RESUMO
OBJECTIVE: Governments use vaccination mandates, of different degrees of coerciveness, to encourage or require childhood vaccination. We elicited the views of well-informed community members on the public acceptability of using childhood vaccination mandates in Australia. METHODS: Four community juries were conducted in Canberra, Launceston, Cairns and Melbourne, Australia between 2021 and 2022. We recruited 51 participants from diverse backgrounds, genders and ages through random digit dialling and social media. Two juries were held in metropolitan areas, and two in regional/rural settings. Outcome measures included jury verdicts and reasons in response to structured questions. RESULTS: All juries were concerned about collective protection and individual rights but prioritised the former over the latter. A majority in all juries supported mandates but juries disagreed with respect to the appropriate mandate types. All juries endorsed using the least restrictive or coercive means to encourage vaccination (providing incentives or education, e.g.) before imposing penalties such as financial losses and school exclusions. The overriding view was that it is fairer to place a direct burden on parents rather than children and that mandates should be designed to avoid inequitable impacts on less advantaged groups in society. Many jurors found conscientious objection acceptable as a controlled option for resolute refusers, provided that overall vaccination coverage remains high. CONCLUSION: This paper gives policymakers access to the reasons that Australians have for supporting or opposing different mandates under conditions of high knowledge, understanding and deliberation regarding policy options. Sustaining high rates of vaccination requires high levels of co-operation between governments, public health actors and the public. Our findings highlight the importance of considering public values in the design and implementation of vaccination mandates. PATIENT AND PUBLIC INVOLVEMENT: We sought input from individuals who did and did not vaccinate during the study design. The views and perspectives of nonvaccinating parents were presented in the evidence to juries. We deliberately excluded nonvaccinating individuals from participating, as the divisive and often hostile nature of the topic, and their minority status, made it difficult to ensure they would feel safe as members of the jury without overrepresenting their perspective in the sample. Two related projects engaged directly with these parents.
Assuntos
Programas Obrigatórios , Vacinação , Humanos , Austrália , Feminino , Masculino , Vacinação/legislação & jurisprudência , Adulto , Pessoa de Meia-Idade , Criança , Adolescente , Opinião Pública , Adulto Jovem , Pais/psicologiaRESUMO
An accelerated local injection site reaction following Bacille Calmette-Guérin (BCG) vaccination has been associated with underlying active tuberculosis (TB) in high TB-prevalence settings. The clinical significance of this accelerated BCG reaction in individuals without TB symptoms, particularly in low TB-prevalence countries, is unclear. Using safety surveillance data and baseline interferon-gamma release assays (IGRA) within an international randomised trial of BCG vaccination in healthcare workers (the BRACE trial), we aimed to determine the incidence, and investigate for clinical implications, of an accelerated BCG reaction in asymptomatic adults in low and high TB-prevalence settings. An accelerated BCG reaction occurred in 755/1984 (38 %) of BCG-vaccinees. Although more frequently painful, tender, erythematous and/or swollen within the first fourteen days of vaccination, compared with non-accelerated reactions, the majority of injection site reactions were mild and did not meet criteria for an adverse event. Prior mycobacterial exposure, through prior BCG vaccination (OR 2.46, 95%CI 1.93-3.13, p < 0.001) or latent TB infection (OR 4.17, 95%CI 1.16-14.93, p = 0.03), and female sex (OR 1.27, 95%CI 1.03-1.57, p = 0.02), were key determinants for the occurrence of an accelerated BCG reaction. The development of an accelerated local reaction to BCG vaccination in an individual without prior history of BCG vaccination, should prompt consideration of further investigations for potential underlying TB infection.
RESUMO
BACKGROUND: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. METHODS AND FINDINGS: OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). CONCLUSIONS: Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. TRIAL REGISTRATION: Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).
Assuntos
Vacina contra Difteria, Tétano e Coqueluche , Esquemas de Imunização , Imunoglobulina E , Humanos , Lactente , Método Duplo-Cego , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Feminino , Masculino , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Austrália , Vacinas Combinadas/imunologia , Vacinas Combinadas/efeitos adversos , Vacinas Combinadas/administração & dosagem , Vacina contra Coqueluche/imunologia , Vacina contra Coqueluche/efeitos adversos , Vacina contra Coqueluche/administração & dosagem , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/prevenção & controle , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Vacinas Anti-Haemophilus/efeitos adversos , Vacinas Anti-Haemophilus/administração & dosagem , Coqueluche/prevenção & controle , Coqueluche/imunologia , Imunogenicidade da Vacina , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologiaRESUMO
Mutations in GBA1 cause Gaucher disease and are the most important genetic risk factor for Parkinson's disease. However, analysis of transcription at this locus is complicated by its highly homologous pseudogene, GBAP1. We show that >50% of short RNA-sequencing reads mapping to GBA1 also map to GBAP1. Thus, we used long-read RNA sequencing in the human brain, which allowed us to accurately quantify expression from both GBA1 and GBAP1. We discovered significant differences in expression compared to short-read data and identify currently unannotated transcripts of both GBA1 and GBAP1. These included protein-coding transcripts from both genes that were translated in human brain, but without the known lysosomal function-yet accounting for almost a third of transcription. Analyzing brain-specific cell types using long-read and single-nucleus RNA sequencing revealed region-specific variations in transcript expression. Overall, these findings suggest nonlysosomal roles for GBA1 and GBAP1 with implications for our understanding of the role of GBA1 in health and disease.
Assuntos
Glucosilceramidase , Pseudogenes , Humanos , Glucosilceramidase/genética , Glucosilceramidase/metabolismo , Pseudogenes/genética , Encéfalo/metabolismo , Anotação de Sequência Molecular , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Gaucher/genética , Análise de Sequência de RNA/métodosRESUMO
Abstract: This report summarises Australia's spontaneous (passive) surveillance data for adverse events following immunisation (AEFI) for coronavirus disease 2019 (COVID-19) vaccines in 2021 reported to the Therapeutic Goods Administration (TGA). The TGA strongly promoted and facilitated adverse event reporting in preparation for, and during, the COVID-19 vaccine rollout as a core component of the most intensive vaccine safety monitoring ever conducted in Australia. There were 111,348 AEFI reports for COVID-19 vaccines administered in 2021, an annual AEFI reporting rate of 271.4 per 100,000 doses of COVID-19 vaccines administered to people aged ≥ 12 years. The annual AEFI reporting rate for non-COVID-19 vaccines in 2021 was 30.6 per 100,000 doses administered to people of all ages. Overall, the most frequently reported symptoms were headache, adverse events classified as 'gastrointestinal nonspecific symptoms and therapeutic procedures', myalgia, pyrexia and fatigue, which were consistent with common expected adverse events following COVID-19 vaccines used in Australia. The most commonly reported adverse events of special interest were myocarditis and/or pericarditis, followed by thrombosis and thromboembolism, and anaphylaxis. Of all COVID-19 vaccine AEFI reports, 762 (0.7%) included a fatal outcome, of which over 80% were in people aged ≥ 60 years. Thirteen deaths reported in 2021 were assessed as likely to be causally linked to vaccination. This report confirms the value of spontaneous post-marketing vaccine pharmacovigilance, especially in the context of new vaccines using novel vaccine technologies and near whole-of-population pandemic vaccination programs. The most frequently reported AEFI for COVID-19 vaccines were common, mild and temporary (lasting 1 or 2 days), and consistent with clinical trial and active surveillance data. Ongoing safety monitoring detected rare, unexpected conditions, such as myocarditis/pericarditis and thrombosis with thrombocytopenia syndrome (TTS), which were investigated and confirmed as safety signals, resulting in changes to vaccine recommendations and product information. The outcomes of TGA monitoring were published in weekly vaccine safety reports. Overall, COVID-19 vaccine safety monitoring provided critical information on the risks of vaccine related adverse events that enabled decisionmakers to undertake informed risk-benefit assessments.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Vacinas contra COVID-19 , COVID-19 , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Austrália/epidemiologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , Vacinação/efeitos adversosRESUMO
Abstract: This report summarises Australia's spontaneous surveillance data for adverse events following immunisation (AEFI) for 2021 reported to the Therapeutic Goods Administration (TGA) and describes reporting trends over the 22-year period 1 January 2000 to 31 December 2021. This report excludes AEFI reports featuring pandemic coronavirus disease 2019 (COVID-19) vaccines, which are reported separately. There were 3,452 AEFI reports for non-COVID-19 vaccines administered in 2021, an annual AEFI reporting rate of 13.4 per 100,000 population compared with 14.9 per 100,000 population in 2020. This small decrease in the AEFI reporting rate in 2021 could potentially be related to an increased focus on COVID-19 vaccines and related AEFI, which are not included in this report. AEFI reporting rates for individual vaccines in 2021 were similar to 2020, as were the most commonly reported adverse events. Of the six deaths following vaccination in 2021 reported to the TGA, none were found to have a causal relationship with vaccination.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Vacinas contra COVID-19 , COVID-19 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Austrália/epidemiologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , Vacinação/efeitos adversosRESUMO
There are 90 independent genome-wide significant genetic risk variants for Parkinson's disease (PD) but currently only five nominated loci for PD progression. The biology of PD progression is likely to be of central importance in defining mechanisms that can be used to develop new treatments. We studied 6766 PD patients, over 15,340 visits with a mean follow-up of between 4.2 and 15.7 years and carried out genome-wide survival studies for time to a motor progression endpoint, defined by reaching Hoehn and Yahr stage 3 or greater, and death (mortality). There was a robust effect of the APOE ε4 allele on mortality in PD. We also identified a locus within the TBXAS1 gene encoding thromboxane A synthase 1 associated with mortality in PD. We also report 4 independent loci associated with motor progression in or near MORN1, ASNS, PDE5A, and XPO1. Only the non-Gaucher disease causing GBA1 PD risk variant E326K, of the known PD risk variants, was associated with mortality in PD. Further work is needed to understand the links between these genomic variants and the underlying disease biology. However, these may represent new candidates for disease modification in PD.
RESUMO
Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%-68.2%), compared with 63.4% in the control group (95% CI 61.8%-65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%-20.7%), compared with 18.8% in the control group (95% CI 17.4%-20.2%) a difference of +0.6 percentage points (95% CI -1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.
RESUMO
BACKGROUND: Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection. METHODS: Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment. RESULTS: 807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups. CONCLUSIONS: Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here.
Assuntos
COVID-19 , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Biomédica , COVID-19/etnologia , COVID-19/epidemiologia , Minorias Étnicas e Raciais/estatística & dados numéricos , Doenças do Sistema Nervoso/etnologia , Neurociências , Seleção de Pacientes , Estudos Prospectivos , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Immunisation against herpes zoster is recommended for adults aged ≥ 50 years. Two vaccines, a live attenuated (ZVL, Zostavax®) and an adjuvant recombinant subunit (HZ/su, Shingrix®), are available in Australia. Immunisation guidelines are shifting their recommendations towards HZ/su because of higher efficacy in preventing herpes zoster and associated complications. However, there are limited post-marketing data comparing the safety profiles of these vaccines. METHODS: Data from SmartVax, an active surveillance system for monitoring adverse events following immunisation (AEFIs) utilised by > 450 clinics throughout Australia, were analysed. Data from patients aged ≥ 50 years, who received ZVL or HZ/su, from 1 June 2021 to 31 May 2022, at clinics that utilised SmartVax were included. The proportion of records where patients who reported any, local, and systemic AEFIs after receiving ZVL or HZ/su were compared using multivariable logistic regression models. RESULTS: Data from 10,392 immunisation records (n = 8341 ZVL; n = 2051 HZ/su) were included. The proportion of AEFIs reported was higher with HZ/su (41.9 % [any], 33.8 % [local], 25.2 % [systemic]) than with ZVL (8.7 % [any], 6.2 % [local], 3.5 % [systemic]). After controlling for demographic variables, HZ/su presented a 6-fold increase in the odds (OR 6.44; 95 %CI: 5.57-7.46) of a reported AEFI compared to ZVL. Only 59 (0.6 %) of vaccinations lead to medical attention being sought due to an AEFI. CONCLUSIONS: While rates of AEFIs was higher with HZ/su than ZVL, most AEFIs were mild and did not require medical attention. Our findings support the change in vaccine recommendations and the use of HZ/su in immunisation programs.
Assuntos
Vacina contra Herpes Zoster , Herpes Zoster , Vigilância de Produtos Comercializados , Humanos , Vacina contra Herpes Zoster/efeitos adversos , Vacina contra Herpes Zoster/administração & dosagem , Vacina contra Herpes Zoster/imunologia , Austrália/epidemiologia , Herpes Zoster/prevenção & controle , Herpes Zoster/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Vacinação/efeitos adversos , Idoso de 80 Anos ou mais , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Herpesvirus Humano 3/imunologia , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricosRESUMO
Super-resolution and single-molecule microscopies have been increasingly applied to complex biological systems. A major challenge of these approaches is that fluorescent puncta must be detected in the low signal, high noise, heterogeneous background environments of cells and tissue. We present RASP, Radiality Analysis of Single Puncta, a bioimaging-segmentation method that solves this problem. RASP removes false-positive puncta that other analysis methods detect and detects features over a broad range of spatial scales: from single proteins to complex cell phenotypes. RASP outperforms the state-of-the-art methods in precision and speed using image gradients to separate Gaussian-shaped objects from the background. We demonstrate RASP's power by showing that it can extract spatial correlations between microglia, neurons, and α-synuclein oligomers in the human brain. This sensitive, computationally efficient approach enables fluorescent puncta and cellular features to be distinguished in cellular and tissue environments, with sensitivity down to the level of the single protein. Python and MATLAB codes, enabling users to perform this RASP analysis on their own data, are provided as Supporting Information and links to third-party repositories.
Assuntos
Encéfalo , HumanosRESUMO
OBJECTIVE: Prior experience of an adverse event following immunisation is a known barrier to vaccination. Limited Australian data evaluating adverse event recurrence among children exists to inform clinical decisions. We aimed to assess adverse event following immunisation recurrence among children with prior adverse events and to evaluate if family history increased adverse event risk. METHODS: A prospective cohort study was conducted from March 3rd until August 18th, 2023. Children ≤ 16 years with prior adverse events following immunisation in themselves or family were recruited from specialist immunisation clinics at two quaternary paediatric hospitals. Adverse event outcomes were collected via surveys administered at presentation, three, and eight days post vaccination, and analysed by key characteristics and potential risk factors. RESULTS: Forty three of forty nine (43/49, 87.8 %) children enrolled received further vaccines. Of those who completed the follow up surveys, 50.0 % (16/32) reported an adverse event. Recurrence of prior adverse events occurred for 23.3 % (10/43, 95 % CI: 11.8 % - 38.6 %) of the cohort. Two of twelve (2/12, 16.7 %) participants with prior serious adverse events who received further vaccines reported a serious adverse event recurrence. No post review serious adverse events were observed in children with prior non serious adverse events. Neurological conditions were a risk factor for prior (neurological condition 3/3 versus no neurological condition 2/40, p < 0.001) and post review (neurological condition 2/3 versus no neurological condition 0/28, p = 0.006) post vaccination seizures. Family history had no relationship to post review adverse events (family history 5/8 versus no family history 11/23, p = 0.685). CONCLUSION: Revaccination is safe for the majority of children with a personal or family history of adverse event following immunisation.
Assuntos
Vacinação , Vacinas , Criança , Humanos , Austrália , Imunização Secundária , Estudos Prospectivos , Vacinação/efeitos adversos , Vacinas/efeitos adversos , AdolescenteRESUMO
Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.
Assuntos
Encefalopatias , Humanos , Acetilação , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encefalopatias/genética , Padrões de Herança , Mutação , Fosfatos/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/metabolismoRESUMO
Intestine remains the least frequently transplanted solid organ, although the survival and quality-of-life benefits of transplant to individuals with irreversible intestinal failure have been well demonstrated. The trend seen over the past 15 years of fewer listings and fewer transplants appears to be continuing, most noticeably in infants, children, and adolescents. There were only 146 additions to the intestine waiting list in 2022, and the proportion of adult candidates continues to increase, so that now 61% of the intestine waiting list are adult candidates. There has been little change in the distribution by sex, race and ethnicity, or primary diagnosis on the waiting list, or for those receiving transplant. The transplant rate for adults has decreased to 55.6 transplants per 100 patient-years, but the pediatric transplant rate remains relatively stable at 22.8 transplants per 100 patient-years. The decrease in transplant rates for adults is primarily the result of falling rates for those listed for combined intestine-liver, and this is reflected in the pretransplant mortality rates, which are twice as high for candidates in need of both organs compared with those listed for intestine alone. Overall, intestine transplant numbers decreased to a total of 82 intestine transplants in 2022, only one above the lowest ever value of 81 in 2019. No major changes were seen in the immunosuppression protocols, with most recipients having induction therapy and tacrolimus-based maintenance. Graft failure rates appear to have improved at 1, 3, and 5 years for intestine without liver, but this is not seen for combined intestine-liver. Graft and patient survival are better for pediatric recipients compared with adult recipients for both liver-inclusive and liver-exclusive transplant. Rates of posttransplant lymphoproliferative disorder are higher for recipients of intestine without liver.
Assuntos
Transplante de Fígado , Obtenção de Tecidos e Órgãos , Adulto , Lactente , Adolescente , Humanos , Criança , Estados Unidos/epidemiologia , Intestinos/transplante , Terapia de Imunossupressão , Listas de Espera , Etnicidade , Sobrevivência de Enxerto , Doadores de TecidosRESUMO
INTRODUCTION: Children with chronic medical diseases are at an unacceptable risk of hospitalisation and death from influenza and SARS-CoV-2 infections. Over the past two decades, behavioural scientists have learnt how to design non-coercive 'nudge' interventions to encourage positive health behaviours. Our study aims to evaluate the impact of multicomponent nudge interventions on the uptake of COVID-19 and influenza vaccines in medically at-risk children. METHODS AND ANALYSES: Two separate randomised controlled trials (RCTs), each with 1038 children, will enrol a total of approximately 2076 children with chronic medical conditions who are attending tertiary hospitals in South Australia, Western Australia and Victoria. Participants will be randomly assigned (1:1) to the standard care or intervention group. The nudge intervention in each RCT will consist of three text message reminders with four behavioural nudges including (1) social norm messages, (2) different messengers through links to short educational videos from a paediatrician, medically at-risk child and parent and nurse, (3) a pledge to have their child or themselves vaccinated and (4) information salience through links to the current guidelines and vaccine safety information. The primary outcome is the proportion of medically at-risk children who receive at least one dose of vaccine within 3 months of randomisation. Logistic regression analysis will be performed to determine the effect of the intervention on the probability of vaccination uptake. ETHICS AND DISSEMINATION: The protocol and study documents have been reviewed and approved by the Women's and Children's Health Network Human Research Ethics Committee (HREC/22/WCHN/2022/00082). The results will be published via peer-reviewed journals and presented at scientific meetings and public forums. TRIAL REGISTRATION NUMBER: NCT05613751.
Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , Influenza Humana/prevenção & controle , Criança , Vacinas contra Influenza/administração & dosagem , Austrália , Vacinação , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/uso terapêutico , Doença Crônica , Feminino , Envio de Mensagens de Texto , Adolescente , Instituições de Assistência Ambulatorial , Comportamentos Relacionados com a Saúde , Sistemas de Alerta , Pré-Escolar , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , MasculinoRESUMO
The Scientific Registry of Transplant Recipients has previously reported the effects of adjusting for demographic variables, including race, in the Centers for Medicare & Medicaid Services (CMS) organ procurement organization (OPO) performance metrics: donation rate and transplant rate. CMS chose not to adjust for most demographic variables other than age (for the transplant rate), arguing that there is no biological reason that these variables would affect the organ donation/utilization decision. However, organ donation is a process based on altruism and trust, not a simple biological phenomenon. Focusing only on biological impacts on health ignores other pathways through which demographic factors can influence OPO outcomes. In this study, we update analyses of demographic adjustment on the OPO metrics for 2020 with a specific focus on adjusting for race. We find that adjusting for race would lead to 8 OPOs changing their CMS tier rankings, including 2 OPOs that actually overperform the national rate among non-White donors improving from a tier 3 ranking (facing decertification without possibility of recompeting) to a tier 2 ranking (allowing the possibility of recompeting). Incorporation of stratified and risk-adjusted metrics in public reporting of OPO performance could help OPOs identify areas for improvement within specific demographic categories.
Assuntos
Transplante de Órgãos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Humanos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Estados Unidos , Doadores de Tecidos/provisão & distribuição , Grupos Raciais , Centers for Medicare and Medicaid Services, U.S. , Sistema de RegistrosRESUMO
BACKGROUND: Intussusception is the primary cause of acute bowel obstruction in infants. The majority of cases <2 years of age are classed as idiopathic, with viral infection implicated as one of the causes. Coronavirus disease 2019 (COVID-19) public health measures led to significant decreases in communicable disease prevalence. During these times, reductions in intussusception frequency were greater than would be expected with our previous understanding of its infectious etiology. METHODS: We conducted a retrospective, multistate, ecological study over a 12-year period. Monthly case numbers of "intussusception"-coded admissions (code K56.1; International Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification) were acquired from state-wide admissions data sets from New South Wales, Victoria, and Queensland, representing 77.62% of the eligible Australian population. These counts within differing jurisdictional lockdowns were compared with non-lockdown periods in order to investigate a correlation between intussusception frequency and lockdown periods. RESULTS: We found a negative association between intussusception frequency and lockdown periods in both eligible states. The largest reductions were seen in the <2-year age groups, with Victoria experiencing a 62.7% reduction (rate ratio, 0.37; P < .001) and New South Wales a 40.1% reduction (0.599; P = .006) during lockdown times. Controls for variations in lockdown restrictions between both regional and metropolitan areas also showed expected decreases. CONCLUSIONS: Our ecological study demonstrates significant decreases in the frequency of pediatric intussusception admissions during the COVID-19 lockdown periods. The unexpected magnitude of the reductions suggests that the true proportion of infectious disease-caused idiopathic intussusception is greatly underestimated.
Assuntos
COVID-19 , Intussuscepção , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Intussuscepção/epidemiologia , Intussuscepção/etiologia , Lactente , Estudos Retrospectivos , Pré-Escolar , Criança , Masculino , Feminino , Austrália/epidemiologia , Adolescente , Recém-Nascido , Adulto , Hospitalização/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto Jovem , Idoso , New South Wales/epidemiologia , Queensland/epidemiologia , Vitória/epidemiologiaRESUMO
OBJECTIVE: Pancreata recovered for research are included as a success (or positive) in the Centers for Medicare and Medicaid Services' (CMS) donation and organ transplantation rate metrics for recertification of organ procurement organizations (OPOs). MATERIALS AND METHODS: Given these metrics directly incentivize recovery of pancreata for research, this study tracks trends in recovery of pancreata for research across the implementation of the CMS metrics. RESULTS: In the 26 months before the December 2, 2020, publication of the CMS metrics, research pancreata as a percent of organs transplanted, including research pancreata, was 1.7% nationally, including as much as 10.8% of organs transplanted within any OPO. In the 26 months after the CMS metrics were published, research pancreata increased to 5.1% of organs counted as transplants nationally, including as much as 20.3% within any OPO. If research pancreata were excluded from the CMS metrics, 6 OPOs would change their CMS evaluation status for recertification purposes: 2 would move up a tier and 4 would move down a tier. CONCLUSIONS: Procurement of research pancreata has increased since the publication of the CMS performance metrics, OPOs vary in their recovery of pancreata for research, and recovery of pancreata for research can affect recertification of OPOs.