A senescence-mimicking (senomimetic) VEGFR TKI side-effect primes tumor immune responses via IFN/STING signaling.

Tyrosine kinase inhibitors (TKIs) that block the vascular endothelial growth factor receptors (VEGFRs) disrupt tumor angiogenesis but also have many unexpected side-effects that impact tumor cells directly. This includes the induction of molecular markers associated with senescence, a form of cellular aging that typically involves growth arrest. We have shown that VEGFR TKIs can hijack these aging programs by transiently inducting senescence-markers (SMs) in tumor cells to activate senescence-associated secretory programs that fuel drug resistance. Here we show that these same senescence-mimicking ('senomimetic') VEGFR TKI effects drive an enhanced immunogenic signaling that, in turn, can alter tumor response to immunotherapy. Using a live-cell sorting method to detect beta-galactosidase, a commonly used SM, we found that subpopulations of SM-expressing (SM+) tumor cells have heightened interferon (IFN) signaling and increased expression of IFN-stimulated genes (ISGs). These ISG increases were under the control of the STimulator of INterferon Gene (STING) signaling pathway, which we found could be directly activated by several VEGFR TKIs. TKI-induced SM+ cells could stimulate or suppress CD8 T-cell activation depending on host:tumor cell contact while tumors grown from SM+ cells were more sensitive to PD-L1 inhibition in vivo, suggesting that offsetting immune-suppressive functions of SM+ cells can improve TKI efficacy overall. Our findings may explain why some (but not all) VEGFR TKIs improve outcomes when combined with immunotherapy and suggest that exploiting senomimetic drug side-effects may help identify TKIs that uniquely 'prime' tumors for enhanced sensitivity to PD-L1 targeted agents.

The effectiveness of evidence-based healthcare educational interventions on healthcare professionals' knowledge, skills, attitudes, professional practice and healthcare outcomes: Systematic review and meta-analysis.

OBJECTIVE: The primary aim of this systematic review is to assess the effectiveness of evidence-based healthcare (EBHC) educational interventions on healthcare professionals' knowledge, skills, attitudes, behaviour of EBHC, clinical process and care outcomes. A secondary aim of the review is to assess the effects of important pedagogical moderating factors for EBHC educational interventions. METHOD: This systematic review used a forward and backward citation search strategy on the Web of Science platform (date of inception to 28 April 2023). Only randomised controlled trials (RCTs) and cluster RCTs which compared EBHC educational interventions for healthcare professionals were included. A random effects meta-analysis was undertaken for EBHC compared with an active and nonactive control for all outcomes. RESULTS: Sixty-one RCTs were identified which included a total of 5208 healthcare professionals. There was a large effect for EBHC educational interventions compared with waiting list/no treatment/sham control on knowledge (SMD, 2.69; 95% CI, 1.26-4.14, GRADE Low), skills (SMD, 0.88; 95% CI, 0.25-1.73, Very Low Certainty), attitude (SMD, 0.81; 95% CI, 0.16-1.47, Very Low Certainty) and behaviour of EBHC (SMD, 0.82; 95% CI, 0.25-1.40, Very Low Certainty). Over time the effect of EBHC educational interventions substantially decreased with no evidence of effect at 6 months for any outcome except behaviour (SMD,1.72; 95% CI, 0.74-2.71, Low Certainty). There was some evidence that blended learning, active learning and consistency in the individual delivering the intervention may be important positive moderating factors. CONCLUSION: These findings suggest that EBHC educational interventions may have a large short-term effect on improving healthcare professionals' knowledge, skills, attitude and behaviour of EBHC. These effects may be longer-lasting regarding EBHC behaviour. In terms of pedagogy, blended learning, active learning, and consistency of the individual delivering the intervention may be important positive moderating factors.

What do States Recommend We Teach Adolescents about Sexual Consent? A Content Analysis of K-12 Health Education Standards in the US.

Although universities in the US commonly implement sexual consent education programs for students that focus on understanding how to communicate sexual consent, it remains unclear to what extent sexual consent education is taking place in grades K-12. The goal of this study was to assess K-12 health education standards recommendations for sexual consent education. We conducted a content analysis of health education standards from 43 states in the US to evaluate the guidelines provided to health educators across different grade levels. Using inductive and deductive coding, we identified six themes related to sexual consent. These themes were: 1) defining sexual consent, 2) explaining the legal standard of sexual consent, 3) defining personal space, 4) promoting healthy decision-making, 5) emphasizing good communication skills, and 6) defining healthy relationships. Fewer states directly focused on sexual consent education; instead, they provided information that could indirectly relate to consent, such as discussions on relationships and personal space. Across grade levels, topics related to sexual consent became more prevalent as adolescents progressed through school. While many states' health standards do not explicitly discuss sexual consent, they may implicitly address consent through other topics. Educators and policymakers should advocate for more explicit and detailed education on sexual consent in the K-12 school system. This could help increase the number of students educated on sexual consent before entering higher education, potentially reducing rates of sexual violence, and promoting healthier sexual behaviors and attitudes.

Pilot evaluation of a behavioral weight loss program for adults with physical disabilities: State of Slim Everybody usability and feasibility.

Background: People with physical disabilities (PWD) have a higher prevalence of obesity than populations without disability, but most evidence-based weight loss programs have not included this population. The State of Slim (SOS) program is an evidence-based weight loss program that has demonstrated success in producing weight loss in populations without disability, but it has not been adapted for or evaluated in PWD. Methods: The SOS program was systematically adapted using the evidence-informed Guidelines, Recommendations, and Adaptations Including Disability (GRAIDs) framework. A total of 35 participants enrolled in the State of Slim Everybody program. The program was offered entirely online. Body weight, attendance, and food log completion were also tracked weekly. The program length was 16.5 h and included weekly group instruction, with optional one-on-one sessions provided upon request. Following completion, participants completed post-evaluation surveys on overall satisfaction with the program. The primary outcomes were program effectiveness (i.e., body weight), usability, and feasibility. Results: Thirty-two out of 35 participants completed the program, representing a retention rate of 91.4%. Average weight loss was 10.9% (9.9 ± 0.7 kg (t (31) = -13.3, p =< 0.0001)). On a 1 (dissatisfied/completely useless) to 5 (very satisfied/completely helpful) Likert scale, the average score for overall program satisfaction was 4.8 ± 0.1 and program helpfulness 4.6 ± 0.1. Conclusion: The State of Slim Everybody program demonstrated significant weight loss and good usability and feasibility in PWD. Existing adaptation frameworks can be used to create inclusive health promotion programs for adults with physical disabilities.

Commentary on packing vs non-packing of pilonidal sinus cavities after incision and drainage.

Pilonidal sinus disease (PSD) manifests as an inflammatory skin condition typically emerging within the anal cleft. The prevalence of this disease varies in high income countries. This disease is associated with significant physical and psychosocial distress. Surgery is an option for managing PSD; yet, surgical methods vary, and a universally accepted gold standard approach is lacking, leading to current practices that are diverse and subject to ongoing debate. One such point of contention revolves around the decision to use packing or opt for a non-packing approach following surgery. Mohamedahmed et al (2021) conducted a systematic review to evaluate the comparative outcomes of packing versus non-packing of an abscess cavity following incision and drainage of cutaneous abscess on any part of the body. This commentary aims to critically appraise the methods used within the review by Mohamedahmed et al (2021) and expand upon the findings in the context of treatment and management of PSD.

Should carbohydrate-modified diets be the first option for weight loss in people with impaired glucose metabolism? A scoping review.

While the "precision nutrition" movement is at an early stage of development, several investigations have compared low-fat versus carbohydrate (CHO)-modified diets (i.e., low-or-reduced-CHO, low glycemic index/load diets, and high-fiber) in people with normal versus impaired glucose metabolism. The purpose of this scoping review was to summarize evidence in support of the hypothesis that CHO-modified diets are more effective for weight loss among people with impaired glucose metabolism. Fifteen articles were included in this review: seven retrospective analyses of randomized clinical trials and eight prospective randomized clinical trials with prespecified hypotheses related to a diet (low-fat vs. CHO-modified) × phenotype (normal vs. impaired) interaction. Evidence in support of the hypothesis was identified in six of seven retrospective and three of eight prospective studies, which led to a recommendation of CHO-modified diets as a first-line option for people with impaired glucose metabolism. However, the evidence in support of this recommendation is relatively weak, and dietary prescriptions should consider additional contextual information that may influence overall dietary adherence. Additional and rigorous research using innovative randomized experimental approaches is needed for stronger dietary weight loss recommendations based on pretreatment glycemic status.

Pain and diet: A summary of the evidence for the role of diet modification in chronic pain.

Chronic pain constitutes a significant burden to patients and healthcare systems. For many patients, the only option is to attempt to manage their pain within their daily lives. Here, we review evidence provided by three systematic reviews for the effect of diet and diet supplements on patients' experience of chronic pain.

Competency Framework for Podiatric Medicine Training: A Validation Report Based on an Adapted E-Delphi Across Canada.

OBJECTIVES: Competency-based medical education has been introduced into many health professional curricula. Based on CanMEDs, a framework has recently been developed for podiatric medicine education in Canada. This study aimed to validate the framework through a consensus of various podiatric medicine experts across Canada. METHODS: An adapted Delphi method was used for content validation. Two structured online questionnaires were used to gather expert opinions and agreement on the roles and core competencies described in the framework previously developed. The validation consensus threshold was set at a minimum of 80% agreement. The summary of comments and suggestions was used to reformulate certain items after the research team reached a consensus. RESULTS: Out of the 51 experts invited from the Canadian Podiatric Medicine Association, 19 completed the first-round questionnaire (mean podiatric experience = 24.5 years; standard deviation 17.6). After the first round, "Podiatric Expert", "Communicator" and "Scholar" roles have been modified. After these modifications, a consensus was obtained at the second round completed by 13 experts. Overall, 95% of the experts agreed that the competency framework was relevant even if some indicators would need to be adapted to suit the requirements of each province and territory. CONCLUSION: This validated framework supports the excellence and the quality of our podiatric educational program. It also promotes the adoption of a uniform education of podiatrists in Canada and worldwide.

Weight history of individuals with and without physical disability in the International Weight Control Registry.

Background: People with physical disabilities (PWD) have an increased risk of obesity and related comorbidities compared with people without physical disabilities (PWoD). Previously identified contributors to weight loss maintenance pose challenges to PWD. However, it is not known if PWD experience less success in weight management. Methods: Six hundred and nine participants in the International Weight Control Registry (IWCR) were eligible for this analysis (PWD, n = 174; PWoD, n = 435). Self-reported weight history metrics were compared using general linear models. Perceived weight history category was compared using Chi-squared tests. Importance of diet and physical activity strategies for weight management were compared using Wilcoxon rank-signed tests. Results: PWD reported higher current body mass index (BMI) (36.1 ± 0.7 vs. 31.0 ± 0.5; p < 0.0001) and more weight loss attempts (9.1 ± 0.7 vs. 7.1 ± 0.4; p = 0.01) than PWoD. Current weight loss percentage (PWD 13.0 ± 1.0; PWoD, 13.0 ± 0.6; p = 0.97) and weight loss category (χ 2 [3, N = 609] = 2.9057, p = 0.41) did not differ between the groups. There were no differences in any weight strategy between PWD who were successful and those who regained. Conclusions: PWD and PWoD in the IWCR achieved similar levels of weight maintenance success. However, higher BMI and more weight loss attempts suggest that PWD may face challenges with weight management. More research is needed to identify strategies leading to success for PWD.

Long-term follow-up of torpedo maculopathy: a case series and mini-review.

BACKGROUND: Torpedo maculopathy (TM) is a rare, congenital condition characterized by an oval-shaped, chorioretinal lesion in the temporal macula of unknown etiology. To our knowledge, the longest reported follow-up of TM is 5 years. Herein we report 10 years of follow-up on two patients with TM to further characterize the long-term natural history of the condition. CASE REPORTS: Two patients with torpedo maculopathy were examined at baseline and then again at 5 years and 10 years from baseline. Eyes were evaluated using color fundus photography, automated perimetry, fundus autofluorescence and spectral domain optical coherence tomography. Visual function of both patients remained stable throughout the observation period. In case 1, there was no evidence of change in lesion morphology over the 10 year observation period. Case 2 showed progression of cystic degeneration of the neurosensory retina within the torpedo lesion. Case 1 reported a history of supernumerary teeth and underwent gene sequence with deletion/duplication analyses of the APC gene but no clinically significant variants were detected. CONCLUSIONS: Our findings support the position that TM is a nonprogressive condition with long-term stability of visual function. Genetic analysis of case 1 failed to detect any association with Gardner syndrome.

Improving risk models for patients having emergency bowel cancer surgery using linked electronic health records: a national cohort study.

BACKGROUND: Life-saving emergency major resection of colorectal cancer (CRC) is a high-risk procedure. Accurate prediction of postoperative mortality for patients undergoing this procedure is essential for both healthcare performance monitoring and preoperative risk assessment. Risk-adjustment models for CRC patients often include patient and tumour characteristics, widely available in cancer registries and audits. The authors investigated to what extent inclusion of additional physiological and surgical measures, available through linkage or additional data collection, improves accuracy of risk models. METHODS: Linked, routinely-collected data on patients undergoing emergency CRC surgery in England between December 2016 and November 2019 were used to develop a risk model for 90-day mortality. Backwards selection identified a 'selected model' of physiological and surgical measures in addition to patient and tumour characteristics. Model performance was assessed compared to a 'basic model' including only patient and tumour characteristics. Missing data was multiply imputed. RESULTS: Eight hundred forty-six of 10 578 (8.0%) patients died within 90 days of surgery. The selected model included seven preoperative physiological and surgical measures (pulse rate, systolic blood pressure, breathlessness, sodium, urea, albumin, and predicted peritoneal soiling), in addition to the 10 patient and tumour characteristics in the basic model (calendar year of surgery, age, sex, ASA grade, TNM T stage, TNM N stage, TNM M stage, cancer site, number of comorbidities, and emergency admission). The selected model had considerably better discrimination compared to the basic model (C-statistic: 0.824 versus 0.783, respectively). CONCLUSION: Linkage of disease-specific and treatment-specific datasets allowed the inclusion of physiological and surgical measures in a risk model alongside patient and tumour characteristics, which improves the accuracy of the prediction of the mortality risk for CRC patients having emergency surgery. This improvement will allow more accurate performance monitoring of healthcare providers and enhance clinical care planning.

Reliability and Validity of the International Physical Activity Questionnaire Adapted to Include Adults With Physical Disability.

BACKGROUND: People with physical disabilities (PWD) participate in less physical activity than people without physical disabilities (PWoD), which increases the risk for several negative health consequences. Comparing physical activity between PWD and PWoD remains a challenge since no reliable and valid survey exists to measure physical activity in both populations. The International Physical Activity Questionnaire (IPAQ) was adapted to be inclusive of PWD using a recently developed survey adaption framework; however, the adapted IPAQ has not been assessed for reliability and validity. The objective of this study was to assess the reliability and validity of the adapted IPAQ. METHODS: To assess test-retest reliability, the adapted IPAQ was completed twice within a 72-hour period by 172 individuals (PWD: n = 102, PWoD: n = 70) and compared using intraclass correlation coefficients. Using Spearman rho, convergent validity and construct validity were assessed in 62 individuals by comparing the adapted IPAQ against the original instrument and activity monitor measured step count, respectively. RESULTS: The adapted IPAQ demonstrated moderate test-retest reliability, with intraclass correlation coefficients of total scores for the total sample of .690 (95% confidence interval [CI] .581-.770) and among subgroup analysis (PWD, .640, 95% CI, .457-.761; PWoD, .758, 95% CI, .610-.850). Correlation coefficients were also good for the assessment of convergent validity of total score (.727; 95% CI, .579-.829; P < .001). Construct validity assessment yielded moderate coefficient (.406; 95% CI, .166-.596; P = .001). CONCLUSIONS: The adapted IPAQ demonstrated acceptable reliability and validity and is appropriate for use in PWD and PWoD.

Methods for using Bing's AI-powered search engine for data extraction for a systematic review.

Data extraction is a time-consuming and resource-intensive task in the systematic review process. Natural language processing (NLP) artificial intelligence (AI) techniques have the potential to automate data extraction saving time and resources, accelerating the review process, and enhancing the quality and reliability of extracted data. In this paper, we propose a method for using Bing AI and Microsoft Edge as a second reviewer to verify and enhance data items first extracted by a single human reviewer. We describe a worked example of the steps involved in instructing the Bing AI Chat tool to extract study characteristics as data items from a PDF document into a table so that they can be compared with data extracted manually. We show that this technique may provide an additional verification process for data extraction where there are limited resources available or for novice reviewers. However, it should not be seen as a replacement to already established and validated double independent data extraction methods without further evaluation and verification. Use of AI techniques for data extraction in systematic reviews should be transparently and accurately described in reports. Future research should focus on the accuracy, efficiency, completeness, and user experience of using Bing AI for data extraction compared with traditional methods using two or more reviewers independently.

Optimizing Virtual Health Technologies Through a Performance-based Readiness Model: Lessons From the Field Deployment of National Emergency Tele-Critical Care Network.

INTRODUCTION: The advancement of the Army's National Emergency Tele-Critical Care Network (NETCCN) and planned evolution to an Intelligent Medical System rest on a digital transformation characterized by the application of analytic rigor anchored and machine learning.The goal is an enduring capability for telecritical care in support of the Nation's warfighters and, more broadly, for emergency response, crisis management, and mass casualty situations as the number and intensity of disasters increase nationwide. That said, technology alone is unlikely to solve the most pressing issues in operational medicine and combat casualty care. MATERIALS AND METHODS: A total performance system (TPS) creates opportunities to address vulnerabilities and overcome barriers to success. As applied during the NETCCN project, the TPS captures the best performance-centric information and know-how, increasing the potential to save lives, improve readiness, and accomplish missions. RESULTS: The purpose of this project was to apply a performance-based readiness model to aid in the evaluation of Army telehealth technologies. Through various user-facing surveys, polls, and reporting techniques, the project aimed to measure the perceived value of telehealth technologies within a sample of the project team member population. By providing a detailed approach to the collection of lessons learned, researchers were able to determine the importance of information and methods versus a focus on technology alone. The use of an emoji-based feedback assessment indicated that most lessons learned were helpful to the project team. CONCLUSIONS: Through the NETCCN TPS, we have been able to address product-related measures, knowledge of product efficacy, project metrics, and many implementation considerations that can be further investigated by setting and engagement type. Through the Technology in Disaster Environments learning accelerator, it was possible to rapidly acquire, process, organize, and disseminate best practices and learnings in near real time, providing a critical feedback and improvement loop.

Cognitive frailty in older adults with diabetes: prevalence and risk factors.

In older adults living with diabetes, there is a higher prevalence of frailty and a greater risk of cognitive impairment. Cognitive frailty is defined by the presence of both and is associated with an increased risk of mortality. A systematic review was undertaken to estimate the prevalence of cognitive frailty in community-dwelling older adults living with diabetes and associated risk factors. This commentary critically appraises the review and explores the implications of the findings for community practice.

Raising the U.S. Army Height-Weight (Body Mass Index) Standards: Quantifying Metabolic Risk.

BACKGROUND & OBJECTIVES: The U.S. Army fell 25% short of its recruitment goal in 2022 and therefore, increasing the eligibility pool for potential recruits is of interest. Raising the body mass index (BMI) standards for eligibility presents a path to increase the recruitable population; however, there may be additional costs incurred due to attendant health risks that may be present in individuals with higher BMI. METHODS: We filtered the 2017-2020 National Health and Nutrition Examination Survey by age (17-25 years) and BMI (up to 30 kg/m2). A k-means cluster analysis was performed on the filtered dataset for the variables used to determine metabolic syndrome. Metabolic syndrome Clusters were characterized through summary statistics and compared over clinical measurements and questionnaire responses. RESULTS: Five distinct clusters were identified and mean BMI in two clusters (Clusters1 and 3) exceeded the current U.S. Army BMI thresholds. Of these two clusters, Cluster 1 members had metabolic syndrome. Cluster 3 members were at higher risk for metabolic syndrome compared to members of Clusters 2, 4, and 5. Mean waist circumference was slightly lower in Cluster 3 compared to Cluster 1. None of the clusters had significant differences in depression scores, poverty index, or frequency of dental visits. CONCLUSIONS: Potential recruits from Cluster 1 have excessive health risk and may incur substantial cost to the U.S. Army if enlisted. However, potential recruits from Cluster 3 appear to add little risk and offer an opportunity to increase the pool for recruiting.

Advancing pressure ulcer prevention: evaluating the impact of patient and lay carer education.

Decubitus ulcers, also known as bed ulcers or pressure ulcers, result from prolonged pressure on the skin, with contributing factors such as shear forces, friction and excessive moisture. Pressure ulcers have significant physical, social and psychological consequences for patients and impose a substantial financial burden on healthcare providers. Patient and caregiver education has been suggested as a potential approach for preventing pressure ulcers. In order to investigate the potential preventive impact, O'Connor et al (2021) conducted a Cochrane systematic review. Their study aimed to assess the effectiveness of educational interventions for patients and caregivers in preventing pressure ulcers. This commentary aims to critically appraise the methods used within the Cochrane systematic review by O'Connor et al (2022) and expand on the findings in the context of clinical practice.

Wound cleansing and care in treating leg ulcers: a commentary on a Cochrane systematic review.

Leg ulcers pose a significant challenge to healthcare services, requiring effective wound cleansing strategies to promote healing and prevent complications. Large amounts of nursing time is spent managing patients with venous leg ulcers (VLUs), with an average appointment time of approximately 30 minutes. Yet, there is a lack of clear guidance for the treatment of VLUs, with nurses adopting a wide range of cleansing practices. This commentary provides an overview of existing evidence on wound cleansing and care in treating leg ulcers, for the benefit of healthcare professionals working within clinical practice.

Effectiveness of mobility training for frail older adults living in the community.

Frailty in older adults is a major health concern for individuals, families and society. Increasing physical activity helps to reduce frailty in older adults and improve health outcomes. Mobility is also essential to independence and well-being in older adults. A systematic review was undertaken to explore the impact of mobility training on older persons living with frailty in the community. This commentary critically appraises the review and explores the implications for practice.