An 8-year pragmatic observation evaluation of the benefits of allogeneic HCT in older and medically infirm patients with AML.

We designed a prospective, observational study enrolling patients presenting for treatment of acute myeloid leukemia (AML) at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), and function in: the entire cohort, those aged ≥65 years, those with high comorbidity burden, intermediate cytogenetic risk, adverse cytogenetic risk, and first complete remission with or without measurable residual disease. Patient were assessed 8 times over 2 years. Time-dependent regression models were used. Among 692 patients that were evaluable, 46% received HCT with a 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in most subgroups. Although function, social life, performance status, and depressive symptoms were better for those selected for HCT, these health advantages were lost after receiving HCT. Recipients and nonrecipients of HCT similarly ranked and expected cure as main goal of therapy, whereas physicians had greater expectations for cure than the former. Accounting for health impairments negates survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is mostly owing to selection of the healthier candidates. Considering patients' overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT. This trial was registered at www.clinicaltrials.gov as #NCT01929408.

The political economy of infant and young child feeding: confronting corporate power, overcoming structural barriers, and accelerating progress.

Despite increasing evidence about the value and importance of breastfeeding, less than half of the world's infants and young children (aged 0-36 months) are breastfed as recommended. This Series paper examines the social, political, and economic reasons for this problem. First, this paper highlights the power of the commercial milk formula (CMF) industry to commodify the feeding of infants and young children; influence policy at both national and international levels in ways that grow and sustain CMF markets; and externalise the social, environmental, and economic costs of CMF. Second, this paper examines how breastfeeding is undermined by economic policies and systems that ignore the value of care work by women, including breastfeeding, and by the inadequacy of maternity rights protection across the world, especially for poorer women. Third, this paper presents three reasons why health systems often do not provide adequate breastfeeding protection, promotion, and support. These reasons are the gendered and biomedical power systems that deny women-centred and culturally appropriate care; the economic and ideological factors that accept, and even encourage, commercial influence and conflicts of interest; and the fiscal and economic policies that leave governments with insufficient funds to adequately protect, promote, and support breastfeeding. We outline six sets of wide-ranging social, political, and economic reforms required to overcome these deeply embedded commercial and structural barriers to breastfeeding.

Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies.

OBJECTIVES: Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) at Week 16. Here, the objective is to report the efficacy and safety of BKZ at Week 52. METHODS: BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) comprised a 16-week, double-blind, placebo-controlled period, then a 36-week maintenance period. From Week 16, all patients received subcutaneous BKZ 160 mg every 4 weeks. RESULTS: Improvements versus placebo in Assessment of SpondyloArthritis International Society ≥40% response (primary endpoint), Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels and MRI inflammation of the sacroiliac joints/spine at Week 16 were sustained to Week 52 in BKZ-randomised patients. At Week 52, responses of patients switching from placebo to BKZ at Week 16 were comparable to BKZ-randomised patients. At Week 52, ≥1 treatment-emergent adverse events (TEAEs) were reported in 183 (75.0%) and 249 (75.5%) patients with nr-axSpA and r-axSpA, respectively. Serious TEAEs occurred in 9 (3.7%) patients with nr-axSpA and 20 (6.1%) patients with r-axSpA. Oral candidiasis was the most frequent fungal infection (nr-axSpA: 18 (7.4%); r-axSpA: 20 (6.1%)). Uveitis occurred in three (1.2%) and seven (2.1%) patients with nr-axSpA and r-axSpA, and inflammatory bowel disease in two (0.8%) and three (0.9%). CONCLUSIONS: At Week 52, dual inhibition of IL-17A and IL-17F with BKZ resulted in sustained efficacy across the axSpA spectrum; the safety profile was consistent with the known safety of BKZ. TRIAL REGISTRATION NUMBER: NCT03928704; NCT03928743.

Extending duration of letermovir prophylaxis in haploidentical stem cell transplantation.

Not available.

A proposal to recognize investment in breastfeeding as a carbon offset.

Policy-makers need to rethink the connections between the economy and health. The World Health Organization Council on the Economics of Health for All has called for human and planetary health and well-being to be moved to the core of decision-making to build economies for health. Doing so involves valuing and measuring what matters, more and better health financing, innovation for the common good and rebuilding public sector capacity. We build on this thinking to argue that breastfeeding should be recognized in food and well-being statistics, while investments in breastfeeding should be considered a carbon offset in global financing arrangements for sustainable food, health and economic systems. Breastfeeding women nourish half the world's infants and young children with immense quantities of a highly valuable milk. This care work is not counted in gross domestic product or national food balance sheets, and yet ever-increasing commercial milk formula sales are counted. Achieving global nutrition targets for breastfeeding would realize far greater reductions in greenhouse gas emissions than decarbonizing commercial milk formula manufacturing. New metrics and financing mechanisms are needed to achieve the health, sustainability and equity gains from more optimal infant and young child feeding. Properly valuing crucial care and environmental resources in global and national measurement systems would redirect international financial resources away from expanding carbon-emitting activities, and towards what really matters, that is, health for all. Doing so should start with considering breastfeeding as the highest quality, local, sustainable first-food system for generations to come.

Les responsables politiques doivent repenser les liens entre économie et santé. Le Conseil de l'Organisation mondiale de la Santé sur l'économie de la santé pour tous a demandé que le bien-être et la santé, aussi bien de l'humain que de la planète, soient désormais au cœur du processus de prise de décisions afin de créer des économies au service de la santé. Il est donc impératif d'identifier et de valoriser ce qui compte, d'accroître et d'optimiser le financement de la santé, d'innover pour le bien commun et de renforcer les capacités du secteur public. En partant de cette réflexion, nous plaidons pour une reconnaissance de l'allaitement dans les statistiques relatives à l'alimentation et au bien-être, et estimons que tout investissement réalisé dans ce domaine devrait être considéré comme un crédit-carbone dans le cadre des modalités financières mondiales liées aux systèmes économiques et sanitaires ainsi qu'à une alimentation durable. Les femmes allaitantes nourrissent la moitié des enfants en bas âge dans le monde avec d'immenses quantités de lait extrêmement précieux. Ces activités de soins ne sont pas comptabilisées dans le produit intérieur brut ou les bilans alimentaires nationaux, contrairement aux ventes de lait maternisé en constante progression. Atteindre les cibles mondiales de nutrition pour l'allaitement contribuerait davantage à réduire les émissions de gaz à effet de serre que décarboner la production de lait maternisé. De nouveaux paramètres et mécanismes de financement sont nécessaires pour bénéficier des avantages en matière de santé, de durabilité et d'équité qui découlent d'une meilleure alimentation des nourrissons et jeunes enfants. Valoriser correctement les principales ressources consacrées à l'environnement et aux soins dans les systèmes de mesure nationaux et mondiaux permettrait de détourner les moyens financiers internationaux du développement d'activités à fort taux d'émissions pour les rediriger vers ce qui compte vraiment, c'est-à-dire la santé pour tous. Et pour y parvenir, la première étape consisterait à reconnaître l'allaitement comme l'aliment de base, local, durable et de qualité pour les générations futures.

Los responsables de formular las políticas deben volver a plantearse las conexiones entre la economía y la salud. El Consejo sobre la Economía de la Salud para Todos de la Organización Mundial de la Salud ha pedido que la salud y el bienestar humanos y del planeta se sitúen en el centro de la toma de decisiones a fin de desarrollar economías para la salud. Esto requiere valorar y medir lo que importa, más y mejor financiación sanitaria, innovación para el bien común y reconstrucción de la capacidad del sector público. Nos basamos en este pensamiento para argumentar que la lactancia materna debería reconocerse en las estadísticas de alimentación y bienestar, mientras que las inversiones en lactancia materna deberían considerarse como una compensación de emisiones de carbono en los acuerdos globales de financiación para sistemas alimentarios, sanitarios y económicos sostenibles. Las mujeres lactantes alimentan a la mitad de los bebés y niños pequeños del mundo con inmensas cantidades de una leche muy valiosa. Este trabajo de cuidados no se contabiliza en el producto interior bruto ni en los balances alimentarios nacionales y, sin embargo, sí se contabilizan las ventas cada vez mayores de leche de fórmula comercial. Alcanzar los objetivos mundiales de nutrición para la lactancia materna supondría una reducción mucho mayor de las emisiones de gases de efecto invernadero que descarbonizar la fabricación de leche de fórmula comercial. Se necesitan nuevas métricas y mecanismos de financiación para lograr los beneficios en materia de salud, sostenibilidad y equidad de una alimentación más óptima de los bebés y los niños pequeños. Una valoración adecuada de los cuidados esenciales y de los recursos medioambientales en los sistemas de medición globales y nacionales redirigiría los recursos financieros internacionales lejos de la expansión de las actividades que emiten carbono, y hacia lo que realmente importa, es decir, la salud para todos. En este contexto, habría que empezar por considerar la lactancia materna como el sistema de primera alimentación de mayor calidad, local y sostenible para las generaciones futuras.

Successful Crizotinib-targeted Therapy of Pediatric Unresectable ERC1::ALK Fusion Sarcoma.

Anaplastic lymphoma kinase ( ALK )-fusion sarcomas are rare part of the emerging theoretically targetable tyrosine kinase RAS::MAPK pathway fusion myopericytic-ovoid sarcomas. We report our clinicopathologic and treatment experience with an ALK fusion sarcoma. A novel ELKS/RAB6-interacting/CAST family member 1 - unaligned ALK fusion infiltrative nonmetastatic low-grade sarcoma of the right hand of a 15-month-old male was treated with crizotinib, an ALK tyrosine kinase inhibitor as oral monotherapy, inducing complete radiographic and clinical resolution by 10 months and sustained response now over 12 months after elective discontinuation. Crizotinib can successfully be used to treat unresectable novel ALK fusion sarcomas.

Pseudoendocrine sarcoma: a rare new entity with unique radiologic and pathologic/molecular characteristics.

Pseudoendocrine sarcoma is a rare, recently described intermediate grade sarcoma of uncertain phenotype that most commonly affects the paraspinal location in older patients with a distinctive endocrine/paraganglioma-like morphology and unique CTNNB1 point mutation. While these tumors appear as epithelial or even benign endocrine tumors, these lack markers for such and are highlighted by nuclear expression of beta-catenin. This case is the first among the previously reported only twenty-five cases of this entity, including one original series and a few case reports, to correlate the radiologic imaging with the pathologic features. Furthermore, this case illustrates the oldest-to-date patient with this unique location as a palpable painful chest wall/paraspinal location, with new morphologic observations and, finally, this is only the second case to have this specific CTNNB1 hotspot point mutation for this rare entity.

Persisting gaps in dementia carer wellbeing and education: A qualitative exploration of dementia carer experiences.

AIMS: To explore the emotional wellbeing of dementia carers in the lead up to and during transition of a person living with dementia to a residential aged care facility. DESIGN: An interpretative qualitative study. METHODS: Semi-structured interviews were conducted with informal carers of person living with dementia between February and June 2023. Data were analysed using an inductive thematic approach and resulted in three themes. RESULTS: The majority of carers were adult children (n = 19) and six were wives. Carers lived across metropolitan (n = 20) and regional settings (n = 5) in the most populous state of Australia. Three themes were identified which were attributed to different aspects of the carer role: (1) Carer emotional journey as dementia progresses - impacted by knowledge and lack of support; (2) Questioning decision making-underpinned by knowledge and confidence; and (3) Challenges in re-establishing identity - impacted by ongoing concerns. CONCLUSION: As dementia progresses carers of person living with dementia consistently reported gaps in knowledge including how to access support. Specifically, this study identified the need for more to be done to help carers to develop the skills needed for their role, including participation in care planning and identifying care preferences for the future. Nurses can play a key role in promoting referral to services that support carers. Findings offer practical solutions to ameliorate carer stress and promote shared decision making. REPORTING METHOD: This research was guided by the Consolidated Criteria for Reporting Qualitative Research.

Development of a Culture-Common Formal Characteristics of Behavior - Temperament Markers Inventory (FCB-TMI-CC).

The goal was to create a brief temperament inventory grounded in the Regulative Theory of Temperament (FCB-TMI-CC), with a user-friendly, online applicability for studies in different cultures. As the regulative role of temperament is strongly revealed under meaningful stress, the study was planned within the time of the COVID-19 pandemic. To ensure high diversity in terms of culture, economic and environmental conditions, data from nine countries (Poland, United States of America, Italy, Japan, Argentina, South Korea, Ireland, United Kingdom and Kazakhstan) were utilized (min. N = 200 per country). Validation data were gathered on the level of COVID-19 stressors, posttraumatic stress disorder (PTSD), depression, anxiety and stress symptoms, and Big Five personality traits. Multigroup confirmatory factor analysis served as the basis for the inventory's construction. The final culture-common version includes 37 items (5-6 in each of the 7 scales) and covers the core aspects of temperament dimensions. Temperament structure was confirmed to be equivalent across measured cultures. The measurement is invariant at the level of factor loadings and the reliability (internal consistency) and theoretical validity of the scales were at least acceptable. Therefore, the FCB-TMI-CC may serve as a valuable tool for studying temperament across diverse cultures and facilitate cross-cultural comparisons.

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials.

OBJECTIVES: Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum. METHODS: In parallel 52-week trials, patients with active disease were randomised 1:1 (nr-axSpA) or 2:1 (r-axSpA) to bimekizumab 160 mg every 4 weeks:placebo. From week 16, all patients received bimekizumab 160 mg every 4 weeks. Primary (Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40)) and secondary endpoints were assessed at week 16. Here, efficacy and treatment-emergent adverse events (TEAEs) are reported up to week 24. RESULTS: 254 patients with nr-axSpA and 332 with r-axSpA were randomised. At week 16, primary (ASAS40, nr-axSpA: 47.7% bimekizumab vs 21.4% placebo; r-axSpA: 44.8% vs 22.5%; p<0.001) and all ranked secondary endpoints were met in both trials. ASAS40 responses were similar across TNFi-naïve and TNFi-inadequate responder patients. Improvements were observed in Ankylosing Spondylitis Disease Activity Score (ASDAS) states and objective measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine. Most frequent TEAEs with bimekizumab (>3%) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis. More fungal infections (all localised) were observed with bimekizumab vs placebo; no major adverse cardiovascular events (MACE) or active tuberculosis were reported. Incidence of uveitis and adjudicated inflammatory bowel disease was low. CONCLUSIONS: Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with nr-axSpA and r-axSpA.

Multisite 11-year experience of less-intensive vs intensive therapies in acute myeloid leukemia.

Less-intensive induction therapies are increasingly used in older patients with acute myeloid leukemia (AML). Using an AML composite model (AML-CM) assigning higher scores to older age, increased comorbidity burdens, and adverse cytogenetic risks, we defined 3 distinct prognostic groups and compared outcomes after less-intensive vs intensive induction therapies in a multicenter retrospective cohort (n = 1292) treated at 6 institutions from 2008 to 2012 and a prospective cohort (n = 695) treated at 13 institutions from 2013 to 2017. Prospective study included impacts of Karnofsky performance status (KPS), quality of life (QOL), and physician perception of cure. In the retrospective cohort, recipients of less-intensive therapies were older and had more comorbidities, more adverse cytogenetics, and worse KPS. Less-intensive therapies were associated with higher risks of mortality in AML-CM scores of 4 to 6, 7 to 9, and ≥10. Results were independent of allogeneic transplantation and similar in those age 70 to 79 years. In the prospective cohort, the 2 groups were similar in baseline QOL, geriatric assessment, and patient outcome preferences. Higher mortality risks were seen after less-intensive therapies. However, in models adjusted for age, physician-assigned KPS, and chance of cure, mortality risks and QOL were similar. Less-intensive therapy recipients had shorter length of hospitalization (LOH). Our study questions the survival and QOL benefits (except LOH) of less-intensive therapies in patients with AML, including those age 70 to 79 years or with high comorbidity burdens. A randomized trial in older/medically infirm patients is required to better assess the value of less-intensive and intensive therapies or their combination. This trial was registered at www.clinicaltrials.gov as #NCT01929408.

Strategies to Mitigate the Drug-Drug Interaction between Nirmatrelvir/Ritonavir and Tacrolimus in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Azole Antifungals: Results of a Case Series.

INTRODUCTION: Nirmatrelvir/ritonavir (NIM/r) inhibits tacrolimus metabolism resulting in a profound drug-drug interaction that is further complicated by the use of azole antifungals. CASE PRESENTATIONS: We describe three strategies, in 4 patient cases, for the initiation of NIM/r in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients on tacrolimus at the time of diagnosis. Patients 1 and 2 (strategy 1) experienced prolonged, elevated tacrolimus concentrations after an empiric 33% reduction in tacrolimus dose and adjustment of azole antifungal at NIM/r initiation (strategy 1) and with complete discontinuation of tacrolimus and azole antifungal at NIM/r initiation (strategy 2). Patients 3 and 4 (strategy 3) did not experience elevated tacrolimus concentrations on NIM/r treatment with complete discontinuation of tacrolimus and azole antifungal and a 12-24-h delay in NIM/r initiation. Reinitiation of tacrolimus after NIM/r completion resulted in variable tacrolimus concentrations. CONCLUSION: NIM/r-tacrolimus is a serious drug-drug interaction which can be mitigated by early discontinuation of tacrolimus and azole antifungals, close monitoring, and reinitiation of tacrolimus and antifungal 48-72 h after completion of therapy.

Cutaneous VCL::ALK fusion ovoid-spindle cell neoplasm.

Cutaneous VCL::ALK fusion spindle (ovoid) cell tumor is unique. Recently emerged RAS::MAP tyrosine kinase fusion sarcomas more commonly involve subcutis, skeletal muscle and even bone. We share our experience with a novel cutaneous VCL::ALK spindle cell tumor. An 11-year-old male presented with a back pedunculated pink-red papule thought to be a pyogenic granuloma. Biopsy histopathology revealed an epithelial collarette with pedunculated tumor extending to deep dermis/subcutis interface. The combination of spindled and epithelioid cells, an ovoid myopericytoid appearance within myxoid to collagenous stroma, low to moderate MIB1 and focal S100 protein without SOX10 immunostaining, were suggestive of a novel RAS::MAPK tyrosine kinase fusion sarcoma that is well described. ALK immunostain being positive, a next-generation sequencing comprehensive fusion panel was performed to reveal a VCL::ALK fusion. While epithelioid fibrous histiocytoma shares this fusion and similar dermal location and collarette pedunculation, this and other entities were excluded by older patient age, deeper dermal involvement, ovoid-to-spindled morphology, central pericytoid vasculature, myxoid stroma, moderate cellularity with low to moderate MIB1 expression, superficial ulceration, and focal S100 protein expression. Complete excision was performed with favorable follow-up to date. This novel VCL::ALK fusion spindle (ovoid) cell tumor of the dermis is best considered as part of the recently emerged RAS::MAP tyrosine kinase fusion sarcomas.

Intravascular fasciitis of the scalp as a complication of ICP monitor placement: a case report and review of the literature.

BACKGROUND/IMPORTANCE: There are only 56 documented cases of intravascular fasciitis, a rare variant of nodular fasciitis. Of these cases, only 2 involved the scalp. This lesion is amenable to surgical resection, making it important to differentiate it from soft tissue malignancies of the scalp. CLINICAL PRESENTATION: We report an unusual case of intravascular fasciitis involving the scalp at the site of an intracranial pressure (ICP) monitor of a 13-year-old male patient. The lesion was surgically excised with no recurrence upon 1-month follow-up. CONCLUSION: Intravascular fasciitis is a benign, reactive proliferation of soft tissue that may arise at sites of prior trauma. It appears as a soft, painless, mobile lesion, and immunohistochemical studies are required to differentiate it from malignant lesions. The standard of care is surgical resection of the lesion.

Acceptability and Preferences of Dry HR HPV Self-Sampling Mailed Kits Among Canadian Women: A Cross-Sectional Study.

Human papillomavirus (HPV), a sexually transmitted disease, is identified as the source of 99.7% of cervical cancers. Screening for cervical cancer using oncogenic HPV (high-risk [HR] HPV) detection is more sensitive than traditional cytology. However, few Canadian data exist on HR HPV self-sampling. OBJECTIVE: To evaluate the acceptability of HR HPV self-sampling by patients, the percentage of correctly collected samples, the return rate of mailed kits, and the HPV positivity rate in a population sample based on different cervical cancer risk factors. METHODS: We conducted an observational cross-sectional study on HPV primary cervical cancer screening with self-collected cervicovaginal samples through mail service. RESULTS: A total of 400 kits were mailed and 310 kits were returned, making a return rate of 77.5%. Of these, 84.2% of patients were very satisfied with this method and 95.8% (297/310) of patients would choose self-sampling over cytology as their primary screening method. All patients would recommend this screening method to their friends or family members. Of the samples, 93.8% could be analyzed correctly and the HPV positivity rate was 11.7%. CONCLUSION: In this large and random sample, there was a strong interest in self-testing. Offering HR HPV self-sampling could increase access to cervical cancer screening. The self-screening method could also be a part of the solution to reaching under-screened populations, in particular, those who do not have a family doctor or avoid gynaecologic exams because of pain or anxiety.

Diagnostic errors in musculoskeletal oncology and possible mitigation strategies.

The objective of this paper is to explore sources of diagnostic error in musculoskeletal oncology and potential strategies for mitigating them using case examples. As musculoskeletal tumors are often obvious, the diagnostic errors in musculoskeletal oncology are frequently cognitive. In our experience, the most encountered cognitive biases in musculoskeletal oncologic imaging are as follows: (1) anchoring bias, (2) premature closure, (3) hindsight bias, (4) availability bias, and (5) alliterative bias. Anchoring bias results from failing to adjust an early impression despite receiving additional contrary information. Premature closure is the cognitive equivalent of "satisfaction of search." Hindsight bias occurs when we retrospectively overestimate the likelihood of correctly interpreting the examination prospectively. In availability bias, the radiologist judges the probability of a diagnosis based on which diagnosis is most easily recalled. Finally, alliterative bias occurs when a prior radiologist's impression overly influences the diagnostic thinking of another radiologist on a subsequent exam. In addition to cognitive biases, it is also important for radiologists to acknowledge their feelings when making a diagnosis to recognize positive and negative impact of affect on decision making. While errors decrease with radiologist experience, the lack of application of medical knowledge is often the primary source of error rather than a deficiency of knowledge, emphasizing the need to foster clinical reasoning skills and assist cognition. Possible solutions for reducing error exist at both the individual and the system level and include (1) improvement in knowledge and experience, (2) improvement in clinical reasoning and decision-making skills, and (3) improvement in assisting cognition.

Social Participation Experiences of Families Raising a Young Child With Autism Spectrum Disorder: Implications for Mental Health and Well-Being.

IMPORTANCE: Social participation (SP) is an important facilitator of positive mental health for children and families. Children are dependent on their families to mediate SP, yet families of children with autism spectrum disorder (C-ASD) seemingly limit SP because of behavioral and functional challenges in community environments. The resulting isolation can affect the child's and the family's mental health. OBJECTIVE: To distill the essence of everyday SP experiences in the community of families raising C-ASD. DESIGN: Data collected via in-depth, semistructured interviews with a purposive sample and analyzed in the phenomenological tradition. SETTING: Community. PARTICIPANTS: We recruited seven families with English-speaking parents (ages 18-64 yr) raising one C-ASD (age 2-8 yr). Families with more than one C-ASD or those whose C-ASD was diagnosed with complex medical condition or a neurological or genetic disorder were excluded. RESULTS: The essence of experiences of SP emerged in the form of three themes depicting the mismatch between societal expectations for SP and families' experience: (1) "the struggle," (2) "it's hard to feel like you belong," and (3) what we "have to do." CONCLUSIONS AND RELEVANCE: As a collective, families expressed desire for everyday community SP and could do so only in select environments with core groups. The findings, as interpreted through the lens of mental health promotion, reveal opportunities to reduce barriers and to promote meaningful family SP so as to facilitate positive mental health and well-being through the transactional intersecting characteristics of the child with ASD, the family, and the community. What This Article Adds: This study illuminates the experience of SP of families raising a young C-ASD, highlighting both supports and barriers. Practitioners can use this information to potentially prevent isolation and promote both child and family mental health and well-being.

Regulating the marketing of foods for infants and young children: Lessons from assessment of gaps in monitoring and enforcement in Thailand.

Breast milk substitute (BMS) marketing harms breastfeeding and public health. To control BMS marketing, the Member States of the World Health Organization is called upon to adopt all provisions of the International Code of Marketing of Breastmilk Substitutes (the Code) into national law. In 2017, Thailand adopted many provisions of the Code through the Control of Marketing Promotion of Infant and Young Child Food Act B.E. 2560 (the Act), including the establishment of a compliance monitoring system and enforcement mechanisms. Nevertheless, recent research showed widespread violations. This study aims to assess gaps in the monitoring system and the Act's enforcement in its first three years of operation. This qualitative research study employed in-depth interviews between April and June 2020 with 34 key informants (KIs) from the Thai government, academia and civil society organisations. KIs identified gaps in six areas that could be mitigated to increase compliance with the Act. These gaps are unclear provisions on coverage of the Act; communications with retailers and the public; lack of strong direction and processes; inadequate budget allocations; skilled and confident human resources; and external factors which facilitate BMS marketing. Recommendations may be relevant for other countries and include revising and clarifying the Act, developing targeted communication strategies; providing clear monitoring direction including through setting key performance indicators related to the Act; and providing sufficient budget and training for authorised and support officers. Strengthening the health system and workplace support for breastfeeding and social marketing would also help address wider structural factors.

Natural spring water gargle samples as an alternative to nasopharyngeal swabs for SARS-CoV-2 detection using a laboratory-developed test.

The objective of this study was to validate the use of spring water gargle (SWG) as an alternative to oral and nasopharyngeal swab (ONPS) for SARS-CoV-2 detection with a laboratory-developed test. Healthcare workers and adults from the general population, presenting to one of two COVID-19 screening clinics in Montréal and Québec City, were prospectively recruited to provide a gargle sample in addition to the standard ONPS. The paired specimens were analyzed using thermal lysis followed by a laboratory-developed nucleic acid amplification test (LD-NAAT) to detect SARS-CoV-2, and comparative performance analysis was performed. An individual was considered infected if a positive result was obtained on either sample. A total of 1297 adult participants were recruited. Invalid results (n = 18) were excluded from the analysis. SARS-CoV-2 was detected in 144/1279 (11.3%) participants: 126 from both samples, 15 only from ONPS, and 3 only from SWG. Overall, the sensitivity was 97.9% (95% CI: 93.7-99.3) for ONPS and 89.6% (95% CI: 83.4-93.6; p = 0.005) for SWG. The mean ONPS cycle threshold (Ct ) value was significantly lower for the concordant paired samples as compared to discordant ones (22.9 vs. 32.1; p < 0.001). In conclusion, using an LD-NAAT with thermal lysis, SWG is a less sensitive sampling method than the ONPS. However, the higher acceptability of SWG might enable a higher rate of detection from a population-based perspective. Nonetheless, in patients with a high clinical suspicion of COVID-19, a repeated analysis with ONPS should be considered. The sensitivity of SWG using NAAT preceded by chemical extraction should be evaluated.

ALK rearrangements in infantile fibrosarcoma-like spindle cell tumours of soft tissue and kidney.

AIMS: Recurrent alterations in receptor tyrosine kinase (RTK) and downstream effectors are described in infantile fibrosarcoma (IFS)/cellular congenital mesoblastic nephroma (cCMN) and a subset of spindle cell sarcomas, provisionally designated 'NTRK-rearranged' spindle cell neoplasms. These two groups of tumours demonstrate overlapping morphologies and harbour alterations in NTRK1/2/3, RET, MET, ABL1, ROS1, RAF1 and BRAF, although their relationship is not fully elucidated. We describe herein a cohort of paediatric tumours with clinicopathological features not typical for inflammatory myofibroblastic tumour, but rather with similarities to cCMN/IFS harbouring ALK fusions. METHODS AND RESULTS: Clinicopathological features were assessed and partner agnostic targeted RNA sequencing on clinically validated platforms were performed. Tumours occurred in patients aged from 2 to 10 years (median age 2 years) with a 2:2 male to female ratio and an average size of 8.4 cm. Two tumours arose in soft tissues and two in the kidney. Morphological features included spindle to ovoid cells arranged in long fascicles or haphazardly within a myxoid to collagenised stroma; a subset of cases had either dilated, ectatic vessels or focal perivascular hyalinosis. By immunohistochemistry, all cases tested showed cytoplasmic expression of anaplastic lymphoma kinase (ALK) and one case demonstrated co-expression of CD34 and S100. CONCLUSIONS: This series of ALK-rearranged IFS-like tumours expands the spectrum of targetable kinases altered in these tumours and reinforces the potential overlap between IFS/cCMN-like tumours and the provisional entity of 'NTRK-rearranged' spindle cell neoplasms.