Estimating and Rewarding the Value of Healthcare Interventions Beyond the Healthcare Sector: A Conceptual Framework.

BACKGROUND: Evaluating healthcare interventions for their impacts beyond health outcomes may result in recognition of changes in human capital, income level, tax revenue, and government spending, which could affect economic growth and population health. In this paper, we document instances where current health technology assessment (HTA) practices fail to account for the impacts of healthcare interventions on broader society beyond the healthcare sector. METHODS: We propose a novel conceptual framework, highlighting its three components (distributional cost-effectiveness analysis [DCEA], input-output model, and voting scheme) and their contributions to capturing the economic and societal ripple effects of healthcare interventions. This manuscript also outlines a case study in which the framework is applied to the reassessment of a previously evaluated digital health therapeutic for the treatment of opioid use disorder (OUD) compared with standard of care, demonstrating its practical application. RESULTS: The DCEA health value metric indicates that digital therapeutic is more equitable, favoring socioeconomically disadvantaged groups, while standard of care exacerbates health inequality by benefiting the already advantaged. Additionally, digital therapeutic shows potential for boosting productivity, raising income, and creating jobs, supporting its consideration by employer-sponsored health plans to optimize resource allocation for treating OUD. CONCLUSION: The conceptual framework provides insights for enhancing HTAs to incorporate the broader economic and societal impacts of healthcare interventions. By integrating DCEA, extended HTA analysis with input-output modeling, and a voting scheme, decision makers can make informed choices aligned with societal priorities, although further research and validation are necessary for practical implementation across diverse healthcare contexts.

Trajectories of Health Care Contact Days for Patients With Stage IV Non-Small Cell Lung Cancer.

Importance: Patients with stage IV non-small cell lung cancer (NSCLC) experience substantial morbidity and mortality. Contact days (ie, the number of days with health care contact outside the home) measure how much of a person's life is consumed by health care, yet little is known about patterns of contact days for patients with NSCLC. Objective: To describe the trajectories of contact days in patients with stage IV NSCLC and how trajectories vary by receipt of cancer-directed treatment in routine practice. Design, Setting, and Participants: A retrospective, population-based decedent cohort study was conducted in Ontario, Canada. Participants included adults aged 20 years or older who were diagnosed with stage IV NSCLC (January 1, 2014, to December 31, 2017) and died (January 1, 2014, to December 31, 2019); there was a maximum 2-year follow-up. Data analysis was conducted from February 22 to August 16, 2023. Exposure: Systemic cancer-directed therapy (yes or no) and type of therapy (chemotherapy vs immunotherapy vs targeted therapy). Main Outcomes and Measures: Contact days (days with health care contact, outpatient or institution-based, outside the home) were identified through administrative data. The weekly percentage of contact days and fitted models with cubic splines were quantified to describe trajectories from diagnosis until death. Results: A total of 5785 decedents with stage IV NSCLC were included (median age, 70 [IQR 62-77] years; 3108 [53.7%] were male, and 1985 [34.3%] received systemic therapy). The median overall survival was 108 (IQR, 49-426) days, median contact days were 36 (IQR, 21-62), and the median percentage that were contact days was 33.3%. A median of 5 (IQR, 2-10) days were spent with specialty palliative care. Patients who did not receive systemic therapy had a median overall survival of 66 (IQR, 34-130) days and median contact days of 28 (IQR, 17-44), of which a median of 5 (IQR, 2-9) days were spent with specialty palliative care. Overall and for subgroups, normalized trajectories followed a U-shaped distribution: contact days were most frequent immediately after diagnosis and before death. Patients who received targeted therapy had the lowest contact day rate during the trough (10.6%; vs immunotherapy, 15.4%; vs chemotherapy, 17.7%). Conclusions and Relevance: In this cohort study, decedents with stage IV NSCLC had a median survival in the order of 3.5 months and spent 1 in every 3 days alive interacting with the health care system outside the home. These results highlight the need to better support patients and care partners, benchmark appropriateness, and improve care delivery.

People with Intellectual Disabilities, Dysphagia and Post-Covid Syndrome.

People with Intellectual Disability (ID) were more likely to contract COVID-19 infection and more likely to die from the consequences. However, there is no evidence on the long-term impact of COVID-19 infection in people with ID. Post-Covid Syndrome (PCS) is an established diagnosis that requires specialist clinical support. To date there is no data on how common PCS is in people with ID, or how symptoms present. Dysphagia is identified as a clinical marker because of the known association with PCS, and the clear objective diagnostic criteria applicable through specialist assessment. This investigation presents a cohort of people with ID, who developed dysphagia/worsening of dysphagia post diagnosis with COVID-19. Cases were identified through support from the Royal College of Speech and Language Therapists. Data was collected by electronic survey, including application of the COVID-19 Yorkshire Rehabilitation Scale-modified (C19-YRSm). The C19-YRSm is a validated assessment tool for PCS and it's impact upon functional disability. This case series identifies that symptoms consistent with PCS are present in people with ID, post-COVID-19 infection. The risk of diagnostic overshadowing or misdiagnosis is high due to the subjective nature and the quality of PCS symptoms. People with ID who develop PCS may not be readily identified by clinical services and therefore not be accessing the specialist medical support required. Furthermore, changes in behaviour secondary to PCS may lead to unnecessary increased prescribing of psychotropic medication which in itself risks worsening dysphagia. Dysphagia could be an important bellwether to identify PCS in people with ID.

Association of antibiotic exposure with residual cancer burden in HER2-negative early stage breast cancer.

Antibiotic exposure during immunotherapy (IO) has been shown to negatively affect clinical outcomes in various cancer types. The aim of this study was to evaluate whether antibiotic exposure in patients with high-risk early-stage HER2-negative breast cancer (BC) undergoing treatment with neoadjuvant pembrolizumab impacted residual cancer burden (RCB) and pathologic complete response (pCR) in the pembrolizumab-4 arm of the ISPY-2 clinical trial. Patients received pembrolizumab for four cycles concurrently with weekly paclitaxel for 12 weeks, followed by four cycles of doxorubicin plus cyclophosphamide every 2 or 3 weeks. Patients who received at least one dose of systemic antibiotics concurrently at the time of immunotherapy (IO) were included in the antibiotic exposure group (ATB+). All other participants were included in the control group (ATB-). RCB index and PCR rates were compared between the ATB+ and ATB- groups using t-tests and Chi-squared tests, and linear and logistic regression models, respectively. Sixty-six patients were included in the analysis. 18/66 (27%) patients were in the ATB+ group. Antibiotic use during IO was associated with a higher mean RCB index (1.80 ± 1.43 versus 1.08 ± 1.41) and a lower pCR rate (27.8% versus 52.1%). The association between antibiotic use and the RCB index remained significant in multivariable linear regression analysis (RCB index-coefficient 0.86, 95% CI 0.20-1.53, P = 0.01). Our findings suggest that concurrent antibiotic exposure during neoadjuvant pembrolizumab in HER2-negative early-stage BC is associated with higher RCB. Further validation in larger cohorts is needed to confirm these findings.

UK paediatric speech and language therapists' perceptions on the use of telehealth in current and future clinical practice: An application of the APEASE criteria.

BACKGROUND: Telehealth for paediatric speech and language therapy became one of the most salient modes of service delivery during the COVID-19 pandemic. Evidence for speech and language therapy services via telehealth in comparison to face-to-face delivery demonstrates promising outcomes, and studies have begun to explore practitioner and client experiences. However, across the literature, many critical elements of services are overlooked, and there is a need to frame the evidence base within a theoretical model that can draw out practical implications that consider the range of factors having an impact on clinical implementation in real-world contexts. The APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side-effects, and Equity) criteria offer such a model. The current study explored practising UK speech and language therapists' (SLTs) clinical experience of telehealth through the lens of the APEASE criteria and aimed to identify recommendations for future service provision from the practitioner perspective. METHODS: An online survey structured using the APEASE criteria was developed in collaboration with the UK Royal College of Speech and Language Therapists. Quantitative data were analysed using descriptive statistics and qualitative data were analysed using reflexive thematic analysis. RESULTS: Four hundred and thirty-eight qualified and practicing UK paediatric SLTs completed the survey. Telehealth was broadly acceptable and practicable to SLTs yet there remains some uncertainty about its efficacy and cost-effectiveness compared to face-to-face interventions and how equitable it is for different population groups. SLTs reported that effective implementation of telehealth services was dependent upon several contextual factors; affordability was a perceived barrier to clients having access to telehealth resources, intervention via telehealth was perceived as more acceptable than assessment, and whilst many SLTs welcomed aspects of telehealth, there were concerns about the physical and mental health consequences for practitioners. Six themes for the future development of telehealth in paediatric speech and language therapy were identified: (1) balanced and tailored services; (2) technology and equipment; (3) information and communication; (4) capacity building; (5) monitoring and evaluation; and (6) leadership and governance. CONCLUSIONS: Outcomes highlight promising, concerning and uncertain aspects of telehealth in paediatric speech and language therapy. SLTs value a flexible and tailored approach to service delivery and recommend that effective leadership, clear communication, ongoing policy and guidance development, upskilling of users and careful evaluation of impact are required to ensure optimal implementation. The APEASE criteria offer a valuable opportunity to enhance and streamline practice and research to ensure sustainable implementation of telehealth in the paediatric speech and language therapy services of tomorrow. WHAT THIS PAPER ADDS: What is already known on this subject The COVID-19 pandemic led to the increased use of telehealth as a main mode of service delivery in paediatric speech and language therapy. Pre-COVID-19, evidence for the use of telehealth in this field included small-scale experimental studies that reported on children with particular disorders and explored telehealth outcomes in comparison to face-to-face delivery. The realities of at-scale clinical practice were not well-represented, and critical elements of service such as cost-effectiveness were often overlooked in the paediatric literature. Furthermore, despite emerging global evidence for temporary telehealth responses to the crisis in speech and language therapy, the long-term and future use of telehealth remains unclear. What this paper adds to existing knowledge The current study applied the lens of the APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side-effects, and Equity) criteria, which were used in this case to consider socioeconomic, ecological and cultural factors to capture an overarching understanding of the use of telehealth in paediatric speech and language therapy, and to inform the role of telehealth in future, longer-term and at-scale service development. Results indicated emerging trends in UK paediatric speech and language therapists' (SLTs') perceptions of telehealth and SLTs perceived a hybrid approach to service delivery, combining mostly face-to-face services with some telehealth, was likely to continue in the future. We identified six themes to guide the future development of telehealth in paediatric speech and language therapy services: (1) balanced and tailored services; (2) technology and equipment; (3) information and communication; (4) capacity building; (5) monitoring and evaluation; and (6) leadership and governance. What are the potential or actual clinical implications of this work? UK SLTs believe that speech and language therapy services using telehealth should be reflective, tailored and flexible to meet the requirements and circumstances of the children, young people and families served, as well as the physical and emotional needs of practitioners. SLTs recommend that this service development is clearly communicated to all stakeholders and suggested that those using telehealth should be supported through appropriate training, and ongoing effectiveness should be monitored. Telehealth is here to stay and the APEASE criteria offer a unique opportunity to ensure sustainable models of service delivery; to support co-ordinated leadership at the local, national and international levels and the development of policy and clinical guidance.

Clinical characteristics, racial inequities, and outcomes in patients with breast cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) cohort study.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

CK1δ and CK1ε Signaling Sustains Mitochondrial Metabolism and Cell Survival in Multiple Myeloma.

Multiple myeloma remains an incurable malignancy due to acquisition of intrinsic programs that drive therapy resistance. Here we report that casein kinase-1δ (CK1δ) and CK1ε are therapeutic targets in multiple myeloma that are necessary to sustain mitochondrial metabolism. Specifically, the dual CK1δ/CK1ε inhibitor SR-3029 had potent in vivo and ex vivo anti-multiple myeloma activity, including against primary multiple myeloma patient specimens. RNA sequencing (RNA-seq) and metabolic analyses revealed inhibiting CK1δ/CK1ε disables multiple myeloma metabolism by suppressing genes involved in oxidative phosphorylation (OxPhos), reducing citric acid cycle intermediates, and suppressing complexes I and IV of the electron transport chain. Finally, sensitivity of multiple myeloma patient specimens to SR-3029 correlated with elevated expression of mitochondrial genes, and RNA-seq from 687 multiple myeloma patient samples revealed that increased CSNK1D, CSNK1E, and OxPhos genes correlate with disease progression and inferior outcomes. Thus, increases in mitochondrial metabolism are a hallmark of multiple myeloma progression that can be disabled by targeting CK1δ/CK1ε. SIGNIFICANCE: CK1δ and CK1ε are attractive therapeutic targets in multiple myeloma whose expression increases with disease progression and connote poor outcomes, and that are necessary to sustain expression of genes directing OxPhos.

Prevalence of swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19: the PHOSP-COVID analysis.

OBJECTIVE: Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19. DESIGN: Multicentre prospective observational cohort study using questionnaire data at visit 1 (2-7 months post discharge) and visit 2 (10-14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations. SETTING: 64 UK acute hospital Trusts. PARTICIPANTS: Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19. MAIN OUTCOME MEASURES: Self-reported swallow, communication, voice and cognitive compromise. RESULTS: Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001). CONCLUSION: Swallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues.

Cost-Effectiveness of Aripiprazole Tablets with Sensor versus Oral Atypical Antipsychotics for the Treatment of Schizophrenia Using a Patient-Level Microsimulation Modeling Approach.

Objective: Strategies designed to track drug ingestion may improve medication adherence and clinical outcomes in adults with schizophrenia. This study aimed to estimate the cost-effectiveness of aripiprazole tablets with sensor (AS; Abilify MyCite®) versus generic oral atypical antipsychotics (AAPs) in schizophrenia from the United States payer and societal perspectives over 12 months. Methods: An individual-level microsimulation was developed to generate individual trajectories using data from a phase 3b multicenter, open-label, mirror-image trial in adults with schizophrenia treated prospectively for 6 months with AS. The patient's clinical characteristics and outcomes were computed as a function of the Positive and Negative Syndrome Scale (PANSS) scores. Direct and indirect medical cost estimates were sourced from the literature; EuroQol 5-Dimensions (EQ-5D) utilities were derived using risk equations based on patient and clinical characteristics. Scenario analyses were also conducted to assess outcomes under the assumption of treatment durability over 12 months. Results: Over 12 months, AS showed a 12.2% improvement in PANSS score. AS had an incremental cost of $2168 and incremental cost savings of $22,343 from the payer and societal perspectives, respectively, with an incremental quality-adjusted life-year (QALY) gain of 0.0298 versus oral AAPs. Further, AS resulted in a 28.2% reduction in hospitalizations over 12 months. At a willingness-to-pay of $100,000 per QALY, the net monetary benefit over 12 months was $25,323 from the payer perspective. Under the assumption of the durability of the treatment effect of AS, the findings were similar to those of the base case analyses, though with greater cost savings and QALYs gained with AS. The results from the sensitivity analyses were consistent with those of the base case analysis. Conclusion: AS may be a cost-effective strategy, with lower costs and improved quality of life among patients with schizophrenia over 12 months, from the payer and societal perspectives.

Clinical Characteristics, Racial Inequities, and Outcomes in Patients with Breast Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1,383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32 - 1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70 - 6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83 - 12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63 - 3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20 - 2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66 - 3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89 - 22.6]). Hispanic ethnicity, timing and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to Non-Hispanic White patients.

Nonlinear association between body mass index and overall survival in advanced NSCLC patients treated with immune checkpoint blockade.

BACKGROUND: We investigated the association of body mass index (BMI) modeled as a continuous variable with survival outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). METHODS: We performed a single-institution retrospective analysis of consecutively diagnosed locally advanced or metastatic NSCLC patients treated with single-agent ICI in the first line or recurrent setting. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and objective response rate (ORR). BMI was modeled using a four-knot restricted cubic spline. Multiple Cox regression was used for survival analysis. RESULTS: Two hundred patients were included (female 54%; never smoker 12%). Adenocarcinoma was the most common histology (61%). Median age was 67 years, median BMI was 25.9 kg/m2, and 65% of patients had Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1. On multivariable analysis, only BMI and ECOG PS were independently associated with OS (p < 0.01). Mortality risk decreased as the BMI increased from 20 to 30 kg/m2 (HR 0.49, 95% CI 0.28-0.84); however, it was reversed as the BMI surpassed ~ 30 kg/m2. Compared to ECOG PS ≥ 2, patients with ECOG PS of 0-1 had a longer OS (HR 0.42, 95% CI 0.28-0.63). Similar trends were observed with PFS and ORR, but the strength of the association was weaker. CONCLUSION: We observed a nonlinear association between BMI and OS following treatment with ICI in advanced NSCLC. Risk of death increases at both extremes of BMI with a nadir that exists around 30 kg/m2.

Allied health professional research engagement and impact on healthcare performance: A systematic review protocol.

BACKGROUND: Existing evidence suggests that clinician and organization engagement in research can improve healthcare processes of care and outcomes. However, current evidence has considered the relationship across all healthcare professions collectively. With the increase in allied health clinical academic and research activity, it is imperative for healthcare organizations, leaders and managers to understand engagement in research within these specific clinical fields. This systematic review aims to identify the effect of engagement in research by allied health professionals (AHPs) and organizations on healthcare performance. METHODS: This systematic review has a two-stage search strategy. The first stage will be to screen a previous systematic review examining the effectiveness of engagement in research in health and social care to identify relevant papers published pre-2012. The search strategy used in the previous review will then be rerun, but with a specific focus on allied health. This multi-database search will identify publications from 2012 to date. Only studies that assessed the effectiveness of allied health engagement in research will be included. All stages of the review will be conducted by two reviewers independently, plus documented discussions with the wider research team when discrepancies occur. This systematic review protocol follows the EQUATOR reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P). DISCUSSION: The findings of this review will make a significant contribution to the evidence base around the effect of allied health engagement in research on healthcare performance. It will provide insights for clinicians and managers looking to understand the consequences of developing AHP research capability and capacity. The findings of this review will also aim to make recommendations for future evaluation approaches for engagement in research interventions. TRIAL REGISTRATION: This systematic review protocol has been registered with PROSPERO, registration number CRD42021253461. WHAT THIS PAPER ADDS: What is already known on the subject This study will provide valuable evidence for professionals and policymakers seeking to understand engagement in research in the allied health disciplines. Where supported by the data, there may be recommendations for future research regarding specific variables to be considered when planning and evaluating engagement in research in allied health practice. What this paper adds to existing knowledge A previous systematic review identified a positive association between clinician and organization engagement in research and improved processes of care and health outcomes. The reviews' findings have been used as a justification for clinicians and organizations to increase research capacity. That review evaluated literature published before 2012 and the studies that were identified predominantly reported on engagement in research by medics and nurses. An updated review is now required to include research published since 2012. This review will specifically focus on the effect of engagement in research within allied health disciplines. What are the potential or actual clinical implications of this work? Research activity among AHPs is gaining momentum. Given this growth in AHP research activity and the rise in dedicated clinical academic roles, a contemporary review to identify the specific effect of AHP engagement in research on healthcare performance is prudent. The findings will inform clinicians, clinical managers and leaders of the potential impact of research activities by AHP clinicians and organizations. This will support the planning and development of initiatives focused on research capacity, capability and culture within allied health.

Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19.

Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration: ClinicalTrials.gov Identifier: NCT04354701.

Demographics, Outcomes, and Risk Factors for Patients with Sarcoma and COVID-19: A CCC19-Registry Based Retrospective Cohort Study.

BACKGROUND: Patients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19. METHODS: We performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021. Demographics, sarcoma histologic type, treatments, and COVID-19 outcomes were analyzed. RESULTS: of 281 patients, 49% (n = 139) were hospitalized, 33% (n = 93) received supplemental oxygen, 11% (n = 31) were admitted to the ICU, and 6% (n = 16) received mechanical ventilation. A total of 23 (8%) died within 30 days of COVID-19 diagnosis and 44 (16%) died overall at the time of analysis. When evaluated by sarcoma subtype, patients with bone sarcoma and COVID-19 had a higher mortality rate than patients from a matched SEER cohort (13.5% vs 4.4%). Older age, poor performance status, recent systemic anti-cancer therapy, and lung metastases all contributed to higher COVID-19 severity. CONCLUSIONS: Patients with sarcoma have high rates of severe COVID-19 and those with bone sarcoma may have the greatest risk of death.

Impact of the COVID-19 Pandemic on Healthcare Resource Utilization in Individuals with Major Depressive Disorder.

Objective: To estimate the impact COVID-19 pandemic on healthcare resource utilization (HCRU) among individuals with major depressive disorder (MDD). Method: A retrospective cohort study was conducted to compare HCRU in the twelve months prior to and six months following pandemic onset among 1,318,709 individuals with MDD and propensity-score matched controls. Outcomes were monthly rates of all-cause and MDD-specific outpatient, inpatient, and prescription medication HCRU. Piecewise random effects models were used to adjust for patient-level clustering, trends over time, and pre-pandemic factors. Results: In the first month following onset, outpatient HCRU declined with primary care visits down 25.1%. Following this initial decline, outpatient HCRU increased, exceeding pre-pandemic rates within three months. By April 2020, three quarters of all psychotherapy sessions were delivered by telehealth, followed by psychiatry (62.3%), and primary care visits (30.1%). The use of telehealth remained highest for psychotherapy and psychiatry (representing 67.6% and 54.2% of visits, respectively, in September 2020). All-cause partial-day hospitalizations declined 50.5% and remained depressed through July 2020 (down 18.3%). Beginning in the first month post-onset, prescription medication HCRU increased for all antidepressant and antipsychotic medication classes: serotonin modulators ( + 11.8%), bupropion ( + 10.4%), SSRIs ( + 9.0%), SNRIs ( + 8.6%), and atypical antipsychotics ( + 7.5%). Conclusions: Following pandemic onset, individuals with MDD realized an immediate, but short-lived, reduction in primary care HCRU. Telehealth use remained elevated through the first six months. The most significant and sustained reduction in HCRU was noted for partial-day hospitalizations and all-cause ED visits.

Oncolytic H-1 Parvovirus Hijacks Galectin-1 to Enter Cancer Cells.

Clinical studies in glioblastoma and pancreatic carcinoma patients strongly support the further development of H-1 protoparvovirus (H-1PV)-based anticancer therapies. The identification of cellular factors involved in the H-1PV life cycle may provide the knowledge to improve H-1PV anticancer potential. Recently, we showed that sialylated laminins mediate H-1PV attachment at the cell membrane. In this study, we revealed that H-1PV also interacts at the cell surface with galectin-1 and uses this glycoprotein to enter cancer cells. Indeed, knockdown/out of LGALS1, the gene encoding galectin-1, strongly decreases the ability of H-1PV to infect and kill cancer cells. This ability is rescued by the re-introduction of LGALS1 into cancer cells. Pre-treatment with lactose, which is able to bind to galectins and modulate their cellular functions, decreased H-1PV infectivity in a dose dependent manner. In silico analysis reveals that LGALS1 is overexpressed in various tumours including glioblastoma and pancreatic carcinoma. We show by immunohistochemistry analysis of 122 glioblastoma biopsies that galectin-1 protein levels vary between tumours, with levels in recurrent glioblastoma higher than those in primary tumours or normal tissues. We also find a direct correlation between LGALS1 transcript levels and H-1PV oncolytic activity in 53 cancer cell lines from different tumour origins. Strikingly, the addition of purified galectin-1 sensitises poorly susceptible GBM cell lines to H-1PV killing activity by rescuing cell entry. Together, these findings demonstrate that galectin-1 is a crucial determinant of the H-1PV life cycle.

Editorial Perspective: Speaking up for developmental language disorder - the top 10 priorities for research.

Developmental language disorder (DLD) is one of the most common neurodevelopmental conditions, yet is chronically underserved, with far fewer children receiving clinical services than expected from prevalence estimates, and very little research attention relative to other neurodevelopmental conditions of similar prevalence and severity. This editorial describes a research priority-setting exercise undertaken by the Royal College of Speech and Language Therapists, which aims to redress this imbalance. From consultations with researchers, practitioners and individuals with lived experience, 10 research priorities emerge. Our goal is to share these priorities with the wider research community, to raise awareness and encourage research collaboration to improve outcomes for young people with DLD.

Exceptional response to afatinib in a patient with persistent G719A EGFR-mutant NSCLC.

We present a patient with metastatic NSCLC harboring a compound EGFR mutation with co-occurring G719A and T790M mutation. T790M mutation was treatment emergent mutation when patient was on early generation tyrosine kinase inhibitors. Initial Guardant 360 showed that G719A was the dominant clone. Following, osimertinib, the patient had only a radiographic disease stabilization and then developed both clinical and radiographic progression. On progression, T790M was undetectable but G719A continued to be the dominant clone. Subsequent administration of afatinib led to a clinical and radiological response. To our knowledge, this is the first case report describing co-occurrence of EGFR G719A and T790M mutations and the clonal evolution during treatment with anti-EGFR therapies.