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INTRODUCTION: Traumatic brain injury (TBI) and spinal cord injury (SCI) are both major contributors to permanent disability globally, with an estimated 27 million new cases of TBI and 0.93 million new cases of SCI globally in 2016. In Australia, the National Disability Insurance Scheme (NDIS) provides support to people with disability. Reports from the NDIS suggest that the cost of support for people with TBI and SCI has been increasing dramatically, and there is a lack of independent analysis of the drivers of these increases. This data linkage seeks to better understand the participant transition between rehabilitation hospitals and the NDIS and the correlation between functional independence in rehabilitation and resource allocation in the NDIS. METHODS AND ANALYSIS: This is a retrospective, population-based cohort study using Australia-wide NDIS participant data and rehabilitation hospital episode data. The linked dataset provides a comparison of functional independence against which to compare the NDIS resource allocation to people with TBI and SCI. This protocol outlines the secure and separated data linkage approach employed in linking partially identified episode data from the Australasian Rehabilitation Outcomes Centre (AROC) with identified participant data from the NDIS. The linkage employs a stepwise deterministic linkage approach. Statistical analysis of the linked dataset will consider the relationship between the functional independence measure score from the rehabilitation hospital and the committed funding supports in the NDIS plan. This protocol sets the foundation for an ongoing data linkage between rehabilitation hospitals and the NDIS to assist transition to the NDIS. ETHICS AND DISSEMINATION: Ethics approval is from the Macquarie University Human Research Ethics Committee. AROC Data Governance Committee and NDIS Data Management Committee have approved this project. Research findings will be disseminated to key stakeholders through peer-reviewed publications in scientific journals and presentations to clinical and policy audiences via AROC and NDIS.
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Seguro por Deficiência , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/reabilitação , Austrália , Estudos Retrospectivos , Seguro por Deficiência/estatística & dados numéricos , Hospitais de Reabilitação , Armazenamento e Recuperação da Informação , Pessoas com Deficiência/reabilitação , Lesões Encefálicas/reabilitação , Lesões Encefálicas/economiaRESUMO
OBJECTIVE: To assess whether recombinant zoster vaccine (RZV) is associated with an increased risk of new-onset gout among US adults aged ≥50 years. METHODS: We conducted a real-world, retrospective safety study with a self-controlled risk interval (SCRI) design using administrative claims data. We included health plan members aged ≥50 years with RZV exposure, followed by incident gout within 60 days. Days 1-30 following RZV exposure were considered the risk window (RW), and days 31-60 were considered the control window (CW). We estimated the risk ratio (RR) of gout in the RW versus CW, using a conditional Poisson model. The primary analysis estimated the risk of incident gout following any RZV dose. Sensitivity analyses evaluated dose 1- and dose 2-specific risks, risk among patients compliant with recommended dose spacing of 60-183 days, adjustment for seasonality, and restriction to the pre-COVID-19 era (before December 1, 2019). RESULTS: A total of 461,323 individuals received ≥1 RZV dose; we included 302 individuals (mean age 72.5 years; 66 % male) with evidence of new-onset gout within 60 days in SCRI analyses. A total of 153 (50.7 %) individuals had gout events in the RW and 149 (49.3 %) in the CW (RR 1.03; 95 % confidence interval 0.81, 1.29). All sensitivity analyses had consistent results, with no association of RZV with incident gout. CONCLUSION: In a population of US adults aged ≥50 years, there was no statistically significant increase in the risk of gout during the 30 days immediately after RZV exposure, compared with a subsequent 30-day CW.
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BACKGROUND: Antimicrobial resistance (AMR) represents a significant threat to global health with Neisseria gonorrhoea emerging as a key pathogen of concern. In Australia, the Australian Gonococcal Surveillance Program (AGSP) plays a critical role in monitoring resistance patterns. However, antibiotic susceptibility test (AST) uptake - a crucial component for effective resistance surveillance - remains to be a limiting factor. The study aims to model the processes involved in generating AST tests for N. gonorrhoea isolates within the Australian healthcare system and assess the potential impact of systematic and policy-level changes. METHODS: Two models were developed. The first model was a mathematical stochastic health systems model (SHSM) and a Bayesian Belief Network (BBN) to simulate the clinician-patient dynamics influencing AST initiation. Key variables were identified through systematic literature review to inform the construction of both models. Scenario analyses were conducted with the modification of model parameters. RESULTS: The SHSM and BBN highlighted clinician education and the use of clinical support tools as effective strategies to improve AST. Scenario analysis further identified adherence to guidelines and changes in patient-level factors, such as persistence of symptoms and high-risk behaviours, as significant determinants. Both models supported the notion of mandated testing to achieve higher AST initiation rates but with considerations necessary regarding practicality, laboratory constraints, and culture failure rate. CONCLUSION: The study fundamentally demonstrates a novel approach to conceptualising the patient-clinician dynamic within AMR testing utilising a model-based approach. It suggests targeted interventions to educational, support tools, and legislative framework as feasible strategies to improve AST initiation rates. However, the research fundamentally highlights substantial research gaps in the underlying understanding of AMR.
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Antibacterianos , Gonorreia , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae , Neisseria gonorrhoeae/efeitos dos fármacos , Humanos , Austrália/epidemiologia , Gonorreia/microbiologia , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Teorema de Bayes , Farmacorresistência Bacteriana , Modelos Teóricos , Política de SaúdeRESUMO
Background: We compared rates of successful polyethylene glycol (PEG) nerve fusion between two epineural suture repairs (2SR) and five epineural suture repairs (5SR) in a rat sciatic nerve transection neurorrhaphy model. We hypothesise that the two and five epineural neural suture repair groups will achieve a similar rate of PEG fusion. Methods: Twenty-five Lewis rats underwent bilateral sciatic nerve transection. Primary neurorrhaphy (PN) consisting of 2SR in one hind limb and 5SR in the contralateral hind limb was performed utilizing PEG fusion. Successful PEG fusion was confirmed by a distal muscle twitch after nerve stimulation proximal to the nerve fusion site. Sciatic nerve conduction velocity (SNCV) across the repair site and the force generated by tibialis anterior muscle (TAM) contraction were also compared between the 2SR and 5SR groups. Results: Success rates were 100% for the 2SR and the 5SR groups. No statistically significant differences in SNCV (P = 0.444) or isometric tetanic TAM contractile force (P = 0.820) were observed between 2SR and 5SR in the setting of PEG fusion. Conclusion: These findings demonstrate no significant difference in successful PEG fusion between the 2SR and 5SR groups. In addition, the findings demonstrate no statistically significant differences in SNCV or isometric tetanic TAM contractile force following sciatic nerve transection when performing a 2SR or 5SR PN in the setting of PEG fusion. Successful PEG fusion can be achieved acutely with either a two or five-epineural suture repair in a rat model.
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Sensorimotor synchronization (SMS) refers to the temporal coordination of an external stimulus with movement. Our previous work revealed that while SMS with visual flashing patterns was less consistent than with auditory or tactile patterns, it was still evident in a sample of nonmusicians. Although previous studies have speculated the potential role of auditory imagery, its contribution to visual SMS performance is not well quantified. Utilizing a synchronization-continuation finger-tapping task with a visual stimulus that included implied motion, we aimed to examine how participants' imagery ability, musicality, and rhythm perception affected SMS performance. We quantified participants' SMS consistency in synchronization (with visual cues) and continuation (without visual cues) phases. Participants also performed a perception task assessing their ability to detect temporal perturbations in the visual rhythm and completed musical ability and imagery questionnaires. Our linear regression model for SMS consistency included the trial phase, self-reported auditory imagery control and musicality, and visual rhythm perception as predictors. Significant effects of trial phase and auditory imagery scores on SMS consistency suggested that participants performed SMS more consistently while the guiding visual stimulus was present and that the higher one's self-reported auditory imagery ability, the better their SMS when continuing with unguided rhythm. One's visual rhythm perception accuracy significantly correlated with SMS consistency during the synchronization phase, and there was no correlation between rhythm perception and auditory imagery control. Overall, our results suggested relatively independent contributions of auditory imagery and visual rhythm perception to SMS with visual rhythm. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Percepção Auditiva , Imaginação , Música , Desempenho Psicomotor , Percepção Visual , Humanos , Masculino , Feminino , Percepção Auditiva/fisiologia , Adulto , Imaginação/fisiologia , Percepção Visual/fisiologia , Desempenho Psicomotor/fisiologia , Adulto Jovem , Percepção do Tempo/fisiologia , AdolescenteRESUMO
Varicella zoster virus (VZV) is a highly contagious human herpes virus responsible for causing chickenpox (varicella) and shingles (herpes zoster). Despite the approval of a highly effective vaccine, Shingrix®, the global incidence of herpes zoster is increasing and the economic burden to the health care system and society are substantial due to significant loss of productivity and health complications, particularly among elderly and immunocompromised individuals. This is primarily because access to the vaccines remains mostly limited to countries within developed economies, such as USA and Canada. Therefore, similarly effective vaccines against VZV that are more accessible to the rest-of-the-world are necessary. In this study, we aimed to evaluate immunogenicity and memory response induced by three mRNA-LNP-based vaccine candidates targeting VZV's surface glycoprotein E (gE). C57BL/6 mice were immunized with each candidate vaccine, and humoral and cellular immune responses were assessed. Our results demonstrate that the mRNA-LNP-based vaccine candidates elicited robust and durable humoral responses specific to the gE antigen. Notably, mice vaccinated with the mRNA-LNP vaccines exhibited significantly higher antigen-specific T-cell cytokine production compared to the group receiving Shingrix®, the current standard of care vaccine. Additionally, mRNA-LNP vaccines induced long-lasting memory response, as evidenced by detection of persistent gE-specific Long-Lived Plasma Cells (LLPCs) and memory T cells four months after final immunization. These findings underscore the potential of our mRNA-LNP-based vaccine candidates in generating potent immune responses against VZV, offering promising prospects for their clinical development as an effective prophylactic vaccine against herpes zoster.
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Background: Bioblitzes are a tool for the rapid appraisal of biodiversity and are particularly useful in remote and understudied regions and for understudied taxa. Lichens are an example of an often overlooked group, despite being widespread in virtually all terrestrial ecosystems and having many important ecological functions. New information: We report the lichens and allied fungi collected during the 2018 terrestrial bioblitz conducted on Calvert Island on the Central Coast of British Columbia, Canada. We identified 449 specimens belonging to 189 species in 85 genera, increasing the total number of species known from Calvert Island to 194, and generated Internal Transcribed Spacer (ITS) sequences for 215 specimens from 121 species. Bryoriafurcellata, Chaenothecopsislecanactidis and C.nigripunctata were collected for the first time in British Columbia. We also found Pseudocyphellariarainierensis, which is listed as Special Concern on the federal Species at Risk Act, and other rarely reported species in British Columbia including Opegraphasphaerophoricola, Protomicarealimosa, Raesaeneniahuuskonenii and Sareadifformis. We demonstrate that DNA barcoding improves the scope and accuracy of expert-led bioblitzes by facilitating the detection of cryptic species and allowing for consistent identification of chemically and morphologically overlapping taxa. Despite the spatial and temporal limitations of our study, the results highlight the value of intact forest ecosystems on the Central Coast of British Columbia for lichen biodiversity, education and conservation.
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BACKGROUND: Evidence on the comparative effectiveness of respiratory biologics remains sparse. OBJECTIVE: We sought to evaluate the comparative effectiveness of omalizumab, mepolizumab, benralizumab, and dupilumab in a matched retrospective cohort of patients with asthma. METHODS: We identified patients with asthma aged ≥18 years who were incident users of these biologics between November 1, 2018, and June 30, 2023, in administrative claims data from the Food and Drug Administration's Sentinel System and Merative MarketScan Commercial Database. We compared asthma-related exacerbations and hospitalizations in the 12 months since biologic prescription in pairwise comparisons of propensity score-matched cohorts. Covariates used in matching included age, sex, allergic comorbidities, baseline asthma medications use, and the Charlson Comorbidity Index. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using negative binomial regression models. RESULTS: A total of 893 patients on mepolizumab, 1300 on benralizumab, 1170 on omalizumab, and 1863 on dupilumab were identified. The average age was 55 years, and two-thirds of the participants were female. At baseline, over 80% of these individuals had an active prescription for an inhaled corticosteroid. Almost half of patients on dupilumab had concomitant nasal polyposis compared with 6% to 13% of patients on the other biologics. Covariates were balanced after matching. In matched analyses, dupilumab was associated with the lowest incidence of exacerbations over the follow-up period (vs dupilumab): mepolizumab (IRR: 1.36; 95% CI: 1.12, 1.64), omalizumab (IRR: 1.33; 95% CI: 1.13, 1.58), benralizumab (IRR: 1.19; 95% CI: 1.00, 1.41). For exacerbations leading to hospitalizations, benralizumab and mepolizumab were associated with the lowest incidence of hospitalizations, and the greatest difference was between mepolizumab versus dupilumab (IRR: 0.76; 95% CI: 0.56, 1.03). CONCLUSIONS: Dupilumab was associated with the lowest incidence of overall exacerbations, and mepolizumab with the lowest incidence of asthma hospitalizations in this administrative claims-based cohort of individuals with asthma. Despite matching propensity scores, residual confounding, such as baseline eosinophil count, may explain some of these findings.
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Antiasmáticos , Asma , Produtos Biológicos , Hospitalização , Humanos , Asma/tratamento farmacológico , Asma/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Produtos Biológicos/uso terapêutico , Hospitalização/estatística & dados numéricos , Estudos Retrospectivos , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Progressão da Doença , Resultado do TratamentoRESUMO
Background: Polyethylene glycol (PEG) is a synthetic, biodegradable, and hyperosmotic material promising in the treatment of acute peripheral nerve injuries. Our team set out to investigate the impact of fibrin glue upon PEG fusion in a rat model. Methods: Eighteen rats underwent sciatic nerve transection and PEG fusion. Electrophysiologic testing was performed to measure nerve function and distal muscle twitch. Fibrin glue was applied and testing repeated. Due to preliminary findings, fibrin glue was applied to an uncut nerve in five rodents and testing was conducted before and after glue application. Mann-Whitney U tests were used to compare median values between outcome measures. A Shapiro-Wilk test was used to determine normality of data for each comparison, significance set at a P value less than 0.05. Results: PEG fusion was confirmed in 13 nerves with no significant change in amplitude (P = 0.054), latency (P = 0.114), or conduction velocity (P = 0.114). Stimulation of nerves following PEG fusion produced distal muscle contraction in 100% of nerves. Following application of fibrin glue, there was a significant reduction in latency (P = 0.023), amplitude (P < 0.001), and conduction velocity (P = 0.023). Stimulation of the nerve after application of fibrin glue did not produce distal muscle twitch. Five uncut nerves with fibrin glue application blocked distal muscle contraction following stimulation. Conclusions: Our data suggest that fibrin glue alters the nerve's function. The immediate confirmation of PEG fusion via distal muscle twitch is blocked with application fibrin glue in this experimental model. Survival and functional outcome studies are necessary to understand if this has implications on the long-term functional outcomes.