Health Belief Model to Assess Mpox Knowledge, Attitudes, and Practices among Residents and Staff, Cook County Jail, Illinois, USA, July-August 2022.

In summer 2022, a case of mpox was confirmed in a resident at the Cook County Jail (CCJ) in Chicago, Illinois, USA. We conducted in-depth interviews with CCJ residents and staff to assess mpox knowledge, attitudes, and practices; hygiene and cleaning practices; and risk behaviors. We characterized findings by using health belief model constructs. CCJ residents and staff perceived increased mpox susceptibility but were unsure about infection severity; they were motivated to protect themselves but reported limited mpox knowledge as a barrier and desired clear communication to inform preventive actions. Residents expressed low self-efficacy to protect themselves because of contextual factors, including perceived limited access to cleaning, disinfecting, and hygiene items. Our findings suggest correctional facilities can support disease prevention by providing actionable and tailored messages; educating residents and staff about risk and vaccination options; and ensuring access to and training for hygiene, cleaning, and disinfecting supplies.

Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Gemcitabine combination therapies induce apoptosis in uterine carcinosarcoma patient-derived organoids.

Uterine carcinosarcoma (UCS) is a rare but aggressive endometrial cancer. Survival outcomes for women diagnosed with UCS remain poor with lower survival than those of endometrioid or high-grade serous uterine cancers. The histopathological hallmark of carcinosarcoma is the presence of both sarcomatous and carcinomatous elements. The survival rates for UCS have not improved for over 40 years; therefore, there is a profound need to identify new treatments. To investigate novel chemotherapy treatment combinations for UCS, we generated a UCS patient-derived organoid (PDO) cell line from a patient that received neoadjuvant treatment with paclitaxel and carboplatin. The PDO cell line (UCS1) was grown in three-dimensional domes. The PDO domes were treated with six individual chemotherapies or nine combinations of those six drugs. Cell death in response to chemotherapy was assessed. We found that the six monotherapies had minimal effectiveness at inducing cell death after 48 h of treatment. The combination of paclitaxel and carboplatin (which is the standard-of-care chemotherapy treatment for UCS) led to a small increase in apoptosis compared with the monotherapies. Importantly, when either carboplatin or paclitaxel was combined with gemcitabine, there was an appreciable increase in cell death. In conclusion, for the UCS1 patient-derived tumor cells, gemcitabine combinations were more effective than carboplatin/paclitaxel. Our data support the use of PDOs to predict responses to second-line chemotherapy.

N-acetyl Cysteine Supplementation to Alleviate Skin Picking Disorder: A Case Report.

There are body-focused repetitive behaviors, such as skin picking, trichotillomania, or nail biting, for which therapeutic interventions are available and can be tried, but unfortunately, there are no FDA-approved medications specifically for them. These disorders can cause functional impairment, disrupt activities of daily living, and be burdensome for both the patients and their loved ones. This case report will discuss an over-the-counter vitamin supplement, N-acetyl cysteine (NAC), that can be used safely but is often overlooked.

Patient-reported outcomes in integrated health and social care: A scoping review.

Background: Patient-reported outcomes (PROs) have potential to support integrated health and social care research and practice; however, evidence of their utilisation has not been synthesised. Objective: To identify PRO measures utilised in integrated care and adult social care research and practice and to chart the evidence of implementation factors influencing their uptake. Design: Scoping review of peer-reviewed literature. Data sources: Six databases (01 January 2010 to 19 May 2023). Study selection: Articles reporting PRO use with adults (18+ years) in integrated care or social care settings. Review methods: We screened articles against pre-specified eligibility criteria; 36 studies (23%) were extracted in duplicate for verification. We summarised the data using thematic analysis and descriptive statistics. Results: We identified 159 articles reporting on 216 PRO measures deployed in a social care or integrated care setting. Most articles used PRO measures as research tools. Eight (5.0%) articles used PRO measures as an intervention. Articles focused on community-dwelling participants (35.8%) or long-term care home residents (23.9%), with three articles (1.9%) focussing on integrated care settings. Stakeholders viewed PROs as feasible and acceptable, with benefits for care planning, health and wellbeing monitoring as well as quality assurance. Patient-reported outcome measure selection, administration and PRO data management were perceived implementation barriers. Conclusion: This scoping review showed increasing utilisation of PROs in adult social care and integrated care. Further research is needed to optimise PROs for care planning, design effective training resources and develop policies and service delivery models that prioritise secure, ethical management of PRO data.

Protocol for a mixed-methods study to develop and feasibility test a digital system for the capture of patient-reported outcomes (PROs) in patients receiving chimeric antigen receptor T-cell (CAR-T) therapies (the PRO-CAR-T study).

INTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care. METHODS AND ANALYSIS: Multiphase, mixed-methods study involving multiple stakeholder groups (patients, family members, carers, clinicians, academics/researchers and policy-makers). The intervention development phase comprises a Delphi study to select PRO measures for the digital system, a codesign workshop and consensus meetings to establish thresholds for notifications to the clinical team if a patient reports severe symptoms or side effects. Usability testing will evaluate how users interact with the digital system and, lastly, we will evaluate ePRO system feasibility with 30 CAR-T patients (adults aged 18+ years) when used in addition to usual care. Feasibility study participants will use the ePRO system to submit self-reports of symptoms, treatment tolerability and quality of life at specific time points. The CAR-T clinical team will respond to system notifications triggered by patients' submitted responses with actions in line with standard clinical practice. Feasibility measures will be collected at prespecified time points following CAR T-cell infusion. A qualitative substudy involving patients and clinical team members will explore acceptability of the ePRO system. ETHICS AND DISSEMINATION: Favourable ethical opinion was granted by the Health and Social Care Research Ethics Committee B(HSC REC B) (ref: 23/NI/0104) on 28 September 2023. Findings will be submitted for publication in high-quality, peer-reviewed journals. Summaries of results, codeveloped with the Blood and Transplant Research Unit Patient and Public Involvement and Engagement group, will be disseminated to all interested groups. TRIAL REGISTRATION NUMBER: ISCTRN11232653.

Recommendations to address respondent burden associated with patient-reported outcome assessment.

Patient-reported outcomes (PROs) are increasingly used in healthcare research to provide evidence of the benefits and risks of interventions from the patient perspective and to inform regulatory decisions and health policy. The use of PROs in clinical practice can facilitate symptom monitoring, tailor care to individual needs, aid clinical decision-making and inform value-based healthcare initiatives. Despite their benefits, there are concerns that the potential burden on respondents may reduce their willingness to complete PROs, with potential impact on the completeness and quality of the data for decision-making. We therefore conducted an initial literature review to generate a list of candidate recommendations aimed at reducing respondent burden. This was followed by a two-stage Delphi survey by an international multi-stakeholder group. A consensus meeting was held to finalize the recommendations. The final consensus statement includes 19 recommendations to address PRO respondent burden in healthcare research and clinical practice. If implemented, these recommendations may reduce PRO respondent burden.

Pan-cancer Genomic Analysis of AXL Mutations Reveals a Novel, Recurrent, Functionally Activating AXL W451C Alteration Specific to Myxofibrosarcoma.

Myxofibrosarcoma (MFS) is a common soft tissue sarcoma of the elderly that typically shows low tumor mutational burden, with mutations in TP53 and in genes associated with cell cycle checkpoints ( RB1 , CDKN2A ). Unfortunately, no alterations or markers specific to MFS have been identified and, as a consequence, there are no effective targeted therapies. The receptor tyrosine kinase AXL, which drives cellular proliferation, is targetable by new antibody-based therapeutics. Expression of AXL messenger RNA is elevated in a variety of sarcoma types, with the highest levels reported in MFS, but the pathogenic significance of this finding remains unknown. To assess a role for AXL abnormalities in MFS, we undertook a search for AXL genomic alterations in a comprehensive genomic profiling database of 463,546 unique tumors (including 19,879 sarcomas, of which 315 were MFS) interrogated by targeted next-generation DNA and/or RNA sequencing. Notably, the only genomic alterations recurrent in a specific sarcoma subtype were AXL W451C (n = 8) and AXL W450C (n = 2) mutations. The tumors involved predominantly older adults (age: 44 to 81 [median: 72] y) and histologically showed epithelioid and spindle-shaped cells in a variably myxoid stroma, with 6 cases diagnosed as MFS, 3 as undifferentiated pleomorphic sarcoma (UPS), and 1 as low-grade sarcoma. The AXL W451C mutation was not identified in any non-sarcoma malignancy. A review of publicly available data sets revealed a single AXL W451C-mutant case of UPS that clustered with MFS/UPS by methylation profiling. Functional studies revealed a novel activation mechanism: the W451C mutation causes abnormal unregulated dimerization of the AXL receptor tyrosine kinase through disulfide bond formation between pairs of mutant proteins expressing ectopic cysteine residues. This dimerization triggers AXL autophosphorylation and activation of downstream ERK signaling. We further report sarcomas of diverse histologic subtypes with AXL gene amplifications, with the highest frequency of amplification identified in MFS cases without the W451C mutation. In summary, the activating AXL W451C mutation appears highly specific to MFS, with a novel mechanism to drive unregulated signaling. Moreover, AXL gene amplifications and messenger RNA overexpression are far more frequent in MFS than in other sarcoma subtypes. We conclude that these aberrations in AXL are distinct features of MFS and may aid diagnosis, as well as the selection of available targeted therapies.

Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".

The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.

Composite Bioprinted Hydrogels Containing Porous Polymer Microparticles Provide Tailorable Mechanical Properties for 3D Cell Culture.

The mechanical and architectural properties of the three-dimensional (3D) tissue microenvironment can have large impacts on cellular behavior and phenotype, providing cells with specialized functions dependent on their location. This is especially apparent in macrophage biology where the function of tissue resident macrophages is highly specialized to their location. 3D bioprinting provides a convenient method of fabricating biomaterials that mimic specific tissue architectures. If these printable materials also possess tunable mechanical properties, they would be highly attractive for the study of macrophage behavior in different tissues. Currently, it is difficult to achieve mechanical tunability without sacrificing printability, scaffold porosity, and a loss in cell viability. Here, we have designed composite printable biomaterials composed of traditional hydrogels [nanofibrillar cellulose (cellulose) or methacrylated gelatin (gelMA)] mixed with porous polymeric high internal phase emulsion (polyHIPE) microparticles. By varying the ratio of polyHIPEs to hydrogel, we fabricate composite hydrogels that mimic the mechanical properties of the neural tissue (0.1-0.5 kPa), liver (1 kPa), lungs (5 kPa), and skin (10 kPa) while maintaining good levels of biocompatibility to a macrophage cell line.

Mothers' Experiences During the 2022 Infant Formula Shortage in Washington D.C.

INTRODUCTION: An unprecedented shortage of infant formula occurred in the United States (U.S.) in 2022 and posed widespread challenges to infant feeding nationwide. The purpose of this study is to investigate mothers' experiences during the 2022 infant formula shortage and its perceived impacts on infants' diet and health. METHODS: Mothers (n = 45) of infants under 8 months old from Washington D.C. were invited to participate in a virtual study meeting during the summer of 2022. Mothers completed surveys regarding their demographics, infants' anthropometrics, infant feeding practices, information they have received about infant feeding, and knowledge about infant feeding practices. They then participated in a qualitative interview about their experiences during the infant formula shortage. RESULTS: Overarching themes were: the shortage (1) had adverse impacts on mothers' mental and emotional health; (2) had significant financial and intangible costs; (3) led to changes in infant feeding practices; (4) social and family networks were helpful in navigating the shortage; and (5) mothers felt fortunate to have resources to breastfeed and/or obtain formula. DISCUSSION: The infant formula shortage adversely impacted mothers' mental and emotional health, and was costly, in terms of financial and intangible costs. Findings demonstrate the need to develop clinical and policy approaches to support mothers in feeding their infants and provide education about safe infant feeding practices.

MS care: integrating advanced therapies and holistic management.

Lifestyle and environmental factors are key determinants in disease causality and progression in neurological conditions, including multiple sclerosis (MS). Lack of exercise, poor diet, tobacco smoking, excessive alcohol intake, social determinants of health, concomitant medications, poor sleep and comorbidities can exacerbate MS pathological processes by impacting brain health and depleting neurological reserves, resulting in more rapid disease worsening. In addition to using disease-modifying therapies to alter the disease course, therapeutic strategies in MS should aim to preserve as much neurological reserve as possible by promoting the adoption of a "brain-healthy" and "metabolically-healthy" lifestyle. Here, we recommend self-regulated lifestyle modifications that have the potential to improve brain health, directly impact on disease progression and improve outcomes in people with MS. We emphasise the importance of self-management and adopting a multidisciplinary, collaborative and person-centred approach to care that encompasses the healthcare team, family members and community support groups.

Chronic Use of Proton Pump Inhibitors: A Potential Link to Amino Acid Deficiency and the Development of Depression.

In recent years, the gut-brain axis (GBA) has been implicated in several vital physiological processes, including digestion, immunity, inflammation, and mood regulation. Disruption of this network is tied to the development of several pathological conditions, including mood disorders, inflammatory bowel diseases, and dementia. Proton pump inhibitors (PPI) are among the most utilized and easily accessible medications worldwide. Although they are effective at treating conditions, including gastroesophageal reflux disorder (GERD), peptic ulcer disease, Zollinger-Ellison syndrome, and erosive esophagitis, PPIs have several mechanisms that may precipitate protein and, thus, amino acid malnutrition. Our patient is a 34-year-old female with a longstanding history of GERD treated with proton-pump inhibitors who presented to the psychiatry clinic complaining of a six-month history of depression without extraneous psychosocial factors. Although the patient refused psychiatric intervention, she desired an answer for her symptoms, leading to the discovery of a severe tyrosine deficiency. As tyrosine is critical in the process of neurotransmitter synthesis, replenishment of the amino acid along with discontinuation of proton-pump inhibitors was found to relieve her depressive symptoms within a few short months. In this report, we seek to establish a link between the chronic use of proton-pump inhibitor medications and the development of mood disorders.