An indirect treatment comparison (ITC) and matching-adjusted indirect comparison (MAIC) between a 15-valent (V114) and a 20-valent (PCV20) pneumococcal conjugate vaccine among healthy infants.

OBJECTIVES: Immunogenicity between 15-valent V114 (PCV15) and 20-valent PCV20 pneumococcal conjugate vaccines in healthy infants is compared in an indirect treatment comparison and matching-adjusted indirect comparison. Hypotheses: immunogenicity of V114 is non-inferior to PCV20 for all PCV13 serotypes, and superior to PCV20 for serotype 3 based on lower bound margins. METHODS: Two phase 3 pivotal studies on 3 + 1 pediatric vaccination schedule at age 2, 4, 6, and 12-15 months compared V114 (N = 858) to PCV13 (N = 856) and PCV20 (N = 1001) to PCV13 (N = 987). Infant's age and race in V114 study were matched to those in PCV20 study. Primary endpoints were serotype-specific Immunoglobulin G (IgG) response rate difference (RRD) 30 days post-dose (PD)3; IgG geometric mean concentration (GMC) ratios 30 days PD3 and PD4. RESULTS: V114 was non-inferior (marginRRD>-10%-point; marginGMCratio >0.5) to PCV20 (p-value <0.001) for all endpoints. V114 was superior (marginRRD >0%-point; marginGMCratio >1.2) to PCV20 (p-value <0.001) for serotype 3: RRD was 34.5% (95%CI 27.9%-41.1%) PD3, and IgG GMC ratios were 2.39 (95%CI 2.12-2.68) PD3 and 2.15 (95%CI 1.90-2.41) PD4. CONCLUSION: Immune response to V114 administered in a 3 + 1 schedule in healthy infants was considered non-inferior to PCV20 for all 13 PCV13 serotypes and superior for serotype 3 PD3 and PD4. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers NCT03893448, NCT04382326.

Pleural-based giant solitary fibrous tumour with associated hypoglycaemia: unusual presentation with pulmonary hypertension in a patient with Doege-Potter syndrome.

Refractory hypoglycaemia in a patient with a solitary fibrous tumour (SFT) is very rare and was first reported in 1930 independently by Doege and Potter, leading to it being named 'Doege-Potter syndrome'. Here, we report the unusual case of a 77-year-old woman with a giant solitary fibrous pleural tumour who presented with complicating pulmonary hypertension and associated heart failure with hypoglycaemia, and subsequently underwent curative resection of the pleural mass with clinical improvement.

Occupational multi-level responsiveness: Describing the skills used by occupational therapists working with children seeking asylum in Australia.

BACKGROUND: Children seeking asylum face occupational deprivation and human rights violations. No research has investigated how occupational therapists work with child asylum seekers. The World Federation of Occupational Therapists promotes the Canadian Model of Client-Centred Enablement (CMCE) for occupational therapists working to promote human rights. AIMS/OBJECTIVES: This research investigates use of CMCE skills to investigate skills occupational therapists use when working with child asylum seekers in Australian immigration detention. MATERIAL AND METHODS: Interpretive description guided this investigation and purposive sampling was used to recruit 10 occupational therapists. Semi-structured interviews were conducted and thematically analysed. RESULTS: Occupational multi-level responsiveness, an overarching practice skill, involved keying into individual, family and socio-political levels to respond to occupational injustices. A wide array of practice skills extending beyond the CMCE framework were used in a nuanced and interwoven manner spanning multiple levels. CONCLUSIONS: Occupational multi-level responsiveness described occupational therapists working across macro-, meso- and micro-levels. SIGNIFICANCE: Understanding and enacting occupational multi-level responsiveness may support occupational therapists to plan and implement effective strategies when tackling occupational injustices. The skills identified may be applicable to other complex socio-political fields of practice. More research is needed. Further research should also investigate the occupational experiences of children seeking asylum. KEY POINTSOccupational therapists working with child asylum seekers in Australia take a multi-level approach, responding to individuals, families and socio-political structures.A three pronged approach to implementation of the occupational therapy practice process could support multi-level responsiveness to enhance practice that addresses occupational injustices.CMCE skills are not exhaustive and therapists discussed using other skills beyond those listed in the CMCE. Additional skills reflected humility and efforts towards more equal relationships between therapists and clients.

Cell-intrinsic melanin fails to protect melanocytes from ultraviolet-mutagenesis in the absence of epidermal melanin.

Melanin is a free-radical scavenger, antioxidant, and broadband absorber of ultraviolet (UV) radiation which protects the skin from environmental carcinogenesis. However, melanin synthesis and UV-induced reactive melanin species are also implicated in melanocyte genotoxicity. Here, we attempted to reconcile these disparate functions of melanin using a UVB-sensitive, NRAS-mutant mouse model, TpN. We crossed TpN mice heterozygous for an inactivating mutation in Tyrosinase to produce albino and black littermates on a C57BL/6J background. These animals were then exposed to a single UVB dose on postnatal day three when keratinocytes in the skin have yet to be melanized. Approximately one-third (35%) of black mice were protected from UVB-accelerated tumor formation. However, melanoma growth rates, tumor mutational burdens, and gene expression profiles were similar in melanomas from black and albino mice. Skin from albino mice contained more cyclobutane pyrimidine dimer (CPD) positive cells than black mice 1-h post-irradiation. However, this trend gradually reversed over time with CPDs becoming more prominent in black than albino melanocytes at 48 h. These results show that in the absence of epidermal pigmentation, melanocytic melanin limits the tumorigenic effects of acute UV exposure but fails to protect melanocytes from UVB-induced mutagenesis.

A Graph Coarsening Algorithm for Compressing Representations of Single-Cell Data with Clinical or Experimental Attributes.

Graph-based algorithms have become essential in the analysis of single-cell data for numerous tasks, such as automated cell-phenotyping and identifying cellular correlates of experimental perturbations or disease states. In large multi-patient, multi-sample single-cell datasets, the analysis of cell-cell similarity graphs representations of these data becomes computationally prohibitive. Here, we introduce cytocoarsening, a novel graph-coarsening algorithm that significantly reduces the size of single-cell graph representations, which can then be used as input to downstream bioinformatics algorithms for improved computational efficiency. Uniquely, cytocoarsening considers both phenotypical similarity of cells and similarity of cells' associated clinical or experimental attributes in order to more readily identify condition-specific cell populations. The resulting coarse graph representations were evaluated based on both their structural correctness and the capacity of downstream algorithms to uncover the same biological conclusions as if the full graph had been used. Cytocoarsening is provided as open source code at https://github.com/ChenCookie/cytocoarsening.

An evaluation of Neuroprotective Developmental Care (NDC/Possums Programs) in the First 12 Months of Life.

BACKGROUND: Transitioning to motherhood is an important life event. Stress often arises due to feeding concerns, infant crying, and sleep problems. Neuroprotective Developmental Care (NDC) also known as the Possums programs provides an evidence-based, consistent and holistic approach to maternal and infant wellbeing. OBJECTIVES: To understand maternal characteristics at point of services access and an exploratory evaluation of effectiveness of NDC/Possums services. METHODS: All mothers accessing NDC/Possums services via clinical services or self-paced online modules were invited to participate in a baseline survey. Follow up occurred when infants were 6 and 12 months of age. Participants who completed the 6-month survey were compared against their own baseline surveys. Those who completed the survey at 12-months were compared against their own baseline surveys. A pseudo-control group who had completed the baseline survey with infants 12 months of age was also compared to those who had accessed NDC/Possums services prior to 12 months of age (termed 'intervention' group). RESULTS: Crying time, mothers' perceptions of infant sleep problems, mothers' own sleep, mothers' Acceptance and Action Questionnaire (AAQ) scores and the mothers' Edinburgh Postnatal Depression Scale (EPDS) scores showed statistically significant improvements from baseline to 12-month old follow-up. Significant differences were also found between the pseudo-control group and 'intervention' groups. CONCLUSIONS FOR PRACTICE: This results indicate that accessing NDC/Possums services is efficacious in addressing infant's crying, the mother's perceptions of their baby's sleep problems, the mother's own sleep satisfaction, the mother's experiential avoidance, and the mother's risk of postnatal depression. NDC is relevant to public health, clinical service delivery and education for health professionals.

Efficacy of early interventions with active parent implementation in low-and-Middle income countries for young children with cerebral palsy to improve child development and parent mental health outcomes: a systematic review.

PURPOSE: To determine the efficacy of interventions with active parent implementation for young children with cerebral palsy (CP) to improve child and parent outcomes in low-middle income countries (LMICs). METHODS: Five databases were systematically searched. Randomised or comparison studies evaluating interventions with the training of the parent and/or home practice components to implement with their child with CP (<60 months of age) were included. The modified Downs and Black scale assessed methodological quality. Data were pooled to calculate mean differences and 95% confidence intervals (95% CI). RESULTS: Searches yielded 189 unique articles. 11 studies from ten papers of moderate to high quality were included. Parent-implemented general developmental interventions had a small negative effect on gross motor function compared to interventionist-implemented therapy. Parent-implemented upper limb training compared to interventionist-implemented neurodevelopmental therapy had a small positive effect on bimanual hand function. Parent-implemented functional feeding training had a large significant effect on chewing function compared to parent-implemented oral motor exercises. Parent-implemented interventions targeting general child development and feeding had mixed effects on parent stress outcomes. CONCLUSIONS: Parent-implemented interventions in LMICs are promising to improve child bimanual hand and chewing function. Further research evaluating the efficacy of parent-implemented interventions to improve parent mental health is needed.Implications for Rehabilitation:Intensive motor training-based interventions with active parent implementation were effective to improve child gross motor, bimanual hand, and chewing function in young children with CP compared to passive, generic interventionist-implemented or health education interventions.Interventions with active parent implementation had mixed results to improve parent mental health, however, this was frequently not assessed. A consistent level of support and training provided to parents may be required to have a positive effect on parent stress.To further understand the feasibility of early interventions with active parent implementation in LMICs, data on adherence to home practice dose and session attendance and a qualitative understanding of contextual and child factors influencing parent implementation is needed.

UVB mutagenesis differs in Nras- and Braf-mutant mouse models of melanoma.

BRAF-mutant melanomas are more likely than NRAS-mutant melanomas to arise in anatomical locations protected from chronic sun damage. We hypothesized that this discrepancy in tumor location is a consequence of the differential sensitivity of BRAF and NRAS-mutant melanocytes to ultraviolet light (UV)-mediated carcinogenesis. We tested this hypothesis by comparing the mutagenic consequences of a single neonatal, ultraviolet-AI (UVA; 340-400 nm) or ultraviolet-B (UVB; 280-390 nm) exposure in mouse models heterozygous for mutant Braf or homozygous for mutant Nras Tumor onset was accelerated by UVB, but not UVA, and the resulting melanomas contained recurrent mutations affecting the RING domain of MAP3K1 and Actin-binding domain of Filamin A. Melanomas from UVB-irradiated, Braf-mutant mice averaged twice as many single-nucleotide variants and five times as many dipyrimidine variants than tumors from similarly irradiated Nras-mutant mice. A mutational signature discovered in UVB-accelerated tumors mirrored COSMIC signatures associated with human skin cancer and was more prominent in Braf- than Nras-mutant murine melanomas. These data show that a single UVB exposure yields a greater burden of mutations in murine tumors driven by oncogenic Braf.

Mothers' perspectives on the influences shaping their early experiences with infants at risk of cerebral palsy in India.

BACKGROUND: Accurate diagnosis of cerebral palsy (CP) high-risk status is now possible in infants less than six months corrected age. Parents play a central role in providing nurturing care and implementing early intervention approaches. To design interventions tailored to needs of parents and understand how to improve parental support, this study aimed to understand the influences shaping parent experiences with an infant at high-risk of CP in West Bengal, India. METHODS AND PROCEDURES: This phenomenological qualitative study was conducted with parents of infants at high-risk of CP in West Bengal, India. Individual in-depth interviews explored experiences with health providers, supports for caregiving and challenges of parenting. Interviews were conducted in English with concurrent translation and analysed using thematic analysis. OUTCOMES AND RESULTS: Main themes included: limited finances and social networks shape decisions and caregiving practices; trust in the formal health care system; views of disability including explanations for their infant's condition and expectations for the child's future, and everyday adaptations required to meet infants' needs. CONCLUSIONS AND IMPLICATIONS: Low cost models of early intervention may alleviate the financial burden and stress on families. Dependence on health care professionals for care management is a barrier to family-delivered approaches to care.

Developing interprofessional collaboration between clinicians, interpreters, and translators in healthcare settings: outcomes from face-to-face training.

Interprofessional collaboration between clinicians, interpreters, and translators is crucial to providing care for consumers with limited English proficiency. Interprofessional training for these professions has been overlooked outside of the medical field. This study investigated whether face-to-face training for speech pathologists, interpreters, and translators improved their knowledge, confidence, practice, and attitudes to engage in interprofessional collaboration. It also examined whether single-profession training for speech pathologists can produce similar training outcomes when delivered to multiple healthcare professions. Thirty interpreters and translators (30 training), 49 speech pathologists (27 training, 22 control), and a mixed group of 24 clinicians from eight professions (16 training, 8 control) completed surveys before, after, and two months after their respective training event. Training outcomes were similar across cohorts. Knowledge and confidence improved and were maintained after two months. Attitudes toward interprofessional collaboration were positive despite perceptions of challenge, and this was largely unchanged after training. Intent to implement optimal practices after training was greater than self-reported practices two months later. While years of professional experience did not affect training outcomes for clinicians, knowledge improvement for interpreters was associated with having less professional experience. Findings highlight the need to reevaluate service planning, policy, and workforce development strategies alongside foundation level training to deliver effective interprofessional education for clinicians, interpreters, and translators in healthcare settings.

Lessons of the month: Co-infection with SARS-CoV-2 and influenza B virus in a patient with community-acquired pneumonia.

Why we only infrequently detect or report two or more respiratory viruses co-infecting an adult host is poorly understood. We report a rare case where influenza B and SARS-CoV-2 caused viral pneumonia in a 74-year-old man diagnosed during the UK winter epidemic/pandemic for these organisms and discuss concepts of co-infection.

Lessons of the month 1: A case of rhombencephalitis as a rare complication of acute COVID-19 infection.

A 40-year-old man developed acute brainstem dysfunction 3 days after hospital admission with symptoms of the novel SARS-CoV-2 infection (COVID-19). Magnetic resonance imaging showed changes in keeping with inflammation of the brainstem and the upper cervical cord, leading to a diagnosis of rhombencephalitis. No other cause explained the patient's abnormal neurological findings. He was managed conservatively with rapid spontaneous improvement in some of his neurological signs and was discharged home with continued neurology follow up.

Chronic disease self-management programs for Aboriginal and Torres Strait Islander people: Factors influencing participation in an urban setting.

ISSUE ADDRESSED: Evidence suggests that participation in a Chronic Disease Self-Management (CDSM) program improves the health of clients. Many factors are known to influence participation in these programs for the broader Australian population. However, less is known about why Aboriginal and Torres Strait Islanders choose to participate. This study identifies key factors that support or enable Aboriginal and Torres Strait Islanders to participate in a CDSM program in an urban setting. METHODS: Twelve focus groups were undertaken with a total of 102 participants who were diagnosed with or at risk of chronic disease. These participants were recruited from the Work It Out program, a CDSM program comprising exercise and health education. The Work It Out program is specifically designed for Aboriginal and Torres Strait Islanders and delivered by an Aboriginal led and community-controlled organisation in South-East and Central Queensland. The study received ethical clearance through the Behavioural and Social Sciences Ethical Review Committee at The University of Queensland (Approval Number 2011001283). RESULTS: Findings indicate that key features of program design based on a culturally responsive approach influences participation. The main features are as follows: providing easy access to the program; permitting flexibility in attendance; a group environment; the approach of program staff that prioritises relationship building; personalised and integrated care; communicating result regularly; and ensuring community ownership of the program. CONCLUSION: These findings are useful to consider when designing a health program for Aboriginal and Torres Strait Islanders. Programs which are culturally responsive and include the design features identified in this study are more likely to increase participation amongst Aboriginal and Torres Strait Islanders. SO WHAT?: Increasing participation of Aboriginal and Torres Strait Islanders in CDSM programs using the design features identified in the paper may contribute significantly in closing the health disparity gap.

Does attending Work It Out - a chronic disease self-management program - affect the use of other health services by urban Aboriginal and Torres Strait Islander people with or at risk of chronic disease? A comparison between program participants and non-participants.

Work It Out is a holistic chronic disease self-management program for urban Aboriginal and Torres Strait Islander people in Queensland, which is part of an integrated and comprehensive system of care for chronic disease management. This study examines differences in primary healthcare services use between Work It Out participants and non-participants. This retrospective observational study of services use, analysed data extracted from the clinical medical records system and Work It Out program assessments. General practitioner and allied health services use were compared among the participants and non-participants using logistic regression models and zero-truncated Poisson and negative binomial regression models. Compared with non-participants, Work It Out participants were more likely to use GP management plans, GP team care arrangements, GP mental health consultation and subsequent allied health services. Among those who used the services more than once, Work It Out participants had higher service use rates than non-participants for Aboriginal and Torres Strait Islander health assessments, GP management plans, team care arrangements and podiatry, physiotherapy and dietetic services. Engagement in Work It Out can facilitate the use of primary healthcare services, which are important for chronic disease management for urban Aboriginal and Torres Strait Islander people.

Seeking virtual social support through blogging: A content analysis of published blog posts written by people with chronic pain.

OBJECTIVE: People with chronic pain often have limited avenues for social support. Social isolation often develops as their abilities to engage in daily social and vocational activities decrease. With recent advancements in technology and increasing use of social media, virtual platforms such as blogging may provide opportunities for social support. This study analyzed published blog posts of people with chronic pain to investigate how social support occurs through blogging for chronic pain blog users and the nature of such online interactions. METHODS: A total of 810 blog posts published from January 2014 to December 2015 on 44 publicly accessible chronic pain blogs were collected and analyzed through qualitative phenomenological thematic analysis. RESULTS: The Virtual Online Support Sequence (VOSS) was identified through the exchange of online comments; this sequence defines the process by which virtual social support can be established through the process of chronic pain blogging. Three subthemes were also identified in relation to social support in the online blogging environment: (a) the virtual community of pain blogging; (b) establishing social support through the VOSS; and (c) recounting everyday experiences related to pain. CONCLUSIONS: These findings suggest that blogging can be useful in seeking, receiving and providing social support for people with chronic pain. Understanding this mechanism behind establishing virtual social support may potentially encourage people with chronic pain to pursue additional support online if they have limited face-to-face opportunities.

Intentional strengths interviewing in occupational justice research.

BACKGROUND: Occupational justice research can generate knowledge about societal conditions that support participation in meaningful occupations. This is useful because occupational therapy's human rights goal is to create societal conditions that are conducive to occupational engagement. Participants in this research field are likely to be vulnerable and need special ethical considerations. However, no model exists to support ethical considerations for vulnerable participants in occupational justice research. AIM: This study aimed to develop a model for additional ethical considerations for occupational justice research with vulnerable participants. MATERIALS AND METHODS: A secondary analysis was carried out on data from a previous study with asylum seekers. Data included semi-structured interview transcripts with seven asylum seekers, researcher memos, and text from the researcher's written report. Template analysis was employed. RESULTS: The Intentional Strengths Interviewing model was developed. It has three component strategies: strengths-informed interview processes, strengths questioning, and strengths responding. CONCLUSION AND SIGNIFICANCE: This model might be considered in the design of future occupational justice research involving vulnerable participants in order to best support their inclusion. This model might support future occupational justice research and might be evaluated in other contexts.

Human rights in occupational therapy education: A step towards a more occupationally just global society.

BACKGROUND/AIM: Education on human rights will place occupational therapists in a strong position to address societal inequities that limit occupational engagement for many client groups. The imminent changes to the Minimum Standard for the Education of Occupational Therapists engender efforts towards social change and will require university-level human rights education. This education might enhance the profession's influence on disadvantaging social structures in order to effect social change. To contribute to the evidence base for social change education in occupational therapy, this research aims to understand the knowledge, skills, confidence and learning experiences of occupational therapy students who completed a human rights course. METHODS: Final year occupational therapy students responded to questionnaires which included listing human rights, a human rights scale measuring knowledge and confidence for working towards human rights, and open questions. Numbers of rights listed, knowledge scores and confidence scores were calculated. Responses to the open questions were thematically analysed. RESULTS: After completing a human rights course, students had good knowledge and moderate confidence to work with human rights. Three themes were identified including 'learning about human rights', 'learning about structural, societal and global perspectives on occupational engagement' and 'learning how occupational therapists can work with groups, communities and populations: becoming articulate and empowered'. CONCLUSIONS: Human rights education fosters the development of occupational therapists who are skilled, knowledgeable, confident and empowered to address occupational injustices, according to these research findings. To develop a more occupationally just global society, education that considers iniquitous social structures and human rights is necessary.