Functional Diversity of Memory CD8 T Cells is Spatiotemporally Imprinted.

Tissue-resident memory CD8 T cells (TRM) kill infected cells and recruit additional immune cells to limit pathogen invasion at barrier sites. Small intestinal (SI) TRM cells consist of distinct subpopulations with higher expression of effector molecules or greater memory potential. We hypothesized that occupancy of diverse anatomical niches imprints these distinct TRM transcriptional programs. We leveraged human samples and a murine model of acute systemic viral infection to profile the location and transcriptome of pathogen-specific TRM cell differentiation at single-transcript resolution. We developed computational approaches to capture cellular locations along three anatomical axes of the small intestine and to visualize the spatiotemporal distribution of cell types and gene expression. TRM populations were spatially segregated: with more effector- and memory-like TRM preferentially localized at the villus tip or crypt, respectively. Modeling ligand-receptor activity revealed patterns of key cellular interactions and cytokine signaling pathways that initiate and maintain TRM differentiation and functional diversity, including different TGFß sources. Alterations in the cellular networks induced by loss of TGFßRII expression revealed a model consistent with TGFß promoting progressive TRM maturation towards the villus tip. Ultimately, we have developed a framework for the study of immune cell interactions with the spectrum of tissue cell types, revealing that T cell location and functional state are fundamentally intertwined.

CAR T-cell Therapy for Diffuse Large B-cell Lymphoma in Canada: A Cost-Utility Analysis.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is a novel cell therapy for treating non-Hodgkin lymphoma. The development of CAR T-cell therapy has transformed oncology treatment by offering a potential cure. However, due to the high cost of these therapies, and the large number of eligible patients, decision makers are faced with difficult funding decisions. Our objective was to assess the cost-effectiveness of tisagenlecleucel for adults with relapsed/refractory diffuse large B-cell lymphoma in Canada using updated survival data from the recent JULIET trial. METHODS: We developed an individual-simulated discrete event simulation model to assess the costs and quality-adjusted life-years (QALY) of tisagenlecleucel compared with salvage chemotherapy. Survival estimates were obtained from a published clinical trial and retrospective analysis. If patients remained progression free for 5 y, they were assumed to be in long-term remission. Costing and utility data were obtained from reports and published sources. A Canadian health care payer perspective was used, and outcomes were modeled over a lifetime horizon. Costs and outcomes were discounted at 1.5% annually, with costs reported in 2021 Canadian dollars. A probabilistic analysis was used, and model parameters were varied in 1-way sensitivity analyses and scenario analyses. RESULTS: After we incorporated the latest clinical evidence, tisagenlecleucel led to an additional cost of $503,417 and additional effectiveness of 2.48 QALYs, with an incremental cost-effectiveness ratio of $202,991 compared with salvage chemotherapy. At a willingness-to-pay threshold of $100,000/QALY, tisagenlecleucel had a 0% likelihood of being cost-effective. CONCLUSIONS: At the current drug price, tisagenlecleucel was not found to be a cost-effective option. These results heavily depend on assumptions regarding long-term survival and the price of CAR T. Real-world evidence is needed to reduce uncertainty. HIGHLIGHTS: For patients with diffuse large B-cell lymphoma who failed 2 or more lines of systemic therapy, CAR T was not found to be a cost-effective treatment option at a willingness-to-pay threshold of $100,000.These results heavily depend on the expected long-term survival. The uncertainty in the model may be improved using real-world evidence reported in the future.

Health utilities in adults with hemophilia A: A retrospective cohort study.

INTRODUCTION: Haemophilia A negatively affects a patient's quality of life. There is a limited amount of health utility data (a measure of health-related quality of life) available for patients with haemophilia A. This information is crucial for cost-effectiveness analysis for haemophilia A treatment. OBJECTIVES: The goal of this project is to elicit the health utilities and factors impacting utility values for haemophilia A patients in Canada. METHODS: This is a population-based, cross-sectional, retrospective study of health utilities in patients with haemophilia A using Patient Report Outcomes Burdens and Experiences (PROBE) components from the Canadian Bleeding Disorders Registry (CBDR). A review of the mean utilities for three severity states, defined by clotting factor VIII level, was completed. A multiple linear regression analysis was completed to examine the determinants of health utilities including age, treatment type, chronic pain status, number of limited joints, and bleed rate. RESULTS: The average utility values (and standard deviations) for patients with haemophilia A in Canada are .79(.17), .76(.20), and .77(.19) for patients with severe, moderate, and mild haemophilia. The regression showed chronic pain status and the number of additional comorbidities as major significant factors (p-value < .001) in haemophilia A utility. Haemophilia severity was shown to be a major factor with smaller p-value (p-value < .05). CONCLUSIONS: Haemophilia A patients have lower utility than the general population. Chronic pain was shown to be a significant, major factor in health-related quality of life. Our study is essential for valuing health outcomes in haemophilia A-related cost-effectiveness analysis.

Impact of new direct-acting antiviral therapy on the prevalence and undiagnosed proportion of chronic hepatitis C infection.

BACKGROUND: Patients with chronic hepatitis C (CHC) can be cured with the new highly effective interferon-free combination treatments (DAA) that were approved in 2014. However, CHC is a largely silent disease, and many individuals are unaware of their infections until the late stages of the disease. The impact of wider access to effective treatments and improved awareness of the disease on the number of infections and the number of patients who remain undiagnosed is not known in Canada. Such evidence can guide the development of strategies and interventions to reduce the burden of CHC and meet World Health Organization's (WHO) 2030 elimination targets. The purpose of this study is to use a back-calculation framework informed by provincial population-level health administrative data to estimate the prevalence of CHC and the proportion of cases that remain undiagnosed in the three most populated provinces in Canada: British Columbia (BC), Ontario and Quebec. METHODS: We have conducted a population-based retrospective analysis of health administrative data for the three provinces to generate the annual incidence of newly diagnosed CHC cases, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and HCV treatment initiations. For each province, the data were stratified in three birth cohorts: individuals born prior to 1945, individuals born between 1945 and 1965 and individuals born after 1965. We used a back-calculation modelling approach to estimate prevalence and the undiagnosed proportion of CHC. The historical prevalence of CHC was inferred through a calibration process based on a Bayesian Markov chain Monte Carlo (MCMC) algorithm. The algorithm constructs the historical prevalence of CHC for each cohort by comparing the model-generated outcomes of the annual incidence of the CHC-related health events against the data set of observed diagnosed cases generated in the retrospective analysis. RESULTS: The results show a decreasing trend in both CHC prevalence and undiagnosed proportion in BC, Ontario and Quebec. In 2018, CHC prevalence was estimated to be 1.23% (95% CI: .96%-1.62%), .91% (95% CI: .82%-1.04%) and .57% (95% CI: .51%-.64%) in BC, Ontario and Quebec respectively. The CHC undiagnosed proportion was assessed to be 35.44% (95% CI: 27.07%-45.83%), 34.28% (95% CI: 26.74%-41.62%) and 46.32% (95% CI: 37.85%-52.80%) in BC, Ontario and Quebec, respectively, in 2018. Also, since the introduction of new DAA treatment in 2014, CHC prevalence decreased from 1.39% to 1.23%, .97% to .91% and .65% to .57% in BC, Ontario and Quebec respectively. Similarly, the CHC undiagnosed proportion decreased from 38.78% to 35.44%, 38.70% to 34.28% and 47.54% to 46.32% in BC, Ontario and Quebec, respectively, from 2014 to 2018. CONCLUSIONS: We estimated that the CHC prevalence and undiagnosed proportion have declined for all three provinces since the new DAA treatment has been approved in 2014. Yet, our findings show that a significant proportion of HCV cases remain undiagnosed across all provinces highlighting the need to increase investment in screening. Our findings provide essential evidence to guide decisions about current and future HCV strategies and help achieve the WHO goal of eliminating hepatitis C in Canada by 2030.

Design and conduct of a randomized controlled feeding trial in a residential setting with mitigation for COVID-19.

BACKGROUND: Evaluating effects of different macronutrient diets in randomized trials requires well defined infrastructure and rigorous methods to ensure intervention fidelity and adherence. METHODS: This controlled feeding study comprised two phases. During a Run-in phase (14-15 weeks), study participants (18-50 years, BMI, ≥27 kg/m2) consumed a very-low-carbohydrate (VLC) diet, with home delivery of prepared meals, at an energy level to promote 15 ± 3% weight loss. During a Residential phase (13 weeks), participants resided at a conference center. They received a eucaloric VLC diet for three weeks and then were randomized to isocaloric test diets for 10 weeks: VLC (5% energy from carbohydrate, 77% from fat), high-carbohydrate (HC)-Starch (57%, 25%; including 20% energy from refined grains), or HC-Sugar (57%, 25%; including 20% sugar). Outcomes included measures of body composition and energy expenditure, chronic disease risk factors, and variables pertaining to physiological mechanisms. Six cores provided infrastructure for implementing standardized protocols: Recruitment, Diet and Meal Production, Participant Support, Assessments, Regulatory Affairs and Data Management, and Statistics. The first participants were enrolled in May 2018. Participants residing at the conference center at the start of the COVID-19 pandemic completed the study, with each core implementing mitigation plans. RESULTS: Before early shutdown, 77 participants were randomized, and 70 completed the trial (65% of planned completion). Process measures indicated integrity to protocols for weighing menu items, within narrow tolerance limits, and participant adherence, assessed by direct observation and continuous glucose monitoring. CONCLUSION: Available data will inform future research, albeit with less statistical power than originally planned.

Hepatitis C Attributable Healthcare Costs and Mortality among Immigrants: A Population-Based Matched Cohort Study.

Background: Data on the economic burden of chronic hepatitis C (CHC) among immigrants are limited. Our objective was to estimate the CHC-attributable mortality and healthcare costs among immigrants in Ontario, Canada. Methods: We conducted a population-based matched cohort study among immigrants diagnosed with CHC between May 31, 2003, and December 31, 2018, using linked health administrative data. Immigrants with CHC (exposed) were matched 1 : 1 to immigrants without CHC (unexposed) using a combination of hard (index date, sex, and age) and propensity-score matching. Net costs (2020 Canadian dollars) collected from the healthcare payer perspective were calculated using a phase-of-care approach and used to estimate long-term costs adjusted for survival. Results: We matched 5,575 exposed individuals with unexposed controls, achieving a balanced match. The mean age was 47 years, and 52% was male. On average, 10.5% of exposed and 3.5% of unexposed individuals died 15 years postindex (relative risk = 2.9; 95% confidence interval (CI): 2.6-3.5). The net 30-day costs per person were $88 (95% CI: 55 to 122) for the prediagnosis, $324 (95% CI: 291 to 356) for the initial phase, $1,016 (95% CI: 900 to 1,132) for the late phase, and $975 (95% CI: -25 to 1,974) for the terminal phase. The mean net healthcare cost adjusted for survival at 15 years was $90,448. Conclusions: Compared to unexposed immigrants, immigrants infected with CHC have higher mortality rates and greater healthcare costs. These findings will support the planning of HCV elimination efforts among key risk groups in the province.

Effect of the COVID-19 pandemic on mental health visits in primary care: an interrupted time series analysis from nine INTRePID countries.

Background: The COVID-19 pandemic impacted mental health disorders, affecting both individuals with pre-existing conditions and those with no prior history. However, there is limited evidence regarding the pandemic's impact on mental health visits to primary care physicians. The International Consortium of Primary Care Big Data Researchers (INTRePID) explored primary care visit trends related to mental health conditions in Argentina, Australia, Canada, China, Norway, Peru, Singapore, Sweden, and the USA. Methods: We conducted an interrupted time series analysis in nine countries to examine changes in rates of monthly mental health visits to primary care settings from January 1st, 2018, to December 31st, 2021. Sub-group analysis considered service type (in-person/virtual) and six categories of mental health conditions (anxiety/depression, bipolar/schizophrenia/other psychotic disorders, sleep disorders, dementia, ADHD/eating disorders, and substance use disorder). Findings: Mental health visit rates increased after the onset of the pandemic in most countries. In Argentina, Canada, China, Norway, Peru, and Singapore, this increase was immediate ranged from an incidence rate ratio of 1·118 [95% CI 1.053-1.187] to 2.240 [95% CI 2.057-2.439] when comparing the first month of pandemic with the pre-pandemic trend. Increases in the following months varied across countries. Anxiety/depression was the leading reason for mental health visits in most countries. Virtual visits were reported in Australia, Canada, Norway, Peru, Sweden, and the USA, accounting for up to 40% of the total mental health visits. Interpretation: Findings suggest an overall increase in mental health visits, driven largely by anxiety/depression. During the COVID-19 pandemic, many of the studied countries adopted virtual care in particular for mental health visits. Primary care plays a crucial role in addressing mental ill-health in times of crisis. Funding: Canadian Institutes of Health Research grant #173094 and the Rathlyn Foundation Primary Care EMR Research and Discovery Fund.

Validation of case-ascertainment algorithms using health administrative data to identify people who inject drugs in Ontario, Canada.

OBJECTIVES: Health administrative data can be used to improve the health of people who inject drugs by informing public health surveillance and program planning, monitoring, and evaluation. However, methodological gaps in the use of these data persist due to challenges in accurately identifying injection drug use (IDU) at the population level. In this study, we validated case-ascertainment algorithms for identifying people who inject drugs using health administrative data in Ontario, Canada. STUDY DESIGN AND SETTING: Data from cohorts of people with recent (past 12 months) IDU, including those participating in community-based research studies or seeking drug treatment, were linked to health administrative data in Ontario from 1992 to 2020. We assessed the validity of algorithms to identify IDU over varying look-back periods (ie, all years of data [1992 onwards] or within the past 1-5 years), including inpatient and outpatient physician billing claims for drug use, emergency department (ED) visits or hospitalizations for drug use or injection-related infections, and opioid agonist treatment (OAT). RESULTS: Algorithms were validated using data from 15,241 people with recent IDU (918 in community cohorts and 14,323 seeking drug treatment). An algorithm consisting of ≥1 physician visit, ED visit, or hospitalization for drug use, or OAT record could effectively identify IDU history (91.6% sensitivity and 94.2% specificity) and recent IDU (using 3-year look back: 80.4% sensitivity, 99% specificity) among community cohorts. Algorithms were generally more sensitive among people who inject drugs seeking drug treatment. CONCLUSION: Validated algorithms using health administrative data performed well in identifying people who inject drugs. Despite their high sensitivity and specificity, the positive predictive value of these algorithms will vary depending on the underlying prevalence of IDU in the population in which they are applied.

An economic evaluation of community pharmacy-dispensed naloxone in Canada.

Aims: To determine the cost-effectiveness of pharmacy-based intranasal (IN) and intramuscular (IM) naloxone distribution in Canada. Methods: We developed a state-transition model for pharmacy-based naloxone distribution, every 3 years, to illicit, prescription, opioid-agonist therapy and nonopioid use populations compared to no naloxone distribution. We used a monthly cycle length, lifetime horizon and a Canadian provincial Ministry of Health perspective. Transition probabilities, cost and utility data were retrieved from the literature. Costs (2020) and quality-adjusted life years (QALY) were discounted 1.5% annually. Microsimulation, 1-way and probabilistic sensitivity analyses were conducted. Results: Distribution of naloxone to all Canadians compared to no distribution prevented 151 additional overdose deaths per 10,000 persons, with an incremental cost-effectiveness ratio (ICER) of $50,984 per QALY for IM naloxone and an ICER of $126,060 per QALY for IN naloxone. Distribution of any naloxone to only illicit opioid users was the most cost-effective. One-way sensitivity analysis showed that survival rates for illicit opioid users were most influenced by the availability of either emergency medical services or naloxone. Conclusion: Distribution of IM and IN naloxone to all Canadians every 3 years is likely cost-effective at a willingness-to-pay threshold of $140,000 Canadian dollars/QALY (~3 × gross domestic product from the World Health Organization). Distribution to people who use illicit opioids was most cost-effective and prevented the most deaths. This is important, as more overdose deaths could be prevented through nationwide public funding of IN naloxone kits through pharmacies, since individuals report a preference for IN naloxone and these formulations are easier to use, save lives and are cost-effective. Can Pharm J (Ott) 2024;157:xx-xx.

Feasibility of hepatitis C elimination by screening and treatment alone in high-income countries.

BACKGROUND AND AIMS: Despite the availability of highly effective direct-acting antiviral therapy, chronic hepatitis C (CHC) continues to cause a major public health burden. In many high-income countries, treatment rates have been declining, which was exacerbated by the impact of the COVID-19 pandemic, threatening the ability to meet the World Health Organization (WHO)'s targets for eliminating HCV as a public health threat by 2030. We sought to model the impact of CHC in Canada, a resource-rich country with ongoing immigration from HCV-endemic regions; which relies exclusively on risk-based screening for case identification. APPROACH AND RESULTS: We developed an agent-based model to characterize the HCV epidemic in a high-income country with ongoing immigration. Combinations of prevention such as harm reduction, screening, and treatment strategies were considered. Model parameters were estimated from the literature and calibrated against historical HCV data. Sensitivity analyses were performed to assess uncertainty. Under the current status quo of risk-based screening, we predict the incidence of CHC-induced decompensated cirrhosis, HCC, and liver-related deaths would decrease by 79.4%, 76.1%, and 62.1%, respectively, between 2015 and 2030, but CHC incidence would only decrease by 11.1%. The results were sensitive to HCV transmission rate and an annual number of people initiating treatment. CONCLUSIONS: Current risk-based screening, and subsequent treatment, will be inadequate to achieve WHO goals. With extensive scale-up in screening, and treatment, the mortality target may be achievable, but the target for preventing new CHC cases is unlikely reachable, highlighting the importance of developing enhanced harm-reduction strategies for HCV elimination.

Relationship Between Availability of Urologists and Primary Care Providers and Stage of Diagnosis for Invasive Urinary Bladder Cancer.

INTRODUCTION: With no recommended screening approach, urinary bladder cancer patients rely on referral to urologists to ensure timely diagnosis of bladder cancer. This requires coordination between primary and specialty care. We provide estimates of the relative association between primary care physician and urologist density on stage of urinary bladder cancer diagnosis. METHODS: We used 2010 to 2016 Pennsylvania Cancer Registry data to identify all adult patients diagnosed with bladder cancer. Our primary outcome was locoregional stage of diagnosis, since treatment modality changes and prognosis worsens beyond this stage. Based on patient's residential location at the time of diagnosis we defined both density of urologists and number of primary care providers (defined as providers per population) within the patient's county. We used univariate and multivariate logistic regression to estimate the association between provider density and likelihood of locoregional stage of diagnosis. We also controlled for age, sex, race/ethnicity, insurance type, and year. RESULTS: Our sample included 11,771 urinary bladder cancer patients with 10,607 diagnosed at locoregional stage and 1164 at distant stage. Multivariate regression results show primary care density was associated with significantly higher odds of locoregional stage of diagnosis (odds ratio of 1.05 [95% CI: 1.02-1.08]) while urologist density was associated with significantly lower odds of locoregional stage (odds ratio of 0.65 [95% CI: 0.48-0.89]). CONCLUSIONS: We found primary care density but not urologist density was associated with earlier stage of diagnosis, highlighting the importance of access to primary care and need for timely referral to urologic care.

Development and validation of HBV surveillance models using big data and machine learning.

BACKGROUND: The construction of a robust healthcare information system is fundamental to enhancing countries' capabilities in the surveillance and control of hepatitis B virus (HBV). Making use of China's rapidly expanding primary healthcare system, this innovative approach using big data and machine learning (ML) could help towards the World Health Organization's (WHO) HBV infection elimination goals of reaching 90% diagnosis and treatment rates by 2030. We aimed to develop and validate HBV detection models using routine clinical data to improve the detection of HBV and support the development of effective interventions to mitigate the impact of this disease in China. METHODS: Relevant data records extracted from the Family Medicine Clinic of the University of Hong Kong-Shenzhen Hospital's Hospital Information System were structuralized using state-of-the-art Natural Language Processing techniques. Several ML models have been used to develop HBV risk assessment models. The performance of the ML model was then interpreted using the Shapley value (SHAP) and validated using cohort data randomly divided at a ratio of 2:1 using a five-fold cross-validation framework. RESULTS: The patterns of physical complaints of patients with and without HBV infection were identified by processing 158,988 clinic attendance records. After removing cases without any clinical parameters from the derivation sample (n = 105,992), 27,392 cases were analysed using six modelling methods. A simplified model for HBV using patients' physical complaints and parameters was developed with good discrimination (AUC = 0.78) and calibration (goodness of fit test p-value >0.05). CONCLUSIONS: Suspected case detection models of HBV, showing potential for clinical deployment, have been developed to improve HBV surveillance in primary care setting in China. (Word count: 264).

This study has developed a suspected case detection model for HBV, which can facilitate early identification and treatment of HBV in the primary care setting in China, contributing towards the achievement of WHO's elimination goals of HBV infections.We utilized the state-of-art natural language processing techniques to structure the data records, leading to the development of a robust healthcare information system which enhances the surveillance and control of HBV in China.

Technical note: Generalizable and promptable artificial intelligence model to augment clinical delineation in radiation oncology.

BACKGROUND: Efficient and accurate delineation of organs at risk (OARs) is a critical procedure for treatment planning and dose evaluation. Deep learning-based auto-segmentation of OARs has shown promising results and is increasingly being used in radiation therapy. However, existing deep learning-based auto-segmentation approaches face two challenges in clinical practice: generalizability and human-AI interaction. A generalizable and promptable auto-segmentation model, which segments OARs of multiple disease sites simultaneously and supports on-the-fly human-AI interaction, can significantly enhance the efficiency of radiation therapy treatment planning. PURPOSE: Meta's segment anything model (SAM) was proposed as a generalizable and promptable model for next-generation natural image segmentation. We further evaluated the performance of SAM in radiotherapy segmentation. METHODS: Computed tomography (CT) images of clinical cases from four disease sites at our institute were collected: prostate, lung, gastrointestinal, and head & neck. For each case, we selected the OARs important in radiotherapy treatment planning. We then compared both the Dice coefficients and Jaccard indices derived from three distinct methods: manual delineation (ground truth), automatic segmentation using SAM's 'segment anything' mode, and automatic segmentation using SAM's 'box prompt' mode that implements manual interaction via live prompts during segmentation. RESULTS: Our results indicate that SAM's segment anything mode can achieve clinically acceptable segmentation results in most OARs with Dice scores higher than 0.7. SAM's box prompt mode further improves Dice scores by 0.1∼0.5. Similar results were observed for Jaccard indices. The results show that SAM performs better for prostate and lung, but worse for gastrointestinal and head & neck. When considering the size of organs and the distinctiveness of their boundaries, SAM shows better performance for large organs with distinct boundaries, such as lung and liver, and worse for smaller organs with less distinct boundaries, like parotid and cochlea. CONCLUSIONS: Our results demonstrate SAM's robust generalizability with consistent accuracy in automatic segmentation for radiotherapy. Furthermore, the advanced box-prompt method enables the users to augment auto-segmentation interactively and dynamically, leading to patient-specific auto-segmentation in radiation therapy. SAM's generalizability across different disease sites and different modalities makes it feasible to develop a generic auto-segmentation model in radiotherapy.

Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors.

PURPOSE: Risk factors of gallbladder cancer (GBC) are not well-defined resulting in greater than 60% of GBCs being diagnosed incidentally following cholecystectomy performed for presumed benign indications. As most localized GBCs require more extensive oncologic surgery beyond cholecystectomy, this study aims to examine factors associated with incidentally found GBC to improve preoperative and intraoperative diagnoses. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Database from 2007 to 2017 was used to identify cholecystectomies performed with and without a final diagnosis of GBC. Univariate and multivariable logistic regressions were used to compare demographic, intraoperative, and postoperative characteristics among those with and without a diagnosis of GBC. RESULTS: The incidence of GBC was observed to be 0.11% (441/403,443). Preoperative factors associated with risk of GBC included age > 60 (OR 6.51, p < .001), female sex (OR 1.75, p < .001), history of weight loss (2.58, p < .001), and elevated preoperative alkaline phosphatase level (OR 1.67, p = .001). Open approach was associated with 7 times increased risk of GBC compared to laparoscopic approach (OR 7.33, p < .001). In addition to preoperative factors and surgical approach, longer mean operative times (127 min vs 70.7 min, p < .001) were significantly associated with increased risk of GBC compared to benign final pathology. CONCLUSION: This study demonstrates that those with incidentally discovered GBC at cholecystectomy are unique from those undergoing cholecystectomy for benign indications. By identifying predictors of GBC, surgeons can choose high risk individuals for pre-operative oncologic evaluation and consider better tools for identifying GBC such as intraoperative frozen pathology.

Characterising the effectiveness of social determinants of health-focused hepatitis B interventions: a systematic review.

Social determinants of health are important in designing effective interventions for hepatitis B virus (HBV) infection. This systematic review characterises equity-oriented, social determinants of health-focused HBV interventions, and describes their effectiveness in terms of the prevention, care, or treatment of HBV in high-income countries. We searched electronic databases for central concepts of 'HBV', 'equity', 'social determinants of health', 'intervention', and 'Organization for Economic Co-operation and Development (OECD) countries'. Screening and data abstraction were conducted independently by two reviewers. Data were abstracted from 66 studies; articles with a comparative study design (n=36) were included in the narrative synthesis, highlighting social determinants of health domains of interventions, HBV-relevant health outcomes, and extra-health social determinants of health effects (ie, those effects that extend beyond health outcomes). Synthesis aligned with six emergent themes corresponding to HBV prevention and care: knowledge and education, diagnosis and screening, immunisation, care initiation, engagement with clinical care and treatment, and upstream prevention. Studies presented a heterogeneous array of HBV-relevant health outcomes. Most interventions were tailored for social determinants of health domains of race, ethnicity, culture, and language; drug use; and socioeconomic status. Across the themes, at least two-thirds of interventions showed comparative effectiveness for addressing HBV. Extra-health social determinants of health outcomes were observed for two studies. Considerable diversity in population-level approaches was observed regarding intervention goals and effectiveness; most interventions were effective at enhancing the prevention, care, or treatment of HBV.

The value of the accelerated approval pathway: real-world outcomes associated with reducing the time between innovations.

Aim: We investigated the effect of shortening time between innovations with the accelerated approval (AA) pathway on patient outcomes for three solid tumors. Methods: This real-world analysis evaluated patients receiving sequential AA pathway-approved innovations after initial treatment with existing therapies in three solid tumor case studies. Outcomes attributable to AA were estimated and assumed approval occurred at the time of conversion to approval and extrapolated to the US population. Results: Survival gains from accessing innovative therapies were 2.3-3.8-times higher when using the AA pathway. At the US population level, AA was associated with ∼8000 life-years gained across all three tumor case studies. Conclusion: In areas of rapid clinical development, the value of existing therapies can be enhanced by earlier access to AA pathway innovations and should be considered when evaluating the AA program.

What is this study about? The US Food and Drug Administration's accelerated approval pathway provides patients with access to innovative drugs sooner than standard regulatory pathways. Using three case studies in solid tumors, this study measured how many patients on current cancer drugs received future cancer drugs because of the accelerated approval pathway and asked whether quicker access to new drugs resulted in them living longer. What were the results? In three cancer case studies, the accelerated approval pathway led to more patients receiving future cancer drugs. Patients who received future drugs through the AA pathway lived longer than patients who did not have access to them. What do the results of the study mean? The accelerated approval pathway is important because it can improve outcomes of current cancer drugs by giving patients additional treatments to choose from in the future and therefore a chance to live longer. Policymakers should consider this when thinking about making changes to the accelerated approval pathway.

Latent Heterogeneity of Online Sexual Experiences and Associations With Sexual Risk Behaviors and Behavioral Health Outcomes in Chinese Young Adults: Cross-Sectional Study.

BACKGROUND: Online sexual experiences (OSEs) are becoming increasingly common in young adults, but existing papers have reported only on specific types of OSEs and have not shown the heterogeneous nature of the repertoire of OSEs. The use patterns of OSEs remain unclear, and the relationships of OSEs with sexual risk behaviors and behavioral health outcomes have not been evaluated. OBJECTIVE: This study aimed to examine the latent heterogeneity of OSEs in young adults and the associations with sexual risk behaviors and behavioral health outcomes. METHODS: The 2021 Youth Sexuality Study of the Hong Kong Family Planning Association phone interviewed a random sample of 1205 young adults in Hong Kong in 2022 (male sex: 613/1205, 50.9%; mean age 23.0 years, SD 2.86 years) on lifetime OSEs, demographic and family characteristics, Patient Health Questionnaire-4 (PHQ-4) scores, sex-related factors (sexual orientation, sex knowledge, and sexual risk behaviors), and behavioral health outcomes (sexually transmitted infections [STIs], drug use, and suicidal ideation) in the past year. Sample heterogeneity of OSEs was analyzed via latent class analysis with substantive checking of the class profiles. Structural equation modeling was used to examine the direct and indirect associations between the OSE class and behavioral health outcomes via sexual risk behaviors and PHQ-4 scores. RESULTS: The data supported 3 latent classes of OSEs with measurement invariance by sex. In this study, 33.1% (398/1205), 56.0% (675/1205), and 10.9% (132/1205) of the sample were in the abstinent class (minimal OSEs), normative class (occasional OSEs), and active class (substantive OSEs), respectively. Male participants showed a lower prevalence of the abstinent class (131/613, 21.4% versus 263/592, 44.4%) and a higher prevalence of the active class (104/613, 17.0% versus 28/592, 4.7%) than female participants. The normative class showed significantly higher sex knowledge than the other 2 classes. The active class was associated with male sex, nonheterosexual status, higher sex desire and PHQ-4 scores, and more sexual risk behaviors than the other 2 classes. Compared with the nonactive (abstinent and normative) classes, the active class was indirectly associated with higher rates of STIs (absolute difference in percentage points [Δ]=4.8%; P=.03) and drug use (Δ=7.6%; P=.001) via sexual risk behaviors, and with higher rates of suicidal ideation (Δ=2.5%; P=.007) via PHQ-4 scores. CONCLUSIONS: This study provided the first results on the 3 (abstinent, normative, and active) latent classes of OSEs with distinct profiles in OSEs, demographic and family characteristics, PHQ-4 scores, sex-related factors, and behavioral health outcomes. The active class showed indirect associations with higher rates of STIs and drug use via sexual risk behaviors and higher rates of suicidal ideation via PHQ-4 scores than the other 2 classes. These results have implications for the formulation and evaluation of targeted interventions to help young adults.

Challenges and Implications for Menopausal Health and Help-Seeking Behaviors in Midlife Women From the United States and China in Light of the COVID-19 Pandemic: Web-Based Panel Surveys.

BACKGROUND: The global population of women of menopausal age is quickly increasing. The COVID-19 pandemic has led to an accelerated increase in the use of telehealth services, especially technological solutions targeting women's health. Understanding the factors behind midlife women's help-seeking behaviors amidst the pandemic will assist in the development of person-centered holistic telehealth solutions targeting menopausal and postreproductive health. OBJECTIVE: This study aimed to compare the factors underlying help-seeking for menopausal distress among midlife women in the United States and China. METHODS: We conducted 2 web-based panel surveys in the United States using Amazon Mechanical Turk and in China using Credamo between July and October 2022. A total of 1002 American and 860 Chinese women aged between 40 and 65 years took part in the survey. The survey was designed based on the Health Belief Model with questions related to their menopausal knowledge, perceived severity of menopausal symptoms, perceived susceptibility to menopausal distress, perceived benefits of help-seeking, perceived COVID-19- and non-COVID-19-related barriers against help-seeking, self-efficacy, and motivation to seek help. Structural equations models were fitted for the data using full information maximum likelihood to manage missing data. RESULTS: Knowledge was not directly related to help-seeking motivation in both samples. Among the Chinese sample, knowledge was negatively related to perceived severity but positively related to COVID-19-related barriers; in turn, higher perceived severity, benefits, COVID-19-related barriers, and self-efficacy and lower non-COVID-19-related barriers were related to more motivation to seek help. In the US sample, knowledge was negatively related to perceived severity, susceptibility, benefits, barriers (COVID-19- and non-COVID-19-related), and self-efficacy; in turn, higher self-efficacy, COVID-19-related barriers, and benefits were associated with more help-seeking motivation. The factors explained 53% and 45.3% of the variance of help-seeking motivation among the American and Chinese participants, respectively. CONCLUSIONS: This study revealed disparate pathways between knowledge, health beliefs, and the motivation for help-seeking among American and Chinese midlife women with respect to menopausal distress. Our findings show that knowledge may not directly influence help-seeking motivation. Instead, perceived benefits and self-efficacy consistently predicted help-seeking motivation. Interestingly, concern over COVID-19 infection was related to higher help-seeking motivation in both samples. Hence, our findings recommend the further development of telehealth services to (1) develop content beyond health education and symptom management that serves to enhance the perceived benefits of addressing women's multidimensional menopausal health needs, (2) facilitate patient-care provider communication with a focus on self-efficacy and a propensity to engage in help-seeking behaviors, and (3) target women who have greater midlife health concerns in the postpandemic era.

Real-world Trends, Rural-urban Differences, and Socioeconomic Disparities in Utilization of Narrow versus Broad Next-generation Sequencing Panels.

Advances in genetic technology have led to the increasing use of genomic panels in precision oncology practice, with panels ranging from a couple to hundreds of genes. However, the clinical utilization and utility of oncology genomic panels, especially among vulnerable populations, is unclear. We examined the association of panel size with socioeconomic status and clinical trial matching. We retrospectively identified 9,886 eligible adult subjects in the Mayo Clinic Health System who underwent genomic testing between January 1, 2016 and June 30, 2020. Patient data were retrieved from structured and unstructured data sources of institutional collections, including cancer registries, clinical data warehouses, and clinical notes. Socioeconomic surrogates were approximated using the Area Deprivation Index (ADI) corresponding to primary residence addresses. Logistic regression was performed to analyze relationships between ADI or rural/urban status and (i) use of genomic test by panel size; (ii) clinical trial matching status. Compared with patients from the most affluent areas, patients had a lower odds of receiving a panel test (vs. a single-gene test) if from areas of higher socioeconomic deprivation [OR (95% confidence interval (CI): 0.71 (0.61-0.83), P < 0.01] or a rural area [OR (95% CI): 0.85 (0.76-0.96), P < 0.01]. Patients in areas of higher socioeconomic deprivation were less likely to be matched to clinical trials if receiving medium panel tests [(OR) (95% CI): 0.69 (0.49-0.97), P = 0.03]; however, there was no difference among patients receiving large panel tests (P > 0.05) and rural patients were almost 2x greater odds of being matched if receiving a large panel test [(OR) (95% CI): 1.76 (1.21-2.55), P < 0.01]. SIGNIFICANCE: We identified socioeconomic and rurality disparities in the use of genomic tests and trial matching by panel size, which may have implications for equal access to targeted therapies. The lack of association between large panel tests and clinical trial matching by socioeconomic status, suggests a potential health equity impact, while removing barriers in access to large panels for rural patients may improve access to trials. However, further research is needed.