Inclusion of Individuals With Lived Experiences in the Development of a Digital Intervention for Co-Occurring Depression and Cannabis Use: Mixed Methods Investigation.

BACKGROUND: Existing interventions for co-occurring depression and cannabis use often do not treat both disorders simultaneously and can result in higher rates of symptom relapse. Traditional in-person interventions are often difficult to obtain due to financial and time limitations, which may further prevent individuals with co-occurring depression and cannabis use from receiving adequate treatment. Digital interventions can increase the scalability and accessibility for these individuals, but few digital interventions exist to treat both disorders simultaneously. Targeting transdiagnostic processes of these disorders with a digital intervention-specifically positive valence system dysfunction-may yield improved access and outcomes. OBJECTIVE: Recent research has highlighted a need for the inclusion of individuals with lived experiences to assist in the co-design of interventions to enhance scalability and relevance of an intervention. Thus, the purpose of this study is to describe the process of eliciting feedback from individuals with elevated depressed symptoms and cannabis use and co-designing a digital intervention, Amplification of Positivity-Cannabis Use Disorder (AMP-C), focused on improving positive valence system dysfunction in these disorders. METHODS: Ten individuals who endorsed moderate to severe depressive symptoms and regular cannabis use (2-3×/week) were recruited online via Meta ads. Using a mixed methods approach, participants completed a 1-hour mixed methods interview over Zoom (Zoom Technologies Inc) where they gave their feedback and suggestions for the development of a mental health app, based on an existing treatment targeting positive valence system dysfunction, for depressive symptoms and cannabis use. The qualitative approach allowed for a broader investigation of participants' wants and needs regarding the engagement and scalability of AMP-C, and the quantitative approach allowed for specific ratings of intervention components to be potentially included. RESULTS: Participants perceived the 13 different components of AMP-C as overall helpful (mean 3.9-4.4, SD 0.5-1.1) and interesting (mean 4.0-4.9, SD 0.3-1.1) on a scale from 1 (not at all) to 5 (extremely). They gave qualitative feedback for increasing engagement in the app, including adding a social component, using notifications, and being able to track their symptoms and progress over time. CONCLUSIONS: This study highlights the importance of including individuals with lived experiences in the development of interventions, including digital interventions. This inclusion resulted in valuable feedback and suggestions for improving the proposed digital intervention targeting the positive valence system, AMP-C, to better match the wants and needs of individuals with depressive symptoms and cannabis use.

Network Analysis to Visualize Qualitative Results: Example From a Qualitative Content Analysis of The National Child Abuse Hotline.

Data visualization, such as figures created through network analysis, may be one way to present more complete information from qualitative analysis. Segments of qualitatively coded data can be treated as objects in network analysis, thus creating visual representations of the code frequency (i.e., nodes) and the co-occurrence (i.e., edges). By sharing an example of network analysis applied to qualitative data, and then comparing our process with other applications, our goal is to help other researchers reflect on how this approach may support their interpretation and visualization of qualitative data. A total of 265 de-identified transcripts between help-seekers and National Child Abuse Hotline crisis counselors were included in the network analysis. Post-conversation surveys, including help-seekers' perceptions of the conversations, were also included in the analysis. Qualitative content analysis was conducted, which was quantified as the presence or absence of each code within a transcript. Then, we divided the dataset based on help-seekers' perceptions. Individuals who responded that they "Yes/Maybe" felt more hopeful after the conversation were in the "hopeful" dataset, while those who answered "No" were in the "unhopeful" dataset. This information was imported to UCINET to create co-occurrence matrices. Gephi was used to visualize the network. Overall, code co-occurrence networks in hopeful conversations were denser. Furthermore, the average degree was higher in these hopeful conversations, suggesting more codes were consistently present. Codes in hopeful conversations included information, counselor support, and problem-solving. Conversely, non-hopeful conversations focused on information. Overall, network analysis revealed patterns that were not evident through traditional qualitative analysis.

Fracture Risk Prediction Using the Fracture Risk Assessment Tool in Individuals With Cancer.

Importance: The Fracture Risk Assessment Tool (FRAX) is a fracture risk prediction tool for 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Whether FRAX is useful in individuals with cancer is uncertain. Objective: To determine the performance of FRAX for predicting incident fractures in individuals with cancer. Design, Setting, and Participants: This retrospective population-based cohort study included residents of Manitoba, Canada, with and without cancer diagnoses from 1987 to 2014. Diagnoses were identified through the Manitoba Cancer Registry. Incident fractures to March 31, 2021, were identified in population-based health care data. Data analysis occurred between January and March 2023. Main Outcomes and Measures: FRAX scores were computed for those with bone mineral density (BMD) results that were recorded in the Manitoba BMD Registry. Results: This study included 9877 individuals with cancer (mean [SD] age, 67.1 [11.2] years; 8693 [88.0%] female) and 45 877 individuals in the noncancer cohort (mean [SD] age, 66.2 [10.2] years; 41 656 [90.8%] female). Compared to individuals without cancer, those with cancer had higher rates of incident MOF (14.5 vs 12.9 per 1000 person-years; P < .001) and hip fracture (4.2 vs 3.5 per 1000 person-years; P = .002). In the cancer cohort, FRAX with BMD results were associated with incident MOF (HR per SD increase, 1.84 [95% CI, 1.74-1.95]) and hip fracture (HR per SD increase, 3.61 [95% CI, 3.13-4.15]). In the cancer cohort, calibration slopes for FRAX with BMD were 1.03 for MOFs and 0.97 for hip fractures. Conclusions and Relevance: In this retrospective cohort study, FRAX with BMD showed good stratification and calibration for predicting incident fractures in patients with cancer. These results suggest that FRAX with BMD can be a reliable tool for predicting incident fractures in individuals with cancer.

Reduced cardiovascular and metabolic responses during eccentric stepping exercise: A pilot study.

This study compared cardiovascular and metabolic responses during concentric and eccentric stepping. Eight participants (5 m, 3f; 22 ± 2 years) performed maximal concentric and eccentric ramp incremental tests on a modified stepping ergometer. Subsequently, three randomized 15-min constant-power tests were performed (1) concentric stepping at 90% of the concentric lactate threshold (LT), (2) eccentric stepping at the same power, and (3) eccentric stepping at the same oxygen uptake (V̇O2). At equivalent power (36 ± 6 W, p = 0.62), eccentric stepping resulted in 46 ± 8% lower V̇O2, 16 ± 6% lower heart rate (HR), and 11 ± 5% lower mean arterial blood pressure compared to concentric (p < 0.01). Matching V̇O2 required 65 ± 19% more power during eccentric stepping (p < 0.01). During this test, eccentric V̇O2 and HR continued to increase, resulting in a 22 ± 29% higher V̇O2 and 19 ± 16% higher HR in the final minute (p < 0.001). Reduced cardiorespiratory demand during eccentric stepping at the same power as concentric demonstrates a higher eccentric power is required to produce the same V̇O2. However, despite being below the concentric LT, eccentric V̇O2 and HR continued to increase past the predicted steady state, indicating a higher exercise intensity.

Sensorimotor control of functional joint stability: Scientific concepts, clinical considerations, and the articuloneuromuscular cascade paradigm in peripheral joint injury.

Human movement depends on sensorimotor control. Sensorimotor control refers to central nervous system (CNS) control of joint stability, posture, and movement, all of which are effected via the sensorimotor system. Given the nervous, muscular, and skeletal systems function as an integrated "neuromusculoskeletal system" for the purpose of executing movement, musculoskeletal conditions can result in a cascade of impairments that affect negatively all three systems. The purpose of this article is to revisit concepts in joint stability, sensorimotor control of functional joint stability (FJS), joint instability, and sensorimotor impairments contributing to functional joint instability. This article differs from historical work because it updates previous models of joint injury and joint instability by incorporating more recent research on CNS factors, skeletal muscle factors, and tendon factors. The new 'articuloneuromuscular cascade paradigm' presented here offers a framework for facilitating further investigation into physiological and biomechanical consequences of joint injury and, in turn, how these follow on to affect physical activity (functional) capability. Here, the term 'injury' represents traumatic joint injury with a focus is on peripheral joint injury. Understanding the configuration of the sensorimotor system and the cascade of post-injury sensorimotor impairments is particularly important for clinicians reasoning rational interventions for patients with mechanical instability and functional instability. Concurrently, neurocognitive processing and neurocognitive performance are also addressed relative to feedforward neuromuscular control of FJS. This article offers itself as an educational resource and scientific asset to contribute to the ongoing research and applied practice journey for developing optimal peripheral joint injury rehabilitation strategies.

Cost-effectiveness intervention thresholds for romosozumab and teriparatide in the treatment of osteoporosis in the UK.

Sequential romosozumab-to-alendronate or sequential teriparatide-to-alendronate can be a cost-effective treatment option for postmenopausal women at very high risk of fracture. PURPOSE: To estimate the 10-year probability of a major osteoporotic fracture (MOF) at which sequential treatment with romosozumab or teriparatide followed by alendronate, compared with alendronate alone, becomes cost-effective in a UK setting. METHODS: A microsimulation model with a Markov structure was used to simulate fractures, costs, and quality-adjusted life years (QALYs), in women receiving sequential treatment with either romosozumab or teriparatide followed by alendronate, compared with alendronate alone. Patients aged 50 to 90 years with a recent MOF, hip or spine fracture were followed from the start of a 5-year treatment until the age of 100 years or death. The analysis had a healthcare perspective. Efficacy of romosozumab, teriparatide and alendronate was derived from phase III randomised controlled trials. Resource use and unit costs were derived from the literature. Cost-effectiveness intervention threshold (CEIT), defined as the 10-year probability of a major osteoporotic fracture at which treatment becomes cost-effective, was compared with clinically appropriate intervention thresholds for bone-forming treatment in women with very high fracture risk as recommended by the UK National Osteoporosis Guideline Group (NOGG). RESULTS: The base case analysis showed that sequential romosozumab-to-alendronate treatment was cost-effective from a 10-year MOF probability of 18-35% and above depending on age and site of sentinel fracture at a willingness to pay (WTP) of £30,000. For teriparatide-to-alendronate, treatment was cost-effective at a 10-year MOF probability of 27-57%. The results were sensitive to pricing of the drugs but relatively insensitive to treatment duration, romosozumab persistence assumptions, and site of sentinel fracture. The CEITs for romosozumab-to-alendronate treatment were lower than the clinical thresholds from the age of 70 years meaning that treatment could be considered both cost-effective and aligned with the NOGG treatment guidelines. By contrast, for teriparatide-to-alendronate the CEITs were higher than the clinical thresholds irrespective of age. However, cost-effective scenarios were found in the presence of strong clinical risk factors in addition to a recent sentinel fracture. CONCLUSION: The results of this study indicate that sequential romosozumab-to-alendronate or teriparatide-to-alendronate treatment can be a cost-effective treatment option for postmenopausal women at very high risk of fracture.

Global wastewater surveillance for pathogens with pandemic potential: opportunities and challenges.

Wastewater surveillance holds great promise as a sensitive method to detect spillover of zoonotic infections and early pandemic emergence, thereby informing risk mitigation and public health response. Known viruses with pandemic potential are shed in human stool or urine, or both, and the experiences with SARS-CoV-2, monkeypox virus, and Zika virus highlight the feasibility of community-based wastewater surveillance for pandemic viruses that have different transmission routes. We reviewed human shedding and wastewater surveillance data for prototype viruses representing viral families of concern to estimate the likely sensitivity of wastewater surveillance compared with that of clinical surveillance. We examined how data on wastewater surveillance detection, together with viral genetic sequences and animal faecal biomarkers, could be used to identify spillover infections or early human transmission and adaptation. The opportunities and challenges associated with global wastewater surveillance for the prevention of pandemics are described in this Personal View, focusing on low-income and middle-income countries, where the risk of pandemic emergence is the highest. We propose a research and public health agenda to ensure an equitable and sustainable solution to these challenges.

Cardiac Troponin to Adjudicate Subclinical Heart Failure in Diabetic Patients and a Murine Model of Metabolic Syndrome.

BACKGROUND: Cardiovascular disease, kidney health, and metabolic disease (CKM) syndrome is associated with significant morbidity and mortality, particularly from congestive heart failure (CHF). Guidelines recommend measurement of cardiac troponin (cTn) to identify subclinical heart failure (HF) in diabetics/CKM. However, appropriate thresholds and the impact from routine screening have not been elucidated. METHODS: cTnI was assessed using the Abbott high sensitivity (hs)-cTnI assay in outpatients with physician-ordered hemoglobin A1c (Hb A1c) and associated with cardiac comorbidities/diagnoses, demographics, and estimated glomerular filtration rate (eGFR). Risk thresholds used in CKM staging guidelines of >10 and >12 ng/L for females and males, respectively, were used. Multivariate logistic regression was applied. hs-cTnI was assessed in a high-fat-diet induced murine model of obesity and diabetes. RESULTS: Of 1304 patients, 8.0% females and 15.7% males had cTnI concentrations above the risk thresholds. Thirty-one (4.2%) females and 23 (4.1%) males had cTnI above the sex-specific 99% upper reference limit. A correlation between hs-cTnI and Hb A1c (R = 0.2) and eGFR (R = -0.5) was observed. hs-cTnI concentrations increased stepwise based on A1C of <5.7% (median = 1.5, IQR:1.3-1.8), 5.7%-6.4% (2.1, 2.0-2.4), 6.5%-8.0% (2.8, 2.5-3.2), and >8% (2.8, 2.2-4.3). Male sex (P < 0.001), eGFR (P < 0.001), and CHF (P = 0.004) predicted elevated hs-cTnI. Obese and diabetic mice had increased hs-cTnI (7.3 ng/L, 4.2-10.4) relative to chow-fed mice (2.6 ng/L, 1.3-3.8). CONCLUSION: A high proportion of outpatients with diabetes meet criteria for subclinical HF using hs-cTnI measurements. Glucose control is independently associated with elevated cTnI, a finding replicated in a murine model of metabolic syndrome.

On the basis of sex and sleep: the influence of the estrous cycle and sex on sleep-wake behavior.

The recurrent hormonal fluctuations within reproductive cycles impact sleep-wake behavior in women and in rats and mice used in preclinical models of sleep research. Strides have been made in sleep-related clinical trials to include equal numbers of women; however, the inclusion of female rodents in neuroscience and sleep research is lacking. Female animals are commonly omitted from studies over concerns of the effect of estrus cycle hormones on measured outcomes. This review highlights the estrous cycle's broad effects on sleep-wake behavior: from changes in sleep macroarchitecture to regionally specific alterations in neural oscillations. These changes are largely driven by cycle-dependent ovarian hormonal fluctuations occurring during proestrus and estrus that modulate neural circuits regulating sleep-wake behavior. Removal of estrous cycle influence by ovariectomy ablates characteristic sleep changes. Further, sex differences in sleep are present between gonadally intact females and males. Removal of reproductive hormones via gonadectomy in both sexes mitigates some, but not all sex differences. We examine the extent to which reproductive hormones and sex chromosomes contribute to sex differences in sleep-wake behavior. Finally, this review addresses the limitations in our understanding of the estrous cycle's impact on sleep-wake behavior, gaps in female sleep research that are well studied in males, and the implications that ignoring the estrous cycle has on studies of sleep-related processes.

Tumor suppressor heterozygosity and homologous recombination deficiency mediate resistance to front-line therapy in breast cancer.

The co-occurrence of germline and somatic oncogenic alterations is frequently observed in breast cancer, but their combined biologic and clinical significance has not been evaluated. To assess the role of germline-somatic interactions on outcomes in routine practice, we developed an integrated clinicogenomic pipeline to analyze the genomes of over 4,500 patients with breast cancer. We find that germline (g) BRCA2 -associated tumors are enriched for RB1 loss-of-function mutations and manifest poor outcomes on standard-of-care, front-line CDK4/6 inhibitor (CDK4/6i) combinations. Amongst these tumors, g BRCA2 -related homologous recombination deficiency (HRD) as well as baseline RB1 LOH status promote acquisition of RB1 loss-of- function mutations under the selective pressure of CDK4/6i, causing therapy resistance. These findings suggest an alternative therapeutic strategy using sequential targeting of HRD in g BRCA- associated breast cancers through PARP inhibitors prior to CDK4/6i therapy to intercept deleterious RB1 -loss trajectories and thus suppress the emergence of CDK4/6 inhibitor resistance. More broadly, our findings demonstrate how germline-somatic driven genomic configurations shape response to systemic therapy and can be exploited therapeutically as part of biomarker-directed clinical strategies.

Rapid synthesis and screening of natively paired antibodies against influenza hemagglutinin stem via oPool+ display.

Antibody discovery is crucial for developing therapeutics and vaccines as well as understanding adaptive immunity. However, the lack of approaches to synthesize antibodies with defined sequences in a high-throughput manner represents a major bottleneck in antibody discovery. Here, we presented oPool+ display, which combines oligo pool synthesis and mRNA display to construct and characterize many natively paired antibodies in parallel. As a proof-of-concept, we applied oPool+ display to rapidly screen the binding activity of >300 natively paired influenza hemagglutinin (HA) antibodies against the conserved HA stem domain. Structural analysis of 16.ND.92, one of the identified HA stem antibodies, revealed a unique binding mode distinct from other known broadly neutralizing HA stem antibodies with convergent sequence features. Yet, despite such differences, 16.ND.92 remained broadly reactive and conferred in vivo protection. Overall, this study not only established an experimental platform that can be applied in both research and therapeutics to accelerate antibody discovery, but also provides molecular insights into antibody responses to the influenza HA stem, which is a major target for universal influenza vaccine development.

Updated practice guideline for dual-energy X-ray absorptiometry (DXA).

The introduction of dual-energy X-ray absorptiometry (DXA) technology in the 1980s revolutionized the diagnosis, management and monitoring of osteoporosis, providing a clinical tool which is now available worldwide. However, DXA measurements are influenced by many technical factors, including the quality control procedures for the instrument, positioning of the patient, and approach to analysis. Reporting of DXA results may be confounded by factors such as selection of reference ranges for T-scores and Z-scores, as well as inadequate knowledge of current standards for interpretation. These points are addressed at length in many international guidelines but are not always easily assimilated by practising clinicians and technicians. Our aim in this report is to identify key elements pertaining to the use of DXA in clinical practice, considering both technical and clinical aspects. Here, we discuss technical aspects of DXA procedures, approaches to interpretation and integration into clinical practice, and the use of non-bone mineral density measurements, such as a vertebral fracture assessment, in clinical risk assessment.

L5-S1 facet joint pathology in pelvic ring injuries.

BACKGROUND: The authors believe that the L5-S1 facet joint injury in the setting of pelvic fractures is underappreciated by orthopedic traumatologists. The purpose of this study was to draw attention to the L5/S1 facet joint in the setting of pelvic ring injuries. METHODS: This was a retrospective comparative study of all patients greater than or equal to 18 years of age with an acute pelvic ring injury (AO/OTA 62 B to C) presenting to a single level I trauma center. The primary objective was to determine demographic and injury characteristics associated with L5-S1 facet joint injuries in patients with pelvic ring injuries. The secondary objective was to determine the proportion of L5-S1 facet joint injuries that were missed on initial radiographic workup. RESULTS: There were 476 patients included in the analysis, 53 (11.1%) of whom had an L5-S1 facet joint injury. Patients with an L5-S1 injury were more likely to be younger (44.1 vs. 53.2 years, p = 0.001) and experience a high energy mechanism of injury (95.0% vs. 78.0%, p = 0.002). Certain injury patterns were associated with L5-S1 facet joint injuries: any sacral fracture (96.2% vs. 73.8%, p < 0.001), Denis zone 2 fractures (43.4% vs. 20.1%, p < 0.001), Denis zone 3 fractures (34.0% vs. 4.7%, p < 0.001), bilateral displaced sacral fractures (18.9% vs. 3.5%, p < 0.001), and L5 transverse process fractures (64.2% vs. 18.0%, p < 0.001). Only 16.0% of radiology reports identified an L5-S1 injury. CONCLUSIONS: Orthopedic traumatologists should scrutinize imaging for L5-S1 facet joint injuries in the presence of pelvic ring injuries, especially in patients with certain sacral fracture patterns.

Learning curves for adoption of robotic bariatric surgery: a systematic review of safety, efficiency and clinical outcomes.

Robotic bariatric surgery may overcome challenges associated with laparoscopy, potentially achieving technically superior results. This review aims to summarise current literature reporting on learning curves for surgeons newly adopting robotic bariatrics and implications for safety, efficiency and outcomes. A systematic review was performed in line with the PRISMA guidelines. Electronic databases PubMed and MEDLINE were searched and articles reporting on learning curves in robotic bariatric surgery were identified. Studies that reported changes in outcome over time, or learning curves for surgeons newly adopting robotic bariatric surgery were included in this review. Eleven studies reporting on 1237 patients were included in this review. Most surgeons reported prior bariatric surgical experience. Differences were noted regarding the approach and adoption of robotics. Ten studies found significant reduction in operative time, with the shortest learning curve of 11 cases. Reporting of clinical outcomes was limited. Three studies reported statistically significant improvement in outcomes after the learning curve. Long-term outcomes were in line with current literature, though none assessed differences between learning curve groups. Reported learning curves in robotic bariatric surgery is variable, with limited reporting of clinical outcomes. With appropriate mentorship, surgeons can improve efficiency, safety and clinical outcomes, maximising the benefits of minimally invasive surgery.

Developing an exercise intervention to minimise hip bone mineral density loss following traumatic lower limb amputation: a Delphi study.

OBJECTIVE: To elicit expert opinion and gain consensus on specific exercise intervention parameters to minimise hip bone mineral density (BMD) loss following traumatic lower limb amputation. METHODS: In three Delphi rounds, statements were presented to a panel of 13 experts from six countries. Experts were identified through publications or clinical expertise. Round 1 involved participants rating their agreement with 22 exercise prescription statements regarding BMD loss post amputation using a 5-point Likert scale. Agreement was deemed as 3-4 on the scale (agree/strongly agree). Statements of <50% agreement were excluded. Round 2 repeated remaining statements alongside round 1 feedback. Round 3 allowed reflection on round 2 responses considering group findings and the chance to change or maintain the resp onse. Round 3 statements reaching ≥70% agreement were defined as consensus. RESULTS: All 13 experts completed rounds 1, 2 and 3 (100% completion). Round 1 excluded 12 statements and added 1 statement (11 statements for rounds 2-3). Round 3 reached consensus on nine statements to guide future exercise interventions. Experts agreed that exercise interventions should be performed at least 2 days per week for a minimum of 6 months, including at least three different resistance exercises at an intensity of 8-12 repetitions. Interventions should include weight-bearing and multiplanar exercises, involve high-impact activities and be supervised initially. CONCLUSION: This expert Delphi process achieved consensus on nine items related to exercise prescription to minimise hip BMD loss following traumatic lower limb amputation. These recommendations should be tested in future interventional trials.

Validating, Implementing, and Monitoring Machine Learning Solutions in the Clinical Laboratory Safely and Effectively.

BACKGROUND: Machine learning solutions offer tremendous promise for improving clinical and laboratory operations in pathology. Proof-of-concept descriptions of these approaches have become commonplace in laboratory medicine literature, but only a scant few of these have been implemented within clinical laboratories, owing to the often substantial barriers in validating, implementing, and monitoring these applications in practice. This mini-review aims to highlight the key considerations in each of these steps. CONTENT: Effective and responsible applications of machine learning in clinical laboratories require robust validation prior to implementation. A comprehensive validation study involves a critical evaluation of study design, data engineering and interoperability, target label definition, metric selection, generalizability and applicability assessment, algorithmic fairness, and explainability. While the main text highlights these concepts in broad strokes, a supplementary code walk-through is also provided to facilitate a more practical understanding of these topics using a real-world classification task example, the detection of saline-contaminated chemistry panels.Following validation, the laboratorian's role is far from over. Implementing machine learning solutions requires an interdisciplinary effort across several roles in an organization. We highlight the key roles, responsibilities, and terminologies for successfully deploying a validated solution into a live production environment. Finally, the implemented solution must be routinely monitored for signs of performance degradation and updated if necessary. SUMMARY: This mini-review aims to bridge the gap between theory and practice by highlighting key concepts in validation, implementation, and monitoring machine learning solutions effectively and responsibly in the clinical laboratory.

Thrombosed persistent median artery in a medical sonographer.

The use of gray-scale and color Doppler ultrasound as a first-line imaging modality for wrist pain can be advantageous, especially in cases of clinically suspected carpal tunnel syndrome. This report presents the case of a medical sonographer who exhibited acute wrist pain secondary to a thrombosed persistent median artery after excessive stress loading on her scanningwrist. Ultrasound is able to easily diagnose this rare condition, which may at times be associated with carpal tunnel symptoms due to mass effect from the expanded aberrant artery.

Predictive Performance of Cardiovascular Risk Scores in Cancer Survivors From the UK Biobank.

Background: Cardiovascular preventive strategies are guided by risk scores with unknown validity in cancer cohorts. Objectives: This study aimed to evaluate the predictive performance of 7 established cardiovascular risk scores in cancer survivors from the UK Biobank. Methods: The predictive performance of QRISK3, Systematic Coronary Risk Evaluation 2 (SCORE2)/Systematic Coronary Risk Evaluation for Older Persons (SCORE-OP), Framingham Risk Score, Pooled Cohort equations to Prevent Heart Failure (PCP-HF), CHARGE-AF, QStroke, and CHA2DS2-VASc was calculated in participants with and without a history of cancer. Participants were propensity matched on age, sex, deprivation, health behaviors, family history, and metabolic conditions. Analyses were stratified into any cancer, breast, lung, prostate, brain/central nervous system, hematologic malignancies, Hodgkin lymphoma, and non-Hodgkin lymphoma. Incident cardiovascular events were tracked through health record linkage over 10 years of follow-up. The area under the receiver operating curve, balanced accuracy, and sensitivity were reported. Results: The analysis included 31,534 cancer survivors and 126,136 covariate-matched controls. Risk score distributions were near identical in cases and controls. Participants with any cancer had a significantly higher incidence of all cardiovascular outcomes than matched controls. Performance metrics were significantly worse for all risk scores in cancer cases than in matched controls. The most notable differences were among participants with a history of hematologic malignancies who had significantly higher outcome rates and poorer risk score performance than their matched controls. The performance of risk scores for predicting stroke in participants with brain/central nervous system cancer was very poor, with predictive accuracy more than 30% lower than noncancer controls. Conclusions: Existing cardiovascular risk scores have significantly worse predictive accuracy in cancer survivors compared with noncancer comparators, leading to an underestimation of risk in this cohort.