Timothy Mark Earls Davis

Background: Socio‐economic status (SES) is strongly linked to health outcomes but remains difficult to measure accurately. Conventional approaches based on large geographical units (e.g. postcodes) may obscure SES effects evident at smaller scales. Aims: We aimed to address key limitations of postcode‐based socio‐economic analyses by developing and demonstrating a more geographically precise small‐area approach. Methods: We developed an online platform ( https://onlinecalc.app/SEIFA_SA1/ ) that integrates small‐area SES data across multiple Australian Census periods and expresses SES as percentile rankings, preserving relative positionality over time and reducing inconsistencies introduced by Census method updates. To illustrate its utility, we analysed Australian participants from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, linking each participant's residential collection district (~200 households) to Index of Relative Socio‐economic Disadvantage (IRSD) and Index of Economic Resources (IER) percentiles 5‐yearly from 1986 to 2006. Results: In 5147 participants, lower area‐level SES was consistently associated with prevalent cardiovascular disease (CVD) across all census years, while lower SES among participants who experienced new on‐trial CVD events was evident in census data from the decade before trial entry (1986–1996) and not in 2001 or later. Among participants randomised to placebo, lower SES tertiles (2001–2006 Census) were associated with higher rates of new on‐trial CVD (6.9% vs 9.8% and 7.0% vs 10.0% for upper vs lower IRSD and IER tertiles respectively; both P for trend = 0.027), whereas this association was not observed in fenofibrate‐treated participants, in whom total CVD events were reduced overall by 11% ( P = 0.035). Conclusion: Assessing SES at smaller geographical scales provides a more sensitive measure of socio‐economic disparities influencing cardiovascular risk. This approach underscores the value of high‐resolution census data for improving equity‐focused health research and policy.

Objective: To determine whether micronutrient intake and/or supplementation is associated with prevalent diabetes‐related foot ulcer (DFU) and/or incident hospitalisation for DFU in type 2 diabetes. Research Design and Methods: Participants with type 2 diabetes from the community‐based Fremantle Diabetes Study Phase II (FDS2; 1499 participants, mean age 65.4 years, 51.8% males, recruited 2008–2011) were followed from entry to first hospitalization for/with DFU, death or 31 December 2016 (whichever came first). Cox proportional hazards modelling identified independent associates of prevalent DFU or first DFU hospitalization. Results: Self‐reported food frequency, including dietary intake of vitamin C, zinc and iron, taking vitamin supplements and B12 and iron levels were not independent associates of either prevalent DFU or incident DFU hospitalisation. Independent associates of prevalent DFU included younger age at diabetes diagnosis, being unmarried, retinopathy, distal symmetrical polyneuropathy (DSPN), previous diabetes‐related amputation, peripheral revascularisation or bypass. Incident DFU hospitalisation was independently associated with male sex, marital status, age at diagnosis of diabetes, HbA _1c , a history of DFU, a history of peripheral revascularisation/bypass, heart rate, and ln(NT‐proBNP). Conclusions: Associates of prevalent and incident DFU included traditional risk factors such as DSPN and peripheral arterial disease. There was no association between nutritional status or taking vitamin supplements and prevalent DFU or incident DFU hospitalisation in people with type 2 diabetes.

Background: There are scant and variable data concerning the incidence of malaria in infants in endemic areas. This study evaluated the impact of maternal antimalarial treatment given postpartum on malaria incidence and growth/development in infants from coastal Papua New Guinea (PNG). Methods: In an open-label, randomised controlled trial conducted in Madang Province, PNG, 183 mothers were randomised to no treatment (NT) or to artemisinin combination therapy (ACT) with further random allocation to artemether–lumefantrine or dihydroartemisinin–piperaquine. Their infants were assessed monthly over the next 6 months including for malaria identified by microscopy and/or polymerase chain reaction (PCR). Results: Of 151 infants who completed study procedures, 2 developed slide-positive malaria (1 Plasmodium falciparum, 1 Plasmodium vivax; 1.3% [95% confidence interval {CI} 0.2 to 5.2]). Three others had PCR-detected infections (two P. falciparum, one P. vivax). The overall 6-month incidence of slide-/PCR-positive malaria was 3.3% (95% CI 1.2 to 8.0). Four of the five cases occurred in infants whose mothers were randomised to NT. There were no statistically significant between-group differences in infant growth and developmental milestones. Conclusions: The risk of malaria in early infancy in coastal PNG is low and infections are typically asymptomatic. Postpartum maternal ACT did not influence infant growth or development.

Aims: To utilise Fremantle Diabetes Study Phase II (FDS2) data to examine the association between Type 2 diabetes and incident aortic valve replacement (AVR) and to investigate potential risk factors in Type 2 diabetes. Methods: We followed 1430 FDS2 participants (mean age 66 years, 53% males) and 5720 age‐, sex‐, and postcode‐matched people without diabetes from entry (2008–2011) to end‐2021 for AVR ascertained from validated linked databases. Incidence rate ratios (IRRs) were calculated. Cox proportional hazards and competing risk models generated cause‐specific (cs) and subdistribution (sd) hazard ratios (HRs) for incident AVR. Results: At baseline, 11 participants with Type 2 diabetes (0.8%) and 37 without diabetes (0.6%) had undergone AVR ( p = 0.589). There were 24 (1.7%) and 40 (0.7%) first incident AVR hospitalisations, respectively, in the two groups during 73,498 person‐years of follow‐up (IRR 2.40 [95% confidence interval (CI) 1.38, 4.08], p = 0.0007). In pooled analyses, Type 2 diabetes had similar csHR (2.38 [1.43, 3.96]) and sdHR (2.34 [1.41, 3.88]), with increasing age and male sex as other statistically significant covariates. In Type 2 diabetes, incident AVR was bivariably associated with baseline blood glucose‐lowering treatment intensity ( p = 0.003) and with distal symmetrical polyneuropathy (DSPN) after age and sex adjustment ( p = 0.025). Conclusions: Type 2 diabetes more than doubles the risk of AVR after adjusting for the competing risk of death. People with Type 2 diabetes going on to require AVR were more intensively managed and were more likely to have DSPN at baseline.

The PromarkerD test accurately predicts diabetic kidney disease. We aimed to determine whether PromarkerD and/or its constituent biomarkers would also identify an increased risk of distal sensory polyneuropathy (DSPN) complicating type 2 diabetes (T2D). We selected 160 community-based adults without baseline DSPN (mean age 69 years, 56% males), 80 of whom were free of DSPN after four years and 80 who developed DSN based on the vibration perception threshold. Baseline plasma apolipoprotein A-IV (ApoA4), CD5 antigen-like protein (CD5L) and insulin-like growth factor binding protein 3 (IBP3) concentrations were measured and PromarkerD risk scores were generated. Logistic regression modelling assessed associations between PromarkerD risk and its component proteins and incident DSPN. At Year 4, 77 of 151 with valid data (51%) had developed DSPN. The PromarkerD area under the receiver operating characteristic curve was 0.53 (95% CI 0.43–0.62). The odds ratio for the PromarkerD score for identifying incident DSPN was 0.97 (95% CI 0.82–1.16, P = 0.76), with similar non-significant results for plasma ApoA4, CD5L, and IBP3. PromarkerD and its constituent protein concentrations, each with some preclinical or epidemiological evidence of an association with DSPN, did not predict incident DSPN over 4 years of follow-up. These data support microangiopathy-specific pathophysiological mechanisms in T2D.

Context: It is uncertain whether subclinical hypothyroidism (SCH) contributes to intrinsic renal dysfunction in people with type 2 diabetes mellitus (T2DM). Objective: To investigate whether SCH persisting over 4 years is associated with incident impairment of renal function in people with T2DM. Design: Longitudinal observational study. Setting: Urban population of people with type 2 diabetes living in the community and enrolled in a prospective observational study of diabetes. Participants: 725 without known thyroid dysfunction at baseline and at follow-up. Main Outcome Measures: Changes in estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (ACR) in participants stratified by thyroid status at baseline and follow-up into those with euthyroidism or transient or persistent subclinical (SCH)/overt hypothyroidism. Results: After a mean ± SD 4.3 ± 0.4 years, 683 participants had stable euthyroidism, 18 transient SCH/overt hypothyroidism, and 24 persistent SCH/overt hypothyroidism. No significant changes in eGFR were observed in any group. Those with persistent SCH/overt hypothyroidism demonstrated a significant increase in ACR, which was not seen in those with euthyroidism and transient SCH/overt hypothyroidism (ΔACR 22.0 ± 81.4 vs 0.4 ± 36.7 and −0.3 ± 5.7 mg/mmol, respectively, P = .027). Similar results were seen when those with baseline ACR > 30 mg/mmol were excluded. Conclusion: Persistent SCH/overt hypothyroidism was associated with incident increased albuminuria not observed in euthyroid participants. Assessment of thyroid function in all patients with T2DM may be indicated, as some previous studies provide evidence that thyroxine replacement may ameliorate albuminuria.