High intensity interval training as a novel treatment for impaired awareness of hypoglycaemia in people with type 1 diabetes (HIT4HYPOS): a randomised parallel-group study.

AIMS/HYPOTHESIS: Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes may develop through a process referred to as habituation. Consistent with this, a single bout of high intensity interval exercise as a novel stress stimulus improves counterregulatory responses (CRR) to next-day hypoglycaemia, referred to as dishabituation. This longitudinal pilot study investigated whether 4 weeks of high intensity interval training (HIIT) has sustained effects on counterregulatory and symptom responses to hypoglycaemia in adults with type 1 diabetes and IAH. METHODS: HIT4HYPOS was a single-centre, randomised, parallel-group study. Participants were identified using the Scottish Diabetes Research Network (SDRN) and from diabetes outpatient clinics in NHS Tayside, UK. The study took place at the Clinical Research Centre, Ninewells Hospital and Medical School, Dundee, UK. Participants were aged 18-55 years with type 1 diabetes of at least 5 years' duration and HbA1c levels <75 mmol/mol (<9%). They had IAH confirmed by a Gold score ≥4, modified Clarke score ≥4 or Dose Adjustment For Normal Eating [DAFNE] hypoglycaemia awareness rating of 2 or 3, and/or evidence of recurrent hypoglycaemia on flash glucose monitoring. Participants were randomly allocated using a web-based system to either 4 weeks of real-time continuous glucose monitoring (RT-CGM) or RT-CGM+HIIT. Participants and investigators were not masked to group assignment. The HIIT programme was performed for 20 min on a stationary exercise bike three times a week. Hyperinsulinaemic-hypoglycaemic (2.5 mmol/l) clamp studies with assessment of symptoms, hormones and cognitive function were performed at baseline and after 4 weeks of the study intervention. The predefined primary outcome was the difference in hypoglycaemia-induced adrenaline (epinephrine) responses from baseline following RT-CGM or RT-CGM+HIIT. RESULTS: Eighteen participants (nine men and nine women) with type 1 diabetes (median [IQR] duration 27 [18.75-32] years) and IAH were included, with nine participants randomised to each group. Data from all study participants were included in the analysis. During the 4 week intervention there were no significant mean (SEM) differences between RT-CGM and RT-CGM+HIIT in exposure to level 1 (28 [7] vs 22 [4] episodes, p=0.45) or level 2 (9 [3] vs 4 [1] episodes, p=0.29) hypoglycaemia. The CGM-derived mean glucose level, SD of glucose and glucose management indicator (GMI) did not differ between groups. During the hyperinsulinaemic-hypoglycaemic clamp studies, mean (SEM) change from baseline was greater for the noradrenergic responses (RT-CGM vs RT-CGM+HIIT: -988 [447] vs 514 [732] pmol/l, p=0.02) but not the adrenergic responses (-298 [687] vs 1130 [747] pmol/l, p=0.11) in those participants who had undergone RT-CGM+HIIT. There was a benefit of RT-CGM+HIIT for mean (SEM) change from baseline in the glucagon CRR to hypoglycaemia (RT-CGM vs RT-CGM+HIIT: 1 [4] vs 16 [6] ng/l, p=0.01). Consistent with the hormone response, the mean (SEM) symptomatic response to hypoglycaemia (adjusted for baseline) was greater following RT-CGM+HIIT (RT-CGM vs RT-CGM+HIIT: -4 [2] vs 0 [2], p<0.05). CONCLUSIONS/INTERPRETATION: In this pilot clinical trial in people with type 1 diabetes and IAH, we found continuing benefits of HIIT for overall hormonal and symptomatic CRR to subsequent hypoglycaemia. Our findings also suggest that HIIT may improve the glucagon response to insulin-induced hypoglycaemia. TRIAL REGISTRATION: ISRCTN15373978. FUNDING: Sir George Alberti Fellowship from Diabetes UK (CMF) and the Juvenile Diabetes Research Foundation.

The metabolome as a diagnostic for maximal aerobic capacity during exercise in type 1 diabetes.

AIMS/HYPOTHESIS: Our aim was to characterise the in-depth metabolic response to aerobic exercise and the impact of residual pancreatic beta cell function in type 1 diabetes. We also aimed to use the metabolome to distinguish individuals with type 1 diabetes with reduced maximal aerobic capacity in exercise defined by V ˙ O 2peak . METHODS: Thirty participants with type 1 diabetes (≥3 years duration) and 30 control participants were recruited. Groups did not differ in age or sex. After quantification of peak stimulated C-peptide, participants were categorised into those with undetectable (<3 pmol/l), low (3-200 pmol/l) or high (>200 pmol/l) residual beta cell function. Maximal aerobic capacity was assessed by V ˙ O 2peak test and did not differ between control and type 1 diabetes groups. All participants completed 45 min of incline treadmill walking (60% V ˙ O 2peak ) with venous blood taken prior to exercise, immediately post exercise and after 60 min recovery. Serum was analysed using targeted metabolomics. Metabolomic data were analysed by multivariate statistics to define the metabolic phenotype of exercise in type 1 diabetes. Receiver operating characteristic (ROC) curves were used to identify circulating metabolomic markers of maximal aerobic capacity ( V ˙ O 2peak ) during exercise in health and type 1 diabetes. RESULTS: Maximal aerobic capacity ( V ˙ O 2peak ) inversely correlated with HbA1c in the type 1 diabetes group (r2=0.17, p=0.024). Higher resting serum tricarboxylic acid cycle metabolites malic acid (fold change 1.4, p=0.001) and lactate (fold change 1.22, p=1.23×10-5) differentiated people with type 1 diabetes. Higher serum acylcarnitines (AC) (AC C14:1, F value=12.25, p=0.001345; AC C12, F value=11.055, p=0.0018) were unique to the metabolic response to exercise in people with type 1 diabetes. C-peptide status differentially affected metabolic responses in serum ACs during exercise (AC C18:1, leverage 0.066; squared prediction error 3.07). The malic acid/pyruvate ratio in rested serum was diagnostic for maximal aerobic capacity ( V ˙ O 2peak ) in people with type 1 diabetes (ROC curve AUC 0.867 [95% CI 0.716, 0.956]). CONCLUSIONS/INTERPRETATION: The serum metabolome distinguishes high and low maximal aerobic capacity and has diagnostic potential for facilitating personalised medicine approaches to manage aerobic exercise and fitness in type 1 diabetes.

Elevations in plasma glucagon are associated with reduced insulin clearance after ingestion of a mixed-macronutrient meal in people with and without type 2 diabetes.

AIMS/HYPOTHESIS: The temporal suppression of insulin clearance after glucose ingestion is a key determinant of glucose tolerance for people without type 2 diabetes. Whether similar adaptations are observed after the ingestion of a mixed-macronutrient meal is unclear. METHODS: In a secondary analysis of data derived from two randomised, controlled trials, we studied the temporal responses of insulin clearance after the ingestion of a standardised breakfast meal consisting of cereal and milk in lean normoglycaemic individuals (n=12; Lean-NGT), normoglycaemic individuals with central obesity (n=11; Obese-NGT) and in people with type 2 diabetes (n=19). Pre-hepatic insulin secretion rates were determined by the deconvolution of C-peptide, and insulin clearance was calculated using a single-pool model. Insulin sensitivity was measured by an oral minimal model. RESULTS: There were divergent time course changes in insulin clearance between groups. In the Lean-NGT group, there was an immediate post-meal increase in insulin clearance compared with pre-meal values (p<0.05), whereas insulin clearance remained stable at baseline values in Obese-NGT or declined slightly in the type 2 diabetes group (p<0.05). The mean AUC for insulin clearance during the test was ~40% lower in the Obese-NGT (1.3 ± 0.4 l min-1 m-2) and type 2 diabetes (1.4 ± 0.7 l min-1 m-2) groups compared with Lean-NGT (1.9 ± 0.5 l min-1 m-2; p<0.01), with no difference between the Obese-NGT and type 2 diabetes groups. HOMA-IR and glucagon AUC emerged as predictors of insulin clearance AUC, independent of BMI, age or insulin sensitivity (adjusted R2=0.670). Individuals with increased glucagon AUC had a 40% reduction in insulin clearance AUC (~ -0.75 l min-1 m-2; p<0.001). CONCLUSIONS/INTERPRETATION: The ingestion of a mixed-macronutrient meal augments differing temporal profiles in insulin clearance among individuals without type 2 diabetes, which is associated with HOMA-IR and the secretion of glucagon. Further research investigating the role of hepatic glucagon signalling in postprandial insulin kinetics is warranted. TRIAL REGISTRATION: ISRCTN17563146 and ISRCTN95281775.

Clarifying and expanding equity in assessment by considering three orientations: Fairness, inclusion and justice.

CONTEXT: Despite increasing discussion and scholarship, equity in assessment is rarely defined and distinguished in a way that allows for shared understanding in medical education. This paper seeks to clarify and expand the conversation about equity in assessment by critically reviewing three distinct and evolving orientations toward equity in assessment. Orientations refers to the positions, attitudes, interests or priorities individuals can hold toward equity in assessment. The three orientations include fairness-oriented assessment, assessment for inclusion and justice-oriented assessment. While fairness-oriented assessment is a prevailing orientation in medical education, assessment for inclusion and justice-oriented assessment, originally developed in other fields of education, deserve careful consideration. METHODS: In this paper, the authors explore unique underpinning assumptions of each orientation by critically examining the foundational literature of each orientation. They reflect on the unique perspectives each orientation provides, including the actions one might take and what advantages and disadvantages might result from looking at equity in assessment from any one orientation. CONCLUSIONS: Informed by this reflection, the authors propose that to more effectively advance equity in assessment in medical education, those working in the field should clearly identify their respective orientations, intentionally choose methods, tools and measures aligned with their orientations and expand their work by exploring alternative orientations.

Twelve tips for creating a works in progress conference that builds capacity for educational scholarship and creates a scholarly community.

Educators have implemented various strategies to build capacity for education scholarship, and often, these strategies focus on a specific set of interested individuals. We perceived a need for a strategy to engage a health professions education community with peer support. The purpose of these 12 tips is to describe an approach in place for nearly two decades that concurrently advances education scholarship and fosters a community that welcomes novices to experts. The approach is based on principles that not only build capacity and community but also stress the importance of alignment with the institution's missions. The tips guide setting up, conducting, and sustaining such an approach.

How Might we Build an Equitable Future? Design Justice, a Counternarrative to Dominant Approaches in Medical Education.

PHENOMENON: Marginalized individuals in medicine face many structural inequities which can have enduring consequences on their progress. Therefore, inequity must be addressed by dismantling underlying unjust policies, environments, and curricula. However, once these injustices have been taken apart, how do we build more just systems from the rubble? Many current strategies to address this question have foundational values of urgency, solutionism, and top-down leadership. APPROACH: This paper explores a counternarrative: Design Justice. As a set of guiding principles, Design Justice centers the experiences and perspectives of marginalized individuals and communities. These principles include mutual accountability and transparency, co-ownership, and community-led outcomes, and honoring local, traditional, Indigenous knowledge. FINDINGS: Rooted in critical scholarship and critical design, Design Justice recognizes the interconnectedness of various forms of marginalization and works to critically examine power dynamics that exist in every design process. These co-created principles act as practical guardrails, directing progress toward justice. INSIGHTS: This paper begins with an overview of Design Justice's history in critical scholarship and critical design, providing foundational background knowledge for medical educators, scholars, and leaders in key concepts of justice and design. We explore how the Design Justice principles were developed and have been applied across sectors, highlighting its applications, including education applications. Finally, we raise critical questions about medical education prompted by Design Justice.

Adapting to compromised routines: Parental perspectives on physical activity and health for children and adolescents with type 1 diabetes in the UK during COVID-19 lockdown.

PURPOSE: To determine how COVID-19 lockdown impacted physical activity (PA) levels, wellbeing, and diabetes management in children (aged 0-17 years) with type 1 diabetes (T1D), from the perspectives of their parent/guardian. DESIGN AND METHODS: This qualitative descriptive study is part of a larger, parallel mixed-methods design study, which incorporated a cross-sectional survey and semi-structured one-to-one interviews. Interviewees were recruited from the survey, which was distributed to parents of children/adolescents with T1D in the UK. Interviews explored diabetes management, mental and physical wellbeing, changes in PA levels, sleep quality before/during lockdown, and the effects of lockdown on the individual and their family. The interviews were transcribed and the data were analysed thematically. RESULTS: 14 interviews were conducted with parents. Thematic analysis generated a central theme of routine disruption, with four further themes on diabetes management routines, harnessing the opportunities of lockdown, weighing up risk, and variable impact on wellbeing. CONCLUSIONS: Maintaining or increasing PA during COVID-19 lockdown was associated with better diabetes management, sleep, and wellbeing for children/adolescents with T1D, despite significant disruption to established routines. Use of technology during the pandemic contributed positively to wellbeing. PRACTICE IMPLICATIONS: It is crucial to emphasize the significance of maintaining a well-structured routine when treating patients with type 1 diabetes. A consistent routine, incorporating regular physical exercise and good sleep hygiene, will help with managing overall diabetes control.

Underpinning the Food Matrix Regulation of Postexercise Myofibrillar Protein Synthesis by Comparing Salmon Ingestion With the Sum of Its Isolated Nutrients in Healthy Young Adults.

BACKGROUND: Protein is most commonly consumed as whole foods as opposed to single nutrients. However, the food matrix regulation of the postprandial muscle protein synthetic response has received little attention. OBJECTIVES: The purpose of this study was to assess the effects of eating salmon (SAL) and of ingesting the same nutrients as an isolated mixture of crystalline amino acids and fish oil (ISO) on the stimulation of postexercise myofibrillar protein synthesis (MPS) and whole-body leucine oxidation rates in healthy young adults. METHODS: Ten recreationally active adults (24 ± 4 y; 5 men, 5 women) performed an acute bout of resistance exercise, followed by the ingestion of SAL or ISO in a crossover fashion. Blood, breath, and muscle biopsies were collected at rest and after exercise during primed continuous infusions of L-[ring-2H5]phenylalanine and L-[1-13C]leucine. All data are presented as means ± SD and/or mean differences (95% CIs). RESULTS: Postprandial essential amino acid (EAA) concentrations peaked earlier (P = 0.024) in the ISO group than those in the SAL group. Postprandial leucine oxidation rates increased over time (P < 0.001) and peaked earlier in the ISO group (1.239 ± 0.321 nmol/kg/min; 63 ± 25 min) than those in the SAL group (1.230 ± 0.561 nmol/kg/min; 105 ± 20 min; P = 0.003). MPS rates for SAL (0.056 ± 0.022 %/h; P = 0.001) and ISO (0.046 ± 0.025 %/h; P = 0.025) were greater than the basal rates (0.020 ± 0.011 %/h) during the 0- to 5-h recovery period, with no differences between conditions (P = 0.308). CONCLUSION: We showed that the postexercise ingestion of SAL or ISO stimulate postexercise MPS rates with no differences between the conditions. Thus, our results indicate that ingesting protein from SAL as a whole-food matrix is similarly anabolic to ISO in healthy young adults. This trial was registered at www. CLINICALTRIALS: gov as NCT03870165.

Recommendations from Diabetes UK's 2022 diabetes and physical activity workshop.

AIMS: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of diabetes and physical activity and provide recommendations to researchers and research funders on how best to address them. METHODS: A 1-day research workshop was conducted, bringing together researchers, people living with diabetes, healthcare professionals, and members of staff from Diabetes UK to identify and prioritise recommendations for future research into physical activity and diabetes. RESULTS: Workshop attendees prioritised four key themes for further research: (i) better understanding of the physiology of exercise in all groups of people: in particular, what patient metabolic characteristics influence or predict the physiological response to physical activity, and the potential role of physical activity in beta cell preservation; (ii) designing physical activity interventions for maximum impact; (iii) promoting sustained physical activity across the life course; (iv) designing physical activity studies for groups with multiple long-term conditions. CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to diabetes and physical activity and calls on the research community to develop applications in these areas and funders to consider how to stimulate research in these areas.

Identifying behavioural barriers and facilitators to engaging men in a community-based lifestyle intervention to improve physical and mental health and well-being.

BACKGROUND: There are few community-based lifestyle interventions designed to target physical and mental health of men. We conducted a qualitative focus group study with men to explore their perceived barriers and facilitators to uptake and engagement with interventions designed to improve their physical and mental health and wellbeing. METHODS: A volunteer sampling approach (advertisements posted on a premier league football club's social media) was used to recruit men aged 28 to 65 years who were interested in improving their physical and/or mental health and wellbeing. Focus group discussions were conducted at a local premier league football club to 1) explore men's perceived barriers and facilitators to uptake of community-based interventions; 2) identify health issues considered important to address; 3) obtain participant views on how to best engage men in community-based interventions; and 4) use the findings to inform the development of a multibehavioural complex community-based intervention (called 'The 12th Man'). RESULTS: Six focus group discussions were conducted (duration 27 to 57 min) involving 25 participants (median age 41 years, IQR = 21 years). Thematic analyses generated seven themes: 'Lifestyle behaviours for both mental health and physical health'; 'work pressures are barriers to engaging with lifestyle behaviour change'; previous injuries are barriers to engagement in physical activity and exercise'; personal and peer group relationships impact on lifestyle behaviour change'; relationships between body image and self-confidence on mastery of skills for physical activity and exercise'; building motivation and personalised goal setting'; and 'credible individuals increase uptake and continued engagement with lifestyle behaviour change'. CONCLUSIONS: Findings suggest that a multibehavioural community-based lifestyle intervention designed for men should promote parity of esteem between physical and mental health. It should also acknowledge individual needs and preferences, emotions in the context of goal setting and planning, and be delivered by a knowledgeable and credible professional. The findings will inform the development of a multibehavioural complex community-based intervention ('The 12th Man').

Ageing modifies acute resting blood pressure responses to incremental consumption of dietary nitrate: a randomised, cross-over clinical trial.

Beetroot (BR) is a rich source of nitrate (NO3-) that has been shown to reduce blood pressure (BP). Yet, no studies have examined the vascular benefits of BR in whole-food form and whether the effects are modified by age. This study was a four-arm, randomised, open-label, cross-over design in twenty-four healthy adults (young n 12, age 27 ± 4 years, old n 12, age 64 ± 5 years). Participants consumed whole-cooked BR at portions of (NO3- content in brackets) 100 g (272 mg), 200 g (544 mg) and 300 g (816 mg) and a 200-ml solution containing 1000 mg of potassium nitrate (KNO3) on four separate occasions over a 4-week period (≥7-d washout period). BP, plasma NO3- and nitrite (NO2-) concentrations, and post-occlusion reactive hyperaemia via laser Doppler, were measured pre- and up to 5-h post-intervention. Data were analysed by repeated-measures ANOVA. Plasma NO2- concentrations were higher in the young v. old at baseline and post-intervention (P < 0·05). All NO3- interventions decreased systolic and diastolic BP in young participants (P < 0·05), whereas only KNO3 (at 240-300 min post-intake) significantly decreased systolic (-4·8 mmHg, -3·5 %, P = 0·024) and diastolic (-5·4 mmHg, -6·5 %, P = 0·007) BP in older participants. In conclusion, incremental doses of dietary NO3- reduced systolic and diastolic BP in healthy young adults whereas in the older group a significant decrease was only observed with the highest dose. The lower plasma NO2- concentrations in older participants suggest that there may be mechanistic differences in the production of NO from dietary NO3- in young and older populations.

Dietary fat intake is associated with insulin resistance and an adverse vascular profile in patients with T1D: a pooled analysis.

BACKGROUND: Insulin resistance (IR) increases vascular risk in individuals with Type 1 Diabetes (T1D). We aimed to investigate the relationship between dietary intake and IR, as well as vascular biomarkers in T1D. METHODS: Baseline data from three randomised controlled trials were pooled. Estimated glucose disposal rate (eGDR) was used as an IR marker. Employing multivariate nutrient density substitution models, we examined the association between macronutrient composition and IR/vascular biomarkers (tumour necrosis factor-α, fibrinogen, tissue factor activity, and plasminogen activator inhibitor-1). RESULTS: Of the 107 patients, 50.5% were male with mean age of 29 ± 6 years. Those with lower eGDR were older with a longer diabetes duration, higher insulin requirements, and an adverse vascular profile (p < 0.05). Patients with higher degrees of IR had higher total energy intake (3192 ± 566 vs. 2772 ± 268 vs. 2626 ± 395 kcal/d for eGDR < 5.1 vs. 5.1-8.6 vs. ≥ 8.7 mg/kg/min, p < 0.001) and consumed a higher absolute and proportional amount of fat (47.6 ± 18.6 vs. 30.4 ± 8.1 vs. 25.8 ± 10.4%, p < 0.001). After adjusting for total energy intake, age, sex, and diabetes duration, increased carbohydrate intake offset by an isoenergetic decrease in fat was associated with higher eGDR (ß = 0.103, 95% CI 0.044-0.163). In contrast, increased dietary fat at the expense of dietary protein intake was associated with lower eGDR (ß = - 0.119, 95% CI - 0.199 to - 0.040). Replacing fat with 5% isoenergetic amount of carbohydrate resulted in decreased vascular biomarkers (p < 0.05). CONCLUSION: Higher fat, but not carbohydrate, intake is associated with increased IR and an adverse vascular profile in patients with T1D.

COVID-19 epidemic modelling for policy decision support in Victoria, Australia 2020-2021.

BACKGROUND: Policy responses to COVID-19 in Victoria, Australia over 2020-2021 have been supported by evidence generated through mathematical modelling. This study describes the design, key findings, and process for policy translation of a series of modelling studies conducted for the Victorian Department of Health COVID-19 response team during this period. METHODS: An agent-based model, Covasim, was used to simulate the impact of policy interventions on COVID-19 outbreaks and epidemic waves. The model was continually adapted to enable scenario analysis of settings or policies being considered at the time (e.g. elimination of community transmission versus disease control). Model scenarios were co-designed with government, to fill evidence gaps prior to key decisions. RESULTS: Understanding outbreak risk following incursions was critical to eliminating community COVID-19 transmission. Analyses showed risk depended on whether the first detected case was the index case, a primary contact of the index case, or a 'mystery case'. There were benefits of early lockdown on first case detection and gradual easing of restrictions to minimise resurgence risk from undetected cases. As vaccination coverage increased and the focus shifted to controlling rather than eliminating community transmission, understanding health system demand was critical. Analyses showed that vaccines alone could not protect health systems and need to be complemented with other public health measures. CONCLUSIONS: Model evidence offered the greatest value when decisions needed to be made pre-emptively, or for questions that could not be answered with empiric data and data analysis alone. Co-designing scenarios with policy-makers ensured relevance and increased policy translation.

An MR fingerprinting approach for quantitative inhomogeneous magnetization transfer imaging.

PURPOSE: Magnetization transfer (MT) and inhomogeneous MT (ihMT) contrasts are used in MRI to provide information about macromolecular tissue content. In particular, MT is sensitive to macromolecules, and ihMT appears to be specific to myelinated tissue. This study proposes a technique to characterize MT and ihMT properties from a single acquisition, producing both semiquantitative contrast ratios and quantitative parameter maps. THEORY AND METHODS: Building on previous work that uses multiband RF pulses to efficiently generate ihMT contrast, we propose a cyclic steady-state approach that cycles between multiband and single-band pulses to boost the achieved contrast. Resultant time-variable signals are reminiscent of an MR fingerprinting acquisition, except that the signal fluctuations are entirely mediated by MT effects. A dictionary-based low-rank inversion method is used to reconstruct the resulting images and to produce both semiquantitative MT ratio and ihMT ratio maps, as well as quantitative parameter estimates corresponding to an ihMT tissue model. RESULTS: Phantom and in vivo brain data acquired at 1.5 Tesla demonstrate the expected contrast trends, with ihMT ratio maps showing contrast more specific to white matter, as has been reported by others. Quantitative estimation of semisolid fraction and dipolar T1 was also possible and yielded measurements consistent with literature values in the brain. CONCLUSION: By cycling between multiband and single-band pulses, an entirely MT-mediated fingerprinting method was demonstrated. This proof-of-concept approach can be used to generate semiquantitative maps and quantitatively estimate some macromolecular-specific tissue parameters.

Pharmacokinetic Profile of Incremental Oral Doses of Dietary Nitrate in Young and Older Adults: A Crossover Randomized Clinical Trial.

BACKGROUND: Dietary nitrate consumption can increase concentrations of nitrate and nitrite in blood, saliva, and urine. Whether the change in concentrations is influenced by age is currently unknown. OBJECTIVES: We aimed to measure changes in nitrate and nitrite concentrations in plasma, urine, and saliva and exhaled NO concentrations after single incremental doses of dietary nitrate in young and older healthy adults. METHODS: Twelve young (18-35 y old) and 12 older (60-75 y old) healthy, nonsmoking participants consumed single doses of 100 g, 200 g, 300 g whole beetroot (BR) and 1000 mg potassium nitrate (positive control) ≥7 d apart in a crossover, randomized clinical trial. Plasma nitrate and nitrite concentrations and exhaled NO concentrations were measured over a 5-h period. Salivary nitrate and nitrite concentrations were measured over a 12-h period and urinary nitrate over a 24-h period. Time, intervention, age, and interaction effects were measured with repeated-measures ANOVAs. RESULTS: Dose-dependent increases were seen in plasma, salivary, and urinary nitrate after BR ingestion (all P ≤ 0.002) but there were no differences between age groups at baseline (all P ≥ 0.56) or postintervention (all P ≥ 0.12). Plasma nitrite concentrations were higher in young than older participants at baseline (P = 0.04) and after consumption of 200 g (P = 0.04; +25.7 nmol/L; 95% CI: 0.97, 50.3 nmol/L) and 300 g BR (P = 0.02; +50.3 nmol/L; 95% CI: 8.57, 92.1 nmol/L). Baseline fractional exhaled NO (FeNO) concentrations were higher in the younger group [P = 0.03; +8.60 parts per billion (ppb); 95% CI: 0.80, 16.3 ppb], and rose significantly over the 5-h period, peaking 5 h after KNO3 consumption (39.4 ± 4.5 ppb; P < 0.001); however, changes in FeNO were not influenced by age (P = 0.276). CONCLUSIONS: BR is a source of bioavailable dietary nitrate in both young and older adults and can effectively raise nitrite and nitrate concentrations. Lower plasma nitrite and FeNO concentrations were found in older subjects, confirming the impact of ageing on NO bioavailability across different systems.This trial was registered at www.isrctn.com as ISRCTN86706442.

Capturing the real-world benefit of residual ß-cell function during clinically important time-periods in established Type 1 diabetes.

AIMS: Many individuals with type 1 diabetes retain residual ß-cell function, with increased endogenous insulin secretion associated with reduced hyperglycaemia, hypoglycaemia and glycaemic variability. However, it is unknown when these improvements occur during the day. Dysglycaemia is common in overnight and postprandial periods and associated with diabetes complications. Therefore, this study aimed to determine the influence of residual ß-cell function upon nocturnal and postprandial glycaemic control in established type 1 diabetes. METHODS: Under free-living conditions, 66 participants wore a blinded continuous glucose monitor (CGM), kept a food diary, and completed a stimulated urine C-peptide creatinine (UCPCR) test. Nocturnal, and postprandial CGM outcomes (participant means and discrete event analysis) were compared between UCPCR groups: undetectable (Cpepund ), low (Cpeplow : 0.001-0.19 nmol/mmol) and high (Cpephigh : ≥0.2 nmol/mmol). RESULTS: Greater ß-cell function was associated with incremental improvements in glycaemia. Cpephigh spent significantly greater time in normoglycaemia than Cpepund overnight (76 ± 20% vs. 58 ± 20%, p = 0.005) and 0-300 mins postprandially (68 ± 22% vs. 51 ± 22%, p = 0.045), while also having reducing nocturnal variability (SD 1.12 ± 0.41 vs. 1.52 ± 0.43 mmol/L, p = 0.010). Analysis of individual events, controlling for diabetes duration, BMI, basal insulin, use of a continuous or flash glucose monitor and (for postprandial) meal type, carbohydrate and bolus insulin intake, replicated the group findings, additionally demonstrating Cpepund had increased hyperglycaemia versus Cpeplow overnight and increased postprandial hypoglycaemic events compared with Cpephigh . For all participants, breakfast had a significantly higher incremental area under the curve than lunch and dinner. CONCLUSIONS: Residual ß-cell function is associated with improved nocturnal and postprandial glycaemic control. These data may be of clinical importance for identifying specific periods and individuals where further glycaemic management strategies would be beneficial.

Relative protein intake and associations with markers of physical function in those with type 2 diabetes.

AIMS: To examine the independent associations between relative protein intake (g kg-1  day 1 ) and markers of physical function in those with type 2 diabetes, while also comparing with current guidelines for protein intake. METHODS: This analysis reports data from the ongoing Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) study. Functional assessments included: Short Physical Performance Battery (SPPB), 60 s sit-to-stand (STS-60), 4-m gait speed, time to rise from a chair (×5) and handgrip strength. Participants also completed a self-reported 4 day diet diary. Regression analyses assessed whether relative protein intake was associated with markers of physical function. Interaction terms assessed whether the associations were modified by sex, age, HbA1c or body mass index (BMI). RESULTS: 413 participants were included (mean ± SD:age = 65.0 ± 7.7 years, 33% female, BMI = 30.6 ± 5.1 kg/m2 ). The average total protein intake was 0.88 ± 0.31 g kg-1  day-1 . 33% of individuals failed to meet the reference nutrient intake for the United Kingdom (≥0.75 g kg-1  day-1 ), and 87% for European recommendations (≥1.2 g kg-1  day-1 ). After adjustment, each 0.5 g/kg of protein intake was associated with an 18.9% (95% CI: 2.3, 35.5) higher SPPB score, 22.7% (1.1, 44.3) more repetitions in STS-60, 21.1% (4.5, 37.7) faster gait speed and 33.2% (16.9, 49.5) lower chair rise time. There were no associations with handgrip strength or any interactions. CONCLUSIONS: Relative protein intake was positively associated with physical function outcomes, even after consideration of total energy intake. As a number of individuals were below the current guidelines, protein intake may be a modifiable factor of importance for people with type 2 diabetes.

External support factors utilized by patients in coping with cancer: a European perspective.

PURPOSE: The article presents the results of research on psychosocial aspects of living with cancer in the Slovak Republic focusing on hospitalized and outpatient cancer patients in treatment during the curative stage of the disease. Assessing cancer patient's interest in receiving help from individual members of a multidisciplinary team was a part of the research. METHODS: The research was done through a questionnaire designed to focus on individual psychosocial aspects of cancer treatment. The research sample included 67 hospitalized patients and 61 outpatients. Execution of research was conducted in the individual clinical workplaces. RESULTS: When calculating the interest of cancer patients in spiritual counseling during oncological treatment, hospitalized patients indicated significant interest (p = .014). Similarly, hospitalized patients indicated more interest in using psychological counseling (p = .040) as well as in consultation with the social worker with a significant difference of (p = .017). Interest in the aid of a physical therapist was exhibited more significantly with hospitalized patients (p = .000). Significant interest in hospitalized patients using additional members of the multidisciplinary team was statistically significant (p = .017). Outpatient cancer patients indicated significant interest in finding information about medical conditions on the Internet (p = .000). For items addressing an interest in meeting people with cancer in self-help groups, there was no significant difference between outpatient and hospital patients (p = .298) as with talking to other patients who had cancer (p = .207). CONCLUSION: External support factors are important in helping patients cope with cancer. Health professionals can help patients mitigate the various difficulties associated with cancer.

Enhancing epidemiological surveillance of the emergence of the SARS-CoV-2 Omicron variant using spike gene target failure data, England, 15 November to 31 December 2021.

When SARS-CoV-2 Omicron emerged in 2021, S gene target failure enabled differentiation between Omicron and the dominant Delta variant. In England, where S gene target surveillance (SGTS) was already established, this led to rapid identification (within ca 3 days of sample collection) of possible Omicron cases, alongside real-time surveillance and modelling of Omicron growth. SGTS was key to public health action (including case identification and incident management), and we share applied insights on how and when to use SGTS.

Replace, amplify, transform: a qualitative study of how postgraduate trainees and supervisors experience and use telehealth for instruction in ambulatory patient care.

BACKGROUND: Little is known about using telehealth patient visits as an educational mode. Therefore, rapid implementation of telehealth during the COVID-19 pandemic had to be done without understanding how to optimize telehealth for education. With the likely sustained/post-pandemic use of telehealth in ambulatory patient care, filling gaps in our understanding of how telehealth can be used for instruction in this context is critical. This study sought to understand perceptions of pediatric postgraduate trainees and supervisors on the use of telehealth for instruction in ambulatory settings with the goal of identifying effective ways to enhance learning during telehealth visits. METHODS: In May-June of 2020, the authors purposefully sampled first- and third-year postgraduate trainees and supervising attendings from pediatric fellowship programs at one institution that implemented telehealth for instructional activities. They conducted semi-structured interviews; interviews lasted a median of 51 min (trainees) and 41 min (supervisors). They conducted interviews and data analysis iteratively until reaching saturation. Using thematic analysis, they created codes and constructed themes from coded data. They organized themes using the Replace-Amplify-Transform (RAT) model, which proposes that technology can replace in-person learning and/or amplify and transform learning. RESULTS: First-year trainees (n = 6), third-year trainees (n = 5) and supervisors (n = 6) initially used telehealth to replace in-person learning. However, skills that could be practiced in telehealth visits differed from in-person visits and instructional activities felt rushed or awkward. Trainees and supervisors adapted and used telehealth to amplify learning by enhancing observation and autonomy. They also transformed learning, using telehealth to develop novel skills. CONCLUSIONS: To harness telehealth for instructional activities, our findings indicated that trainees and supervisors should shift from using it as a direct replacement for in-person education to taking advantage of novel opportunities to amplify and transform education in PGME. The authors provide data-driven recommendations to help PGME trainees, supervisors and educators capitalize on the educational advantages of telehealth.