Egg-sensitised infants have elevated CD4+ effector memory T regulatory cells from birth.

BACKGROUND: IgE-mediated sensitisation to egg is common in infants. In some cases, the processes leading to egg sensitisation are established in early life, even before introduction to solid foods. The underlying mechanisms remain poorly understood. METHODS: We performed detailed immune cell phenotyping of peripheral blood mononuclear cells and determined in vitro cytokine responses following allergen specific and non-specific immune stimulation. To determine if unique immune profiles were linked to early-life egg sensitisation, we compared 92 infants at 4-6 months of age, with (EggCAP+, n = 41) and without (EggCAP-, n = 51) early egg sensitisation. Additionally, 47 cord blood samples were analysed. For a subset of participants (n = 39), matching cord blood mononuclear cells were assessed by flow cytometry to establish the impact of IgE sensitisation on immune developmental trajectories. RESULTS: EggCAP+ infants were found to exhibit a unique immune phenotype characterised by increased levels of circulating CD4+ T regulatory cells (Treg), CD4+ effector memory (EM) Treg and increased expression of the IgE receptor, FcεR1, on basophils. The increased CD4+ EM Treg profiles were already present in cord blood samples from EggCAP+ infants. A general Th2-skewing of the immune system was observed based on increased IL-13 production following phytohemagglutinin stimulation and by comparing immune developmental trajectories, EggCAP+ infants displayed an expansion of basophils and reduced levels of CD4- T cells compared to EggCAP- infants. CONCLUSIONS: Immunological profiles associated with egg sensitisation are detectable in infant circulation at 4-6 months of age and at birth. Understanding the immune mechanisms underlying early-life sensitisation could provide important insights for future food allergy prevention strategies.

Understanding the uptake of virtual care for first and return outpatient appointments in child and adolescent mental health services: a mixed-methods study.

OBJECTIVE: To describe patterns of virtual and in-person outpatient mental health service use and factors that may influence the choice of modality in a child and adolescent service. DESIGN: A pragmatic mixed-methods approach using routinely collected administrative data between 1 April 2020 and 31 March 2022 and semi-structured interviews with clients, caregivers, clinicians and staff. Interview data were coded according to the Consolidated Framework for Implementation Research (CFIR) and examined for patterns of similarity or divergence across data sources, respondents or other relevant characteristics. SETTING: Child and adolescent outpatient mental health service, Nova Scotia, Canada. PARTICIPANTS: IWK Health clinicians and staff who had participated in virtual mental healthcare following its implementation in March 2020 and clients (aged 12-18 years) and caregivers of clients (aged 3-18 years) who had received treatment from an IWK outpatient clinic between 1 April 2020 and 31 March 2022 (n=1300). Participants (n=48) in semi-structured interviews included nine clients aged 13-18 years (mean 15.7 years), 10 caregivers of clients aged 5-17 years (mean 12.7 years), eight Community Mental Health and Addictions booking and registration or administrative staff and 21 clinicians. RESULTS: During peak pandemic activity, upwards of 90% of visits (first or return) were conducted virtually. Between waves, return appointments were more likely to be virtual than first appointments. Interview participants (n=48) reported facilitators and barriers to virtual care within the CFIR domains of 'outer setting' (eg, external policies, client needs and resources), 'inner setting' (eg, communications within the service), 'individual characteristics' (eg, personal attributes, knowledge and beliefs about virtual care) and 'intervention characteristics' (eg, relative advantage of virtual or in-person care). CONCLUSIONS: Shared decision-making regarding treatment modality (virtual vs in-person) requires consideration of client, caregiver, clinician, appointment, health system and public health factors across episodes of care to ensure accessible, safe and high-quality mental healthcare.

Implementation of a Knowledge Management System in Mental Health and Addictions: Mixed Methods Case Study.

BACKGROUND: Mental health and addictions (MHA) care is complex and individualized and requires coordination across providers and areas of care. Knowledge management is an essential facilitator and common challenge in MHA services. OBJECTIVE: This paper aimed to describe the development of a knowledge management system (KMS) and the associated processes in 1 MHA program. We also aimed to examine the uptake and use, satisfaction, and feedback on implementation among a group of pilot testers. METHODS: This project was conducted as a continuous quality-improvement initiative. Integrated stakeholder engagement was used to scope the content and design the information architecture to be implemented using a commercially available knowledge management platform. A group of 30 clinical and administrative staff were trained and tested with the KMS over a period of 10 weeks. Feedback was collected via surveys and focus groups. System analytics were used to characterize engagement. The content, design, and full-scale implementation planning of the KMS were refined based on the results. RESULTS: Satisfaction with accessing the content increased from baseline to after the pilot. Most testers indicated that they would recommend the KMS to a colleague, and satisfaction with KMS functionalities was high. A median of 7 testers was active each week, and testers were active for a median of 4 days over the course of the pilot. Focus group themes included the following: the KMS was a solution to problems for staff members, functionality of the KMS was important, quality content matters, training was helpful and could be improved, and KMS access was required to be easy and barrier free. CONCLUSIONS: Knowledge management is an ongoing need in MHA services, and KMSs hold promise in addressing this need. Testers in 1 MHA program found a KMS that is easy to use and would recommend it to colleagues. Opportunities to improve implementation and increase uptake were identified. Future research is needed to understand the impact of KMSs on quality of care and organizational efficiency.

Evidence of maternal transfer of antigen-specific antibodies in serum and breast milk to infants at high-risk of S. pneumoniae and H. influenzae disease.

Introduction: Children in low-mid income countries, and First Nations children in high-income countries, experience disproportionately high rates of Streptococcus pneumoniae and Haemophilus influenzae infections and diseases including pneumonia and otitis media. We previously observed that infants from Papua New Guinea had no evidence of waning maternal immunity for H. influenzae-specific antibodies. In this study, we assessed S. pneumoniae and H. influenzae antibody titres in Australian First Nation mothers and infants to determine antigen-specific antibody ontogenies and whether H. influenzae antibody titres in infants were due to low maternal antibody titres or lack of placental transfer. Methods: Breast milk, infant nasopharyngeal swabs and ear assessment data were collected 1-, 2-, 7-months post-birth as well as maternal, cord and 7-month-old infant sera, from 85 Australian Aboriginal and Torres Strait Islander mother-infant pairs. Serum IgG and breast milk IgG and IgA antibody titres to S. pneumoniae antigens (PspA1, PspA2, CbpA, Ply) and H. influenzae antigens (PD, ChimV4, OMP26, rsPilA) were measured. Results: IgG titres in maternal and cord sera were similar for all antigens, except Ply (higher in cord; p=0.004). Sera IgG titres at 7-months of age were lower than cord sera IgG titres for all S. pneumoniae antigens (p<0.001). Infant sera IgG titres were higher than cord sera for H. influenzae PD (p=0.029), similar for OMP26 (p=0.817) and rsPilA (p=0.290), and lower for ChimV4 (p=0.004). Breast milk titres were similar for all antigens at 1, 2 and 7-months except OMP26 IgA (lower at 7-months than 1-month; p=0.035), PspA2 IgG (p=0.012) and Ply IgG that increased by 7-months (p=0.032). One third of infants carried nontypeable Haemophilus influenzae (NTHi), 45% carried S. pneumoniae and 52% had otitis media (OM) observed at least once over the 7-months. 73% of infants who carried either S. pneumoniae or NTHi, also had otitis media observed. Conclusions: Similarities between maternal and cord IgG titres, and absence of waning, support a lack of maternal H. influenzae IgG antibodies available for cross-placental transfer. Increased maternal anti-PD IgG could offer some protection from early carriage with NTHi, and maternal immunisation strategies should be considered for passive-active immunisation of infants to protect against S. pneumoniae and H. influenzae diseases. Trial registration: ClinicalTrials.gov NCT00714064 and NCT00310349.

Choice and Partnership Approach to community mental health and addiction services: a realist-informed scoping review.

OBJECTIVES: The Choice and Partnership Approach (CAPA) was developed to create an accessible, child-centred and family-centred model of child and adolescent mental health service delivery that is adaptable to different settings. We sought to describe the state of evidence regarding the extent, outcomes and contextual considerations of CAPA implementation in community mental health services. DESIGN: Scoping review. DATA SOURCES: Published and grey literature were searched using MEDLINE, Embase, CINAHL, PsycINFO, Scopus and Google to 13 and 20 July 2022, respectively. ELIGIBILITY CRITERIA: We included reports focused on the implementation, outcomes (clinical, programme or system) or a discussion of contextual factors that may impact CAPA implementation in either child and adolescent or adult mental health services. DATA EXTRACTION AND SYNTHESIS: Data were extracted using a codebook that reflected the five domains of the Consolidated Framework for Implementation Research (CFIR) and reviewed for agreement and accuracy. Data were synthesised according to the five CFIR domains. RESULTS: Forty-eight reports describing 36 unique evaluations were included. Evaluations were observational in nature; 10 employed pre-post designs. CAPA implementation, regardless of setting, was largely motivated by long wait times. Characteristics of individuals (eg, staff buy-in or skills) were not reported. Processes of implementation included facilitative leadership, data-informed planning and monitoring and CAPA training. Fidelity to CAPA was infrequently measured (n=9/36) despite available tools. Health system outcomes were most frequently reported (n=28/36); few evaluations (n=7/36) reported clinical outcomes, with only three reporting pre/post CAPA changes. CONCLUSIONS: Gaps in evidence preclude a systematic review and meta-analysis of CAPA implementation. Measurement of clinical outcomes represents an area for significant improvement in evaluation. Consistent measurement of model fidelity is essential for ensuring the accuracy of outcomes attributed to its implementation. An understanding of the change processes necessary to support implementation would be strengthened by more comprehensive consideration of contextual factors.

Feasibility of Text Messages for Enhancing Therapeutic Engagement Among Youth and Caregivers Initiating Outpatient Mental Health Treatment: Mixed Methods Study.

BACKGROUND: Pathways to mental health services for youth are generally complex and often involve numerous contact points and lengthy delays. When starting treatment, there are a host of barriers that contribute to low rates of therapeutic engagement. Automated text messages offer a convenient, low-cost option for information sharing and skill building, and they can potentially activate positive behaviors in youth and caregivers prior to beginning formal therapy. To date, there is little evidence for the feasibility of initiating transdiagnostic text messages during the early stages of youth and caregiver contact with community outpatient mental health services. OBJECTIVE: To develop and test the feasibility of implementing 2 novel text messaging campaigns aimed at youth clients and their caregivers during the early stages of engaging with outpatient mental health services. METHODS: A multidisciplinary panel of experts developed two 12-message interventions with youth and caregivers prior to deployment. Each message included a link to an external interactive or multimedia resource to extend skill development. Enrollment of youth aged 13 to 18 years, their caregivers, or both occurred at 2 early treatment timepoints. At both time points, text messages were delivered automatically 2 times a week for 6 weeks. Analytics and survey data were collected in 2 phases, between January and March 2020 and between January and May 2021. Enrollment, willingness to persist in using the intervention, engagement, satisfaction, perceived value, and impact were measured. Descriptive statistics were used to summarize youth and caregiver outcomes. RESULTS: A total of 41 caregivers and 36 youth consented to participate. Follow-up survey response rates were 54% (22/41) and 44%, (16/36) respectively. Over 1500 text messages were sent throughout the study. More than three-quarters (14/16, 88%) of youth reported that they learned something new and noticed a change in themselves due to receiving the texts; the same proportion (14/16, 88%) of youth said they would recommend the text messages to others. Youth ranked the first text message, related to coping with difficult emotions, as the most helpful of the series. Caregivers reported acting differently due to receiving the texts. Over two-thirds of caregivers were satisfied with the texts (16/22, 73%) and would recommend them to others (16/22, 73%). Caregivers perceived diverse levels of value in the text topics, with 9 of the 12 caregiver texts rated by at least one caregiver as the most helpful. CONCLUSIONS: Results are preliminary but show that brief, core skill-focused text messages for youth clients and caregivers in community outpatient mental health services are feasible. Both youth and caregivers reported promising knowledge and behavior change with exposure to only 12 messages over 6 weeks. A larger study with statistical power to detect changes in both perceived helpfulness and engagement is required to confirm the effectiveness of this type of transdiagnostic intervention.

An Innovative Model of Pediatric Emergency Department Mental Health Care: Protocol for a Multicenter Type 1 Effectiveness-Implementation Cluster Randomized Trial.

Over the past decade, visits to American and Canadian emergency departments (EDs) for child and youth mental health care have increased substantially.1,2 Acute mental health crises can occur as a result of a variety of concerns, including those that are life threatening (eg, suicide attempts), pose safety concerns (eg, suicidal intentions, aggressive behaviors, alcohol and other drug use), and are physically distressing to the child or youth (eg, panic attacks). ED health care providers play a vital role in assessing the safety and well-being of the child or youth and referring them to services for ongoing care.3,4 During the ED visit, assessment and care should pinpoint risks, inform treatment, and consider family needs and preferences as part of a patient-centered approach. Yet, this approach to care is not widely adopted in EDs. Most EDs do not require the use of pediatric-specific mental health tools to guide assessments or have patient-centered procedures in place to guide the care of patients with mental health emergencies.5-7 Our team believes these limitations have led to the provision of acute mental health care that can lack sufficient quality and efficiency. This study protocol describes a trial designed to evaluate if a novel mental health care bundle that was co-designed with parents and youth results in greater improvements in the well-being of children and youth 30 days after seeking ED care for mental health and/or substance misuse concerns compared with existing care protocols. We hypothesize that the bundle will positively impact child and youth well-being, while also providing cost-effective health care system benefits.

Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study.

BACKGROUND: Lower airway biofilms are hypothesised to contribute to poor treatment outcomes among children with chronic lung disease; however, data are scarce. We aimed to determine the presence and prevalence of biofilm in bronchoalveolar lavage from children with protracted bacterial bronchitis (PBB) or bronchiectasis; whether biofilm was associated with signs of lower airway infection; and whether biofilms were consistent with an upper or lower airway origin. METHODS: In this cross-sectional study, fluorescent microscopy techniques were used to detect biofilm in archived bronchoalveolar lavage specimens from a paediatric cohort (age <18 years) with PBB or bronchiectasis who were prospectively recruited to observational studies of chronic cough at Royal Children's Hospital (Brisbane, Australia) or Royal Darwin Hospital (Darwin, Australia). Children with cystic fibrosis were excluded. Lower airway infection was defined as bronchoalveolar lavage neutrophil percentage of 15% or more, or a culture of a bacterial pathogen at 104 colony-forming units per mL or more, or both. Biofilms were subtyped as either of lower airway origin (unrelated to squamous epithelial cells) or of upper airway origin (observed in close association with squamous epithelial cells). Bronchoalveolar lavages were considered contaminated with upper airway secretions if the squamous cell proportion was more than ten cells per 1000 nucleated cells (>1%). Primary outcomes were the prevalence of each biofilm subtype among children with PBB compared with children with bronchiectasis. Secondary outcomes were the prevalence of each biofilm subtype among children with signs of lower airway infection compared to children without. FINDINGS: Biofilm testing was performed on 144 bronchoalveolar lavage specimens collected between Jan 1, 2011, and Dec 16, 2014, and preserved at -80°C before biofilm testing (69 children with PBB from Brisbane and 75 children with bronchiectasis from Darwin). The prevalence of lower airway biofilms (unrelated to squamous epithelial cells) was similar among the children with PBB (25 [36%] of 69) and children with bronchiectasis (31 [41%] of 75; odds ratio [OR] 1·24, 95% CI 0·63-2·43), but higher among children with signs of lower airway infection (46 [48%] of 95) than children without (eight [19%] of 43; OR 4·11, 95% CI 1·73-9·78), irrespective of the underlying diagnosis. By contrast, upper airway biofilms (associated with squamous epithelial cells) were more prevalent among children with bronchiectasis (32 [43%] of 75) than children with PBB (16 [23%] of 69; OR 2·47, 95% CI 1·20-5·08) and were unrelated to lower airway infection. Upper airway contamination was uncommon (eight [11%] of 71) and was not evident in 23 (79%) of 29 bronchoalveolar lavages that were positive for upper airway biofilms. INTERPRETATION: Lower airway biofilms are prevalent, but not ubiquitous, in bronchoalveolar lavage from children with PBB or bronchiectasis, suggesting anti-biofilm therapies might be beneficial for some children. Detection of upper airway biofilms in bronchoalveolar lavage that did not have signs of contamination suggests that microaspiration might be important in some children. Specimen quality measures are recommended for future studies to account for the presence of upper airway biofilms. FUNDING: Financial Markets for Children Project Grant, National Health and Medical Research Council of Australia, Rebecca L Cooper Medical Research Foundation, Queensland Children's Hospital Foundation, and BrightSpark Foundation.

Australian Aboriginal Otitis-Prone Children Produce High-Quality Serum IgG to Putative Nontypeable Haemophilus influenzae Vaccine Antigens at Lower Titres Compared to Non-Aboriginal Children.

Background: Nontypeable Haemophilus influenzae (NTHi) is the most common bacterial otopathogen associated with otitis media (OM). NTHi persists in biofilms within the middle ears of children with chronic and recurrent OM. Australian Aboriginal children suffer exceptionally high rates of chronic and recurrent OM compared to non-Aboriginal children. NTHi protein vaccines comprised of antigens associated with both adhesion and persistence in a biofilm are under development and could be beneficial for children with chronic and recurrent OM. Understanding the ontogeny of natural antibody development to these antigens provides insight into the value of vaccinating with particular antigens. Methods: An in-house multiplex fluorescent bead immunoassay was used to measure serum IgG titres and avidity for three putative vaccine antigens: recombinant soluble PilA (rsPilA), ChimV4, and outer membrane protein 26 (OMP26) in sera from Australian Aboriginal otitis-prone children (n=77), non-Aboriginal otitis-prone children (n=70) and non-otitis-prone children (n=36). Serum IgG titres were adjusted for age, and geometric mean concentrations (GMCs) were compared between groups using a univariate analysis model. Antibody avidity was calculated as a relative avidity index and compared between groups using ANOVA. Results: Australian Aboriginal otitis-prone children had lower serum IgG titres to rsPilA and ChimV4 than non-Aboriginal otitis-prone children (p<0.001), and non-otitis-prone children (p<0.020). No differences were observed between serum IgG titres from non-Aboriginal otitis-prone children and non-otitis-prone children. There were also no differences in the proportion of high avidity IgG specific for these antigens between these groups. Serum IgG titres to OMP26 were similar between all groups (p>0.670) although otitis-prone children had a higher proportion of high avidity antibodies to this antigen. Conclusions: Australian Aboriginal otitis-prone children had lower serum IgG titres to 2/3 major NTHi vaccine candidate antigens, suggesting these children are unable to develop persistent IgG responses due to repeated NTHi exposure. These reduced IgG titres may relate to earlier and more frequent exposure to diverse NTHi strains in Aboriginal children through carriage or infection. These data suggest that Aboriginal children may benefit from immunisation with vaccines containing these antigens to increase titres of protective antibodies.

Sleep Disordered Breathing and Recurrent Tonsillitis Are Associated With Polymicrobial Bacterial Biofilm Infections Suggesting a Role for Anti-Biofilm Therapies.

Background: The underlying pathogenesis of pediatric obstructive sleep disordered breathing (SDB) and recurrent tonsillitis (RT) are poorly understood but need to be elucidated to develop less invasive treatment and prevention strategies. Methods: Children aged between 1- and 16-years undergoing adenoidectomy, tonsillectomy or adenotonsillectomy for SDB (n=40), RT alone (n=18), or both SDB and RT (SDB+RT) (n=17) were recruited with age-matched healthy controls (n=33). Total bacterial load and species-specific densities of nontypeable Haemophilus influenzae (NTHi), Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae and Moraxella catarrhalis were measured by qPCR in nasopharyngeal swabs, oropharyngeal swabs, adenoid and tonsillar tissue from children with SDB, SDB+RT and RT, and in naso- and oro- pharyngeal swabs from healthy children. A subset of tonsil biopsies were examined for biofilms using 16S rRNA FISH (n=3/group). Results: The 5 bacterial species were detected in naso- and oro- pharyngeal samples from all children. These species were frequently detected in adenotonsillar tissue (except S. aureus, which was absent in adenoids) from children with SDB, SDB+RT and RT. NTHi and S. aureus were observed in tonsils from 66.7-88.2% and 33.3-58.8% of children respectively. Similar total and species-specific bacterial densities were observed in adenotonsillar tissue from children with SDB, SDB+RT or RT. Nasopharyngeal and oropharyngeal swabs were more likely to have multiple bacterial species co-detected than adenotonsillar tissue where one or two targeted species predominated. Polymicrobial biofilms and intracellular bacteria were observed in tonsils from children with adenotonsillar disease. Conclusions: Antimicrobials, particularly anti-biofilm therapies, may be a strategy for managing children with SDB.

Text Message Interventions in Adolescent Mental Health and Addiction Services: Scoping Review.

BACKGROUND: The vast majority of adolescent mental health and substance use disorders go undiagnosed and undertreated. SMS text messaging is increasingly used as a method to deliver adolescent health services that promote psychological well-being and aim to protect adolescents from adverse experiences and risk factors critical for their current and future mental health. To date, there has been no comprehensive synthesis of the existing literature on the extent, range, and implementation contexts of these SMS text message interventions. OBJECTIVE: The objective of this scoping review was to map and categorize gaps in the current body of peer-reviewed research around the use of SMS text messaging-based interventions for mental health and addiction services among adolescents. METHODS: A scoping review was conducted according to Levac's adaptation of Arksey and O'Malley's methodological framework for scoping reviews in six iterative stages. A search strategy was cocreated and adapted for five unique databases. Studies were screened using Covidence software. The PICO (patient, intervention, comparator, outcome) framework and input from multiple stakeholder groups were used to structure and pilot a data extraction codebook. Data were extracted on study methodology and measures, intervention design, and implementation characteristics, as well as policy, practice, and research implications. RESULTS: We screened 1142 abstracts. Of these, 31 articles published between 2013 and 2020 were eligible for inclusion. Intervention engagement was the most common type of outcome measured (18/31), followed by changes in cognitions (16/31; eg, disease knowledge, self-awareness) and acceptability (16/31). Interventions were typically delivered in less than 12 weeks, and adolescents received 1-3 messages per week. Bidirectional messaging was involved in 65% (20/31) of the studies. Limited descriptions of implementation features (eg, cost, policy implications, technology performance) were reported. CONCLUSIONS: The use of SMS text messaging interventions is a rapidly expanding area of research. However, lack of large-scale controlled trials and theoretically driven intervention designs limits generalizability. Significant gaps in the literature were observed in relation to implementation considerations, cost, clinical workflow, bidirectionality of texting, and level of personalization and tailoring of the interventions. Given the growth of mobile phone-based interventions for this population, a rigorous program of large-scale, well-designed trials is urgently required.

Nasal Delivery of a Commensal Pasteurellaceae Species Inhibits Nontypeable Haemophilus influenzae Colonization and Delays Onset of Otitis Media in Mice.

Nasopharyngeal colonization with nontypeable Haemophilus influenzae (NTHi) is a prerequisite for developing NTHi-associated infections, including otitis media. Therapies that block NTHi colonization may prevent disease development. We previously demonstrated that Haemophilus haemolyticus, a closely related human commensal, can inhibit NTHi colonization and infection of human respiratory epithelium in vitro We have now assessed whether Muribacter muris (a rodent commensal from the same family) can prevent NTHi colonization and disease in vivo using a murine NTHi otitis media model. Otitis media was modeled in BALB/c mice using coinfection with 1 × 104.5 PFU of influenza A virus MEM H3N2, followed by intranasal challenge with 5 × 107 CFU of NTHi R2866 Specr Mice were pretreated or not with an intranasal inoculation of 5 × 107 CFU M. muris 24 h before coinfection. NTHi and M. muris viable counts and inflammatory mediators (gamma interferon [IFN-γ], interleukin-1ß [IL-1ß], IL-6, keratinocyte chemoattractant [KC], and IL-10) were measured in nasal washes and middle ear tissue homogenate. M. muris pretreatment decreased the median colonization density of NTHi from 6 × 105 CFU/ml to 9 × 103 CFU/ml (P = 0.0004). Only 1/12 M. muris-pretreated mice developed otitis media on day 5 compared to 8/15 mice with no pretreatment (8% versus 53%, P = 0.0192). Inflammation, clinical score, and weight loss were also lower in M. muris-pretreated mice. We have demonstrated that a single dose of a closely related commensal can delay onset of NTHi otitis media in vivo Human challenge studies investigating prevention of NTHi colonization are warranted to reduce the global burden of otitis media and other NTHi diseases.

Vaginal Intraepithelial Neoplasia: A Retrospective Study of Treatment and Outcomes Among a Cohort of UK Women.

OBJECTIVES: The aim of the study was to analyze the clinical features of women found to have vaginal intraepithelial neoplasia (VaIN), the treatment modalities that they were offered, and clinical outcomes after treatment and follow-up. MATERIALS AND METHODS: This is a retrospective review of all cases of biopsy-proven or treated VaIN occurring for a 15-year period at Southend University Hospital, United Kingdom. RESULTS: Eighty-eight cases of VaIN were identified. The age range was from 24 to 76 years, and 39% of cases were low grade (VaIN 1) and 60% high grade (VaIN 2 and 3). Sixty-five percent of patients had either already undergone or would go on to have treatment for cervical intraepithelial neoplasia. Of those with low-grade disease, 86% were managed conservatively with a 97% success rate. Similarly, with high-grade disease, 77% were managed with laser treatment with a success rate of 76% for primary treatment. Of the 6 cases of high-grade disease treated conservatively, 50% subsequently needed active treatment. There was 1 case of progression to vaginal cancer (1.3%). CONCLUSIONS: Vaginal intraepithelial neoplasia remains an uncommon premalignant condition. It can affect women of all ages and is commoner in those who are immunosuppressed. Observation of low-grade disease is safe and the abnormality often resolves spontaneously. For persistent disease or higher-grade abnormalities, there are many treatment options but laser vaporization is the most commonly used. However, because of the nature of VaIN, recurrence is common even after treatment and further management can be challenging. The overall rate of malignant progression is small but protracted follow-up may be necessary.

The Choice and Partnership Approach to community mental health and addictions services: a realist-informed scoping review protocol.

INTRODUCTION: Early identification and appropriate treatment of child and adolescent mental health disorders can often be hampered by patchwork services with poorly planned or unclear pathways. The Choice and Partnership Approach (CAPA) is an evidence-based transformational model of community (community-based or outpatient) mental health and addictions services for children and adolescents that aims to better match services to needs and to improve timely access to care. CAPA has been variably implemented across jurisdictions but has not been comprehensively evaluated for its impact on system and client outcomes. Our research question is, 'To what degree does CAPA work, for whom and under what circumstances?'. The purpose of this review is twofold: (1) to gain an understanding of the extent and outcomes of the implementation of CAPA in community mental health and addictions services; and (2) to identify the role of context as it influences the implementation of CAPA and resulting client and system outcomes. METHODS AND ANALYSIS: We will conduct a realist-informed scoping review of the literature related to CAPA in either child and adolescent or adult community mental health and addictions services. Relevant studies, reports and documentation will be identified by searching the following online databases: MEDLINE, Embase, CINAHL, PsycINFO, Academic Search Premier, ERIC, Web of Science, Cochrane, Dissertations Abstracts, NCBI Bookshelf, PubMed Central and the Canadian Health Research Collection. The search strategy was developed by a health sciences library scientist and informed by a multidisciplinary team comprising methodological and content knowledge experts. The search will gather evidence from multiple online databases of peer-reviewed literature and grey literature repositories. All articles will be independently assessed for inclusion by pairs of reviewers. The key themes derived from a thematic analysis of extracted data will be presented in a narrative overview. ETHICS AND DISSEMINATION: Research ethics review is not required for this scoping review. The results will be disseminated through meetings with stakeholders (including clients and families, clinicians and decision-makers), conference presentations and peer-reviewed publication. The results of this review will inform an overarching programme of research, policy and quality indicator development to ultimately improve mental health and addictions care and subsequent mental health outcomes for children and adolescents.

Evaluating the HEADS-ED Screening Tool in a Hospital-Based Mental Health and Addictions Central Referral Intake System: A Prospective Cohort Study.

OBJECTIVES: We evaluated the use of a mental health (MH) screening tool in a hospital-based centralized MH referral telephonic intake process. The tool is used to guide psychosocial screening in several domains: home; education; activities and peers; drugs and alcohol; suicidality; emotions, thoughts, and behaviors; and discharge resources (HEADS-ED). We wanted to understand the use of the tool to guide next step in care decision-making over the telephone. METHODS: Intake workers used the HEADS-ED tool to guide the assessment processes, identified areas of MH need, and made decisions about next step in care. We completed a retrospective chart review of all callers to the intake system over 4 months to gather initial decision at intake and subsequent steps in treatment. χ2 and analysis of variance tests were used to examine differences between HEADS-ED scores and next step in care. RESULTS: A total of 674 patients aged 3 to 19 years (mean age = 11.7 years, SD = 0.6; girls = 50.0%) called for services. Significant mean differences were found on total HEADS-ED scores between treatment options (F4,641 = 75.76; P < .001). Decision validity indicated that 86% (n = 506 of 587) of initial referrals matched treatments that were actually received. Uptake of the tool was 100%, and interrater reliability indicated strong agreement between raters (intraclass correlation coefficient = 0.82; P < .001). CONCLUSIONS: With our results, we support the use of the HEADS-ED tool in a telephone-based MH intake system to help guide the initial assessment and inform decision-making about fit of next step in care, both within the health center-based MH system and in the community.

The Impact of the Hippocratic Oath in 2018: The Conflict of the Ideal of the Physician, the Knowledgeable Humanitarian, Versus the Corporate Medical Allegiance to Financial Models Contributes to Burnout.

The tradition in medical school includes taking the Hippocratic Oath usually at graduation. The purpose of this review is to examine what that oath has been, what forms it currently has, and the implications for physicians in today's healthcare environment. The changes in health economics affect physicians as they try to follow the oath's allegiance to the individual patient's needs. At times, this goal conflicts with the perspective of the financial world's controls of insurance companies and medical groups and institutions. This difference of the physicians' ethical perspectives from the business leaders regarding the philosophy of the value of the individual's health and life may be related to some aspect of physician burnout.

Improving Access to Child and Adolescent Mental Health Care: The Choice and Partnership Approach.

OBJECTIVE: The Choice and Partnership Approach (CAPA) is designed to improve access and quality of pediatric mental health care. We tested whether CAPA improved access in an academic pediatric hospital. METHOD: We used de-identified administrative data to compare access pre- (2011) and post-CAPA (2013). RESULTS: Wait time to first appointment in 2011 was 225.3 days (95% CI = [211.0, 239.6], N = 364), compared to 93.0 days (95% CI = [89.2, 96.8], N = 838) in 2013 (p<.001). Mean wait time between the first and second appointments was 59.2 days (95% CI = [46.5, 71.9], N = 86) in 2011, compared to 95.9 days (95% CI = [90.3, 101.5], N = 487) in 2013 (p < .001). However, overall mean wait time from referral to second appointment decreased from 271.2 days (95% CI = [236.5, 305.9], N = 86) in 2011 to 168.9 days (95% CI = [161.6, 176.2], N = 487) in 2013 (p < .001). Provider productivity increased from 32.6 to 57.0 first appointments/FTE/year. Depending on the question, 65 to 95% of parents and children gave positive answers about CAPA. CONCLUSIONS: CAPA implementation was associated with more patients served, decreased waiting time to first appointment, and higher productivity.

OBJECTIF: L'approche choix et partenaires (CAPA) est destinée à améliorer l'accès et la qualité des soins de santé mentale pédiatriques. Nous avons vérifié si CAPA améliorait l'accès dans un hôpital pédiatrique universitaire. MÉTHODE: Nous avons utilisé des données administratives dépersonnalisées pour comparer l'accès avant 2011 et après-CAPA (2013). RÉSULTATS: Le temps d'attente pour un premier rendez-vous en 2011 était de 225,3 jours (IC à 95% = [211,0, 239,6], N = 364), comparé à 93,0 jours (IC à 95% = [89,2, 96,8], N = 838) en 2013 (p < 0,001). Le temps d'attente moyen entre le premier et le deuxième rendez-vous était de 59,2 jours (IC à 95% = [46,5, 71,9], N = 86) en 2011, comparé à 95,9 jours (IC à 95% = [90,3, 101,5], N = 487) en 2013 (p < 0,001). Cependant, le temps d'attente moyen global de l'aiguillage au deuxième rendez-vous est passé de 271,2 jours (IC à 95% = [236,5, 305,9], N = 86) en 2011 à 168,9 jours (IC à 95% = [161,6, 176,2], N = 487) en 2013 (p < 0,001). La productivité des prestataires a augmenté de 32,6 à 57,0 premiers rendezvous/ETP/année. Dépendamment de la question, 65 à 95% des parents et des enfants ont donné des réponses positives à l'endroit de CAPA. CONCLUSIONS: La mise en oeuvre de CAPA était associée à plus de parents servis, à un temps d'attente réduit pour le premier rendez-vous, et à une plus grande productivité.

A GCSFR/CSF3R zebrafish mutant models the persistent basal neutrophil deficiency of severe congenital neutropenia.

Granulocyte colony-stimulating factor (GCSF) and its receptor (GCSFR), also known as CSF3 and CSF3R, are required to maintain normal neutrophil numbers during basal and emergency granulopoiesis in humans, mice and zebrafish. Previous studies identified two zebrafish CSF3 ligands and a single CSF3 receptor. Transient antisense morpholino oligonucleotide knockdown of both these ligands and receptor reduces neutrophil numbers in zebrafish embryos, a technique widely used to evaluate neutrophil contributions to models of infection, inflammation and regeneration. We created an allelic series of zebrafish csf3r mutants by CRISPR/Cas9 mutagenesis targeting csf3r exon 2. Biallelic csf3r mutant embryos are viable and have normal early survival, despite a substantial reduction of their neutrophil population size, and normal macrophage abundance. Heterozygotes have a haploinsufficiency phenotype with an intermediate reduction in neutrophil numbers. csf3r mutants are viable as adults, with a 50% reduction in tissue neutrophil density and a substantial reduction in the number of myeloid cells in the kidney marrow. These csf3r mutants are a new animal model of human CSF3R-dependent congenital neutropenia. Furthermore, they will be valuable for studying the impact of neutrophil loss in the context of other zebrafish disease models by providing a genetically stable, persistent, reproducible neutrophil deficiency state throughout life.

Inflammasome-independent NLRP3 augments TGF-ß signaling in kidney epithelium.

Tubulointerstitial inflammation and fibrosis are strongly associated with the outcome of chronic kidney disease. We recently demonstrated that the NOD-like receptor, pyrin domain containing-3 (NLRP3) contributes to renal inflammation, injury, and fibrosis following unilateral ureteric obstruction in mice. NLRP3 expression in renal tubular epithelial cells (TECs) was found to be an important component of experimental disease pathogenesis, although the biology of NLRP3 in epithelial cells is unknown. In human and mouse primary renal TECs, NLRP3 expression was increased in response to TGF-ß1 stimulation and associated with epithelial-mesenchymal transition (EMT) and the expression of α-smooth muscle actin (αSMA) and matrix metalloproteinase (MMP) 9. TGF-ß1-induced EMT and the induction of MMP-9 and αSMA were significantly decreased in mouse Nlrp3(-/-) renal TECs, suggesting a role for Nlrp3 in TGF-ß-dependent signaling. Although apoptosis-associated speck-like protein containing a CARD domain(-/-) TECs demonstrated a phenotype similar to that of Nlrp3(-/-) cells in response to TGF-ß1, the effect of Nlrp3 on MMP-9 and αSMA expression was inflammasome independent, as IL-1ß, IL-18, MyD88, and caspase-1 were dispensable. Smad2 and Smad3 phosphorylation in response to TGF-ß1 was attenuated in Nlrp3(-/-) and apoptosis-associated speck-like protein containing a CARD domain(-/-) cells, accounting for the dampened EMT and TGF-ß1 responsiveness in these cells. Consistent with these findings, overexpression of NLRP3 in 293T cells resulted in increased Smad3 phosphorylation and activity. Taken together, these data support a novel and direct role for NLRP3 in promoting TGF-ß signaling and R-Smad activation in epithelial cells independent of the inflammasome.