Publications by authors named "S Duffy"

1,525 Publications

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Applying a framework to assess the impact of cardiovascular outcomes improvement research.

Health Res Policy Syst 2021 Apr 21;19(1):67. Epub 2021 Apr 21.

Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia.

Background: Health and medical research funding agencies are increasingly interested in measuring the impact of funded research. We present a research impact case study for the first four years of an Australian National Health and Medical Research Council funded Centre of Research Excellence in Cardiovascular Outcomes Improvement (2016-2020). The primary aim of this paper was to explore the application of a research impact matrix to assess the impact of cardiovascular outcomes improvement research.

Methods: We applied a research impact matrix developed from a systematic review of existing methodological frameworks used to measure research impact. This impact matrix was used as a bespoke tool to identify and understand various research impacts over different time frames. Data sources included a review of existing internal documentation from the research centre and publicly available information sources, informal iterative discussions with 10 centre investigators, and confirmation of information from centre grant and scholarship recipients.

Results: By July 2019, the impact on the short-term research domain category included over 41 direct publications, which were cited over 87 times (median journal impact factor of 2.84). There were over 61 conference presentations, seven PhD candidacies, five new academic collaborations, and six new database linkages conducted. The impact on the mid-term research domain category involved contributions towards the development of a national cardiac registry, cardiovascular guidelines, application for a Medicare Benefits Schedule reimbursement item number, introduction of patient-reported outcome measures into several databases, and the establishment of nine new industry collaborations. Evidence of long-term impacts were described as the development and use of contemporary management for aortic stenosis, a cardiovascular risk prediction model and prevention targets in several data registries, and the establishment of cost-effectiveness for stenting compared to surgery.

Conclusions: We considered the research impact matrix a feasible tool to identify evidence of academic and policy impact in the short- to midterm; however, we experienced challenges in capturing long-term impacts. Cost containment and broader economic impacts represented another difficult area of impact to measure.
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http://dx.doi.org/10.1186/s12961-021-00710-4DOI Listing
April 2021

Targeted encouragement of GP consultations for possible cancer symptoms: a randomised controlled trial.

Br J Gen Pract 2020 Dec 9. Epub 2020 Dec 9.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London.

Background: For some common cancers, survival is lower in the UK than in comparable high-income countries.

Aim: To assess the effectiveness of a targeted postal intervention (to promote awareness of cancer symptoms and earlier help seeking) on patient consultation rates.

Design And Setting: A two-arm randomised controlled trial was carried out on patients aged 50-84 years registered at 23 general practices in rural and urban areas of Greater London, Greater Manchester, and the North East of England.

Method: Patients who had not had a consultation at their general practice in the previous 12 months and had at least two other risk factors for late presentation with cancer were randomised to intervention and control arms. The intervention consisted of a posted letter and leaflet. Primary outcome was the number of consultations at the practice with patients randomised to each arm in the 6 months subsequent to posting the intervention. All patients with outcome data were included in the intention-to-treat analyses.

Results: In total, 1513 patients were individually randomised to the intervention ( = 783) and control ( = 730) arms between Nov 2016 - May 2017; outcome data were available for 749 and 705 patients, respectively, with a statistically significantly higher rate of consultation in the intervention arm compared with the control arm: 436 versus 335 consultations (relative risk 1.40, 95% confidence interval = 1.11 to 1.77, = 0.004). There was, however, no difference in the numbers of patients consulting.

Conclusion: Targeted interventions of this nature can change behaviour; there is a need to develop interventions that can be more effective at engaging patients with primary care. This study demonstrates that targeted interventions promoting both awareness of possible cancer symptoms and earlier health seeking, can change behaviour. There is a need to develop and test interventions that can be more effective at engaging the most at-risk patients.
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http://dx.doi.org/10.3399/bjgp20X713489DOI Listing
December 2020

Trainee Perspectives Regarding Advanced Clinical Global Health Fellowships in North America.

Am J Trop Med Hyg 2021 Apr 19. Epub 2021 Apr 19.

1Division of Global Health, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts.

Postgraduate clinical global health (GH) training is a rapidly evolving field. To understand and improve training opportunities, we sought the perspectives of current and former trainees related to their advanced clinical training or global health fellowships and the anticipated impact on their careers. Clinical GH fellowships across North America were identified through websites and previous studies. An e-mail was sent to program directors to invite all current and former GH fellows to complete a web-based questionnaire. We contacted 100 GH fellowship programs. Fifty-two fellows from 10 different specialties completed the survey. The median fellowship length was 23.3 months, with an annual median of 4.8 months spent in low-income and middle-income countries, which was less than their reported ideal of 6 months. The majority reported satisfaction, the anticipation of career benefits, and that they would recommend fellowship training to others. Challenges included insufficient funding, mentorship, and formal curricula. Conducting research in high-income countries was a significant negative predictor of fellowship satisfaction. Most fellows (73.1%) were not at all or only a little concerned about the absence of fellowship accreditation, with only 17.3% desiring accreditation. Survey respondents were largely satisfied with their training and valued program flexibility and educational opportunities, including advanced tropical medicine certificates or diplomas. However, to improve fellowship training, improvements are needed in mentorship, standardized curricula, institutional support, and funding. For GH fellowship training to be effective and sustainable, institutions will need to balance the needs of fellows, training programs, and the communities (low-, middle-, and high-income countries) where the fellows serve.
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http://dx.doi.org/10.4269/ajtmh.20-1589DOI Listing
April 2021

Periprocedural myocardial injury and coronary artery disease in patients undergoing transcatheter aortic valve replacement.

Cardiovasc Revasc Med 2021 Apr 9. Epub 2021 Apr 9.

Department of Cardiology, Alfred Hospital, Victoria, Australia; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address:

Background/purpose: PPMI and CAD are common in patients undergoing TAVR. Despite several studies evaluating their interaction as well as the influence these factors play on outcomes, there remains no consensus. We sought to evaluate the impact of peri-procedural myocardial injury (PPMI) and incidental coronary artery disease (iCAD) on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR).

Methods/materials: We analyzed prospective data from 400 patients undergoing TAVI for severe aortic stenosis between 2008 and 2018 to determine rates of PPMI (troponin 15× the upper limit of normal) and iCAD (≥50% stenosis) and their impact on long-term mortality.

Results: Mean age was 83 ± 6 years; 45% were female. PPMI was observed in 65% (254/400). On multivariable logistic regression analysis, higher left ventricular ejection fraction (LVEF) (OR 1.04, 95%CI 1.01-1.06, p = 0.002), and first generation valves (OR 3.00, 95%CI 1.75-5.15, p < 0.001) were independently associated with PPMI, while oral anticoagulation was inversely associated (OR 0.48, 95%CI 0.28-0.82, p = 0.007). PPMI was not associated with 30-day, 1-year or long-term mortality. After excluding previous bypass grafting, iCAD was observed in 40% (129/324). In patients with iCAD, PCI was associated with reduced long-term mortality compared to medical management in adjusted analysis (OR 0.37, 95%CI 0.16-0.88, p = 0.03).

Conclusions: PPMI and iCAD in patients undergoing TAVR are common. PPMI is associated with older generation valves and higher LVEF rather than traditional cardiovascular risk factors. In our study, PPMI was not associated with long-term mortality. However, in patients with iCAD, PCI was associated with reduced long-term mortality compared to medical management.
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http://dx.doi.org/10.1016/j.carrev.2021.04.006DOI Listing
April 2021

The cannabinoid system and microglia in health and disease.

Neuropharmacology 2021 Apr 9:108555. Epub 2021 Apr 9.

Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, UNSW Sydney, NSW, 2052, Australia. Electronic address:

Recent years have yielded significant advances in our understanding of microglia, the immune cells of the central nervous system (CNS). Microglia are key players in CNS development, immune surveillance, and the maintenance of proper neuronal function throughout life. In the healthy brain, homeostatic microglia have a unique molecular signature. In neurological diseases, microglia become activated and adopt distinct transcriptomic signatures, including disease-associated microglia (DAM) implicated in neurodegenerative disorders. Homeostatic microglia synthesise the endogenous cannabinoids 2-arachidonoylglycerol and anandamide and express the cannabinoid receptors CB1 and CB2 at constitutively low levels. Upon activation, microglia significantly increase their synthesis of endocannabinoids and upregulate their expression of CB2 receptors, which promote a protective microglial phenotype by enhancing their production of neuroprotective factors and reducing their production of pro-inflammatory factors. Here, we summarise the effects of the microglial cannabinoid system in the CNS demyelinating disease multiple sclerosis, the neurodegenerative diseases Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, chronic inflammatory and neuropathic pain, and psychiatric disorders including depression, anxiety and schizophrenia. We discuss the therapeutic potential of cannabinoids in regulating microglial activity and highlight the need to further investigate their specific microglia-dependent immunomodulatory effects.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108555DOI Listing
April 2021

Poorer Theory of Mind in Amnestic Mild Cognitive Impairment Is Associated with Decreased Functional Connectivity in the Default Mode Network.

J Alzheimers Dis 2021 Apr 5. Epub 2021 Apr 5.

School of Psychology, University of Sydney, Sydney, Australia.

Background: Older adults living with amnestic mild cognitive impairment (aMCI) not only demonstrate impairments in Theory of Mind (ToM), relative to adults with non-amnestic MCI (naMCI), but are also at a higher risk of developing dementia.

Objective: Our primary objective was to ascertain whether default mode network (DMN) functional connectivity was differentially associated with ToM abilities between MCI subgroups.

Methods: Using functional magnetic resonance imaging, we investigated alterations in resting-state functional connectivity within the brain's DMN in a sample of 43 older adults with aMCI (n = 19) and naMCI (n = 24), previously reported to demonstrate poorer ToM abilities.

Results: Compared to naMCI, the aMCI subgroup revealed a significant association between poorer ToM performance and reduced functional connectivity between the bilateral temporal pole (TempP) and the left lateral temporal cortex (LTC) (LTC_L-TempP_L: b = -0.06, t(33) = -3.53, p = 0.02; LTC_L-TempP_R: b = -0.07,t(33) = -3.20, p = 0.03); between the right TempP and the dorsal medial prefrontal cortex (dMPFC) (b = -0.04, t(33) = -3.02, p = 0.03) and between the left and right TempP (b = -0.05, t(33) = -3.26, p = 0.03). In the naMCI subgroup, the opposite relationship was present between the bilateral TempP and the left LTC (Combined correlation: r = -0.47, p = 0.02), however, not between the right TempP and the dMPFC (r = -0.14, p = 0.51) or the left and right TempP (r = -0.31, p = 0.14).

Conclusion: Our findings suggest that alterations in functional connectivity within the DMN involving temporal and frontal lobe regions are associated with ToM deficits in aMCI.
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http://dx.doi.org/10.3233/JAD-201284DOI Listing
April 2021

The clinical features, management options and complications of paediatric femoral fractures.

Eur J Orthop Surg Traumatol 2021 Apr 11. Epub 2021 Apr 11.

Bristol Children's Hospital, Bristol, UK.

This article discusses the incidence, applied anatomy and classification of paediatric femoral fractures based on critical appraisal of the available evidence. The aim is to identify techniques that are relevant to contemporary practice whilst excluding the technical details of individual procedures that are beyond the scope of this review. Injuries of the proximal, diaphyseal and distal segments are considered individually as there are considerations that are specific to each anatomical site. Femoral neck fractures are rare injuries and require prompt anatomical reduction and stable fixation to minimise the potentially devastating consequences of avascular necrosis. Diaphyseal fractures are relatively common, and there is a spectrum of management options that depend on patient age and size. Distal femoral fractures often involve the physis, which contributes up to 70% of femoral length. Growth arrest is common consequence of fractures in this region, resulting in angular and length-related deformity. Long-term surveillance is recommended to identify deformity in evolution and provide an opportunity for early intervention. Deliberate injury should be considered in all fractures, particularly distal femoral physeal injuries and fractures in the non-walking child.
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http://dx.doi.org/10.1007/s00590-021-02933-1DOI Listing
April 2021

Bioactive half-sandwich Rh and Ir bipyridyl complexes containing artemisinin.

J Inorg Biochem 2021 Mar 3;219:111408. Epub 2021 Mar 3.

Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK. Electronic address:

Reaction of dihydroartemisinin (DHA) with 4-methyl-4'-carboxy-2,2'-bipyridine yielded the new ester derivative L1. Six novel organometallic half-sandwich chlorido Rh(III) and Ir(III) complexes (1-6) containing pentamethylcyclopentadienyl, (Cp*), tetramethylphenylcyclopentadienyl (Cp), or tetramethylbiphenylcyclopentadienyl (Cp), and N,N-chelated bipyridyl group of L1, have been synthesized and characterized. The complexes were screened for inhibitory activity against the Plasmodium falciparum 3D7 (sensitive), Dd2 (multi-drug resistant) and NF54 late stage gametocytes (LSGNF54), the parasite strain Trichomonas vaginalis G3, as well as A2780 (human ovarian carcinoma), A549 (human alveolar adenocarcinoma), HCT116 (human colorectal carcinoma), MCF7 (human breast cancer) and PC3 (human prostate cancer) cancer cell lines. They show nanomolar antiplasmodial activity, outperforming chloroquine and artemisinin. Their activities were also comparable to dihydroartemisinin. As anticancer agents, several of the complexes showed high inhibitory effects, with Ir(III) complex 3, containing the tetramethylbiphenylcyclopentadienyl ligand, having similar IC values (concentration for 50% of maximum inhibition of cell growth) as the clinical drug cisplatin (1.06-9.23 μM versus 0.24-7.2 μM, respectively). Overall, the iridium complexes (1-3) are more potent compared to the rhodium derivatives (4-6), and complex 3 emerges as the most promising candidate for future studies.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111408DOI Listing
March 2021

Rescue PCI in the management of STEMI: Contemporary results from the Melbourne Interventional Group registry.

Int J Cardiol Heart Vasc 2021 Apr 15;33:100745. Epub 2021 Mar 15.

Department of Cardiology, Ballarat Health Services, Ballarat, Victoria, Australia.

Background: Fibrinolysis is an important reperfusion strategy in the management of ST-elevation myocardial infarction (STEMI) when timely access to primary percutaneous coronary intervention (PPCI) is unavailable. Rescue PCI is generally thought to have worse outcomes than PPCI in STEMI. We aimed to determine short- and long-term outcomes of patients with rescue PCI versus PPCI for treatment of STEMI.

Methods And Results: Patients admitted with STEMI (excluding out-of-hospital cardiac arrest) within the Melbourne Interventional Group (MIG) registry between 2005 and 2018 treated with either rescue PCI or PPCI were included in this retrospective cohort analysis. Comparison of 30-day major adverse cardiac events (MACE) and long-term mortality between the two groups was performed. There were 558 patients (7.1%) with rescue PCI and 7271 with PPCI. 30-day all-cause mortality (rescue PCI 6% vs. PPCI 5%, p = 0.47) and MACE (rescue PCI 10.3% vs. PPCI 8.9%, p = 0.26) rates were similar between the two groups. Rates of in-hospital major bleeding (rescue PCI 6% vs. PPCI 3.4%, p = 0.002) and 30-day stroke (rescue PCI 2.2% vs. PPCI 0.8%, p < 0.001) were higher following rescue PCI. The odds ratio for haemorrhagic stroke in the rescue PCI group was 10.3. Long-term mortality was not significantly different between the groups (rescue PCI 20% vs. PPCI 19%, p = 0.33).

Conclusions: With contemporary interventional techniques and medical therapy, rescue PCI remains a valuable strategy for treating patients with failed fibrinolysis where PPCI is unavailable and it has been suggested in extenuating circumstances where alternative revascularisation strategies are considered.
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http://dx.doi.org/10.1016/j.ijcha.2021.100745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988313PMC
April 2021

Association between lifetime depression history, hippocampal volume and memory in non-amnestic mild cognitive impairment.

Eur J Neurosci 2021 Mar 25. Epub 2021 Mar 25.

Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, NSW, Australia.

Hippocampal subfield volume loss in older adults with amnestic mild cognitive impairment (aMCI) and depression history are associated with amyloid beta and tau pathology, thereby increasing the risk for Alzheimer's disease (AD). However, no studies have exclusively examined distinct alterations in hippocampal subfields in non-amnestic MCI (naMCI) in relation to depression history. Here, we used both longitudinal and transverse hippocampal segmentation methods using the automated Freesurfer software to examine whether a lifetime depression history is associated with differences in hippocampal head/body/tail (H/B/T) and key subfield volumes (CA1, subiculum, dentate gyrus) in older adults with naMCI. Further, we explored whether differences in hippocampal H/B/T and subfield volumes were associated with structured and unstructured verbal encoding and retention, comparing those with and without a depression history. The naMCI with a depression history group demonstrated larger or relatively preserved right CA1 volumes, which were associated with better unstructured verbal encoding and as well as structured verbal memory retention. This association between memory encoding and hippocampal CA1 and total head volume was significantly different to those with no depression history. The relationship between right CA1 volume and memory retention was also moderated by depression history status F (5,143)=7.84, p<0.001, R = 0.22. Those participants taking antidepressants had significantly larger hippocampal subiculum (p= 0.008), and right hippocampal body (p=0.004) and better performance on structured encoding (p=0.011) and unstructured memory retention (p=0.009). These findings highlight the importance of lifetime depression history and antidepressant use on the hippocampus and encoding and memory retention in naMCI.
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http://dx.doi.org/10.1111/ejn.15207DOI Listing
March 2021

Discovery of Potent and Fast-Acting Antimalarial Bis-1,2,4-triazines.

J Med Chem 2021 Apr 24;64(7):4150-4162. Epub 2021 Mar 24.

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia.

Novel 3,3'-disubstituted-5,5'-bi(1,2,4-triazine) compounds with potent activity against parasites were recently discovered. To improve the pharmacokinetic properties of the triazine derivatives, a new structure-activity relationship (SAR) investigation was initiated with a focus on enhancing the metabolic stability of lead compounds. These efforts led to the identification of second-generation highly potent antimalarial bis-triazines, exemplified by triazine , which exhibited significantly improved metabolic stability (8 and 42 μL/min/mg protein in human and mouse liver microsomes). The disubstituted triazine dimer was also observed to suppress parasitemia in the Peters 4-day test with a mean ED value of 1.85 mg/kg/day and exhibited a fast-killing profile, revealing a new class of orally available antimalarial compounds of considerable interest.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00044DOI Listing
April 2021

Overview of the contemporary management of supracondylar humeral fractures in children.

Eur J Orthop Surg Traumatol 2021 Mar 20. Epub 2021 Mar 20.

Consultant Paediatric Orthopaedic Surgeon, Bristol Children's Hospital, Bristol, UK.

Purpose: Supracondylar fractures are common injuries accounting for approximately 15% of all fractures in children with a large body of literature on this subject.

Methods:  This article critically appraises the available evidence to provide an overview of the treatment options including the role and timing of surgery, the geometry of wire fixation and the management of nerve and arterial injury.

Conclusion:  Management decisions are based on a number of considerations particularly fracture stability. Closed reduction and percutaneous K-wire stabilisation are commonly recommended for an unstable displaced fracture. These techniques are however associated with the potential for iatrogenic neurological injury. Vascular injury is also rare but must be recognised and treated promptly to avoid significant permanent morbidity.
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http://dx.doi.org/10.1007/s00590-021-02932-2DOI Listing
March 2021

Colorectal cancer risk following polypectomy in a multicentre, retrospective, cohort study: an evaluation of the 2020 UK post-polypectomy surveillance guidelines.

Gut 2021 Mar 5. Epub 2021 Mar 5.

Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK.

Objective: Colonoscopy surveillance aims to reduce colorectal cancer (CRC) incidence after polypectomy. The 2020 UK guidelines recommend surveillance at 3 years for 'high-risk' patients with ≥2 premalignant polyps (PMPs), of which ≥1 is 'advanced' (serrated polyp (or adenoma) ≥10 mm or with (high-grade) dysplasia); ≥5 PMPs; or ≥1 non-pedunculated polyp ≥20 mm; 'low-risk' patients without these findings are instead encouraged to participate in population-based CRC screening. We examined the appropriateness of these risk classification criteria and recommendations.

Design: Retrospective analysis of patients who underwent colonoscopy and polypectomy mostly between 2000 and 2010 at 17 UK hospitals, followed-up through 2017. We examined CRC incidence by baseline characteristics, risk group and number of surveillance visits using Cox regression, and compared incidence with that in the general population using standardised incidence ratios (SIRs).

Results: Among 21 318 patients, 368 CRCs occurred during follow-up (median: 10.1 years). Baseline CRC risk factors included age ≥55 years, ≥2 PMPs, adenomas with tubulovillous/villous/unknown histology or high-grade dysplasia, proximal polyps and a baseline visit spanning 2-90 days. Compared with the general population, CRC incidence without surveillance was higher among those with adenomas with high-grade dysplasia (SIR 1.74, 95% CI 1.21 to 2.42) or ≥2 PMPs, of which ≥1 was advanced (1.39, 1.09 to 1.75). For low-risk (71%) and high-risk (29%) patients, SIRs without surveillance were 0.75 (95% CI 0.63 to 0.88) and 1.30 (1.03 to 1.62), respectively; for high-risk patients after first surveillance, the SIR was 1.22 (0.91 to 1.60).

Conclusion: These guidelines accurately classify post-polypectomy patients into those at high risk, for whom one surveillance colonoscopy appears appropriate, and those at low risk who can be managed by non-invasive screening.
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http://dx.doi.org/10.1136/gutjnl-2020-323411DOI Listing
March 2021

Comparison of Long-Term Outcomes After Percutaneous Coronary Intervention in Patients With Insulin-Treated Versus Non-Insulin Treated Diabetes Mellitus.

Am J Cardiol 2021 Mar 3. Epub 2021 Mar 3.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia; Department of Cardiology, Royal Melbourne Hospital, Melbourne, Australia; Department of Medicine, University of Melbourne, Melbourne, Australia. Electronic address:

There are conflicting data on whether patients with insulin-treated diabetes mellitus (ITDM) have poorer outcomes compared with non-insulin treated diabetic (non-ITDM) patients following percutaneous coronary intervention (PCI). We therefore compared clinical outcomes following PCI in ITDM versus non-ITDM patients. We prospectively collected data on 4,579 patients with diabetes underwent PCI between 2005 and 2014 in a large multicenter registry and dichotomized them as having ITDM (n = 1,111) or non-ITDM (n = 3,468). The non-ITDM group was further divided into diet control only (diet-DM; n = 786) and those taking oral hypoglycemic agents (OHG-DM; n = 2,639), and clinical outcomes were compared with ITDM patients. Median follow-up for long-term mortality was 4.2 years (IQR 2.0 to 6.6 years). ITDM patients were more likely to be female, obese, and have severe renal impairment (all p <0.001). Procedural characteristics were similar other than a greater use of drug-eluting stents in ITDM patients. On multivariable analysis, ITDM was an independent predictor of 12-month major adverse cardiovascular and cerebrovascular events (MACCE; OR 1.26, 95% CI 1.02 to1.55, p = 0.03). Dividing the non-ITDM group further by treatment, a progressively higher rate of 12-month MACCE across the 3 groups was observed (13.5% vs 17.9% vs 21.8%; p <0.001). Long-term mortality was similar in the diet-DM and OHG-DM groups, but significantly higher in the ITDM group on Kaplan-Meier analysis (log-rank p <0.001). In conclusion, there is a clear gradient of adverse outcomes with escalation of therapy from diet control to OHGs to insulin.
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http://dx.doi.org/10.1016/j.amjcard.2021.02.025DOI Listing
March 2021

Artificial Intelligence Techniques That May Be Applied to Primary Care Data to Facilitate Earlier Diagnosis of Cancer: Systematic Review.

J Med Internet Res 2021 Mar 3;23(3):e23483. Epub 2021 Mar 3.

Primary Care Unit, Department of Public Health & Primary Care, University of Cambridge, Cambridge, United Kingdom.

Background: More than 17 million people worldwide, including 360,000 people in the United Kingdom, were diagnosed with cancer in 2018. Cancer prognosis and disease burden are highly dependent on the disease stage at diagnosis. Most people diagnosed with cancer first present in primary care settings, where improved assessment of the (often vague) presenting symptoms of cancer could lead to earlier detection and improved outcomes for patients. There is accumulating evidence that artificial intelligence (AI) can assist clinicians in making better clinical decisions in some areas of health care.

Objective: This study aimed to systematically review AI techniques that may facilitate earlier diagnosis of cancer and could be applied to primary care electronic health record (EHR) data. The quality of the evidence, the phase of development the AI techniques have reached, the gaps that exist in the evidence, and the potential for use in primary care were evaluated.

Methods: We searched MEDLINE, Embase, SCOPUS, and Web of Science databases from January 01, 2000, to June 11, 2019, and included all studies providing evidence for the accuracy or effectiveness of applying AI techniques for the early detection of cancer, which may be applicable to primary care EHRs. We included all study designs in all settings and languages. These searches were extended through a scoping review of AI-based commercial technologies. The main outcomes assessed were measures of diagnostic accuracy for cancer.

Results: We identified 10,456 studies; 16 studies met the inclusion criteria, representing the data of 3,862,910 patients. A total of 13 studies described the initial development and testing of AI algorithms, and 3 studies described the validation of an AI algorithm in independent data sets. One study was based on prospectively collected data; only 3 studies were based on primary care data. We found no data on implementation barriers or cost-effectiveness. Risk of bias assessment highlighted a wide range of study quality. The additional scoping review of commercial AI technologies identified 21 technologies, only 1 meeting our inclusion criteria. Meta-analysis was not undertaken because of the heterogeneity of AI modalities, data set characteristics, and outcome measures.

Conclusions: AI techniques have been applied to EHR-type data to facilitate early diagnosis of cancer, but their use in primary care settings is still at an early stage of maturity. Further evidence is needed on their performance using primary care data, implementation barriers, and cost-effectiveness before widespread adoption into routine primary care clinical practice can be recommended.
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http://dx.doi.org/10.2196/23483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970165PMC
March 2021

Chromosome level reference of Atlantic halibut Hippoglossus hippoglossus provides insight into the evolution of sexual determination systems.

Mol Ecol Resour 2021 Mar 2. Epub 2021 Mar 2.

Biology Department, Dalhousie University, Halifax, NS, Canada.

Changes in the genetic mechanisms that control sexual determination have occurred independently across the tree of life, and with exceptional frequency in teleost fishes. To investigate the genomic changes underlying the evolution of sexual determination, we sequenced a chromosome-level genome, multitissue transcriptomes, and reduced representation population data for the Atlantic halibut (Hippoglossus hippoglossus), which has an XY/XX sex determination mechanism and has recently diverged (0.9-3.8 Ma) from the Pacific halibut (Hippoglossus stenolepis), which has a ZZ/ZW system. We used frequency and coverage-based population approaches to identify a putative sex-determining factor, GSDF. We characterized regions with elevated heterozygosity and linkage disequilibrium indicating suppression of recombination across a nascent sex chromosome. We detected testis-specific expression of GSDF, the sequence of which is highly conserved across flatfishes. Based on evidence from genome-wide association, coverage, linkage disequilibrium, testis and brain transcriptomes, and sequence conservation with other flatfishes, we propose a mechanism for the recent evolution of an XY sex-determination mechanism in Atlantic halibut. Changes to the ancestral sex-determining gene DMRT1 in regulating the downstream gene GSDF probably coincided with GSDF, or a proximal regulatory element of it, becoming the primary sex-determining factor. Our results suggest changes to a small number of elements can have drastic repercussions for the genomic substrate available to sex-specific evolutionary forces, providing insight into how certain elements repeatedly evolve to control sex across taxa. Our chromosome-level assembly, multitissue transcriptomes, and population genomic data provide a valuable resource and understanding of the evolution of sexual systems in fishes.
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http://dx.doi.org/10.1111/1755-0998.13369DOI Listing
March 2021

Beneficial Effect of Consecutive Screening Mammography Examinations on Mortality from Breast Cancer: A Prospective Study.

Radiology 2021 Mar 2:203935. Epub 2021 Mar 2.

From the Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, England (S.W.D., R.M.); Department of Mammography, Falun Central Hospital, Falun, Sweden (L.T.); School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei City, Taiwan (A.M.F.Y., S.L.S.C.); Department of Diagnostic Radiology, University of Turku, Turku, Finland (P.B.D.); Department of Cancer Control Sciences, American Cancer Society, Atlanta, Ga (R.A.S.); Regional Cancer Center, Umeå University, Umeå, Sweden (H.J.); Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden (S.T.); Department of Health Care Management, College of Management, Chang Gung University, Taoyuan, Taiwan (S.Y.H.C.); Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (S.Y.H.C.); Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan (S.Y.H.C., G.H.H.J., M.M.S.K., C.Y.H., T.H.H.C.); Regional Cancer Center, Uppsala University Hospital, Uppsala, Sweden (J.A.); Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, England (L.H.); and Department of Surgical Sciences, Uppsala University, Uppsala, Sweden (L.H.).

Background Previously, the risk of death from breast cancer was analyzed for women participating versus those not participating in the last screening examination before breast cancer diagnosis. Consecutive attendance patterns may further refine estimates. Purpose To estimate the effect of participation in successive mammographic screening examinations on breast cancer mortality. Materials and Methods Participation data for Swedish women eligible for screening mammography in nine counties from 1992 to 2016 were linked with data from registries and regional cancer centers for breast cancer diagnosis, cause, and date of death (Uppsala University ethics committee registration number: 2017/147). Incidence-based breast cancer mortality was calculated by whether the women had participated in the most recent screening examination prior to diagnosis only (intermittent participants), the penultimate screening examination only (lapsed participants), both examinations (serial participants), or neither examination (serial nonparticipants). Rates were analyzed with Poisson regression. We also analyzed incidence of breast cancers proving fatal within 10 years. Results Data were available for a total average population of 549 091 women (average age, 58.9 years ± 6.7 [standard deviation]). The numbers of participants in the four groups were as follows: serial participants, 392 135; intermittent participants, 41 746; lapsed participants, 30 945; and serial nonparticipants, 84 265. Serial participants had a 49% lower risk of breast cancer mortality (relative risk [RR], 0.51; 95% CI: 0.48, 0.55; < .001) and a 50% lower risk of death from breast cancer within 10 years of diagnosis (RR, 0.50; 95% CI: 0.46, 0.55; < .001) than serial nonparticipants. Lapsed and intermittent participants had a smaller reduction. Serial participants had significantly lower risk of both outcomes than lapsed or intermittent participants. Analyses correcting for potential biases made little difference to the results. Conclusion Women participating in the last two breast cancer screening examinations prior to breast cancer diagnosis had the largest reduction in breast cancer death. Missing either one of the last two examinations conferred a significantly higher risk. © RSNA, 2021
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http://dx.doi.org/10.1148/radiol.2021203935DOI Listing
March 2021

Health Behavior Resources Available to Farmers in Rural Ohio.

J Agromedicine 2021 Feb 28:1-8. Epub 2021 Feb 28.

College of Nursing, the Ohio State University, Department of Veterans Affairs Healthcare System, Columbus, Ohio, USA.

Poor health habits correlate with morbidity and mortality. Rural communities often have decreased access to prevention programs and health care. As a state highly dependent on agriculture, this study identifies rural health services for Ohio farmers. This cross-sectional, descriptive study surveys key informants in Ohio at rural health clinics, critical access hospitals, health departments, Ohio State University (OSU) Extension offices, migrant clinics, and Federally Qualified Health Centers about the types of services available to address eight health behaviors. Key informants were invited via email and U.S. Postal Service to complete an electronic survey. After service types were identified, additional information to describe format, barriers to delivery and perceived importance of the service was asked. Of Ohio's 75 rural counties, 51 counties are represented in the data by at least one participating organization. Nutrition/healthy eating-related health services are provided most often by organizations (95.8%) and sleep services were least often reported (49.5%). The other health behaviors services (sun/UV exposure, physical activity, mental health, tobacco cessation, alcohol/substance abuse, and opioid abuse) fell in-between. Organizations are most likely to offer health education resources in print or web-based format across all health behaviors except for sleep, where social media promotion are the most common. The largest barrier to providing any type of health service is a lack of personnel. Providing health behavior services to farmers and farm families is important for improving their overall health. Documenting available services will assist the rural health community in future collaborative wellness projects.
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http://dx.doi.org/10.1080/1059924X.2021.1893882DOI Listing
February 2021

Including a general practice endorsement letter with the testing kit in the Bowel Cancer Screening Programme: Results of a cluster randomised trial.

J Med Screen 2021 Feb 27:969141321997480. Epub 2021 Feb 27.

Department of Applied Health Research, University College London, London, UK.

Objectives: To evaluate the effect of general practitioner endorsement accompanying the screening kit rather than with the invitation letter on participation in the NHS Bowel Cancer Screening Programme and on the socioeconomic gradient in participation in the Programme.

Methods: The NHS Bowel Cancer Screening Programme in England is delivered via five regional hubs. In early 2016, we carried out a cluster-randomised trial, with hub-day of invitation as the randomisation unit. We randomised 150 hub-days of invitation to the intervention group, GP endorsement on the letter accompanying the guaiac faecal occult blood testing kit (75 hub-days, 197,366 individuals) or control, usual letter (75 hub-days, 197,476 individuals). The endpoint was participation, defined as return of a valid kit within 18 weeks of initial invitation. Because of the cluster randomisation, data were analysed by a hierarchical logistic regression, allowing a random effect for date of invitation. Socioeconomic status was represented by the index of multiple deprivation.

Results: Participation was 59.4% in the intervention group and 58.7% in the control group, a significant difference ( = 0.04). There was no heterogeneity of the effect of intervention by index of multiple deprivation. We found that there was some confounding between date and screening episode order (first or subsequent screen). This in turn may have induced confounding with age and slightly diluted the result.

Conclusions: General practitioner endorsement induces a modest increase in participation in bowel cancer screening, but does not affect the socioeconomic gradient. When considering cluster randomisation as a research method, careful scrutiny of potential confounding is indicated in advance if possible and in analysis otherwise.
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http://dx.doi.org/10.1177/0969141321997480DOI Listing
February 2021

Benefits and harms of breast cancer mammography screening for women at average risk of breast cancer: A systematic review for the European Commission Initiative on Breast Cancer.

J Med Screen 2021 Feb 25:969141321993866. Epub 2021 Feb 25.

CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Objectives: Mammography screening is generally accepted in women aged 50-69, but the balance between benefits and harms remains controversial in other age groups. This study systematically reviews these effects to inform the European Breast Cancer Guidelines.

Methods: We searched PubMed, EMBASE and Cochrane Library for randomised clinical trials (RCTs) or systematic reviews of observational studies in the absence of RCTs comparing invitation to mammography screening to no invitation in women at average breast cancer (BC) risk. We extracted data for mortality, BC stage, mastectomy rate, chemotherapy provision, overdiagnosis and false-positive-related adverse effects. We performed a pooled analysis of relative risks, applying an inverse-variance random-effects model for three age groups (<50, 50-69 and 70-74). GRADE (Grading of Recommendations Assessment, Development and Evaluation) was used to assess the certainty of evidence.

Results: We identified 10 RCTs including 616,641 women aged 38-75. Mammography reduced BC mortality in women aged 50-69 (relative risk (RR) 0.77, 95%CI (confidence interval) 0.66-0.90, ) and 70-74 (RR 0.77, 95%CI 0.54-1.09, ), with smaller reductions in under 50s (RR 0.88, 95%CI 0.76-1.02, ). Mammography reduced stage IIA+ in women 50-69 (RR 0.80, 95%CI 0.64-1.00, ) but resulted in an overdiagnosis probability of 23% (95%CI 18-27%) and 17% (95%CI 15-20%) in under 50s and 50-69, respectively (). Mammography was associated with 2.9% increased risk of invasive procedures with benign outcomes ().

Conclusions: For women 50-69, high certainty evidence that mammography screening reduces BC mortality risk would support policymakers formulating strong recommendations. In other age groups, where the net balance of effects is less clear, conditional recommendations will be more likely, together with shared decision-making.
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http://dx.doi.org/10.1177/0969141321993866DOI Listing
February 2021

Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion.

Eur J Med Chem 2021 Mar 4;214:113253. Epub 2021 Feb 4.

The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010, Australia. Electronic address:

The emerging resistance to combination therapies comprised of artemisinin derivatives has driven a need to identify new antimalarials with novel mechanisms of action. Central to the survival and proliferation of the malaria parasite is the invasion of red blood cells by Plasmodium merozoites, providing an attractive target for novel therapeutics. A screen of the Medicines for Malaria Venture Pathogen Box employing transgenic P. falciparum parasites expressing the nanoluciferase bioluminescent reporter identified the phenylsulfonyl piperazine class as a specific inhibitor of erythrocyte invasion. Here, we describe the optimization and further characterization of the phenylsulfonyl piperazine class. During the optimization process we defined the functionality required for P. falciparum asexual stage activity and determined the alpha-carbonyl S-methyl isomer was important for antimalarial potency. The optimized compounds also possessed comparable activity against multidrug resistant strains of P. falciparum and displayed weak activity against sexual stage gametocytes. We determined that the optimized compounds blocked erythrocyte invasion consistent with the asexual activity observed and therefore the phenylsulfonyl piperazine analogues described could serve as useful tools for studying Plasmodium erythrocyte invasion.
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http://dx.doi.org/10.1016/j.ejmech.2021.113253DOI Listing
March 2021

Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer, hormone receptor positive, HER-2 negative.

Br J Cancer 2021 Feb 18. Epub 2021 Feb 18.

Michael G. DeGroote Cochrane Canada and McGRADE Centres; Department of Health Research Methods, Evidence and Impact, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.

Background: Predicting the risk of recurrence and response to chemotherapy in women with early breast cancer is crucial to optimise adjuvant treatment. Despite the common practice of using multigene tests to predict recurrence, existing recommendations are inconsistent. Our aim was to formulate healthcare recommendations for the question "Should multigene tests be used in women who have early invasive breast cancer, hormone receptor-positive, HER2-negative, to guide the use of adjuvant chemotherapy?"

Methods: The European Commission Initiative on Breast Cancer (ECIBC) Guidelines Development Group (GDG), a multidisciplinary guideline panel including experts and three patients, developed recommendations informed by systematic reviews of the evidence. Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision frameworks were used. Four multigene tests were evaluated: the 21-gene recurrence score (21-RS), the 70-gene signature (70-GS), the PAM50 risk of recurrence score (PAM50-RORS), and the 12-gene molecular score (12-MS).

Results: Five studies (2 marker-based design RCTs, two treatment interaction design RCTs and 1 pooled individual data analysis from observational studies) were included; no eligible studies on PAM50-RORS or 12-MS were identified and the GDG did not formulate recommendations for these tests.

Conclusions: The ECIBC GDG suggests the use of the 21-RS for lymph node-negative women (conditional recommendation, very low certainty of evidence), recognising that benefits are probably larger in women at high risk of recurrence based on clinical characteristics. The ECIBC GDG suggests the use of the 70-GS for women at high clinical risk (conditional recommendation, low certainty of evidence), and recommends not using 70-GS in women at low clinical risk (strong recommendation, low certainty of evidence).
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http://dx.doi.org/10.1038/s41416-020-01247-zDOI Listing
February 2021

Detection of involved margins in breast specimens with X-ray phase-contrast computed tomography.

Sci Rep 2021 Feb 11;11(1):3663. Epub 2021 Feb 11.

Department of Medical Physics and Biomedical Engineering, University College London, Gower St, London, WC1E 6BT, UK.

Margins of wide local excisions in breast conserving surgery are tested through histology, which can delay results by days and lead to second operations. Detection of margin involvement intraoperatively would allow the removal of additional tissue during the same intervention. X-ray phase contrast imaging (XPCI) provides soft tissue sensitivity superior to conventional X-rays: we propose its use to detect margin involvement intraoperatively. We have developed a system that can perform phase-based computed tomography (CT) scans in minutes, used it to image 101 specimens approximately half of which contained neoplastic lesions, and compared results against those of a commercial system. Histological analysis was carried out on all specimens and used as the gold standard. XPCI-CT showed higher sensitivity (83%, 95% CI 69-92%) than conventional specimen imaging (32%, 95% CI 20-49%) for detection of lesions at margin, and comparable specificity (83%, 95% CI 70-92% vs 86%, 95% CI 73-93%). Within the limits of this study, in particular that specimens obtained from surplus tissue typically contain small lesions which makes detection more difficult for both methods, we believe it likely that the observed increase in sensitivity will lead to a comparable reduction in the number of re-operations.
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http://dx.doi.org/10.1038/s41598-021-83330-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878478PMC
February 2021

Difference in a decade: percutaneous coronary interventions in Australia.

Intern Med J 2021 Jan;51(1):138-139

Department of Cardiology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/imj.15150DOI Listing
January 2021

Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study.

BMJ Open 2021 Feb 10;11(2):e041500. Epub 2021 Feb 10.

Healthy Brain Ageing Program, The University of Sydney School of Psychology, Sydney, New South Wales, Australia

Introduction: Melatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI).

Methods And Analysis: The study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia.

Ethics And Dissemination: This protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings.

Trial Registration Number: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190).

Protocol Version: V.8 15 October 2020.
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http://dx.doi.org/10.1136/bmjopen-2020-041500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878132PMC
February 2021

Sleep-Dependent Memory in Older People With and Without MCI: The Relevance of Sleep Microarchitecture, OSA, Hippocampal Subfields, and Episodic Memory.

Cereb Cortex 2021 Feb 10. Epub 2021 Feb 10.

School of Psychology, University of Sydney, Sydney, New South Wales, 2000, Australia.

This study aimed to determine if, relative to cognitively healthy controls, sleep-dependent memory consolidation (SDMC) is diminished in mild cognitive impairment (MCI), a group at high risk of conversion to dementia. We also sought to determine whether SDMC is associated with sleep characteristics, daytime episodic memory, and hippocampal integrity. Participants with MCI (n = 43) and controls (n = 20) underwent clinical and neuropsychological profiling. From polysomnography, apnea hypopnea index (AHI) and non-REM sleep spindle characteristics were derived. From magnetic resonance imaging, hippocampal subfield volumes were computed. Participants learned a novel 32-item word-pair prior to sleep; morning retention of the word-pairs was used to determine SDMC. Results showed that SDMC did not differ between MCI and controls, but there was a large effect size decrement in SDMC in those with multiple domain MCI (Hedge's g = 0.85). In MCI, poorer SDMC was correlated with CA1 and CA3 hippocampal atrophy, shorter spindle duration, and worse daytime episodic memory. In controls, poorer SDMC was associated with higher AHI. Impaired daytime memory consolidation, reduced hippocampal volumes, shorter sleep spindles, and greater sleep apnea severity are indicators of diminished SDMC in older adults and should be explored in future studies.
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http://dx.doi.org/10.1093/cercor/bhaa406DOI Listing
February 2021

Obesity and Oxidative Stress in Older Adults At Risk for Dementia: A Magnetic Resonance Spectroscopy Study.

Alzheimer Dis Assoc Disord 2021 Jan 27. Epub 2021 Jan 27.

Healthy Brain Ageing Program, Brain and Mind Centre & Charles Perkins Centre School of Psychology, Faculty of Science Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research Central Clinical School, Faculty of Medicine and Health Discipline of Exercise and Sport Science, Faculty of Health Sciences School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW Sunshine Coast Mind and Neuroscience-Thompson Institute, University of Sunshine Coast, Sunshine Coast, QLD, Australia.

Objective: This study aimed to investigate the relationship between obesity and oxidative stress in older adults at risk for dementia. It also aimed to explore the influence of physical activity on the relationship between obesity and oxidative stress in this at risk cohort.

Methods: Older adults at risk for dementia underwent comprehensive medical, neuropsychological, and psychiatric assessment. At risk was defined as participants with subjective or mild cognitive impairment. Glutathione was assessed by magnetic resonance spectroscopy in the left hippocampus and the anterior and posterior cingulate cortex. Body mass index (BMI) was calculated and classified as healthy (BMI <25 kg/m2) or overweight/obese (BMI ≥25 kg/m2).

Results: Sixty-five older adults (mean age=66.2 y) were included for analysis. The overweight/obese group had significantly greater glutathione in the hippocampus compared with the healthy weight group (t=-2.76, P=0.008). No significant difference in glutathione was observed between groups in the anterior or posterior cingulate. In the overweight/obese group, a higher BMI was associated with a diabetes diagnosis and lower total time engaging in physical activity (r=-0.36, P=0.025), however, glutathione did not correlate with activity levels across groups.

Conclusion: This study demonstrates that changes in in vivo markers of oxidative stress are present in overweight/obese older adults at risk for dementia. Future research should explore the relationship with diabetes and the longitudinal relationship between BMI and oxidative stress, and response to therapeutic interventions.
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http://dx.doi.org/10.1097/WAD.0000000000000434DOI Listing
January 2021

Effect of Age on Clinical Outcomes in Elderly Patients (>80 Years) Undergoing Percutaneous Coronary Intervention: Insights From a Multi-Centre Australian PCI Registry.

Heart Lung Circ 2021 Jan 18. Epub 2021 Jan 18.

Alfred Health, Melbourne VIC3004, Australia; The University of Melbourne, Parkville, VIC, Australia. Electronic address:

Objectives: To evaluate the effect of age in an all-comers population undergoing percutaneous coronary intervention (PCI).

Background: Age is an important consideration in determining appropriateness for invasive cardiac assessment and perceived clinical outcomes.

Methods: We analysed data from 29,012 consecutive patients undergoing PCI in the Melbourne Interventional Group (MIG) registry between 2005 and 2017. 25,730 patients <80 year old (78% male, mean age 62±10 years; non-elderly cohort) were compared to 3,282 patients ≥80 year old (61% male, mean age 84±3 years; elderly cohort).

Results: The elderly cohort had greater prevalence of hypertension, diabetes and previous myocardial infarction (all p<0.001). Elderly patients were more likely to present with acute coronary syndromes, left ventricular ejection fraction <45% and chronic kidney disease (p<0.0001). In-hospital, 30-day and long-term all-cause mortality (over a median of 3.6 and 5.1 years for elderly and non-elderly cohorts, respectively) were higher in the elderly cohort (5.2% vs. 1.9%; 6.4% vs. 2.2%; and 43% vs. 14% respectively, all p<0.0001). In multivariate Cox regression analysis, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m (HR 3.8, 95% CI: 3.4-4.3), cardiogenic shock (HR 3.0, 95% CI: 2.6-3.4), ejection fraction <30% (HR 2.5, 95% CI: 2.1-2.9); and age ≥80 years (HR 2.8, 95% CI: 2.6-3.1) were independent predictors of long-term all-cause mortality (all p<0.0001).

Conclusion: The elderly cohort is a high-risk group of patients with increasing age being associated with poorer long-term mortality. Age, thus, should be an important consideration when individualising treatment in elderly patients.
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http://dx.doi.org/10.1016/j.hlc.2020.12.003DOI Listing
January 2021