Research ethics and artificial intelligence for global health: perspectives from the global forum on bioethics in research.

BACKGROUND: The ethical governance of Artificial Intelligence (AI) in health care and public health continues to be an urgent issue for attention in policy, research, and practice. In this paper we report on central themes related to challenges and strategies for promoting ethics in research involving AI in global health, arising from the Global Forum on Bioethics in Research (GFBR), held in Cape Town, South Africa in November 2022. METHODS: The GFBR is an annual meeting organized by the World Health Organization and supported by the Wellcome Trust, the US National Institutes of Health, the UK Medical Research Council (MRC) and the South African MRC. The forum aims to bring together ethicists, researchers, policymakers, research ethics committee members and other actors to engage with challenges and opportunities specifically related to research ethics. In 2022 the focus of the GFBR was "Ethics of AI in Global Health Research". The forum consisted of 6 case study presentations, 16 governance presentations, and a series of small group and large group discussions. A total of 87 participants attended the forum from 31 countries around the world, representing disciplines of bioethics, AI, health policy, health professional practice, research funding, and bioinformatics. In this paper, we highlight central insights arising from GFBR 2022. RESULTS: We describe the significance of four thematic insights arising from the forum: (1) Appropriateness of building AI, (2) Transferability of AI systems, (3) Accountability for AI decision-making and outcomes, and (4) Individual consent. We then describe eight recommendations for governance leaders to enhance the ethical governance of AI in global health research, addressing issues such as AI impact assessments, environmental values, and fair partnerships. CONCLUSIONS: The 2022 Global Forum on Bioethics in Research illustrated several innovations in ethical governance of AI for global health research, as well as several areas in need of urgent attention internationally. This summary is intended to inform international and domestic efforts to strengthen research ethics and support the evolution of governance leadership to meet the demands of AI in global health research.

Clinical Outcomes of Renal Transplant Recipients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Clinical outcomes of patients with renal transplant (RT) undergoing percutaneous coronary intervention (PCI) remain poorly elucidated. METHOD: Between 2014 and 2021, data were analysed for the following three groups of patients undergoing PCI enrolled in a multicentre Australian registry: (1) RT recipients (n=226), (2) patients on dialysis (n=992), and (3) chronic kidney disease (CKD) patients (estimated glomerular filtration rate [eGFR], 30‒60 mL/min per 1.73 m2) without previous RT (n=15,534). Primary outcome was 30-day major adverse cardiac and cerebrovascular events (MACCEs)-composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularisation, and stroke. RESULTS: RT recipients were younger than dialysis and patients with CKD (61±10 vs 68±12 vs 78±8.2 years, p<0.001). Patients with RT less frequently had severe left ventricular dysfunction compared with dialysis and CKD groups (6.7% vs 14% and 8.5%); however more, often presented with acute coronary syndrome (58% vs 52% and 48%), especially STEMI (all p<0.001). Patients with RT and CKD had lower rates of 30-day MACCE (4.4% and 6.8% vs 11.6%, p<0.001) than the dialysis group. Three-year survival was similar between RT and CKD groups, however was lower in the dialysis group (80% and 83% vs 60%, p<0.001). After adjustment, dialysis was an independent predictor of 30-day MACCE (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.44‒2.50, p<0.001), however RT was not (OR 0.91, CI 0.42‒1.96, p=0.802). Both RT (hazard ratio [HR] 2.07, CI 1.46‒2.95, p<0.001) and dialysis (HR 1.35, CI 1.02‒1.80, p=0.036) heightened the hazard of long-term mortality. CONCLUSIONS: RT recipients have more favourable clinical outcomes following PCI compared with patients on dialysis. However, despite having similar short-term outcomes to patients with CKD, the hazard of long-term mortality is significantly greater for RT recipients.

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.

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.

Safety and efficacy of a reduced frequency viral monitoring strategy for Epstein-Barr virus, cytomegalovirus, and BK polyomavirus post-kidney transplant: A quality assurance initiative.

BACKGROUND: There is variability in recommended viral monitoring protocols after kidney transplant. In response to increased demand for laboratory testing during the COVID-19 pandemic, the Transplant Manitoba Adult Kidney Program updated its monitoring protocols for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and BK polyomavirus (BKV) to a reduced frequency. METHODS: This single-center nested case-control study evaluated 252 adult kidney transplant recipients transplanted from 2015 to 2021, with the updated protocols effective on March 19th 2020. Cases included recipients transplanted after the protocol update who developed CMV, EBV, and BKV DNAemia and were matched to controls with DNAemia transplanted prior to the protocol update. The primary outcome was the difference in maximum DNA load titers between cases and matched controls. Secondary outcomes included time to initial DNAemia detection and DNAemia clearance. Safety outcomes of tissue-invasive viral disease were described. RESULTS: There were 216 recipients transplanted preupdate and 36 recipients postupdate. There was no difference between cases and controls in maximum or first DNA load titers for EBV, CMV, or BKV. Cases experienced earlier EBV DNAemia detection (26 (IQR 8, 32) vs. 434 (IQR 96, 1184) days, p = .005). Median follow-up was significantly longer for recipients transplanted preupdate (4.3 vs. 1.3 years, p < .0001). After adjusting for follow-up time, there was no difference in DNAemia clearance or tissue-invasive viral disease. CONCLUSION: Our findings suggest that reduced frequency viral monitoring protocols may be safe and cost-effective. This quality assurance initiative should be extended to detect longer-term and tissue-invasive disease outcomes.

No-Reflow Prediction in Acute Coronary Syndrome During Percutaneous Coronary Intervention: The NORPACS Risk Score.

BACKGROUND: Suboptimal coronary reperfusion (no reflow) is common in acute coronary syndrome percutaneous coronary intervention (PCI) and is associated with poor outcomes. We aimed to develop and externally validate a clinical risk score for angiographic no reflow for use following angiography and before PCI. METHODS: We developed and externally validated a logistic regression model for prediction of no reflow among adult patients undergoing PCI for acute coronary syndrome using data from the Melbourne Interventional Group PCI registry (2005-2020; development cohort) and the British Cardiovascular Interventional Society PCI registry (2006-2020; external validation cohort). RESULTS: A total of 30 561 patients (mean age, 64.1 years; 24% women) were included in the Melbourne Interventional Group development cohort and 440 256 patients (mean age, 64.9 years; 27% women) in the British Cardiovascular Interventional Society external validation cohort. The primary outcome (no reflow) occurred in 4.1% (1249 patients) and 9.4% (41 222 patients) of the development and validation cohorts, respectively. From 33 candidate predictor variables, 6 final variables were selected by an adaptive least absolute shrinkage and selection operator regression model for inclusion (cardiogenic shock, ST-segment-elevation myocardial infarction with symptom onset >195 minutes pre-PCI, estimated stent length ≥20 mm, vessel diameter <2.5 mm, pre-PCI Thrombolysis in Myocardial Infarction flow <3, and lesion location). Model discrimination was very good (development C statistic, 0.808; validation C statistic, 0.741) with excellent calibration. Patients with a score of ≥8 points had a 22% and 27% risk of no reflow in the development and validation cohorts, respectively. CONCLUSIONS: The no-reflow prediction in acute coronary syndrome risk score is a simple count-based scoring system based on 6 parameters available before PCI to predict the risk of no reflow. This score could be useful in guiding preventative treatment and future trials.

A Methodological Study to Compare Alternative Modes of Administration with Value EQ-5D Using Preference-Elicitation Techniques.

OBJECTIVES: Time trade-off (TTO) and discrete choice experiment (DCE) preference-elicitation techniques can be administered using face-to-face interviews (F2F), unassisted online (UO) surveys, or remote-assisted (RA) interviews. The objective of this study was to explore how the mode of administration affects the quality and reliability of preference-elicitation data. METHODS: EQ-5D-5L health states were valued using composite TTO (cTTO) and DCE approaches by the UK general population. Participants were allocated to 1 of 2 study groups. Group A completed both F2F and UO surveys (n = 271), and group B completed both RA and UO surveys (n = 223). The feasibility of survey completion and the reliability and face-validity of data collected were compared across all modes of administration. RESULTS: Fewer participants reported receiving sufficient guidance on the cTTO tasks during the UO survey compared with the 2 assisted modes. Participants across all modes typically reported receiving sufficient guidance on the DCE tasks. cTTO data were less reliable from the UO survey compared with both assisted modes, but there were no differences in DCE data reliability. cTTO data from all modes demonstrated face-validity; however, the UO survey produced higher utilities for moderate and severe health states than both assisted modes. Both F2F and RA modes provided comparably reliable data. CONCLUSIONS: The reliability of DCE data is not affected by the mode of administration. Interviewer-assisted modes of administration (F2F or RA) yield more reliable cTTO data than unassisted surveys. Both F2F and RA surveys produced similar-quality data.

The Political Economy of Digital Health Equity: Structural Analysis.

Digital technologies have produced many innovations in care delivery and enabled continuity of care for many people when in-person care was impossible. However, a growing body of research suggests that digital health can also exacerbate health inequities for those excluded from its benefits for reasons of cost, digital literacy, and structural discrimination related to characteristics such as age, race, ethnicity, and socioeconomic status. In this paper, we draw on a political economy perspective to examine structural barriers to progress in advancing digital health equity at the policy level. Considering the incentive structures and investments of powerful actors in the field, we outline how characteristics of neoliberal capitalism in Western contexts produce and sustain digital health inequities by describing 6 structural challenges to the effort to promote health equity through digital health, as follows: (1) the revenue-first incentives of technology corporations, (2) the influence of venture capital, (3) inequitable access to the internet and digital devices, (4) underinvestment in digital health literacy, (5) uncertainty about future reimbursement of digital health, and (6) justified mistrust of digital health. Building on these important challenges, we propose future immediate and long-term directions for work to support meaningful change for digital health equity.

Twelve Weeks of Progressive Resistance Training Positively Improves Physical Fitness and Golf Swing Performance in Talented Youth Golfers.

ABSTRACT: Shaw, J, Gould, ZI, Oliver, JL, and Lloyd, RS. Twelve weeks of progressive resistance training positively improves physical fitness and golf swing performance in talented youth golfers. J Strength Cond Res XX(X): 000-000, 2024-This aim of this study was to investigate the effects of a 12-week resistance training program in talented junior golfers. Eighteen talented youth golfers were pair matched by maturity status and handicap, and subsequently allocated to an experimental (EXP) or control group. During the 12-week intervention, both groups continued with their normal golf practice while the EXP group also completed a progressive twice-weekly resistance training program. At baseline, subjects performed multiple trials of an isometric midthigh pull (IMTP), countermovement jump (CMJ), standing long jump, golf movement screen (GMS), and isometric plank hold. Club head speed (CHS) and carry distance for a 6-iron and driver were also measured using a commercial launch monitor. When controlled for maturity offset, there were significant (p < 0.05) interaction effects in favor of the EXP group for absolute (g = 1.29) and relative (g = 2.06) peak force for the IMTP, CMJ absolute (g = 0.73) and relative (g = 0.66) peak power, jump height (g = 1.05), modified reactive strength index (g = 1.30), lateral (g = 0.48-0.88) and horizontal jump distance (g = 1.20), and GMS total score (g = 1.07). Significant interaction effects were also reported in 6-iron and driver CHS and carry distance in favor of the EXP group (p < 0.05; g = 0.41-1.64). These findings indicate that twice-weekly resistance training in combination with regular golf practice can stimulate increases in measures of strength, power, and movement competency in youth golfers, which should contribute to enhanced golf swing performance.

Preventing severe hypoglycemia in adults with type 2 diabetes (PHT2): Design, delivery and evaluation framework for a randomized controlled trial.

BACKGROUND: Severe hypoglycemia is a common and feared complication of medications used to lower blood glucose levels in individuals with diabetes. Psychoeducational interventions can prevent severe hypoglycemia in individuals with type 1 diabetes (T1D). We aim to determine the effectiveness of this approach among adults with type 2 diabetes (T2D) at elevated risk for severe hypoglycemia. METHODS: Preventing Hypoglycemia in Type 2 diabetes (PHT2) is a two-arm, parallel, randomized controlled trial. Participants are eligible if they are adults with T2D receiving care at an integrated group practice in Washington state and have experienced one or more episodes of severe hypoglycemia in the prior 12 months or have impaired awareness of hypoglycemia (Gold score ≥ 4). Participants are randomized to proactive nurse care management with or without my hypo compass, an evidence-based, psychoeducational intervention combining group and individual self-management training. For this study, my hypo compass was adapted to be suitable for adults with T2D and from an in-person to a virtual intervention over videoconference and telephone. The primary outcome is any self-reported severe hypoglycemia in the 12 months following the start of the intervention. Secondary outcomes include biochemical measures of hypoglycemia, self-reported hypoglycemia awareness, fear of hypoglycemia, and emergency department visits and hospitalizations for severe hypoglycemia. The study includes a process evaluation to assess implementation fidelity and clarify the causal pathway. CONCLUSION: The PHT2 trial will compare the effectiveness of two approaches for reducing severe hypoglycemia in adults with T2D. TRIAL REGISTRATION: clinicaltrials.gov, # NCT04863872.

Administering selected subscales of patient-reported outcome questionnaires to reduce patient burden and increase relevance: a position statement on a modular approach.

Patient-reported outcome (PRO) questionnaires considered in this paper contain multiple subscales, although not all subscales are equally relevant for administration in all target patient populations. A group of measurement experts, developers, license holders, and other scientific-, regulatory-, payer-, and patient-focused stakeholders participated in a panel to discuss the benefits and challenges of a modular approach, defined here as administering a subset of subscales out of a multi-scaled PRO measure. This paper supports the position that it is acceptable, and sometimes preferable, to take a modular approach when administering PRO questionnaires, provided that certain conditions have been met and a rigorous selection process performed. Based on the experiences and perspectives of all stakeholders, using a modular approach can reduce patient burden and increase the relevancy of the items administered, and thereby improve measurement precision and eliminate wasted data without sacrificing the scientific validity and utility of the instrument. The panelists agreed that implementing a modular approach is not expected to have a meaningful impact on item responses, subscale scores, variability, reliability, validity, and effect size estimates; however, collecting additional evidence for the impact of context may be desirable. It is also important to recognize that adequate rationale and evidence (e.g., of fit-for-purpose status and relevance to patients) and a robust consensus process that includes patient perspectives are required to inform selection of subscales, as in any other measurement circumstance, is expected. We believe that the considerations discussed within (content validity, administration context, and psychometric factors) are relevant across multiple therapeutic areas.

A Review of Meaningful Change Thresholds for EORTC QLQ-C30 and FACT-G Within Oncology.

OBJECTIVES: This literature review provides an overview of meaningful change thresholds for the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and the Functional Assessment of Cancer Therapy - General (FACT-G) used across hematological cancers and solid tumors (melanoma, lung, bladder, and prostate). METHODS: Embase, MEDLINE, and PubMed were searched to identify relevant oncology publications from 2016 to 2021. Label claims from the US Food and Drug Administration and the European Medicines Agency for 7 recently approved drugs (pembrolizumab, atezolizumab, glasdegib, gilteritinib, tisagenlecleucel, axicabtagene ciloleucel, and daratumumab plus hyaluronidase-fihj) were reviewed. RESULTS: Publications providing guidance on meaningful change thresholds for the QLQ-C30 displayed a growing trend away from broad "legacy" thresholds of 10 points for all QLQ-C30 scales), toward deriving "contemporary" thresholds (eg, subscale specific, population specific). Contemporary publications generally provide guidance on selecting thresholds for specific scales that account for improved or worsening thresholds (eg, QLQ-C30 subscales). This trend was not clear for FACT-G, with less new guidance available. Most clinical trials used in regulatory label submissions have used thresholds of 10 points for the QLQ-C30 subscales and 3 to 7 points for the FACT-G total score. Despite the availability of more recent guidelines, contemporary meaningful change thresholds seem slow to emerge in the published literature and regulatory labels. CONCLUSIONS: Trialists should consider using contemporary thresholds, rather than legacy thresholds, for QLQ-C30 endpoints. Thresholds derived for a similar patient-population should be used where available. Further work is required to provide these across a broader range of cancer sites.

Modelling Health State Utilities as a Transformation of Time to Death in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: When utilities are analyzed by time to death (TTD), this has historically been implemented by 'grouping' observations as discrete time periods to create health state utilities. We extended the approach to use continuous functions, avoiding assumptions around groupings. The resulting models were used to test the concept with data from different regions and different country tariffs. METHODS: Five-year follow-up in advanced non-small cell lung cancer (NSCLC) was used to fit six continuous TTD models using generalized estimating equations, which were compared with progression-based utilities and previously published TTD groupings. Sensitivity analyses were performed using only patients with a confirmed death, the last year of life only, and artificially censoring data at 24 months. The statistically best-fitting model was then applied to data subsets by region and different EQ-5D-3L country tariffs. RESULTS: Continuous (natural) [Formula: see text] and [Formula: see text] models outperformed other continuous models, grouped TTD, and progression-based models in statistical fit (mean absolute error and Quasi Information Criterion). This held through sensitivity and scenario analyses. The pattern of reduced utility as a patient approaches death was consistent across regions and EQ-5D tariffs using the preferred [Formula: see text] model. CONCLUSIONS: The use of continuous models provides a statistically better fit than TTD groupings, without the need for strong assumptions about the health states experienced by patients. Where a TTD approach is merited for use in modelling, continuous functions should be considered, with the scope for further improvements in statistical fit by both widening the number of candidate models tested and the therapeutic areas investigated.

Assessing the Content Validity of Preference-Based Measures in Cancer.

OBJECTIVES: This study assessed the content validity of generic and condition-specific preference-based measures (PBMs) with patients treated for cancer, evaluated against 10 Consensus-Based Standards for the Selection of Health Measurement Instruments criteria for good content validity, to best inform measurement strategies regarding the use of PBMs in oncology development programs and real-world applications. METHODS: Individual, semistructured interviews were conducted with patients who received drug treatment for cancer in the United Kingdom (n = 47) and the United States (n = 49). During the interview, patients completed 3 generic PBMs (EQ-5D-5L, EuroQol Health and Wellbeing measure-Short Form, Château Santé Base) and 2 condition-specific PBMs (Quality of Life Utility-Core 10 Dimension, Functional Assessment of Cancer Therapy Eight Dimension [FACT-8D]). Interviews were conducted via teleconference, audio recorded, and transcribed verbatim. Transcripts were coded using thematic and content analysis methods. RESULTS: Condition-specific measures were evaluated as having better relevancy than generic PBMs. Overall, the FACT-8D was evaluated as holding the best content validity in terms of relevancy, and the EuroQol Health and Wellbeing measure-Short Form received the most favorable evaluation of relevancy for generic PBMs. All measures demonstrated comparable comprehensiveness, with all suggested by patients to be missing concepts. The EQ-5D-5L was evaluated best in terms of comprehensibility. This was followed by the Quality of Life Utility-Core 10 Dimension and FACT-8D; both received similar evaluations. CONCLUSIONS: All measures were generally seen by patients as adequate in capturing appropriate aspects of health-related quality of life for measuring cancer outcomes, although together condition-specific measures were evaluated as having better relevancy than generic PBMs. Further health-related quality of life instrument development is encouraged, particularly with regard to the longer-term detrimental impacts of cancer and treatment side effects. Other developments could include new cancer-specific tools inclusive of conventional health items, treatment impacts, and psychological items.

The Influence of Using Novel Predictive Technologies on Judgments of Stigma, Empathy, and Compassion among Healthcare Professionals.

BACKGROUND: Our objective was to evaluate whether the description of a machine learning (ML) app or brain imaging technology to predict the onset of schizophrenia or alcohol use disorder (AUD) influences healthcare professionals' judgments of stigma, empathy, and compassion. METHODS: We randomized healthcare professionals (N = 310) to one vignette about a person whose clinician seeks to predict schizophrenia or an AUD, using a ML app, brain imaging, or a psychosocial assessment. Participants used scales to measure their judgments of stigma, empathy, and compassion. RESULTS: Participants randomized to the ML vignette endorsed less anger and more fear relative to the psychosocial vignette, and the brain imaging vignette elicited higher pity ratings. The brain imaging and ML vignettes evoked lower personal responsibility judgments compared to the psychosocial vignette. Physicians and nurses reported less empathy than clinical psychologists. CONCLUSIONS: The use of predictive technologies may reinforce essentialist views about mental health and substance use that may increase specific aspects of stigma and reduce others.

Novel therapeutic targets and emerging treatments for atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality worldwide. Even with excellent control of low-density lipoprotein cholesterol (LDL-C) levels, adverse cardiovascular events remain a significant clinical problem worldwide, including among those without any traditional ASCVD risk factors. It is necessary to identify novel sources of residual risk and to develop targeted strategies that address them. Lipoprotein(a) has become increasingly recognized as a new cardiovascular risk determinant. Large-scale clinical trials have also signalled the potential additive cardiovascular benefits of decreasing triglycerides beyond lowering LDL-C levels. Since CANTOS (Anti-inflammatory Therapy with Canakinumab for Atherosclerotic Disease) demonstrated that antibodies against interleukin-1ß may decrease recurrent cardiovascular events in secondary prevention, various anti-inflammatory medications used for rheumatic conditions and new monoclonal antibody therapeutics have undergone rigorous evaluation. These data build towards a paradigm shift in secondary ASCVD prevention, underscoring the value of targeting multiple biological pathways in the management of both lipid levels and systemic inflammation. Evolving knowledge of the immune system, and the gut microbiota may result in opportunities for modifying previously unrecognized sources of residual inflammatory risk. This review provides an overview of novel therapeutic targets for ASCVD and emerging treatments with a focus on mechanisms, efficacy, and safety.

Hypoglycaemia symptom frequency, severity, burden, and utility among adults with type 1 diabetes and impaired awareness of hypoglycaemia: Baseline and 24-week findings from the HypoCOMPaSS study.

AIMS: To determine the frequency, severity, burden, and utility of hypoglycaemia symptoms among adults with type 1 diabetes (T1D) and impaired awareness of hypoglycaemia (IAH) at baseline and week 24 following the HypoCOMPaSS awareness restoration intervention. METHODS: Adults (N = 96) with T1D (duration: 29 ± 12 years; 64% women) and IAH completed the Hypoglycaemia Burden Questionnaire (HypoB-Q), assessing experience of 20 pre-specified hypoglycaemia symptoms, at baseline and week 24. RESULTS: At baseline, 93 (97%) participants experienced at least one symptom (mean ± SD 10.6 ± 4.6 symptoms). The proportion recognising each specific symptom ranged from 15% to 83%. At 24 weeks, symptom severity and burden appear reduced, and utility increased. CONCLUSIONS: Adults with T1D and IAH experience a range of hypoglycaemia symptoms. Perceptions of symptom burden or utility are malleable. Although larger scale studies are needed to confirm, these findings suggest that changing the salience of the symptomatic response may be more important in recovering protection from hypoglycaemia through regained awareness than intensifying symptom frequency or severity.