ABSTRACT
OBJECTIVE: To describe the use of privacy preserving linkage methods operationally in Australia, and to present insights and key learnings from their implementation. METHODS: Privacy preserving record linkage (PPRL) utilising Bloom filters provides a unique practical mechanism that allows linkage to occur without the release of personally identifiable information (PII), while still ensuring high accuracy. RESULTS: The methodology has received wide uptake within Australia, with four state linkage units with privacy preserving capability. It has enabled access to general practice and private pathology data amongst other, both much sought after datasets previous inaccessible for linkage. CONCLUSION: The Australian experience suggests privacy preserving linkage is a practical solution for improving data access for policy, planning and population health research. It is hoped interest in this methodology internationally continues to grow.
ABSTRACT
BACKGROUND: Health Information Managers (HIMs) play a crucial role in the management and governance of health information ensuring the accuracy, confidentiality and accessibility of health data for clinical care and business operational purposes. This role also extends to education and training in the workplace. OBJECTIVE: The aim of this scoping review was to explore and elucidate the role played by HIMs when they undertake a health workplace-based (healthcare organisation or service) educational role and/or functions as evidenced in the existing body of literature. METHOD: A scoping review of the literature to investigated the importance of the educator role for HIM health workplace-based educators. A three-step search strategy was designed to ensure a comprehensive exploration of relevant research. RESULTS: Of 63 articles assess for eligibility, 14 were included in the final analysis. All included articles acknowledged the importance of the HIM-educator workplace-based role. Half of the included articles had been published within the last 7 years. Only 8 of the 14 articles provided some description of HIM-educator attributes, suggesting that these characteristics remain unexplored. DISCUSSION: Findings from this scoping review have shed light on the limitations within the current available literature concerning the attributes of HIM health workplace-based educators. The findings also highlight an important gap in knowledge concerning the qualities of these HIM-educators. CONCLUSION: This identified gap in the literature signals a need for further exploration and investigation into the specific attributes, skills, and characteristics that define effective HIM-educators undertaking a health workplace-based educational role.
ABSTRACT
BACKGROUND: The COVID-19 pandemic placed an additional mental health burden on individuals and families, resulting in widespread service access problems. Digital mental health interventions suggest promise for improved accessibility. Recent reviews have shown emerging evidence for individual use and early evidence for multiusers. However, attrition rates remain high for digital mental health interventions, and additional complexities exist when engaging multiple family members together. OBJECTIVE: As such, this scoping review aims to detail the reported evidence for digital mental health interventions designed for family use with a focus on the build and design characteristics that promote accessibility and engagement and enable cocompletion by families. METHODS: A systematic literature search of MEDLINE, Embase, PsycINFO, Web of Science, and CINAHL databases was conducted for articles published in the English language from January 2002 to March 2024. Eligible records included empirical studies of digital platforms containing some elements designed for cocompletion by related people as well as some components intended to be completed without therapist engagement. Platforms were included in cases in which clinical evidence had been documented. RESULTS: Of the 9527 papers reviewed, 85 (0.89%) met the eligibility criteria. A total of 24 unique platforms designed for co-use by related parties were identified. Relationships between participants included couples, parent-child dyads, family caregiver-care recipient dyads, and families. Common platform features included the delivery of content via structured interventions with no to minimal tailoring or personalization offered. Some interventions provided live contact with therapists. User engagement indicators and findings varied and included user experience, satisfaction, completion rates, and feasibility. Our findings are more remarkable for what was absent in the literature than what was present. Contrary to expectations, few studies reported any design and build characteristics that enabled coparticipation. No studies reported on platform features for enabling cocompletion or considerations for ensuring individual privacy and safety. None examined platform build or design characteristics as moderators of intervention effect, and none offered a formative evaluation of the platform itself. CONCLUSIONS: In this early era of digital mental health platform design, this novel review demonstrates a striking absence of information about design elements associated with the successful engagement of multiple related users in any aspect of a therapeutic process. There remains a large gap in the literature detailing and evaluating platform design, highlighting a significant opportunity for future cross-disciplinary research. This review details the incentive for undertaking such research; suggests design considerations when building digital mental health platforms for use by families; and offers recommendations for future development, including platform co-design and formative evaluation.
Subject(s)
COVID-19 , Family , Humans , Family/psychology , Mental Health Services , Telemedicine , Mental Health , SARS-CoV-2 , PandemicsABSTRACT
Emergency department (ED) overcrowding remains a persistent challenge in global public health, leading to detrimental outcomes for patients and healthcare professionals. Traditional approaches to improve this issue have been insufficient, prompting exploration of novel strategies such as virtual care interventions. Our team developed the first comprehensive statewide virtual ED in Australia, the Victorian Virtual Emergency Department, offering an alternative to in-person care for non-life-threatening emergencies. Here, we present the development and ongoing refinement of this pioneering virtual care service, aiming to provide insights for hospital administrators and policymakers seeking to implement patient-centric care solutions worldwide. By sharing our model of care, we hope to guide further work toward addressing the global problem of over crowded EDs.
ABSTRACT
INTRODUCTION: Telehealth service provision and uptake has rapidly increased since the COVID-19 pandemic, allowing healthcare to be delivered safely and reducing non-essential face-to-face (F2F) contact. In Australia, the expansion of subsidisation of telehealth during COVID has led to its permanent installation within Australian primary care in 2022. However, little is known about consumer preferences and experiences with these services, particularly in relation to allied health practice (AHP). Previous studies on telehealth services have focused on general practice rather than allied health (AH) and broader primary care. Given that AH professionals make up a large proportion of the Australian healthcare workforce, the purpose of this study is to explore consumer preferences and experiences with telehealth AHP healthcare. METHODS AND ANALYSIS: This study uses a mixed methods research design that incorporates three independent but interrelated phases. Phase 2 of the study will use a focus group methodology to discuss consumer attitudes and experiences via a semistructured interview format. Phase 3 involves a discrete choice experiment (DCE) involving a large online survey conducted across the general population. The DCE will be informed by the qualitative findings from phases 1 and 2. The experiment aims to elicit consumer preferences in relation to AH services delivered through telehealth or F2F consultations, based on several hypothetical scenarios and preferences over several different dimensions. ETHICS AND DISSEMINATION: Ethics approval has been obtained from La Trobe University (approval number HEC23404). Findings will be disseminated as reports, presentations and peer-reviewed journal articles.
Subject(s)
COVID-19 , Consumer Behavior , Telemedicine , Humans , Australia , COVID-19/epidemiology , SARS-CoV-2 , Focus Groups , Research Design , Patient Preference , Surveys and Questionnaires , Pandemics , Allied Health PersonnelABSTRACT
Acute Disseminated Encephalomyelitis (ADEM) and Transverse Myelitis (TM) are within the group of immune mediated disorders of acquired demyelinating syndromes. Both have been described in temporal association following various vaccinations in case reports and case series and have been evaluated in observational studies. A recent analysis conducted by The Global Vaccine Data Network (GVDN) observed an excess of ADEM and TM cases following the adenoviral vectored ChAdOx1 nCoV-19 (AZD1222) and mRNA-1273 vaccines, compared with historically expected background rates from prior to the pandemic. Further epidemiologic studies were recommended to explore these potential associations. We utilized an Australian vaccine datalink, Vaccine Safety Health-Link (VSHL), to perform a self-controlled case series analysis for this purpose. VSHL was selected for this analysis as while VSHL data are utilised for GVDN association studies, they were not included in the GVDN observed expected analyses. The VSHL dataset contains vaccination records sourced from the Australian Immunisation Register, and hospital admission records from the Victorian Admitted Episodes Dataset for 6.7 million people. These datasets were used to determine the relative incidence (RI) of G040 (ADEM) and G373 (TM) ICD-10-AM coded admissions in the 42-day risk window following COVID-19 vaccinations as compared to control periods either side of the risk window. We observed associations between ChAdOx1 adenovirus vector COVID-19 vaccination and ADEM (all dose RI: 3.74 [95 %CI 1.02,13.70]) and TM (dose 1 RI: 2.49 [95 %CI: 1.07,5.79]) incident admissions. No associations were observed between mRNA COVID-19 vaccines and ADEM or TM. These findings translate to an extremely small absolute risk of ADEM (0.78 per million doses) and TM (1.82 per million doses) following vaccination; any potential risk of ADEM or TM should be weighed against the well-established protective benefits of vaccination against COVID-19 disease and its complications. This study demonstrates the value of the GVDN collaboration leveraging large population sizes to examine important vaccine safety questions regarding rare outcomes, as well as the value of linked population level datasets, such as VSHL, to rapidly explore associations that are identified.
Subject(s)
COVID-19 , Encephalomyelitis, Acute Disseminated , Myelitis, Transverse , Vaccines , Humans , Australia/epidemiology , ChAdOx1 nCoV-19 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Encephalomyelitis, Acute Disseminated/chemically induced , Encephalomyelitis, Acute Disseminated/epidemiology , Myelitis, Transverse/etiology , Myelitis, Transverse/complications , Vaccination/adverse effectsABSTRACT
BACKGROUND: Mental illness has become a prevalent issue impacting adolescents worldwide. Many barriers, including stigma and poor health literacy, prevent this population group from accessing reliable mental health care services. Synchronous text-therapy counseling is an underused therapeutic approach in combating adolescent mental illness. Phone-based text therapy is uniquely placed to offer personalized counseling to adolescents through a familiar and engaging treatment modality. OBJECTIVE: This rapid review aims to understand the clinical effectiveness, usability, and accessibility of phone-based text therapy for youth mental health. METHODS: Cochrane CENTRAL, Embase, PubMed, and PsycINFO were used to search for suitable literature. Five groups of keywords were used: those related to (1) "therapy," (2) "text," (3) "phone," (4) "youth," and (5) "mental health." Eligibility criteria were formed through the PICO (Population, Intervention, Control, and Outcome) framework. Studies were included if a synchronous phone-based text therapy intervention was used in an adolescent population, with an age range of 12-24 years. Only literature available in full-text, English, and a peer-reviewed journal was considered. Furthermore, a date limit of 5 years was set to reflect the recent development of digital interventions for mental health. Pertinent information from each study was tabulated, and a narrative synthesis was used to assess, describe, and organize the included studies comprehensively and concisely. RESULTS: Of the 771 studies dual screened, 7 studies were included in this rapid review. Most of the exclusions occurred due to the use of the wrong intervention, such as asynchronous messaging. The selected studies had a low risk of bias and were suitable for the review. All interventional trials demonstrated reductions in mental health symptoms, primarily depression and anxiety. Most studies displayed high usability among participants, while data were unclear regarding accessibility. CONCLUSIONS: This review reveals the high potential of phone-based text therapy as an intervention for adolescents experiencing mental illness. We hope that this review promotes further refinement of text-based phone therapies and encourages future research on this subject matter.
ABSTRACT
We previously reported a protective antibody response in mice immunized with synthetic microparticle vaccines made using layer-by-layer fabrication (LbL-MP) and containing the conserved T1BT* epitopes from the P. falciparum circumsporozoite protein. To further optimize the vaccine candidate, a benchtop tangential flow filtration method (LbL-by-TFF) was developed and utilized to produce vaccine candidates that differed in the status of base layer crosslinking, inclusion of a TLR2 ligand in the antigenic peptide, and substitution of serine or alanine for an unpaired cysteine residue in the T* epitope. Studies in mice revealed consistent superiority of the Pam3Cys-modified candidates and a modest benefit of base layer crosslinking, as evidenced by higher and more persistent antibody titers (up to 18 months post-immunization), a qualitative improvement of T-cell responses toward a Th1 phenotype, and greater protection from live parasite challenges compared to the unmodified prototype candidate. Immunogenicity was also tested in a non-human primate model, the rhesus macaque. Base layer-crosslinked LbL-MP loaded with T1BT* peptide with or without covalently linked Pam3Cys elicited T1B-specific antibody responses and T1BT*-specific T-cell responses dominated by IFNγ secretion with lower levels of IL-5 secretion. The Pam3Cys-modified construct was more potent, generating antibody responses that neutralized wild-type P. falciparum in an in vitro hepatocyte invasion assay. IgG purified from individual macaques immunized with Pam3Cys.T1BT* LbL-MP protected naïve mice from challenges with transgenic P. berghei sporozoites that expressed the full-length PfCS protein, with 50-88% of passively immunized mice parasite-free for ≥15 days. Substitution of serine for an unpaired cysteine in the T* region of the T1BT* subunit did not adversely impact immune potency in the mouse while simplifying the manufacture of the antigenic peptide. In a Good Laboratory Practices compliant rabbit toxicology study, the base layer-crosslinked, Pam3Cys-modified, serine-substituted candidate was shown to be safe and immunogenic, eliciting parasite-neutralizing antibody responses and establishing the dose/route/regimen for a clinical evaluation of this novel synthetic microparticle pre-erythrocytic malaria vaccine candidate.
ABSTRACT
OBJECTIVE: To investigate public willingness to share sensitive health information for research, health policy and clinical practice. METHODS: A total of 1,003 Australian respondents answered an online, attribute-driven, survey in which participants were asked to accept or reject hypothetical choice sets based on a willingness to share their health data for research and frontline-medical support as part of an integrated health system. The survey consisted of 5 attributes: Stakeholder access for analysis (Analysing group); Type of information collected; Purpose of data collection; Information governance; and Anticipated benefit; the results of which were analysed using logistic regression. RESULTS: When asked about their preference for sharing their health data, respondents had no preference between data collection for the purposes of clinical practice, health policy or research, with a slight preference for having government organisations manage, govern and curate the integrated datasets from which the analysis was being conducted. The least preferred option was for personal health records to be integrated with insurance records or for their data collected by privately owned corporate organisations. Individuals preferred their data to be analysed by a public healthcare provider or government staff and expressed a dislike for any private company involvement. CONCLUSIONS: The findings from this study suggest that Australian consumers prefer to share their health data when there is government oversight, and have concerns about sharing their anonymised health data for clinical practice, health policy or research purposes unless clarity is provided pertaining to its intended purpose, limitations of use and restrictions to access. Similar findings have been observed in the limited set of existing international studies utilising a stated preference approach. Evident from this study, and supported by national and international research, is that the establishment and preservation of a social license for data linkage in health research will require routine public engagement as a result of continuously evolving technological advancements and fluctuating risk tolerance. Without more work to understand and address stakeholder concerns, consumers risk being reluctant to participate in data-sharing and linkage programmes.
Subject(s)
Health Policy , Health Records, Personal , Humans , Australia , Information Dissemination , Surveys and QuestionnairesABSTRACT
INTRODUCTION: Experiences and determinants connected with type 2 diabetes mellitus-associated erectile dysfunction (T2DMED) in health appointments are not well understood and infrequently reported. This systematic review was undertaken to synthesise evidence of the experiences, facilitators, and barriers around screening ED in men with T2DM during health service consultations. METHODS: The review report was based on the guidelines provided by the Joanna Briggs Institute for conducting mixed-method systematic reviews. Eight electronic databases were searched, including Web of Science, Embase via Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO, ProQuest, PubMed, PsychInfo via Ovid, MEDLINE via Ovid, Portal Garuda. Additionally, the review manually looked through the reference lists of the studies we included. Erectile dysfunction, type 2 diabetes mellitus, screening and barriers were initially used as keywords in the search strategy. All identified primary studies written in English and Bahasa Indonesia, and published between 2001 and 2022 were meticulously screened following an agreed set of inclusion criteria. FINDINGS: Out of 3468 papers screened, only six were chosen for the review. These included three cross-sectional studies, two qualitative studies, and one mixed-method study. The study quality of the included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. Based on the checklist criteria, the studies ranged between 5/10 to 9/10 in terms of quality. After synthesizing the findings, four main categories were identified including the willingness to discuss T2DMED, the barriers experienced and perceived, the limited understanding of T2DMED, and the support expected by men with T2DM. DISCUSSION: Many men kept quiet about their struggles with T2DMED, hoping to bring it up as a topic of discussion during healthcare consultations. Barriers such as embarrassment, a sense of helplessness and reluctance to seek help, financial constraints, and dismissive healthcare professionals hindered them from addressing this issue. Both the participating men and healthcare professionals lacked a comprehensive understanding of T2DMED. RECOMMENDATIONS: It is important to provide education tailored to men's specific needs and improve awareness about T2DM-associated ED. Creating a more T2DMED-friendly environment could be a potential solution to increase early screening and management. Future research should investigate potential barriers that prevent HCPs from identifying and addressing T2MED since their absence in the identified studies highlights this need. SYSTEMATIC REVIEW REGISTRATION: CRD42021292454.
Subject(s)
Diabetes Mellitus, Type 2 , Erectile Dysfunction , Male , Humans , Erectile Dysfunction/etiology , Diabetes Mellitus, Type 2/complications , Cross-Sectional Studies , Qualitative Research , EmotionsABSTRACT
Biofilms consist of bacterial cells surrounded by a matrix of extracellular polymeric substance (EPS), which protects the colony from many countermeasures, including antibiotic treatments. Growth and formation of bacterial biofilms are affected by nutrients available in the environment. In the oral cavity, the presence of sucrose affects the growth of Streptococcus mutans that produce acids that erode enamel and form dental caries. Biofilm formation on dental implants commonly leads to severe infections and can restrict osseointegration necessary for the implant to be successful. This work determines the effect of sucrose concentration on biofilm EPS formation and adhesion of Streptococcus mutans, a common oral colonizer, to titanium substrates simulating common dental implants. Biofilm formation and profiles are visualized at high magnification with scanning electron microscopy (SEM). Large mounds and complex structures consisting of bacterial cells and EPS can be seen in biofilms at sucrose concentrations that are favorable for biofilm growth. The laser spallation technique is used to apply stress wave loading to the biofilm, causing the biofilm to delaminate at a critical tensile stress threshold. The critical tensile stress threshold is the adhesion strength. Because laser spallation applies the stress loading to the rear of the substrate, bulk adhesion properties of the biofilm can be determined despite the heterogenous composition and low cohesion strength of the biofilm. Statistical analysis reveals that adhesion strength of biofilms initially increase with increasing sucrose concentration and then decrease as sucrose concentration continues to increase. The adhesion strength of bacterial biofilms to the substrate in this study is compared to the adhesion of osteoblast-like cells to the same substrates published previously. When sucrose is present in the biofilm growth environment, S. mutans adhesion is higher than that of the osteoblast-like cells. Results of this study suggest sucrose-mediated S. mutans biofilms may outcompete osteoblasts in terms of adhesion during osseointegration, which could explain higher rates of peri-implant disease associated with high sugar diets. Further studies demonstrating adhesion differentials between biofilms and cells including co-cultures are needed and motivated by the present work.
ABSTRACT
A recent focus of ecosystem services research has been on the definition of biophysical outcomes and measures most closely linked to social welfare. There is a particular need to identify biophysical outcomes corresponding to existence values. (Values associated with existence apart from any current or future use). We review economic and ecological evidence to answer two key questions: First, what are ideal characteristics of linking indicators for existence values? Linking indicators should be: understandable, subject to direct sensory perception, represented at relevant temporal and spatial scales, comprehensive, and quantifiable in a repeatable manner. Second, what types of ecosystem outcomes are most likely to be associated with these values? We distinguish between indicators of taxa and ecological landscapes, and then multiple subcategories within each. Our fundamental conclusion is that while there are general principles informing the specification of linking indicators of existence values, there is no compact set of indicators or measures that applies universally. The case-specific nature of these issues-general guidelines notwithstanding-implies the need for sustained partnerships between social and biophysical scientists to address questions of indicator choice.
ABSTRACT
Background: Erectile dysfunction (ED) often affects men with type 2 diabetes mellitus (T2DM) due to microvascular damage. However, medical interventions are not always appropriate. Aim: This scoping review aimed to answer the following question: What evidence is available about the effects of non-medical and non-invasive healthcare interventions to improve ED in men with T2DM? Method: Potential studies were collected from the Cumulative Index to Nursing and Allied Health Literature via EBSCO, Embase via Ovid, MEDLINE via Ovid, Web of Science, PubMed, ProQuest, and PsycINFO via Ovid. Findings: From 2,611 identified titles, 17 studies, including 11 interventional and 6 observational studies, were included. Four main alternatives to medical interventions were identified from the included studies. Amongst these, four studies recommended patient education on lifestyle modification, twelve studies encouraged dietary changes and physical activities, two studies emphasized the use of vacuum erectile device, and three studies suggested the application of low-intensity extracorporeal shockwave therapy by healthcare professionals. Discussion: Dietary modification and physical activities were promoted as effective interventions to help maintaining the erectile function in men with T2DM. Several methods of patient education were identified as the approach to facilitate lifestyle modification in men with T2DM-associated ED. The positive outcomes of this review support early ED screening to help preventing T2DM complications such as ED in men. Further, T2DM management is a shared responsibility between the men and healthcare professionals. Despite the success of Vacuum Erectile Device and Low-intensity Extracorporeal Shockwave Therapy in regaining erectile function, further research is needed in this area based on the recommendations of the American Urological Association. Moreover, the health and quality of life of men with T2DM must be improved.
ABSTRACT
Neuropsychiatric adverse events have been previously reported following deep brain stimulation (DBS) for Parkinson's disease (PD). Most cases described have involved DBS of the subthalamic nucleus (STN). We report a unique case of acute-onset and reversible psychosis, suicidality, and depressive symptoms following DBS of the globus pallidus internus (GPi) and review the relevant literature.
ABSTRACT
BACKGROUND: Epidemiologic studies show that smokers have a lower incidence of Parkinson's disease. Nicotine has been hypothesized to slow progression in early Parkinson's disease. METHODS: In a double-blind, placebo-controlled multicenter trial, we randomly assigned patients with Parkinson's disease, diagnosed within 18 months, who were in Hoehn and Yahr disease stage less than or equal to 2 (range from 0 to 5; higher scores indicate greater impairment), who were therapy naïve (except for stable monoamine-oxidase-B inhibition), and not requiring dopaminergic therapy, to transdermal nicotine or placebo. The primary end point was change in Unified Parkinson's Disease Rating Scale parts IIII (Total UPDRS) score (range from 0 to 172; higher scores indicate greater impairment) between baseline and 60 weeks (52 weeks of trial therapy, 8 weeks of washout). The first secondary end point was change in Total UPDRS from baseline to 52 weeks. Differences between groups were estimated using the HodgesLehmann (HL) method and tested with the exact two-sided stratified MannWhitneyWilcoxon test according to the intention-to-treat principle. RESULTS: Among 163 participants, 101 were assessed for the primary end point. Mean worsening of Total UPDRS was 3.5 in the placebo versus 6.0 in the nicotine group (HL-difference with 95% CI: 3 [6 to 0], P=0.06). For the first secondary end point, analysis of 138 participants showed a mean worsening of 5.4 in the placebo versus 9.1 in the nicotine group (HL-difference with 95% CI: 4 [7 to 1]). Dropout was mainly because of early treatment discontinuation or adverse events. Cutaneous adverse effects at the patch application site were common. In all, 34.6% of participants initiated dopaminergic therapy during participation. CONCLUSIONS: One-year transdermal nicotine treatment did not slow progression in early Parkinson's disease. (Funded by the Michael J. Fox Foundation for Parkinson's Research and others; ClinicalTrials.gov number, NCT01560754; EudraCT number, 2010-020299-42.)
Subject(s)
Parkinson Disease , Humans , Parkinson Disease/drug therapy , Antiparkinson Agents , Nicotine , Dopamine/therapeutic use , Administration, CutaneousABSTRACT
Layer-by-layer microparticle (LbL-MP) fabrication was used to produce synthetic vaccines presenting a fusion peptide containing RSV G protein CX3C chemokine motif and a CD8 epitope of the RSV matrix protein 2 (GM2) with or without a covalently linked TLR2 agonist (Pam3.GM2). Immunization of BALB/c mice with either GM2 or Pam3.GM2 LbL-MP in the absence of adjuvant elicited G-specific antibody responses and M2-specific CD8+ T-cell responses. Following challenge with RSV, mice immunized with the GM2 LbL-MP vaccine developed a Th2-biased immune response in the lungs with elevated levels of IL-4, IL-5, IL-13, and eotaxin in the bronchoalveolar lavage (BAL) fluid and a pulmonary influx of eosinophils. By comparison, mice immunized with the Pam3.GM2 LbL-MP vaccine had considerably lower to non-detectable levels of the Th2 cytokines and chemokines and very low numbers of eosinophils in the BAL fluid post-RSV challenge. In addition, mice immunized with the Pam3.GM2 LbL-MP also had higher levels of RSV G-specific IgG2a and IgG2b in the post-challenge BAL fluid compared to those immunized with the GM2 LbL-MP vaccine. While both candidates protected mice from infection following challenge, as evidenced by the reduction or elimination of RSV plaques, the inclusion of the TLR2 agonist yielded a more potent antibody response, greater protection, and a clear shift away from Th2/eosinophil responses. Since the failure of formalin-inactivated RSV (FI-RSV) vaccines tested in the 1960s has been hypothesized to be partly due to the ablation of host TLR engagement by the vaccine and inappropriate Th2 responses upon subsequent viral infection, these findings stress the importance of appropriate engagement of the innate immune response during initial exposure to RSV G CX3C.
ABSTRACT
BACKGROUND: Chronic kidney disease (CKD) is a major global health problem that affects approximately one in 10 adults. Up to 90% of individuals with CKD go undetected until its progression to advanced stages, invariably leading to death in the absence of treatment. The project aims to fill information gaps around the burden of CKD in the Western Australian (WA) population, including incidence, prevalence, rate of progression, and economic cost to the health system. METHODS: Given the sensitivity of the information involved, the project employed a privacy preserving record linkage methodology to link data from four major pathology providers in WA to hospital records, to establish a CKD registry with continuous medical record for individuals with biochemical specification for CKD. This method uses encrypted personal identifying information in a probability-based linkage framework (Bloom filters) to help mitigate risk while maximizing linkage quality. RESULTS: The project developed interoperable technology to create a transparent CKD data catalogue which is linkable to other datasets. This technology has been designed to support the aspirations of the research program to provide linked de-identified pathology, morbidity, and mortality data that can be used to derive insights to enable better CKD patient outcomes. The cohort includes over 1 million individuals with creatinine results over the period 2002 to 2021. CONCLUSION: Using linked data from across the care continuum, researchers are able to evaluate the effectiveness of service delivery and provide evidence for policy and program development. The CKD registry will enable an innovative review of the epidemiology of CKD in WA. Linking pathology records can identify cases of CKD that are missed in the early stages due to disaggregation of results, enabling identification of at-risk populations that represent targets for early intervention and management.
Subject(s)
Privacy , Renal Insufficiency, Chronic , Adult , Australia , Creatinine , Humans , Medical Record Linkage/methods , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Semantic WebABSTRACT
AIM: In 2020, the European Kidney Function Consortium (EKFC) published a new creatinine-based equation to estimate glomerular filtration rate (eGFR) to overcome known limitations in existing equations. The aim of this study is to model the potential impact on service referral and health expenditure of routine reporting of eGFR using the EKFC equation as compared to the CKD-EPI equation in a Western Australian population. METHODS: eGFR was calculated for 760 614 patients with 2 368 234 creatinine results using the CKD-EPI and EKFC formulas. Patients were grouped into a CKD cohort if they had at least two eGFR results of <60 ml/min/1.73 m2 from tests at least 90 days apart. The impact of each equation on the reclassification of CKD stages, CKD cohort classification, the rate of change in eGFR and direct health costs were assessed. RESULTS: About 90.66% of patients had a lower eGFR when calculated using the EKFC equation. About 12.6% of individuals were classified into a different CKD stage using the EKFC equation with 97.43% of these patients classified into a higher (more advanced) stage. There was a 25.9% increase in the number of patients identified as having CKD when calculated using the EKFC equation. Direct health costs also increased with the use of EKFC reporting. CONCLUSION: Use of the EKFC equation will increase population prevalence of CKD and will result in a shift to higher stages of CKD. This has implications for monitoring and referral of patients within specialist services and has the potential to increase the need for multidisciplinary care.
Subject(s)
Renal Insufficiency, Chronic , Australia/epidemiology , Creatinine , Glomerular Filtration Rate , Humans , Kidney , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiologyABSTRACT
BACKGROUND: Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson's disease. METHODS: In this phase 2 trial, we randomly assigned participants with early-stage Parkinson's disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks. The primary end point was the change from baseline to week 52 in the sum of scores on parts I, II, and III of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 236, with higher scores indicating greater impairment). Secondary end points included the dopamine transporter levels in the putamen of the hemisphere ipsilateral to the clinically more affected side of the body, as measured by 123I-ioflupane single-photon-emission computed tomography (SPECT). RESULTS: A total of 316 participants were enrolled; 105 were assigned to receive placebo, 105 to receive 1500 mg of prasinezumab, and 106 to receive 4500 mg of prasinezumab. The baseline mean MDS-UPDRS scores were 32.0 in the placebo group, 31.5 in the 1500-mg group, and 30.8 in the 4500-mg group, and mean (±SE) changes from baseline to 52 weeks were 9.4±1.2 in the placebo group, 7.4±1.2 in the 1500-mg group (difference vs. placebo, -2.0; 80% confidence interval [CI], -4.2 to 0.2; P = 0.24), and 8.8±1.2 in the 4500-mg group (difference vs. placebo, -0.6; 80% CI, -2.8 to 1.6; P = 0.72). There was no substantial difference between the active-treatment groups and the placebo group in dopamine transporter levels on SPECT. The results for most clinical secondary end points were similar in the active-treatment groups and the placebo group. Serious adverse events occurred in 6.7% of the participants in the 1500-mg group and in 7.5% of those in the 4500-mg group; infusion reactions occurred in 19.0% and 34.0%, respectively. CONCLUSIONS: Prasinezumab therapy had no meaningful effect on global or imaging measures of Parkinson's disease progression as compared with placebo and was associated with infusion reactions. (Funded by F. Hoffmann-La Roche and Prothena Biosciences; PASADENA ClinicalTrials.gov number, NCT03100149.).
Subject(s)
Antibodies, Monoclonal, Humanized , Antiparkinson Agents , Parkinson Disease , alpha-Synuclein , Antibodies, Monoclonal, Humanized/therapeutic use , Antiparkinson Agents/therapeutic use , Dopamine Plasma Membrane Transport Proteins/therapeutic use , Double-Blind Method , Humans , Parkinson Disease/drug therapy , Treatment Outcome , alpha-Synuclein/antagonists & inhibitorsABSTRACT
OBJECTIVE: To provide a review of prediction models that have been used to measure clinical or pathological progression of chronic kidney disease (CKD). DESIGN: Scoping review. DATA SOURCES: Medline, EMBASE, CINAHL and Scopus from the year 2011 to 17th February 2022. STUDY SELECTION: All English written studies that are published in peer-reviewed journals in any country, that developed at least a statistical or computational model that predicted the risk of CKD progression. DATA EXTRACTION: Eligible studies for full text review were assessed on the methods that were used to predict the progression of CKD. The type of information extracted included: the author(s), title of article, year of publication, study dates, study location, number of participants, study design, predicted outcomes, type of prediction model, prediction variables used, validation assessment, limitations and implications. RESULTS: From 516 studies, 33 were included for full-text review. A qualitative analysis of the articles was compared following the extracted information. The study populations across the studies were heterogenous and data acquired by the studies were sourced from different levels and locations of healthcare systems. 31 studies implemented supervised models, and 2 studies included unsupervised models. Regardless of the model used, the predicted outcome included measurement of risk of progression towards end-stage kidney disease (ESKD) of related definitions, over given time intervals. However, there is a lack of reporting consistency on details of the development of their prediction models. CONCLUSIONS: Researchers are working towards producing an effective model to provide key insights into the progression of CKD. This review found that cox regression modelling was predominantly used among the small number of studies in the review. This made it difficult to perform a comparison between ML algorithms, more so when different validation methods were used in different cohort types. There needs to be increased investment in a more consistent and reproducible approach for future studies looking to develop risk prediction models for CKD progression.