New South Wales Department of Health

Pancreatic ductal adenocarcinoma (PDAC) remains highly resistant to treatment, with mortality rates largely unchanged despite advances in cancer therapies. For ∼80% of borderline, non-resectable, or metastatic cases, chemotherapy is predominantly palliative, underscoring the need for improved drug delivery approaches. This study presents the development, characterization and in vivo evaluation of a novel polymeric implant loaded with 5-fluorouracil, irinotecan, and oxaliplatin (FIRINOX). Scanning electron microscopy of FIRINOX implants showed internal microstructure was preserved upon drug loading, while micro-CT and X-ray imaging revealed valuable insights into the morphology and degradation of implants retrieved from in vivo experiments. In murine PDAC models, dose-escalation identified 4 × FIRINOX implants as the maximum tolerated dose, while 2 × implants achieved significant therapeutic efficacy at lower doses than IV administration, without compromising animal safety. In healthy pigs, 20 × FIRINOX implants were well-tolerated, as confirmed by histopathology and blood analysis. Finally, laser ablation-inductively coupled plasma-mass spectrometry imaging and microbiome analysis confirmed localized drug perfusion within tissues, and minimal off-target effects, including preservation of gut microbiota diversity. These findings support the potential of this implantable platform to improve outcomes in borderline or non-resectable PDAC and enhance tolerability of cytotoxic chemotherapy through localized, controlled delivery, addressing a key gap where current treatment options are limited.

SummaryNewborn screening (NBS) for spinal muscular atrophy (SMA) enables rapid diagnosis and pre-symptomatic treatment of infants with bi-allelic SMN1 deletions. Standard PCR-based assays detect ∼95% of cases by identifying the absence of SMN1 exon 7; however, rare sequence variants can escape detection. We describe two newborns (in Germany and Australia) identified by NBS as lacking SMN1 but subsequently shown to carry a single SMN1 copy—with no SMN2 in P1 and one SMN2 copy in P2. Gene-specific long-range PCR and Sanger sequencing revealed two distinct 4-bp deletions in SMN1 exon 7 (c.855_858delAGAA [p.Arg288AlafsTer5] in P1 and c.861_864delAAGG [p.Arg288AlafsTer5] in P2). Both variants disrupt the reverse primer-binding site used in NBS assays and cause the same frameshift p.Arg288AlafsTer5, predicted to be deleterious. A plethora of assays demonstrated preserved exon 7 splicing, markedly reduced SMN protein abundance, and wild-type-like protein thermostability. In vivo, expression of the p.Arg288AlafsTer5 protein in zebrafish fully rescued the progressive motor and survival defects of smn1-deficient mutants. These findings raise the possibility that this novel SMN isoform has enhanced functional efficiency relative to the wild type. Population data (gnomAD) suggest that ∼800 individuals of European ancestry may carry these variants in trans with an SMN1 deletion, yet none have been reported with SMA. Based on our data, no therapy was initiated. Both children remain healthy at 24 months of age, avoiding >US$4 million in potential treatment costs. These findings challenge the assumption that complete loss of full-length SMN invariably causes SMA and suggest that very low levels of this novel SMN isoform can sustain normal motor development.

This cross-sectional study assesses the potential impact of a smartwatch hypertension notification feature for US adults who have not been diagnosed with hypertension.

Multiple sessions of walking with blood flow restriction (BFR) of the legs can improve cardiovascular fitness, muscle strength and hypertrophy in older adults. However, it is unclear whether BFR impairs walking balance acutely, potentially increasing falls risk during BFR training for this at-risk population. Does bilateral BFR of the legs acutely worsen walking balance of older adults? Ten older adults (mean age: 73, SD: 3 y) walked for 10 min on a treadmill at 50 %, 60 % and 70 % of their fast walking speed, with 10 cm-wide cuffs on the proximal thigh of both legs inflated to 0 % (no cuff), 40 % or 60 % of arterial occlusion pressure. We measured four characteristics of walking balance which were selected a priori and combined into a gait quality index predictive of future falls in older adults: autocorrelation of vertical accelerations; magnitude and harmonicity of sideways accelerations; and magnitude of the dominant period of forwards accelerations. Walking balance worsened with BFR, independent of walking speed, for all outcomes except the magnitude of the dominant period of forwards accelerations, with worse balance observed with increasing cuff pressure. Compared to no BFR, gait quality declined 12 % when walking with 50 % occlusion and declined 20 % with 60 % occlusion (p < 0.001). Our findings suggest that BFR results in poorer acute walking balance, with a dose-response relationship for cuff pressure. Supervised walking trials are warranted to further assess the safety of BFR training in community settings and whether these balance-related changes may stimulate beneficial chronic balance adaptations.

Timely, accurate reporting of pregnancy vaccination coverage is key to evaluating pregnancy immunisation programs. We compared influenza and pertussis vaccination reporting on the New South Wales (NSW) Perinatal Data Collection (PDC) and the Australian Immunisation Register (AIR) to understand coverage, reporting, timing of vaccination and provider type. This retrospective population-based cohort study in NSW, Australia, included people giving birth at ≥20 weeks gestation (2017-2022) on the NSW PDC (total number of pregnancies 555,553), linked to AIR-reported influenza and pertussis vaccinations. The main outcomes of interest were influenza and pertussis coverage according to: (1) the PDC; and (2) linked AIR records. We assessed agreement between data sources (i.e. whether an AIR record during the pregnancy existed if vaccine receipt was reported on the PDC, and vice versa) by year (influenza: 2021-2022, pertussis: 2017-2022) and selected characteristics (2022). Provider type and timing for vaccinations reported to the AIR are described (2022). PDC-reported influenza and pertussis coverage peaked in 2020 (influenza: 58.8%, pertussis: 79.0%), decreasing thereafter (influenza: 49.1%, pertussis: 77.6% in 2022). AIR-reported influenza and pertussis vaccination coverage increased (influenza: 34.7% in 2021 to 44.8% in 2022; pertussis: 24.4% in 2017 to 51.6% in 2022). Agreement between the AIR and PDC improved over time but remained suboptimal (influenza: 75.5%, pertussis: 56.6% in 2022). AIR and PDC agreement differed most by antenatal care model, particularly for pertussis vaccinations. In 2022, of pregnancy vaccinations reported to the AIR, >75% were provided in general practices. Co-administration occurred infrequently (8.8%). Despite mandated reporting to the AIR, there was significant underreporting of pregnancy vaccinations to the AIR when compared with the NSW PDC. National collection of accurate and timely data on pregnancy vaccination coverage is needed to monitor vaccine uptake, and identify and monitor strategies to improve uptake, particularly with the new pregnancy respiratory syncytial virus vaccine program in 2025. We identified co-administration as a potential strategy to improve influenza vaccination coverage during pregnancy.

The National Neisseria Network (NNN), Australia, established in 1979, comprises reference laboratories in each state and territory. Since 1981, the NNN has reported data for the Australian Gonococcal Surveillance Programme (AGSP), on antimicrobial susceptibility profiles for Neisseria gonorrhoeae isolated from each jurisdiction for an agreed group of agents. The antibiotics reported represent current or potential agents used for the treatment of gonorrhoea, and include ceftriaxone, azithromycin, ciprofloxacin and penicillin. More recently, gentamicin and tetracycline are included in the AGSP Annual Report. Ceftriaxone, combined with azithromycin, is the recommended treatment regimen for gonorrhoea in Australia. Historically, there were substantial geographic differences in susceptibility patterns across the country, with certain remote regions of the Northern Territory and Western Australia having low gonococcal antimicrobial resistance rates. In these regions, an oral treatment regimen comprising amoxycillin, probenecid, and azithromycin was recommended. However, since January 2023, increasing reports of penicillin-resistant N. gonorrhoeae in the Northern Territory have changed treatment recommendations to align with the majority of Australia.1Additional data on other antibiotics are reported in the AGSP Annual Report. The AGSP has a programme-specific quality assurance process.