The feasibility, acceptability and appropriateness of screening for frailty in Australians aged 75 years and over attending Australian general practice.

Background Globally, frailty is associated with a high prevalence of avoidable hospital admissions and emergency department visits, with substantial associated healthcare and personal costs. International guidelines recommend incorporation of frailty identification and care planning into routine primary care workflow to support patients who may be identified as pre-frail/frail. Our study aimed to: (1) determine the feasibility, acceptability, appropriateness and determinants of implementing a validated FRAIL Scale screening Tool into general practices in two disparate Australian regions (Sydney North and Brisbane South); and (2) map the resources and referral options required to support frailty management and potential reversal. Methods Using the FRAIL Scale Tool, practices screened eligible patients (aged ≥75years) for risk of frailty and referred to associated management options. The percentage of patients identified as frail/pre-frail, and management options and referrals made by practice staff for those identified as frail/pre-frail were recorded. Semi-structured qualitative interviews were conducted with practice staff to understand the feasibility, acceptability, appropriateness and determinants of implementing the Tool. Results The Tool was implemented by 19 general practices in two Primary Health Networks and 1071 consenting patients were assessed. Overall, 80% of patients (n =860) met the criterion for frailty: 33% of patients (n =352) were frail, and 47% were pre-frail (n =508). They were predominantly then referred for exercise prescription, medication reviews and geriatric assessment. The Tool was acceptable to staff and patients and compatible with practice workflows. Conclusions This study demonstrates that frailty is identified frequently in Australians aged ≥75years who visit their general practice. It's identification, linked with management support to reverse or reduce frailty risk, can be readily incorporated into the Medicare-funded annual 75+ Health Assessment.

Systematic Review and Meta-analysis of Laparoscopic Versus Open Radical Nephrectomy for Paediatric Renal Tumors With Focus on Wilms' Tumor.

OBJECTIVE: To summarize and evaluate the outcomes of laparoscopic radical nephrectomy (LRN) and compare its safety and efficacy with open radical nephrectomy (ORN) in pediatric renal tumors (RT) and Wilms' tumors (WT). BACKGROUND: ORN is the gold standard treatment for pediatric RT, consisting predominantly of WT. LRN is gaining popularity but remains controversial in pediatric surgical oncology. METHODS: A systematic search was performed for all eligible studies on LRN and comparative studies between LRN and ORN in pediatric RT and WT. Meta-analysis, subgroup analysis, and sensitivity analysis were conducted. The main endpoints were cancer-related outcomes and surgical morbidity. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. RESULTS: No levels I to II studies were identified. LRN was feasible in nearly 1 in 5 pediatric RT and WT after neoadjuvant chemotherapy, with pooled mid-term oncological outcomes (<7% local recurrence, >90% event-free survival) comparable with those of ORN. There was no strong evidence of an increased risk of intraoperative tumor spillage, but lymph node harvest was inadequate in LRN. Large tumors crossing the ipsilateral spinal border were associated with a trend for intraoperative complications and positive margins. Pooled complications rate and hospital stay duration were similar between LRN and ORN. Long-term (>3 years) outcomes are unknown. CONCLUSIONS: Available level III evidence indicates that LRN is a safe alternative to ORN for carefully selected cases, with similar spillage rates and mid-term oncological outcomes. However, there was no advantage in surgical morbidity and lymph node harvest was inadequate with LRN. Tumor-matched-group studies with long-term follow-up are required. LEVEL OF EVIDENCE: Level III.

The Queensland Virtual Integrated Practice (VIP) partnership program pilot study: an Australian-first model of care to support rural general practice.

BACKGROUND: There is a critical lack of medical workforce internationally, and this is particularly notable in rural and remote Australia where strategies to address workforce shortages are urgently required. This pilot study aimed to implement and evaluate a Virtual Integrated Practice (VIP) Program in the Australian rural primary care setting. METHODS: The VIP model was developed using co-creation methodology and involves an urban GP joining a rural general practice team to provide ongoing care to patients remotely via secure telehealth. The pilot study was conducted in two western Queensland general practices, commencing in October 2021 with one rural practice and extending to an additional rural practice from November 2022. Evaluation included a retrospective review of service, billing and cost data, and an online survey for patients. Ethical approval was obtained from the University of Queensland Human Research Ethics Committee (Project number: 2021/HE002434). RESULTS: There were 1468 services provided through to December 2022, including general consults (n = 1197), therapeutic procedures (n = 68), mental health treatment plans (n = 68) and chronic disease management plans (n = 59). Patients were predominantly female (73.1%) and did not have their appointment at the practice (57.8%). Among 1282 occasions of service, less than 20% of consultations (n = 224) required support from staff (e.g., a nurse), and more than half were repeat patient encounters (53.0%). Survey respondents (n = 45) indicated that they were satisfied (9.3%) or highly satisfied (90.7%) with the care provided, and importantly, 95.5% of respondents reported that the service improved their access to the GP. More than 20% of respondents indicated that they would attend the Emergency Department if virtual care was not available. CONCLUSIONS: Data from this pilot study has informed translation to an additional 20 vulnerable rural general practices in three further rural regions in Queensland in 2023 and evaluation is ongoing. This pilot study demonstrates the feasibility and acceptability of an innovative, digitally supported community-focussed, healthcare initiative to arrest the decline in rural general practice workforce, improve patient care access and support rural practice viability.

An eConsultant versus a hospital-based outpatient consultation for general (internal) medicine: a costing analysis.

BACKGROUND: The eConsultant model of care is an outpatient substitution approach which has been evaluated and implemented extensively internationally. It provides an asynchronous, digital, clinician-to-clinician advice service, giving primary care physicians remote access to specialist support for patient care within 3 business days. Results from initial trials of the eConsultant model in Australia support international evidence of reduced wait times and improved access to specialist input, avoidance of face-to-face hospital outpatient visits, and better integrated care. This study compared the cost of delivery of an eConsultant episode of care with that of a hospital-based outpatient appointment. METHODS: A cost-minimisation analysis, using a decision analytic model, was used to compare the two approaches. eConsultant costs were calculated from specialist reported data (minutes spent preparing the response; the number of patients referred subsequently for a hospital-based outpatient appointment) and administration staff data (time spent recording the occasion-of-service). Outpatient costs were calculated using finance data and information from outpatient clinic managers at the hospital-based outpatient clinic. The primary outcome was incremental cost saving per patient from a hospital system perspective. Uncertainty was explored using one-way sensitivity analyses and characterised with probabilistic sensitivity analysis using 10,000 Monte Carlo simulations. RESULTS: The traditional referral pathway cost estimate was $587.20/consult compared to $226.13/consult for an eConsultant episode: an efficiency saving of $361.07 per patient. The incremental difference between eConsultant and traditional care was most sensitive to the cost estimate of an outpatient attendance, the time for a specialist to complete an eConsult, and the probability of a patient requiring a face-to-face hospital-based attendance following an eConsult. However, at the upper bounds of each of these estimates, an eConsult remained the most cost-efficient model. In 96.5% of the Monte Carlo simulations eConsult was found to be more cost efficient than the traditional approach. CONCLUSIONS: The eConsultant model of care was associated with a 61.5% efficiency gain, allowing diversion of support to hospital-based outpatient appointments.

Supporting complex care in general practice via an eConsultant model of care: the Australian specialist perspective.

BACKGROUND: Accessing timely specialist physician advice and guidance is of critical importance to both Australian GP specialists (GPs) and their patients. The traditional method of referral, triage and subsequent face-to-face (FTF) consultation is facing challenges from an ever increasing volume of referrals and the needs of underserved populations. In response to such issues, electronic consults (eConsults) have been successfully used internationally to provide GPs with a means of asynchronously accessing specialist physician advice and guidance within 72h. Few studies have addressed the potential impact of eConsults from the view of the non-GP specialist receiving the request, and none specifically related to specialist adult medicine physicians. The aim of this study was to determine the perceptions of current Royal Australasian College of Physicians (RACP) adult medicine Fellows towards establishing an eConsult model of care within their own clinical practice. METHODS: Semi-structured interviews were conducted with 14 RACP adult medicine Fellows between December 2019 and February 2020. Purposive and snowball sampling strategies were used to recruit physicians of differing ages and gender from diverse specialties and healthcare settings. The data were subjected to a descriptive thematic analysis. RESULTS: We describe five key themes of relevance to study participants: (1) improved access to non-GP specialist care; (2) the business model in relation to remuneration and time; (3) enhanced GP-Physician relationships; (4) impact on physician work-life balance; and (5) the need for a structured model of care. There was broad consensus that a significant number of outpatient referrals to adult medicine physicians would be more appropriately addressed in primary care with support via an asynchronous eConsult arrangement. RACP Fellows agreed this could improve access to timely specialist advice, place downward pressure on outpatient FTF clinic waiting times and reduce unnecessary patient travel. CONCLUSION: These findings identify the drivers and barriers to the establishment of an Australian eConsultant model of care from the adult medicine physician's perspective.

The Palestinian primary ciliary dyskinesia population: first results of the diagnostic and genetic spectrum.

Background: Diagnostic testing for primary ciliary dyskinesia (PCD) started in 2013 in Palestine. We aimed to describe the diagnostic, genetic and clinical spectrum of the Palestinian PCD population. Methods: Individuals with symptoms suggestive of PCD were opportunistically considered for diagnostic testing: nasal nitric oxide (nNO) measurement, transmission electron microscopy (TEM) and/or PCD genetic panel or whole-exome testing. Clinical characteristics of those with a positive diagnosis were collected close to testing including forced expiratory volume in 1 s (FEV1) Global Lung Index z-scores and body mass index z-scores. Results: 68 individuals had a definite positive PCD diagnosis, 31 confirmed by genetic and TEM results, 23 by TEM results alone, and 14 by genetic variants alone. 45 individuals from 40 families had 17 clinically actionable variants and four had variants of unknown significance in 14 PCD genes. CCDC39, DNAH11 and DNAAF11 were the most commonly mutated genes. 100% of variants were homozygous. Patients had a median age of 10.0 years at diagnosis, were highly consanguineous (93%) and 100% were of Arabic descent. Clinical features included persistent wet cough (99%), neonatal respiratory distress (84%) and situs inversus (43%). Lung function at diagnosis was already impaired (FEV1 z-score median -1.90 (-5.0-1.32)) and growth was mostly within the normal range (z-score mean -0.36 (-3.03-2.57). 19% individuals had finger clubbing. Conclusions: Despite limited local resources in Palestine, detailed geno- and phenotyping forms the basis of one of the largest national PCD populations globally. There was notable familial homozygosity within the context of significant population heterogeneity.

Biallelic variants in CEP164 cause a motile ciliopathy-like syndrome.

Ciliopathies may be classed as primary or motile depending on the underlying ciliary defect and are usually considered distinct clinical entities. Primary ciliopathies are associated with multisystem syndromes typically affecting the brain, kidney, and eye, as well as other organ systems such as the liver, skeleton, auditory system, and metabolism. Motile ciliopathies are a heterogenous group of disorders with defects in specialised motile ciliated tissues found within the lung, brain, and reproductive system, and are associated with primary ciliary dyskinesia, bronchiectasis, infertility and rarely hydrocephalus. Primary and motile cilia share defined core ultra-structures with an overlapping proteome, and human disease phenotypes can reflect both primary and motile ciliopathies. CEP164 encodes a centrosomal distal appendage protein vital for primary ciliogenesis. Human CEP164 mutations are typically described in patients with nephronophthisis-related primary ciliopathies but have also been implicated in motile ciliary dysfunction. Here we describe a patient with an atypical motile ciliopathy phenotype and biallelic CEP164 variants. This work provides further evidence that CEP164 mutations can contribute to both primary and motile ciliopathy syndromes, supporting their functional and clinical overlap, and informs the investigation and management of CEP164 ciliopathy patients.

Offsite primary care providers using telehealth to support a sustainable workforce in rural and remote general practice: A rapid review of the literature.

INTRODUCTION: Rural and remote general practices face increasing demands for care without the workforce required to meet patient needs. The coronavirus pandemic has created an opportunity to explore sustainable, telehealth-driven solutions to this chronic and complex problem. OBJECTIVE: This review examined interventions using offsite primary care providers to deliver ongoing patient care via telehealth to support rural and remote general practices. We aimed to understand the impact of such interventions on the Quadruple Aim (patient experience, provider experience, health care costs, and health outcomes). DESIGN: A rapid review of studies published from 2011 and grey literature published from 2016. FINDINGS: Six studies met the eligibility criteria. No eligible Australian studies were identified. Most studies investigated ongoing primary care services provided via telehealth by offsite pharmacists. Patients and rural primary care staff reported positive experiences with the interventions. One study demonstrated potential return on investment for rural practices. While one study reported clinically and statistically significant improvements in health outcomes over time, two studies did not observe statistically significant differences in health outcomes between intervention and control cohorts. DISCUSSION: The Quadruple Aim should be carefully considered when designing, implementing, and evaluating interventions that involve offsite primary care providers using telehealth to support a sustainable workforce in rural and remote general practice. CONCLUSION: Sustainable solutions to workforce shortages in rural and remote general practice are needed urgently. Using offsite primary care providers to deliver telehealth and support practices in these regions is one possible solution that warrants further investigation, particularly in Australia.

The use of temozolomide in paediatric metastatic phaeochromocytoma/paraganglioma: A case report and literature review.

There is increasing evidence to support the use of temozolomide therapy for the treatment of metastatic phaeochromocytoma/paraganglioma (PPGL) in adults, particularly in patients with SDHx mutations. In children however, very little data is available. In this report, we present the case of a 12-year-old female with a SDHB-related metastatic paraganglioma treated with surgery followed by temozolomide therapy. The patient presented with symptoms of palpitations, sweating, flushing and hypertension and was diagnosed with a paraganglioma. The primary mass was surgically resected six weeks later after appropriate alpha- and beta-blockade. During the surgery extensive nodal disease was identified that had been masked by the larger paraganglioma. Histological review confirmed a diagnosis of a metastatic SDHB-deficient paraganglioma with nodal involvement. Post-operatively, these nodal lesions demonstrated tracer uptake on 18F-FDG PET-CT. Due to poor tumour tracer uptake on 68Ga-DOTATATE and 123I-MIBG functional imaging studies radionuclide therapy was not undertaken as a potential therapeutic option for this patient. Due to the low tumour burden and lack of clinical symptoms, the multi-disciplinary team opted for close surveillance for the first year, during which time the patient continued to thrive and progress through puberty. 13 months after surgery, evidence of radiological and biochemical progression prompted the decision to start systemic monotherapy using temozolomide. The patient has now completed ten cycles of therapy with limited adverse effects and has benefited from a partial radiological and biochemical response.

Implementing a general practitioner-to-general physician eConsult service (eConsultant) in Australia.

BACKGROUND: In response to lengthy wait times for specialist outpatient appointments, electronic consultation (eConsult) services have developed globally, providing asynchronous, secure and timely communication between general practitioner (GP) and specialist. This study aims to track adoption of a Queensland eConsultant service in two Australian Primary Health Networks (Western Queensland and Brisbane South) to understand key barriers and enablers to adoption and inform modification of the implementation strategy.  METHODS: Our theory-informed mixed-methods evaluation assessed implementation between July 2020 and March 2022. Adoption and implementation activities were prospectively recorded in bespoke tracking spreadsheets with implementation activities coded against the Expert Recommendations for Implementing Change (ERIC) strategies. Semi-structured interviews with GPs and stakeholders informed by the Consolidated Framework for Implementation Research (CFIR) were conducted to understand determinants of implementation.  RESULTS: Of the 40 practices invited to take part in the eConsultant service, 20 (50%) enrolled. Of the 97 GPs who consented, 38 sent at least one Request for Advice (RFA) to the eConsultant with a total of 112 RFA sent. Implementation was predominantly guided by eight strategies. Qualitative interviews were conducted with 11 GPs and 4 stakeholders (12 from rural/remote regions, 11 females and two sole practitioners). Interviewees felt the eConsultant service supported outpatient appointment avoidance and provided efficient, timely access to specialist support for GPs and their patients. Barriers identified to using eConsultant related to digital infrastructure, competing priorities, and keeping the service 'front of mind'. Key enablers identified were the relative advantage of eConsultant over other options, patient benefits and COVD-19 facilitating the use of digital technology. CONCLUSIONS: This evaluation highlighted service enablers as well as user priorities for broader implementation. A focus on a well-integrated digital system and availability of a variety of eConsultant specialties are seen as key strategies to embedding the eConsultant option in GP advice processes in Australia.

Temporal Whole-Transcriptomic Analysis of Characterized In Vitro and Ex Vivo Primary Nasal Epithelia.

Air-liquid interface (ALI) cell culture of primary airway progenitors enables the differentiation and recapitulation of a pseudostratified epithelium in vitro, providing a highly useful tool for researching respiratory health and disease. Previous studies into gene expression in ALI-cultures compared to ex vivo nasal brushings have been limited in the number of time-points and/or the number of genes studied. In this study physiological and global transcriptomic changes were assessed in an extended in vitro 63-day human healthy nasal epithelium ALI-culture period and compared to ex vivo nasal brushing samples. Ex vivo nasal brushing samples formed distinct transcriptome clusters to in vitro ALI-cultured nasal epithelia, with from day 14 onwards ALI samples best matching the ex vivo samples. Immune response regulation genes were not expressed in the in vitro ALI-culture compared to the ex vivo nasal brushing samples, likely because the in vitro cultures lack an airway microbiome, lack airborne particles stimulation, or did not host an immune cell component. This highlights the need for more advanced co-cultures with immune cell representation to better reflect the physiological state. During the first week of ALI-culture genes related to metabolism and proliferation were increased. By the end of week 1 epithelial cell barrier function plateaued and multiciliated cell differentiation started, although widespread ciliation was not complete until day 28. These results highlight that time-points at which ALI-cultures are harvested for research studies needs to be carefully considered to suit the purpose of investigation (transcriptomic and/or functional analysis).

Towards an artificial human lung: modelling organ-like complexity to aid mechanistic understanding.

Respiratory diseases account for over 5 million deaths yearly and are a huge burden to healthcare systems worldwide. Murine models have been of paramount importance to decode human lung biology in vivo, but their genetic, anatomical, physiological and immunological differences with humans significantly hamper successful translation of research into clinical practice. Thus, to clearly understand human lung physiology, development, homeostasis and mechanistic dysregulation that may lead to disease, it is essential to develop models that accurately recreate the extraordinary complexity of the human pulmonary architecture and biology. Recent advances in micro-engineering technology and tissue engineering have allowed the development of more sophisticated models intending to bridge the gap between the native lung and its replicates in vitro Alongside advanced culture techniques, remarkable technological growth in downstream analyses has significantly increased the predictive power of human biology-based in vitro models by allowing capture and quantification of complex signals. Refined integrated multi-omics readouts could lead to an acceleration of the translational pipeline from in vitro experimental settings to drug development and clinical testing in the future. This review highlights the range and complexity of state-of-the-art lung models for different areas of the respiratory system, from nasal to large airways, small airways and alveoli, with consideration of various aspects of disease states and their potential applications, including pre-clinical drug testing. We explore how development of optimised physiologically relevant in vitro human lung models could accelerate the identification of novel therapeutics with increased potential to translate successfully from the bench to the patient's bedside.

Living with Loss: study protocol for a randomized controlled trial evaluating an internet-based perinatal bereavement program for parents following stillbirth and neonatal death.

BACKGROUND: Stillbirth and neonatal death are devastating pregnancy outcomes with long-lasting psychosocial consequences for parents and families, and wide-ranging economic impacts on health systems and society. It is essential that parents and families have access to appropriate support, yet services are often limited. Internet-based programs may provide another option of psychosocial support for parents following the death of a baby. We aim to evaluate the efficacy and acceptability of a self-guided internet-based perinatal bereavement support program "Living with Loss" (LWL) in reducing psychological distress and improving the wellbeing of parents following stillbirth or neonatal death. METHODS: This trial is a two-arm parallel group randomized controlled trial comparing the intervention arm (LWL) with a care as usual control arm (CAU). We anticipate recruiting 150 women and men across Australia who have experienced a stillbirth or neonatal death in the past 2 years. Participants randomized to the LWL group will receive the six-module internet-based program over 8 weeks including automated email notifications and reminders. Baseline, post-intervention, and 3-month follow-up assessments will be conducted to assess primary and secondary outcomes for both arms. The primary outcome will be the change in Kessler Psychological Distress Scale (K10) scores from baseline to 3-month follow-up. Secondary outcomes include perinatal grief, anxiety, depression, quality of life, program satisfaction and acceptability, and cost-effectiveness. Analysis will use intention-to-treat linear mixed models to examine psychological distress symptom scores at 3-month follow-up. Subgroup analyses by severity of symptoms at baseline will be undertaken. DISCUSSION: The LWL program aims to provide an evidence-based accessible and flexible support option for bereaved parents following stillbirth or neonatal death. This may be particularly useful for parents and healthcare professionals residing in rural regions where services and supports are limited. This RCT seeks to provide evidence of the efficacy, acceptability, and cost-effectiveness of the LWL program and contribute to our understanding of the role digital services may play in addressing the gap in the availability of specific bereavement support resources for parents following the death of a baby, particularly for men. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12621000631808 . Registered prospectively on 27 May 2021.

Gonadotrophin-independent Precocious Puberty Secondary to an Estrogen Secreting Adrenal Tumor.

BACKGROUND: Adrenal masses are rare in children and most commonly present with clinical features of virilization in the absence of activation of the pituitary axis-gonadotrophin-independent precocious puberty. OBSERVATIONS: We report an unusual case of a 7-year-old girl who presented with clinical signs suggestive of exposure to both androgens and estrogens. Imaging revealed a left-sided adrenal mass with no evidence of metastasis. She underwent successful laparoscopic unilateral adrenalectomy. Histology confirmed an adrenal adenoma. CONCLUSION: We conclude that adrenocortical tumors should be considered in children presenting with gonadotrophin-independent precocious puberty and raised estrogens.

Lower airway clinical outcome measures for use in primary ciliary dyskinesia research: a scoping review.

OBJECTIVES: Disease-specific, well-defined and validated clinical outcome measures are essential in designing research studies. Poorly defined outcome measures hamper pooling of data and comparisons between studies. We aimed to identify and describe pulmonary outcome measures that could be used for follow-up of patients with primary ciliary dyskinesia (PCD). METHODS: We conducted a scoping review by systematically searching MEDLINE, Embase and the Cochrane Database of Systematic Reviews online databases for studies published from 1996 to 2020 that included ≥10 PCD adult and/or paediatric patients. RESULTS: We included 102 studies (7289 patients). 83 studies reported on spirometry, 11 on body plethysmography, 15 on multiple-breath washout, 36 on high-resolution computed tomography (HRCT), 57 on microbiology and 17 on health-related quality of life. Measurement and reporting of outcomes varied considerably between studies (e.g. different scoring systems for chest HRCT scans). Additionally, definitions of outcome measures varied (e.g. definition of chronic colonisation by respiratory pathogen), impeding direct comparisons of results. CONCLUSIONS: This review highlights the need for standardisation of measurements and reporting of outcome measures to enable comparisons between studies. Defining a core set of clinical outcome measures is necessary to ensure reproducibility of results and for use in future trials and prospective cohorts.

Feasibility of an asynchronous general practitioner-to-general physician eConsultant outpatient substitution program: A Queensland pilot study.

BACKGROUND AND OBJECTIVES: The use of an 'eConsultant' to support the family physician is an established outpatient substitution model in North America. This pilot study investigates the feasibility of the eConsultant model for complex chronic disease management within the Australian setting. METHOD: This pilot study was implemented in one urban and four rural/remote general practices in one state. The general practitioner (GP) sent a request for advice (RFA), a clinical summary with a specific clinical question/s, via secure messaging to a physician working remotely. Responses were required for GP/patient follow-up within 72 hours. RESULTS: The mean (standard deviation [SD]) time for general physician reply was 2.1 (1.2) days, and mean (SD) time from initial to subsequent GP/patient review was 14.8 (16.7) days. Only 13.3% of eConsultations required a subsequent face-to-face outpatient department appointment. DISCUSSION: The eConsultant model is feasible in Australia, with potential for improving access and reducing time to non-GP specialist input.