Publications by authors named "Catherine Martin"

181 Publications

Dexamethasone and Surgical-Site Infection.

N Engl J Med 2021 05;384(18):1731-1741

From Royal Perth Hospital (T.B.C., P.C., K.M.H.), the University of Western Australia (T.B.C., E.O., K.M.H.), Murdoch University (K.M.H.), and Fiona Stanley Hospital (E.O.), Perth, and the Alfred Hospital (P.S.M., A.C.C., L.A.B.), Monash University (T.B.C., P.S.M., A.B.F., A.C.C., L.A.B., K.L., C.M.), the University of Melbourne (K.L., D.S.), and Royal Melbourne Hospital (K.L.), Melbourne, VIC - all in Australia; the Chinese University of Hong Kong, Hong Kong (M.T.V.C.); and Auckland City Hospital and the University of Auckland - both in Auckland, New Zealand (T.G.S.).

Background: The glucocorticoid dexamethasone prevents nausea and vomiting after surgery, but there is concern that it may increase the risk of surgical-site infection.

Methods: In this pragmatic, international, noninferiority trial, we randomly assigned 8880 adult patients who were undergoing nonurgent, noncardiac surgery of at least 2 hours' duration, with a skin incision length longer than 5 cm and a postoperative overnight hospital stay, to receive 8 mg of intravenous dexamethasone or matching placebo while under anesthesia. Randomization was stratified according to diabetes status and trial center. The primary outcome was surgical-site infection within 30 days after surgery. The prespecified noninferiority margin was 2.0 percentage points.

Results: A total of 8725 participants were included in the modified intention-to-treat population (4372 in the dexamethasone group and 4353 in the placebo group), of whom 13.2% (576 in the dexamethasone group and 572 in the placebo group) had diabetes mellitus. Of the 8678 patients included in the primary analysis, surgical-site infection occurred in 8.1% (354 of 4350 patients) assigned to dexamethasone and in 9.1% (394 of 4328) assigned to placebo (risk difference adjusted for diabetes status, -0.9 percentage points; 95.6% confidence interval [CI], -2.1 to 0.3; P<0.001 for noninferiority). The results for superficial, deep, and organ-space surgical-site infections and in patients with diabetes were similar to those of the primary analysis. Postoperative nausea and vomiting in the first 24 hours after surgery occurred in 42.2% of patients in the dexamethasone group and in 53.9% in the placebo group (risk ratio, 0.78; 95% CI, 0.75 to 0.82). Hyperglycemic events in patients without diabetes occurred in 22 of 3787 (0.6%) in the dexamethasone group and in 6 of 3776 (0.2%) in the placebo group.

Conclusions: Dexamethasone was noninferior to placebo with respect to the incidence of surgical-site infection within 30 days after nonurgent, noncardiac surgery. (Funded by the Australian National Health and Medical Research Council and others; PADDI Australian New Zealand Clinical Trials Registry number, ACTRN12614001226695.).
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http://dx.doi.org/10.1056/NEJMoa2028982DOI Listing
May 2021

Rapamycin Added to Diet in Late Mid-Life Delays Age-Related Hearing Loss in UMHET4 Mice.

Front Cell Neurosci 2021 7;15:658972. Epub 2021 Apr 7.

Kresge Hearing Research Institute, Department of Otolaryngology, Head and Neck Surgery, University of Michigan, Ann Arbor, MI, United States.

Our previous study demonstrated rapamycin added to diet at 4 months of age had significantly less age-related outer hair cell loss in the basal half of the cochlea at 22 months of age compared to mice without rapamycin. The present study tested adding rapamycin to diet later in life, at 14 months of age, and added a longitudinal assessment of auditory brain stem response (ABR). The present study used UMHET4 mice, a 4 way cross in which all grandparental strains lack the Cdh23 allele that predisposes to early onset, progressive hearing loss. UMHET4 mice typically have normal hearing until 16-17 months, then exhibit threshold shifts at low frequencies/apical cochlea and later in more basal high frequency regions. ABR thresholds at 4, 12, 24, and 48 kHz were assessed at 12, 18, and 24 months of age and compared to baseline ABR thresholds acquired at 5 months of age to determine threshold shifts (TS). There was no TS at 12 months of age at any frequency tested. At 18 months of age mice with rapamycin added to diet at 14 months had a significantly lower mean TS at 4 and 12 kHz compared to mice on control diet with no significant difference at 24 and 48 kHz. At 24 months of age, the mean 4 kHz TS in rapamycin diet group was no longer significantly lower than the control diet group, while the 12 kHz mean remained significantly lower. Mean TS at 24 and 48 kHz in the rapamycin diet group became significantly lower than in the control diet group at 24 months. Hair cell counts at 24 months showed large loss in the apical half of most rapamycin and control diet mice cochleae with no significant difference between groups. There was only mild outer hair cell loss in the basal half of rapamycin and control diet mice cochleae with no significant difference between groups. The results show that a later life addition of rapamycin can decrease age-related hearing loss in the mouse model, however, it also suggests that this decrease is a delay/deceleration rather than a complete prevention.
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http://dx.doi.org/10.3389/fncel.2021.658972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058174PMC
April 2021

Exploratory examination of the effects of d-amphetamine on active-state functional connectivity: Influence of impulsivity and sensation-seeking status.

Exp Clin Psychopharmacol 2021 Mar 25. Epub 2021 Mar 25.

Department of Behavioral Science.

Recent advances in diagnostic research identified that individuals with higher impulsivity and sensation-seeking scores tend to report more positive subjective responses to stimulant drugs such as amphetamine. The current exploratory study hypothesized that differences in underlying mesocorticolimbic circuitry may mediate the relationship between personality and responses to stimulants due to its previously established implication in reward processes as well as the overlap between its dopaminergic projections and the pharmacodynamics of many stimulants. Forty participants (20 female) were recruited with relatively high- and low-impulsivity and sensation-seeking scores as defined by the Zuckerman-Kuhlman Personality Questionnaire (Form IIIR; Zuckerman, Kuhlman, Joireman, Teta, & Kraft, 1993) for a double-blind, placebo-controlled, intranasal amphetamine administration study conducted within an MRI scanner. Active state seed-to-voxel connectivity analyses assessed the effects of amphetamine, personality, subjective responses to amphetamine, and their interactions with mesocorticolimbic seeds on data collected during monetary incentive delay and go/no-go task performance. Results indicated that amphetamine administration largely disrupted brain activity as evidenced by connectivity values shifting toward no correlation among brain stem, striatal, and frontal cortex regions. Additionally, associations of impulsivity and connectivity between ventral tegmental and medial orbitofrontal as well as lateral orbitofrontal and putamen regions were inverted from negative to positive during the placebo and amphetamine conditions, respectively. Personality was unrelated to subjective responses to amphetamine. Results are interpreted as providing evidence of underlying differences in mesocorticolimbic circuitry being a potential target for requisite diagnostic and treatment strategies implicated with stimulant use disorders, but further research is needed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/pha0000406DOI Listing
March 2021

Outcomes Of Non-Cystic Fibrosis Related Bronchiectasis Post Lung Transplantation.

Intern Med J 2021 Mar 3. Epub 2021 Mar 3.

Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Australia.

Background: Lung transplantation is a recognised treatment for end-stage lung disease due to bronchiectasis. Non-CF bronchiectasis and CF are often combined into one cohort, however outcomes for non-CF bronchiectasis patients varies between centres, and in comparison to those for CF.

Aims: To compare lung transplantation mortality and morbidity of bronchiectasis (non-CF) patients to those with CF and other indications.

Methods: Retrospective analysis of patients undergoing lung transplantation between 01 January 2008-31 December 2013. Time to and cause of lung allograft loss was censored on 01 April 2018. A case-note review was conducted on a sub-group of 78 patients, to analyse hospital admissions as a marker of morbidity.

Results: 341 patients underwent lung transplantation, 22 (6%) had bronchiectasis compared to 69 (20%) with CF. The 5-year survival for the bronchiectasis group was 32%, compared to CF 69%, obstructive lung disease (OLD) 64%, pulmonary hypertension 62% and ILD 55% (p = 0.008). Lung allograft loss due to CLAD with predominant infection was significantly higher in the bronchiectasis group at 2 years. The rate of acute admissions was 2.24 higher in the bronchiectasis group when compared to OLD (p = 0.01). Patients with bronchiectasis spent 45.81 days in hospital per person year after transplantation compared with 18.21 days for CF.

Conclusions: Bronchiectasis patients in this study had a lower 5-year survival and poorer outcomes in comparison to other indications including CF. Bronchiectasis should be considered a separate entity to CF in survival analysis. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15256DOI Listing
March 2021

Developing a nursing dependency scoring tool for children's palliative care: the impact on hospice care.

Int J Palliat Nurs 2021 Feb;27(1):37-45

Deputy Director of Clinical Services, Martin House Children's Hospice, Wetherby, UK.

Background: Occupancy is commonly used to measure bed management in hospices. However, the increasing complexity of children and young people and growing dependence on technology mean that this is no longer effective.

Aim: To develop a dependency tool that enables the hospice to safely and effectively manage the use of beds for planned short breaks (respite care), preserving capacity for children requiring symptom management and end-of-life care.

Methods: A comprehensive literature review and existing tools were used to inform the development of the Martin House Dependency Tool Framework. Training was provided to staff and the tool was piloted before applying it across the hospice caseload.

Findings: The tool has been used on 431 children (93.1% of caseload). The tool enabled consistency of assessment and more effective management of resources, due to a contemporaneous understanding of the clinical needs of those on the caseload.

Conclusion: The tool has enabled consistent and transparent assessment of children, improving safety, effectiveness and responsiveness, and the management of the workforce and resources.
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http://dx.doi.org/10.12968/ijpn.2021.27.1.37DOI Listing
February 2021

Mitral valve repair rates in degenerative mitral valve disease correlate with surgeon and hospital procedural volume.

J Card Surg 2021 Apr 22;36(4):1419-1426. Epub 2021 Feb 22.

Department of Cardiothoracic Surgery, Monash Health, and Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia.

Study Aim: To determine the relationship between surgeon and hospital procedural volume, and mitral valve repair rates and 30-day mortality for degenerative mitral regurgitation (MR), in Australian cardiac surgical centers.

Methods: A total of 4420 patients who underwent elective surgery for degenerative MR between January 2008 and December 2017 in the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Database were retrospectively included. Univariate and multivariate regression analyses examined surgeon and hospital procedural volumes for associations with repair rate and mortality.

Results: Repair rates varied widely by caseload; from 62.57% to 79.53% for lowest to highest volume surgeons; and from 54.56% to 77.54% for lowest to highest volume hospitals. Compared to surgeons performing ≤5 procedures/annum, surgeons performing 10.1-20/annum were more likely to repair the valve (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.09-5.28, p = .03), particularly if performing more than 20/annum (OR 2.88, 95% CI 1.09-7.60, p = .03). Compared to hospitals performing ≤10/annum, those performing any number of procedures more than 10 demonstrated an increased likelihood of repair (caseload 10.1-20/year OR 1.96, 95% CI 1.25-3.07, p = .003) though odds did not increase above this threshold. Low incidence of 30-day mortality (63 of 4414, 1.43%) limited analysis of contributing variables; procedural volume did not confer a survival benefit.

Conclusions: Surgeon and hospital caseload were significantly associated with repair rates of degenerative MR. A threshold minimum of 10 procedures annually for surgeons and hospitals should be utilized to maximize repair rates, and ideally of 20 for surgeons. Mortality was low and may not be significantly impacted by procedural volume.
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http://dx.doi.org/10.1111/jocs.15310DOI Listing
April 2021

Depression scores improve with continuous positive airway pressure in specialized sleep clinics: real-world data.

J Clin Sleep Med 2021 Jun;17(6):1201-1209

Department of Respiratory Medicine, Alfred Health, Melbourne, Australia.

Study Objectives: To assess changes in Hospital Anxiety and Depression Scale (HADS) scores after continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea.

Methods: Consecutive patients attending the Alfred Health sleep clinic, diagnosed with obstructive sleep apnea, and prescribed CPAP were recruited. The primary outcome was a change in the HADS depression (HADS-D) and anxiety (HADS-A) subscales from the time of diagnosis to follow-up. Secondary analysis compared high (> 4 hours) and low (< 4 hours) CPAP adherence groups and change in depression cases, defined by HADS-D ≥ 8, and anxiety cases, defined by HADS-A ≥ 11.

Results: We included 108 participants in the final analysis. Adherence groups were well matched in baseline mood, sleepiness, and apnea variables. Overall age (mean ± standard deviation) was 56.1 ± 12.8 years, and there was a median (interquartile ratio) apnea-hypopnea-index of 42.7 (27.5-58.1) or median (interquartile ratio) oxygen-desaturation-index of 43.0 (26.0-74.0). The median duration of CPAP therapy was 1.3 years. The HADS-D decreased after CPAP by -1.4 (adjusted 95% confidence interval, -2.1 to -0.6; P = .001). Patients with high-CPAP adherence (n = 84) had a tendency towards a greater reduction in HADS-D (-1.5) compared with those with low-CPAP adherence (n = 24; -0.3; adjusted P = .19). Depression cases (HADS-D ≥ 8) decreased by 13.1% in the high-CPAP-adherence group (P = .03) and increased by 4.1% in the low-CPAP-adherence group (P = .71). The HADS-A decreased after CPAP by -1.8 (adjusted 95% confidence interval, -1.8 to -0.4; P = .004). There was no significant difference between adherence groups or anxiety cases (HADS-A > 11).

Conclusions: Specialized obstructive sleep apnea treatment with CPAP reduces depression scores, with a trend toward greater reduction in those with high CPAP adherence.
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http://dx.doi.org/10.5664/jcsm.9164DOI Listing
June 2021

Hypoxic Preconditioning Induces Neuronal Differentiation of Infrapatellar Fat Pad Stem Cells through Epigenetic Alteration.

ACS Chem Neurosci 2021 02 29;12(4):704-718. Epub 2021 Jan 29.

Department of Biomedical Science, Bharathidasan University, Tiruchirappalli 620024, India.

Hypoxia is considered a key factor in cellular differentiation and proliferation, particularly during embryonic development; the process of early neurogenesis also occurs under hypoxic conditions. Apart from these developmental processes, hypoxia preconditioning or mild hypoxic sensitization develops resistance against ischemic stroke in deteriorating tissues. We therefore hypothesized that neurons resulting from hypoxia-regulated neuronal differentiation could be the best choice for treating brain ischemia, which contributes to neurodegeneration. In this study, infrapatellar fat pad (IFP), an adipose tissue present beneath the knee joint, was used as the stem cell source. IFP-derived stem cells (IFPSCs) are totally adherent and are mesenchymal stem cells. The transdifferentiation protocol involved hypoxia preconditioning, the use of hypoxic-conditioned medium, and maintenance in maturation medium with α-lipoic acid. The differentiated cells were characterized using microscopy, reverse transcription PCR, real time PCR, and immunocytochemistry. To evaluate the epigenetic reprogramming of IFPSCs to become neuron-like cells, methylation microarrays were performed. Hypoxia preconditioning stabilized and allowed for the translocation of hypoxia inducible factor 1α into the nucleus and induced achaete-scute homologue 1 and doublecortin expression. Following induction, the resultant cells expressed neuronal markers neuron-specific enolase, neurofilament-light chain, growth associated protein 43, synaptosome associated protein 25, and β-III tubulin. The differentiated neural-lineage cells had functional gene expression pertaining to neurotransmitters, their release, and their receptors. The molecular signaling mechanisms regulated developmental neurogenesis. Furthermore, the physiological condition regulated neurotransmitter respecification or switching during IFPSC differentiation to neurons. Thus, differentiated neurons were fabricated against the ischemic region to treat neurodegenerative diseases.
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http://dx.doi.org/10.1021/acschemneuro.0c00728DOI Listing
February 2021

Comparison of Sb2-Infliximab with Originator-Infliximab in the Measurement of Serum Concentrations A Short Communication.

Ther Drug Monit 2021 Jan 22. Epub 2021 Jan 22.

Department of Gastroenterology, Alfred Hospital and Monash University, Melbourne, Victoria School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria.

Background: The optimal use of infliximab depends on the measurement of trough levels with subsequent appropriate dose adjustment. With the introduction of biosimilars, it is important to demonstrate that the biosimilar behaves similarly in the assay utilized as the originator-infliximab, for which the assays were developed. In this study, the authors aimed to compare the concentrations of SB2-infliximab (Renflexis®) with that of originator-infliximab (Remicade®) when added to serum from healthy subjects and those with inflammatory bowel disease (IBD) when measured by commonly employed commercial assays.

Methods: Sera from two healthy controls, two patients with ulcerative colitis (one with quiescent disease, one with active disease), and two patients with Crohn's disease (one with quiescent disease, one with active disease) were spiked with SB2-infliximab or originator-infliximab at 0-20 μg/mL. Concentrations were measured using three commonly used assay kits (Lisa-Tracker®, Shikari Q-Inflix®, Promonitor IFX®) and one rapid test (Quantum Blue®). The results were compared using Bland-Altman techniques.

Results: Close agreement was observed between measured concentrations for all assays, irrespective of the origin of the serum. Limits of agreement varied between at worst -0.302 and 0.465 μg/mL, with the mean difference between the molecules being at worst 0.04 μg/mL (95% confidence intervals -0.011, 0.093).

Conclusions: The originator and SB-2 biosimilar-infliximab behaved similarly in several currently utilized assays in terms of their concentrations in biological fluids. Clinicians can be confident that therapeutic drug monitoring using platforms designed and developed for the originator-infliximab can be applied to SB-2-infliximab.
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http://dx.doi.org/10.1097/FTD.0000000000000866DOI Listing
January 2021

Updated prevalence, predictors and treatment outcomes for bronchiolitis obliterans syndrome after allogeneic stem cell transplantation.

Respir Med 2020 Dec 28;177:106286. Epub 2020 Dec 28.

Alfred Health, Melbourne, Australia.

Introduction: Bronchiolitis obliterans syndrome (BOS) after allogeneic haemopoietic stem cell transplant (HSCT) is an under-recognised and difficult to treat disease. This occurs in the context of limited clinical research and inconsistent diagnostic criteria.

Method: Retrospective data was collected on 275 patients who underwent allogeneic HSCT at an Australian tertiary hospital between 2007 and 2017. The prevalence of BOS, defined by 2014 National Institute of Health criteria, as well as predictors for BOS and mortality were determined. Treatment outcomes, using serial spirometry, were compared between patients who received early versus late immunosuppression for BOS.

Results: The prevalence of BOS was 9.1%. Myeloablative conditioning (OR: 2.7, 95%CI: 1.13-6.50, p = 0.03) and extra-pulmonary chronic graft-versus-host disease (OR 2.62, 95% CI: 1.04-6.60, p = 0.04) were associated with BOS. There was reduced median survival in the BOS group compared with the non-BOS group, but this was not statistically significant (4.1years (IQR: 2.8, 6.8) versus 4.6years (IQR: 2.4, 7.8), respectively, p = 0.33). The vast majority (87.5%) of BOS patients failed to attain improvement in FEV1 at 12 months, regardless of treatment strategy. Patients who underwent a late immunosuppression strategy had worse mean FEV1 decline compared to those who received early immunosuppression (-36.3% versus -1.6%, respectively, p = 0.03).

Conclusion: BOS is a common and progressive disease following HSCT and is largely refractory to current treatment strategies. Compared to late immunosuppression, early augmentation of immunosuppression may slow lung function deterioration in the short term. However, further research is urgently needed to identify effective prevention and treatment strategies for BOS.
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http://dx.doi.org/10.1016/j.rmed.2020.106286DOI Listing
December 2020

Redox potential in human semen: Validation and qualification of the MiOX assay.

Andrologia 2021 Mar 30;53(2):e13938. Epub 2020 Dec 30.

Andrology Department, The Doctors Laboratory, London, UK.

Seminal oxidative stress (OS) is a major contributing factor to male infertility. Semen analysis cannot identify reactive oxygen species (ROS), which can be measured using a chemiluminescence assay. Measurement of redox potential provides a more comprehensive assessment of OS, although the test has yet to be fully validated. This study aimed to validate the MiOX analyser for measuring static oxidation-reduction potential (sORP). Results demonstrated that duplicate measurements must be taken, sensors must be batch tested, and sockets should be regularly changed to avoid inconsistency in measurement. Measurement of sORP using MiOX exhibited good reproducibility across different operators (p = 0.469), analysers (p = 0.963) and days (p = 0.942). It is not affected by mechanical agitation (p = 0.522) or snap freezing and thawing (p = 0.823). The stability of sORP over time requires further verification, particularly in samples with high initial sORP. Measurement is temperature sensitive between 2 and 37°C, significantly increasing with increasing temperature (p = 0.0004). MiOX is a more stable assay for assessing OS than chemiluminescence methods and permits greater flexibility for sample handling. MiOX could be implemented to complement semen analysis as part of routine diagnostic testing for male infertility and may be useful in identifying contributing factors to idiopathic infertility.
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http://dx.doi.org/10.1111/and.13938DOI Listing
March 2021

Adverse impact of chronic kidney disease on clinical outcomes following percutaneous coronary intervention.

Catheter Cardiovasc Interv 2021 May 16;97(6):E801-E809. Epub 2020 Dec 16.

Department of Cardiology, Alfred Health, Melbourne, Australia.

Aims: We aimed to assess the impact of the severity of chronic kidney disease (CKD) with long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI).

Methods: We analyzed data on consecutive patients undergoing PCI enrolled in the Victorian Cardiac Outcomes Registry (VCOR) from January 2014 to December 2018. Patients were stratified into tertiles of renal function; estimated glomerular filtration (eGFR) ≥60, 30-59 and < 30 ml/min/1.73 m (including dialysis). The primary outcome was long-term all-cause mortality obtained from linkage with the Australian National Death Index (NDI). The secondary endpoint was a composite of 30 day major adverse cardiac and cerebrovascular events.

Results: We identified a total of 51,480 patients (eGFR ≥60, n = 40,534; eGFR 30-59, n = 9,521; eGFR <30, n = 1,425). Compared with patients whose eGFR was ≥60, those with eGFR 30-59 and eGFR<30 were on average older (77 and 78 vs. 63 years) and had a greater burden of cardiovascular risk factors. Worsening CKD severity was independently associated with greater adjusted risk of long-term NDI mortality: eGFR<30 hazard ratio 4.21 (CI 3.7-4.8) and eGFR 30-59; 1.8 (CI 1.7-2.0), when compared to eGFR ≥60, all p < .001.

Conclusion: In this large, multicentre PCI registry, severity of CKD was associated with increased risk of all-cause mortality underscoring the high-risk nature of this patient cohort.
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http://dx.doi.org/10.1002/ccd.29436DOI Listing
May 2021

Enhancing undergraduate nursing curricula to cultivate person-centred care for culturally and linguistically diverse older people.

Nurse Educ Pract 2021 Jan 25;50:102936. Epub 2020 Nov 25.

Department of Nursing and Midwifery, Faculty of Education and Health Sciences, Health Research Institute, University of Limerick, Ireland. Electronic address:

With an ageing global community and widening socio-cultural diversity, nurse educators are increasingly challenged to align responsive undergraduate nursing curricula to rapidly changing healthcare environments. In future-proofing nurse education, educators need to collectively examine ways of interconnecting and developing gerontological and cultural competence within undergraduate curricula. However, there is limited guidance as to how this can be achieved in already compacted curricula. We suggest that this could be achieved by critically examining undergraduate curricula to make explicit how they can be adapted to educate nurses in the provision of culturally competent person-centred care. This approach could help nurse educators adapt student nurse preparation to meet the needs of culturally diverse older people and their families.
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http://dx.doi.org/10.1016/j.nepr.2020.102936DOI Listing
January 2021

Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations.

J Hepatol 2021 May 1;74(5):1087-1096. Epub 2020 Dec 1.

Department of Women and Children's Health, King's College London, London, UK. Electronic address:

Background & Aims: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of stillbirth. This study aimed to assess the relationship between bile acid concentrations and fetal cardiac dysfunction in patients with ICP who were or were not treated with ursodeoxycholic acid (UDCA).

Methods: Bile acid profiles and NT-proBNP, a marker of ventricular dysfunction, were assayed in umbilical venous serum from 15 controls and 76 ICP cases (36 untreated, 40 UDCA-treated). Fetal electrocardiogram traces were obtained from 43 controls and 48 ICP cases (26 untreated, 22 UDCA-treated). PR interval length and heart rate variability (HRV) parameters were measured in 2 behavioral states (quiet and active sleep).

Results: In untreated ICP, fetal total serum bile acid (TSBA) concentrations (r = 0.49, p = 0.019), hydrophobicity index (r = 0.20, p = 0.039), glycocholate concentrations (r = 0.56, p = 0.007) and taurocholate concentrations (r = 0.44, p = 0.039) positively correlated with fetal NT-proBNP. Maternal TSBA (r = 0.40, p = 0.026) and alanine aminotransferase (r = 0.40, p = 0.046) also positively correlated with fetal NT-proBNP. There were no significant correlations between maternal or fetal serum bile acid concentrations and fetal HRV parameters or NT-proBNP concentrations in the UDCA-treated cohort. Fetal PR interval length positively correlated with maternal TSBA in untreated (r = 0.46, p = 0.027) and UDCA-treated ICP (r = 0.54, p = 0.026). Measures of HRV in active sleep and quiet sleep were significantly higher in untreated ICP cases than controls. HRV values in UDCA-treated cases did not differ from controls.

Conclusions: Elevated fetal and maternal serum bile acid concentrations in untreated ICP are associated with an abnormal fetal cardiac phenotype characterized by increased NT-proBNP concentration, PR interval length and HRV. UDCA treatment partially attenuates this phenotype.

Lay Summary: The risk of stillbirth in intrahepatic cholestasis of pregnancy (ICP) is linked to the level of bile acids in the mother which are thought to disrupt the baby's heart rhythm. We found that babies of women with untreated ICP have abnormally functioning hearts compared to those without ICP, and the degree of abnormality is closely linked to the level of harmful bile acids in the mother and baby's blood. Babies of women with ICP who received treatment with the drug UDCA do not have the same level of abnormality in their hearts, suggesting that UDCA could be a beneficial treatment in some ICP cases, although further clinical trials are needed to confirm this.
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http://dx.doi.org/10.1016/j.jhep.2020.11.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062912PMC
May 2021

Effects of radiofrequency field exposure on proteotoxic-induced and heat-induced HSF1 response in live cells using the bioluminescence resonance energy transfer technique.

Cell Stress Chaperones 2021 Jan 16;26(1):241-251. Epub 2020 Oct 16.

CNRS, IMS laboratory, UMR5218, Bordeaux University, F-33400, Talence, France.

As of today, only acute effects of RF fields have been confirmed to represent a potential health hazard and they are attributed to non-specific heating (≥ 1 °C) under high-level exposure. Yet, the possibility that environmental RF impact living matter in the absence of temperature elevation needs further investigation. Since HSF1 is both a thermosensor and the master regulator of heat-shock stress response in eukaryotes, it remains to assess HSF1 activation in live cells under exposure to low-level RF signals. We thus measured basal, temperature-induced, and chemically induced HSF1 trimerization, a mandatory step on the cascade of HSF1 activation, under RF exposure to continuous wave (CW), Global System for Mobile (GSM), and Wi-Fi-modulated 1800 MHz signals, using a bioluminescence resonance energy transfer technique (BRET) probe. Our results show that, as expected, HSF1 is heat-activated by acute exposure of transiently transfected HEK293T cells to a CW RF field at a specific absorption rate of 24 W/kg for 30 min. However, we found no evidence of HSF1 activation under the same RF exposure condition when the cell culture medium temperature was fixed. We also found no experimental evidence that, at a fixed temperature, chronic RF exposure for 24 h at a SAR of 1.5 and 6 W/kg altered the potency or the maximal capability of the proteasome inhibitor MG132 to activate HSF1, whatever signal used. We only found that RF exposure to CW signals (1.5 and 6 W/kg) and GSM signals (1.5 W/kg) for 24 h marginally decreased basal HSF1 activity.
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http://dx.doi.org/10.1007/s12192-020-01172-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736596PMC
January 2021

Thiopurines and their optimization during infliximab induction and maintenance: A retrospective study in Crohn's disease.

J Gastroenterol Hepatol 2021 Apr 10;36(4):990-998. Epub 2020 Sep 10.

Department of Gastroenterology, Alfred Hospital, Melbourne, Victoria, Australia.

Background And Aim: Combining therapy with a thiopurine is favored when commencing infliximab in Crohn's disease; however, the optimal 6-thioguanine nucleotide (TGN) level and how long to continue thiopurines after induction are uncertain. We aimed to compare outcomes after induction and during maintenance in combination therapy versus infliximab monotherapy in Crohn's and to examine whether TGN levels were associated with outcomes.

Methods: Crohn's patients induced with infliximab with or without concomitant thiopurines were retrospectively identified. Response to induction and clinical outcomes in subsequent 6-month maintenance semesters were analyzed. A TGN level ≥235 pmol/8 × 10 red blood cells was considered therapeutic.

Results: In 89 patients, response to induction was higher in combination therapy than monotherapy (74 vs 47%, P = 0.04). This benefit was only seen in patients with a therapeutic TGN (odds ratio 3.72, confidence interval 1.07-13.0, P = 0.04). Combination therapy during induction yielded a three times longer time to subsequent need for treatment escalation or treatment failure compared with monotherapy (29 vs 9 months, P = 0.01), with both therapeutic and subtherapeutic TGNs independent predictors on multivariate analysis. Among 370 semesters, there was no difference in outcomes between combination therapy and monotherapy (P = 0.42), nor when combination semesters were stratified by therapeutic versus subtherapeutic TGN (P = 0.56). In semester 1 only, a significantly higher remission rate was observed with therapeutic compared with subtherapeutic TGN (76% vs 33%, P = 0.02).

Conclusions: Combination therapy dosed with an optimized thiopurine was superior to infliximab monotherapy for induction of response, durability of response, and clinical outcomes in the first 6 months following induction. Thereafter, combination therapy yielded no clinical advantage, supporting consideration of thiopurine withdrawal on a case-by-case basis.
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http://dx.doi.org/10.1111/jgh.15245DOI Listing
April 2021

Identifying Conversational Strategies for Psychiatrists in Discussing Substance Use with Adolescent Patients.

Health Commun 2020 Sep 1:1-7. Epub 2020 Sep 1.

Department of Psychiatry, University of Kentucky.

Child and adolescent psychiatrists are uniquely positioned to discuss substance use with high risk patients; however, there has been little research about these conversations and their characteristics. To identify communication strategies for navigating conversations about substance use with adolescent patients, we conducted 21 in-depth interviews with practicing child and adolescent psychiatrists. Findings from this study identify four strategies that child and adolescent psychiatrists reported as being successful: expressing empathy, avoiding resistance, honoring autonomy, and managing family involvement. In addition to describing these strategies, we briefly describe a theoretical framework that might help to explain the perceived success of these strategies, and we offer recommendations for how to apply our findings to improve psychiatric practice.
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http://dx.doi.org/10.1080/10410236.2020.1816309DOI Listing
September 2020

Sex Differences in Radial Access for Percutaneous Coronary Intervention in Acute Coronary Syndrome Are Independent of Body Size.

Heart Lung Circ 2021 Jan 24;30(1):108-114. Epub 2020 Aug 24.

Monash Cardiovascular Research Centre, Monash University, Melbourne, Vic, Australia; Monash Heart, Monash Medical Centre, Melbourne, Vic, Australia; Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, Vic, Australia. Electronic address:

Background: Radial access reduces bleeding and is associated with improved survival following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). We evaluated the association between sex, markers of body size and radial access, and its impact on bleeding and mortality following PCI for ACS.

Methods And Results: From 2013-2016, consecutive patients treated with PCI for ACS across 30 centres were prospectively entered into the Victorian Cardiac Outcomes Registry and followed for 30 days. Multivariate logistic regression was used to analyse predictors of the primary endpoint of PCI access site and secondary endpoints of major bleeding and mortality. A total of 16,330 ACS patients (40.9% ST elevation myocardial infarction [STEMI]) underwent PCI (23.5% female). Women were older with significantly lower weight and height compared to men. Women had lower radial access use (41.6% versus 51.0%, p<0.001), with higher 30-day major bleeding (2.4% versus 1.4%, p<0.001) and mortality (4.4% versus 3.4%, p<0.001) than men. Female sex independently predicted lower radial access use (OR 0.75, 95% CI 0.68-0.83, p<0.001) while body surface area, height and body mass index did not. Female sex was an independent predictor of higher 30-day major bleeding (OR 1.38, 95% CI 1.05-1.81, p=0.019) and mortality in STEMI patients (OR 1.31, 95% CI 1.01-1.70. p=0.039). Radial access was associated with lower major bleeding (OR 0.70, 95% CI 0.53-0.91, p=0.009) and mortality (OR 0.60, 95% CI 0.48-0.75, p<0.001).

Conclusions: Radial access, despite being associated with lower bleeding and mortality, was used less frequently in women, independent of co-morbidities and objective markers of body size.
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http://dx.doi.org/10.1016/j.hlc.2020.06.023DOI Listing
January 2021

Effects of Radiofrequency Radiation on Gene Expression: A Study of Gene Expressions of Human Keratinocytes From Different Origins.

Bioelectromagnetics 2020 Oct 19;41(7):552-557. Epub 2020 Aug 19.

Inserm, EHESP, Institut de Recherche en Santé, Environnement et Travail (IRSET), UMR_S 1085, University of Rennes, F-35000, Rennes, France.

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http://dx.doi.org/10.1002/bem.22287DOI Listing
October 2020

Assessing adolescent tobacco use in a substance use treatment program with self-report and biological measures.

Addict Behav 2020 08 29;107:106424. Epub 2020 Mar 29.

University of Kentucky, College of Medicine, Department of Psychiatry, 245 Fountain Court, Lexington, KY 40509, United States.

Tobacco use in adolescents can alter their lifetime health outcomes. Despite the importance of early identification and treatment, adolescent tobacco use, including that of electronic vapor products (e.g., e-cigarettes), is often missed. In a state-funded substance use treatment program, we added biological measures, including urinary cotinine and exhaled carbon monoxide to self-report measures to assess recent and lifetime tobacco use. We conducted a retrospective review of the de-identified charts to examine the feasibility of screening for self-report and biological measures of tobacco use. Self-report, urinary cotinine, and exhaled carbon monoxide samples were obtained at every visit, including intake and follow-up. There were 52 adolescents with a total of 400 clinic visits to the program. Of those 400 visits, 258 included self-reported tobacco use and 142 included a denial of using any form of tobacco. However, of those 142 visits with a negative self-report of tobacco, 31 tested positive for cotinine and 6 had positive exhaled carbon monoxide. Although 111 of the 142 had negative cotinine, 5 had positive carbon monoxide, but all of those self-reported recent cannabis use. Despite using a sensitive measure of self-report of tobacco use, almost 22% of visits had a discordant self-report with a biological measure that indicated tobacco use. Considering the lifelong impact of adolescent tobacco use, clinicians should consider augmenting self-report with biological measures of tobacco use. Identification of tobacco use in adolescents with substance use can assist clinicians in providing education about tobacco use, such as electronic vapor products, and individualizing treatments.
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http://dx.doi.org/10.1016/j.addbeh.2020.106424DOI Listing
August 2020

Reducing Medication Risks in Older Adult Drinkers.

Gerontol Geriatr Med 2020 Jan-Dec;6:2333721420910936. Epub 2020 Mar 2.

University of Kentucky College of Public Health, Lexington, USA.

Prevalent concomitant alcohol and medication use among older adults is placing this group at risk for adverse health events. Given limited existing interventions to address concomitant alcohol and medication risk (AMR), a brief educational intervention was demonstrated. The purpose of the current study was to examine change in AMR behaviors 3 months post-education among older adult drinkers. A convenience sample of 58 older adult drinkers (mean age = 72) was recruited and followed ( = 40; 70% at follow-up), from four pharmacies in rural Virginia. Findings indicated decreased alcohol consumption in high-risk drinkers. Future research should explore methods to sustain reduced AMR.
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http://dx.doi.org/10.1177/2333721420910936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052447PMC
March 2020

Reducing Medication Risks in Older Adult Drinkers.

Gerontol Geriatr Med 2020 Jan-Dec;6:2333721420910936. Epub 2020 Mar 2.

University of Kentucky College of Public Health, Lexington, USA.

Prevalent concomitant alcohol and medication use among older adults is placing this group at risk for adverse health events. Given limited existing interventions to address concomitant alcohol and medication risk (AMR), a brief educational intervention was demonstrated. The purpose of the current study was to examine change in AMR behaviors 3 months post-education among older adult drinkers. A convenience sample of 58 older adult drinkers (mean age = 72) was recruited and followed ( = 40; 70% at follow-up), from four pharmacies in rural Virginia. Findings indicated decreased alcohol consumption in high-risk drinkers. Future research should explore methods to sustain reduced AMR.
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http://dx.doi.org/10.1177/2333721420910936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052447PMC
March 2020

A competent bidrug loaded water soluble chitosan derivative for the effective inhibition of breast cancer.

Sci Rep 2020 03 4;10(1):3991. Epub 2020 Mar 4.

Crystal Growth Centre, Anna University, Chennai, 600025, India.

Drug resistance and damage caused to the normal cells are the drawbacks which have limited the use of the existing effective anticancer drugs. Attainment of a steady and extended release by encapsulating dual drugs into biocompatible and biodegradable vehicles is the key to enable the use of these drugs for effective inhibition of cancer. In this study, carboxymethyl chitosan (CMCS), a proficient water-soluble derivative of chitosan has been synthesized using chemical route and used for the delivery of 5-Fluorouracil and doxorubicin individually as well as in combination. Carboxymethylation occuring at -NH and OH sites of chitosan, has been confirmed using FTIR. EDX and Fluorescence studies elucidate the encapsulation of 5-Fluorouracil and doxorubicin into CMCS. The capability of CMCS to release the drugs in a more sustained and prolonged manner is evident from the obtained release profiles. About 14.9 µg/ml is enough to cause 50% cell death by creating oxidative stress and effectuating DNA fragmentation. Amidst the existing reports, the uniqueness of this work lies in using this rare coalition of drugs for the suppression of breast cancer and in reducing the side effects of drugs by encapsulating them into CMCS, which is evidenced by the high hemocompatibilty of the samples.
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http://dx.doi.org/10.1038/s41598-020-60888-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055325PMC
March 2020

Evaluation of the Effect of Chronic 94 GHz Exposure on Gene Expression in the Skin of Hairless Rats .

Radiat Res 2020 04 3;193(4):351-358. Epub 2020 Mar 3.

Institut de Recherche Biomédicale des Armées (IRBA), F-91223 Brétigny, France.

Millimeter waves (MMW) are broadband frequencies that have recently been used in several applications in wireless communications, medical devices and nonlethal weapons [i.e., the nonlethal weapon, Active Denial Systems, (ADS) operating at 94-95 GHz, CW]. However, little information is available on their potential effects on humans. These radio-frequencies are absorbed and stopped by the first layer of the skin. In this study, we evaluated the effects of 94 GHz on the gene expression of skin cells. Two rat populations consisting of 17 young animals and 14 adults were subjected to chronic long-term 94 GHz MMW exposure. Each group of animals was divided into exposed and sham subgroups. The two independent exposure experiments were conducted for 5 months with rats exposed 3 h per day for 3 days per week to an incident power density of 10 mW/cm, which corresponded to twice the ICNIRP limit of occupational exposure for humans. At the end of the experiment, skin explants were collected and RNA was extracted. Then, the modifications to the whole gene expression profile were analyzed with a gene expression microarray. Without modification of the animal's temperature, long-term chronic 94 GHz-MMW exposure did not significantly modify the gene expression of the skin on either the young or adult rats.
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http://dx.doi.org/10.1667/RR15470.1DOI Listing
April 2020

Risk Factors for Diabetic Peripheral Neuropathy and Cardiovascular Autonomic Neuropathy in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study.

Diabetes 2020 05 12;69(5):1000-1010. Epub 2020 Feb 12.

University of Michigan Medical School, Ann Arbor, MI.

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated that intensive glucose control reduced the risk of developing diabetic peripheral neuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). We evaluated multiple risk factors and phenotypes associated with DPN and CAN in this large, well-characterized cohort of participants with type 1 diabetes, followed for >23 years. DPN was defined by symptoms, signs, and nerve conduction study abnormalities in ≥2 nerves; CAN was assessed using standardized cardiovascular reflex tests. Generalized estimating equation models assessed the association of DPN and CAN with individual risk factors measured repeatedly. During DCCT/EDIC, 33% of participants developed DPN and 44% CAN. Higher mean HbA was the most significant risk factor for DPN, followed by older age, longer duration, greater height, macroalbuminuria, higher mean pulse rate, β-blocker use, and sustained albuminuria. The most significant risk factor for CAN was older age, followed by higher mean HbA, sustained albuminuria, longer duration of type 1 diabetes, higher mean pulse rate, higher mean systolic blood pressure, β-blocker use, estimated glomerular filtration rate <60 mL/min/1.73 m, higher most recent pulse rate, and cigarette smoking. These findings identify risk factors and phenotypes of participants with diabetic neuropathy that can be used in the design of new interventional trials and for personalized approaches to neuropathy prevention.
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http://dx.doi.org/10.2337/db19-1046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171957PMC
May 2020

Sex differences in optimal medical therapy following myocardial infarction according to left ventricular ejection fraction.

Eur J Prev Cardiol 2020 12 3;27(19):2348-2350. Epub 2020 Feb 3.

Monash Cardiovascular Research Centre, Monash University, Australia.

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http://dx.doi.org/10.1177/2047487319900875DOI Listing
December 2020

Acute Toxoplasmosis among Canadian Deer Hunters Associated with Consumption of Undercooked Deer Meat Hunted in the United States.

Emerg Infect Dis 2020 02;26(2):199-205

We conducted a recent investigation in Quebec, Canada, concerning Canadian deer hunters who went to the United States to hunt deer and returned with symptoms of fever, severe headache, myalgia, and articular pain of undetermined etiology. Further investigation identified that a group of 10 hunters from Quebec attended a hunting retreat in Illinois (USA) during November 22-December 4, 2018. Six of the 10 hunters had similar symptoms and illness onset dates. Serologic tests indicated a recent toxoplasmosis infection for all symptomatic hunters, and the risk factor identified was consumption of undercooked deer meat. Among asymptomatic hunters, 2 were already immune to toxoplasmosis, 1 was not immune, and the immune status of 1 remains unknown. Outbreaks of acute toxoplasmosis infection are rare in North America, but physicians should be aware that such outbreaks could become more common.
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http://dx.doi.org/10.3201/eid2602.191218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986818PMC
February 2020

Twelve-month outcomes of MAKINGtheLINK: A cluster randomized controlled trial of a school-based program to facilitate help-seeking for substance use and mental health problems.

EClinicalMedicine 2020 Jan 3;18:100225. Epub 2020 Jan 3.

Victorian Department of Education and Training, Melbourne, Victoria 6200, Australia.

Background: Young people experiencing mental health problems are often reluctant to seek help, particularly from professionals (i.e., doctors or mental health workers). MAKINGtheLINK is a school-based intervention that aims to help adolescents overcome barriers to seeking professional help for mental health and substance use problems.

Methods: A cluster randomised controlled trial was conducted to evaluate the 12-month outcomes of MAKINGtheLINK among 2447 participants (Mean age=14.9 years, SD=0.5 years, 50% male). Randomisation resulted in 1130 students from 11 schools allocated to receive the intervention, and 1317 students from 10 schools allocated to the wait-list control group. After the baseline assessment, follow-ups were conducted at 6-weeks ( = 2045), 6-months ( = 1874), and 12-months ( = 1827). The primary outcome measure was help-seeking behaviour, from both formal (e.g., health professionals) and informal (e.g., friends, family members) sources. The trial was registered with the Australia and New Zealand Clinical Trials Register (ANZCTR) on the 27th of February 2013 (registration number ACTRN12613000235707).

Findings: The intervention was not associated with overall help-seeking at the 12-month follow-up ( = 0.99, odds ratio [OR]=1.00, 95% CI for OR = 0.70-1.42), or help-seeking for depression ( = 0.28, OR = 1.21, 95%CI =0.86-1.69), stress and anxiety ( = 0.73, OR = 1.04, 95%CI = 0.74-1.47), or alcohol/other drugs ( = 0.84, OR=1.12, CI=0.37-3.37). However, the intervention was associated with increased help-seeking from formal sources (compared to informal sources) both overall (  0.005, OR = 1.81, 95%CI = 1.19-2.75), as well as for depression ( = 0.01, OR=2.09, 95%CI=1.19-3.67), and stress and anxiety ( < 0.006, OR = 1.72, 95%CI = 1.17-2.54).

Interpretation: Rates of help-seeking remained unchanged following the intervention. However, MAKINGtheLINK effectively improved the quality of adolescent help-seeking behaviour by increasing help-seeking from formal sources. As prompt treatment is essential in reducing the long-term impact of early onset mental health problems, MAKINGtheLINK has the potential to make a significant contribution to existing early intervention and prevention efforts.

Funding: National Health and Medical Research Council (APP1047492).
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http://dx.doi.org/10.1016/j.eclinm.2019.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948229PMC
January 2020

Does sex predict quality of life after acute coronary syndromes: an Australian, state-wide, multicentre prospective cohort study.

BMJ Open 2019 12 18;9(12):e034034. Epub 2019 Dec 18.

Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia

Objective: Women have reported higher mortality and major adverse cardiovascular events (MACE) following acute coronary syndromes (ACSs) compared with men. With this in mind, we aimed to identify predictors of poor quality of life (QoL) post-ACS as our primary outcome. We examined predictors of MACE, major cerebrovascular events and major bleeding as our secondary outcome.

Design: Prospective cohort study.

Setting: 30 metropolitan centres across the Victorian Cardiac Outcomes Registry network.

Participants: 16 517 patients treated with percutaneous coronary intervention (PCI) for ACS (22.9% females). Selection/inclusion criteria: consecutive patients with successful or attempted PCI for ACS from 2013 to 2016, alive at 30 days post-PCI.

Exclusion Criteria: patients not fulfilling ACS criteria. At 30 days, 2497 (64.7% females) completed the QoL EQ-5D-3L instrument.

Primary And Secondary Outcome Measures: QoL, assessed using the EuroQo-5Dimensions (EQ-5D-3L) instrument by telephone at 30 days. Independent predictors of QoL were identified by univariate and multivariate logistic regression analyses.

Results: Women were significantly older with more diabetes, cerebrovascular disease and renal failure. Regarding the primary outcome, female sex was independently associated with moderate/severe impairment in all EQ-5D-3L domains including mobility (OR 2.38, 95% CI 2.06 to 2.75, p<0.001), personal care (OR 2.14, 95% CI 1.73 to 2.66, p<0.001), activities of daily living (OR 1.84, 95% CI 1.63 to 2.08, p<0.001), pain/discomfort (OR 1.44, 95% CI 1.24 to 1.67, p<0.001) and anxiety/depression (OR 1.49, 95% CI 1.30 to 1.70, p<0.001). Women had significantly lower self-rated Visual Analogue Scale scores (80.0 for both groups, IQR 60-85 vs 70-90, p<0.001). There was no significant difference between the sexes in secondary outcomes.

Conclusions: Female sex was a predictor of poorer QoL following PCI for ACS including significantly higher pain, anxiety and depression. This was independent of age, comorbidities and ACS presentation. There is a clinical need for a tailored approach in female ACS management, for example, emphasis on management of depressive and anxiety symptoms.
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http://dx.doi.org/10.1136/bmjopen-2019-034034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937071PMC
December 2019