Associations between gender and health-related quality of life in people with IgE-mediated food allergy and their caregivers: A systematic review.

OBJECTIVE: Understanding factors that impact health-related quality of life (HRQL) is essential to inform personalised food allergy management. However, there are inconsistencies about the impact of gender on HRQL in food allergy. This review aimed to collate all investigations of the association between gender and total or subdomain HRQL scores of individuals with food allergy and their caregivers. DESIGN: This is a narrative systematic review. We descriptively synthesised and compared HRQL outcomes by participant and parent genders according to statistical and clinical significance. Study quality was assessed using the ROBINS-I, inclusive of all domains. Sensitivity analysis of non-interventional studies was conducted using the ROBINS-E. DATA SOURCES: A systematic search of Medline and Embase databases was conducted on 4 April 2022 and updated on 5 December 2023. ELIGIBILITY CRITERIA: Studies were eligible for inclusion if they reported original data on the association between any sex and/or gender and HRQL, as measured with any validated instrument, in populations with IgE-mediated food allergy. Interventional and non-interventional studies were eligible. RESULTS: A comparison of 34 eligible studies (10 interventional and 24 non-interventional) indicated females with food allergy (62.5% of studies of children, 83.3% of studies of adults) and mothers of children with food allergy (50% of studies of caregivers) experienced poorer self-reported baseline HRQL than their counterparts, notably in domains of physical, emotional or food anxiety-related well-being. Gender differences in child HRQL after food allergen immunotherapy were observed. However, selective reporting in included interventional studies meant the direction of this association could not be determined. The proxy-reported total HRQL of participants was not affected by caregiver gender, nor was caregiver HRQL likely impacted by child gender. CONCLUSIONS: Gender should be considered an important modifier of participant HRQL outcomes in food allergy studies. Purposeful exploration of HRQL in all genders is needed to fully understand the implications of this construct on the lived experience of food allergy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42022329901).

Cost-Effectiveness of Screening Strategies for Familial Hypercholesterolaemia: An Updated Systematic Review.

BACKGROUND: OBJECTIVE: This study aimed to systematically synthesise the cost-effectiveness of screening strategies to detect heterozygous familial hypercholesterolemia (FH). METHODS: We searched seven databases from inception to 2 February , 2023, for eligible cost-effective analysis (CEA) that evaluated screening strategies for FH versus the standard care for FH detection. Independent reviewers performed the screening, data extraction and quality evaluation. Cost results were adapted to 2022 US dollars (US$) to facilitate comparisons between studies using the same screening strategies. Cost-effectiveness thresholds were based on the original study criteria. RESULTS: A total of 21 studies evaluating 62 strategies were included in this review, most of the studies (95%) adopted a healthcare perspective in the base case, and majority were set in high-income countries. Strategies analysed included cascade screening (23 strategies), opportunistic screening (13 strategies), systematic screening (11 strategies) and population-wide screening (15 strategies). Most of the strategies relied on genetic diagnosis for case ascertainment. The most common comparator was no screening, but some studies compared the proposed strategy versus current screening strategies or versus the best next alternative. Six studies evaluated screening in children while the remaining were targeted at adults. From a healthcare perspective, cascade screening was cost-effective in 78% of the studies [cost-adapted incremental cost-effectiveness ratios (ICERs) ranged from dominant to 2022 US$ 104,877], opportunistic screening in 85% (ICERs from US$4959 to US$41,705), systematic screening in 80% (ICERs from US$2763 to US$69,969) and population-wide screening in 60% (ICERs from US$1484 to US$223,240). The most common driver of ICER identified in the sensitivity analysis was the long-term cost of lipid-lowering treatment. CONCLUSIONS: Based on reported willingness to pay thresholds for each setting, most CEA studies concluded that screening for FH compared with no screening was cost-effective, regardless of the screening strategy. Cascade screening resulted in the largest health benefits per person tested.

Lipid-Lowering Strategies for Primary Prevention of Coronary Heart Disease in the UK: A Cost-Effectiveness Analysis.

AIM: We aimed to assess the cost effectiveness of four different lipid-lowering strategies for primary prevention of coronary heart disease initiated at ages 30, 40, 50, and 60 years from the UK National Health Service perspective. METHODS: We developed a microsimulation model comparing the initiation of a lipid-lowering strategy to current standard of care (control). We included 458,692 participants of the UK Biobank study. The four lipid-lowering strategies were: (1) low/moderate-intensity statins; (2) high-intensity statins; (3) low/moderate-intensity statins and ezetimibe; and (4) inclisiran. The main outcome was the incremental cost-effectiveness ratio for each lipid-lowering strategy compared to the control, with 3.5% annual discounting using 2021 GBP (£); incremental cost-effectiveness ratios were compared to the UK willingness-to-pay threshold of £20,000-£30,000 per quality-adjusted life-year. RESULTS: The most effective intervention, low/moderate-intensity statins and ezetimibe, was projected to lead to a gain in quality-adjusted life-years of 0.067 per person initiated at 30 and 0.026 at age 60 years. Initiating therapy at 40 years of age was the most cost effective for all lipid-lowering strategies, with incremental cost-effectiveness ratios of £2553 (95% uncertainty interval: 1270, 3969), £4511 (3138, 6401), £11,107 (8655, 14,508), and £1,406,296 (1,121,775, 1,796,281) per quality-adjusted life-year gained for strategies 1-4, respectively. Incremental cost-effectiveness ratios were lower for male individuals (vs female individuals) and for people with higher (vs lower) low-density lipoprotein-cholesterol. For example, low/moderate-intensity statin use initiated from age 40 years had an incremental cost-effectiveness ratio of £5891 (3822, 9348), £2174 (772, 4216), and was dominant (i.e. cost saving; -2,760, 350) in female individuals with a low-density lipoprotein-cholesterol of ≥ 3.0, ≥ 4.0 and ≥ 5.0 mmol/L, respectively. Inclisiran was not cost effective in any sub-group at its current price. CONCLUSIONS: Low-density lipoprotein-cholesterol lowering from early ages is a more cost-effective strategy than late intervention and cost effectiveness increased with the increasing lifetime risk of coronary heart disease.

Interaction Between Baseline Participant Factors and Treatment Effects Following Peanut Oral Immunotherapy.

BACKGROUND: The Probiotic Peanut Oral Immunotherapy-003 multicenter randomized trial found that both probiotic peanut oral immunotherapy (PPOIT) and peanut OIT alone (OIT) were effective compared with placebo in inducing clinical remission after 18 months of treatment, and improving health-related quality of life (HRQL) at 12 months after treatment. Understanding treatment effect modifiers can optimize outcomes through precision care. OBJECTIVES: This post hoc study examined baseline clinical and demographic participant factors that modified treatment effects. METHODS: The study sample included 201 children (aged 1-10 years) with challenge-confirmed peanut allergy. Exposure variables were baseline clinical and demographic factors. Outcomes were remission (double-blind, placebo-controlled food challenge, cumulative 4,950-mg peanut protein at 8 weeks after treatment) and HRQL (change in Food Allergy Quality of Life Questionnaire-Parent Form score). Interactions between baseline factors and treatment effects on remission and HRQL were explored with regression models. RESULTS: A higher degree of peanut sensitivity (large peanut skin prick test, high peanut specific IgE, and low reaction-eliciting dose at study entry challenge) and other concurrent allergic conditions (multiple food allergies, asthma, or wheeze) were associated with the decreased likelihood of attaining remission after both PPOIT and OIT treatment. History of anaphylaxis was associated with the reduced likelihood of remission after PPOIT compared with OIT. For the HRQL outcome, there was evidence that sex, history of anaphylaxis, and age modified treatment effects. CONCLUSIONS: Baseline participant factors modify PPOIT and OIT effects on remission and HRQL. Considering modifiers of treatment effect during participant selection may optimize treatment success and clinical trial design toward specific outcomes, such as the achievement of remission.

Cost-effectiveness analysis of probiotic peanut oral immunotherapy (PPOIT) versus placebo in Australian children with peanut allergy alongside a randomised trial.

OBJECTIVE: To compared the cost-effectiveness of coadministration of a probiotic adjuvant with peanut oral immunotherapy (PPOIT) with placebo (no treatment) in children with peanut allergy. DESIGN: Prospectively planned cost-effectiveness analysis alongside a randomised control trial. SETTING: The Royal Children's Hospital, Melbourne, Australia. PARTICIPANTS: 56 children with peanut allergy aged 1-10 years at recruitment. INTERVENTION: A daily dose of probiotic Lactobacillus rhamnosus CGMCC 1.3724 (NCC4007) and peanut oral immunotherapy administered for 1.5 years. MAIN OUTCOMES MEASURES: Costs were considered from a healthcare system perspective and included costs of treatment delivery and adverse events. Effectiveness outcomes included rate of sustained unresponsiveness (SU) and quality-adjusted life years (QALYs). The cost-effectiveness of PPOIT versus placebo was analysed using patient-level data. Time horizon was 10 years from commencement of PPOIT treatment, comprising 1.5 years of treatment (actual data), 4 years of post-treatment follow-up (actual data), and 4.5 years of extrapolation thereafter (modelling). RESULTS: Healthcare cost per patient over 10 years was higher for PPOIT compared with placebo ($A9355 vs $A1031, p<0.001). Over half of the per patient healthcare cost (53%) in the PPOIT group was attributable to treatment delivery, while the remaining cost was attributable to adverse events. Both measures of effectiveness were superior in the PPOIT group: the average SU rate over 10 years was 54% for PPOIT versus 6% for placebo (p<0.001); QALYs over 10 years were 9.05 for PPOIT versus 8.63 for placebo (p<0.001). Overall, cost per year of SU achieved was $A1694 (range $A1678, $A1709) for PPOIT compared with placebo, and cost per additional QALY gained was $A19 386 (range $A19 024, $A19 774). CONCLUSIONS: Cost per QALY gained using PPOIT compared with no treatment is approximately $A20 000 (£10 000) and is well below the conventional value judgement threshold of $A50 000 (£25 000) per QALY gained, thus deemed good value for money ($A1= £0.5 approximately). TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12608000594325; Post-results.

Sea stars resist wasting through active immune and collagen systems.

Epidemics are becoming more common and severe, however, pinpointing the causes can be challenging, particularly in marine environments. The cause of sea star wasting (SSW) disease, the ongoing, largest known panzootic of marine wildlife, is unresolved. Here, we measured gene expression longitudinally of 24 adult Pisaster ochraceus sea stars, collected from a recovered site, as they remained asymptomatic (8 individuals) or naturally progressed through SSW (16 individuals) in individual aquaria. Immune, tissue integrity and pro-collagen genes were more highly expressed in asymptomatic relative to wasting individuals, while hypoxia-inducible factor 1-α and RNA processing genes were more highly expressed in wasting relative to asymptomatic individuals. Integrating microbiome data from the same tissue samples, we identified genes and microbes whose abundance/growth was associated with disease status. Importantly, sea stars that remained visibly healthy showed that laboratory conditions had little effect on microbiome composition. Lastly, considering genotypes at 98 145 single-nucleotide polymorphism, we found no variants associated with final health status. These findings suggest that animals exposed to the cause(s) of SSW remain asymptomatic with an active immune response and sustained control of their collagen system while animals that succumb to wasting show evidence of responding to hypoxia and dysregulation of RNA processing systems.

Association of Reaction Symptoms and Eliciting Dose With Health-Related Quality of Life in Children With Peanut Allergy.

BACKGROUND: Food allergy adversely affects the health-related quality of life (HRQoL) of patients. It is unclear whether factors such as the reaction eliciting dose (ED) and the nature of allergic reaction symptoms affect HRQoL. OBJECTIVE: To explore associations between reaction ED or the nature of allergic symptoms and HRQoL among children with peanut allergy. METHODS: This study was a secondary analysis of baseline data from the PPOIT-003 randomized trial in 212 children aged 1 to 10 years with challenge-confirmed peanut allergy. Children's past reaction symptoms were collected by clinicians during screening. Associations between variables of interest and parent-reported child-proxy HRQoL were examined by univariable and multivariable linear regression. RESULTS: Mean age of study participants was 5.9 years; 63.2% were male. Children with a low reaction ED of 80 mg peanut protein had significantly poorer HRQoL (ß = -0.81; 95% CI, -1.61 to -0.00; P = .049) compared with children with a high ED of 2,500 mg peanut protein. Gastrointestinal symptoms (ß = 0.45; 95% CI, 0.03-0.87; P = .037), lower airway symptoms (ß = 0.46; 95% CI, 0.05-0.87; P = .030), multisystem involvement (ß = 0.71; 95% CI, 0.25-1.16; P = .003), or anaphylaxis (ß = 0.46; 95% CI, 0.04-0.87; P = .031) during a previous reaction were associated with worse HRQoL. CONCLUSIONS: Peanut-allergic children with a lower allergen reaction threshold experienced a greater negative HRQoL impact compared with children with higher reaction thresholds. In addition, specific past allergic reaction symptoms were associated with comparatively worse HRQoL. Children experiencing these symptoms and those with lower reaction ED require increased clinical support to manage the food allergy and are likely to benefit from interventions that can improve HRQoL.

Enhancing the Detection and Care of Heterozygous Familial Hypercholesterolemia in Primary Care: Cost-Effectiveness and Return on Investment.

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is under-detected and undertreated. A general practitioner-led screening and care program for HeFH effectively identified and managed patients with HeFH. We evaluated the cost-effectiveness and the return on investment of an enhanced-care strategy for HeFH in primary care in Australia. METHODS: We developed a multistate Markov model to estimate the outcomes and costs of a general practitioner-led detection and management strategy for HeFH in primary care compared with the standard of care in Australia. The population comprised individuals aged 50 to 80 years, of which 44% had prior cardiovascular disease. Cardiovascular risk, HeFH prevalence, treatment effects, and acute and chronic health care costs were derived from published sources. The study involved screening for HeFH using a validated data-extraction tool (TARB-Ex), followed by a consultation to improve care. The detection rate of HeFH was 16%, and 74% of the patients achieved target LDL-C (low-density lipoprotein cholesterol). Quality-adjusted life years, health care costs, productivity losses, incremental cost-effectiveness ratio, and return on investment ratio were evaluated, outcomes discounted by 5% annually, adopting a health care and a societal perspective. RESULTS: Over the lifetime horizon, the model estimated a gain of 870 years of life lived and 1033 quality-adjusted life years when the general practitioner-led program was employed compared with standard of care. This resulted in an incremental cost-effectiveness ratio of AU$14 664/quality-adjusted life year gained from a health care perspective. From a societal perspective, this strategy, compared with standard of care was cost-saving, with a return on investment of AU$5.64 per dollar invested. CONCLUSIONS: An enhanced general practitioner-led model of care for HeFH is likely to be cost-effective.

The Short Food Allergy Quality of Life Questionnaire (FAQLQ-12) for Adults.

BACKGROUND: The Food Allergy Quality of Life Questionnaire (FAQLQ) is the most widely used measure to assess health-related quality of life in food allergy. However, its length can lead to a series of disadvantages, such as reduced or incomplete participation and boredom and disengagement, affecting data quality, reliability, and validity. OBJECTIVE: We shortened the well-known FAQLQ for adults and propose the FAQLQ-12. METHODS: We applied reference-standard statistical analyses, mixing classic test theory and item response theory to identify relevant items for the new short form and confirm its structure fit and reliability. More specifically, we employed discrimination, difficulty, and information levels (item response theory), confirmatory factor analysis, Pearson's correlations, and reliability analysis (McDonald ω and Cronbach α). RESULTS: We chose items with the highest discrimination values to compose the shortened FAQLQ because they were among the ones with the best difficulty levels and the highest amount of individual information. We retained three items per factor because this number allowed for acceptable reliability levels, resulting in 12 items. The FAQLQ-12 presented a better model fit compared with the complete version. The correlation patterns and reliability levels were similar for both the 29 and 12 versions. CONCLUSIONS: Although the full version of the FAQLQ remains a reference standard to assess food allergy quality of life, the FAQLQ-12 is introduced as a powerful and beneficial alternative. It can help participants, researchers, and clinicians in specific settings, such as dealing with time and budget limitations, and provides high-quality and reliable responses.

Long-term cost-effectiveness of implementing a lifestyle intervention during pregnancy to reduce the incidence of gestational diabetes and type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to determine the long-term cost-effectiveness and return on investment of implementing a structured lifestyle intervention to reduce excessive gestational weight gain and associated incidence of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus. METHODS: A decision-analytic Markov model was used to compare the health and cost-effectiveness outcomes for (1) a structured lifestyle intervention during pregnancy to prevent GDM and subsequent type 2 diabetes; and (2) current usual antenatal care. Life table modelling was used to capture type 2 diabetes morbidity, mortality and quality-adjusted life years over a lifetime horizon for all women giving birth in Australia. Costs incorporated both healthcare and societal perspectives. The intervention effect was derived from published meta-analyses. Deterministic and probabilistic sensitivity analyses were used to capture the impact of uncertainty in the model. RESULTS: The model projected a 10% reduction in the number of women subsequently diagnosed with type 2 diabetes through implementation of the lifestyle intervention compared with current usual care. The total net incremental cost of intervention was approximately AU$70 million, and the cost savings from the reduction in costs of antenatal care for GDM, birth complications and type 2 diabetes management were approximately AU$85 million. The intervention was dominant (cost-saving) compared with usual care from a healthcare perspective, and returned AU$1.22 (95% CI 0.53, 2.13) per dollar invested. The results were robust to sensitivity analysis, and remained cost-saving or highly cost-effective in each of the scenarios explored. CONCLUSIONS/INTERPRETATION: This study demonstrates significant cost savings from implementation of a structured lifestyle intervention during pregnancy, due to a reduction in adverse health outcomes for women during both the perinatal period and over their lifetime.

Projecting the Health and Economic Burden of Cardiovascular Disease Among People with Type 2 Diabetes, 2022-2031.

OBJECTIVE: The aim was to project the health and economic outcomes of cardiovascular disease (CVD) among people with type 2 diabetes from Australian public healthcare and societal perspectives over the next decade. METHODS: A dynamic multistate model with yearly cycles was developed to project cardiovascular events among Australians with type 2 diabetes aged 40-89 years from 2022 to 2031. CVD risk (myocardial infarction [MI] and stroke) in the type 2 diabetes population was estimated using the 2013 pooled cohort equation, and recurrent cardiovascular event rates in the type 2 diabetes with established CVD population were obtained from the global Reduction of Atherothrombosis for Continued Health (REACH) registry. Costs and utilities were derived from published sources. Outcomes included fatal and non-fatal MI and stroke, years of life lived, quality-adjusted life years (QALYs), total healthcare costs, and total productivity losses. The annual discount rate was 5%, applied to outcomes and costs. RESULTS: Between 2022 and 2031, a total of 83,618 non-fatal MIs (95% uncertainty interval [UI] 83,170-84,053) and 58,774 non-fatal strokes (95% UI 58,458-59,013) were projected. Total years of life lived and QALYs (discounted) were projected to be 9,549,487 (95% UI 9,416,423-9,654,043) and 6,632,897 (95% UI 5,065,606-7,591,679), respectively. Total healthcare costs and total lost productivity costs (discounted) were projected to be 9.59 billion Australian dollars (AU$) (95% UI 1.90-30.45 billion) and AU$9.07 billion (95% UI 663.53 million-33.19 billion), respectively. CONCLUSIONS: CVD in people with type 2 diabetes will substantially impact the Australian healthcare system and society over the next decade. Future work to investigate different strategies to optimize the control of risk factors for the prevention and treatment of CVD in type 2 diabetes in Australia is warranted.

Endpoints and Outcomes After Immunotherapy for Food Allergy: What Is Meaningful for Patients?

Multiple novel interventions for food allergy are currently at various stages of development with the goal of reducing or eliminating allergic reactions. However, the relative success of these therapeutics in achieving meaningful, long-term improvements to patients' lives is difficult to determine as there is currently very limited understanding of the degree of alignment between clinical trial efficacy endpoints and patient-centered outcomes. Furthermore, outcome measures used in clinical trials of food allergy immunotherapies vary widely, are often misinterpreted, and not necessarily consistent with what patients expect to achieve through treatment. This review aims to assist clinicians in critically interpreting outcomes reported in clinical trials and accurately communicating risks and outcomes to patients when practicing shared decision-making.

Varying Approaches to Management of IgE-Mediated Food Allergy in Children Around the World.

Food allergy is a chronic disease that affects individuals of all ages and is a significant public health problem globally. This narrative overview examines clinical management strategies for IgE-mediated food allergy in children around the world to understand variations in practice. Information was drawn from clinical practice guidelines, recent research, the websites of professional and governmental bodies with expertise in food allergy, and clinical experts from a broad cross-section of geographical regions. The structure and delivery of clinical services, allergen avoidance and food labeling, and resources to support the management of allergic reactions in the community are discussed in detail. The adoption of emerging food immunotherapies is also explored. Wide variations in clinical management of food allergy were apparent across the different countries. Common themes were continuing issues with access to specialist care and recognition of the need to balance risk reduction with dietary and social restrictions to avoid unnecessary detrimental impacts on the quality of life of food allergy sufferers. Findings highlight the need for standardized presentation of practice and priorities, and may assist clinicians and researchers when engaging with government and funding agencies to address gaps.

Beyond the case numbers: Social determinants and contextual factors in patient narratives of recovery from COVID-19.

OBJECTIVE: This study aimed to describe and contextualise COVID-19 recovery from the perspective of patient-lived experience, to inform the evolving public health response to the pandemic. METHODS: Narrative interviews were completed with 37 adult Australians between six and 10 months following their COVID-19 diagnosis. Verbatim transcripts were analysed thematically and trustworthiness was supported by multiple strategies to ensure rigour. RESULTS: Three themes were identified: 1) trajectories of recovery, 2) back to 'some sort of normal' and 3) the importance of work. Resumed participation in activities of daily life, the influence of social determinants of health and the impact of contextual factors were prominent features in the recovery narratives. CONCLUSIONS: The COVID-19 pandemic presents both challenges and opportunities for public health systems to formulate appropriate responses and make improvements. Behind the case numbers, patient narratives described the uncertainty, diversity and multiple pathways to recovery that need to inform public health policy. IMPLICATIONS FOR PUBLIC HEALTH: Looking beyond the case numbers reveals a complex landscape characterised by uncertainty, diversity and multiple pathways to recovery. The pandemic presents challenges and opportunities for public health in Australia and New Zealand, lived experience expertise is crucial to the formulation of an effective response.

Projected Return on Investment From Implementation of a Lifestyle Intervention to Reduce Adverse Pregnancy Outcomes.

Importance: Structured antenatal diet and physical activity interventions have been shown to be associated with reduced adverse pregnancy outcomes and recommended to be routinely offered to all pregnant women. The health cost implications of population-level implementation are unclear. Objective: To estimate the budget impact associated with integrating structured diet and physical activity interventions into routine antenatal care. Design, Setting, and Participants: This economic evaluation was conducted from the perspective of Australian health funders. An open-source decision-tree model was constructed to compare the projected budget outcomes of implementing lifestyle intervention vs usual care. Scenario, deterministic, and probabilistic sensitivity analysis were completed. The study setting was Australian health services, and the study population was all Australian women projected to give birth in the years 2022 to 2026 (approximately 330 000 per year). Interventions: Structured diet and physical activity intervention provided by trained health professionals, integrated into routine antenatal care. Comparator was usual care, which currently in Australia does not include routine structured lifestyle interventions. Main Outcomes and Measures: Return on investment (ROI) ratio for lifestyle intervention (cost of intervention divided by cost savings attributable to reduced maternal and infant adverse events) from the perspective of Australian health care funders. Adverse events were obtained from a published meta-analysis and population data. Costs were estimated from aggregate trial data and clinical pathways and valued at the year incurred. Results: Intervention offered an ROI ratio of 4.75 over the 5-year program; hence every Australian dollar spent on implementation produced an estimated return of A$4.75. The projected total 5-year intervention cost was A$205 million ($151 million), with cost offsets (from reduced incidence of adverse pregnancy outcomes) of A$1022 million ($755 million), and health budget savings of A$807 million (95% CI, A$129 million to A$1639 million) ($596 million [95% CI, $95 million to $1211 million]); 93.3% of the 10 000 iterations were within cost saving, and results were robust to scenario and sensitivity analyses. Conclusions and Relevance: This economic evaluation found that providing access to structured diet and physical activity lifestyle interventions for all pregnant Australian women was estimated to provide strong return on investment for health funders. The open-source model developed can be used by other jurisdictions and health services to explore cost implications of implementation within their patient population.

Measuring the Impact of Food Immunotherapy on Health-Related Quality of Life in Clinical Trials.

Food allergy is a common, and often lifelong, disorder with considerable negative impact on the quality of life of those affected and their families. While several promising immunotherapies for food allergy have either been approved or are in late-phase clinical trials based on demonstrated effectiveness at inducing desensitization, evidence of benefit in terms of improving patient-centered outcomes is inconsistent. Historically, health-related quality of life has not been prioritized as an endpoint in food immunotherapy trials and, even when included, findings have been undermined by methodological limitations of the measurement instruments used and issues with data interpretation. This review highlights the importance of measuring health-related quality of life as an endpoint in food immunotherapy trials and discusses the strengths and limitations of available evidence in this regard, with a focus on the appropriate use of assessment instruments and interpretation of findings. There remains much to learn regarding the impact of food immunotherapies on patient wellbeing, both during treatment and over the longer term. Our aim is to assist clinicians, researchers, policy makers and consumers in their interpretation of the existing literature, and to promote greater scientific rigor in the design and selection of outcome measurement frameworks for future studies evaluating the efficacy of immunotherapy treatments for food allergy.

Implementing specialised vestibular physiotherapy in an emergency department: a process evaluation.

BACKGROUND: Dizziness and vertigo-like symptoms, often caused by common peripheral vestibular disorders such as benign paroxysmal positional vertigo (BPPV), may significantly impact function and quality of life. These symptoms often result in emergency department (ED) presentations. Evidence-based clinical practice guidelines strongly recommend using physical assessment and treatment manoeuvres for the assessment, diagnosis and treatment of these symptoms. This study aimed to evaluate the process of implementing specialised vestibular physiotherapy (SPV) in an emergency department from the clinician's perspective. METHODS: This implementation study utilised a retrospective mixed-methods process evaluation to understand how SVP operated in an Australian emergency department. The i-PARiHS framework was embedded within the methodology and analytical approach of the study to ensure a comprehensive approach closely aligned to implementation science. Nine clinicians retrospectively completed the Organisational Readiness for Change Assessment (ORCA), Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM). Seven clinicians also participated in a focus group or interview. RESULTS: A range of barriers and facilitators to the implementation process were identified by participants, some of which spanned multiple domains of the i-PARiHS framework. Relationships with service leaders, champions and medical staff were pivotal facilitators to implementation, along with a generally held perception that SVP was acceptable and feasible. The main barrier identified was a lack of capacity to deliver and facilitate this innovation within the physiotherapy workforce and the broader multidisciplinary recipients. CONCLUSIONS: This study demonstrates that the process of implementing an SVP service in an ED context was generally well-received by clinicians but also involved some challenges and barriers. Services looking to implement SVP in the ED should aim to build stakeholder relationships; develop a shared vision with clear goals and intended outcomes; embed the innovation in organisation processes, procedures and policies; and increase workforce capacity to deliver and facilitate SVP to guide their approach to this innovation.

Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial.

BACKGROUND: Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy. METHODS: PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide [SA], Melbourne [VIC], and Perth [WA]) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (≥3 mm) or peanut-specific IgE (≥0·35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour [50% peanut protein]) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 × 1010 colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Clinical Trials Registry, 12616000322437. FINDINGS: Between July 4, 2016, and Sept 21, 2020, 201 participants were enrolled and included in the intention-to-treat analysis. 36 (46%) of 79 children in the PPOIT group and 42 (51%) of 83 children in the OIT group achieved sustained unresponsiveness compared with two (5%) of 39 children in the placebo group (risk difference 40·44% [95% CI 27·46 to 53·42] for PPOIT vs placebo, p<0·0001), with no difference between PPOIT and OIT (-5·03% [-20·40 to 10·34], p=0·52). Treatment-related adverse events were reported in 72 (91%) of 79 children in the PPOIT group, 73 (88%) of 83 children in the OIT group, and 28 (72%) of 39 children in the placebo group. Exposure-adjusted incidence of adverse events was 10·58 in the PPOIT group, 11·36 in the OIT, and 2·09 in the placebo group (ratio 0·92 [95% CI 0·85 to 0·99] for PPOIT vs OIT, p=0·042; 4·98 [4·11-6·03] for PPOIT vs placebo, p<0·0001; 5·42 [4·48-6·56] for OIT vs placebo, p<0·0001), with differences seen primarily in gastrointestinal symptoms and in children aged 1-5 years. During the 12-month post-treatment period, 60 (85%) of 71 participants in the PPOIT group, 60 (86%) of 70 participants in the OIT group, and six (18%) of 34 participants in the placebo group were eating peanut; rescue epinephrine use was infrequent (two [3%] of 71 in the PPOIT group, four [6%] of 70 in the OIT group, and none in the placebo group). INTERPRETATION: Both PPOIT and OIT were effective at inducing sustained unresponsiveness. Addition of a probiotic did not improve efficacy of OIT, but might offer a safety benefit compared with OIT alone, particularly in preschool children. FUNDING: National Health and Medical Research Council Australia and Prota Therapeutics.