Artificial Intelligence-Based Co-Facilitator (AICF) for Detecting and Monitoring Group Cohesion Outcomes in Web-Based Cancer Support Groups: Single-Arm Trial Study.

BACKGROUND: Commonly offered as supportive care, therapist-led online support groups (OSGs) are a cost-effective way to provide support to individuals affected by cancer. One important indicator of a successful OSG session is group cohesion; however, monitoring group cohesion can be challenging due to the lack of nonverbal cues and in-person interactions in text-based OSGs. The Artificial Intelligence-based Co-Facilitator (AICF) was designed to contextually identify therapeutic outcomes from conversations and produce real-time analytics. OBJECTIVE: The aim of this study was to develop a method to train and evaluate AICF's capacity to monitor group cohesion. METHODS: AICF used a text classification approach to extract the mentions of group cohesion within conversations. A sample of data was annotated by human scorers, which was used as the training data to build the classification model. The annotations were further supported by finding contextually similar group cohesion expressions using word embedding models as well. AICF performance was also compared against the natural language processing software Linguistic Inquiry Word Count (LIWC). RESULTS: AICF was trained on 80,000 messages obtained from Cancer Chat Canada. We tested AICF on 34,048 messages. Human experts scored 6797 (20%) of the messages to evaluate the ability of AICF to classify group cohesion. Results showed that machine learning algorithms combined with human input could detect group cohesion, a clinically meaningful indicator of effective OSGs. After retraining with human input, AICF reached an F1-score of 0.82. AICF performed slightly better at identifying group cohesion compared to LIWC. CONCLUSIONS: AICF has the potential to assist therapists by detecting discord in the group amenable to real-time intervention. Overall, AICF presents a unique opportunity to strengthen patient-centered care in web-based settings by attending to individual needs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/21453.

Understanding Elderly Chinese Cancer Patients in a Multicultural Clinical Setting: Embracing Mortality and Addressing Misperceptions of Vulnerability.

Chinese patients face higher risks of gastrointestinal (GI) cancers and greater cancer-related deaths than Canadian-born patients. The older population encounters barriers to quality healthcare, impacting their well-being and survival. Previous studies highlighted Chinese immigrant perceptions of not requiring healthcare support. During the COVID-19 pandemic, their underutilization of healthcare services garnered attention. The present study explores the experiences of older Chinese cancer patients to improve culturally sensitive cancer care. A total of twenty interviews carried out in Cantonese and Mandarin were conducted with Chinese immigrants, aged 60 or above, diagnosed with Stage 3 or 4 GI cancer. These interviews were transcribed verbatim, translated, and subjected to qualitative descriptive analysis. Among older Chinese immigrant patients, a phenomenon termed "Premature Acceptance: Normalizing Death and Dying" was observed. This involved four key themes: 1. acceptance and letting go, 2. family first, 3. self-sufficiency, and 4. barriers to supportive care. Participants displayed an early acceptance of their own mortality, prioritizing family prosperity over their own quality of life. Older Chinese patients normalize the reality of facing death amidst cancer. They adopt a pragmatic outlook, acknowledging life-saving treatments while willingly sacrificing their own support needs to ease family burdens. Efforts to enhance health literacy require culturally sensitive programs tailored to address language barriers and differing values among this population. A strengths-based approach emphasizing family support and practical aspects of care may help build resilience and improve symptom management, thereby enhancing their engagement with healthcare services.

Estimating Gender Differences in the Association between Cognitive Resilience and Mild Cognitive Impairment Incidence.

INTRODUCTION: Recent evidence suggests that the influence of verbal intelligence and education on the onset of subjective cognitive decline may be modulated by gender, where education contributes less to cognitive resilience (CR) in women than in men. This study aimed to examine gender differences in the association between CR and mild cognitive impairment (MCI) incidence in an Australian population-based cohort. METHODS: We included 1,806 participants who had completed at least the first two waves and up to four waves of assessments in the Personality and Total Health (PATH) Through Life study (baseline: 49% female, male = 62.5, SD = 1.5, age range = 60-66 years). CR proxies included measures of educational attainment, occupation skill, verbal intelligence, and leisure activity. Discrete-time survival analyses were conducted to examine gender differences in the association between CR proxies and MCI risk, adjusting for age and apolipoprotein E4 status. RESULTS: Gender differences were only found in the association between occupation and MCI risk, where lower occupation skill was more strongly associated with higher risk in men than in women (odds ratio [OR] = 1.30, 95% confidence interval [CI] [1.07, 1.57]). In both genders, after adjusting for education and occupation, one SD increase in leisure activity was associated with lower MCI risk by 32% (OR = 0.76, 95% CI [0.65, 0.89]). Higher scores in verbal intelligence assessment were associated with reduced risk of MCI by 28% (OR = 0.78, 95% CI [0.69, 0.89]). CONCLUSION: Occupational experience may contribute to CR differently between genders. Life course cognitive engagement and verbal intelligence may be more protective against MCI than education and occupation for both men and women.

Employment needs of and barriers for Chinese youth and young adults with Autism Spectrum Conditions in Ontario, Canada.

BACKGROUND: Cultural-based literature focusing on Asian autistic immigrants living in Western countries is very limited. AIMS: The present study is a quality improvement exercise aiming to fill the gap by investigating the employment needs of and barriers for Chinese autistic youth and young adults in Ontario, Canada. METHODS & PROCEDURES: 71 individuals diagnosed with autism and 24 diagnosed with other mental illnesses, aged 12-29, participated in an online survey regarding their work readiness, work skills, interests, health and cultural concerns. Analyses were conducted to compare the autistic group and the mental health group. OUTCOMES & RESULTS: Results show that the autistic sample has inferior (1) work habits related skills, (2) work style related skills, (3) level of independence, (4) skills to perform routine daily activities, (5) interpersonal skills at work, and (6) ability to tolerate visual and moving stimuli in the work environment. It is also found that the autistic group has more symptoms of depression, anxiety, and autism than that of the non-autistic group. CONCLUSIONS & IMPLICATIONS: The study shed light into the unique needs and barriers of Chinese autistic young adults and the service gap in supporting their transition to employment.

Risk-based lung cancer screening performance in a universal healthcare setting.

Globally, lung cancer is the leading cause of cancer death. Previous trials demonstrated that low-dose computed tomography lung cancer screening of high-risk individuals can reduce lung cancer mortality by 20% or more. Lung cancer screening has been approved by major guidelines in the United States, and over 4,000 sites offer screening. Adoption of lung screening outside the United States has, until recently, been slow. Between June 2017 and May 2019, the Ontario Lung Cancer Screening Pilot successfully recruited 7,768 individuals at high risk identified by using the PLCOm2012noRace lung cancer risk prediction model. In total, 4,451 participants were successfully screened, retained and provided with high-quality follow-up, including appropriate treatment. In the Ontario Lung Cancer Screening Pilot, the lung cancer detection rate and the proportion of early-stage cancers were 2.4% and 79.2%, respectively; serious harms were infrequent; and sensitivity to detect lung cancers was 95.3% or more. With abnormal scans defined as ones leading to diagnostic investigation, specificity was 95.5% (positive predictive value, 35.1%), and adherence to annual recall and early surveillance scans and clinical investigations were high (>85%). The Ontario Lung Cancer Screening Pilot provides insights into how a risk-based organized lung screening program can be implemented in a large, diverse, populous geographic area within a universal healthcare system.

Integrating Smoking Cessation Into Low-Dose Computed Tomography Lung Cancer Screening: Results of the Ontario, Canada Pilot.

INTRODUCTION: Low-dose computed tomography screening in high-risk individuals reduces lung cancer mortality. To inform the implementation of a provincial lung cancer screening program, Ontario Health undertook a Pilot study, which integrated smoking cessation (SC). METHODS: The impact of integrating SC into the Pilot was assessed by the following: rate of acceptance of a SC referral; proportion of individuals who were currently smoking cigarettes and attended a SC session; the quit rate at 1 year; change in the number of quit attempts; change in Heaviness of Smoking Index; and relapse rate in those who previously smoked. RESULTS: A total of 7768 individuals were recruited predominantly through primary care physician referral. Of these, 4463 were currently smoking and were risk assessed and referred to SC services, irrespective of screening eligibility: 3114 (69.8%) accepted referral to an in-hospital SC program, 431 (9.7%) to telephone quit lines, and 50 (1.1%) to other programs. In addition, 4.4% reported no intention to quit and 8.5% were not interested in participating in a SC program. Of the 3063 screen-eligible individuals who were smoking at baseline low-dose computed tomography scan, 2736 (89.3%) attended in-hospital SC counseling. The quit rate at 1 year was 15.5% (95% confidence interval: 13.4%-17.7%; range: 10.5%-20.0%). Improvements were also observed in Heaviness of Smoking Index (p < 0.0001), number of cigarettes smoked per day (p < 0.0001), time to first cigarette (p < 0.0001), and number of quit attempts (p < 0.001). Of those who reported having quit within the previous 6 months, 6.3% had resumed smoking at 1 year. Furthermore, 92.7% of the respondents reported satisfaction with the hospital-based SC program. CONCLUSIONS: On the basis of these observations, the Ontario Lung Screening Program continues to recruit through primary care providers, to assess risk for eligibility using trained navigators, and to use an opt-out approach to referral for cessation services. In addition, initial in-hospital SC support and intensive follow-on cessation interventions will be provided to the extent possible.

Therapist Feedback and Implications on Adoption of an Artificial Intelligence-Based Co-Facilitator for Online Cancer Support Groups: Mixed Methods Single-Arm Usability Study.

BACKGROUND: The recent onset of the COVID-19 pandemic and the social distancing requirement have created an increased demand for virtual support programs. Advances in artificial intelligence (AI) may offer novel solutions to management challenges such as the lack of emotional connections within virtual group interventions. Using typed text from online support groups, AI can help identify the potential risk of mental health concerns, alert group facilitator(s), and automatically recommend tailored resources while monitoring patient outcomes. OBJECTIVE: The aim of this mixed methods, single-arm study was to evaluate the feasibility, acceptability, validity, and reliability of an AI-based co-facilitator (AICF) among CancerChatCanada therapists and participants to monitor online support group participants' distress through a real-time analysis of texts posted during the support group sessions. Specifically, AICF (1) generated participant profiles with discussion topic summaries and emotion trajectories for each session, (2) identified participant(s) at risk for increased emotional distress and alerted the therapist for follow-up, and (3) automatically suggested tailored recommendations based on participant needs. Online support group participants consisted of patients with various types of cancer, and the therapists were clinically trained social workers. METHODS: Our study reports on the mixed methods evaluation of AICF, including therapists' opinions as well as quantitative measures. AICF's ability to detect distress was evaluated by the patient's real-time emoji check-in, the Linguistic Inquiry and Word Count software, and the Impact of Event Scale-Revised. RESULTS: Although quantitative results showed only some validity of AICF's ability in detecting distress, the qualitative results showed that AICF was able to detect real-time issues that are amenable to treatment, thus allowing therapists to be more proactive in supporting every group member on an individual basis. However, therapists are concerned about the ethical liability of AICF's distress detection function. CONCLUSIONS: Future works will look into wearable sensors and facial cues by using videoconferencing to overcome the barriers associated with text-based online support groups. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/21453.

Cocreating Meaning Through Expressive Writing and Reading for Cancer Caregivers.

PURPOSE: Caregivers of patients with cancer cope with socioemotional challenges, which can adversely affect their well-being. We developed an intervention, expressive writing and reading (EWR), to promote emotional processing and social connectedness among caregivers. In a single-arm pilot study, we assessed its feasibility and perceived usefulness. METHODS: Caregivers participated in weekly 1.5-hour EWR workshops offered over 20 weeks. After 4 sessions, they completed semistructured interviews, which were analyzed using qualitative descriptive analysis. FINDINGS: Of 65 caregivers approached, 25 were eligible, 18 consented, and 9 (50%) caregivers completed at least 4 workshops and the interview. Their responses revealed 3 themes: "inner processing," "interpersonal learning," and "enhanced processing and preparedness." Perceived benefits of EWR included emotional and cognitive processing (individual and collaborative), learning from the emotions and experiences of other caregivers, and preparing for upcoming challenges. CONCLUSIONS: Expressive writing and reading can be a safe and cost-effective supportive intervention for caregivers of patients with cancer.

Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies.

INTRODUCTION: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. METHODS: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed. RESULTS: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). DISCUSSION: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection.

Optimal T follicular helper (Tfh) cells function is important to promote the development of germinal centers and maturation of high affinity antigen-specific B cells. We have found that the expression of CXCR3 defines distinct Tfh subsets: CXCR3+ Th1-like Tfh cells mainly producing single IFN-γ and dual IL-21/IFN-γ and CXCR3- Th2-like Tfh cells mainly producing single IL-4 and dual IL-21/IL-4 cytokines. CXCR3- Th2-like Tfhs are significantly reduced during ongoing HIV replication. While the percentage of Th2-like Tfh cells correlates with that of total and cycling HIV-specific B cells, the percentage of CXCR3+ Th1-like Tfhs correlates with HIV-specific B cells expressing T-bet and CXCR3. Of note, only IL-4 and IL-21 cytokines boosted efficient maturation of HIV-specific B cells while IFN-γ induced expression of T-bet and CXCR3 in B cells. Interestingly, total and HIV-specific CXCR3+ B cells showed lower rate of somatic hypermutation, as compared to CXCR3- B cells. Therefore, the imbalance in Th2/Th1-like Tfhs affects B cell responses in viremic HIV infection.

Providing Care Beyond Therapy Sessions With a Natural Language Processing-Based Recommender System That Identifies Cancer Patients Who Experience Psychosocial Challenges and Provides Self-care Support: Pilot Study.

BACKGROUND: The negative psychosocial impacts of cancer diagnoses and treatments are well documented. Virtual care has become an essential mode of care delivery during the COVID-19 pandemic, and online support groups (OSGs) have been shown to improve accessibility to psychosocial and supportive care. de Souza Institute offers CancerChatCanada, a therapist-led OSG service where sessions are monitored by an artificial intelligence-based co-facilitator (AICF). The AICF is equipped with a recommender system that uses natural language processing to tailor online resources to patients according to their psychosocial needs. OBJECTIVE: We aimed to outline the development protocol and evaluate the AICF on its precision and recall in recommending resources to cancer OSG members. METHODS: Human input informed the design and evaluation of the AICF on its ability to (1) appropriately identify keywords indicating a psychosocial concern and (2) recommend the most appropriate online resource to the OSG member expressing each concern. Three rounds of human evaluation and algorithm improvement were performed iteratively. RESULTS: We evaluated 7190 outputs and achieved a precision of 0.797, a recall of 0.981, and an F1 score of 0.880 by the third round of evaluation. Resources were recommended to 48 patients, and 25 (52%) accessed at least one resource. Of those who accessed the resources, 19 (75%) found them useful. CONCLUSIONS: The preliminary findings suggest that the AICF can help provide tailored support for cancer OSG members with high precision, recall, and satisfaction. The AICF has undergone rigorous human evaluation, and the results provide much-needed evidence, while outlining potential strengths and weaknesses for future applications in supportive care.

Mobilization of innate and adaptive antitumor immune responses by the RNP-targeting antibody ATRC-101.

Immunotherapy approaches focusing on T cells have provided breakthroughs in treating solid tumors. However, there remains an opportunity to drive anticancer immune responses via other cell types, particularly myeloid cells. ATRC-101 was identified via a target-agnostic process evaluating antibodies produced by the plasmablast population of B cells in a patient with non-small cell lung cancer experiencing an antitumor immune response during treatment with checkpoint inhibitor therapy. Here, we describe the target, antitumor activity in preclinical models, and data supporting a mechanism of action of ATRC-101. Immunohistochemistry studies demonstrated tumor-selective binding of ATRC-101 to multiple nonautologous tumor tissues. In biochemical analyses, ATRC-101 appears to target an extracellular, tumor-specific ribonucleoprotein (RNP) complex. In syngeneic murine models, ATRC-101 demonstrated robust antitumor activity and evidence of immune memory following rechallenge of cured mice with fresh tumor cells. ATRC-101 increased the relative abundance of conventional dendritic cell (cDC) type 1 cells in the blood within 24 h of dosing, increased CD8+ T cells and natural killer cells in blood and tumor over time, decreased cDC type 2 cells in the blood, and decreased monocytic myeloid-derived suppressor cells in the tumor. Cellular stress, including that induced by chemotherapy, increased the amount of ATRC-101 target in tumor cells, and ATRC-101 combined with doxorubicin enhanced efficacy compared with either agent alone. Taken together, these data demonstrate that ATRC-101 drives tumor destruction in preclinical models by targeting a tumor-specific RNP complex leading to activation of innate and adaptive immune responses.

A Continuing Educational Program Supporting Health Professionals to Manage Grief and Loss.

Health professionals working in oncology face the challenge of a stressful work environment along with impacts of providing care to those suffering from a life-threatening illness and encountering high levels of patient loss. Longitudinal exposure to loss and suffering can lead to grief, which over time can lead to the development of compassion fatigue (CF). Prevalence rates of CF are significant, yet health professionals have little knowledge on the topic. A six-week continuing education program aimed to provide information on CF and support in managing grief and loss and consisted of virtual sessions, case-based learning, and an online community of practice. Content included personal, health system, and team-related risk factors; protective variables associated with CF; grief models; and strategies to help manage grief and loss and to mitigate against CF. Participants also developed personal plans. Pre- and post-course evaluations assessed confidence, knowledge, and overall satisfaction. A total of 189 health professionals completed the program (90% nurses). Reported patient loss was high (58.8% > 10 deaths annually; 12.2% > 50). Improvements in confidence and knowledge across several domains (p < 0.05) related to managing grief and loss were observed, including use of grief assessment tools, risk factors for CF, and strategies to mitigate against CF. Satisfaction level post-program was high. An educational program aiming to improve knowledge of CF and management of grief and loss demonstrated benefit.

A systematic review of the associations, mediators and moderators of life satisfaction, positive affect and happiness in near-centenarians and centenarians.

OBJECTIVE: Results from studies investigating life satisfaction, positive affect and happiness of near-centenarians (95+) and centenarians are inconsistent. This is the first systematic review to summarise the extant literature on the subjective well-being of this unique age group. METHOD: Seven electronic databases (PubMed, MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science and the Cochrane database for systematic reviews) were systematically searched. Subjective well-being was defined as life satisfaction, positive affect and happiness. A narrative synthesis of relevant articles was undertaken. RESULTS: Of 28 studies eligible for inclusion in this review, 20 predominantly examined life satisfaction, 11 positive affect and 4 happiness. Sex and other demographic variables were not significant predictors of subjective well-being. In contrast, greater perceived health was significantly associated with higher levels of life satisfaction and positive affect. Fatigue and visual impairment were significantly correlated with lower levels of life satisfaction and positive affect. However, there was considerable heterogeneity in the findings on physical, cognitive and social associations, mediators and moderators. CONCLUSION: The large discrepancy of results in the literature may be explained by methodological differences between studies. Centenarian research needs a clearer definition of life satisfaction, positive affect and happiness as their operationalisation is inconsistent. An international consortium of centenarian studies could facilitate cross-cultural comparisons on subjective well-being. Future research should be directed towards interventions that promote subjective well-being in the oldest-old.

The Impact of Radiologist Screening Mammogram Reading Volume on Performance in the Ontario Breast Screening Program.

PURPOSE: Although some studies have shown increasing radiologists' mammography volumes improves performance, there is a lack of evidence specific to digital mammography and breast screening program performance targets. This study evaluates the relationship between digital screening volume and meeting performance targets. METHODS: This retrospective cohort study included 493 radiologists in the Ontario Breast Screening Program who interpreted 1,762,173 screening mammograms in participants ages 50-90 between 2014 and 2016. Associations between annual screening volume and meeting performance targets for abnormal call rate, positive predictive value (PPV), invasive cancer detection rate (CDR), sensitivity, and specificity were modeled using mixed-effects multivariate logistic regression. RESULTS: Most radiologists read 500-999 (36.7%) or 1,000-1,999 (31.0%) screens annually, and 18.5% read ≥2,000. Radiologists who read ≥2,000 annually were more likely to meet abnormal call rate (OR = 3.85; 95% CI: 1.17-12.61), PPV (OR = 5.36; 95% CI: 2.53-11.34), invasive CDR (OR = 4.14; 95% CI: 1.50-11.46), and specificity (OR = 4.07; 95% CI: 1.89-8.79) targets versus those who read 100-499 screens. Radiologists reading 1,000-1,999 screens annually were more likely to meet PPV (OR = 2.32; 95% CI: 1.22-4.40), invasive CDR (OR = 3.36; 95% CI: 1.49-7.59) and specificity (OR = 2.00; 95% CI: 1.04-3.84) targets versus those who read 100-499 screens. No significant differences were observed for sensitivity. CONCLUSIONS: Annual reading volume requirements of 1,000 in Canada are supported as screening volume above 1,000 was strongly associated with achieving performance targets for nearly all measures. Increasing the minimum volume to 2,000 may further reduce the potential limitations of screening due to false positives, leading to improvements in overall breast screening program quality.

Pathways to Acceptance in Participants of Advanced Cancer Online Support Groups.

Background and Objectives: Individuals with cancer, especially advanced cancer, are faced with numerous difficulties associated with the disease, including an earlier death than expected. Those who are able to confront and accept the hardships associated with the disease in a way that aligns with their beliefs benefit from more positive psychological outcomes compared to those who are aware of their diagnosis but are unable to accept it. To date, there is limited research exploring factors contributing to illness and death acceptance in the context of advanced cancer in group therapy settings. Materials and Methods: The current study used a Directed Content Analysis approach on transcripts of online advanced cancer support groups to investigate if and how Yalom's existential factors played a role in the emergence of acceptance. Results: The online support group platform, combined with the help of facilitators, offered supportive environments for individuals seeking help with cancer-related distress by helping patients move towards acceptance. Some participants had already begun the process of accepting their diagnosis before joining the group, others developed acceptance during the group process, while a few continued to be distressed. Our analysis revealed the emergence of four themes related to illness acceptance: (1) Facilitator-Initiated Discussion, including sub-themes of Mindfulness, Relaxation and Imagery, Changing Ways of Thinking, and Spirituality; (2) Personal attitudes, including sub-themes of Optimism and Letting Go of Control; (3) Supportive Environment, including the sub-themes of Providing Support to Others and Receiving Support from Others; and (4) Existential Experience, which included sub-themes of Living with the Diagnosis for an Extended Amount of Time, Legacy and Death Preparations, and Appreciating life. Conclusions: With a paradigm shift to online delivery of psychological services, recognizing factors that contribute to acceptance when dealing with advanced cancer may help inform clinical practices. Future studies should explore patient acceptance longitudinally to inform whether it emerges progressively, which has been suggested by Kübler-Ross.

Salmonella Typhi Vi capsule prime-boost vaccination induces convergent and functional antibody responses.

Vaccine development to prevent Salmonella Typhi infections has accelerated over the past decade, resulting in licensure of new vaccines, which use the Vi polysaccharide (Vi PS) of the bacterium conjugated to an unrelated carrier protein as the active component. Antibodies elicited by these vaccines are important for mediating protection against typhoid fever. However, the characteristics of protective and functional Vi antibodies are unknown. In this study, we investigated the human antibody repertoire, avidity maturation, epitope specificity, and function after immunization with a single dose of Vi-tetanus toxoid conjugate vaccine (Vi-TT) and after a booster with plain Vi PS (Vi-PS). The Vi-TT prime induced an IgG1-dominant response, whereas the Vi-TT prime followed by the Vi-PS boost induced IgG1 and IgG2 antibody production. B cells from recipients who received both prime and boost showed evidence of convergence, with shared V gene usage and CDR3 characteristics. The detected Vi antibodies showed heterogeneous avidity ranging from 10 µM to 500 pM, with no evidence of affinity maturation after the boost. Vi-specific antibodies mediated Fc effector functions, which correlated with antibody dissociation kinetics but not with association kinetics. We identified antibodies induced by prime and boost vaccines that recognized subdominant epitopes, indicated by binding to the de­O-acetylated Vi backbone. These antibodies also mediated Fc-dependent functions, such as complement deposition and monocyte phagocytosis. Defining strategies on how to broaden epitope targeting for S. Typhi Vi and enriching for antibody Fc functions that protect against typhoid fever will advance the design of high-efficacy Vi vaccines for protection across diverse populations.

Suicide Risk Screening and Suicide Prevention in Patients With Cancer.

Background: Suicide rates are up to 4 times greater in cancer compared with the general population, yet best practices for institutional suicide prevention are unknown. The objective of this study was to examine the association between suicide risk screening (SRS), clinician response, and suicide mortality at a comprehensive cancer treatment center. Methods: We conducted a naturalistic, retrospective cohort study of patients attending the Princess Margaret Cancer Centre, where routine screening for suicidal intent within the Distress Assessment and Response Tool (DART-SRS) was implemented in 2010. Inverse probability of treatment weighting was used to evaluate the impact of DART-SRS completion on suicide mortality from 2005 to 2014. Chart audits were conducted for clinician response to suicidality, and crude suicide rates over the study period were analyzed. All statistical tests were 2-sided. Results: Among 78 650 cancer patients, 89 (0.1%) died by suicide, of whom only 4 (4.5%) had completed DART-SRS. Among DART-SRS completers (n = 14 517), 69 (0.5%) reported suicidal intent, none of whom died by suicide. DART-SRS completion was associated with increased clinician response to suicidality (17.4% vs 6.7%, P = .04), more psychosocial service usage (30.5% vs 18.3%, P < .001), and lower suicide mortality (hazard ratio = 0.29, 95% confidence interval = 0.28 to 0.31). Crude suicide rates at the Princess Margaret Cancer Centre were lower in patients whose first contact year was after DART-SRS implementation. Conclusion: DART-SRS completion is associated with lower suicide mortality and increased access to psychosocial care, but patients who did not complete DART-SRS were at highest suicide risk. Further research is needed to identify mechanisms to ensure psychosocial and suicidality assessment in cancer patients who do not complete SRS.

Selection of individuals for lung cancer screening based on risk prediction model performance and economic factors - The Ontario experience.

INTRODUCTION: Randomized controlled trials have shown that screening with computed tomography reduces lung cancer mortality but is most effective when applied to high-risk individuals. Accurate lung cancer risk prediction models effectively select individuals for screening. Few pilots or programs have implemented risk models for enrolling individuals for screening in real-world, population-based settings. This report describes implementation of the PLCOm2012 risk prediction model in the Ontario Health (Cancer Care Ontario) lung cancer screening Pilot. METHODS: In the Pilot's Health Technology Assessment, 576 categorical age/pack-years/quit-years scenarios were evaluated using MISCAN microsimulation modeling and cost-effectiveness analyses. A preferred model was selected which provided the most life-years gained per cost. The PLCOm2012 was compared to the preferred MISCAN scenario at a threshold that yielded the same number eligible (risk ≥2.0 %/6-years). RESULTS: The PLCOm2012 had significantly higher sensitivity and predictive value (68.1 % vs 59.6 %, p < 0.0001; 4.90 % vs 4.29 %, p = 0.044), and an Expert Panel selected it for use in the Pilot. The Pilot cancer detection rate was significantly higher than in the NLST (p = 0.009) or NELSON (p = 0.003) and there was a significant shift to early stage compared to historical Ontario Cancer Registry statistics (p < 0.0001). Pre- and post-Pilot evaluations found that conducting quality risk assessments were not excessively time consuming or difficult, and participants' satisfaction was high. CONCLUSIONS: The PLCOm2012 was efficiently implemented in the Pilot in a real-world setting and is being used to transition into a provincial program. Compared to categorical age/pack-years/quit-years criteria, risk assessment using the PLCOm2012 can lead to effective and efficient screening.