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BACKGROUND AND OBJECTIVES: Viral bronchiolitis is a common pediatric illness. Treatment is supportive; however, some children have concurrent serious bacterial infections (cSBIs) requiring antibiotics. Identifying children with cSBI is challenging and may lead to unnecessary treatment. Improved understanding of the prevalence of and risk factors for cSBI are needed to guide treatment. We sought to determine the prevalence of cSBI and identify factors associated with cSBI in children hospitalized with bronchiolitis. METHODS: We performed a retrospective cohort study of children <2 years old hospitalized with bronchiolitis at a free-standing children's hospital from 2012 to 2019 identified by International Classification of Diseases codes. cSBI was defined as bacteremia, urinary tract infection, meningitis, or pneumonia. Risk factors for cSBI were identified using logistic regression. RESULTS: We identified 7871 admissions for bronchiolitis. At least 1 cSBI occurred in 4.2% of these admissions; with 3.5% meeting our bacterial pneumonia definition, 0.4% bacteremia, 0.3% urinary tract infection, and 0.02% meningitis. cSBI were more likely to occur in children with invasive mechanical ventilation (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.78-3.63), a C-reactive protein ≥4 mg/dL (OR 2.20, 95% CI 1.47-3.32), a concurrent complex chronic condition (OR 1.67, 95% CI 1.22-2.25) or admission to the PICU (OR 1.46, 95% CI 1.02-2.07). CONCLUSIONS: cSBI is uncommon among children hospitalized with bronchiolitis, with pneumonia being the most common cSBI. Invasive mechanical ventilation, elevated C-reactive protein, presence of complex chronic conditions, and PICU admission were associated with an increased risk of cSBI.
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Bronquiolitis , Humanos , Lactante , Femenino , Masculino , Estudios Retrospectivos , Bronquiolitis/epidemiología , Bronquiolitis/complicaciones , Factores de Riesgo , Prevalencia , Infecciones Bacterianas/epidemiología , Hospitalización/estadística & datos numéricos , Niño Hospitalizado/estadística & datos numéricos , Infecciones Urinarias/epidemiología , Hospitales PediátricosRESUMEN
BACKGROUND: Birth cohort screening has been implemented in some countries to identify the potentially 'missed population' of undiagnosed chronic Hepatitis C Virus (HCV) in people who may not be found through targeted approaches. AIM: To determine uptake of HCV antibody testing using an oral swab screening method, overall yield, whether those testing positive had risk markers in their primary care record, and cost per case detected. DESIGN AND SETTING: Pilot screening study set in general practices in the Southwest, South London and Yorkshire and Humber. METHOD: Participants consenting were sent an oral swab kit in the post and saliva samples were tested for antibody to HCV. RESULTS: 16,436/98,396 (16.7%) patients consented and were sent an oral swab kit. 12,216 (12.4%) returned a kit, with 31 participants (yield 0.03%) testing positive for HCV antibody. 45% of those positive had a risk marker for HCV on their primary care record. Two (yield 0.002%) were confirmed RNA positive and referred for treatment, both had HCV risk markers. Cost per case detected was £16,000 per HCV antibody and £247,997 per chronic HCV. CONCLUSIONS: Wide-scale screening could be delivered and identified people infected with HCV, however most of these individuals could have been detected through lower-cost targeted screening. Yield and cost per case found were substantially worse than model estimates and targeted screening studies. Birth cohort screening should not be rolled out in primary care in England.
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HIV genotyping is used to assess HIV susceptibility to antiretroviral drugs. The Applied Biosystems HIV-1 Genotyping Kit with Integrase (AB kit, Thermo Fisher Scientific) detects resistance-associated mutations (RAMs) in HIV protease (PR), reverse transcriptase (RT), and integrase (IN). We compared results from the AB kit with results obtained previously with the ViroSeq HIV-1 Genotyping System. DNA amplicons from the AB kit were also analyzed using next-generation sequencing (NGS). HIV RNA was extracted using the MagNA Pure 24 instrument (Roche Diagnostics; 96 plasma samples, HIV subtype B, viral load range: 530-737,741 copies/mL). FASTA files were generated from AB kit data using Exatype (Hyrax Biosciences). DNA amplicons from the AB kit were also analyzed by NGS using the Nextera XT kit (Illumina). Drug resistance was predicted using the Stanford HIV Drug Resistance Database. The mean genetic distance for sequences from ViroSeq and the AB kit was 0.02% for PR/RT and 0.04% for IN; 103 major RAMs were detected by both methods. Four additional major RAMs were detected by the AB kit only. These four major RAMs were also detected by NGS (detected in 18.1%-38.2% of NGS reads). NGS detected 27 major RAMs that were not detected with either of the Sanger sequencing-based kits. All major RAMs detected with ViroSeq were detected with the AB kit; additional RAMs were detected with the AB kit only. DNA amplicons from the AB kit can be used for NGS for more sensitive detection of RAMs.
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Farmacorresistencia Viral , Técnicas de Genotipaje , Infecciones por VIH , Integrasa de VIH , VIH-1 , Secuenciación de Nucleótidos de Alto Rendimiento , VIH-1/genética , VIH-1/efectos de los fármacos , VIH-1/enzimología , VIH-1/aislamiento & purificación , VIH-1/clasificación , Humanos , Infecciones por VIH/virología , Técnicas de Genotipaje/métodos , Farmacorresistencia Viral/genética , Integrasa de VIH/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Genotipo , Juego de Reactivos para Diagnóstico/normas , ARN Viral/genética , Mutación , Transcriptasa Inversa del VIH/genética , Proteasa del VIH/genéticaRESUMEN
The incidence of respiratory syncytial virus (RSV) in adults is inadequately defined and the impact of SARS-CoV-2-related non-pharmaceutical interventions (NPIs) is underexplored. Using laboratory data, we described the detection rate of RSV in adults ≥16 years in Western Australia (WA) between 2017 and 2023. With the exception of 2020, RSV detections rose annually between 2017 and 2023, reaching 50.7 per 100,000 in 2023 (95% confidence interval [CI], 47.9-53.8). RSV testing expanded considerably across the study period, with the testing in 2023 more than five times the 2017 total. The detection rate was highest in adults ≥60 years between 2017 and 2019, particularly those ≥75 years. Following 2020, the detections in all age groups increased, with the highest detection rate in 2023 in those ≥75-years (199.5 per 100,000; 95% CI, 180.5-220). NPIs significantly impacted RSV seasonality; the preceding winter pattern was disrupted, resulting in an absent 2020 winter season and two major summer seasons in 2020/21 and 2021/22. The RSV season began to realign in 2022, reverting to a winter seasonal pattern in 2023 and the largest season in the study period. Ongoing surveillance will be required to understand the stability of these increases and to delineate the impact of new immunisation strategies.
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COVID-19 , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Estaciones del Año , Humanos , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/virología , Adulto , Australia Occidental/epidemiología , Persona de Mediana Edad , Anciano , Adulto Joven , Adolescente , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Femenino , COVID-19/epidemiología , COVID-19/virología , COVID-19/prevención & control , COVID-19/diagnóstico , Masculino , Incidencia , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Anciano de 80 o más AñosRESUMEN
Background: Pneumonia is the leading cause of death in young children globally and is prevalent in the Papua New Guinea highlands. We investigated clinical predictors of hypoxic pneumonia to inform local treatment guidelines in this resource-limited setting. Methods: Between 2013 and 2020, two consecutive prospective observational studies were undertaken enrolling children 0-4 years presenting with pneumonia to health-care facilities in Goroka Town, Eastern Highlands Province. Logistic regression models were developed to identify clinical predictors of hypoxic pneumonia (oxygen saturation <90% on presentation). Model performance was compared against established criteria to identify severe pneumonia. Findings: There were 2067 cases of pneumonia; hypoxaemia was detected in 36.1%. The strongest independent predictors of hypoxic pneumonia were central cyanosis on examination (adjusted odds ratio [aOR] 5.14; 95% CI 3.47-7.60), reduced breath sounds (aOR 2.92; 95% CI 2.30-3.71), and nasal flaring or grunting (aOR 2.34; 95% CI 1.62-3.38). While the model developed to predict hypoxic pneumonia outperformed established pneumonia severity criteria, it was not sensitive enough to be clinically useful at this time. Interpretation: Given signs and symptoms are unable to accurately detect hypoxia, all health care facilities should be equipped with pulse oximeters. However, for the health care worker without access to pulse oximetry, consideration of central cyanosis, reduced breath sounds, nasal flaring or grunting, age-specific tachycardia, wheezing, parent-reported drowsiness, or bronchial breathing as suggestive of hypoxaemic pneumonia, and thus severe disease, may prove useful in guiding management, hospital referral and use of oxygen therapy. Funding: Funded by Pfizer Global and the Bill & Melinda Gates Foundation.
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BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control. METHODS: We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000-2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection. RESULTS: The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants. CONCLUSIONS: The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV.
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Hospitalización , Recien Nacido Prematuro , Infecciones por Virus Sincitial Respiratorio , Humanos , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/prevención & control , Hospitalización/estadística & datos numéricos , Lactante , Recién Nacido , Australia Occidental/epidemiología , Femenino , Virus Sincitial Respiratorio Humano , Factores de Edad , Masculino , Medición de Riesgo , Factores de RiesgoRESUMEN
WHAT IS KNOWN ON THE SUBJECT: Peer research methodologies and methods are increasingly used in research, particularly to benefit from lived experiences. The experiences of peer researchers with severe mental illness are less common, including the impact on them of conducting peer-led research. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: This paper shares the experience of peer research and suggests in the context of food insecurity, that it is not well understood by some healthcare professionals. WHAT ARE THE IMPLICATIONS FOR PRACTICE: Implications include considerations around trauma-informed care and the need for screening for food insecurity in mental healthcare settings. Research implications include providing training for peer research and needing to consider longevity of peer researcher relationships. ABSTRACT: Introduction Food insecurity means that a person does not have access to sufficient nutritious food for normal growth and health. This can lead to health problems such as obesity, heart disease, diabetes and other long term chronic health conditions. People living with a severe mental illness are more likely to experience food insecurity than people without a severe mental illness. Aim The aim of this paper is to present a lived experience narrative of two peer researchers. Peer researchers conducted interviews with adults with severe mental illness from Northern England as part of a funded research project. These interviews discussed experiences of food insecurity and strategies to tackle it and were conducted between March and December 2022. Thesis The following paper does not discuss the results of the interviews themselves. Rather the narrative begins with an overview of peer research, before sharing the experiences of the two peer researchers in undertaking this project. Implications for Practice This includes healthcare professionals understanding food insecurity, what it is and what it is not, thinking about trauma-informed care, and screening for food insecurity. Peer research implications centre on adequate support and training, considerations to longevity of peer research relationships and reducing unnecessary research burden for peer researchers.
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BACKGROUND & AIMS: The abdominal discomfort experienced by patients with colitis may be attributable in part to the presence of small intestinal dysmotility, yet mechanisms linking colonic inflammation with small-bowel motility remain largely unexplored. We hypothesize that colitis results in small intestinal hypomotility owing to a loss of enteroendocrine cells (EECs) within the small intestine that can be rescued using serotonergic-modulating agents. METHODS: Male C57BL/6J mice, as well as mice that overexpress (EECOVER) or lack (EECDEL) NeuroD1+ enteroendocrine cells, were exposed to dextran sulfate sodium (DSS) colitis (2.5% or 5% for 7 days) and small intestinal motility was assessed by 70-kilodalton fluorescein isothiocyanate-dextran fluorescence transit. EEC number and differentiation were evaluated by immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, and quantitative reverse-transcriptase polymerase chain reaction. Mice were treated with the 5-hydroxytryptamine receptor 4 agonist prucalopride (5 mg/kg orally, daily) to restore serotonin signaling. RESULTS: DSS-induced colitis was associated with a significant small-bowel hypomotility that developed in the absence of significant inflammation in the small intestine and was associated with a significant reduction in EEC density. EEC loss occurred in conjunction with alterations in the expression of key serotonin synthesis and transporter genes, including Tph1, Ddc, and Slc6a4. Importantly, mice overexpressing EECs revealed improved small intestinal motility, whereas mice lacking EECs had worse intestinal motility when exposed to DSS. Finally, treatment of DSS-exposed mice with the 5-hydroxytryptamine receptor 4 agonist prucalopride restored small intestinal motility and attenuated colitis. CONCLUSIONS: Experimental DSS colitis induces significant small-bowel dysmotility in mice owing to enteroendocrine loss that can be reversed by genetic modulation of EEC or administering serotonin analogs, suggesting novel therapeutic approaches for patients with symptomatic colitis.
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Colitis , Sulfato de Dextran , Células Enteroendocrinas , Motilidad Gastrointestinal , Intestino Delgado , Animales , Células Enteroendocrinas/metabolismo , Ratones , Colitis/patología , Colitis/inducido químicamente , Colitis/complicaciones , Masculino , Motilidad Gastrointestinal/efectos de los fármacos , Intestino Delgado/patología , Intestino Delgado/efectos de los fármacos , Sulfato de Dextran/toxicidad , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Serotonina/metabolismo , BenzofuranosRESUMEN
AIM: This study aimed to explore food insecurity prevalence and experiences of adults with severe mental illness living in Northern England. METHODS: This mixed-methods cross-sectional study took place between March and October 2022. Participants were adults with self-reported severe mental illness living in Northern England. The survey included demographic, health, and financial questions. Food insecurity was measured using the US Department of Agriculture Adult Food Security measure. Quantitative data were analysed using descriptive statistics and binary logistic regression; and qualitative data using content analysis. RESULTS: In total, 135 participants completed the survey, with a mean age of 44.7 years (SD: 14.1, range: 18-75 years). Participants were predominantly male (53.3%), white (88%) and from Yorkshire (50.4%). The food insecurity prevalence was 50.4% (n = 68). There was statistical significance in food insecurity status by region (p = 0.001); impacts of severe mental illness on activities of daily living (p = 0.02); and the Covid pandemic on food access (p < 0.001). The North West had the highest prevalence of food insecurity (73.3%); followed by the Humber and North East regions (66.7%); and Yorkshire (33.8%). In multivariable binary logistic regression, severe mental illness' impact on daily living was the only predictive variable for food insecurity (odds ratio = 4.618, 95% confidence interval: 1.071-19.924, p = 0.04). CONCLUSION: The prevalence of food insecurity in this study is higher than is reported in similar studies (41%). Mental health practitioners should routinely assess and monitor food insecurity in people living with severe mental illness. Further research should focus on food insecurity interventions in this population.
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OBJECTIVES: To evaluate the effectiveness of maternal pertussis vaccination for preventing pertussis infections in Aboriginal and Torres Strait Islander infants under seven months of age. STUDY DESIGN: Retrospective cohort study; analysis of linked administrative health data. SETTING, PARTICIPANTS: Mother-infant cohort (Links2HealthierBubs) including all pregnant women who gave birth to live infants (gestational age ≥ 20 weeks, birthweight ≥ 400 g) in the Northern Territory, Queensland, and Western Australia during 1 January 2012 - 31 December 2017. MAIN OUTCOME MEASURES: Proportions of women vaccinated against pertussis during pregnancy, rates of pertussis infections among infants under seven months of age, and estimated effectiveness of maternal vaccination for protecting infants against pertussis infection, each by Indigenous status. RESULTS: Of the 19 892 Aboriginal and Torres Strait Islander women who gave birth to live infants during 2012-2017, 7398 (37.2%) received pertussis vaccine doses during their pregnancy, as had 137 034 of 259 526 non-Indigenous women (52.8%; Indigenous v non-Indigenous: adjusted odds ratio, 0.66; 95% confidence interval [CI], 0.62-0.70). The annual incidence of notified pertussis infections in non-Indigenous infants declined from 16.8 (95% CI, 9.9-29) in 2012 to 1.4 (95% CI, 0.3-8.0) cases per 10 000 births in 2017; among Aboriginal and Torres Strait Islander infants, it declined from 47.6 (95% CI, 16.2-139) to 38.6 (95% CI, 10.6-140) cases per 10 000 births. The effectiveness of maternal vaccination for protecting non-Indigenous infants under seven months of age against pertussis infection during 2014-17 was 68.2% (95% CI, 51.8-79.0%); protection of Aboriginal and Torres Strait Islander infants was not statistically significant (36.1%; 95% CI, -41.3% to 71.1%). CONCLUSIONS: During 2015-17, maternal pertussis vaccination did not protect Aboriginal and Torres Strait Islander infants in the NT, Queensland, and WA against infection. Increasing the pertussis vaccination rate among pregnant Aboriginal and Torres Strait Islander women requires culturally appropriate, innovative strategies co-designed in partnership with Indigenous organisations and communities.
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Aborigenas Australianos e Isleños del Estrecho de Torres , Tos Ferina , Embarazo , Lactante , Humanos , Femenino , Estudios Retrospectivos , Tos Ferina/epidemiología , Tos Ferina/prevención & control , Vacunación , MadresRESUMEN
AIM: To assess parental awareness of respiratory syncytial virus (RSV) and the level of acceptance of future RSV prevention strategies. METHODS: A cross-sectional online survey was implemented targeting "future" and "current" parents of children aged ≤5 years in Australia. RESULTS: From 1992 eligible participants, two non-mutually exclusive subgroups were formed: "current" parents (N = 1931) and "pregnant/planning" parents (N = 464: 403 also "current" parents and 61 "future" parents). Participants were predominantly (86.6%) aged 25-39 years and 68.5% with university education. The majority (89.6% current; 78.7% future) had heard of RSV. Of those, 64.2% (current) and 50.0% (future) were aware that pneumonia is associated with RSV; 71.8% (current) and 52.1% (future) were aware that bronchiolitis is associated with RSV. In multivariable logistic regression analyses, Australian-born parents (aOR = 2.47 [95% CI: 1.48-4.12]), living in the eastern states (e.g., New South Wales: aOR = 6.15 [95% CI:2.10-18.04]), with a university-level education (aOR = 2.61 [95% CI:1.38-4.94]) and being a current parent (aOR = 12.26 [95% CI:2.82-53.28]) were associated with higher RSV awareness. There was a high level of acceptance for maternal vaccines (future: 79.3%) and infant immunisation (all: 81.7%). CONCLUSION: While RSV awareness and immunisation acceptance were high, there was limited knowledge of severity of RSV, especially in future parents. Education campaigns need to be developed to increase RSV knowledge.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Lactante , Niño , Embarazo , Femenino , Humanos , Preescolar , Infecciones por Virus Sincitial Respiratorio/prevención & control , Estudios Transversales , Australia , Padres , HospitalizaciónRESUMEN
A genomic cluster of Salmonella Braenderup ST22, a serovar of Salmonella enterica subsp. enterica which causes symptoms of gastrointestinal illness, was notified by Danish authorities to the European Centre for Disease Prevention and Control (ECDC) on 3 May 2021. By 6 July 2021, S. Braenderup outbreak cases (n = 348) had been reported from 12 countries in the European Union/European Economic Area (EU/EEA) and the United Kingdom (UK), including 68 hospitalised cases. With support from affected EU/EEA countries, and in partnership with the European Food Safety Authority (EFSA), ECDC established an international outbreak investigation team to rapidly identify the source and prevent outbreak spread. Consumption information was shared with affected countries through a standard line list, revealing that 124 of 197 cases (63%) reported having eaten (any) melons within 7 days prior to disease onset. The speed and completeness of the investigation, which identified the outbreak vehicle as galia melons imported from Honduras in June 2021, was a direct result of extensive collaboration and information sharing between countries' national food safety and public health authorities. This article describes the outbreak and the benefits, successes, and challenges of multi-country collaboration for consideration in future large foodborne outbreaks across Europe.
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Intoxicación Alimentaria por Salmonella , Salmonella enterica , Humanos , Salmonella/genética , Brotes de Enfermedades , Europa (Continente)/epidemiología , Intoxicación Alimentaria por Salmonella/epidemiología , Salmonella enterica/genéticaRESUMEN
BACKGROUND: Evidence suggests that children who had received an initial priming dose of whole-cell pertussis (wP) vaccine, rather than acellular pertussis (aP) vaccine, had a lower risk of developing IgE-mediated food allergy, the most common cause of anaphylaxis-related hospital presentations of childhood. OBJECTIVE: To assess the association between wP versus aP vaccination in infancy and subsequent hospital presentations for anaphylaxis. METHODS: This study was preregistered under PMID 34874968. Perinatal records for a cohort of New South Wales-born children (1997-1999) receiving their first dose of pertussis-containing vaccine before age 4 months were probabilistically linked to hospital and immunization records. We used adjusted Cox models to estimate hazard ratios (aHRs) and 95% CIs for anaphylaxis-coded hospitalizations. RESULTS: There were 218,093 New South Wales-born children who received a first dose of wP or aP before age 4 months. Among these children, 86 experienced at least one hospitalization for food-induced anaphylaxis at age 5-15 years (range of events per patient, one to three). The person-time of follow-up was 1,476,969 years, and 665,519 years for children vaccinated with wP as a first dose (wP-1 children) and aP as a first dose (aP-1 children), respectively. The incidence rates for first hospitalization for food anaphylaxis were 3.5 (95% CI, 2.6-4.6) and 5.1 (95% CI, 3.5-7.1) per 100,000 child-years among wP-1 children and aP-1 children, respectively (aHR for wP vs aP = 0.47; 95% CI, 0.26-0.83). For first admission for venom anaphylaxis, the incidence rate was 4.9 (95% CI, 3.9-6.2) per 100,000 child-years among wP-1 children and 5.1 (95% CI, 3.5-7.1) per 100,000 child-years among aP-1 children (aHR for wP vs aP = 0.92; 95% CI, 0.53-1.60), and for all-cause anaphylaxis, the incidence rate was 10.6 (95% CI, 9.0-12.4) per 100,000 child-years among wP-1 children and 12.8 (95% CI, 10.2-15.8) per 100,000 child-years among aP-1 children (aHR for wP vs aP = 0.92; 95% CI, 0.53-1.60). CONCLUSION: Vaccination with wP in infancy was associated with a lower risk of hospitalizations for food-induced anaphylaxis (and therefore severe IgE-mediated food allergy) occurring in childhood.
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Acetazolamida/análogos & derivados , Anafilaxia , Hipersensibilidad a los Alimentos , Tetraciclinas , Tos Ferina , Lactante , Humanos , Preescolar , Tos Ferina/prevención & control , Anafilaxia/epidemiología , Estudios de Cohortes , Factor de Transcripción AP-1 , Inmunización Secundaria , Vacuna contra la Tos Ferina , Vacunación , Hipersensibilidad a los Alimentos/epidemiología , Hospitalización , Inmunoglobulina ERESUMEN
WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities. We demonstrate that WDR44 variants associated with more severe disease impair ciliogenesis initiation and ciliary signaling. Because WDR44 negatively regulates ciliogenesis, it was surprising that pathogenic missense variants showed reduced abundance, which we link to misfolding of WDR autonomous repeats and degradation by the proteasome. We discover that disease severity correlates with increased RAB11 binding, which we propose drives ciliogenesis initiation dysregulation. Finally, we discover interdomain interactions between the WDR and NH2-terminal region that contains the RAB11 binding domain (RBD) and show patient variants disrupt this association. This study provides new insights into WDR44 WDR structure and characterizes a new syndrome that could result from impaired ciliogenesis.
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Ciliopatías , Genes Ligados a X , Repeticiones WD40 , Animales , Humanos , Masculino , Encéfalo , Ciliopatías/genética , Cognición , Pez Cebra/genéticaRESUMEN
Food insecurity means that a person does not have access to sufficient nutritious food for normal growth and health. Food insecurity can lead to many health problems such as obesity, heart disease, diabetes, and other long term health conditions. People living with a severe mental illness are more likely to experience food insecurity than people without mental illness. Peer-led in-depth interviews were conducted with adults with severe mental illness from Northern England, during which their experiences of food insecurity and strategies to tackle food insecurity were discussed. Interviews took place between March and December 2022, with interviews being transcribed and analysed using deductive and inductive thematic analysis. Thirteen interviews were conducted, finding that food insecurity in adults with severe mental illness was often a long-standing issue. Unemployment, the cost-of-living crisis and fuel poverty impacted on experiences of food insecurity. Difficulties accessing food banks such as transport, stigma, and the limited selection of available food was also discussed. Strategies to tackle food insecurity centred on making food banks more accessible and improving the quality of available food. Future research should aim to eradicate food insecurity for adults with severe mental illness, as limited research and action focuses on this population group over and above 'mental illness' or 'poor mental health'. Removing barriers to accessing food such as lack of transport, and providing food which is of adequate nutritional quality, should be prioritised, as well as tackling the stigma and accessibility issues surrounding food banks use.
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Respiratory syncytial virus (RSV) reinfection in children is poorly understood. We examined the incidence, characteristics, and outcomes of hospital-attended RSV reinfections in children <16 years in Western Australia between 2012 and 2022. Individuals with repeat RSV detections ≥56 days apart were identified using laboratory data. The incidence of reinfection in the first five years of life was estimated using the total birth population from 2012 to 2017. Clinical data on a subset of reinfection episodes were obtained from two metropolitan pediatric centers. A total of 466 children with hospital-attended reinfections were identified. The median interval between RSV detections was 460 days (interquartile range: 324, 812), with a reinfection rate of 95 per 100,000 individuals (95% confidence interval: 82, 109). Reinfection was most common in children who experienced their first RSV detection <6 months of age. Predisposing factors were identified in 56% of children; children with predisposing factors were older at first and second detections, were more likely to be admitted, and had a longer length of stay. This study highlights the significant burden of hospital-attended RSV reinfections in children with and without predisposing factors. Expanded surveillance with in-depth clinical data is required to further characterize the impact of RSV reinfection.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Niño , Humanos , Lactante , Reinfección , Infecciones por Virus Sincitial Respiratorio/epidemiología , Australia Occidental/epidemiología , HospitalizaciónRESUMEN
Introduction: To assess potential benefits and direct healthcare cost savings with expansion of an existing childhood influenza immunisation program, we developed a dynamic transmission model for the state of Western Australia, evaluating increasing coverage in children < 5 years and routinely immunising school-aged children. Methods: A deterministic compartmental Susceptible-Exposed-Infectious-Recovered age-stratified transmission model was developed and calibrated using laboratory-notification and hospitalisation data. Base case vaccine coverage estimates were derived from 2019 data and tested under moderate, low and high vaccine effectiveness settings. The impact of increased coverage on the burden of influenza, influenza-associated presentations and net costs were assessed using the transmission model and estimated health utilisation costs. Results: Under base case vaccine coverage and moderate vaccine effectiveness settings, 225,460 influenza cases are expected annually across all ages. Direct healthcare costs of influenza were estimated to be A$27,608,286 per annum, dominated by hospital costs. Net cost savings of >$A1.5 million dollars were observed for every 10 % increase in vaccine coverage in children < 5 years. Additional benefits were observed by including primary school age children (5-11 years) in the funded influenza vaccination program - a reduction in cases, presentations, hospitalisations and approximately $A4 million net costs savings were observed for every 10 % increase in coverage. The further addition of older children (12-17 years) resulted in only moderate additional net cost savings figures, compared with a 5-11year-old program alone. Net costs savings were predominantly derived by a reduction in influenza-associated hospitalisation in adults. Conclusions: Any increase in influenza vaccine coverage in children < 5 years, above a base case of 50 % coverage resulted in a substantive reduction in influenza cases, presentations, hospitalisations and net costs when applied to the West Australian population. However, the most impactful pediatric program, from both a disease prevention and costs perspective, would be one that increased vaccination coverage among primary-school aged children.
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BACKGROUND: People living with severe mental illness experience premature mortality from diet-related preventable illnesses. Yet, little research focuses on food insecurity with adults with severe mental illness. This coproduced study aimed to understand the experiences of adults with severe mental illness and food insecurity and strategies to help. METHODS: Following a pragmatism philosophical foundation, we undertook a mixed-methods study involving a survey (online and paper versions) and one-to-one semi-structured interviews (online and telephone) during March 7 to Dec 16, 2022. We recruited participants via existing severe mental illness service user groups and social media in Northern England. Eligible participants were adults (≥18 years) self-reporting a diagnosis of severe mental illness. Ethics approval was obtained from Teesside University and the Health Research Authority (Reference: 22/NR/0010; IRAS ID: 306281), with informed consent given. The target sample size, accounting for a typical survey response rate for people with severe mental illness of 10-20%, was 135. A target sample of 20 interviews was agreed to capture a range of views. Food insecurity was defined as the lack of financial resources needed to ensure someone has reliable access to enough food to meet their dietary, nutritional, and social needs. It is sometimes called food poverty. Quantitative data were analysed using descriptive statistics and binary logistic regression and qualitative data using thematic analysis. FINDINGS: 135 participants completed the survey (mean age 44·67 years [SD 14·1]). Participants were predominantly male (53%, n=72), white (87%, n=117), and from the Yorkshire region (50%, n=68). Overall, prevalence of food insecurity was 50·4% (n=68). Discussion across 13 interviews found food insecurity being a long-rooted experience, including familial and intergenerational experiences of food insecurity: "I grew up with this insecurity around food" (P002). Recommendations for tackling food insecurity centred on food banks, increasing accessibility, and reducing stigma: "I would like to get more information on where the centres are..." (P006) and "I was referred to, erm, a foodbank but it's still the stigma that's attached to it." (P002). INTERPRETATION: We found a higher prevalence of food insecurity in this study than in the general population (being 15%), yet limited research with adults with severe mental illness perpetuates food insecurity intergenerational injustices. Food insecurity should be eliminated. However, in the meanwhile, there should be widespread easy access to food banks offering nutritional foods. Limitations of this research include not reaching target sample size and a lack of ethnic diversity. FUNDING: National Institute of Health and Care Research (NIHR) Research for Patient Benefit.