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Identifying characteristics of absent diabetes discharge coding in observational and trial cohorts
No full textAim: Accurate discharge coding of diabetes following hospital admissions is essential for quality of care, resource planning, and research. However, discharge coding will not record diabetes that is not managed during an admission, introducing selection bias for research relying upon it. This study aimed to identify the prevalence of absent diabetes discharge coding and examine the clinical factors associated with it.
Methods: We analysed data from two studies of inpatients at the Royal Melbourne Hospital: the STOIC-D Surgery randomised controlled trial and the DINGO prospective observational study. Diabetes was defined using clinical criteria: a documented history of diabetes in the clinical record or HbA1c ≥6.5% during the relevant admission. Discharge coding was obtained from hospital administrative records. Multivariable logistic regression was performed among patients with clinically defined diabetes to assess associations between absent diabetes coding status and age, gender, HbA1c, diabetes duration, insulin use, steroid use, length of stay (LOS), and modified Charlson Comorbidity Index (mCCI).
Results: Among 2,648 patients with clinically defined diabetes, 163 (6.2%) were not coded as having diabetes. Absent coding was more common in the DINGO cohort (7.3%) than in the STOIC-D Surgery clinical trial cohort (4.0%). HbA1c (odds ratio [OR] 0.69, 95%CI 0.60– 0.79), diabetes duration (OR 0.68, 95%CI 0.63–0.73), and management with insulin (OR 0.63, 95% CI 0.40–0.98) were each independently associated with lower odds of absent diabetes discharge coding.
Conclusion: Absent diabetes discharge coding is more likely in admissions characterised by a lower HbA1c, shorter duration of diabetes, and management without insulin. Researchers and policy-makers relying on hospital discharge coding to identify individuals with diabetes must be aware of these limitations to avoid mis-representing the prevalence and characteristics of inpatient diabetes
A Prospective, Multicentre Case-Control Trial Examining Factors That Explain Variable Clinical Performance in Post Lingual Adult CI Recipients
No full textThis study investigated which of a range of factors could explain performance in two distinct groups of experienced, adult cochlear implant recipients differentiated by performance on words in quiet: 72 with poorer word scores versus 77 with better word scores. Tests measured the potential contribution of sound processor mapping, electrode placement, neural health, impedance, cognitive, and patient-related factors in predicting performance. A systematically measured sound processor MAP was compared to the subject's walk-in MAP. Electrode placement included modiolar distance, basal and apical insertion angle, and presence of scalar translocation. Neural health measurements included bipolar thresholds, polarity effect using asymmetrical pulses, and evoked compound action potential (ECAP) measures such as the interphase gap (IPG) effect, total refractory time, and panoramic ECAP. Impedance measurements included trans impedance matrix and four-point impedance. Cognitive tests comprised vocabulary ability, the Stroop test, and the Symbol Digits Modality Test. Performance was measured with words in quiet and sentence in noise tests and basic auditory sensitivity measures including phoneme discrimination in noise and quiet, amplitude modulation detection thresholds and quick spectral modulation detection. A range of predictor variables accounted for between 33% and 60% of the variability in performance outcomes. Multivariable regression analyses showed four key factors that were consistently predictive of poorer performance across several outcomes: substantially underfitted sound processor MAP thresholds, higher average bipolar thresholds, greater total refractory time, and greater IPG offset. Scalar translocation, cognitive variables, and other patient related factors were also significant predictors across more than one performance outcome
Accelerated retinal ageing and multimorbidity in middle-aged and older adults
No full textThe aim of this study is to investigate the association between retinal age gap and multimorbidity. Retinal age gap was calculated based on a previously developed deep learning model for 45,436 participants. The number of age-related conditions reported at baseline was summed and categorized as zero, one, or at least two conditions at baseline (multimorbidity). Incident multimorbidity was defined as having two or more age-related diseases onset during the follow-up period. Linear regressions were fit to examine the associations of disease numbers at baseline with retinal age gaps. Cox proportional hazard regression models were used to examine associations of retinal age gaps with the incidence of multimorbidity. In the fully adjusted model, those with multimorbidity and one disease both showed significant increases in retinal age gaps at baseline compared to participants with zero disease number (β = 0.254, 95% CI 0.154, 0.354; P < 0.001; β = 0.203, 95% CI 0.116, 0.291; P < 0.001; respectively). After a median follow-up period of 11.38 (IQR, 11.26-11.53; range, 0.02-11.81) years, a total of 3607 (17.29%) participants had incident multimorbidity. Each 5-year increase in retinal age gap at baseline was independently associated with an 8% increase in the risk of multimorbidity (HR = 1.08, 95% CI 1.02, 1.14, P = 0.008). Our study demonstrated that an increase of retinal age gap was independently associated with a greater risk of incident multimorbidity. By recognizing deviations from normal aging, we can identify individuals at higher risk of developing multimorbidity. This early identification facilitates patients' self-management and personalized interventions before disease onset
Prospective relationships of body appreciation and functionality appreciation with body dissatisfaction and psychological quality of life among sexual minority men
No full textCross-sectional studies indicate that body appreciation and functionality appreciation are independently predictive of positive outcomes, including lower body dissatisfaction and improved psychological wellbeing. Sexual minority (e.g., gay, bisexual) men are underrepresented in positive body image research, warranting an examination of whether positive body image might also engender positive impacts on body image and psychological wellbeing for this population. We examined the longitudinal relationships of body appreciation and functionality appreciation with psychological quality of life (a multidimensional construct that encompasses psychological wellbeing, mental health, and self-worth), body fat dissatisfaction, and muscularity dissatisfaction among 821 sexual minority men. We used cross-lagged panel models to examine the bidirectional relationships of these constructs across three timepoints spanning 18 months. Greater muscularity dissatisfaction, body fat dissatisfaction, and psychological quality of life impairment were associated with lower body appreciation over time. Body appreciation was positively associated with psychological quality of life impairment over time, but did not predict any other outcome over time. Functionality appreciation was an outcome in one model: greater psychological quality of life impairment was associated with lower functionality appreciation over time. Functionality appreciation was not associated with muscularity or body fat dissatisfaction in either direction over time. These findings can guide intervention development. For example, future research might explore the efficacy of interventions for improving body appreciation on men's muscularity dissatisfaction, and vice-versa. Further, interventions for improving men's psychological wellbeing may be beneficial for both their body and functionality appreciation
Clinician's Approach to Antibiotic Treatment and Management of Preterm Prelabour Rupture of Membranes (PPROM) in Australia and Aotearoa New Zealand—A Survey
No full textBACKGROUND: Preterm prelabour rupture of membranes (PPROM) is a common obstetric complication with significant maternal and foetal consequences. There is a lack of contemporary evidence regarding the optimal management of PPROM, including the best antibiotic regimen and management at previable gestations. AIMS: To understand the contemporary management of PPROM among clinicians in Australia and Aotearoa New Zealand. MATERIALS AND METHODS: An anonymous web-based survey was designed and distributed, consisting of 31 questions about individual clinicians' routine management of PPROM across a range of different gestations. RESULTS: The survey was completed by 235 clinicians from across Australia and Aotearoa New Zealand. The majority (225/232, 97%) routinely prescribed prophylactic antibiotics after PPROM, with 90 different antibiotic regimens documented. The most commonly prescribed prophylactic antibiotics were erythromycin (198/225, 88%) and penicillins (103/225, 46%). There was variation in practice regarding the timing of birth after PPROM, with 62% (147/235) routinely delaying birth until after 37 weeks of gestation, and 61% (143/235) expediting birth after 34 weeks of gestation if Group B Streptococcus was cultured antenatally. For previable PPROM (< 22 weeks of gestation), 74% (171/232) of women were routinely admitted to hospital at the time of diagnosis and 77% (173/225) were routinely offered antibiotics. There was significant variation in the earliest gestational ages at which antenatal corticosteroids and resuscitation are offered. CONCLUSIONS: We observed wide variation in clinical practice of management of PPROM. With a lack of national consensus regarding optimal management of this common pregnancy complication, contemporary clinical trials to define best practices are required
Cell Death Signaling and BET Protein Function in a Cytokine Storm Syndrome Model
No full text© 2025 Farzanehsadat RezazadehshojaeeRegulated cell death (RCD) is essential for tissue homeostasis and host defence, but when dysregulated, it drives pathological inflammation. Lytic forms of RCD, including MLKL-driven necroptosis and gasdermin-mediated pyroptosis, amplify immune responses by coupling plasma membrane rupture with cytokine maturation and the release of damage-associated molecular patterns (DAMPs). In cytokine storm syndromes such as hemophagocytic lymphohistiocytosis (HLH), this unchecked inflammation can escalate to systemic cytokine release, multi-organ injury, and fatal outcomes. This thesis examines whether specific cell death programs drive HLH pathogenesis and explores strategies to selectively target these processes for therapeutic intervention.
Using a murine model of secondary HLH (sHLH) I identified the innate immune sensor, the NLRP3 inflammasome, as a central determinant of both lethality and systemic cytokine release. Unexpectedly, combined deletion of the inflammasome-activated cytokines IL-1b and IL-18 did not protect against lethal disease. Instead, lethality was mediated by redundancy between the inflammasome-activated pyroptotic pore-forming gasdermin proteins, GSDMD and GSDME. Disruption of either gasdermin alone provided partial protection from sHLH, whereas combined deletion markedly improved animal survival, establishing inflammasome-triggered pyroptosis rather than its ability to activate IL-1 family cytokines as a dominant driver of pathology. By contrast, the alternate lytic cell death modality, necroptosis, was dispensable in this sHLH model. This work also discovered that bromodomain and extraterminal domain (BET) inhibitors, which block BET protein binding to acetylated histones and their regulation of gene transcription, suppress NLRP3 and IL-1b production to reduce pyroptosis and inflammatory cytokine levels. Consequently, BET inhibitor treatment improved sHLH animal survival, positioning BET proteins as key regulators of hyperinflammation and promising therapeutic targets.
To explore which BET family protein, BRD2, BRD3 or BRD4, regulate NLRP3 and IL-1b levels, I investigated BRD2. Genetic experiments in bone marrow derived macrophages showed that disruption of both the BRD2 bromodomains (BD1 and BD2) that interact with acetylated lysines was necessary to reduce IL-1b protein levels upon LPS stimulation, whereas selective BRD2 BD1 disruption, or deletion of other BET family members, BRD3 or BRD4, had no substantial effect on IL-1b production. This regulation occurred independently of Il1b transcript abundance, implicating a previously unrecognized post-transcriptional or post-translational mechanism under BRD2 control that warrants further investigation. Notably, BET inhibitor mediated loss of NLRP3 protein were not reproduced by BRD2 disruption alone, suggesting redundancy among BET family members in regulating inflammasome priming.
In addition, whole-genome RNA sequencing showed that disruption of both BRD2 bromodomains, but not BD1 alone, had broader transcriptional effects at steady state and after LPS stimulation. Baseline changes implicated bone and cartilage pathways, while LPS responses involved synapse-related translation, underscoring domain-specific regulation of gene expression by BRD2.
Collectively, this thesis shows that NLRP3-mediated pyroptotic cell death, rather than individual cytokines, can be a dominant driver of sHLH, identified BET proteins as critical for inflammasome priming, and uncovered how BRD2 bromodomains regulate IL-1b protein production and are also key for controlling macrophage functioning. These insights identifying a new epigenetic checkpoint in inflammasome signaling support BET proteins as promising therapeutic targets for treating highly lethal cytokine storm syndromes
Impact of windward and effective slope on the roughness effect of ratchet-type surfaces in turbulent channel flow
No full textRatchet-type surfaces, also known as saw-tooth surfaces, represent a special class of anisotropic roughness that breaks the forward–backward statistical symmetry of the flow due to an imbalance between the slopes of their windward and leeward faces. The influence of effective and windward slopes on the fluid dynamic roughness effect of these surfaces is investigated using direct numerical simulations of turbulent channel flow. The simulations are conducted at friction Reynolds number 550 for a series of ratchet-type surfaces with a systematically varied windward slope (WS) at constant effective slope (ES) and vice versa, covering most of the possible range of WS for each ES. The results reveal a strong dependence of the roughness effect on both windward and effective slope of the surfaces, which cannot be captured by existing empirical correlations, including those containing slope-sensitive parameters, and the wind-shade roughness model. Using the present data, improved correlations based on geometrical parameters for prediction of the roughness function and the equivalent sand-grain roughness are proposed for surfaces with a skewed streamwise slope distribution. In addition, the results reveal a significant impact of windward and effective slope on the levels of outer-layer similarity and the mean flow field around the ratchet canopy
Protocol for the comparison of remote versus face-to-face osteoarthritis management programs (COASTAL): A randomized implementation trial
No full textOBJECTIVE: To determine the comparative effectiveness of three evidence-informed approaches to delivering osteoarthritis (OA) care in real-world settings: face-to-face services, telehealth services or a mobile application (app). DESIGN: COASTAL (ACTRN12624000996561) comprises two aims: the primary aim is a three-arm, non-inferiority, comparative-effectiveness, type I hybrid implementation RCT; and the secondary aim is a superiority trial to compare the three interventions separately to an untreated, non-randomized control group. We will recruit 1348 participants (primary aim:1011 interventions; secondary aim:1011 interventions, 337 controls) with knee OA referred to a NSW public Osteoarthritis Chronic Care Program (OACCP). Eligible participants who consent to OACCP participation will be randomized 1:1:1 to receive care through the face-to-face OACCP, a telehealth service, or the "OA Coach" app, over 6-months. All participants will receive a standardized needs assessment; OA education; collaboratively developed, personalized management plan with a focus on therapeutic exercise, physical activity, pain management, and weight-management, according to each arm's mode of delivery. People who have declined OACCP participation will be eligible for the control group. The primary outcome is change in average knee pain during walking at 6-months (11-point NRS). Secondary, implementation, and economic evaluation outcomes will be collected at 6 and 12-months.The protocol was co-developed with people with knee OA, clinicians delivering the services, and other stakeholders. Ethical approval granted by the Northern Sydney Local Health District (2024/ETH01461). CONCLUSION: The results of this trial will provide critical evidence to help people with OA, clinicians, service planners and policymakers choose between different modes of delivering care for knee OA
Exploring the Complexity of the Relationship between Global Life Satisfaction and Satisfaction with Life Domains in Early Adolescents
No full textAbstract
Existing research recognises that the relationship between global life satisfaction (GLS) and domain-specific life satisfaction (DLS) is more complex than those explained by traditional linear models. This study explores the complexity of the GLS-DLS relationship in early adolescents using various statistical models and investigates the relative importance of key life domains contributing to adolescent well-being. The study used the fourth-wave cross-sectional survey data from the International Survey of Children’s Well-Being, which comprises 22,200 observations from early adolescents (51% girls) aged 7–15 years from 20 countries or territories. The relationship between GLS and satisfaction with 12 key life domains was explored using three traditional regression models and one machine learning approach. A series of goodness-of-fit indicators were used to identify the best model. The machine learning approach provided higher explanatory power in understanding the GLS-DLS relationship than the counterpart models using the full sample, and the linear additive model exhibited better accuracy when predicting the GLS in the cross-validation. Among 12 life domains, health, future, possessions, time use, and safety are the top five important domains for early adolescents. However, heterogeneities in the relative importance of the key domains were observed across countries at different economic development levels. Meanwhile, the advantage of a more advanced machine learning approach provides richer information on explaining the complex relationship within the sample. Moreover, policies aimed at improving the well-being of early adolescents through domain-specific life satisfaction should be tailored to each country’s unique context
Cocaine polydrug use and its impact on intentional harm recognition: a high-density EEG study
No full textBackground: Cocaine and stimulant consumption constitute a significant global issue and are associated with impaired social skills. However, the relationship between substance abuse and intentional harm recognition remains unclear. Intentional harm recognition is a crucial social cognitive ability that allows individuals to determine whether a harmful action performed by another person is deliberate or accidental. Methods: The present study examined self-reported, behavioural, and neural responses associated with intentional harm recognition in n = 19 cocaine polydrug users (COC) and n = 19 healthy controls (HC). High-density electroencephalography (hdEEG) was used to measure brain activity during an Intentional Inference Task (IIT), which assesses fast intention recognition in scenarios involving deliberate or unintentional harm to people and objects. This study took place between 2014 and 2015 in Santiago, Chile. Results: Behaviorally, COC exhibited slower reaction times (RT) than HC. Event-related potential (ERP) analysis revealed late frontal differences in HC when attributing intentional harm, while these differences were absent in COC. Conclusions: These findings suggest a potential shift in COC towards emotional over-involvement and away from rational cognitive assessment of social information. The present results provide new insights into the recognition of intentional harm processing in cocaine polydrug users and highlight the potential clinical benefits of interventions focused on socio-emotional regulation training