MIDASim: a fast and simple simulator for realistic microbiome data.

BACKGROUND: Advances in sequencing technology has led to the discovery of associations between the human microbiota and many diseases, conditions, and traits. With the increasing availability of microbiome data, many statistical methods have been developed for studying these associations. The growing number of newly developed methods highlights the need for simple, rapid, and reliable methods to simulate realistic microbiome data, which is essential for validating and evaluating the performance of these methods. However, generating realistic microbiome data is challenging due to the complex nature of microbiome data, which feature correlation between taxa, sparsity, overdispersion, and compositionality. Current methods for simulating microbiome data are deficient in their ability to capture these important features of microbiome data, or can require exorbitant computational time. METHODS: We develop MIDASim (MIcrobiome DAta Simulator), a fast and simple approach for simulating realistic microbiome data that reproduces the distributional and correlation structure of a template microbiome dataset. MIDASim is a two-step approach. The first step generates correlated binary indicators that represent the presence-absence status of all taxa, and the second step generates relative abundances and counts for the taxa that are considered to be present in step 1, utilizing a Gaussian copula to account for the taxon-taxon correlations. In the second step, MIDASim can operate in both a nonparametric and parametric mode. In the nonparametric mode, the Gaussian copula uses the empirical distribution of relative abundances for the marginal distributions. In the parametric mode, a generalized gamma distribution is used in place of the empirical distribution. RESULTS: We demonstrate improved performance of MIDASim relative to other existing methods using gut and vaginal data. MIDASim showed superior performance by PERMANOVA and in terms of alpha diversity and beta dispersion in either parametric or nonparametric mode. We also show how MIDASim in parametric mode can be used to assess the performance of methods for finding differentially abundant taxa in a compositional model. CONCLUSIONS: MIDASim is easy to implement, flexible and suitable for most microbiome data simulation situations. MIDASim has three major advantages. First, MIDASim performs better in reproducing the distributional features of real data compared to other methods, at both the presence-absence level and the relative-abundance level. MIDASim-simulated data are more similar to the template data than competing methods, as quantified using a variety of measures. Second, MIDASim makes few distributional assumptions for the relative abundances, and thus can easily accommodate complex distributional features in real data. Third, MIDASim is computationally efficient and can be used to simulate large microbiome datasets. Video Abstract.

HLA-DQA1*05 Allele Carriage and Anti-TNF Therapy Persistence in Inflammatory Bowel Disease.

INTRODUCTION: Carriage of the HLA-DQA1*05 allele is associated with development of antidrug antibodies (ADAs) to antitumor necrosis factor (anti-TNF) therapy in patients with Crohn's disease. However, ADA is not uniformly associated with treatment failure. We aimed to determine the impact of carriage of HLA-DQA1*05 allele on outcome of biologic therapy evaluated by drug persistence. METHODS: A multicenter, retrospective study of 877 patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy with HLA-DQA1*05 genotypes were generated by imputation from whole genome sequence using the HIBAG package, in R. Primary end point was anti-TNF therapy persistence, (time to therapy failure), segregated by HLA-DQA1*05 allele genotype and development of a risk score to predict anti-TNF therapy failure, incorporating HLA-DQA1*05 allele genotype status (LORisk score). RESULTS: In all, 877 patients receiving anti-TNF therapy were included in our study; 543 (62%) had no copy, 281 (32%) one copy, and 53 (6%) 2 copies of HLA-DQA1*05 allele. Mean time to anti-TNF therapy failure in patients with 2 copies of HLA-DQA1*05 allele was significantly shorter compared with patients with 0 or 1 copy at 700 days' follow-up: 418 vs 541 vs 513 days, respectively (P = .012). Factors independently associated with time to anti-TNF therapy failure included carriage of HLA-DQA1*05 allele (hazard ratio [HR], 1.2, P = .02; female gender HR, 1.6, P < .001; UC phenotype HR, 1.4, P = .009; and anti-TNF therapy type [infliximab], HR, 1.5, P = .002). The LORisk score was significantly associated with shorter time to anti-TNF therapy failure (P < .001). CONCLUSIONS: Carriage of 2 HLA-DQA1*05 alleles is associated with less favorable outcomes for patients receiving anti-TNF therapy with shorter time to therapy failure. HLA-DQA1*05 genotype status in conjunction with clinical factors may aid in therapy selection in patients with IBD.

Our study found carriage of 2 copies of the HLA-DQA1*05 allele is associated with a less favorable response to anti-TNF therapy with shorter time to therapy failure. HLA-DQA1*05 genotype status in conjunction with clinical factors may aid in therapy selection in IBD patients.

Expert Consensus on Pediatric Urodynamics Reporting Using Modified Delphi Technique.

PURPOSE: Urodynamic testing (UDS) is an important tool in the management of pediatric lower urinary tract conditions. There have been notable efforts to standardize pediatric UDS nomenclature and technique, but no formal guidelines exist on essential elements to include in a clinical report. We sought to identify ideal structure and elements of a pediatric UDS assessment based on expert consensus. MATERIALS AND METHODS: Pediatric urologists regularly performing UDS were queried using a Delphi process. Participants were invited representing varied geographic, experience, and societal involvement. Participants underwent 3 rounds of questionnaires between November 2022 and August 2023 focusing on report organization, elements, definitions, and automated electronic health record clinical decision support. Professional billing requirements were also considered. Consensus was defined as 80% agreeing either in favor of or against a topic. Elements without consensus were discussed in subsequent rounds. RESULTS: A diverse sample of 30 providers, representing 27 institutions across 21 US states; Washington, District of Columbia; and Canada completed the study. Participants reported interpreting an average number of 5 UDS reports per week (range 1-22). The finalized consensus report identifies 93 elements that should be included in a pediatric UDS report based on applicable study conditions and findings. CONCLUSIONS: This consensus report details the key elements and structure agreed upon by an expert panel of pediatric urologists. Further standardization of documentation should aid collaboration and research for patients undergoing UDS. Based on this information, development of a standardized UDS report template using electronic health record implementation principles is underway, which will be openly available for pediatric urologists.

IL-6-mediated endothelial injury impairs antiviral humoral immunity after bone marrow transplantation.

Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT), but how this affects immune responses broadly remains unknown. Using a preclinical model of CMV reactivation after BMT, we found compromised antiviral humoral responses induced by IL-6 signaling. IL-6 signaling in T cells maintained Th1 cells, resulting in sustained IFN-γ secretion, which promoted endothelial cell (EC) injury, loss of the neonatal Fc receptor (FcRn) responsible for IgG recycling, and rapid IgG loss. T cell-specific deletion of IL-6R led to persistence of recipient-derived, CMV-specific IgG and inhibited CMV reactivation. Deletion of IFN-γ in donor T cells also eliminated EC injury and FcRn loss. In a phase III clinical trial, blockade of IL-6R with tocilizumab promoted CMV-specific IgG persistence and significantly attenuated early HCMV reactivation. In sum, IL-6 invoked IFN-γ-dependent EC injury and consequent IgG loss, leading to CMV reactivation. Hence, cytokine inhibition represents a logical strategy to prevent endothelial injury, thereby preserving humoral immunity after immunotherapy.

Carbohydrates and protein digestive traits in beef cattle grazing fertilised or mixed tropical pasture.

This study was performed to investigate the nitrogen (N) and carbohydrate digestive traits of grazing heifers. The experiment was carried out at the Federal University of Lavras. The treatments were a Marandu palisadegrass (Urochloa brizantha [Syn, Brachiaria brizantha] Stapf. A. Rich. cv. Marandu) monoculture fertilised with 150 kg N/[ha ∙ year] (FP) or Marandu palisadegrass mixed pasture with forage peanut (MP). The pastures were grazed by six rumen-cannulated zebu heifers. A double cross-over design was used in four periods. Nutritive value, intake and apparent digestibility of forage, ruminal traits and kinetics and N balance were evaluated. Apparent total-tract digestibility of dry matter (DM) and neutral detergent fibre (NDF) were greater for FP than for MP. There was no effect in apparent total-tract digestibility of N. The estimated intestinal digestibility of nutrients was greater on MP than FP. Even though N intake and faecal N output were greater on MP than FP, there was no effect in urine N output. The N balance tended to be greater on MP than FP. The forage peanut, which contains condensed tannins, decreased ruminal fibre degradation, apparent digestibility and ruminal protein degradation, increased N flow from the rumen. Inclusion of forage peanut in the mixed pasture decreased the ruminal fibre degradability but increased N retention by the animals.

Markerless motion capture provides accurate predictions of ground reaction forces across a range of movement tasks.

Measuring or estimating the forces acting on the human body during movement is critical for determining the biomechanical aspects relating to injury, disease and healthy ageing. In this study we examined whether quantifying whole-body motion (segmental accelerations) using a commercial markerless motion capture system could accurately predict three-dimensional ground reaction force during a diverse range of human movements: walking, running, jumping and cutting. We synchronously recorded 3D ground reaction forces (force instrumented treadmill or in-ground plates) with high-resolution video from eight cameras that were spatially calibrated relative to a common coordinate system. We used a commercially available software to reconstruct whole body motion, along with a geometric skeletal model to calculate the acceleration of each segment and hence the whole-body centre of mass and ground reaction force across each movement task. The average root mean square difference (RMSD) across all three dimensions and all tasks was 0.75 N/kg, with the maximum average RMSD being 1.85 N/kg for running vertical force (7.89 % of maximum). There was very strong agreement between peak forces across tasks, with R2 values indicating that the markerless prediction algorithm was able to predict approximately 95-99 % of the variance in peak force across all axes and movements. The results were comparable to previous reports using whole-body marker-based approaches and hence this provides strong proof-of-principle evidence that markerless motion capture can be used to predict ground reaction forces and therefore potentially assess movement kinetics with limited requirements for participant preparation.

Nursing and allied health workforce in Australian public rheumatology departments is inadequate: a cross-sectional observational study.

Rheumatological conditions are complex and impact many facets of daily life. Management of people with rheumatological conditions can be optimised through multidisciplinary care. However, the current access to nursing and allied health professionals in Australia is unknown. A cross-sectional study of nursing and allied health professionals in Australian public rheumatology departments for adult and paediatric services was conducted. The heads of Australian public rheumatology departments were invited to report the health professionals working within their departments, referral pathways, and barriers to greater multidisciplinary care. A total of 27/39 (69.2%) of the hospitals responded. The most common health professionals within departments were nurses (n = 23; 85.2%) and physiotherapists (n = 10; 37.0%), followed by pharmacists (n = 5; 18.5%), psychologists (n = 4; 14.8%), and occupational therapists (n = 4; 14.8%). No podiatrists were employed within departments. Referral pathways were most common for physiotherapy (n = 20; 74.1%), followed by occupational therapy (n = 15; 55.5%), podiatry (n = 13; 48.1%), and psychology (n = 6; 22%). The mean full-time equivalent of nursing and allied health professionals per 100,000 population in Australia was 0.29. Funding was identified as the most common barrier. In Australia, publicly funded multidisciplinary care from nurses and allied health professionals in rheumatology departments is approximately 1.5 days per week on average. This level of multidisciplinary care is unlikely to meet the needs of rheumatology patients. Research is needed to determine the minimum staffing requirements of nursing and allied health professionals to provide optimal care.

Clinical grade multiparametric cell sorting and gene-marking of regulatory T cells.

BACKGROUND AIMS: Regulatory T cells (Tregs) are the main mediators of peripheral tolerance. Treg-directed therapy has shown promising results in preclinical studies of diverse immunopathologies. At present, the clinical applicability of adoptive Treg transfer is limited by difficulties in generating Tregs at sufficient cell dose and purity. METHODS: We developed a Good Manufacturing Practice (GMP) compliant method based on closed-system multiparametric Fluorescence-Activated Cell Sorting (FACS) to purify Tregs, which are then expanded in vitro and gene-marked with a clinical grade retroviral vector to enable in vivo fate tracking. Following small-scale optimization, we conducted four clinical-scale processing runs. RESULTS: We showed that Tregs could be enriched to 87- 92% purity following FACS-sorting, and expanded and transduced to yield clinically relevant cell dose of 136-732×106 gene-marked cells, sufficient for a cell dose of at least 2 × 106 cells/kg. The expanded Tregs were highly demethylated in the FOXP3 Treg-specific demethylated region (TSDR), consistent with bona fide natural Tregs. They were suppressive in vitro, but a small percentage could secrete proinflammatory cytokines, including interferon-γ and interleukin-17A. CONCLUSIONS: This study demonstrated the feasibility of isolating, expanding and gene-marking Tregs in clinical scale, thus paving the way for future phase I trials that will advance knowledge about the in vivo fate of transferred Tregs and its relationship with concomitant Treg-directed pharmacotherapy and clinical response.

MIDASim: a fast and simple simulator for realistic microbiome data.

Background: Advances in sequencing technology has led to the discovery of associations between the human microbiota and many diseases, conditions, and traits. With the increasing availability of microbiome data, many statistical methods have been developed for studying these associations. The growing number of newly developed methods highlights the need for simple, rapid, and reliable methods to simulate realistic microbiome data, which is essential for validating and evaluating the performance of these methods. However, generating realistic microbiome data is challenging due to the complex nature of microbiome data, which feature correlation between taxa, sparsity, overdispersion, and compositionality. Current methods for simulating microbiome data are deficient in their ability to capture these important features of microbiome data, or can require exorbitant computational time. Methods: We develop MIDASim ( MI crobiome DA ta Sim ulator), a fast and simple approach for simulating realistic microbiome data that reproduces the distributional and correlation structure of a template microbiome dataset. MIDASim is a two-step approach. The first step generates correlated binary indicators that represent the presence-absence status of all taxa, and the second step generates relative abundances and counts for the taxa that are considered to be present in step 1, utilizing a Gaussian copula to account for the taxon-taxon correlations. In the second step, MIDASim can operate in both a nonparametric and parametric mode. In the nonparametric mode, the Gaussian copula uses the empirical distribution of relative abundances for the marginal distributions. In the parametric mode, an inverse generalized gamma distribution is used in place of the empirical distribution. Results: We demonstrate improved performance of MIDASim relative to other existing methods using gut and vaginal data. MIDASim showed superior performance by PER-MANOVA and in terms of alpha diversity and beta dispersion in either parametric or nonparametric mode. We also show how MIDASim in parametric mode can be used to assess the performance of methods for finding differentially abundant taxa in a compositional model. Conclusions: MIDASim is easy to implement, flexible and suitable for most microbiome data simulation situations. MIDASim has three major advantages. First, MIDASim performs better in reproducing the distributional features of real data compared to other methods at both presence-absence level and relative-abundance level. MIDASim-simulated data are more similar to the template data than competing methods, as quantified using a variety of measures. Second, MIDASim makes few distributional assumptions for the relative abundances, and thus can easily accommodate complex distributional features in real data. Third, MIDASim is computationally efficient and can be used to simulate large microbiome datasets.

Predictors of oliguria in post-traumatic acute kidney injury.

BACKGROUND: Acute kidney injury is classified by urine output into non-oliguric and oliguric variants. Non-oliguric acute kidney injury has lower morbidity and mortality and accounts for up to 64% of acute kidney injury in hospitalized patients. However, the incidence of non-oliguric acute kidney injury in the trauma population and whether the 2 variants of acute kidney injury share the same risk factors is unknown. We hypothesized that oliguria would be present in the majority of acute kidney injury in severely injured trauma patients and that unique risk factors would predispose patients to the development of oliguria. METHODS: Patients admitted to the trauma intensive care unit and diagnosed with an acute kidney injury between 2016 to 2021 were identified. Cases were categorized based on urine output into oliguric (<400 mL per day) and non-oliguric (>400 mL per day) disease. Risk factors, management, and outcomes were compared. Logistic regression was used to identify risk factors associated with oliguria. RESULTS: A total of 227 patients met inclusion criteria. Non-oliguric acute kidney injury accounted for 74% of all cases and was associated with greater survival (78% vs 35.6%, P < .001). Using logistic regression, female sex, vasopressor use, and a greater net fluid balance at 48 hours were all predictive of oliguria (while controlling for age, race, shock index, massive transfusion, operative intervention, cardiac arrest, and nephrotoxic medication exposure). CONCLUSION: Non-oliguria accounts for the majority of post-traumatic acute kidney injury and is associated with improved survival. Specific risk factors for the development of oliguric acute kidney injury include female sex, vasopressor use, and a higher net fluid balance at 48 hours.

Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia.

Telomerase enables replicative immortality in most cancers including acute myeloid leukemia (AML). Imetelstat is a first-in-class telomerase inhibitor with clinical efficacy in myelofibrosis and myelodysplastic syndromes. Here, we develop an AML patient-derived xenograft resource and perform integrated genomics, transcriptomics and lipidomics analyses combined with functional genetics to identify key mediators of imetelstat efficacy. In a randomized phase II-like preclinical trial in patient-derived xenografts, imetelstat effectively diminishes AML burden and preferentially targets subgroups containing mutant NRAS and oxidative stress-associated gene expression signatures. Unbiased, genome-wide CRISPR/Cas9 editing identifies ferroptosis regulators as key mediators of imetelstat efficacy. Imetelstat promotes the formation of polyunsaturated fatty acid-containing phospholipids, causing excessive levels of lipid peroxidation and oxidative stress. Pharmacological inhibition of ferroptosis diminishes imetelstat efficacy. We leverage these mechanistic insights to develop an optimized therapeutic strategy using oxidative stress-inducing chemotherapy to sensitize patient samples to imetelstat causing substantial disease control in AML.

Applying the antecedent, behaviour, and consequence taxonomy to unintentional firearm injury as determined by a collaborative firearm injury database.

BACKGROUND: Unintentional firearm injury (UFI) remains a significant problem in the USA with respect to preventable injury and death. The antecedent, behaviour and consequence (ABC) taxonomy has been used by law enforcement agencies to evaluate unintentional firearm discharge. Using an adapted ABC taxonomy, we sought to categorise civilian UFI in our community to identify modifiable behaviours. METHODS: Using a collaborative firearm injury database (containing both a university-based level 1 trauma registry and a metropolitan law enforcement database), all UFIs from August 2008 through December 2021 were identified. Perceived threat (antecedent), behaviour and injured party (consequence) were identified for each incident. RESULTS: During the study period, 937 incidents of UFI were identified with 64.2% of incidents occurring during routine firearm tasks. 30.4% of UFI occurred during neglectful firearm behaviour such as inappropriate storage. Most injuries occurred under situations of low perceived threat. UFI involving children was most often due to inappropriate storage of weapons, while cleaning a firearm was the most common behaviour in adults. Overall, 16.5% of UFI involved injury to persons other than the one handling the weapon and approximately 1.3% of UFI resulted in mortality. CONCLUSIONS: The majority of UFI occurred during routine and expected firearm tasks such as firearm cleaning. Prevention programmes should not overlook these modifiable behaviours in an effort to reduce UFIs, complications and deaths.

Peripheral Blood Haploidentical Allogeneic Stem Cell Transplantation in Older Adults with Acute Myeloid Leukemia and Myelodysplastic Syndromes Demonstrates Long Term Survival, Results from Australia and New Zealand Transplant and Cellular Therapies.

There is a limited body of evidence for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in older patients. Previous studies have used a high proportion of bone marrow-derived grafts and a variety of conditioning regimens. In Australia and New Zealand, haplo-HCST is predominantly performed using peripheral blood (PB) with universal use of post-transplantation cyclophosphamide (PTCy). To characterize the outcomes of older recipients undergoing haplo-HSCT for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Data were collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients aged 65 or older receiving a PB haplo-HSCT for AML/MDS between January 2010 and July 2020. A total of 44 patients were included in the analysis. The median follow-up time was 377 days. The median age was 68 (range 65-74) with a median Karnofsky performance status of 90. Thirty patients (68.2%) had AML, whereas 14 (31.8%) had MDS. The median donor age was 40. The most common conditioning regimen was nonmyeloablative fludarabine, cyclophosphamide, and total body irradiation (75%); the remainder of the patients received either melphalan- or busulfan-based regimens, and the majority were reduced intensity, with only 2 patients undergoing myeloablative conditioning. All patients received post-transplantation cyclophosphamide and mycophenolate mofetil, with the majority also receiving tacrolimus (90.5%) and the remainder receiving cyclosporine (9.5%). No patients received anti-thymocyte globulin. Neutrophil engraftment was achieved in 97.6% of patients at a median of 18 days, whereas platelet engraftment was achieved in 92.7% of patients at a median of 28 days. The cumulative incidences of cytomegalovirus (CMV) reactivation and CMV disease were 52.5% and 5.1% at 1 year. The incidence of grade 2-4 acute Graft Versus Host Disease (GVHD) was 18.2%. The incidence of chronic GVHD at 2 years was 40.7%, with extensive chronic GVHD occurring in 17.7% of patients. The incidences of relapse and non-relapse mortality (NRM) at 2 years were 8.8% and 20.7% respectively. The leading causes of death were infection (64.7%) followed by relapse (14.2%). The 2-year overall survival was 74%. Relapse free survival and GVHD free, relapse free survival at 2 years was 70% and 48%. Haplo-HSCT using a peripheral blood graft and PTCy GVHD prophylaxis demonstrates long-term disease control with acceptable rates of NRM for older patients with AML/MDS.

MERIT: Controlling Monte-Carlo error rate in large-scale Monte-Carlo hypothesis testing.

The use of Monte-Carlo (MC) p $$ p $$ -values when testing the significance of a large number of hypotheses is now commonplace. In large-scale hypothesis testing, we will typically encounter at least some p $$ p $$ -values near the threshold of significance, which require a larger number of MC replicates than p $$ p $$ -values that are far from the threshold. As a result, some incorrect conclusions can be reached due to MC error alone; for hypotheses near the threshold, even a very large number (eg, 1 0 6 $$ 1{0}^6 $$ ) of MC replicates may not be enough to guarantee conclusions reached using MC p $$ p $$ -values. Gandy and Hahn (GH)6-8 have developed the only method that directly addresses this problem. They defined a Monte-Carlo error rate (MCER) to be the probability that any decisions on accepting or rejecting a hypothesis based on MC p $$ p $$ -values are different from decisions based on ideal p $$ p $$ -values; their method then makes decisions by controlling the MCER. Unfortunately, the GH method is frequently very conservative, often making no rejections at all and leaving a large number of hypotheses "undecided". In this article, we propose MERIT, a method for large-scale MC hypothesis testing that also controls the MCER but is more statistically efficient than the GH method. Through extensive simulation studies, we demonstrate that MERIT controls the MCER while making more decisions that agree with the ideal p $$ p $$ -values than GH does. We also illustrate our method by an analysis of gene expression data from a prostate cancer study.

Building and maintaining interprofessional collaborative practice in eyecare: Learnings from the Queensland Paediatric Optometry Alignment Program.

PURPOSE: The Queensland Children's Hospital Paediatric Optometry Alignment Program commenced with a pilot phase to assess its feasibility, effectiveness and acceptability. This study identified the barriers that hinder effective interprofessional collaboration and the facilitators that contribute to its success, and assessed changes in optometrists' satisfaction since the pilot phase of the collaborative care programme. METHODS: Qualitative deductive and inductive content analysis was applied to open-ended free-text survey responses collected in 2018 from the optometrists involved in the Program's pilot phase. The responses were coded using the Theoretical Domains Framework (TDF) to categorise barriers and facilitators into key themes. Key behavioural determinants were mapped to the COM-B (Capability, Opportunity, Motivation-Behaviour) elements of the Behaviour Change Wheel model to identify intervention strategies. Intervention recommendations were derived from behaviour change mapping and compared with programme quality improvement initiatives. A cross-sectional explanatory survey informed by the TDF was conducted within the current 2023 cohort, and a longitudinal comparative analysis was carried out using data from the 2018 survey. RESULTS: Among the 97 surveys distributed in 2018, 44 respondents participated; from this group, 38 individuals contributed a total of 200 free-text responses. Facilitators (240 comments) outnumbered barriers (65 comments). Key facilitators were accessible and timely care, professional development, confidence and positive outcome beliefs. Barriers included communication, information handover, credibility, relationships and skill gaps. Optometrists actively engaged in the programme in 2023 reported heightened satisfaction with their involvement, increased confidence and greater engagement in paediatric eyecare delivery. However, challenges in clinical information transfer persist. CONCLUSION: The interprofessional collaborative model of paediatric eyecare has contributed efficiencies within the health system by building paediatric care capacity in the community, fostering professional credibility and promoting interdisciplinary trust. Insights gained should prove valuable for other paediatric eyecare services exploring hospital-to-community care models.

A randomised trial of topical polaprezinc to prevent oral mucositis in patients undergoing haematopoietic stem cell transplantation (ToPaZ study).

PURPOSE: Oral mucositis (OM) is a common complication in haematopoietic stem cell transplantation (HSCT). Polaprezinc, an anti-ulcer drug, has been shown to be effective to prevent OM in several studies when administered topically and systemically. This study aimed to evaluate the effectiveness of topical polaprezinc in patients undergoing HSCT. METHODS: This was an open-label randomised clinical trial comparing polaprezinc and sodium bicarbonate mouthwashes for the prevention of severe OM in HSCT patients. Adult patients who received conditioning regimens at moderate to high risk of developing OM were included. The primary endpoint was the incidence of severe (WHO grades 3-4) OM. The secondary endpoints included duration of grades 3-4 OM, incidence and duration of grades 2-4 OM, patient-reported pain and functional limitations. RESULTS: In total, 108 patients (55 test arm and 53 control arm) were randomised. There was no difference in the incidence of grades 3 to 4 OM (35% test arm versus 36% control arm). The secondary endpoints were not significantly different. In both arms, patients reported more throat pain compared to mouth pain. CONCLUSIONS: Topical polaprezinc had no effect in the prevention of OM in HSCT patients. Further research is required to evaluate the effects of systemic polaprezinc. The OM assessment tool needs to be reviewed as throat mucositis was a main issue in this study. TRIAL REGISTRATION: ACTRN12320001188921 (Date Registered: 10th November 2020).

Ranked severe maternal morbidity index for population-level surveillance at delivery hospitalization based on hospital discharge data.

BACKGROUND: Severe maternal morbidity (SMM) is broadly defined as an unexpected and potentially life-threatening event associated with labor and delivery. The Centers for Disease Control and Prevention (CDC) produced 21 different indicators based on International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) hospital diagnostic and procedure codes to identify cases of SMM. OBJECTIVES: To examine existing SMM indicators and determine which indicators identified the most in-hospital mortality at delivery hospitalization. METHODS: Data from the 1993-2015 and 2017-2019 Healthcare Cost and Utilization Project's National Inpatient Sample were used to report SMM indicator-specific prevalences, in-hospital mortality rates, and population attributable fractions (PAF) of mortality. We hierarchically ranked indicators by their overall PAF of in-hospital mortality. Predictive modeling determined if SMM prevalence remained comparable after transition to ICD-10-CM coding. RESULTS: The study population consisted of 18,198,934 hospitalizations representing 87,864,173 US delivery hospitalizations. The 15 top ranked indicators identified 80% of in-hospital mortality; the proportion identified by the remaining indicators was negligible (2%). The top 15 indicators were: restoration of cardiac rhythm; cardiac arrest; mechanical ventilation; tracheostomy; amniotic fluid embolism; aneurysm; acute respiratory distress syndrome; acute myocardial infarction; shock; thromboembolism, pulmonary embolism; cerebrovascular disorders; sepsis; both DIC and blood transfusion; acute renal failure; and hysterectomy. The overall prevalence of the top 15 ranked SMM indicators (~22,000 SMM cases per year) was comparable after transition to ICD-10-CM coding. CONCLUSIONS: We determined the 15 indicators that identified the most in-hospital mortality at delivery hospitalization in the US. Continued testing of SMM indicators can improve measurement and surveillance of the most severe maternal complications at the population level.