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Uncovering the Link Between Diabetes and Pulmonary Hypertension
Get PDFBackground
Diabetes is a common disorder in the general population with most studies focusing on its role on the left ventricle and coronary artery disease, however it effects on pulmonary hypertension (PH) have not been fully studied. There is a pressing need to more completely explore the cardiovascular impacts of diabetes. The impact of diabetes might vary according to the various forms of PH, their predominant contribution is likely to be in PH due to left heart disease (group II, the most common form of PH).
Thus far, most studies have offered a focussed perspective with data from specialised referral centres, hospital admissions database and targeted community studies. Critically incidence and mortality data has often not been presented. The studies frequently suffer from referral bias, and may not represent true prevalence and prognosis. A large population-based study with clinical information, echocardiographic parameters and mortality data is thus needed to systematically characterise PH in diabetes participants with or without obesity.
Objectives:
1. To determine the relative incidence and predictors of pulmonary arterial hypertension (Group 1) in participants/patients with type 2 diabetes. 2. To determine the incident and prevalent epidemiology of all-cause pulmonary hypertension in a large community-based diabetes cohort linked with echocardiographic data and mortality according to three separate diagnostic criteria: a. Pulmonary hypertension coded using ICD-10 coding system at hospitalisation, with sub-code for WHO group of pulmonary hypertension. b. High probability of pulmonary hypertension based on echocardiographic data, using an estimated right ventricular systolic pressure \u3e40mmHg. c. Intermediate or greater probability of pulmonary hypertension based on echocardiographic data, using an estimated right ventricular systolic pressure \u3e30mmHg.3. To determine the risk of a) mortality over prolonged follow-up and b) rehospitalisation during the cohort follow-up.4. To explore the clinical and echocardiographic phenotype of patients with diabetes, with or without pulmonary hypertension according to the three diagnostic criteria described above.
Methodology
1. Hospitalisation for/with and death from/with PAH, and all cause-mortality were ascertained from validated databases for participants with type 2 diabetes from the longitudinal, community-based Fremantle Diabetes Study Phase 1 (n = 1287) and age-sex-and zip codematched people without diabetes (n=5153) between entry (1993-1996) and end 2017. Incidence rates and incidence rate ratios were calculated. Cox proportional hazards and competing risk models generated cause-specific and sub-distribution hazard ratios for incident PAH.
2. Data from 1,430 participants with type 2 diabetes (mean age 65.5 years, 51.5% males) in the Fremantle Diabetes Study Phase 2 (FDS2) were linked with the National Echocardiographic Database of Australia (NEDA) to ascertain the prevalence and incidence of PH using an estimated right ventricular systolic pressure (eRVSP) \u3e30 mmHg (new suggested threshold) or the conventional \u3e40 mmHg) over a 12-year period. PH prevalence in FDS2 was compared with that in NEDA overall and a geographically close sub-population. Multivariable analyses identified associates of prevalent/incident PH in the FDS2 cohort.
3. We linked data from 1732 participants in the Fremantle Diabetes Study Phase 2 (FDS2) with NEDA. Of these, 417 (mean age 70.5 years, 47.2% males) had an eRVSP measured and 381 (91.4%) had type 2 diabetes. To ascertain the optimum eRSVP cut-off for mortality, ROC analyses for all-cause mortality by diabetes type were undertaken. For homogeneity, only those with T2D diagnosed before the first measured eRVSP (n=350) had survival analyses performed. Multiply-imputed Cox regression identified clinical and echocardiographic associates of all-cause mortality.
Results
1. In the pooled cohort (mean age 64.0 years, 49% males), 49 (3.8%) of the type 2 diabetes participants and 133 (2.6%) of those without diabetes developed PAH during 106,556 personyears of follow-up (incident rate (IR) (95% CI) 262 (194–346) and 151 (127–179) /100,000 person-years, respectively; incident rate ratio (IRR) 1.73 (1.22–2.42), P=0.001). Type 2 diabetes was associated with an unadjusted csHR of 1.97 (1.42–2.74) and sdHR of 1.44 (1.04–2.00) (P ≤ 0.03); after adjustment for age, sex, and co-morbidities, these were 1.43 (0.83–2.47) and 1.36 (0.97–1.91), respectively (P ≥ 0.07).
2. Of 275 FDS2 participants (19.2%) with pre-entry echocardiography, 90 had eRVSP \u3e30 mmHg and 35 had eRVSP \u3e40 mmHg (prevalences 32.7% (95% CI 27.3–38.7%) and 12.7% (9.1–17.4%), respectively), prevalences that are 35–50% greater than national/local NEDA general population estimates. Moreover, 70 (5.0%) and 123 (9.2%) FDS2 participants were identified with incident PH at the respective eRVSP thresholds (incidence (95% CI) 7.6 (6.0– 9.7) and 14.2 (11.8–17.0)/1000 person-years), paralleling data from recognised high-risk conditions such as systemic sclerosis. The baseline plasma N-terminal pro-brain natriuretic peptide concentration was the strongest independent associate of prevalent/incident PH. Approximately 1 in 8 people with type 2 diabetes have PH using the eRVSP \u3e40 mmHg threshold.
3. There were 141 deaths (40.4%) during 2,348 person-years (6.7±4.0 years) of follow-up. In unadjusted Kaplan-Meier (K-M) analysis, mortality rose with higher eRVSP (log rank test, P\u3c0.001). In unadjusted pairwise comparisons, eRVSP \u3e30-35, \u3e35-40, and \u3e40mmHg had significantly increased mortality compared with eRVSP £30mmHg (P=0.025, P=0.001, P\u3c0.001, respectively). There were 50 deaths in the 173 individuals (29.5%) with eRVSP £30mmHg, and 91 deaths in the 177 (51.4%) with eRVSP \u3e30mmHg, log rank test, P\u3c0.001. In fully adjusted models (including age, Aboriginal descent, body mass index, diabetes duration and left heart disease), eRVSP\u3e30mmHg was associated with 2.5 times higher allcause mortality.
Conclusions
Type 2 diabetes is associated with an increased risk of PAH but this is no longer significant after adjustment for other explanatory variables and the competing risk of death. However, the more common forms of PH (including PH due to left heart disease, Group 2) is more common in the setting of type 2 diabetes than the general population, and PH should be considered as part of regular clinical assessment of individuals with type 2 diabetes. Lastly, the presence of PH (at an eRVSP threshold \u3e30mmHg) is associated with a significant risk for mortality in this group of patients, underlying the importance of screening for PH in type 2 diabetes, and instituting appropriate preventative or treatment measures to decrease the risk of mortality
Exploring sensory ethnography in open inquiry: what does River want me to know?
Get PDFThis presentation features a creative and narrative research approach to research relationality and wisdom-seeking with place. A multi-modal practice-based approach will be outlined as a pathway that can be developed by people of any background. Through transdisciplinary methods in sensory ethnography and creative geography, I notice my sensed relatedness, or entanglement, with the cosmological Being of River. Deeply influenced by Indigenous listening methods I understand sensory engagement with River as ecologically essential research, and describe a practice-based pathway to learn from, and to think with” water.
This research responds to the invitations of Indigenous Elders, and wild places, to listen and create with them. It supports cultural change, and ultimately a transition out of extractive into regenerative models of Earth-centric living. The theoretical framing draws on vitalist, animist ecologies, and co-operative inquiry. Creative practice will be explored in places of significant ecological importance, including Martuwarra (Fitzroy River) in WA; Balan (Clarence River) in Northern NSW; and the Ganga (Ganges) River (India). The methods and practices contribute to developing processual, non-dual forms of Earth and multi-species justice, and Earth-centric ways of living
‘Hidden, Not Forgotten: The 1980s WA Aboriginal Land Inquiry\u27
Get PDFThree years after the Kimberley Noonkanbah Dispute, and six years after introduction of the Aboriginal Land Rights (Northern Territory) Act in the NT, the Aboriginal Land Inquiry (ALI) was established by a newly elected WA State Labor Government in May 1983. Led by Paul Seaman QC, it was sometimes known as ‘The Seaman Inquiry’. The content of the Inquiry’s report based on two years state-wide consultation and research did not become legislation. Notably, the WA Aboriginal Land Inquiry took place nine years before the momentous 1992 High Court of Australia Mabo Decision and active implementation of the National Native Title Act in 1993/1994. This seminar will be introduced and guided by Professor Sandy Toussaint, who worked on the Aboriginal Land Inquiry in 1983-1984. Paying homage to those Aboriginal women and men who contributed to the continuing depth of material that emerged so long ago, emphases will include the how and why the ALI was established by the Labor State Government in the 1980s, its cultural and political processes, and the implications of the ALI\u27s final report and instructions to government. Possible comparisons with contemporary life and the 1993/1994 Federal Native Title Act will also be raised. Questions welcome during the seminar or online
Responsiveness and meaningful thresholds of PROMIS pain interference, fatigue, and physical function forms in adults with idiopathic inflammatory myopathies: Report from the OMERACT Myositis Working Group
No full textBackground: A series of qualitative studies conducted by the OMERACT Myositis Working Group identified pain interference, fatigue, and physical function as highly important life impact domains for adults with idiopathic inflammatory myositis (IIM). In this study, our goal was to assess the responsiveness and minimal important difference of PROMIS pain interference (6a), fatigue (7a), and physical function (8b).
Methods: Adults with IIM from USA, Netherlands, Korea, Sweden, and Australia with two clinical visits were enrolled in this prospective study. Anchor questions on a Likert scale were collected at baseline, and manual muscle testing (MMT), physician and patient reported global disease activity, and PROMIS instruments were collected at both visits. Responsiveness was assessed with i) ANOVA, ii) paired t-test, effect size and standardized response mean, and iii) Pearson correlation. Minimal important difference (MID), minimal important change (MIC) and minimal detectable change (MDC) values were calculated.
Results: 114 patients with IIM (median age 60, 60 % female) completed both visits. Changes in PROMIS instruments were significantly different among anchor categories. Patients who reported improvement had a significant improvement in their PROMIS scores with at least medium effect size, while patients who reported worsening and stability did not show a significant change with weak effect size. PROMIS instruments had weak to moderate correlations with MMT, patient and physician global disease activity. MID was approximately 2–3 points for Pain Interference and 3–4 points for Fatigue and Physical Functio
Transitive path decompositions of Cartesian products of complete graphs
No full textAn H-decomposition of a graph is a partition of its edge set into subgraphs isomorphic to H. A transitive decomposition is a special kind of H-decomposition that is highly symmetrical in the sense that the subgraphs (copies of H) are preserved and transitively permuted by a group of automorphisms of . This paper concerns transitive H-decompositions of the graph KnKn where H is a path. When n is an odd prime, we present a construction for a transitive path decomposition where the paths in the decomposition are considerably large compared to the number of vertices. Our main result supports well-known Gallai’s conjecture and an extended version of Ringel’s conjecture
High prevalence of adult and nonadult scurvy in an early agricultural transition site from Mainland Southeast Asia was associated with decreased survivorship
No full textObjectives: The osteological paradox recognizes that the presence of lesions is not always directly related with increased mortality. When combined with the clinical, historical, and epidemiological literature on scurvy, survivorship analysis, a form of statistical analysis to assess the relationship between the presence of diseases in the archeological record and survival, helps determine the overall burden of the disease both in terms of morbidity and mortality. This article explores the relationship between scurvy and survivorship in 26 adults from Man Bac, a Neolithic site from northern Vietnam together with prepublished evidence of scurvy in the nonadult population (n = 44).
Methods: Diagnosis of scurvy included differential diagnosis combined with the Snoddy, A. M. E., Buckley, H. R., Elliott, G. E., Standen, V. G., Arriaza, B. T., & Halcrow, S. E. (2018). Macroscopic features of scurvy in human skeletal remains: A literature synthesis and diagnostic guide. American Journal of Physical Anthropology, 167(4), 876–895. https://doi.org/10.1002/ajpa.23699 threshold criteria and the Brickley, M. B., & Morgan, B. (2023). Assessing diagnostic certainty for scurvy and rickets in human skeletal remains. American Journal of Biological Anthropology, 181, 637–645 diagnostic certainty approaches. Kaplan–Meier survival curves were produced to assess the relationship between the presence of probable scurvy and age-at-death.
Results: The prevalence of probable scurvy in adults (35%) was considerably lower than reported for the nonadults (80%). Almost all lesions observed in the adults were in a mixed stage of healing. Kaplan–Meier analysis demonstrated no difference in survivorship between infants and children (\u3c15 years) with or without probable scurvy, whereas a meaningful difference was observed for the adults and adolescents (15+ years).
Conclusions: The findings demonstrate that scurvy considerably decreased survivorship to older age categories. The degree of lesion remodeling, however, indicates that scurvy was not necessarily the direct cause of death but contributed to an overall disease burden that was ultimately fata
Outcomes of ACL reconstruction utilizing supercritical CO2 -sterilized allografts
No full textBackground: Allograft tendons are perceived to have a high ACL graft failure rate in primary anterior cruciate ligament (ACL) reconstruction (ACLR). Historical series may be biased by graft processing methods that degrade the biomechanical properties of donor tendons such as irradiation. Supercritical carbon dioxide (SCCO2) is a validated method of terminally sterilizing biomaterials at physiological temperatures without irradiation, but in vivo use of SCCO2-processed tendon allografts for primary ACLR has not been reported to date.
Hypothesis: ACLR with SCCO2 allografts would result in acceptable failure rates, subjective knee scores, and clinical evaluation at 2 years postoperatively.
Study Design: Case series; Level of evidence, 4.
Methods: Patients underwent primary ACLR with terminally sterilized SCCO2-processed human gracilis, peroneus longus, semitendinosus, tibialis anterior, and tibialis posterior tendon allografts. Patient demographics were collected, along with tendon donor age and sex. At 1 year postoperatively, subjective International Knee Documentation Committee (IKDC) and ACL–Return to Sport After Injury (ACL-RSI) scores were collected, as well as clinical evaluation. At 2 years postoperatively, the IKDC and ACLRSI scores were repeated, and return to sports and further knee injuries were recorded.
Results: A total of 144 patients with a medianage of 26 (IQR 14) years formed the study group. Patients were predominately male (58%). The loss to follow-up rate was 8% (n = 12). The mean age of allograft tendon donors was 37 (range 17-58) years, and the majority were male (83%). The mean allograft diameter was 8.9 6 1.0 mm. At 2 years, ACL graft failureoccurred in 5% (n = 7). All graft failureswere in patients aged 25 years (P = .007). Neither donor age (40 or \u3e40 years) nor donor sex was associated with graft failure (P . .05). The median IKDC subjective score was 95 and ACL-RSI score was 75. There were no revisions for sepsis within the first 2 years postoperatively.
Conclusion: SCCO2 processing of allograft tendons demonstrated satisfactory clinical and patient-reported outcomes at 24 months postoperatively in a consecutive series of patients with primary ACLR, with similar ACL graft failure rates and subjective knee scores compared with those reported in published series of hamstring tendon autograft and fresh frozen nonirradiated allograft
An artificial intelligence algorithm for detection of severe aortic stenosis: A clinical cohort study
No full textBackground: Identifying individuals with severe aortic stenosis (AS) at high risk of mortality remains challenging using current clinical imaging methods.
Objective: The purpose of this study was to evaluate an artificial intelligence decision support algorithm (AI-DSA) to augment the detection of severe AS within a well-resourced health care setting.
Methods: Agnostic to clinical information, an AI-DSA trained to identify echocardiographic phenotype associated with an aortic valve area (AVA)\u3c1 cm2 using minimal input data (excluding left ventricular outflow tract measures) was applied to routine transthoracic echocardiograms (TTE) reports from 31,141 U.S. Medicare beneficiaries at an academic medical center (2003-2017).
Results: S Performance of AI-DSA to detect the phenotype associated with an AVA\u3c1 cm2 was excellent (sensitivity 82.2%, specificity 98.1%, negative predictive value 9.2%, c-statistic ¼ 0.986). In addition to identifying clinical severe AS cases, AI-DSA identified an additional 1,034 (3.3%) individuals with guideline-defined moderate AS but with a similar clinical and TTE phenotype to those with severe AS with low rates of aortic valve replacement (6.6%). Five-year mortality was 75.9% in those with known severe AS, 73.5% in those with a similar phenotype to severe AS, and 44.6% in those without severe AS. The AI-DSA continued to perform well to identify severe AS among those with a depressed left ventricular ejection fraction. Overall rates of aortic valve replacement remained low, even in those with an AVA\u3c1 cm2 (21.9%)
Conclusions: Without relying on left ventricular outflow tract measurements, an AI-DSA used echocardiographic reports to reliably identify the phenotype of severe AS. These results suggest possible utility for this AI-DSA to enhance detection of severe AS individuals at risk for adverse outcome