Publications by authors named "Timothy Jones"

580 Publications

Meal-time glycaemia in adults with type 1 diabetes using multiple daily injections vs insulin pump therapy following carbohydrate-counting education and bolus calculator provision.

Diabetes Res Clin Pract 2021 Aug 26;179:109000. Epub 2021 Aug 26.

Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia; Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia; NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia. Electronic address:

Aims: To compare meal-time glycaemia in adults with type 1 diabetes mellitus (T1D) managed with multiple daily injections (MDI) vs. insulin pump therapy (IPT), using self-monitoring blood glucose (SMBG), following diabetes education.

Methods: Adults with T1D received carbohydrate-counting education and a bolus calculator: MDI (Roche Aviva Expert) and IPT (pump bolus calculator). All then wore 3-weeks of masked-CGM (Enlite, Medtronic). Meal-times were assessed by two approaches: 1) Set time-blocks (breakfast 06:00-10:00hrs; lunch 11:00-15:00hrs; dinner 17:00-21:00hrs) and 2) Bolus-calculator carbohydrate entries signalling meal commencement. Post-meal masked-CGM time-in-range (TIR) 3.9-10.0 mmol/L was the primary outcome.

Results: MDI(n = 61) and IPT (n = 59) participants were equivalent in age, sex, diabetes duration and HbA1c. Median (IQR) education time provided did not differ (MDI: 1.1 h (0.75, 1.5) vs. IPT: 1.1 h (1.0, 2.0); p = 0.86). Overall, daytime (06:00-24:00hrs), lunch and dinner TIR did not differ for MDI vs. IPT participants but was greater for breakfast with IPT in both analyses with a mean difference of 12.8%, (95 CI 4.8, 20.9); p = 0.002 (time-block analysis).

Conclusion: After diabetes education, MDI and IPT use were associated with similar day-time glycemia, though IPT users had significantly greater TIR during the breakfast period. With education, meal-time glucose levels are comparable with use of MDI vs. pumps.
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http://dx.doi.org/10.1016/j.diabres.2021.109000DOI Listing
August 2021

The relationship between meal carbohydrate quantity and the insulin to carbohydrate ratio required to maintain glycaemia is non-linear in young people with type 1 diabetes: A randomized crossover trial.

Diabet Med 2021 Aug 20:e14675. Epub 2021 Aug 20.

Department of Paediatric Endocrinology and Diabetes, John Hunter Children's Hospital, Newcastle, New South Wales, Australia.

Objective: To determine if the relationship between meal carbohydrate quantity and the insulin to carbohydrate ratio (ICR) required to maintain glycaemia is linear in people with type 1 diabetes.

Methods: We used an open labelled randomized four-arm cross-over study design. Participants (N = 31) aged 12-27 years, HbA1c ≤ 64 mmol/mol (8.0%) received insulin doses based on the individual's ICR and the study breakfast carbohydrate quantity and then consumed four breakfasts containing 20, 50, 100 and 150 g of carbohydrate over four consecutive days in randomized order. The breakfast fat and protein percentages were standardized. Postprandial glycaemia was assessed by 5 h continuous glucose monitoring. The primary outcome was percent time in range (TIR) and secondary outcomes included hypoglycaemia, glucose excursion and incremental area under the curve. Statistical analysis included linear mixed modelling and Wilcoxon signed rank tests.

Results: The 20 g carbohydrate breakfast had the largest proportion of TIR (0.74 ± 0.29 p < 0.04). Hypoglycaemia was more frequent in the 50 g (n = 13, 42%) and 100 g (n = 15, 50%) breakfasts compared to the 20 g (n = 6, 20%) and 150 g (n = 7, 26%) breakfasts (p < 0.029). The 150 g breakfast glucose excursion pattern was different from the smaller breakfasts with the lowest glucose excursion 0-2 h and the highest excursion from 3.5 to 5 h.

Conclusions: A non-linear relationship between insulin requirement and breakfast carbohydrate content was observed, suggesting that strengthened ICRs are needed for meals with ≤20 and ≥150 g of carbohydrate. Meals with ≥150 g of carbohydrate may benefit from dual wave bolusing.
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http://dx.doi.org/10.1111/dme.14675DOI Listing
August 2021

Adult-onset recurrent Kawasaki disease: an unusual cause of fever of unknown origin.

BMJ Case Rep 2021 Aug 19;14(8). Epub 2021 Aug 19.

Infectious Diseases, Monklands Hospital, Airdrie, UK.

We present the case of a 20-year-old man with a background of transposition of the great arteries presenting with fever of unknown origin, who developed a shock like syndrome with respiratory failure necessitating intubation. After extensive investigation, a diagnosis of adult-onset Kawasaki disease was made, and he was successfully treated with IVIg and corticosteroids. We present the clinical findings clinicians should be aware of, and review the literature on managing this rare presentation in adult, highlighting the importance of early diagnosis in improving outcomes. Both children and adults with Kawasaki disease require long-term follow-up, as they remain at increased risk of both coronary artery aneurysms and early acute coronary syndrome.
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http://dx.doi.org/10.1136/bcr-2021-243704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378382PMC
August 2021

Effects of dietary fat and protein on glucoregulatory hormones in adolescents and young adults with type 1 diabetes.

J Clin Endocrinol Metab 2021 Aug 19. Epub 2021 Aug 19.

Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.

Context: Dietary fat and protein impact postprandial hyperglycaemia in people with type 1 diabetes, but the underlying mechanisms are poorly understood. Glucoregulatory hormones are also known to modulate gastric emptying and may contribute to this effect.

Objective: Investigate the effects of fat and protein on glucagon like peptide (GLP-1), glucagon-dependent insulinotropic polypeptide (GIP) and glucagon secretion.

Design: Two cross-over euglycaemic insulin clamp clinical trials.

Setting: Two Australian paediatric diabetes centres.

Participants: 12-21years (n=21) with type 1 diabetes for ≥1year.

Intervention(s): Participants consumed a low protein (LP) or high protein (HP) meal in Study 1, and low protein/low fat (LPLF) or high protein/high fat (HPHF) meal in Study 2, all containing 30g carbohydrate. An insulin clamp was used to maintain postprandial euglycaemia and plasma glucoregulatory hormones were measured every 30 minutes for 5-hours. Data from both cohorts (n=11,10) were analysed separately.

Main Outcome: Area under the curve of GLP-1, GIP and glucagon.

Results: Meals low in fat and protein had minimal effect on GLP-1, while there was sustained elevation after the HP (80.3±16.8pmol/L) vs LP (56.9±18.6), P=0.016, and HPHF (103.0±26.9) vs LPLF (69.5±31.9) meals, P=0.002. The prompt rise in GIP after all meals was greater after the HP (190.2±35.7pmol/L) vs LP (152.3±23.3), P=0.003, and HPHF (258.6±31.0) vs LPLF (151.7±29.4), P<0.001. A rise in glucagon was also seen in response to protein, HP (292.5±88.1pg/mL) vs LP (182.8±48.5), P=0.010.

Conclusions: The impact of fat and protein on postprandial glucose excursions may be mediated by the differential secretion of glucoregulatory hormones. Further studies to better understand these mechanisms may lead to improved personalised postprandial glucose management.
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http://dx.doi.org/10.1210/clinem/dgab614DOI Listing
August 2021

Continuous subcutaneous insulin infusion alters microRNA expression and glycaemic variability in children with type 1 diabetes.

Sci Rep 2021 Aug 17;11(1):16656. Epub 2021 Aug 17.

NHMRC Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

To determine whether continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) therapy from near-diagnosis of type 1 diabetes is associated with reduced glycaemic variability (GV) and altered microRNA (miRNAs) expression. Adolescents (74% male) within 3-months of diabetes diagnosis (n = 27) were randomized to CSII (n = 12) or MDI. HbA1c, 1-5-Anhydroglucitol (1,5-AG), high sensitivity C-peptide and a custom TaqMan qPCR panel of 52 miRNAs were measured at baseline and follow-up (median (LQ-UQ); 535 (519-563) days). There were no significant differences between groups in baseline or follow-up HbA1c or C-peptide, nor baseline miRNAs. Mean ± SD 1,5-AG improved with CSII vs. MDI (3.1 ± 4.1 vs. - 2.2 ± - 7.0 mg/ml respectively, P = 0.029). On follow-up 11 miRNAs associated with diabetes vascular complications had altered expression in CSII-users. Early CSII vs. MDI use is associated with lower GV and less adverse vascular-related miRNAs. Relationships with future complications are of interest.
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http://dx.doi.org/10.1038/s41598-021-95824-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370996PMC
August 2021

Antidiuretic hormone and the activation of glucose production during high intensity aerobic exercise.

Metabol Open 2021 Sep 24;11:100113. Epub 2021 Jul 24.

Department of Exercise Science and Health, School of Human Sciences, The University of Western Australia, Perth, W.A., Australia.

Objective: This study aimed to investigate the role that antidiuretic hormone (ADH) may play in the activation of glucose production during high intensity aerobic exercise.

Materials/methods: This study was part of larger study based on a repeated measures cross-over study design and involved ten adult participants who exercised in the morning at 80 % Opeak for up to 40 min or until exhaustion. During and after exercise, the participants were subjected to a morning euglycaemic/euinsulinaemic clamp while [6,6-H]glucose was infused and blood sampled to measure the endogenous rate of glucose appearance (Ra) and ADH levels.

Results: The levels of plasma ADH were 1.8 ± 0.2 pmol/L (mean ± SEM) at rest and increased to 10.5 ± 2.1 pmol/L at the end of exercise (mean ± SEM), which lasted 8.5-40 min. In response to exercise, glucose Ra also rose significantly (p < 0.05), but there was no significant association between changes in ADH levels and glucose Ra (r = 0.49; p = 0.150).

Conclusions: Although the significant increase in glucose Ra and ADH levels during high intensity aerobic exercise suggest for the first time that these processes may be causally related, there was no significant association between these variables, maybe because of the small sample size and varying exercise durations. Hence, the importance of the causal role that ADH may play in the exercise-mediated activation of hepatic glucose production warrants further in depth investigations.
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http://dx.doi.org/10.1016/j.metop.2021.100113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333141PMC
September 2021

Exercise-induced hypoxia among emergency department patients admitted for suspected COVID-19.

Emerg Med J 2021 Aug 6. Epub 2021 Aug 6.

Infectious Diseases, Monklands General Hospital, Airdrie, UK.

Background: Exercise-induced hypoxia (EIH) has been assessed at ED triage as part of an assessment of COVID-19; however, evidence supporting this practice is incomplete. We assessed the use of a 1-minute sit-to-stand exercise test among ED patients admitted for suspected COVID-19.

Methods: A case note review of all ED patients assessed for suspected COVID-19 between March and May 2020 at Monklands University Hospital was conducted. Demographic characteristics, clinical parameters, baseline blood tests and radiographic findings, hospital length of stay, intensive care and maximum oxygen requirement were obtained for those admitted. Using logistic regression, the association between EIH at admission triage and COVID-19 diagnosis was explored adjusting for confounding clinical parameters.

Results: Of 127 ED patients admitted for possible COVID-19, 37 were ultimately diagnosed with COVID-19. 36.4% of patients with COVID-19 and EIH had a normal admission chest radiograph. In multivariate analysis, EIH was an independent predictor of COVID-19 (adjusted OR 3.73 (95% CI (1.25 to 11.15)), as were lymphocyte count, self-reported exertional dyspnoea, C-reactive peptide and radiographic changes.

Conclusions: This observational study demonstrates an association between EIH and a COVID-19 diagnosis. Over one-third of patients with COVID-19 and EIH exhibited no radiographic changes. EIH may represent an additional tool to help predict a COVID-19 diagnosis at initial presentation and may assist in triaging need for admission.
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http://dx.doi.org/10.1136/emermed-2021-211220DOI Listing
August 2021

The Blood Neutrophil Count After 1 Month of Treatment Predicts the Radiologic Severity of Lung Disease at Treatment End.

Chest 2021 Jul 28. Epub 2021 Jul 28.

Department of Clinical Immunology, Royal Free London NHS Foundation Trust, London, England; Institute of Immunity and Transplantation, University College London, Royal Free Campus, London, England. Electronic address:

Background: Lung disease after tuberculous confers significant morbidity. However, the determinants of persistent lung damage in TB are not well established. We investigated associations between TB-associated radiologic changes and sociodemographic factors, surrogates of bacillary burden, and blood inflammatory markers at initiation of therapy and after 1 month.

Research Question: What are the predictors of radiologic severity at the end of TB treatment for TB?

Study Design And Methods: We collected data from patients treated for drug-sensitive pulmonary TB at our center over a 5.5-year period. We recorded age, sex, ethnicity, smoking status, symptom duration, sputum smear grade, time to culture positivity, and blood results (C-reactive protein and neutrophil count) at baseline and after 1 month of treatment. Chest radiographs obtained at baseline, 2 months, and end of treatment were assessed independently by two radiologists and scored using a validated system. Relationships between predictor variables and radiologic outcomes were assessed using linear or binary logistic regression.

Results: We assessed 154 individuals with a mean age of 37 years, 63% of whom were men. In a multivariate analysis, baseline radiologic severity correlated with sputum smear grade (P = 0.003) and neutrophil count (P < 0.001). At end of treatment, only the 1-month neutrophil count was associated significantly with overall radiologic severity in the multivariate analysis (r = 0.34; P = 0.003) and remained significant after controlling for baseline radiologic scores. The 1-month neutrophil count also was the only independent correlate of volume loss and pleural thickening at the end of treatment and was significantly higher in patients with persistent cavitation or effusion vs those without.

Interpretation: Persistent neutrophilic inflammation after 1 month of TB therapy is associated with poor radiologic outcome, suggesting a target for interventions to minimize lung disease after tuberculous.
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http://dx.doi.org/10.1016/j.chest.2021.07.041DOI Listing
July 2021

Insourcing and scaling a telemedicine solution in under 2 weeks: Lessons for the digital transformation of health care.

Healthc (Amst) 2021 Sep 19;9(3):100568. Epub 2021 Jul 19.

University of Pennsylvania Health System, Penn Medicine Center for Health Care Innovation, 3400 Civic Center Blvd, 14(th) Floor South Pavilion, Philadelphia, PA, 19104, USA; University of Pennsylvania Health System, Office of the Chief Medical Information Officer, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA; University of Pennsylvania Health System, Cardiology, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA. Electronic address:

The Covid-19 pandemic required rapid scale of telemedicine as well as other digital workflows to maintain access to care while reducing infection risk. Both patients and clinicians who hadn't used telemedicine before were suddenly faced with a multi-step setup process to log into a virtual meeting. Unlike in-person examination rooms, locking a virtual meeting room was more error-prone and posed a risk of multiple patients joining the same online session. There was administrative burden on the practice staff who were generating and manually sending links to patients, and educating patients on device set up was time-consuming and unsustainable. A solution had to be deployed rapidly system-wide, without the usual roll out across months. Our answer was to design and implement a novel EHR-integrated web application called the Switchboard, in just two weeks. The Switchboard leverages a commercial, cloud-based video meeting platform and facilitates an end-to-end virtual care encounter workflow, from pre-visit reminders to post-visit SMS text message-based measurement of patient experience, with tools to extend contact-less workflows to in-person appointments. Over the first 11 months of the pandemic, the in-house platform has been adopted across 6 hospitals and >200 practices, scaled to 8,800 clinicians who at their peak conducted an average of 30,000 telemedicine appointments/week, and enabled over 10,000-20,000 text messages/day to be exchanged through the platform. Furthermore, it enabled our organization to convert from an average of 75% of telehealth visits being conducted via telephone to 75% conducted via video within weeks.
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http://dx.doi.org/10.1016/j.hjdsi.2021.100568DOI Listing
September 2021

T-Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes.

Diabetes 2021 08 18;70(8):1754-1766. Epub 2021 Mar 18.

Mater Young Adult Health Centre, Mater Misericordiae Ltd, South Brisbane, Queensland, Australia.

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of diabetic kidney disease (DKD). In type 1 diabetes, increased urinary albumin-to-creatinine ratio (uACR) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule-1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. DKD risk was assigned in youth with type 1 diabetes ( = 100; 20.0 ± 2.8 years; males/females, 54:46; HbA 66.1 [12.3] mmol/mol; diabetes duration 10.7 ± 5.2 years; and BMI 24.5 [5.3] kg/m) and 10-year historical uACR, HbA, and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared with streptozotocin diabetes in mice. Kidney biopsies were used to examine infiltration of KIM-1-expressing T cells in DKD and compared with other chronic kidney disease. Individuals at high risk for DKD had persistent elevations in uACR defined by area under the curve (AUC; uACR, 29.7 ± 8.8 vs. 4.5 ± 0.5; < 0.01 vs. low risk) and early kidney dysfunction, including ∼8.3 mL/min/1.73 m higher estimated glomerular filtration rates (modified Schwartz equation; < 0.031 vs. low risk) and plasma KIM-1 concentrations (∼15% higher vs. low risk; < 0.034). High-risk individuals had greater glycemic variability and increased peripheral blood T-cell KIM-1 expression, particularly on CD8 T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1 T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high-risk youth with diabetes showed elevated collagen IV and sodium-glucose cotransporter 2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8 T-cell production of KIM-1.
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http://dx.doi.org/10.2337/db20-1081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385614PMC
August 2021

The chemical composition and toxicological effects of fine particulate matter (PM) emitted from different cooking styles.

Environ Pollut 2021 Jul 7;288:117754. Epub 2021 Jul 7.

The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China. Electronic address:

The mass, chemical composition and toxicological properties of fine particulates (PM) emitted from cooking activities in three Hong Kong based restaurants and two simulated cooking experiments were characterized. Extracts from the PM samples elicited significant biological activities [cell viability, generation of reactive oxygen species (ROS), DNA damage and inflammation effect (TNF-α)] in a dose-dependent manner. The composition of PAHs, oxygenated PAHs (OPAHs) and azaarenes (AZAs) mixtures differed between samples. The concentration ranges of the Σ30PAHs, Σ17OPAHs and Σ4AZAs and Σ7Carbonyls in the samples were 9627-23,452 pg m, 503-3700 pg m, 33-263 pg m and 158 - 5328 ng m, respectively. Cell viability caused by extracts from the samples was positively correlated to the concentration of benzo[a]anthracene, indeno[1,2,3-cd]pyrene and 1,4-naphthoquinone in the PM extracts. Cellular ROS production (upon exposure to extracts) was positively correlated with the concentrations of PM, decaldehyde, acridine, Σ17OPAHs and 7 individual OPAHs. TNF-α showed significant positive correlations with the concentrations of most chemical species (elemental carbon, 16 individual PAHs including benzo[a]pyrene, Σ30PAHs, SO, Ca, Ca, Na, K, Ti, Cr, Mn, Fe, Cu and Zn). The concentrations of Al, Ti, Mn, Σ30PAHs and 8 individual PAHs including benzo[a]pyrene in the samples were positively correlated with DNA damage caused by extracts from the samples. This study demonstrates that inhalation of PM emitted from cooking could result in adverse human health effects.
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http://dx.doi.org/10.1016/j.envpol.2021.117754DOI Listing
July 2021

Continuous Glucose Monitoring Improves Glycemic Outcomes in Children With Type 1 Diabetes: Real-World Data From a Population-Based Clinic.

Diabetes Care 2021 Sep 19;44(9):e171-e172. Epub 2021 Jul 19.

Department of Diabetes and Endocrinology, Perth Children's Hospital, Nedlands, Western Australia, Australia.

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http://dx.doi.org/10.2337/dc21-0304DOI Listing
September 2021

Proteomic signatures for perioperative oxygen delivery in skin after major elective surgery: mechanistic sub-study of a randomised controlled trial.

Br J Anaesth 2021 Jul 5. Epub 2021 Jul 5.

Translational Medicine & Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK. Electronic address:

Background: Maintaining adequate oxygen delivery (DO) after major surgery is associated with minimising organ dysfunction. Skin is particularly vulnerable to reduced DO. We tested the hypothesis that reduced perioperative DO fuels inflammation in metabolically compromised skin after major surgery.

Methods: Participants undergoing elective oesophagectomy were randomised immediately after surgery to standard of care or haemodynamic therapy to achieve their individualised preoperative DO. Abdominal punch skin biopsies were snap-frozen before and 48 h after surgery. On-line two-dimensional liquid chromatography and ultra-high-definition label-free mass spectrometry was used to characterise the skin proteome. The primary outcome was proteomic changes compared between normal (≥preoperative value before induction of anaesthesia) and low DO (
Results: Paired punch skin biopsies were obtained from 35 participants (mean age: 68 yr; 31% female), of whom 17 underwent oesophagectomy. There were 14/2096 proteins associated with normal (n=10) vs low (n=7) DO after oesophagectomy. Failure to maintain preoperative DO was associated with upregulation of proteins counteracting oxidative stress. Normal DO after surgery was associated with pathways involving leucocyte recruitment and upregulation of an antimicrobial peptidoglycan recognition protein. Immunohistochemistry (n=6 patients) and immunoblots after liver resection (n=12 patients) supported the proteomic findings.

Conclusions: Proteomic profiles in serial skin biopsies identified organ-protective mechanisms associated with normal DO after major surgery.

Clinical Trial Registration: ISRCTN76894700.
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http://dx.doi.org/10.1016/j.bja.2021.06.003DOI Listing
July 2021

Stimulus duration and vestibular sensory evoked potentials (VsEPs).

Hear Res 2021 Sep 16;408:108293. Epub 2021 Jun 16.

University of Nebraska-Lincoln, Department of Special Education and Communication Disorders, Lincoln, NE 68583-0738 USA; University of Rochester, Department of Otolaryngology, Rochester, New York 14642 USA. Electronic address:

Recording the linear vestibular sensory evoked potential (VsEP) relies on moving the head in a prescribed manner to synchronously activate neurons of the gravity receptor organs. One problematic issue in accomplishing this is the potential coactivation of cochlear neurons. Although the major stimulus parameters required to elicit the vestibular response have been characterized, some of the determinants of auditory coactivation have not been clearly addressed. In the present study, we show that the duration of the linear cranial jerk stimulus plays a critical role in avoiding coactivation of auditory responses during VsEP recordings. Acoustic masking procedures are essential when recording the VsEP, particularly when using stimulus durations of less than 1 ms.
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http://dx.doi.org/10.1016/j.heares.2021.108293DOI Listing
September 2021

Glycaemic outcomes in Australasian children and adults with Type 1 Diabetes: failure to meet targets across the age spectrum.

Intern Med J 2021 Jun 18. Epub 2021 Jun 18.

Department of Endocrinology and Diabetes, Perth Children's Hospital, Perth, Australia.

Background: The goal of therapy in Type 1 diabetes (T1D) is to achieve optimal glycaemic targets and reduce complications. Robust data representing glycaemic outcomes across the lifespan are lacking in Australasia.

Aims: To examine contemporary glycaemic outcomes and rate of use of diabetes technologies in Australasian people with T1D.

Methods: Cross-sectional analysis of de-identified data from 18 diabetes centres maintained in the Australasian Diabetes Data Network (ADDN) registry during 2019. Glycaemia was measured using glycated haemoglobin (HbA1c). The proportion of people with T1D achieving the international HbA1c target of <53 mmol/mol (7%) was calculated. Rates of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) use were determined.

Results: 7988 individuals with T1D with 30 575 visits were recorded in the registry. The median (IQR) age was 15.3 (10.0) years and diabetes duration was 5.7 (9.4) years with 49% on multiple daily injections (MDI) and 36% on CSII. The mean HbA1c for the whole cohort was 66 mmol/mol (8.2%). HbA1c increased with age; from 60 mmol/mol (7.6%) in children <10 years, increasing during adolescence and peaking at 73 mmol/mol (8.8%) in the 20-25 years age group. HbA1c target of <53 mmol/mol (7%) was met in 18% of children and 13% of adults. HbA1c was lower on CSII as compared to those on MDI (p < 0.0001).

Conclusions: Only a minority of children and adults achieve the recommended glycaemic goals despite access to specialist care in major diabetes centres. There is a need to identify factors which improve glycaemic outcomes. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15426DOI Listing
June 2021

Effects of Several Therapeutic Agents on Mammalian Vestibular Function: Meclizine, Diazepam, and JNJ7777120.

J Assoc Res Otolaryngol 2021 May 19. Epub 2021 May 19.

Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, 301 Barkley Memorial Center, Lincoln, NE, 68583-0738, USA.

Management of vestibular dysfunction may include treatment with medications that are thought to act to suppress vestibular function and reduce or eliminate abnormal sensitivity to head motions. The extent to which vestibular medications act centrally or peripherally is still debated. In this study, two commonly prescribed medications, meclizine and diazepam, and a candidate for future clinical use, JNJ7777120, were evaluated for their effects on short latency compound action potentials generated by the peripheral vestibular system and corresponding central neural relays (i.e., vestibular sensory-evoked potentials, VsEPs). The effects of the selected drugs developed slowly over the course of two hours in the mouse. Findings indicate that meclizine (600 mg/kg) and diazepam (> 60 mg/kg) can act on peripheral elements of the vestibular maculae whereas diazepam also acts most effectively on central gravity receptor circuits to exert its suppressive effects. The novel pharmacological agent JNJ7777120 (160 mg/kg) acts in the vestibular periphery to enhance macular responses to transient stimuli (VsEPs) while, hypothetically, suppressing macular responses to sustained or slowly changing stimuli.
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http://dx.doi.org/10.1007/s10162-021-00803-5DOI Listing
May 2021

Vasopressor Discontinuation Order in Septic Shock With Reduced Left Ventricular Function.

J Pharm Pract 2021 May 12:8971900211015080. Epub 2021 May 12.

Department of Pharmacy, Augusta University Medical Center, Augusta, GA, USA.

Background: The optimal vasopressor management for septic patients with left ventricular (LV) dysfunction has not been well established, and current evidence is conflicting regarding the optimal vasopressor discontinuation order.

Objective: The objective was to evaluate the impact of LV dysfunction on the hemodynamic management of septic shock by assessing the incidence of clinically significant hypotension after vasopressor discontinuation.

Methods: In this single-center, retrospective cohort study, adult patients were included if they met the Sepsis-3 definition of septic shock, had LV dysfunction (defined as an ejection fraction ≤40%), and received norepinephrine and vasopressin as the last vasopressors discontinued. The primary outcome was the incidence of clinically significant hypotension following discontinuation of vasopressin or norepinephrine. Clinically significant hypotension was defined as a MAP less than 60 mmHg and the need for either: 1) the reinstitution of the previously discontinued agent at any dosage, 2) the receipt of at least 500 mL of a crystalloid at a rate of at least 500 mL/hour, 3) or the receipt of at least 25 grams of albumin 5% at a rate of at least 25 gram/hour. Secondary outcomes included intensive care unit (ICU) and hospital lengths of stay, and ICU and hospital mortality.

Results: A total of 78 patients met inclusion criteria, with 37 patients having vasopressin discontinued first and 41 having norepinephrine discontinued first. Clinically significant hypotension occurred in 28 patients (76%) following the discontinuation of vasopressin, compared to 28 patients (81%) following the discontinuation of norepinephrine (p = 0.61). ICU length of stay was 9 days in the vasopressin discontinued first cohort, compared to 15 days in the norepinephrine discontinued first cohort (p = 0.01). There was no statistically significant difference in mortality observed.

Conclusion: The discontinuation order of norepinephrine and vasopressin did not impact the incidence of clinically significant hypotension in patients with septic shock and LV dysfunction, but may influence ICU length of stay, although other factors may have impacted this finding.
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http://dx.doi.org/10.1177/08971900211015080DOI Listing
May 2021

Sleep in Aneurysmal Subarachnoid Hemorrhage Patients During Critical and Acute Care.

Dimens Crit Care Nurs 2021 Mar-Apr 01;40(2):118-124

Background: Nurses caring for intensive care patients diagnosed with an aneurysmal subarachnoid hemorrhage (aSAH) conduct frequent neurological assessments and vital signs over an extended period during which patients are at risk of vasospasm. The frequency of assessments can negatively impact sleep, resulting in altered thought processes and mood, including delirium. There are 2 types of sleep during the night: non-rapid eye movement (non-REM) sleep and REM sleep (also called stage R). Non-REM sleep is subdivided into 3 stages: stage N1, stage N2, and stage N3. These 4 stages of sleep are referred to as sleep architecture.

Objective: The aim of this study was to explore patterns of sleep in patients with aSAH over time during hospitalization.

Methods: Sleep data of stages and cycles were collected with use of a Fitbit activity tracker in this pilot, exploratory research study. Demographic data included age and gender. Six English-speaking patients, diagnosed with an aneurysmal SAH, confirmed by diagnostic angiogram, were followed in neuro-intensive care unit (ICU), neuro-step-down, neuroscience unit, and inpatient rehabilitation.

Results: There were a total of 226 sleep events. A sleep event encompassed a recorded start and end time on a single date. Each event included several sleep cycles. Each sleep cycle consisted of wakefulness, light sleep, deep sleep, and REM sleep. In 79 sleep events, light and deep sleep did add up to more than 4 hours; only 38 sleep events indicated more than 90 minutes of REM/night; 61 events showed the cycle of light-deep-light-REM cycles; 80 events showed 3 to 5 REM periods/night; and only 46 events demonstrated that the early-morning REM cycle was the longest. The average number of REM cycles increased from ICU (n = 4.6) to rehabilitation (n = 6.5). The percentage of days with sleep cycles also increased from ICU to rehabilitation (42 to 64).

Discussion: "Normal" sleep patterns are disrupted in aSAH patients throughout their hospitalization. Data in this study revealed that the patients do sleep; however, it is rarely organized. Patients were not always able to progress through the expected sleep cycle of light to deep to light to REM. Hospitalized aSAH patients do engage in REM sleep, but its pattern is abnormal. Staff should strategize on minimizing interruptions, clustering care, and minimizing sounds. Nurses should advocate for the frequency of assessments and vital signs based on hospital/unit policy and individual patient needs.
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http://dx.doi.org/10.1097/DCC.0000000000000467DOI Listing
May 2021

Additional Insulin Is Required in Both the Early and Late Postprandial Periods for Meals High in Protein and Fat: A Randomized Trial.

J Clin Endocrinol Metab 2021 Aug;106(9):e3611-e3618

Perth Children's Hospital, Nedlands, WA, 6009, Australia.

Context: The pattern and quantity of insulin required for high-protein high-fat (HPHF) meals is not well understood.

Objective: This study aimed to determine the amount and delivery pattern of insulin required to maintain euglycemia for 5 hours after consuming a HPHF meal compared with a low-protein low-fat (LPLF) meal.

Methods: This randomized crossover clinical trial, conducted at 2 Australian pediatric diabetes centers, included 10 patients (12-21 years of age) with type 1 diabetes for ≥ 1 year. Participants were randomized to HPHF meal (60 g protein, 40 g fat) or LPLF meal (5 g protein, 5 g fat) with identical carbohydrate content (30 g). A modified insulin clamp technique was used to determine insulin requirements to maintain postprandial euglycemia for 5 hours. Total mean insulin requirements over 5 hours were measured.

Results: The total mean insulin requirements for the HPHF meal were significantly greater than for the LPLF meal (11.0 [CI 9.2, 12.8] units vs 5.7 [CI 3.8, 7.5] units; P = 0.001). Extra intravenous insulin was required for HPHF: 0 to 2 hours (extra 1.2 [CI 0.6, 1.6] units/h), 2 to 4 hours (extra 1.1 [CI 0.6, 1.6] units/h), and 4 to 5 hours (extra 0.6 [CI 0.1, 1.1] units/h) after the meal. There were marked inter-individual differences in the quantity of additional insulin (0.3 to 5 times more for HPHF) and the pattern of insulin delivery (0%-85% of additional insulin required in the first 2 hours).

Conclusion: The addition of protein and fat to a standardized carbohydrate meal almost doubled the mean insulin requirement, with most participants requiring half of the additional insulin in the first 2 hours.
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http://dx.doi.org/10.1210/clinem/dgab318DOI Listing
August 2021

Overview and Update on Methods for Cargo Loading into Extracellular Vesicles.

Processes (Basel) 2021 Feb 15;9(2). Epub 2021 Feb 15.

Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.

The enormous library of pharmaceutical compounds presents endless research avenues. However, several factors limit the therapeutic potential of these drugs, such as drug resistance, stability, off-target toxicity, and inadequate delivery to the site of action. Extracellular vesicles (EVs) are lipid bilayer-delimited particles and are naturally released from cells. Growing evidence shows that EVs have great potential to serve as effective drug carriers. Since EVs can not only transfer biological information, but also effectively deliver hydrophobic drugs into cells, the application of EVs as a novel drug delivery system has attracted considerable scientific interest. Recently, EVs loaded with siRNA, miRNA, mRNA, CRISPR/Cas9, proteins, or therapeutic drugs show improved delivery efficiency and drug effect. In this review, we summarize the methods used for the cargo loading into EVs, including siRNA, miRNA, mRNA, CRISPR/Cas9, proteins, and therapeutic drugs. Furthermore, we also include the recent advance in engineered EVs for drug delivery. Finally, both advantages and challenges of EVs as a new drug delivery system are discussed. Here, we encourage researchers to further develop convenient and reliable loading methods for the potential clinical applications of EVs as drug carriers in the future.
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http://dx.doi.org/10.3390/pr9020356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096148PMC
February 2021

Acute hyperglycaemia does not have a consistent adverse effect on exercise performance in recreationally active young people with type 1 diabetes: a randomised crossover in-clinic study.

Diabetologia 2021 Aug 4;64(8):1737-1748. Epub 2021 May 4.

Department of Endocrinology and Diabetes, Perth Children's Hospital, Nedlands, Western Australia, Australia.

Aims/hypothesis: In individuals with type 1 diabetes, chronic hyperglycaemia impairs aerobic fitness. However, the effect of acute marked hyperglycaemia on aerobic fitness is unclear, and the impact of insulin level has not been examined. In this study, we explored if acute hyperglycaemia with higher or low insulin levels affects [Formula: see text] and other exercise performance indicators in individuals with type 1 diabetes.

Methods: Eligible participants were aged 14 to 30 years, with complication-free, type 1 diabetes and HbA ≤ 75 mmol/mol (≤9%). Participants exercised in a clinical laboratory under three clamp (constant insulin, variable glucose infusion) conditions: euglycaemia (5 mmol/l) with 20 mU [m BSA] min insulin (where BSA is body surface area) (Eu20); hyperglycaemia (17 mmol/l) with 20 mU [m BSA] min insulin (Hyper20); and hyperglycaemia (17 mmol/l) with 5 mU [m BSA] min insulin (Hyper5) on separate days. Participants and the single testing assessor were blinded to condition, with participants allocated to randomised testing condition sequences as they were consecutively recruited. Standardised testing (in order) conducted on each of the three study days included: triplicate 6 second sprint cycling, grip strength, single leg static balance, vertical jump and modified Star Excursion Balance Test, ten simple and choice reaction times and one cycle ergometer [Formula: see text] test. The difference between conditions in the aforementioned testing measures was analysed, with the primary outcome being the difference in [Formula: see text].

Results: Twelve recreationally active individuals with type 1 diabetes (8 male, mean ± SD 17.9 ± 3.9 years, HbA 61 ± 11 mmol/mol [7.7 ± 1.0%], 7 ± 3 h exercise/week) were analysed. Compared with Eu20, [Formula: see text] was lower in Hyper20 (difference 0.17 l/min [95% CI 0.31, 0.04; p = 0.02] 6.6% of mean Eu20 level), but Hyper5 was not different (p = 0.39). Compared with Eu20, sprint cycling peak power was not different in Hyper20 (p = 0.20), but was higher in Hyper5 (64 W [95% CI 13, 115; p = 0.02] 13.1%). Hyper20 reaction times were not different (simple: p = 0.12) but Hyper5 reaction times were slower (simple: 11 milliseconds [95% CI 1, 22; p = 0.04] 4.7%) than Eu20. No differences between Eu20 and either hyperglycaemic condition were observed for the other testing measures (p > 0.05).

Conclusions/interpretation: Acute marked hyperglycaemia in the higher but not low insulin state impaired [Formula: see text] but to a small extent. Acute hyperglycaemia had an insulin-dependent effect on sprint cycling absolute power output and reaction time but with differing directionality (positive for sprint cycling and negative for reaction time) and no effect on the other indicators of exercise performance examined. We find that acute hyperglycaemia is not consistently adverse and does not impair overall exercise performance to an extent clinically relevant for recreationally active individuals with type 1 diabetes.

Funding: This research was funded by Diabetes Research Western Australia and Australasian Paediatric Endocrine Group grants.
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http://dx.doi.org/10.1007/s00125-021-05465-9DOI Listing
August 2021

Advanced glycation end products as predictors of renal function in youth with type 1 diabetes.

Sci Rep 2021 May 3;11(1):9422. Epub 2021 May 3.

Mater Research Institute, The University of Queensland, TRI, 37 Kent Street, Brisbane, QLD, 4102, Australia.

To examine if skin autofluorescence (sAF) differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Young adults with type 1 diabetes (N = 100; 20.0 ± 2.8 years; M:F 54:46; FBG-11.6 ± 4.9 mmol/mol; diabetes duration 10.7 ± 5.2 years; BMI 24.5(5.3) kg/m) and healthy controls (N = 299; 20.3 ± 1.8 years; M:F-83:116; FBG 5.2 ± 0.8 mmol/L; BMI 22.5(3.3) kg/m) were recruited. Skin autofluorescence (sAF) and circulating AGEs were measured. In a subset of both groups, kidney function was estimated by GFR and uACR, and DKD risk defined by uACR tertiles. Youth with type 1 diabetes had higher sAF and BMI, and were taller than controls. For sAF, 13.6% of variance was explained by diabetes duration, height and BMI (P = 1.5 × 10). In the sub-set examining kidney function, eGFR and sAF were higher in type 1 diabetes versus controls. eGFR and sAF predicted 24.5% of variance in DKD risk (P = 2.2 × 10), which increased with diabetes duration (51%; P < 2.2 × 10) and random blood glucose concentrations (56%; P < 2.2 × 10). HbA and circulating fructosamine albumin were higher in individuals with type 1 diabetes at high versus low DKD risk. eGFR was independently associated with DKD risk in all models. Higher eGFR and longer diabetes duration are associated with DKD risk in youth with type 1 diabetes. sAF, circulating AGEs, and urinary AGEs were not independent predictors of DKD risk. Changes in eGFR should be monitored early, in addition to uACR, for determining DKD risk in type 1 diabetes.
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http://dx.doi.org/10.1038/s41598-021-88786-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093271PMC
May 2021

Genetic epidemiology of SARS-CoV-2 transmission in renal dialysis units - A high risk community-hospital interface.

J Infect 2021 07 22;83(1):96-103. Epub 2021 Apr 22.

Renal Unit, University Hospital Monklands, Monkscourt Ave, Airdrie ML6 0JS, Canada; Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.

Objectives: Patients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium.

Methods: We combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations.

Results: Of 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated.

Conclusions: Near-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings.
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http://dx.doi.org/10.1016/j.jinf.2021.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061788PMC
July 2021

Investigation of Algal Toxins in a Multispecies Seabird Die-Off in the Bering and Chukchi Seas.

J Wildl Dis 2021 04;57(2):399-407

University of Washington, School of Aquatic and Fishery Sciences, COASST, 1122 NE Boat Street, Box 355020, Seattle, Washington 98195, USA.

Between 2014 and 2017, widespread seabird mortality events were documented annually in the Bering and Chukchi seas, concurrent with dramatic reductions of sea ice, warmer than average ocean temperatures, and rapid shifts in marine ecosystems. Among other changes in the marine environment, harmful algal blooms (HABs) that produce the neurotoxins saxitoxin (STX) and domoic acid (DA) have been identified as a growing concern in this region. Although STX and DA have been documented in Alaska (US) for decades, current projections suggest that the incidence of HABs is likely to increase with climate warming and may pose a threat to marine birds and other wildlife. In 2017, a multispecies die-off consisting of primarily Northern Fulmars (Fulmarus glacialis) and Short-tailed Shearwaters (Ardenna tenuirostris) occurred in the Bering and Chukchi seas. To evaluate whether algal toxins may have contributed to bird mortality, we tested carcasses collected from multiple locations in western and northern Alaska for STX and DA. We did not detect DA in any samples, but STX was present in 60% of all individuals tested and in 88% of Northern Fulmars. Toxin concentrations in Northern Fulmars were within the range of those reported from other STX-induced bird die-offs, suggesting that STX may have contributed to mortalities. However, direct neurotoxic action by STX could not be confirmed and starvation appeared to be the proximate cause of death among birds examined in this study.
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http://dx.doi.org/10.7589/JWD-D-20-00057DOI Listing
April 2021

Preoperative lymphopaenia, mortality, and morbidity after elective surgery: systematic review and meta-analysis.

Br J Anaesth 2021 07 29;127(1):32-40. Epub 2021 Mar 29.

Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Electronic address:

Background: In the general adult population, lymphopaenia is associated with an increased risk for hospitalisation with infection and infection-related death. The quality of evidence and strength of association between perioperative lymphopaenia across different surgical procedures and mortality/morbidity has not been examined by systematic review or meta-analysis.

Methods: We searched MEDLINE, Embase, Web of Science, Google Scholar, and Cochrane databases from their inception to June 29, 2020 for observational studies reporting lymphocyte count and in-hospital mortality rate in adults. We defined preoperative lymphopaenia as a lymphocyte count 1.0-1.5×10 L. Meta-analysis was performed using either fixed or random effects models. Quality was assessed using the Newcastle-Ottawa Scale. The I index was used to quantify heterogeneity. The primary outcome was in-hospital mortality rate and mortality rate at 30 days.

Results: Eight studies met the inclusion criteria for meta-analysis, comprising 4811 patients (age range, 46-91 yr; female, 20-79%). These studies examined preoperative lymphocyte count exclusively. Studies were of moderate to high quality overall, ranking >7 using the Newcastle-Ottawa Scale. Preoperative lymphopaenia was associated with a threefold increase in mortality rate (risk ratio [RR]=3.22; 95% confidence interval [CI], 2.19-4.72; P<0.01, I=0%) and more frequent major postoperative complications (RR=1.33; 95% CI, 1.21-1.45; P<0.01, I=6%), including cardiovascular morbidity (RR=1.77; 95% CI, 1.45-2.15; P<0.01, I=0%), infections (RR=1.45; 95% CI, 1.19-1.76; P<0.01, I=0%), and acute renal dysfunction (RR=2.66; 95% CI, 1.49-4.77; P<0.01, I=1%).

Conclusion: Preoperative lymphopaenia is associated with death and complications more frequently, independent of the type of surgery.

Prospero Registry Number: CRD42020190702.
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http://dx.doi.org/10.1016/j.bja.2021.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258977PMC
July 2021

Minimal Agreement between Internal and External Training Load Metrics across a 2-wk Training Microcycle in Elite Squash.

J Sports Sci Med 2021 03 1;20(1):101-109. Epub 2021 Mar 1.

School of Human Sciences (Exercise and Sport Science) The University of Western Australia, Crawley, Western Australia, Australia.

This study investigated the relationships between internal and external training load metrics across a 2-week 'in-season' microcycle in squash. 134 on-court and 32 off-court 'conditioning' sessions were completed by fifteen elite squash players with an average (±SD) of 11 ± 3 per player. During every session, external load was captured using a tri-axial accelerometer to calculate ; i.e., the instantaneous rate of change of acceleration across 3-dimensional planes. Internal load was measured using heart rate (HR), global (sRPE) and differential RPE (dRPE-Legs, dRPE-Breathing). Additionally, HR was used to calculate Banister's, Edward's and TEAM TRIMPs. Across 166 training sessions, was correlated with TRIMP-Banister (r = 0.43 [95% CI: 0.29-0.55], p < 0.001) and TRIMP-Edwards (r = 0.50 [0.37-0.61], p < 0.001). Association of with TRIMP-TEAM (r = 0.24 [0.09-0.38], p = 0.001) was . There was a correlation between sRPE and (r = 0.46 [0.33-0.57], p < 0.001). Association of sRPE was with TRIMP-Banister (r = 0.68 [0.59-0.76], p = 0.001), with TRIMP-Edwards (r = 0.79 [0.72-0.84], p < 0.001) and with TRIMP-TEAM (r = 0.44 [0.31-0.56], p < 0.001). Both dRPE-Legs (r = 0.95 [0.93-0.96], p < 0.001) and dRPE-Breathing (r = 0.92 [0.89-0.94], p < 0.001) demonstrated nearly correlations with sRPE and with each other (r = 0.91 [0.88-0.93], p < 0.001). Collection of both internal and external training load data is recommended to fully appreciate the physical demands of squash training. During a training microcycle containing a variety of training sessions, interpreting internal or external metrics in isolation may underestimate or overestimate the training stress a player is experiencing.
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http://dx.doi.org/10.52082/jssm.2021.101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919364PMC
March 2021

Four right ventricle to pulmonary artery conduit types.

J Thorac Cardiovasc Surg 2021 Jan 23. Epub 2021 Jan 23.

Department of Cardiac Surgery, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, United Kingdom. Electronic address:

Objective: The most durable valved right ventricle to pulmonary artery conduit for the repair of congenital heart defects in patients of different ages, sizes, and anatomic substrate remains uncertain.

Methods: We performed a retrospective analysis of 4 common right ventricle to pulmonary artery conduits used in a single institution over 30 years, using univariable and multivariable models of time-to-failure to analyse freedom from conduit dysfunction, reintervention, and replacement.

Results: Between 1988 and 2018, 959 right ventricle to pulmonary artery conduits were implanted: 333 aortic homografts, 227 pulmonary homografts, 227 composite porcine valve conduits, and 172 bovine jugular vein conduits. Patients weighed 1.6 to 98.3 kg (median 15.3 kg), and median duration of follow-up was 11.4 years, with 505 (52.2%) conduits developing dysfunction, 165 (17.2%) requiring catheter intervention, and 415 (43.2%) being replaced. Greater patient weight, conduit z-score, type and position, as well as catheter intervention were predictors of freedom from replacement. Multivariable analysis demonstrated inferior durability for smaller composite porcine valve conduits, with excellent durability for larger diameter conduits of the same type. Bovine jugular vein conduit longevity was inferior to that of homografts in all but the smallest patients. Freedom from dysfunction at 8 years was 60.7% for aortic homografts, 72% for pulmonary homografts, 51.2% for composite porcine valve conduits, and 41.3% for bovine jugular vein conduits. Judicious oversizing of the conduit improved conduit durability in all patients, but to the greatest extent in patients weighing 5 to 20 kg.

Conclusions: Pulmonary and aortic homografts had greater durability than xenograft conduits, particularly in patients weighing 5 to 20 kg. Judicious oversizing was the most significant surgeon-modifiable factor affecting conduit longevity.
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http://dx.doi.org/10.1016/j.jtcvs.2020.12.144DOI Listing
January 2021

Understanding parents' decision-making on participation in clinical trials in children's heart surgery: a qualitative study.

BMJ Open 2021 02 23;11(2):e044896. Epub 2021 Feb 23.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Objectives: Few children undergoing heart surgery are recruited to clinical trials and little is known about the views and attitudes of parents towards trials. This study explored parents' perspectives on decision-making about their child's participation in a clinical trial during their elective cardiac surgery.

Design: Qualitative interview study.

Setting: Single-centre substudy of a multicentre, double-blind, randomised controlled trial to investigate the effects of remote ischaemic preconditioning in children undergoing cardiac surgery.

Participants: Parents of children approached to participate in the trial, both consenters and decliners.

Methods: Semistructured interviews were conducted face-to-face or by telephone following discharge, digitally audio-recorded, transcribed and thematically analysed.

Results: Of 46 patients approached for the trial, 24 consenting and 2 declining parents agreed to participate in an interview (21 mothers, 5 fathers). Parental decision-making about research was influenced by (1) potential risks or additional procedures; (2) personal benefit and altruism for the 'cardiac community'; (3) information, preparation, timing and approach; and (4) trust in the clinical team and collaboration with researchers. All of these were placed within the context of their understanding of the trial and knowledge of research.

Conclusions: Parents of children undergoing cardiac surgery attach value to clinical research and are supportive of clinical trials when there is no or minimal perceived additional risk. These findings enhance our understanding of the factors that influence parents' decision-making and should be used to inform the design and conduct of future paediatric surgical trials.

Trial Registration Number: ISRCTN12923441; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-044896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907877PMC
February 2021
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