The future of allergic rhinitis management: A partnership between healthcare professionals and patients.

Allergic rhinitis (AR) is a chronic respiratory condition that internationally continues to be burdensome and impacts quality of life. Despite availability of medicines and guidelines for healthcare providers for the optimal management of AR, optimisation of its management in the community continues to be elusive. The reasons for this are multi-faceted and include both environmental and healthcare related factors. One factor that we can no longer ignore is that AR management is no longer limited to the domain of healthcare provider and that people with AR make their own choices when choosing how to manage their condition, without seeking advice from a health care provider. We must build a bridge between healthcare provider knowledge and guidelines and patient decision-making. With this commentary, we propose that a shared decision-making approach between healthcare professionals and people with AR be developed and promoted, with a focus on patient health literacy. As custodians of AR knowledge, we have a responsibility to ensure it is accessible to those that matter most-the people with AR.

NF1 deficiency drives metabolic reprogramming in ER+ breast cancer.

OBJECTIVE: NF1 is a tumor suppressor gene and its protein product, neurofibromin, is a negative regulator of the RAS pathway. NF1 is one of the top driver mutations in sporadic breast cancer such that 27 % of breast cancers exhibit damaging NF1 alterations. NF1 loss-of-function is a frequent event in the genomic evolution of estrogen receptor (ER)+ breast cancer metastasis and endocrine resistance. Individuals with Neurofibromatosis type 1 (NF) - a disorder caused by germline NF1 mutations - have an increased risk of dying from breast cancer [1-4]. NF-related breast cancers are associated with decreased overall survival compared to sporadic breast cancer. Despite numerous studies interrogating the role of RAS mutations in tumor metabolism, no study has comprehensively profiled the NF1-deficient breast cancer metabolome to define patterns of energetic and metabolic reprogramming. The goals of this investigation were (1) to define the role of NF1 deficiency in estrogen receptor-positive (ER+) breast cancer metabolic reprogramming and (2) to identify potential targeted pathway and metabolic inhibitor combination therapies for NF1-deficient ER + breast cancer. METHODS: We employed two ER+ NF1-deficient breast cancer models: (1) an NF1-deficient MCF7 breast cancer cell line to model sporadic breast cancer, and (2) three distinct, Nf1-deficient rat models to model NF-related breast cancer [1]. IncuCyte proliferation analysis was used to measure the effect of NF1 deficiency on cell proliferation and drug response. Protein quantity was assessed by Western Blot analysis. We then used RNAseq to investigate the transcriptional effect of NF1 deficiency on global and metabolism-related transcription. We measured cellular energetics using Agilent Seahorse XF-96 Glyco Stress Test and Mito Stress Test assays. We performed stable isotope labeling and measured [U-13C]-glucose and [U-13C]-glutamine metabolite incorporation and measured total metabolite pools using mass spectrometry. Lastly, we used a Bliss synergy model to investigate NF1-driven changes in targeted and metabolic inhibitor synergy. RESULTS: Our results revealed that NF1 deficiency enhanced cell proliferation, altered neurofibromin expression, and increased RAS and PI3K/AKT pathway signaling while constraining oxidative ATP production and restricting energetic flexibility. Neurofibromin deficiency also increased glutamine influx into TCA intermediates and dramatically increased lipid pools, especially triglycerides (TG). Lastly, NF1 deficiency alters the synergy between metabolic inhibitors and traditional targeted inhibitors. This includes increased synergy with inhibitors targeting glycolysis, glutamine metabolism, mitochondrial fatty acid transport, and TG synthesis. CONCLUSIONS: NF1 deficiency drives metabolic reprogramming in ER+ breast cancer. This reprogramming is characterized by oxidative ATP constraints, glutamine TCA influx, and lipid pool expansion, and these metabolic changes introduce novel metabolic-to-targeted inhibitor synergies.

The impact of implementing an allergic rhinitis clinical management pathway (AR-CMaP) in the community pharmacy.

Background: The Allergic Rhinitis Clinical Management Pathway (AR-CMaP) was developed to overcome the challenge of implementing current AR guidelines in the Australian community pharmacy practice and support pharmacists in optimally managing patients' AR. Objectives: To evaluate the impact of AR-CMaP on patients' behaviour and pharmacists' needs in managing AR in the pharmacy. Methods: This study used a cross-sectional, pre-post study design in which the primary outcome was the appropriateness of medications purchased from community pharmacies in Australia. Patient data were collected before and after the implementation of AR-CMaP. Pharmacist needs were recorded before and after AR-CMaP training. Data were analysed descriptively. Results: Six pharmacies, 19 pharmacists and a total of 416 patients were included in the study; 206 pre-AR-CMaP implementation and 210 post-AR-CMaP implementation. Pre-AR-CMaP, 22.4% of patients purchased appropriate AR medication compared with 29.0% post-AR-CMaP implementation. Over half the patient cohort (52%) consulted a pharmacist pre-AR-CMaP and 37% consulted a pharmacist post-AR-CMaP implementation. Post-AR-CMaP, pharmacists reported increased awareness of barriers such as patients' lack of time, patients' perceptions about the pharmacist's role and patient choice to self-manage. Pharmacists also rated an increased desire to interact with other health care providers (HCPs) in caring for patients with AR. Conclusions: While there was a non-statistically significant increase in the proportion of patients purchasing optimal AR medication, AR-CMaP did empower patients to self-select their own medication without further detriment. Moreover, following the implementation of AR-CMaP, pharmacists developed a greater awareness of their role in AR management, exemplified by their increased desire to be actively involved in AR management and increased interaction with other HCPs. Future research needs to explore more effective tools to support pharmacists' clinical decision-making and target patients' self-selection of AR medications. This study highlights that there is an ingrained self-reliance of AR decision-making that has become a habit for people living with AR.

Uncovering the Burden of Rhinitis in Patients Purchasing Nonprescription Short-Acting ß-Agonist (SABA) in the Community.

Asthma and rhinitis are common comorbidities that amplify the burden of each disease. They are both characterized by poor symptom control, low adherence to clinical management guidelines, and high levels of patient self-management. Therefore, this study aims to investigate the prevalence of self-reported rhinitis symptoms in people with asthma purchasing Short-Acting Beta Agonist (SABA) reliever medication from a community pharmacy and compare the medication-related behavioral characteristics among those who self-report rhinitis symptoms and those who do not. Data were analyzed from 333 people with asthma who visited one of eighteen community pharmacies in New South Wales from 2017-2018 to purchase SABA and completed a self-administered questionnaire. Participants who reported rhinitis symptoms (71%), compared to those who did not, were significantly more likely to have coexisting gastroesophageal reflux disease (GERD), overuse SABA, and experience side effects. They may have been prescribed daily preventer medication but forget to take it, and worry about its side effects. They were also more likely to experience moderate-to-severe rhinitis (74.0%), inaccurately perceive their asthma as well-controlled (50.0% self-determined vs. 14.8% clinical-guideline defined), and unlikely to use rhinitis medications (26.2%) or daily preventer medication (26.7%). These findings enhance our understanding of this cohort and allow us to identify interventions to improve patient outcomes.

Management of allergic rhinitis symptoms in the pharmacy Pocket guide 2022.

Background: Allergic rhinitis (AR) management requires a coordinated effort from healthcare providers and patients. Pharmacists are key members of these integrated care pathways resolving medication-related problems, optimizing regimens, improving adherence and recommending therapies while establishing liaisons between patients and physicians. Methods: Allergic Rhinitis and its Impact on Asthma (ARIA) first published a reference document on the pharmacist's role in allergic rhinitis management in 2004. Several guidelines were developed over the past 20 years improving the care of allergic rhinitis patients through an evidence-based, integrated care approach. Results: This ARIA/EAACI/FIP Position Paper is based on the latest ARIA in the Pharmacy guidelines and provides: (a) a structured approach to pharmacists identifying people with AR and/or allergic conjunctivitis as well as those at risk of poor disease control; (b) an evidence-based clinical decision support tool for optimising the management of allergic rhinitis in the community pharmacy; and (c) a framework of referral to the physician. Conclusion: This document is not intended to be a mandatory standard of care but is provided as a basis for pharmacists and their staff to develop relevant local standards of care for their patients, within their local practice environment. Pharmacy care varies between countries, and the guide should be adapted to the local situation.

Exploring General Practitioners' Preferences and Experience with Respiratory Inhaler Devices.

INTRODUCTION: Correct inhaler technique is essential for the optimal delivery of inhaled medicines and the successfully management of respiratory conditions. The general practitioner (GP), the prescriber of inhaled medicines, plays a crucial role in educating patients on inhaler technique. However, in the real-world setting, there are barriers. For the GP, it is time and competence and for the patient, it is their ability to recognise inhaler technique as an issue and their ability to maintain correct inhaler technique over time. This study aimed to determine GPs' experience, skills and priority placed on inhaler technique and to identify factor(s) associated with inhaler technique competence. METHODS: This cross-sectional observational study design surveyed GPs' perspectives on inhaler use and preferences for inhaler prescribing within their practice setting. GP inhaler technique was assessed. GPs were recruited through an established network of GP practices. Data collected include (i) practice demographics, (ii) inhaler technique opinions and experience, (iii) inhaler prescribing preferences and (iv) inhaler education history data. Data were analysed descriptively and multivariate logistic regression modelling was used to explore the relationship between outcomes and GPs' ability to use devices correctly. RESULTS: A total of 227 GPs completed the inhaler survey. Sixty-three percent of GPs reported receiving previous inhaler education and 73.3% educated or checked their patients' inhaler technique; 64.5% felt they were somewhat competent in doing so. GPs who reported not demonstrating inhaler technique believed that a pharmacist or a practice nurse would do so. When prescribing new inhaler devices, GPs considered the disease being treated first and then patient's experience with inhalers; they often already have an inhaler preference and this was related to familiarity and perceived ease of use. For GPs, inhaler competence was not associated with their previous inhaler education or the priority placed on inhaler technique. CONCLUSION: GPs do recognise the importance of inhaler technique in respiratory management but their technique can be better supported with regular educational updates to inform them about new inhalers and management practices and to support appropriate inhaler choices for their patients.

Detection of Early Onset Carnitine Palmitoyltransferase II Deficiency by Newborn Screening: Should CPT II Deficiency Be a Primary Disease Target?

Early-onset carnitine palmitoyltransferase II deficiency (CPT II deficiency) (OMIM 600650) can result in severe outcomes, which are often fatal in the neonatal to infantile period. CPT II deficiency is a primary target in the Maritime Newborn Screening Program. We report a case of neonatal-onset CPT II deficiency identified through expanded newborn screening with tandem mass spectrometry. Identification through newborn screening led to early treatment interventions, avoidance of metabolic decompensation, and a better clinical outcome. Newborn screening for CPT II deficiency is highly sensitive and specific with no false positives identified. The only screen positive case detected identified a true positive case. This experience illustrates the importance of newborn screening for CPT II deficiency and demonstrates why reconsideration should be taken to add this disease as a primary newborn screening target.