Reaching for equitable care: High levels of disability-related knowledge and cultural competence only get us so far.

BACKGROUND: Achieving equitable medical care for people with disabilities is a complex challenge with emphasis often placed on the need for improved physician knowledge and cultural competence. Physical medicine and rehabilitation (PM&R) is a specialty dedicated to maximizing patient function, where a focus on working with and learning from patients with complex disabilities informs physician training and patient care. OBJECTIVE: The purpose of this study was to assess barriers to equitable care in PM&R clinics through a structural checklist and semi-structured interviews with clinic staff and physicians. METHODS: We used qualitative analysis with a grounded theory approach to develop a unified explanation of how existing clinic processes and provider attitudes affect equitable access to medical care. RESULTS: We found physicians comfortable with and respectful of patient differences who described leveraging unpaid time and creativity to navigate structural, resource, and awareness barriers. Staff and physicians described current barriers as negatively affecting quality of care, clinic efficiency, and, in some cases, patient and staff safety. CONCLUSION: Our results suggest that high levels of physician disability-related knowledge and cultural competence may be insufficient to the challenge of achieving equitable care.

The association between carotid disease, arterial stiffness and diabetic retinopathy in type 2 diabetes: the Fremantle Diabetes Study Phase II.

AIM: To determine whether macrovascular disease assessed by carotid ultrasonography and arterial stiffness by pulse wave velocity are independently associated with diabetic retinopathy in type 2 diabetes. METHODS: A random subgroup of surviving participants with type 2 diabetes from the Fremantle Diabetes Study Phase II were invited to take part in this sub-study in 2018-2019. In addition to standardized questionnaires, a physical examination and fasting biochemical tests, each underwent dilated colour fundus photography, carotid arterial ultrasonography with measurement of the intima-media thickness (IMT) and quantification of the degree of stenosis, and pulse wave analysis calculation of the carotid-femoral pulse wave velocity (cfPWV). The cross-sectional association between arterial disease parameters and diabetic retinopathy was assessed using generalized estimating equation models which enabled both eyes to be included in the analysis. RESULTS: Some 270 participants [mean ± sd age 72 ± 9 years, 153 (57%) men and median (IQR) diabetes duration 15 (11-22) years] were included in analysis. Of 524 assessable eyes, 82 (16%) had diabetic retinopathy. In multivariable analysis, significant independent associates of diabetic retinopathy were age at diabetes diagnosis (inversely), HbA1c , insulin treatment and urinary albumin to creatinine ratio (all P ≤ 0.022), as well as cfPWV [odds ratio (OR) 1.13, 95% confidence interval (CI) 1.03, 1.23 per 1 m/s increase; P = 0.008] and common carotid artery (CCA) IMT ≥1 mm (OR 2.95, 95% CI 1.21, 7.23; P = 0.018). CONCLUSIONS: The association between diabetic retinopathy and CCA IMT suggests that carotid disease may share cardiovascular risk factors with diabetic retinopathy. The association between diabetic retinopathy and cfPWV may reflect the consequences of altered intravascular haemodynamics.

Risk factors and outcomes of anxiety symptom trajectories in type 2 diabetes: the Fremantle Diabetes Study Phase II.

AIM: To identify determinants and outcomes of 4-year trajectories of anxiety symptoms in a community-based cohort with type 2 diabetes. METHODS: Some 1091 participants in the Fremantle Diabetes Study-Phase II with type 2 diabetes completed the Generalized Anxiety Disorder Scale at baseline and biennially for 4 years, in addition to psychological, biomedical and self-management measures. Latent growth mixture modelling identified trajectories of anxiety symptom severity, and regression models determined predictors of trajectory membership and associated outcomes. RESULTS: Two distinct groups of participants were identified: those with continuously low-no anxiety symptoms (87%) and those with improving but consistently high anxiety symptoms (elevated anxiety; 13%). Higher HbA1c and BMI, macrovascular complications and a history of generalized anxiety and/or major depressive disorder increased the risk of elevated anxiety. Elevated anxiety did not predict change in health-related outcomes over time. Elevated anxiety and depression symptoms were highly comorbid and those with both displayed the most persistent anxiety symptoms. CONCLUSIONS: A subgroup of individuals with type 2 diabetes are at risk of persistently elevated anxiety symptoms. Routine monitoring of the severity of psychological symptoms over time in this population should facilitate earlier and more intensive mood management.

Clinical risk factors for depressive syndrome in Type 2 diabetes: the Fremantle Diabetes Study.

AIMS: To identify early clinical predictors of depressive syndrome in people with Type 2 diabetes. METHODS: Depressive syndrome was assessed in 325 individuals with Type 2 diabetes 15 years after a baseline assessment, which included information on antidepressant use and depressive symptoms obtained using a quality-of-life scale. Follow-up current and lifetime depressive syndrome were assessed using the nine-item Patient Health Questionnaire and the Brief Lifetime Depression Scale and taking account of antidepressant use. Analyses were conducted inclusive and exclusive of antidepressant use where Patient Health Questionnaire criteria were not met. RESULTS: At baseline, the participants were aged 57.2±9.3 years and the median (interquartile range) diabetes duration was 2.2 (0.6-6.0) years. After a mean of 14.7±1.1 years' follow-up, 81 participants (24.9%) had depressive syndrome (14.8% defined by the Patient Health Questionnaire, 10.2% defined by antidepressants) and 31.4% reported lifetime depression, and in 10.2% of participants this preceded diabetes onset. With logistic regression (inclusive of antidepressants), follow-up depressive syndrome was negatively associated with education level [odds ratio 0.39 (95% CI 0.20-0.75)] and antidepressant use [odds ratio 0.11 (95% CI 0.03-0.36)] and was positively associated with depression history before diabetes onset [odds ratio 2.79 (95% CI 1.24-6.27)]. In the model exclusive of antidepressants, depressive syndrome was positively associated with baseline depressive symptoms [odds ratio 2.57 (95% CI 1.32-5.03)] and antidepressant use [odds ratio 3.54 (95% CI 1.20-10.42)] and was negatively associated with education level [odds ratio 0.39 (95% CI 0.19-0.81)]. CONCLUSIONS: Risk factors for depressive syndrome can be identified early after the onset of Type 2 diabetes. The early presence of depressive symptoms or its treatment and/or history of depression are likely indicators of vulnerability. Early risk stratification for late depressive syndrome is feasible in people with Type 2 diabetes and could assist with depression treatment or prevention.

Depression symptoms are persistent in Type 2 diabetes: risk factors and outcomes of 5-year depression trajectories using latent class growth analysis.

AIMS: To describe the long-term trajectories of depression symptom severity in people with Type 2 diabetes, and to identify predictors and associates of these trajectories. METHODS: A community-dwelling cohort of 1201 individuals with Type 2 diabetes from the Fremantle Diabetes Study Phase II was followed for 5 years. The nine-item version of the Patient Health Questionnaire was administered annually to assess depression symptoms, and biomedical and psychosocial measures were assessed at baseline and biennially. Latent class growth analysis was used to identify classes of depression severity trajectories and associated outcomes, and logistic regression models were used to determine predictors of class membership. RESULTS: Three trajectories of depression symptoms were identified: continuously low depression symptoms (85.2%); gradually worsening symptoms that then began to improve (persistent depression - low-start; 7.3%); and gradually improving symptoms which later worsened (persistent depression - high-start; 7.5%). Younger age, being a woman, and a lifetime history of major depressive disorder, were associated with greater risk of persistent depression symptoms. Persistent depression was associated with consistently higher BMI over time, but not with changes in HbA1c or self-monitoring of blood glucose. CONCLUSIONS: A subset of individuals with Type 2 diabetes is at risk of depression symptoms that remain elevated over time. Younger, overweight individuals with a history of depression may benefit from early and intensive depression management and ongoing follow-up as part of routine Type 2 diabetes care.

A population-based study of the association between dysglycaemia and hearing loss in middle age.

AIMS: To investigate the independent associations between hearing loss and dysglycaemia in a sample of middle-aged adults, including separate analysis of those aged < 60 years. METHODS: The first 2023 participants in the cross-sectional Busselton Health Ageing Survey were assessed for hearing loss ≥ 26 dB (better ear) for four-frequency average (4FA) of pure-tone thresholds at 500, 1000, 2000 and 4000 Hz, and high-frequency average (HFA) of pure-tone thresholds at 4000 and 8000 Hz. RESULTS: Valid data from 1864 participants in the Busselton Health Ageing Survey [92.1%; mean ± sd age 56.2 ± 5.5 years, 46.0% men, 120 (7.0%) with diabetes, 274 (14.7%) with prediabetes] were analysed, of whom 103 (5.5%) had four-frequency average hearing loss and 561 (30.1%) had high-frequency average hearing loss. In multivariable analyses, glycaemic status was not independently associated with four-frequency or high-frequency average hearing loss. In the 1286 participants aged < 60 years, there was no relationship between dysglycaemia and high-frequency average hearing loss, but the prevalence of four-frequency average hearing loss increased from 2.3% (95% CI 1.5-3.4) in participants with normoglycaemia to 5.7% (95% CI 3.0-10.6) in those with prediabetes and 10.2% (4.2-21.5) in those with diabetes (trend P = 0.003). In multivariable analysis with normoglycaemia as reference, the odds ratios for four-frequency average hearing loss were 2.84 (95% CI 1.29-6.27) for prediabetes and 5.93 (95% CI 1.67-21.05) for diabetes (P ≤ 0.01) in the < 60 year age group. CONCLUSIONS: There was progressively increasing mid-range hearing loss with worsening glucose tolerance in younger individuals, suggesting dysglycaemia-associated early-onset presbycusis.

Lifetime depression and anxiety increase prevalent psychological symptoms and worsen glycemic control in type 2 diabetes: The Fremantle Diabetes Study Phase II.

AIMS: To determine the contribution of lifetime major depressive disorder (L-MDD) and lifetime generalized anxiety disorder (L-GAD) to current psychological symptom severity, health behaviour and glycaemic control in type 2 diabetes. METHODS: 1285 community-dwelling people with type 2 diabetes (Fremantle Diabetes Study Phase-II; FDS2) completed the PHQ-9 and Brief Life-Time Depression Scale (BLDS) to assess current and past MDD. The Generalized Anxiety Disorder Scale (GADS) and the Generalized Anxiety Disorder Scale-Lifetime (GAD-LT), designed for FDS2, assessed current and past anxiety. Data were analysed using analysis of covariance and multiple mediation models, controlling for age, gender, marital status, and diabetes duration. RESULTS: L-MDD and L-GAD were independently associated with more severe current depression (both P<0.001) and anxiety (both P<0.001) symptoms. Mediation models revealed that, through increasing the severity of current depressive symptoms, L-MDD was associated with higher HbA1c and body mass index (BMI), greater likelihood of current smoking, and reduced self-monitoring of blood glucose (SMBG) (indirect regression path ab, all P<0.001). In combination, L-MDD+L-GAD additionally elevated the risk of higher HbA1c and worse diabetes management, by increasing the severity of current depressive symptoms (indirect regression path ab, all P<0.001). CONCLUSIONS: Lifetime depression and anxiety increase risk of more severe psychological symptoms, hyperglycaemia, and difficulties with health behaviour in type 2 diabetes. Early screening for these disorders at diabetes diagnosis may be warranted to maximize long-term health outcomes.

Dose-response relationship between statin therapy and glycaemia in community-based patients with type 2 diabetes: the Fremantle Diabetes Study.

Although statins may increase glycaemia in type 2 diabetes, available data are from single-dose intervention trials or studies with no adjustment for concomitant changes in blood glucose-lowering therapy. To provide real-life data covering common statin types and doses, glycated haemoglobin (HbA1c) data from patients in the Fremantle Diabetes Study phases I (FDS1) and II (FDS2) and data on stable diabetes treatment before and after statin initiation were analysed. Intensity of statin therapy was categorized as low, moderate or high based on within-group dose regimens with similar serum LDL cholesterol-lowering effects. In pooled analyses of 335 eligible patients in FDS1 and FDS2, there was no change in HbA1c in the low-intensity group (0.04% or 0.4 mmol/mol; n = 159; p = .40), but a mean 0.22% (2.4 mmol/mol) increase in the moderate-intensity group (n = 185; p = .022) and a larger mean increase of 1.05% (11.5 mmol/mol) increase in the high-intensity group (n = 11; p = .023). These real-life data suggest a dose-response relationship between statin treatment intensity and glycaemia that has potential clinical implications.

Metabolic memory and all-cause death in community-based patients with type 2 diabetes: the Fremantle Diabetes Study.

AIMS: To validate the findings, in a usual care setting, of glycaemic intervention trials, which have shown that tight control in patients with recently diagnosed type 2 diabetes protects against death during post-study monitoring, but that it may be deleterious in long-duration diabetes with vascular complications. METHODS: A subset of 531 patients with type 2 diabetes from the community-based observational Fremantle Diabetes Study Phase 1, who attended ≥5 annual reviews (mean follow-up 15.9 years), were categorized by baseline diabetes duration [<1 year (Group 1); 1 to <5 years (Group 2); and ≥5 years (Group 3)]. Glycated haemoglobin (HbA1c) trajectories over the first 5 years were determined [low, medium and high; equivalent to mean HbA1c ≤6.6% (<49 mmol/mol), 6.7-8.0% (50-64 mmol/mol) and ≥8.0% (>64 mmol/mol), respectively]. Kaplan-Meier analysis was used to assess survival by duration and HbA1c trajectory. Cox proportional hazards modelling identified predictors of all-cause death. RESULTS: There was greater mortality in patients with a medium versus those with a low trajectory in Group 1: hazard ratio (HR) 1.99 [95% confidence interval (CI) 1.003-3.94; p = 0.049], and in patients with a high versus a low trajectory in Group 2: HR 2.02 (95% CI 1.11-3.71; p = 0.022). In Group 3, both medium [HR 0.57 (95% CI 0.35-0.92; p = 0.022)] and high [HR 0.56 (95% CI 0.32-0.96); p = 0.035] trajectories were independently and inversely associated with death. CONCLUSIONS: In community-based patients with newly or recently diagnosed type 2 diabetes, poor glycaemic control was an adverse prognostic indicator. Tight control was independently associated with death in patients with diabetes duration ≥5 years. These data parallel intervention trial findings and support individualization of HbA1c targets.

Risk of suicide in Australian adults with diabetes: the Fremantle Diabetes Study.

Type 1 diabetes is associated with increased suicide risk. Data for older diabetic individuals are inconsistent. In longitudinal data from 1413 adults recruited to the Fremantle Diabetes Study from 1993-1996 and 5660 matched non-diabetic residents, followed to end-2012, the age and sex-adjusted sub-hazard ratio (95% confidence interval) for suicide in diabetic versus non-diabetic individuals was 1.16 (0.38-3.51). Older Australians with diabetes are not at increased suicide risk.

The metabolic syndrome and cancer: Is the metabolic syndrome useful for predicting cancer risk above and beyond its individual components?

AIMS: The metabolic syndrome (MetS) is a risk factor for cancer. However, it is not known if the MetS confers a greater cancer risk than the sum of its individual components, which components drive the association, or if the MetS predicts future cancer risk. MATERIALS AND METHODS: We linked 20,648 participants from the Australian and New Zealand Diabetes and Cancer Collaboration with complete data on the MetS to national cancer registries and used Cox proportional hazards models to estimate associations of the MetS, the number of positive MetS components, and each of the five MetS components separately with the risk for overall, colorectal, prostate and breast cancer. Hazard ratios (HR) and 95% confidence intervals (95%CI) are reported. We assessed predictive ability of the MetS using Harrell's c-statistic. RESULTS: The MetS was inversely associated with prostate cancer (HR 0.85; 95% CI 0.72-0.99). We found no evidence of an association between the MetS overall, colorectal and breast cancers. For those with five positive MetS components the HR was 1.12 (1.02-1.48) and 2.07 (1.26-3.39) for overall, and colorectal cancer, respectively, compared with those with zero positive MetS components. Greater waist circumference (WC) (1.38; 1.13-1.70) and elevated blood pressure (1.29; 1.01-1.64) were associated with colorectal cancer. Elevated WC and triglycerides were (inversely) associated with prostate cancer. MetS models were only poor to moderate discriminators for all cancer outcomes. CONCLUSIONS: We show that the MetS is (inversely) associated with prostate cancer, but is not associated with overall, colorectal or breast cancer. Although, persons with five positive components of the MetS are at a 1.2 and 2.1 increased risk for overall and colorectal cancer, respectively, and these associations appear to be driven, largely, by elevated WC and BP. We also demonstrate that the MetS is only a moderate discriminator of cancer risk.

Self-awareness of foot health status in patients with Type 2 diabetes: the Fremantle Diabetes Study Phase II.

AIMS: To determine self-awareness of diabetes-related foot problems and its associates in a community-based cohort of people with Type 2 diabetes. METHODS: A survey concerning diabetic foot problems was administered to 358 consecutive patients with Type 2 diabetes [mean ± SD age 67.4 ± 10.8 years, 56.1% males, median (interquartile range) diabetes duration 9.0 (3.9-16.8) years] attending for detailed clinical, biochemical and questionnaire assessment as part of the longitudinal observational Fremantle Diabetes Study Phase II. RESULTS: Compared with the 213 patients (59.5%) who considered their feet to be normal, the 145 (40.5%) who considered their feet to be abnormal were older, had longer diabetes duration and were more likely to have sensory neuropathic symptoms and self-reported poor circulation (P < 0.001). In those who considered their feet to be normal, 67.9% had peripheral sensory neuropathy (score >2/8 on the Michigan Neuropathy Screening Instrument clinical portion), 9.9% had an ankle-brachial index < 0.9, 6.1% had both peripheral sensory neuropathy and an ankle-brachial index < 0.90, and 86.9% had one or more features on inspection, such as deformity, dry skin, callus and fissures that could facilitate more serious complications, despite the majority having had at least one foot examination by a healthcare professional in the previous year. CONCLUSIONS: Self-assessment of diabetes-related foot problems by patients in the Fremantle Diabetes Study Phase II was unreliable. The present data suggest that self-perceived foot health should be assessed together with foot examination findings. Intensive education and monitoring may be necessary in those who consider their feet to be normal but who have neurovascular, structural and/or other precursors of serious foot pathology.

Incidence and precipitants of hospitalization for pancreatitis in people with diabetes: the Fremantle Diabetes Study.

AIMS: To determine the relative risk of pancreatitis in diabetes, and to establish whether diabetes-related as well as recognized risk factors contribute. METHODS: We studied 1426 participants [mean (SD) age 62.1 (13.3) years, 49.6% male, 90.9% type 2 diabetes, median (interquartile range) diabetes duration 4.0 (1.0-10.0) years] from the community-based Fremantle Diabetes Study Phase I and 5663 matched residents without diabetes from the same geographical area. Pancreatitis hospitalizations between 1982 and 2010 were ascertained using validated data linkage. For Fremantle Diabetes Study Phase I participants, chart review provided data on the likely causes of pancreatitis. RESULTS: A total of 21 Fremantle Diabetes Study Phase I participants (1.5%) were hospitalized for pancreatitis before study entry vs 29 (0.5%) of contemporaneous residents without diabetes. During a mean (SD) of 12.1 (5.4) years of follow-up from entry, 22 (1.6%) Fremantle Diabetes Study Phase I participants were hospitalized for a first-ever episode of pancreatitis on 37 occasions (1.31/1000 person-years) compared with 58 (1.0%) residents without diabetes on 81 occasions during a mean (SD) 13.6 (4.8) years (0.75/1000 person-years). The age- and sex-adjusted hazard ratio (95% CI) for first-ever pancreatitis hospitalization in Fremantle Diabetes Study Phase I participants was 1.73 (1.06-2.83; P=0.029). Chart review of 17 of the 22 Fremantle Diabetes Study Phase I participants (77%) with incident pancreatitis and available case notes revealed that four (24%) presented without objective evidence of pancreatitis, seven (41%) presented with cholelithiasis, three (18%) with excessive alcohol consumption, two (12%) as a complication of elective endoscopic retrograde cholangiopancreatography, and one (6%) with hypertriglyceridaemia. CONCLUSION: Consistent with previously published data, the risk of pancreatitis was higher in community-dwelling Fremantle Diabetes Study Phase I participants but conventional precipitants accounted for confirmed cases. These data question whether diabetes-specific risk factors cause or contribute to pancreatitis.

Personality traits, self-care behaviours and glycaemic control in type 2 diabetes: the Fremantle diabetes study phase II.

AIMS: To determine whether the personality traits of conscientiousness and agreeableness are associated with self-care behaviours and glycaemia in Type 2 diabetes. METHODS: The Big Five Inventory personality traits Agreeableness, Conscientiousness, Extraversion, Neuroticism and Openness were determined along with a range of other variables in 1313 participants with Type 2 diabetes (mean age 65.8 ± 11.1 years; 52.9% men) undertaking their baseline assessment as part of the community-based longitudinal observational Fremantle Diabetes Study Phase II. Age- and sex-adjusted generalized linear modelling was used to determine whether personality was associated with BMI, smoking, self-monitoring of blood glucose and medication taking. Multivariable regression was used to investigate which traits were independently associated with these self-care behaviours and HbA1c . RESULTS: Patients with higher conscientiousness were less likely to be obese or smoke, and more likely to perform self-monitoring of blood glucose and take their medications (P ≤ 0.019), with similar independent associations in multivariate models (P ≤ 0.024). HbA1c was independently associated with younger age, indigenous ethnicity, higher BMI, longer diabetes duration, diabetes treatment, self-monitoring of blood glucose (negatively) and less medication taking (P ≤ 0.009), but no personality trait added to the model. CONCLUSIONS: Although there was no independent association between personality traits and HbA1c , the relationship between high conscientiousness and low BMI and beneficial self-care behaviours suggests an indirect positive effect on glycaemia. Conscientiousness could be augmented by the use of impulse control training as part of diabetes management.

Incidence and predictors of hospitalization for tendon rupture in type 2 diabetes: the Fremantle diabetes study.

AIMS: To determine the incidence and predictors of tendon ruptures requiring hospitalization of representative patients with type 2 diabetes. METHODS: A total of 1296 patients from the longitudinal observational Fremantle Diabetes Study, Phase I, and 5159 de-identified age- and sex-matched control subjects without diabetes from the same urban area were studied. The patients' mean (sd) age was 64.0 (11.3) years and 48.6% of them were male. Their median (interquartile range) diabetes duration was 4.0 (1.0-9.0) years. The main outcome assessed was any tendon rupture requiring hospitalization in the Fremantle Diabetes Study subjects and the matched control subjects. Independent predictors of spontaneous ruptures in the patients from the Fremantle Diabetes Study were assessed using Cox proportional hazards modelling. RESULTS: The incidence rate ratio for any tendon rupture requiring hospitalization in patients vs control subjects was 1.44 (95% CI 1.10-1.87; P = 0.005). Independent predictors of spontaneous ruptures in patients were BMI [hazard ratio 1.05 (95% CI 1.002-1.10] for 1 kg/m2 increase; P = 0.010] and alcohol consumption [hazard ratio 1.52 (95% CI 1.11-2.09) for √1 standard drink/day increase; P = 0.010]. Adjustment of the incidence rate ratio for overall rupture requiring hospitalization for these variables using the BMI and alcohol consumption data from the contemporary Australian general population suggested it could be as high as 1.84. CONCLUSIONS: There is a greater risk of tendon rupture requiring hospitalization in people with type 2 diabetes. Alcohol consumption and adiposity are potentially modifiable risk factors of spontaneous ruptures in patients with diabetes.

Characteristics and prognosis of Asian patients with type 2 diabetes from a multi-racial Australian community: the Fremantle Diabetes Study.

BACKGROUND: Asian migrants represent an expanding proportion of the Australian population and are from a region with an increasing diabetes burden. There are few data detailing the characteristics and outcome of type 2 diabetes in Asian Australians. AIMS: To determine whether the phenotype and prognosis of Asians with type 2 diabetes differ from those in Anglo-Celt (AC) patients from the same Australian community. METHODS: We studied 44 Asian and 796 AC patients from the Fremantle Diabetes Study. Each had a detailed assessment between 1993 and 1996, and was invited to annual reviews for ≥5 years. Data linkage provided additional endpoints to end-2010. Cox proportional hazards modelling was used to determine predictors of cardiovascular disease (CVD) death and all-cause mortality. RESULTS: The prevalence of type 2 diabetes in Asians and the general population in Fremantle was similar (1.5% vs 1.6%; P = 0.60). The Asian patients were younger, less obese and less likely to be hypertensive than the AC subjects, but they had a higher retinopathy prevalence (27.3% vs 13.5%; P = 0.023). During up to 18 years of follow up, 12 Asians and 428 AC patients died, 2 (16.7%) vs 205 (47.9%) from CVD (P = 0.040). Asian ethnicity was independently protective against CVD death (hazard ratio 0.13 (95% confidence interval: 0.02-0.96); P = 0.046) but not all-cause mortality (hazard ratio 0.58 ( 95% confidence interval: 0.31-1.10); P = 0.10). CONCLUSIONS: The phenotype of type 2 diabetes in a relatively small group of well-characterised Asian Australians differed from that in AC patients from the same urban community. Their favourable cardiovascular prognosis may reflect a healthy migrant effect.

Earlier age of dementia onset and shorter survival times in dementia patients with diabetes.

Diabetes is a risk factor for dementia, but relatively little is known about the epidemiology of the association. A retrospective population study using Western Australian hospital inpatient, mental health outpatient, and death records was used to compare the age at index dementia record (proxy for onset age) and survival outcomes in dementia patients with and without preexisting diabetes (n = 25,006; diabetes, 17.3%). Inpatient records from 1970 determined diabetes history in this study population with incident dementia in years 1990-2005. Dementia onset and death occurred an average 2.2 years and 2.6 years earlier, respectively, in diabetic compared with nondiabetic patients. Age-specific mortality rates were increased in patients with diabetes. In an adjusted proportional hazard model, the death rate was increased with long-duration diabetes, particularly with early age onset dementia. In dementia diagnosed before age 65 years, those with a ≥15-year history of diabetes died almost twice as fast as those without diabetes (hazard ratio = 1.9, 95% confidence interval: 1.3, 2.9). These results suggest that, in patients with diabetes, dementia onset occurs on average 2 years early and survival outcomes are generally poorer. The effect of diabetes on onset, survival, and mortality is greatest when diabetes develops before middle age and after 15 years' diabetes duration. The impact of diabetes on dementia becomes progressively attenuated in older age groups.

Colonization with small conidia Aspergillus species is associated with bronchiolitis obliterans syndrome: a two-center validation study.

Aspergillus colonization after lung transplantation may increase the risk for bronchiolitis obliterans syndrome (BOS), a disease of small airways. We hypothesized that colonization with small conidia Aspergillus species would be associated with a greater risk of BOS, based upon an increased likelihood of deposition in small airways. We studied adult primary lung recipients from two large centers; 298 recipients at University of California, Los Angeles and 482 recipients at Duke University Medical Center. We grouped Aspergillus species by conidia diameter≤3.5 µm. We assessed the relationship of colonization with outcomes in Cox models. Pre-BOS colonization with small conidia Aspergillus species, but not large, was a risk factor for BOS (p=0.002, HR 1.44, 95% CI 1.14-1.82), along with acute rejection, single lung and Pseudomonas. Colonization with small conidia species also associated with risk of death (p=0.03, HR 1.30, 95% CI 1.03-1.64). Although other virulence traits besides conidia size may be important, we have demonstrated in two large independent cohorts that colonization with small conidia Aspergillus species increases the risk of BOS and death. Prospective evaluation of strategies to prevent Aspergillus colonization of small airways is warranted, with the goal of preserving lung allograft function as long as possible.

Significance of and risk factors for the development of central airway stenosis after lung transplantation.

Central airways stenosis (CAS) after lung transplant is a poorly understood complication. Objectives of this study were to determine if CAS was associated with chronic rejection or worse survival after transplant as well as to identify factors associated with CAS in a large cohort of lung transplant recipients. Lung transplant recipients transplanted at a single center were retrospectively reviewed for the development of CAS requiring airway dilation. A total of 467 subjects met inclusion criteria with 60 (13%) of these developing CAS requiring intervention. Of these 60 recipients, 22 (37%) had resolution of CAS with bronchoplasty alone, while 32 (53%) ultimately required stent placement. CAS that required intervention was not a risk factor for the development of bronchiolitis obliterans syndrome or worse overall survival. Significant risk factors for the subsequent development of CAS in a time-dependant multivariable model were pulmonary fungal infections and the need for postoperative tracheostomy. While CAS was not associated with BOS or worse survival, it remains an important complication after lung transplant with potentially preventable risk factors.

The association of ulceration of the foot with cardiovascular and all-cause mortality in patients with diabetes: a meta-analysis.

AIMS/HYPOTHESIS: It is well established that diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. Observational studies suggest that a history of diabetic foot ulceration (DFU) may increase this risk further still. We sought to determine to what extent DFU is associated with excess risk over and above diabetes. METHODS: We identified studies reporting on associations of DFU with CVD and all-cause mortality. We obtained data on incident events of all-cause mortality, fatal myocardial infarction and fatal stroke. Study-specific estimates were pooled using a random-effects meta-analysis and the statistical heterogeneity of included studies was assessed using the I (2) statistic. RESULTS: The eight studies included reported on 3,619 events of all-cause mortality during 81,116 person-years of follow-up. DFU was associated with an increased risk of all-cause mortality (RR 1.89, 95% CI 1.60, 2.23), fatal myocardial infarction (2.22, 95% CI 1.09, 4.53) and fatal stroke (1.41, 95% CI 0.61, 3.24). CVD mortality accounted for a similar proportion of deaths in DFU and non-DFU patients. CONCLUSIONS/INTERPRETATION: Patients with DFU have an excess risk of all-cause mortality, compared with patients with diabetes without a history of DFU. This risk is attributable, in part, to a greater burden of CVD. If this result is validated in other studies, strategies should evaluate the role of further aggressive CVD risk modification and ulcer prevention in those with DFU.