The effects of the first UK lockdown for the COVID-19 pandemic on primary-care-recorded cancer and type-2 diabetes mellitus records: A population-based quasi-experimental time series study.

BACKGROUND: COVID-19 disrupted consulting behaviour, healthcare delivery and cancer diagnostic services. This study quantifies the cancer incidence coded in UK general practice electronic health records and deviations from historical trends after the March 2020 national lockdown. For comparison, we study the coded incidence of type-2 diabetes mellitus, which is diagnosed almost entirely within primary care. METHODS: Poisson interrupted time series models investigated the coded incidence of diagnoses in adults aged ≥ 18 years in the Clinical Practice Research Datalink before (01/03/2017-29/02/2020) and after (01/03/2020-28/02/2022) the first lockdown. Datasets were stratified by age, sex, and general practice per 28-day aggregation period. Models captured incidence changes associated with lockdown, both immediately and over time based on historical trends. RESULTS: We studied 189,457 incident cancer and 191,915 incident diabetes records in 1480 general practices over 52,374,197 person-years at risk. During 01/03/2020-28/02/2022, there were fewer incident records of cancer (n = 22,199, 10.49 %, 10.44-10.53 %) and diabetes (n = 15,709, 7.57 %, 7.53-7.61 %) than expected. Within cancers, impacts ranged from no effect (e.g. unknown primary, pancreas, and ovary), to small effects for lung (n = 773, 3.11 %, 3.09-3.13 % fewer records) and female breast (n = 2686, 6.77 %, 6.73-6.81 %), to the greatest effect for bladder (n = 2874, 31.15 %, 31.00-31.31 %). Diabetes and cancer records recovered maximally to 86 % (95 %CI 80.3-92.7 %) and 74 % (95 %CI 70.3-78.6 %) in July 2021 and May 2021, respectively, of their expected values, declining again until the study end. CONCLUSION: The "missing" cancer and diabetes diagnoses in primary care may comprise delayed or missed diagnoses, reduced incidence associated with excess deaths from COVID-19, and potentially increased non-coded recording of diagnoses. Future validation studies must quantify the concordance between primary care and National Cancer Registration Data and Hospital Episode Statistics over the pandemic era.

A qualitative study of stakeholders' experiences with and acceptability of a technology-supported health coaching intervention (SHARE-S) delivered in coordination with cancer survivorship care.

PURPOSE: Healthy cancer survivorship involves patients' active engagement with preventative health behaviors and follow-up care. While clinicians and patients have typically held dual responsibility for activating these behaviors, transitioning some clinician effort to technology and health coaches may enhance guideline implementation. This paper reports on the acceptability of the Shared Healthcare Actions & Reflections Electronic systems in survivorship (SHARE-S) program, an entirely virtual multicomponent intervention incorporating e-referrals, remotely-delivered health coaching, and automated text messages to enhance patient self-management and promote healthy survivorship. METHODS: SHARE-S was evaluated in single group hybrid implementation-effectiveness pilot study. Patients were e-referred from the clinical team to health coaches for three health self-management coaching calls and received text messages to enhance coaching. Semi-structured qualitative interviews were conducted with 21 patient participants, 2 referring clinicians, and 2 health coaches to determine intervention acceptability (attitudes, appropriateness, suitability, convenience, and perceived effectiveness) and to identify important elements of the program and potential mechanisms of action to guide future implementation. RESULTS: SHARE-S was described as impactful and convenient. The nondirective, patient-centered health coaching and mindfulness exercises were deemed most acceptable; text messages were less acceptable. Stakeholders suggested increased flexibility in format, frequency, timing, and length of participation, and additional tailored educational materials. Patients reported tangible health behavior changes, improved mood, and increased accountability and self-efficacy. CONCLUSIONS: SHARE-S is overall an acceptable and potentially effective intervention that may enhance survivors' self-management and well-being. Alterations to tailored content, timing, and dose should be tested to determine impact on acceptability and outcomes.

An exploration into the relationship between insomnia and repetitive negative thinking among cancer survivors.

OBJECTIVE: Insomnia and repetitive negative thinking (RNT) are both prevalent among cancer survivors, yet little work has investigated their interrelationship. To explore the hypothesis that RNT and insomnia are related, we conducted secondary analyses on data from a pilot clinical trial of cognitive behavioral therapy for insomnia (CBT-I) for cancer survivors. METHODS: This study analyzed survey data from 40 cancer survivors with insomnia who participated in a pilot randomized trial of CBT-I. Correlations and linear regression models were used to determine associations between aspects of RNT and related constructs (fear of cancer recurrence [FCR], cancer-specific rumination, worry, and intolerance of uncertainty) and sleep (insomnia and sleep quality), while accounting for psychiatric symptoms such as anxiety and depression. Treatment-related change in RNT was examined using a series of linear mixed models. RESULTS: Evidence for an association between RNT and insomnia among cancer survivors emerged. Higher levels of FCR and cancer-related rumination were correlated with more severe insomnia symptoms and worse sleep quality. Notably, FCR levels predicted insomnia, even after controlling for anxiety and depression. Results identified potential benefits and limitations of CBT-I in addressing RNT that should be examined more thoroughly in future research. CONCLUSIONS: RNT is a potential target to consider in insomnia treatment for cancer survivors.

Results from the Delivery of a Community Health Worker Training to Advance Competencies in Cancer Genomics.

INTRODUCTION: Less than half of eligible Black women are assessed for genetic risk and only 28% engage in recommended HBOC risk-reducing interventions. CHWs are trusted members of the community that work as a liaison between health systems and the community to improve access to services and support cancer prevention efforts, though they are an overlooked to support genetic risk assessment. To address the need and training gaps for CHWs we developed and assessed an online training program called KEEP IT (Keeping Each other Engaged Program via IT). METHODS: The curriculum and modules were developed through engaging a panel of experts in a three-round Delphi process. The process led to creation of 10 modules for the training. Recruitment focused on CHWs who worked in clinical settings or groups providing outreach or health services to Black women. Measures of the training were guided by the RE-AIM framework to evaluate the course and its effectiveness. RESULTS: 46 individuals expressed interest in the training after recruitment. 38 individuals were eligible for the training and 26 completed the course. We found improvements in knowledge and genomics competencies immediately post-course, but the majority of these improvements were not sustained at three-months follow up. The training was highly rated for its relevance to CHW work and overall delivery. Top rated sessions included Hereditary Breast and Ovarian Cancer and Family History and Family History Collection. On average, participants reported discussing HBOC with 17 individuals at three-months follow-up. DISCUSSION: Championing a diverse cancer and genomics workforce can help address the goals of the National Cancer Plan to improve early detection and health equity. Through this training, CHWs gained critical cancer and genomics knowledge that was then applied to their primary roles.

Drinking water sources, quality, and associated health outcomes in Appalachian Virginia: A risk characterization study in two counties.

OBJECTIVES: In the US, violations of drinking water regulations are highest in lower-income rural areas overall, and particularly in Central Appalachia. However, data on drinking water use, quality, and associated health outcomes in rural Appalachia are limited. We sought to assess public and private drinking water sources and associated risk factors for waterborne pathogen exposures for individuals living in rural regions of Appalachian Virginia. METHODS: We administered surveys and collected tap water, bottled water, and saliva samples in lower-income households in two adjacent rural counties in southwest Virginia (bordering Kentucky and Tennessee). Water samples were tested for pH, temperature, conductivity, total coliforms, E. coli, free chlorine, nitrate, fluoride, heavy metals, and specific pathogen targets. Saliva samples were analyzed for antibody responses to potentially waterborne infections. We also shared water analysis results with households. RESULTS: We enrolled 33 households (83 individuals), 82% (n = 27) with utility-supplied water and 18% with private wells (n = 3) or springs (n = 3). 58% (n = 19) reported household incomes of <$20,000/year. Total coliforms were detected in water samples from 33% (n = 11) of homes, E. coli in 12%, all with wells or springs (n = 4), and Aeromonas, Campylobacter, and Enterobacter in 9%, all spring water (n = 3). Diarrhea was reported for 10% of individuals (n = 8), but was not associated with E. coli detection. 34% (n = 15) of saliva samples had detectable antibody responses for Cryptosporidium spp., C. jejuni, and Hepatitis E. After controlling for covariates and clustering, individuals in households with septic systems and straight pipes had significantly higher likelihoods of antibody detection (risk ratios = 3.28, 95%CI = 1.01-10.65). CONCLUSIONS: To our knowledge, this is the first study to collect and analyze drinking water samples, saliva samples, and reported health outcome data from low-income households in Central Appalachia. Our findings indicate that utility-supplied water in this region was generally safe, and individuals in low-income households without utility-supplied water or sewerage have higher exposures to waterborne pathogens.

Strategies to improve postpartum engagement in healthcare after high-risk conditions diagnosed in pregnancy: a narrative review.

Transition from antepartum to postpartum care is important, but often fragmented, and attendance at postpartum visits can be poor. Access to care is especially important for individuals diagnosed antepartum with conditions associated with longer-term implications, including gestational diabetes (GDM) and hypertensive disorders in pregnancy (HDP). Strategies to link and strengthen this transition are essential to support people to attend recommended appointments and testing. This narrative review evaluates what is known about postpartum transition of care after higher-risk antepartum conditions, discusses barriers and facilitators to uptake of recommended testing, and outlines strategies trialled to increase both postpartum attendance and testing. Barriers to attendance frequently overlap with general barriers to accessing healthcare. Specific postpartum challenges include difficulties with transport, coordinating breastfeeding and childcare access. Systemic challenges include inadequate communication to women around implications of health conditions diagnosed in pregnancy, and the importance of postpartum follow up. Uptake of recommended testing after a diagnosis of GDM and HDP is variable but generally suboptimal. Strategies which demonstrate promise include the use of patient navigators, focused education and specialised clinics. Reminder systems have had variable impact. Telehealth and technology are under-utilised in this field but offer promising options particularly with the expansion of virtual healthcare into routine maternity care. Strategies to improve both attendance rates and uptake of testing must be designed to address disparities in healthcare access and tailored to the needs of the community. This review provides a starting point to develop such strategies from the community level to the population level.

Gender inequalities across ethnicities in primary care cancer referrals: scoping review protocol.

BACKGROUND: Early cancer diagnosis is associated with improved mortality and morbidity; however, studies indicate that women and individuals from ethnic minorities experience longer times to diagnosis and worse prognosis compared to their counterparts for various cancers. In countries with a gatekeeper healthcare system, such as UK, most suspected cancer referrals are initiated in primary care. AIM: To understand the extent of evidence available on the relationship between primary care cancer referral pathways and cancer outcomes in relation to gender across different ethnic groups. This will identify research gaps and enable development of strategies to ease potential inequalities in cancer diagnosis. DESIGN & SETTING: A scoping review based on the Joanna Briggs Institute methodology. PRISMA-ScR will be used. METHOD: Electronic databases and private collections of the team members will be searched for studies. Two independent reviewers will carry out the study selection and data extraction. Based on participants, concept and context framework, this review will consider studies after year 2000 that explored the relationship between gender, across various ethnic groups, and cancer outcomes following primary care cancer referral in countries with gatekeeper healthcare systems (UK, New Zealand, Sweden, Australia, Canada, Denmark, Ireland and Norway). Results will be presented as a narrative analysis. CONCLUSION: The results are expected to provide an overview of the discrepancies in primary care cancer referrals based on gender across ethnic groups, which will be crucial to define an appropriate range of strategies to ease any inequalities in primary healthcare cancer diagnosis. OPEN SCIENCE FRAMEWORK PROTOCOL REGISTRATION: https://osf.io/jvtxb.

The role of funded partnerships in working towards decreasing COVID-19 vaccination disparities, United States, March 2021-December 2022.

During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors.

An audit of the maternal medicine clinic: Cancer and pregnancy.

AIMS: To explore the incidence and complexity of women presenting for maternity care who require concurrent cancer care, and to report the birth outcomes of these women. MATERIALS AND METHODS: A retrospective audit of women attending a 'high risk' maternal medicine clinic at an Australian tertiary maternity hospital between 1 October 2021 and 30 April 2023 was conducted. The inclusion criteria were a diagnosis of cancer and a concurrent pregnancy, or a diagnosis of cancer prior to the current pregnancy. Clinic lists and coding data were screened via the electronic medical record to identify potential subjects. Data were collected from the individual maternity and neonatal records. RESULTS: Forty of 705 (5.7%) women attending the maternal medicine clinic met the inclusion criteria, of which ten had a new diagnosis of cancer in pregnancy and 30 presented for maternity care after a previous diagnosis of cancer. Cancer therapy during pregnancy included surgery and chemotherapy. Most pregnancies (92.5%) resulted in term deliveries (≥37 weeks gestation). Four neonates were preterm, and one was small-for-gestational-age. Caesarean section delivery and post-partum haemorrhage were more common than expected, but the rate of other adverse pregnancy outcomes was consistent with the background population. Over half of neonates required neonatal intensive care unit / special care nursery admission but the indications for admission were common, self-limiting conditions, and the length of stay was short (mean <5.0 days). CONCLUSIONS: Approximately 6% of women attending the maternal medicine clinic had a current or previous diagnosis of cancer. Most pregnancies resulted in term deliveries and neonatal outcomes were excellent.

Microneedle array delivery of Yersinia pestis recapitulates bubonic plague.

Fleas transmit Yersinia pestis directly within the dermis of mammals to cause bubonic plague. Syringe-mediated inoculation is widely used to recapitulate bubonic plague and study Y. pestis pathogenesis. However, intradermal needle inoculation is tedious, error prone, and poses a significant safety risk for laboratorians. Microneedle arrays (MNAs) are micron-scale polymeric structures that deliver materials to the dermis, while minimizing the risk of needle sticks. We demonstrated that MNA inoculation is a viable strategy to recapitulate bubonic plague and study bacterial virulence by defining the parameters needed to establish a lethal infection in the mouse model and characterizing the course of infection using live-animal optical imaging. Using MNAs, we also demonstrated that Y. pestis must overcome calprotectin-mediated zinc restriction within the dermis and dermal delivery of an attenuated mutant has vaccine potential. Together, these data demonstrate that MNAs are a safe alternative to study Y. pestis pathogenesis in the laboratory.

Patterns of neurological adverse events among a retrospective cohort of patients receiving immune checkpoint inhibitors.

Aim: Neurological adverse events (NAEs) are infrequent immune checkpoint inhibitor (ICI) outcomes poorly characterized in extant research, complicating their clinical management. Methods: This study characterized the frequency, severity, patterning and timing of NAEs using a large retrospective registry, including all patients who received at least one dose of an ICI from 2/1/2011-4/7/2022 within our health network. Results: Among 3137 patients, there were 54 NAEs (1.72% any grade; 0.8% grade 3-4). Most NAEs were peripheral (57.4%) versus central (42.6%). Melanoma and renal cell carcinoma were significantly associated with NAEs. Conclusion: The incidence of NAEs was rare though higher than many prior case estimates; the timing was consistent with other AEs. NAEs frequently occurred in tumor types known to favor brain metastases.

Immune checkpoint inhibitors are new drugs for cancer. They boost your body's defenses to fight cancer cells. These drugs can be used alone or with other cancer treatments. Most people are okay with these medicines, but some might have problems in different parts of the body. This can be tricky to figure out. Rarely, there can be issues in the brain or nerves. These side effects are rare, happening in about 2 in every 100 people who use the drugs. They are more common in certain cancers like melanoma and kidney cancer. As doctors learn more about these side effects, they can better predict, treat, and prevent them.

Type 3 secretion system induced leukotriene B4 synthesis by leukocytes is actively inhibited by Yersinia pestis to evade early immune recognition.

Subverting the host immune response to inhibit inflammation is a key virulence strategy of Yersinia pestis. The inflammatory cascade is tightly controlled via the sequential action of lipid and protein mediators of inflammation. Because delayed inflammation is essential for Y. pestis to cause lethal infection, defining the Y. pestis mechanisms to manipulate the inflammatory cascade is necessary to understand this pathogen's virulence. While previous studies have established that Y. pestis actively inhibits the expression of host proteins that mediate inflammation, there is currently a gap in our understanding of the inflammatory lipid mediator response during plague. Here we used the murine model to define the kinetics of the synthesis of leukotriene B4 (LTB4), a pro-inflammatory lipid chemoattractant and immune cell activator, within the lungs during pneumonic plague. Furthermore, we demonstrated that exogenous administration of LTB4 prior to infection limited bacterial proliferation, suggesting that the absence of LTB4 synthesis during plague contributes to Y. pestis immune evasion. Using primary leukocytes from mice and humans further revealed that Y. pestis actively inhibits the synthesis of LTB4. Finally, using Y. pestis mutants in the Ysc type 3 secretion system (T3SS) and Yersinia outer protein (Yop) effectors, we demonstrate that leukocytes recognize the T3SS to initiate the rapid synthesis of LTB4. However, several Yop effectors secreted through the T3SS effectively inhibit this host response. Together, these data demonstrate that Y. pestis actively inhibits the synthesis of the inflammatory lipid LTB4 contributing to the delay in the inflammatory cascade required for rapid recruitment of leukocytes to sites of infection.

Cardiovascular health assessment in routine cancer follow-up in community settings: survivor risk awareness and perspectives.

BACKGROUND: Guidelines recommend cardiovascular risk assessment and counseling for cancer survivors. For effective implementation, it is critical to understand survivor cardiovascular health (CVH) profiles and perspectives in community settings. We aimed to (1) Assess survivor CVH profiles, (2) compare self-reported and EHR-based categorization of CVH factors, and (3) describe perceptions regarding addressing CVH during oncology encounters. METHODS: This cross-sectional analysis utilized data from an ongoing NCI Community Oncology Research Program trial of an EHR heart health tool for cancer survivors (WF-1804CD). Survivors presenting for routine care after potentially curative treatment recruited from 8 oncology practices completed a pre-visit survey, including American Heart Association Simple 7 CVH factors (classified as ideal, intermediate, or poor). Medical record abstraction ascertained CVD risk factors and cancer characteristics. Likert-type questions assessed desired discussion during oncology care. RESULTS: Of 502 enrolled survivors (95.6% female; mean time since diagnosis = 4.2 years), most had breast cancer (79.7%). Many survivors had common cardiovascular comorbidities, including high cholesterol (48.3%), hypertension or high BP (47.8%) obesity (33.1%), and diabetes (20.5%); 30.5% of survivors received high cardiotoxicity potential cancer treatment. Less than half had ideal/non-missing levels for physical activity (48.0%), BMI (18.9%), cholesterol (17.9%), blood pressure (14.1%), healthy diet (11.0%), and glucose/ HbA1c (6.0%). While > 50% of survivors had concordant EHR-self-report categorization for smoking, BMI, and blood pressure; cholesterol, glucose, and A1C were unknown by survivors and/or missing in the EHR for most. Most survivors agreed oncology providers should talk about heart health (78.9%). CONCLUSIONS: Tools to promote CVH discussion can fill gaps in CVH knowledge and are likely to be well-received by survivors in community settings. TRIAL REGISTRATION: NCT03935282, Registered 10/01/2020.

Collaborative depression care sensitive to the needs of underserved patients with cancer: Feasibility, acceptability and outcomes.

PURPOSE: A single-arm trial evaluated the feasibility, acceptability, and outcomes of COPE-D, a collaborative care intervention for underserved cancer patients with depression. METHODS: Bilingual (Spanish and English) care managers provided counseling and/or medication management in consultation with physicians. Outcomes were treatment improvement (≥ 5-point reduction in PHQ-9), treatment response (≥ 50% reduction in PHQ-9), suicidal ideation resolution, and changes in depression (PHQ-9), anxiety (GAD-2), sleep disturbance (PSQI), global mental and physical health (PROMIS), social isolation (PROMIS), and qualitative feedback. RESULTS: 193 patients consented to participate. 165 initiated and 141 completed treatment, with 65% and 56% achieving treatment improvement and response, respectively. Outcomes did not differ by ethnicity (31% Hispanic), cancer stage (71% stages III-IV), income, or education. Suicidal ideation, depression, anxiety, sleep disturbance, and social isolation also improved. Qualitative feedback was largely positive. CONCLUSION: COPE-D improved depression and quality of life among underserved patients, with acceptable retention rates.

What does competently delivered neuropsychological assessment feedback look like? Development and validation of a competency evaluation tool.

Objective: Neuropsychological assessment (NP) feedback helps patients and caregivers understand assessment results to maximise their utility and impact in everyday life. Yet feedback practices are inconsistent and there are no evidence-based guidelines for how feedback should be most effectively delivered. The aim of our study was to develop a psychometrically sound feedback competency checklist, the Psychology Competency Assessment Tool - Feedback (PsyCET-F), for use in research, training, and clinical settings. Method: The Delphi method of expert consensus was used to establish checklist items that clearly described competencies important for NP feedback. To examine the inter-rater reliability of the checklist, two experienced neuropsychologists rated the competencies demonstrated by trainee neuropsychologists across four feedback sessions. Results: After two Delphi rounds, consensus was reached on the 20-item checklist. Consensus was defined as at least 80% agreement amongst the panel of 20 experts. Four item categories resulted from the Delphi: (a) Opening the Session; (b) Applying Specific Feedback Techniques; (c) Engagement, Collaboration, and Alliance; and (d) Structuring and Ending the Session. Inter-rater reliability was moderate (κW = 0.79, p <.001, 80.52% agreement) when using a simple coding system, coded as Beginner, Intermediate, Competent, and Skilful; and strong (κW = 0.82, p <.001) when competency level was coded using an 8-point, detailed coding method. Conclusions: The PsyCET-F is psychometrically sound and fit-for-purpose for measuring competencies in giving NP feedback. It can be used in the training of clinicians to develop effective feedback skills. International benchmarking and usability testing will be conducted in a future study.

Adapting Connect for Health pediatric weight management program for telehealth in response to the COVID-19 pandemic.

BACKGROUND: To address the evolving needs and context changes due to the COVID-19 pandemic, we adapted Connect for Health, an evidence-based, primary care, pediatric weight management intervention. The objective of this study is to describe the planned adaptation process to ensure continued and equitable program uptake during the pandemic. METHODS: Guided by adaptation frameworks, we identified the core functions and forms of Connect for Health and then adapted the intervention in response to a changing healthcare context. We engaged stakeholders and surveyed parents of children with a BMI ≥ 85th percentile and pediatric clinicians and examined their experiences using telehealth for pediatric weight management and needs and preferences. Using multivariable logistic regression, we examined the preferences of parents with limited English proficiency regarding key aspects of pediatric weight management. RESULTS: We surveyed 200 parents and 43% had a primary language of Spanish. Parents wanted care to be a combination of in-person and virtual visits (80%). We found that parents with limited English proficiency had a higher odds ratio of affirming in-person visits are better than virtual visits for ensuring their child's health concern can be taken care of (OR: 2.91; 95% CI: 1.36, 6.21), feeling comfortable when discussing personal information (OR: 3.91; 95% CI: 1.82, 8.43), talking about healthy behaviors and setting goals (OR: 3.09; 95% CI: 1.39, 6.90), and talking about mental health and overall well-being (OR: 4.02; 95% CI: 1.83, 8.87) than parents without limited English proficiency. We surveyed 75 clinicians and 60% felt telehealth was a useful tool to provide care for pediatric weight management. Clinicians felt virtual visits did not pose barriers to all aspects of care. Informed by the surveys and stakeholder input, we made clinician- and family-level adaptations while retaining the program's function. CONCLUSIONS: By engaging stakeholders and adapting the program for telehealth, we optimized the reach and fit of Connect for Health to ensure its continued uptake. We have provided a real-world example of how clinical innovations can evolve and how to systematically plan adaptations in response to changing healthcare contexts. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04042493), Registered on August 2, 2019.

Microwave imaging for monitoring breast cancer treatment: A pilot study.

BACKGROUND: Microwave imaging has been proposed for medical applications, creating maps related to water content of tissues. Breast imaging has emerged as a key application because the signals can be coupled directly into the breast and experience limited attenuation in fatty tissues. While the literature contains reports of tumor detection with microwave approaches, there is limited exploration of treatment monitoring. PURPOSE: This study aims to detect treatment-related changes in breast tissue with a low-resolution microwave scanner. METHODS: Microwave scans of 15 patients undergoing treatment for early-stage breast cancer are collected at up to 4 time points: after surgery (baseline), 6 weeks after accelerated partial breast radiation, as well as 1 and 2 years post-treatment. Both the treated and untreated breast are scanned at each time point. The microwave scanner consists of planar transmit and receive arrays and uses signals from 0.1 to 10 GHz. The average microwave frequency properties (permittivity) are calculated for each scan to enable quantitative comparison. Baseline and 6-week results are analyzed with a two-way ANOVA with blocking. RESULTS: Consistent properties are observed for the untreated breast over time, similar to a previous study. Comparison of the scans of the treated and untreated breast suggests increased properties related to treatment, particularly at baseline and 6-weeks following radiotherapy. Analysis of the average properties of the scans with ANOVA indicates statistically significant differences ( p < 0.05 $p < 0.05$ ) in the treated and untreated breast at these time points. CONCLUSIONS: Microwave imaging has the potential to track treatment-related changes in breast tissues.

Incidence of 'Low-Risk but Not No-Risk' Features of Cancer Prior to High-Risk Feature Occurrence: An Observational Cohort Study in Primary Care.

Diagnosing cancer may be expedited by decreasing referral risk threshold. Clinical Practice Research Datalink participants (≥40 years) had a positive predictive value (PPV) ≥3% feature for breast, lung, colorectal, oesophagogastric, pancreatic, renal, bladder, prostatic, ovarian, endometrial or laryngeal cancer in 2016. The numbers of participants with features representing a 1-1.99% or 2-2.99% PPV for same cancer in the previous year were reported, alongside the time difference between meeting the ≥3% criteria and the lower threshold criteria. A total of 8616 participants had a PPV ≥3% feature, of whom 365 (4.2%) and 1147 (13.3%), respectively, met 2-2.99% and 1-1.99% criteria in the preceding year. The median time difference was 131 days (Interquartile Range (IQR) 27 to 256) for the 2-2.99% band and 179 days (IQR 58 to 289) for the 1-1.99% band. Results were heterogeneous across cancer sites. For some cancers, participants may progress from presenting lower- to higher-risk features before meeting urgent referral criteria; however, this was not usually the case. The details of specific features across multiple cancer sites will allow for a tailored approach to future reductions in referral thresholds, potentially improving the efficiency of urgent cancer referrals for the benefit both of individuals and the National Health Service (NHS).

Droplet Tn-Seq identifies the primary secretion mechanism for yersiniabactin in Yersinia pestis.

Nutritional immunity includes sequestration of transition metals from invading pathogens. Yersinia pestis overcomes nutritional immunity by secreting yersiniabactin to acquire iron and zinc during infection. While the mechanisms for yersiniabactin synthesis and import are well-defined, those responsible for yersiniabactin secretion are unknown. Identification of this mechanism has been difficult because conventional mutagenesis approaches are unable to inhibit trans-complementation by secreted factors between mutants. To overcome this obstacle, we utilized a technique called droplet Tn-seq (dTn-seq), which uses microfluidics to isolate individual transposon mutants in oil droplets, eliminating trans-complementation between bacteria. Using this approach, we first demonstrated the applicability of dTn-seq to identify genes with secreted functions. We then applied dTn-seq to identify an AcrAB efflux system as required for growth in metal-limited conditions. Finally, we showed this efflux system is the primary yersiniabactin secretion mechanism and required for virulence during bubonic and pneumonic plague. Together, these studies have revealed the yersiniabactin secretion mechanism that has eluded researchers for over 30 years and identified a potential therapeutic target for bacteria that use yersiniabactin for metal acquisition.