Transient responses and significant toxicities of anti-CD30 CAR T cells for CD30+ lymphomas: results of a phase 1 trial.

ABSTRACT: New treatments are needed for relapsed and refractory CD30-expressing lymphomas. We developed a novel anti-CD30 chimeric antigen receptor (CAR), designated 5F11-28Z. Safety and feasibility of 5F11-28Z-transduced T cells (5F11-Ts) were evaluated in a phase 1 dose escalation clinical trial. Patients with CD30-expressing lymphomas received 300 mg/m2 or 500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine on days -5 to -3, followed by infusion of 5F11-Ts on day 0. Twenty-one patients received 5F11-T infusions. Twenty patients had classical Hodgkin lymphoma, and 1 had anaplastic large-cell lymphoma. Patients were heavily pretreated, with a median of 7 prior lines of therapy and substantial tumor burden, with a median metabolic tumor volume of 66.1 mL (range, 6.4-486.7 mL). The overall response rate was 43%; 1 patient achieved a complete remission. Median event-free survival was 13 weeks. Eleven patients had cytokine release syndrome (CRS; 52%). One patient had grade 3 CRS, and there was no grade 4/5 CRS. Neurologic toxicity was minimal. Nine patients (43%) had new-onset rashes. Two patients (9.5%) received extended courses of corticosteroids for prolonged severe rashes. Five patients (24%) had grade 3/4 cytopenias, with recovery time of ≥30 days, and 2 of these patients (9.5%) had prolonged cytopenias with courses complicated by life-threatening sepsis. The trial was halted early because of toxicity. Median peak blood CAR+ cells per µL was 26 (range, 1-513 cells per µL), but no infiltration of CAR+ cells was detected in lymph node biopsies. 5F11-Ts had low efficacy and substantial toxicities, which limit further development of 5F11-Ts. This trial was registered at www.clinicaltrials.gov as #NCT03049449.

Cough in Children and Adults: Diagnosis, Assessment and Management (CICADA). Summary of an updated position statement on chronic cough in Australia.

INTRODUCTION: Cough is the most common symptom leading to medical consultation. Chronic cough results in significant health care costs, impairs quality of life, and may indicate the presence of a serious underlying condition. Here, we present a summary of an updated position statement on cough management in the clinical consultation. MAIN RECOMMENDATIONS: Assessment of children and adults requires a focused history of chronic cough to identify any red flag cough pointers that may indicate an underlying disease. Further assessment with examination should include a chest x-ray and spirometry (when age > 6 years). Separate paediatric and adult diagnostic management algorithms should be followed. Management of the underlying condition(s) should follow specific disease guidelines, as well as address adverse environmental exposures and patient/carer concerns. First Nations adults and children should be considered a high risk group. The full statement from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia for managing chronic cough is available at https://lungfoundation.com.au/resources/cicada-full-position-statement. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Algorithms for assessment and diagnosis of adult and paediatric chronic cough are recommended. High quality evidence supports the use of child-specific chronic cough management algorithms to improve clinical outcomes, but none exist in adults. Red flags that indicate serious underlying conditions requiring investigation or referral should be identified. Early and effective treatment of chronic wet/productive cough in children is critical. Culturally specific strategies for facilitating the management of chronic cough in First Nations populations should be adopted. If the chronic cough does not resolve or is unexplained, the patient should be referred to a respiratory specialist or cough clinic.

Rapid anti-myeloma activity by T cells expressing an anti-BCMA CAR with a human heavy-chain-only antigen-binding domain.

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater than grade 3. Most anti-MM activity occurred within 2-4 weeks of FHVH-T infusion as shown by decreases in the rapidly changing MM markers serum free light chains, urine light chains, and bone marrow plasma cells. Blood CAR+ cell levels peaked during the time that MM elimination was occurring, between 7 and 15 days after FHVH-T infusion. C-C chemokine receptor type 7 (CCR7) expression on infusion CD4+ FHVH-T correlated with peak blood FHVH-T levels. Single-cell RNA sequencing revealed a shift toward more differentiated FHVH-T after infusion. Anti-CAR antibody responses were detected in 4 of 12 patients assessed. FHVH-T has powerful, rapid, and durable anti-MM activity.

Understanding patient experience of chronic cough in interstitial lung disease.

Rationale: Chronic cough is a common symptom in patients with interstitial lung disease (ILD), negatively contributing to health-related quality of life. Despite this, there is limited information and understanding on the experience of this group of patients with chronic cough. This study aimed to explore the symptom experiences for chronic cough in patients with ILD to identify its characteristics and impacts. Methods: A qualitative study using semi-structured telephone interviews was undertaken in 16 adults with a diagnosis of ILD of any type and severity. Patients were recruited from a quaternary referral centre in Melbourne, Australia. Interviews were transcribed verbatim and coded by two researchers using thematic analysis. Results: Patients (age range: 39-87 years, forced vital capacity: 53-107% predicted and diffusing capacity of the lung for carbon monoxide: 28-89% predicted) experienced a spectrum of cough severity and characteristics, including both dry and productive coughs. The impact of chronic cough included physical symptoms, social and emotional difficulties, and interference with work and vocational participation. Management strategies used to relieve cough included mucolytics, opiates, throat lozenges, warm drinks, pacing, breath control, relaxation exercises, movement, continuous positive airways pressure and supplemental oxygen. Patients expressed a need for further information and education regarding chronic cough, including its triggers and management. Conclusions: This study highlights the experience and significance of chronic cough in patients with ILD. The nature and severity of chronic cough in patients with ILD appears to be more heterogeneous than previously described, with physical, social and emotional impacts contributing to symptom burden.

Associations between prenatal and early-life air pollution exposure and lung function in young children: Exploring influential windows of exposure on lung development.

BACKGROUND: Evidence in the literature suggests that air pollution exposures experienced prenatally and early in life can be detrimental to normal lung development, however the specific timing of critical windows during development is not fully understood. OBJECTIVES: We evaluated air pollution exposures during the prenatal and early-life period in association with lung function at ages 6-9, in an effort to identify potentially influential windows of exposure for lung development. METHODS: Our study population consisted of 222 children aged 6-9 from the Fresno-Clovis metro area in California with spirometry data collected between May 2015 and May 2017. We used distributed-lag non-linear models to flexibly model the exposure-lag-response for monthly average exposure to fine particulate matter (PM2.5) and ozone (O3) during the prenatal months and first three years of life in association with forced vital capacity (FVC), and forced expiratory volume in the first second (FEV1), adjusted for covariates. RESULTS: PM2.5 exposure during the prenatal period and the first 3-years of life was associated with lower FVC and FEV1 assessed at ages 6-9. Specifically, an increase from the 5th percentile of the observed monthly average exposure (7.55 µg/m3) to the median observed exposure (12.69 µg/m3) for the duration of the window was associated with 0.42 L lower FVC (95% confidence interval (CI): -0.82, -0.03) and 0.38 L lower FEV1 (95% CI: -0.75, -0.02). The shape of the lag-response indicated that the second half of pregnancy may be a particularly influential window of exposure. Associations for ozone were not as strong and typically CIs included the null. CONCLUSIONS: Our findings indicate that prenatal and early-life exposures to PM2.5 are associated with decreased lung function later in childhood. Exposures during the latter months of pregnancy may be especially influential.

Biomass Smoke Exposure and Atopy among Young Children in the Western Highlands of Guatemala: A Prospective Cohort Study.

Women and children in rural regions of low-income countries are exposed to high levels of household air pollution (HAP) as they traditionally tend to household chores such as cooking with biomass fuels. Early life exposure to air pollution is associated with aeroallergen sensitization and developing allergic diseases at older ages. This prospective cohort study assigned HAP-reducing chimney stoves to 557 households in rural Guatemala at different ages of the study children. The children's air pollution exposure was measured using personal CO diffusion tubes. Allergic outcomes at 4-5 years old were assessed using skin prick tests and International Study of Asthma and Allergies in Childhood (ISAAC)-based questionnaires. Children assigned to improved stoves before 6 months old had the lowest HAP exposure compared to the other groups. Longer exposure to the unimproved stoves was associated with higher risks of maternal-reported allergic asthma (OR = 2.42, 95% CI: 1.11-5.48) and rhinitis symptoms (OR = 2.01, 95% CI: 1.13-3.58). No significant association was found for sensitization to common allergens such as dust mites and cockroaches based on skin prick tests. Reducing HAP by improving biomass burning conditions might be beneficial in preventing allergic diseases among children in rural low-income populations.

Primary care and the older person with complex needs: reflections on the implementation of a primary–secondary model of integrated care.

The demand and complexity of the health needs of older people is growing. Traditionally siloed, condition-centric care is no longer appropriate. It is costly to the Australian health system and life-threatening to the individual. In parallel to demographic change is increasing global awareness of the impact of social, behavioural, and environmental factors on health outcomes. Although significant when not addressed, the amenable nature of many personal contextual factors is an opportunity to improve health and quality of life. A move away from reactive, episodic models of health care delivery towards patient focussed integrated care is required to meet the changing demands of an aging population. This forum article provides a reflection on the current state of integration for older people with complex needs through the lens of a local community facing model: OPEN ARCH. Australia still has some way to go to establishing system level enablers for an integrated approach to care. However, the OPEN ARCH experience furthers the evidence for ground-up approaches of integrated care that can meet the increasing demand and complexity of older people's needs.

CFTR gene variants, air pollution, and childhood asthma in a California Medicaid population.

Carriers of the cystic fibrosis transmembrane conductance regulator (CFTR) gene ("carriers") have been found to have an increased risk of persistent asthma. However, it is unclear at what level of CFTR function this risk exists and whether it is modified by asthmogens, such as air pollution. We conducted a retrospective cohort study of children born in California between July 2007 and December 2013, linking CFTR genotype data from the California newborn screening program to Medicaid claims records through March 17, 2020 to identify asthma cases, and to air pollution data from CalEnviroScreen 3.0 to identify levels of particulate matter with diameter 2.5 microns or smaller (PM2.5 ). Log-binomial regression models for asthma risk were fitted, adjusting for race/ethnicity and sex. Compared to population controls, carriers had higher risk of asthma (adjusted risk ratio (aRR) = 1.29, 95% confidence interval (CI): 0.98, 1.69; p < 0.1). Other non-CF-causing variants on the second allele did not appear to further increase risk. Genotypes with the greatest asthma risk were F508del with an intron 10 T7 or (TG)11T5 in trans (aRR=1.52, 95% CI: 1.10, 2.12). This association was higher among children living in areas at or above (aRR = 1.80) versus below (aRR = 1.37) the current national air quality standard for PM2.5 , though this difference was not statistically significant (pinteraction > 0.2). These results suggest carriers with CFTR functional levels between 25% and 45% of wildtype are at increased risk of asthma. Knowledge of CFTR genotype in asthmatics may be important to open new CFTR-related treatment options for these patients.

Clinical outcomes in pediatric hydrocephalus patients treated with endoscopic third ventriculostomy and choroid plexus cauterization: a systematic review and meta-analysis.

OBJECTIVE: Endoscopic third ventriculostomy and choroid plexus cauterization (ETV+CPC) is a novel procedure for infant hydrocephalus that was developed in sub-Saharan Africa to mitigate the risks associated with permanent implanted shunt hardware. This study summarizes the hydrocephalus literature surrounding the ETV+CPC intraoperative abandonment rate, perioperative mortality rate, cerebrospinal fluid infection rate, and failure rate. METHODS: This systematic review and meta-analysis followed a prespecified protocol and abides by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy using MEDLINE, EMBASE, PsychInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from database inception to October 2019. Studies included controlled trials, cohort studies, and case-control studies of patients with hydrocephalus younger than 18 years of age treated with ETV+CPC. Pooled estimates were calculated using DerSimonian and Laird random-effects modeling, and the significance of subgroup analyses was tested using meta-regression. The quality of the pooled outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: After screening and reviewing 12,321 citations, the authors found 16 articles that met the inclusion criteria. The pooled estimate for the ETV+CPC failure rate was 0.44 (95% CI 0.37-0.51). Subgroup analysis by geographic income level showed statistical significance (p < 0.01), with lower-middle-income countries having a lower failure rate (0.32, 95% CI 0.28-0.36) than high-income countries (0.53, 95% CI 0.47-0.60). No difference in failure rate was found between hydrocephalus etiology (p = 0.09) or definition of failure (p = 0.24). The pooled estimate for perioperative mortality rate (n = 7 studies) was 0.001 (95% CI 0.00-0.004), the intraoperative abandonment rate (n = 5 studies) was 0.04 (95% CI 0.01-0.08), and the postoperative CSF infection rate (n = 5 studies) was 0.0004 (95% CI 0.00-0.003). All pooled outcomes were found to be low-quality evidence. CONCLUSIONS: This systematic review and meta-analysis provides the most comprehensive pooled estimate for the ETV+CPC failure rate to date and demonstrates, for the first time, a statistically significant difference in failure rate by geographic income level. It also provides the first reported pooled estimates for the risk of ETV+CPC perioperative mortality, intraoperative abandonment, and CSF infection. The low quality of this evidence highlights the need for further research to improve the understanding of these critical clinical outcomes and their relevant explanatory variables and thus to appreciate which patients may benefit most from an ETV+CPC. Systematic review registration no.: CRD42020160149 (https://www.crd.york.ac.uk/prospero/).

Perceptions of Individuals With Chronic Lung Disease on Home Use of Pulse Oximetry.

BACKGROUND: Pulse oximeters are often used at home by patients with chronic respiratory diseases and more recently for remote monitoring of patients with COVID-19. There are no published data outside a supervised telemedicine setting regarding patients' experiences with these devices. Our objective was to explore patients' usage patterns and perceptions of using pulse oximetry at home. METHODS: Patients with chronic respiratory disease who had a pulse oximeter at home were recruited to complete a structured survey. RESULTS: Thirty participants with a range of chronic respiratory diseases (mean age 71 y, 16 females) were recruited. Most participants (83%) used home oxygen therapy. Pulse oximeters were bought online (46.7%), at a pharmacy (40%), at a medical equipment store (6.7%), through a clinic (3.3%), or from an oxygen supplier (3.3%). Use was self-initiated in 56.7% of cases and was based on a health care-related recommendation in 26.7% of cases. Sixty percent of participants used the oximeter daily, with 90% expressing confidence in interpreting their oximeter readings primarily due to education from health care professionals and in-patient experiences. Almost all participants adjusted their activity levels or management based upon oximeter readings. Most participants reported that using a pulse oximeter at home was helpful in judging their physical limitations and provided reassurance and confidence in their disease management. CONCLUSIONS: Subjects appeared confident in their use of home pulse oximetry. Health professionals should identify patients who use pulse oximeters for monitoring and ensure that they are able to interpret readings correctly and, if appropriate, adjust management safely.

Cost-effectiveness of a community-based integrated care model compared with usual care for older adults with complex needs: a stepped-wedge cluster-randomised trial.

Objective: To assess the cost of implementation, delivery and cost-effectiveness (CE) of a flagship community-based integrated care model (OPEN ARCH) against the usual primary care. Design: A 9-month stepped-wedge cluster-randomised trial. Setting and participants: Community-dwelling older adults with chronic conditions and complex care needs were recruited from primary care (14 general practices) in Far North Queensland, Australia. Methods: Costs and outcomes were measured at 3-month windows from the healthcare system and patient's out-of-pocket perspectives for the analysis. Outcomes included functional status (Functional Independence Measure (FIM)) and health-related quality of life (EQ-5D-3L and AQoL-8D). Bayesian CE analysis with 10 000 Monte Carlo simulations was performed using the BCEA package in R (V.3.6.1). Results: The OPEN ARCH model of care had an average cost of $A1354 per participant. The average age of participants was 81, and 55% of the cohort were men. Within-trial multilevel regression models adjusted for time, general practitioner cluster and baseline confounders showed no significant differences in costs, resource use or effect measures regardless of the analytical perspective. Probabilistic sensitivity analysis with 10 000 simulations showed that OPEN ARCH could be recommended over usual care for improving functional independence at a willing to pay above $A600 (US$440) per improvement of one point on the FIM Scale and for avoiding or reducing inpatient stay for any willingness-to-pay threshold up to $A50 000 (US$36 500). Conclusions and implications: OPEN ARCH was associated with a favourable Bayesian CE profile in improving functional status and dependency levels, avoiding or reducing inpatient stay compared with usual primary care in the Australian context. Trial registration number: ACTRN12617000198325.

Intraventricular Masson tumor: case report and systematic review of primary intracranial intravascular papillary endothelial hyperplasia.

Intracranial Masson tumor (intravascular papillary endothelial hyperplasia, IPEH) is a benign lesion that is thought to originate from a reactionary process in response to compromised blood flow. IPEH may be classified into one of three subtypes based on etiology as it may result from the excessive proliferation of endothelial cells within a normal vessel (primary), vascular malformation (type II), or organized hematoma (type III). We report the case of a 79-year-old woman who presented with confusion, gait instability, and urinary incontinence. Neuroimaging revealed a hemorrhagic lesion within the right lateral ventricle, which was successfully resected. To our knowledge, this is the first reported case of an intraventricular IPEH and 33rd case of primary intracranial IPEH. We further performed a systematic review of the literature on all prior type I intracranial IPEH cases and discuss the importance of long-term follow-up in intracranial IPEH.

Traffic-related air pollution, biomarkers of metabolic dysfunction, oxidative stress, and CC16 in children.

BACKGROUND: Previous research has revealed links between air pollution exposure and metabolic syndrome in adults; however, these associations are less explored in children. OBJECTIVE: This study aims to investigate the association between traffic-related air pollutants (TRAP) and biomarkers of metabolic dysregulation, oxidative stress, and lung epithelial damage in children. METHODS: We conducted cross-sectional analyses in a sample of predominantly Latinx, low-income children (n = 218) to examine associations between air pollutants (nitrogen dioxide (NO2), nitrogen oxides (NOx), elemental carbon, polycyclic aromatic hydrocarbons, carbon monoxide (CO), fine particulates (PM2.5)) and biomarkers of metabolic function (high-density lipoprotein (HDL), hemoglobin A1c (HbA1c), oxidative stress (8-isoprostane), and lung epithelial damage (club cell protein 16 (CC16)). RESULTS: HDL cholesterol showed an inverse association with NO2 and NOx, with the strongest relationship between HDL and 3-month exposure to NO2 (-15.4 mg/dL per IQR increase in 3-month NO2, 95% CI = -27.4, -3.4). 8-isoprostane showed a consistent pattern of increasing values with 1-day and 1-week exposure across all pollutants. Non-significant increases in % HbA1c were found during 1-month time frames and decreasing CC16 in 3-month exposure time frames. CONCLUSION: Our results suggest that TRAP is significantly associated with decreased HDL cholesterol in longer-term time frames and elevated 8-isoprostane in shorter-term time frames. TRAP could have the potential to influence lifelong metabolic patterns, through metabolic effects in childhood.

Impact of an integrated community-based model of care for older people with complex conditions on hospital emergency presentations and admissions: a step-wedged cluster randomized trial.

BACKGROUND: Health systems must reorient towards preventative and co-ordinated care to reduce hospital demand and achieve positive and fiscally responsible outcomes for older persons with complex needs. Integrated care models can improve outcomes by aligning primary practice with the specialist health and social services required to manage complex needs. This paper describes the impact of a community-facing program that integrates care at the primary-secondary interface on the rate of Emergency Department (ED) presentation and hospital admissions among older people with complex needs. METHODS: The Older Persons Enablement and Rehabilitation for Complex Health Conditions (OPEN ARCH) study is a multicentre randomised controlled trial with a stepped wedge cluster design. General practitioners (GPs; n = 14) in primary practice within the Cairns region are considered 'clusters' each comprising a mixed number of participants. 80 community-dwelling persons over 70 years of age if non-Indigenous and over 50 years of age if Indigenous were included at baseline with no new participants added during the study. Clusters were randomly assigned to one of three steps that represent the time at which they would commence the OPEN ARCH intervention, and the subsequent intervention duration (3, 6, or 9 months). Each participant was its own control. GPs and participants were not blinded. The primary outcomes were ED presentations and hospital admissions. Data were collected from Queensland Health Casemix data and analysed with multilevel mixed-effects Poisson regression modelling to estimate the effectiveness of the OPEN ARCH intervention. Data were analysed at the cluster and participant levels. RESULTS: Five clusters were randomised to steps 1 and 2, and 4 clusters randomised to step 3. All clusters (n = 14) completed the trial accounting for 80 participants. An effect size of 9% in service use (95% CI) was expected. The OPEN ARCH intervention was found to not make a statistically significant difference to ED presentations or admissions. However, a stabilising of ED presentations and a trend toward lower hospitalisation rates over time was observed. CONCLUSIONS: While this study detected no statistically significant change in ED presentations or hospital admissions, a plateauing of ED presentation and admission rates is a clinically significant finding for older persons with complex needs. Multi-sectoral integrated programs of care require an adequate preparation period and sufficient duration of intervention for effectiveness to be measured. TRIAL REGISTRATION: The OPEN ARCH study received ethical approval from the Far North Queensland Human Research Ethics Committee, HREC/17/QCH/104-1174 and is registered on the Australian and New Zealand Trials Registry, ACTRN12617000198325p .

OPEN ARCH integrated care model: experiences of older Australians and their carers.

There is worldwide recognition of the need to redesign health service delivery with a focus on strengthening primary health care and aligning health and social care through integrated models. A defining feature of integrated models is improved patient and carer experience of care. This study explored the experiences of older people and their carers enrolled in a unique model of integrated care that provides a specialist geriatric intervention in the primary care setting for older adults with complex needs in Far North Queensland. A qualitative exploratory descriptive design using semistructured interviews was used to address the study aims. Seventeen older people and nine carers took part in the study. Data were analysed inductively, guided by the principles of thematic analysis. Three themes emerged: getting by; achieving positive change; and improving and maintaining the OPEN ARCH (Older Persons ENablement And Rehabilitation for Complex Health conditions) approach. The findings indicate that enablement models of integration can be successful in activating positive change towards independence for the older person with complex needs. Understanding patients' and carers' experiences is essential to comprehensive service evaluation.

Traffic-related air pollution is associated with glucose dysregulation, blood pressure, and oxidative stress in children.

BACKGROUND: Metabolic syndrome increases the risk of cardiovascular disease in adults. Antecedents likely begin in childhood and whether childhood exposure to air pollution plays a contributory role is not well understood. OBJECTIVES: To assess whether children's exposure to air pollution is associated with markers of risk for metabolic syndrome and oxidative stress, a hypothesized mediator of air pollution-related health effects. METHODS: We studied 299 children (ages 6-8) living in the Fresno, CA area. At a study center visit, questionnaire and biomarker data were collected. Outcomes included hemoglobin A1c (HbA1c), urinary 8-isoprostane, systolic blood pressure (SBP), and BMI. Individual-level exposure estimates for a set of four pollutants that are constituents of traffic-related air pollution (TRAP) - the sum of 4-, 5-, and 6-ring polycyclic aromatic hydrocarbon compounds (PAH456), NO2, elemental carbon, and fine particulate matter (PM2.5) - were modeled at the primary residential location for 1-day lag, and 1-week, 1-month, 3-month, 6-month, and 1-year averages prior to each participant's visit date. Generalized additive models were used to estimate associations between each air pollutant exposure and outcome. RESULTS: The study population was 53% male, 80% Latinx, 11% Black and largely low-income (6% were White and 3% were Asian/Pacific Islander). HbA1c percentage was associated with longer-term increases in TRAP; for example a 4.42 ng/m3 increase in 6-month average PAH456 was associated with a 0.07% increase (95% CI: 0.01, 0.14) and a 3.62 µg/m3 increase in 6-month average PM2.5 was associated with a 0.06% increase (95% CI: 0.01, 0.10). The influence of air pollutants on blood pressure was strongest at 3 months; for example, a 6.2 ppb increase in 3-month average NO2 was associated with a 9.4 mmHg increase in SBP (95% CI: 2.8, 15.9). TRAP concentrations were not significantly associated with anthropometric or adipokine measures. Short-term TRAP exposure averages were significantly associated with creatinine-adjusted urinary 8-isoprostane. DISCUSSION: Our results suggest that both short- and longer-term estimated individual-level outdoor residential exposures to several traffic-related air pollutants, including ambient PAHs, are associated with biomarkers of risk for metabolic syndrome and oxidative stress in children.

Beyond multimorbidity: primary care and the older person with complex needs.

The aim of this study was to present the health and social characteristics of community-dwelling older people within the Cairns region who were identified by their GP as having complex care needs. This paper reports the subanalysis of baseline data from the Older Persons Enablement and Rehabilitation (OPEN ARCH) stepped wedge randomised controlled trial of an integrated model of care for community-dwelling older people. Data were analysed at the level of the participant and the level of the participant cluster (group of participants from the one GP). Median quality of life, as assessed by the EQ-5D, was higher for females than males (80 vs 70 respectively; P=0.05) and for people living alone than living with family (80 vs 60 respectively; P=0.0940). There was greater functional independence among non-Indigenous than Indigenous participants (median Functional Independence Measure scores of 122 vs 115 respectively; P=0.0937) and the incidence rate (95% confidence intervals) of presentation to the emergency department was sevenfold higher for Indigenous than non-Indigenous participants (11.47 (5.93-20.03) vs 1.65 (0.79-3.04) per 1000 person days respectively). Finally, 61.3% of participants required support to remain living in the community and 44% accessed allied health, with podiatry the most common intervention. The findings indicate that previous hospital utilisation is not a consistent indicator of complexity. Multimorbidity, cultural context and the living and caring situation are considered as matters of complexity, yet variation exists at the participant level.