Capital and Coast District Health Board

Purpose Non-functioning pituitary adenomas (NFPA) are one of the most frequent pituitary adenoma subtypes, yet dedicated management guidelines do not exist. This study aimed to characterise real-world clinical decision-making across the spectrum of NFPA presentations and to identify areas of practice conformity versus heterogeneity within and between specialty groups.Methods A cross-sectional, anonymous electronic survey was administered to endocrinologists, neurosurgeons, ENT surgeons, and radiation oncologists involved in pituitary adenoma care in Australia and New Zealand between January and April 2025. Three clinical scenarios were presented: an incidental microadenoma, an incidental asymptomatic macroadenoma, and a symptomatic macroadenoma with visual compromise. Concordance was defined as greater than 70% agreement on a single response within any group.Results A total of 145 clinicians completed the survey (99 endocrinologists, 31 surgeons, 15 radiation oncologists). Areas of conformity included broad anterior pituitary hormonal evaluation, conservative management of incidental asymptomatic macroadenomas, and active intervention for symptomatic disease with visual loss. Significant heterogeneity was identified in ophthalmological assessment, repeat imaging intervals, post-operative MRI and visual field timing, and multidisciplinary team (MDT) meeting referral rates. Compared to general endocrinologists, pituitary subspecialty endocrinologists were significantly more likely to refer patients for MDT discussion and know the caseload of the surgeon to whom they were referring, and less likely to measure serum cortisol immediately post-operatively.Conclusion This survey identifies clinically important variation in NFPA management, concentrated in domains lacking guideline recommendations. These findings highlight the need for dedicated NFPA guidelines spanning the full spectrum of NFPA presentations.

BACKGROUND:Biologics are generally reserved for severe asthma (SA) after standard treatments have failed. Their recommendation is based on randomized controlled trials, designed to assess efficacy but not the optimal timing for biologic initiation. RESEARCH QUESTION:Does the timing of biologic initiation affect SA outcomes, including remission? STUDY DESIGN AND METHODS:This was a cohort study using data from the International Severe Asthma Registry, the CHRONICLE US SA registry, and the UK Optimum Patient Care Research Database, together comprising data from 26 countries. The duration of time to biologic initiation was described using several proxies (e.g., duration of asthma, potential SA [PSA], lung function impairment, and frequent exacerbations, all pre-biologic). The associations between these proxies and clinical remission, exacerbations, asthma control, lung function, and oral corticosteroid (OCS) use were assessed. RESULTS:9,241 patients were included in the association analyses. Overall, the likelihood of achieving improvement in each outcome post-biologic decreased with increasing time-to-biologic-initiation. The odds of achieving clinical remission 12-months post-biologic initiation were reduced for every 10 years patients had asthma pre-biologic (0.86 [0.84, 0.88], PSA (0.78 [0.63, 0.96]), and lung function impairment (0.24 [ 0.21, 0.28]) and for every 10 grams lifetime cumulative OCS dose (0.54 [0.30, 0.98]). For every 10-years patients had PSA pre-biologic, post-biologic exacerbation rates were 1.08 [1.03, 1.13] times higher, lung function improvement was 2.35% [-3.18, -1.51] less, and the odds of having well- or partly-controlled asthma was 12% lower (0.88 [0.53, 1.47]). INTERPRETATION:Earlier initiation of biologics in individuals with SA is associated with better clinical outcomes, suggesting the need to modify approaches to asthma management from a 'reserve' to a 'preserve' approach: i.e., not reserving biologics for those with long-standing SA, instead preserving patients' lung function and possibly increasing the likelihood of better clinical outcomes with earlier biologic initiation. CLINICAL TRIAL REGISTRATION:CHRONICLE - ClinicalTrials.gov identifier: NCT03373045.

BACKGROUND:Asthma with low levels of type 2 (T2) biomarkers is poorly understood. OBJECTIVE:To characterize severe asthma phenotypes and compare changes in asthma outcomes from pre- to postbiologic treatment along a gradient of T2 involvement. METHODS:This was a registry-based cohort study including data from 24 countries. Biomarker distribution (blood eosinophil count, fractional exhaled nitric oxide, and IgE) was quantified before biologic initiation. Clusters were identified using a 5-component Gaussian finite mixture model and phenotypically characterized. Changes in asthma and health care utilization outcomes between 1-year pre- and postbiologic initiation were compared between clusters and by biologic class. RESULTS:Among 3675 patients, 5 biomarker clusters were identified along a gradient of T2 involvement: cluster A with the lowest T2 involvement (16.4%), cluster B (20.4%), cluster C (22.9%), cluster D (30.3%), and cluster E with the highest T2 involvement (10.0%). In multivariable analysis, biologic use was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. For example, patients in cluster C had a significantly greater increase in forced expiratory volume in 1 second compared with cluster A (difference 0.16 L [95% confidence interval: 0.08, 0.25]; P < .001). The odds of uncontrolled asthma were approximately 0.6 for all clusters compared with cluster A. Overall, exacerbation rates were lower, and greater improvements in lung function and asthma control were noted for anti-IL-5/5 receptor (R) (but not anti-IgE or anti-IL-4Rα) for all clusters compared with cluster A. CONCLUSION:T2-targeting biologics have utility in the management of asthma with low T2 involvement, but more effective therapies are needed. Further research is warranted to identify specific pathogenic pathways at the lower end of the T2 spectrum that can be effectively targeted by biologics.

The transplanting of juvenile and adult mussels onto soft sediments is an emerging technique for the ecological restoration of the biogenic habitat formed by mussels. While these habitats are often found within estuarine systems, the spatial suitability of these environments for restoration is poorly described. The dynamic and variable environmental conditions characteristic of estuaries could represent challenges to the persistence of restored mussel beds. To assess whether there are spatial differences in mussel responses to transplantation within an estuarine environment, six experimental mussel beds of adult green-lipped mussels (Perna canaliculus) were established along an environmental gradient in a small estuarine harbour in northern New Zealand. Transplanted mussel beds were sampled immediately after installation and again at 3 and 9 months later. Minor differences in the density, length and condition index of mussels were identified among the six sites over the course of the study; however, their responses were typically similar across sites. These results suggest that these mussels have the capacity to establish themselves within estuarine environments and that their subsequent performance once transplanted onto the seafloor appears to be determined by other site-specific factors, such as the presence of predators and the degree of exposure to storm waves.

BACKGROUND:Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS:Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS:5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS:Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.