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Objective Influenza reemerged after a 2020–2021 hiatus in 2022, but understanding the resurgence needs pre‐COVID era surveillance. We compared age‐ and ethnicity‐specific incidence of severe acute respiratory infection (SARI) from a hospital network in Auckland, New Zealand, in 2022 against a baseline, 2012–2019. Methods Annual and monthly influenza SARI incidence per 1000 persons by age and ethnic group between 2012 and 2022 was calculated using resident population as the denominator. The hospitals capture most severe illness of the resident population. Results Influenza SARI incidence was highest among <1 year olds (2.62; 95% CI: 1.84–3.61) during 2012–2019, lowest at 6–14 years, and did not significantly increase until 50–64 years (0.35; 95% CI: 0.27–0.45), reaching 1.19 (95% CI: 0.57–1.55) in those ≥75 years. In all age groups, incidence was at least threefold higher in Māori and Pacific Peoples. No influenza SARI was identified in 2020–2021. In 2022, despite an early peak, annual incidence (<65 years) was lower than baseline in all ethnic groups, but incidence (≥65 years) in Māori (2.06; 95% CI: 1.22–3.26) and Pacific (3.94; 95% CI: 2.97–5.13) peoples was higher in 2022 than most baseline years, whereas incidence in NMNP (0.22; 95% CI: 0.14–0.32) was lower than any baseline year. Conclusion After no influenza 2020–2021, Auckland had an early, high, narrow peak in 2022. Stratification by age and ethnicity revealed striking discrepancies in incidence among Māori and Pacific adults over 65 years compared with NMNP adults, with implications for targeted vaccination strategies.

Ocular antibiotics are integral to the prevention and treatment of bacterial ocular infections. This study aimed to describe their utilisation across New Zealand according to patient and healthcare factors. Every subsidy-eligible community dispensing of ocular chloramphenicol, fusidic acid and ciprofloxacin in New Zealand, between 2010 and 2019, was included in this analysis. Number of dispensings/1000 population/year was quantified, stratified by patient age and urban/non-urban health districts. Dispensing rates by ethnicity were determined and were age adjusted. The proportion of dispensings by socioeconomic deprivation quintile was also determined. Chloramphenicol was the most commonly dispensed antibiotic; however, its utilisation decreased over time. Ciprofloxacin use was higher in children, while chloramphenicol use was higher in older patients. Ciprofloxacin usage was higher among Māori and Pasifika ethnicities, while fusidic acid use was lower. Chloramphenicol usage was higher among Pasifika. Antibiotic utilisation was higher in urban health districts, and in the most deprived quintile; both were most marked with ciprofloxacin. The utilisation of publicly funded ocular antibiotics across New Zealand varied between patient subgroups. These findings will help improve the prevention, management and outcomes of bacterial ocular infections, and support wider initiatives in antibiotic stewardship and medicine access equity.

Background/Objectives: Some ophthalmic antibiotics are publicly subsidised in New Zealand (NZ) for off-label use in the ear, however, this utilisation has not previously been described. This study compared the utilisation of ophthalmic chloramphenicol and ciprofloxacin in the eye and ear, among NZ children. Methods: This study involved clinical record review, and included 11,617 prescriptions of ophthalmic chloramphenicol and ciprofloxacin in 2022, for children aged five years or under in Auckland, NZ. Prescriptions of chloramphenicol and ciprofloxacin for eye and ear use were compared by: patient age, gender, ethnicity and socioeconomic deprivation, indication, community or hospital prescribing and number of repeat prescriptions. Statistical analysis was performed using Chi-squared test and multinomial regression. Results: Most ophthalmic ciprofloxacin was used in the ear (84%). In contrast, almost all chloramphenicol was used in the eye (96%). Post-operative use following tympanostomy tube insertion accounted for half of all hospital-prescribed ophthalmic ciprofloxacin used in the ear. Utilisation of chloramphenicol and ciprofloxacin in the eye and ear was similar, with more prescriptions for children aged one year and males, and most children received only one prescription. Māori and Pacific children generally received fewer prescriptions. Pacific children were more likely than Māori children to receive hospital-prescribed ophthalmic ciprofloxacin for use in the ear (adjusted OR 6.7, p = 0.025). Conclusions: These findings highlight the utilisation of ophthalmic ciprofloxacin in the ear in NZ children. These findings will inform decision-making in the public funding of medications, policy development in equitable medication access, and more collaborative efforts to improve antimicrobial use.

Background Forecasting models predicting trends in hospitalization rates have the potential to inform hospital management during seasonal epidemics of respiratory diseases and the associated surges caused by acute hospital admissions. Hospital bed requirements for elective surgery could be better planned if it were possible to foresee upcoming peaks in severe respiratory illness admissions. Forecasting models can also guide the use of intervention strategies to decrease the spread of respiratory pathogens and thus prevent local health system overload. In this study, we explore the capability of forecasting models to predict the number of hospital admissions in Auckland, New Zealand, within a three-week time horizon. Furthermore, we evaluate probabilistic forecasts and the impact on model performance when integrating laboratory data describing the circulation of respiratory viruses. Methods The dataset used for this exploration results from active hospital surveillance, in which the World Health Organization Severe Acute Respiratory Infection (SARI) case definition was consistently used. This research nurse-led surveillance has been implemented in two public hospitals in Auckland and provides a systematic laboratory testing of SARI patients for nine respiratory viruses, including influenza, respiratory syncytial virus, and rhinovirus. The forecasting strategies used comprise automatic machine learning, one of the most recent generative pre-trained transformers, and established artificial neural network algorithms capable of univariate and multivariate forecasting. Results We found that machine learning models compute more accurate forecasts in comparison to naïve seasonal models. Furthermore, we analyzed the impact of reducing the temporal resolution of forecasts, which decreased the model error of point forecasts and made probabilistic forecasting more reliable. An additional analysis that used the laboratory data revealed strong season-to-season variations in the incidence of respiratory viruses and how this correlates with total hospitalization cases. These variations could explain why it was not possible to improve forecasts by integrating this data. Conclusions Active SARI surveillance and consistent data collection over time enable these data to be used to predict hospital bed utilization. These findings show the potential of machine learning as support for informing systems for proactive hospital management.

ObjectiveTo assess the clinical safety and tolerability of a novel MGO Manuka Honey microemulsion (MHME) eye cream for the management of blepharitis in human subjects.Methods and analysisTwenty-five healthy subjects were enrolled in a prospective, randomised, paired-eye, investigator-masked trial. The MHME eye cream (Manuka Health New Zealand) was applied to the closed eyelids of one eye (randomised) overnight for 2 weeks. LogMAR visual acuity, eyelid irritation symptoms, ocular surface characteristics and tear film parameters were assessed at baseline, day 7 and day 14. Expression of markers of ocular surface inflammation (matrix metalloproteinase-9 and interleukin-6) and goblet cell function (MUC5AC) were quantified using impression cytology at baseline and day 14.ResultsThere were no significant changes in visual acuity, eyelid irritation symptoms, ocular surface characteristics, tear film parameters and inflammatory marker expression during the 2-week treatment period in treated and control eyes (all p>0.05), and measurements did not differ significantly between eyes (all p>0.05). No major adverse events were reported. Two subjects experienced transient ocular stinging, presumably due to migration of the product into the eye, which resolved following aqueous irrigation.ConclusionThe MHME eye cream application was found to be well tolerated in healthy human subjects and was not associated with changes in visual acuity, ocular surface characteristics, tear film parameters, expression of markers of inflammation or goblet cell function. The findings support future clinical efficacy trials in patients with blepharitis.Trial registration numberACTRN12616000540415

ObjectiveTo evaluate the in vitro antimicrobial effects of cyclodextrin-complexed and uncomplexed Manuka honey on bacteria commonly associated with blepharitis, and in vivo rabbit eye tolerability of a cyclodextrin-complexed methylglyoxal (MGO) Manuka Honey microemulsion (MHME).Methods and analysis In vitro phase: Bacterial growth inhibition was assessed by area under the growth curve (AUC) for Staphylococcus aureus, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for S. aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa with cyclodextrin-complexed and uncomplexed Manuka honey were determined. In vivo phase: Six rabbits were administered 20 µL of MHME (at 1:10 dilution) to the right eye (treated) and 20 µL of saline to the left eye (control) daily, for 5 days. Tear evaporation, production, osmolarity, lipid layer, conjunctival hyperaemia and fluorescein staining were assessed daily, before and 15 min after instillation.Results In vitro phase: The relative AUC for cyclodextrin-complexed Manuka honey was lower than that of uncomplexed honey at both 250 and 550 mg/kg of MGO (both p <0.05). Cyclodextrin-complexed honey had lower MIC and MBC than uncomplexed honey for both S. aureus and S. epidermidis, but not P. aeruginosa. In vivo phase: No significant changes were observed in the parameters assessed in either treated or control eyes (all p >0.05).ConclusionOverall, antimicrobial potency of cyclodextrin-complexed Manuka honey was greater than uncomplexed honey. No significant immediate or cumulative adverse effects were observed with MHME application on rabbit eyes, supporting future conduct of clinical safety and tolerability trials in human subjects.

Objective To determine the repeatability limits of corneal tomography parameters in patients with advanced and moderately thin keratoconic corneas to assist in planning thickness-based procedural interventions. Methods Prospective, single-centre, repeatability study. Three tomography scans using the Pentacam AXL were obtained from patients with keratoconus with thinnest corneal thickness (TCT) ≦400 µm (sub-400 group) and compared to those with TCT = 450–500 µm (450-plus group). Eyes with previous crosslinking, intraocular surgery, or acute corneal hydrops were excluded. Eyes were age and gender-matched. The within-subject standard deviations for flat keratometry (K1), steep keratometry (K2), maximal keratometry (K max ), astigmatism and TCT were used to calculate respective repeatability limits (r). Intra-class correlation coefficients (ICC) were also analysed. Results The sub-400 group comprised 114 eyes from 114 participants, and the 450-plus group comprised 114 eyes from 114 participants. In the sub-400 group, TCT was amongst the least repeatable parameters (33.92 µm; ICC 0.96), compared with the 450-plus group (14.32 µm; ICC 0.99, p  < 0.01). In the sub-400 group, K1 and K2 of the anterior surface were the most repeatable parameters (r 3.79 and 3.22 respectively; ICC 0.97 and 0.98 respectively) compared with the 450-plus group (r 1.17 and 0.92 respectively; and ICC 0.98 and 0.99 respectively, p  < 0.01). Conclusions The repeatability of corneal tomography measurements is significantly reduced in sub-400 keratoconic corneas when compared to 450-plus corneas. Repeatability limits should be carefully considered when surgical interventions are planned for such patients.

IntroductionImprovements in diagnostic test accuracy across multiple pathogens have resulted in multi-viral point-of-care testing (POCT) via a rapid antigen test (RAT).AimThis study aimed to describe general practice practitioners’ reactions to a pilot respiratory virus surveillance programme during the SARS-CoV-2 pandemic, which enabled surveillance for influenza and other respiratory viruses alongside POCT for SARS-CoV-2.MethodsParticipating general practices collected viral swabs between May and December 2022. Nasopharyngeal swabs were taken for both an immediate COVID-19 RAT and a polymerase chain reaction (PCR) for testing SARS-CoV-2, influenza, respiratory syncytial virus (RSV) and other respiratory viruses. A questionnaire explored practitioners’ experiences and perceptions, addressing project setup, swabbing process and perceived overall value.ResultsOf 4135 swabbed patients, 54% were positive for one of the tested viruses. Involved nurses and doctors reported high adaptability to the swabbing process. Clinicians valued obtaining rapid diagnostic information for patient management and patient communication. While no significant barriers were identified, practitioners acknowledged additional time requirements and potential challenges with swabbing young children.DiscussionThe study demonstrated the feasibility and clinical utility of using POCT swabbing for immediate RAT and subsequent PCR testing for respiratory viruses in general practices when managing a viral pandemic. The data assisted in identifying community transmission of respiratory viruses, provided information for patient management and reinforced positive health messages about viral illnesses. The study suggests potential benefits for both individual patient care and population-based surveillance. The study also identified the potential value of multi-viral POCT testing via a RAT.

Biorepositories enable precision oncology research by sharing clinically annotated genomic data, but it remains unknown whether these data registries reflect the true distribution of cancers in racial and ethnic minorities. Our analysis of Project Genomics Evidence Neoplasia Information Exchange (GENIE), a real-world cancer data registry designed to accelerate precision oncology discovery, indicates that minorities do not have sufficient representation, which may impact the validity of studies directly comparing mutational profiles between racial/ethnic groups and limit generalizability of biomarker discoveries to all populations.

Deubiquitinating enzymes (DUBs) are an emerging drug target class of ~100 proteases that cleave ubiquitin from protein substrates to regulate many cellular processes. A lack of selective chemical probes impedes pharmacologic interrogation of this important gene family. DUBs engage their cognate ligands through a myriad of interactions. We embrace this structural complexity to tailor a chemical diversification strategy for a DUB-focused covalent library. Pairing our library with activity-based protein profiling as a high-density primary screen, we identify selective hits against 23 endogenous DUBs spanning four subfamilies. Optimization of an azetidine hit yields a probe for the understudied DUB VCPIP1 with nanomolar potency and in-family selectivity. Our success in identifying good chemical starting points as well as structure-activity relationships across the gene family from a modest but purpose-build library challenges current paradigms that emphasize ultrahigh throughput in vitro or virtual screens against an ever-increasing scope of chemical space. Deubiquitinases (DUBs) are key signaling enzymes, many of which lack selective inhibitors. Chan et al . pair a DUB-focused covalent library to mass spectrometry activity-based protein profiling, leading to selective hits against 23 endogenous DUBs and a first-in-class VCPIP1 probe with nanomolar potency.