analytical platforms using serum samples collected from 1856 volunteers. We report on our findings for 40 of these analytes and two calculated parameters performed on the Abbott ARCHITECTci8200/ci16200 analysers. Not all samples were analysed for all assays due to volume requirements or assay/instrument availability. Results with elevated interference indices and those deemed unsuitable after clinical evaluation were removed from the database. Reference intervals were partitioned based on the method of Harris and Boyd into three scenarios, combined gender, males and females and age and gender. We have performed a detailed reference interval study on a healthy Australian population considering the effects of sex, age and body mass. These reference intervals may be adapted to other manufacturer's analytical methods using method transference.

High-resolution SNP microarray investigation of copy number variations on chromosome 18 in a control cohort.

Copy number variations (CNVs) as described in the healthy population are purported to contribute significantly to genetic heterogeneity. Recent studies have described CNVs using lymphoblastoid cell lines or by application of specifically developed algorithms to interrogate previously described data. However, the full extent of CNVs remains unclear. Using high-density SNP array, we have undertaken a comprehensive investigation of chromosome 18 for CNV discovery and characterisation of distribution and association with chromosome architecture. We identified 399 CNVs, of which loss represents 98%, 58% are less than 2.5 kb in size and 71% are intergenic. Intronic deletions account for the majority of copy number changes with gene involvement. Furthermore, one-third of CNVs do not have putative breakpoints within repetitive sequences. We conclude that replicative processes, mediated either by repetitive elements or microhomology, account for the majority of CNVs in the healthy population. Genomic instability involving the formation of a non-B structure is demonstrated in one region.

Can a management pathway for chronic cough in children improve clinical outcomes: protocol for a multicentre evaluation.

BACKGROUND: Chronic cough is common and is associated with significant economic and human costs. While cough can be a problematic symptom without serious consequences, it could also reflect a serious underlying illness. Evidence shows that the management of chronic cough in children needs to be improved. Our study tests the hypothesis that the management of chronic cough in children with an evidence-based management pathway is feasible and reliable, and improves clinical outcomes. METHODS/DESIGN: We are conducting a multicentre randomised controlled trial based in respiratory clinics in 5 major Australian cities. Children (n = 250) fulfilling inclusion criteria (new patients with chronic cough) are randomised (allocation concealed) to the standardised clinical management pathway (specialist starts clinical pathway within 2 weeks) or usual care (existing care until review by specialist at 6 weeks). Cough diary, cough-specific quality of life (QOL) and generic QOL are collected at baseline and at 6, 10, 14, 26, and 52 weeks. Children are followed-up for 6 months after diagnosis and cough resolution (with at least monthly contact from study nurses). A random sample from each site will be independently examined to determine adherence to the pathway. Primary outcomes are group differences in QOL and proportion of children that are cough free at week 6. DISCUSSION: The clinical management pathway is based on data from Cochrane Reviews combined with collective clinical experience (250 doctor years). This study will provide additional evidence on the optimal management of chronic cough in children. TRIAL REGISTRATION: ACTRN12607000526471.

Improving response rates to primary and supplementary questionnaires by changing response and instruction burden: cluster randomised trial.

OBJECTIVE: Supplementary questionnaires provide additional information from subgroups, but may have an attritional effect on response rates. We examined the effects of different instruction methods on response rates to a two-part questionnaire. METHODS: The ACT Kindergarten Health Survey comprises a health questionnaire for all school-entry children. A supplementary questionnaire targets children with respiratory symptoms. We cluster-randomised 109 schools in the ACT (4,494 children) to two instruction groups. Group 1 (instruction burden) had instructions to complete the supplementary questionnaire if certain questions in the primary questionnaire were answered. Group 2 (response burden) had instructions to complete both questionnaires irrespective of answers to the primary questionnaire. RESULTS: Instructing all respondents to complete both questionnaires regardless of eligibility resulted in a statistically significantly lower primary questionnaire response rate (82% vs. 87%), but a statistically significantly higher response rate to the supplementary questionnaire (99% vs. 91%). The net effect was a small overall gain (82% vs. 79%) for the response burden group. CONCLUSION: Increasing the response burden had a minor impact on response rate to the primary questionnaire, but increased the response rate for most items to the supplementary questionnaire. IMPLICATIONS: Large surveys may be broken into primary and supplementary questionnaires, if strategies to maximise response rates are used. Questionnaires may need to be modified to take into account the likely attrition on response to either questionnaire resulting from instruction and response burdens.

Respiratory health in Aboriginal and Torres Strait Islander children in the Australian Capital Territory.

OBJECTIVES: To measure the prevalence of respiratory symptoms and atopic disease in Aboriginal and Torres Strait Islander (indigenous) and non-indigenous children in the Australian Capital Territory (ACT). METHODS: A two-stage questionnaire survey of children in the ACT with stage two completed for children identified by parents as having respiratory symptoms or asthma in the first stage cross-sectional survey. Participants in the study were: (i) all new entrant primary schoolchildren aged 4-6 years in 1999, 2000 and 2001, 217 being indigenous children and 10 604 being non-indigenous children (80% of eligible); and (ii) Year 1-6 primary schoolchildren in 2000, with 216 being indigenous children and 14 202 being non-indigenous children (52% of eligible). Respiratory symptoms (including recent wheeze and parent-reported asthma) and other factors were measured by parental questionnaire. RESULTS: Indigenous kindergarten children had more recent wheeze (21%, odds ratio (OR) 1.4 95% confidence interval (CI) 1.0-2.0)) and parent-reported asthma (24%, OR 1.8 95% CI 1.3-2.5) than non-indigenous children (both 15%). However, indigenous children had less eczema (25%, OR 0.7 95% CI 0.5-0.9) and hayfever (14%, OR 0.7 95% CI 0.5-1.0) than non-indigenous children (32% and 19%, respectively). Among children with respiratory symptoms, the symptom severity did not differ between groups, but indigenous children were exposed to more environmental tobacco smoke (ETS) (63%, OR 3.5 95% CI 2.1-5.9) than non-indigenous children (32%). CONCLUSIONS: Indigenous children in the ACT have more respiratory morbidity but less of the atopic diseases of hayfever and eczema than non-indigenous children. Whether the respiratory morbidity represents 'asthma' or results from increased ETS exposure is unclear and needs to be further explored.

The association between synthetic bedding and adverse respiratory outcomes among skin-prick test positive and skin-prick test negative children.

BACKGROUND: Synthetic bedding has been associated with increased child wheeze and also higher allergen levels in several studies. We aimed to examine whether the association between synthetic bedding and adverse respiratory outcomes was more evident among skin-prick test (SPT) positive children. METHODS: A cross-sectional survey involving a population sample of 758 (81% of eligible) school children aged 8-10 years from randomly selected schools in the Australian Capital Territory in 1999. Parental questionnaires for ISAAC respiratory symptoms and child bedding were obtained. SPT results of 10 common allergens were available on 722 of the subjects (77% of those eligible). Synthetic pillow or quilt use was termed synthetic upper bedding. RESULTS: Synthetic quilt use was associated with asthma (Adjusted Odds Ratio 1.67 (1.05, 2.65)), recent wheeze (AOR 1.63 (1.03, 2.59)) and allergic rhinoconjunctivitis (AOR 2.11 (1.33, 3.34)) among SPT-positive children. However, these associations were not apparent for SPT-negative children. Similarly, increasing synthetic upper bedding use was associated with more than 12 episodes of wheeze among SPT-positive children (AOR 1.69 (1.08, 2.64), P=0.02, per category) but not SPT-negative children (AOR 0.77 (0.26, 2.21), P=0.6, per category). CONCLUSION: The apparent association between synthetic upper bedding and adverse respiratory outcomes was evident among SPT-positive but not SPT-negative children. Prospective intervention studies that aim to examine the effect of upper bedding composition on child asthma among SPT-positive children are required.

Loss of interstitial cells of Cajal and development of electrical dysfunction in murine small bowel obstruction.

1. Partial obstruction of the murine ileum led to changes in the gross morphology and ultrastructure of the tunica muscularis. Populations of interstitial cells of Cajal (ICC) decreased oral, but not aboral, to the site of obstruction. Since ICC generate and propagate electrical slow waves in gastrointestinal muscles, we investigated whether the loss of ICC leads to loss of function in partial bowel obstruction. 2. Changes in ICC networks and electrical activity were monitored in the obstructed murine intestine using immunohistochemistry, electron microscopy and intracellular electrophysiological techniques. 3. Two weeks following the onset of a partial obstruction, the bowel increased in diameter and hypertrophy of the tunica muscularis was observed oral to the obstruction site. ICC networks were disrupted oral to the obstruction, and this disruption was accompanied by the loss of electrical slow waves and responses to enteric nerve stimulation. These defects were not observed aboral to the obstruction. 4. Ultrastructural analysis revealed no evidence of cell death in regions where the lesion in ICC networks was developing. Cells with a morphology intermediate between smooth muscle cells and fibroblasts were found in locations that are typically populated by ICC. These cells may have been the redifferentiated remnants of ICC networks. 5. Removal of the obstruction led to the redevelopment of ICC networks and recovery of slow wave activity within 30 days. Neural responses were partially restored in 30 days. 6. These data describe the plasticity of ICC networks in response to partial obstruction. After obstruction the ICC phenotype was lost, but these cells regenerated when the obstruction was removed. This model may be an important tool for evaluating the cellular/molecular factors responsible for the regulation and maintenance of the ICC phenotype.

The relationship between low level nitrogen dioxide exposure and child lung function after cold air challenge.

BACKGROUND: Nitrogen dioxide (NO(2)) or home gas appliance use has been inconsistently associated with adverse respiratory outcomes in childhood. OBJECTIVES: (i) To examine the contribution of home gas appliance type and personal NO(2) exposure. (ii) To examine the relationship between NO(2) exposure and child lung function and respiratory history. (iii) To assess whether these relationships vary by house dust mite sensitization status. METHODS: A cross-sectional survey of 344 children (71% of the eligible group) with a mean age of 9.1 years from four randomly selected schools in the Australian Capital Territory from July to September 1999. Study measurements included a parental questionnaire, NO(2) exposure by passive gas samplers, skin prick testing for 10 aeroallergens and lung function at rest and after cold air challenge. RESULTS: Total NO(2) exposure was low with a mean concentration of 10.1 ppb. No associations were found between NO(2) exposure or gas appliance use and asthma, wheeze or baseline lung function. Personal NO(2) exposure was associated with a reduction in forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) after cold air challenge (adjusted difference - 0.12% (- 0.23% to - 0.01%) per 1 ppb increase). After exclusion of children who had home heating changed because of asthma, gas heater use was also significantly associated with a reduction in this measure (adjusted difference - 2.0% (- 3.7% to - 0.2%)). There was some evidence that these reductions were greater among the non-mite-sensitized children. CONCLUSIONS: The effect of low-level NO(2) exposure on these respiratory outcomes was not marked. The possible effect of low-level NO(2) exposure on non-specific bronchial reactivity requires confirmation. Future studies on NO(2) and respiratory health should include measures of house dust mite sensitization and bronchial hyper-responsiveness.

Asthma screening as part of a routine school health assessment in the Australian Capital Territory.

OBJECTIVE: To determine the feasibility and performance of a routine screen for childhood asthma in new entrants to primary school relative to diagnosis by a paediatrician. DESIGN: Cross-sectional study with a validation substudy. PARTICIPANTS AND SETTING: All 4539 new primary school entrants (mean age, 5.72 years; 95% CI, 5.71-5.74) in the Australian Capital Territory (ACT) in 1999; 180 of these children (73% of the 248 contacted) participated in the validation substudy. MAIN OUTCOME MEASURE: Performance of the screening test relative to a paediatrician's diagnosis of current asthma (defined as a history of wheeze suggestive of a clinical diagnosis of asthma within the past 12 months) based on history and examination. RESULTS: 3748 of the 4539 new primary school entrants (83%) returned completed asthma and respiratory questions. The screening test was positive in 38% of children. Estimated sensitivity was 92% (95% CI, 75%-99%); specificity, 76% (95% CI, 72%-80%); positive predictive value, 51% (95% CI, 41%-63%); negative predictive value, 98% (95% CI, 90%-100%); positive likelihood ratio, 3.8 (95% CI, 2.8-4.8); and negative likelihood ratio, 0.14 (95% CI, 0.02-0.33). CONCLUSIONS: It is feasible to conduct population screens for asthma that have good diagnostic test performance against a specialist paediatrician's diagnosis through school health programs. This approach could facilitate monitoring changes in asthma prevalence over time.

Regulation of pacemaker currents in interstitial cells of Cajal from murine small intestine by cyclic nucleotides.

1. Electrical rhythmicity (slow waves) in gastrointestinal muscles (GI) is generated by interstitial cells of Cajal (ICC). Cultured ICC from the murine small intestine were studied with the patch-clamp technique to characterize regulation of pacemaker currents by cyclic nucleotides. Cyclic nucleotide agonists were also tested on intact strips of murine small intestine. 2. Nitric oxide donors slowed the frequency of pacemaker currents in a concentration-dependent manner. These effects depended on cGMP formation and were reduced by 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The effects of nitric oxide donors were mimicked by membrane-permeable analogues of cGMP. The specific cGMP phosphodiesterase inhibitor zaprinast reduced the frequency of spontaneous pacemaker currents. 3. The cGMP-dependent effects on pacemaker currents were not affected by okadaic acid or KT-5823, an inhibitor of protein kinase G. 4. Forskolin, but not dideoxy forskolin, reduced the frequency of spontaneous pacemaker activity and activated a sustained outward current. The latter was likely to be due to ATP-dependent K+ channels because it was blocked by glibenclamide. 5. The effects of forskolin were not mimicked by membrane-permeable cAMP analogues. A membrane-permeable inhibitor of protein kinase A, myristoylated PKA inhibitor, and the adenylyl cyclase inhibitor SQ-22536, had no effect on responses to forskolin. 6. Responses of intact muscles to cGMP and cAMP agonists were similar to the responses of pacemaker cells. Changes in resting membrane potential and slow wave amplitude, however, were noted in intact jejunal muscles that were not observed in ICC. Differences in responses may have been due to the effects of cyclic nucleotide agonists on smooth muscle cells that would sum with responses of ICC in intact jejunal muscle strips. 7. A cGMP-dependent mechanism regulates slow wave frequency, but this occurs through direct action of cGMP not via protein phosphorylation. Regulation of pacemaker currents by cAMP-dependent mechanisms was not observed.

When doctors lack knowledge and deal with uncertainty.

General practitioners are often confronted with problems, where their knowledge base may be lacking and/or diagnostic uncertainty exists, but competent management is still needed. Sometimes a case brings these issues very much to the fore, and in this case study the problem of familial Mediterranean fever is used to highlight some of the issues involved. This article also summarises this unusual condition which, with recent immigration patterns, may become more frequent in Australasia.

Doing randomized controlled trials in a developing country: some practical realities.

BACKGROUND: Formal randomized controlled trial results are often reported. The difficulties of doing such trial are not. Developing countries represent a new field in which trials can be undertaken. In this context even less is known about the practicalities involved. METHOD AND RESULTS: A randomized, double-blind, parallel study took significantly longer than expected to complete and subject recruitment and participation fell short of expectations. Different recruitment strategies were used and these performed differently in terms of enrolling trialists. Subjects most frequently left the trial in its early stages. CONCLUSIONS: Possible explanations for these findings include the demography of the country, cultural factors, and the existence of an established doctor-patient relationship.

Older urban migrants in rural settings: problems and prospects.

A substantial portion of the current urban to rural migration stream consists of older persons who are choosing to live in countryside residences rather than in towns. This article draws on experiences of older migrants in order to explore some of the objective and subjective implications of residential choice. The data demonstrate that while older persons living in the countryside have less access to goods and services, they are more satisfied, more likely to perceive a net improvement over the former residence, and more attached to their residences. The research suggests that the circumstances of older migrants in rural areas must be closely monitored to determine what effects aging and living costs will have on subsequent residential mobility.