Adjuvant Atezolizumab in Patients with Sarcomatoid Renal Cell Carcinoma: A Prespecified Subgroup Analysis of IMmotion010.

Patients with sarcomatoid renal cell carcinoma (sRCC) have a poor prognosis. In the randomised, double-blind phase 3 IMmotion010 trial (NCT03024996), adjuvant atezolizumab did not demonstrate a disease-free survival (DFS) benefit versus placebo in the overall population of patients with locoregional renal cell carcinoma with an increased risk of recurrence following surgery. This prespecified subgroup analysis of efficacy and safety was completed in 104 patients with sRCC. Baseline characteristics were similar between treatment arms. At a median follow-up of 45 mo, the median DFS was not evaluable (NE; 95% confidence interval [CI], 12 mo-NE) in the atezolizumab arm (n = 37) and 23 mo (95% CI, 11-NE) in the placebo arm (n = 66; hazard ratio 0.77 [95% CI, 0.44-1.4]). In the sRCC subgroup, grade 3/4 treatment-related adverse events (TRAEs) occurred in one patient (2.7%) in the atezolizumab arm and two patients (3.0%) in the placebo arm. By comparison, 54 of 353 patients (15%) and 16 of 317 patients (5.0%) with non-sarcomatoid histology reported grade 3/4 TRAEs in the respective arms. In conclusion, the difference in DFS was not statistically significant between adjuvant atezolizumab and placebo in patients with sRCC. The safety profile was similar between patients with sRCC and non-sRCC. PATIENT SUMMARY: Patients with a specific type of locoregional kidney cancer (tumours with sarcomatoid features) were treated with atezolizumab or placebo after surgery. Slightly more patients treated with atezolizumab lived longer without the disease getting worse than those treated with placebo, although this finding was not statistically significant. The side effects were similar to those seen in patients with other types of kidney cancer treated with atezolizumab in the same study (IMmotion010). In patients with sarcomatoid kidney cancer, atezolizumab was tolerable and may be more effective than placebo, but this requires further study.

Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: The standard of care for locoregional renal cell carcinoma is surgery, but many patients experience recurrence. The objective of the current study was to determine if adjuvant atezolizumab (vs placebo) delayed recurrence in patients with an increased risk of recurrence after resection. METHODS: IMmotion010 is a randomised, double-blind, multicentre, phase 3 trial conducted in 215 centres in 28 countries. Eligible patients were patients aged 18 years or older with renal cell carcinoma with a clear cell or sarcomatoid component and increased risk of recurrence. After nephrectomy with or without metastasectomy, patients were randomly assigned (1:1) to receive atezolizumab (1200 mg) or placebo (both intravenous) once every 3 weeks for 16 cycles or 1 year. Randomisation was done with an interactive voice-web response system. Stratification factors were disease stage (T2 or T3a vs T3b-c or T4 or N+ vs M1 no evidence of disease), geographical region (north America [excluding Mexico] vs rest of the world), and PD-L1 status on tumour-infiltrating immune cells (<1% vs ≥1% expression). The primary endpoint was investigator-assessed disease-free survival in the intention-to-treat population, defined as all patients who were randomised, regardless of whether study treatment was received. The safety-evaluable population included all patients randomly assigned to treatment who received any amount of study drug (ie, atezolizumab or placebo), regardless of whether a full or partial dose was received. This trial is registered with ClinicalTrials.gov, NCT03024996, and is closed to further accrual. FINDINGS: Between Jan 3, 2017, and Feb 15, 2019, 778 patients were enrolled; 390 (50%) were assigned to the atezolizumab group and 388 (50%) to the placebo group. At data cutoff (May 3, 2022), the median follow-up duration was 44·7 months (IQR 39·1-51·0). Median investigator-assessed disease-free survival was 57·2 months (95% CI 44·6 to not evaluable) with atezolizumab and 49·5 months (47·4 to not evaluable) with placebo (hazard ratio 0·93, 95% CI 0·75-1·15, p=0·50). The most common grade 3-4 adverse events were hypertension (seven [2%] patients who received atezolizumab vs 15 [4%] patients who received placebo), hyperglycaemia (ten [3%] vs six [2%]), and diarrhoea (two [1%] vs seven [2%]). 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo had a serious adverse event. There were no treatment-related deaths. INTERPRETATION: Atezolizumab as adjuvant therapy after resection for patients with renal cell carcinoma with increased risk of recurrence showed no evidence of improved clinical outcomes versus placebo. These study results do not support adjuvant atezolizumab for treatment of renal cell carcinoma. FUNDING: F Hoffmann-La Roche and Genentech, a member of the Roche group.

Health promoting and demoting consumption: What accounts for budget share differentials by ethnicity in New Zealand.

Background: Health demoting consumption of alcohol and tobacco are some of the most important risk factors for health loss worldwide, however there is limited information on these consumption risk factors in New Zealand (NZ) and whether inequities in the risk factors are ethnically patterned. Methods: We used three nationally representative Household Economic Survey waves (2006/07, 2009/10, 2012/13) (n = 9030) in NZ to examine household expenditure for key health risk-related components of consumption by ethnicity, and its contributors to the differences using non-parametric, parametric and decomposition methods. Results: Maori households (NZ indigenous population) were significantly poorer (25% less) than non-Maori households in terms of household per capita expenditure. However, our various econometric estimations suggested that, in relative terms, Maori spent more on tobacco and alcohol, and less on healthcare. The gaps become larger at upper quantiles of the budget share distributions; the composition effect (the gap due to differences in individual and household characteristics between Maori and non-Maori) explains most of the tobacco and alcohol budget share gap between the two groups, and less for healthcare. The structure effect (the gap due to returns to/or effect of individual and household characteristics) contributes very little to the budget share gap for tobacco and drink, but increasingly and predominantly when moving along the distribution of healthcare budget share.The differences between Maori and non-Maori in household ownership, education, and income negatively affect budget share on these health demoting consumption (tobacco and alcohol). The household head's age, education, and employment contributed most to the structure effect. Conclusions: Our study suggested ethnic inequities in the health risk consumption behaviour are evidenced in NZ. Interventions targeting education and employment that significantly affect household budget shares on risk factors (i.e., harmful consumption) for health loss may help narrow the gaps.

Estimated Healthcare Costs of Melanoma and Keratinocyte Skin Cancers in Australia and Aotearoa New Zealand in 2021.

Australia and Aotearoa New Zealand have the highest incidence of melanoma and KC in the world. We undertook a cost-of-illness analysis using Markov decision-analytic models separately for melanoma and keratinocyte skin cancer (KC) for each country. Using clinical pathways, the probabilities and unit costs of each health service and medicine for skin cancer management were applied. We estimated mean costs and 95% uncertainty intervals (95% UI) using Monte Carlo simulation. In Australia, the mean first-year costs of melanoma per patient ranged from AU$644 (95%UI: $642, $647) for melanoma in situ to AU$100,725 (95%UI: $84,288, $119,070) for unresectable stage III/IV disease. Australian-wide direct costs to the Government for newly diagnosed patients with melanoma were AU$397.9 m and AU$426.2 m for KCs, a total of AU$824.0 m. The mean costs per patient for melanoma ranged from NZ$1450 (95%UI: $1445, $1456) for melanoma in situ to NZ$77,828 (95%UI $62,525, $94,718) for unresectable stage III/IV disease. The estimated total cost to New Zealand in 2021 for new patients with melanoma was NZ$51.2 m, and for KCs, was NZ$129.4 m, with a total combined cost of NZ$180.5 m. These up-to-date national healthcare costs of melanoma and KC in Australia and New Zealand accentuate the savings potential of successful prevention strategies for skin cancer.

Antiepileptic drugs for the primary and secondary prevention of seizures after stroke.

BACKGROUND: Seizures after stroke are an important clinical problem and may result in poor outcomes. The indications of antiepileptic drugs (AEDs) for seizure prophylaxis after stroke remain unclear. This is an updated version of the Cochrane Review previously published in 2014. OBJECTIVES: To assess the effects of AEDs for the primary and secondary prevention of seizures after stroke. For primary prevention, we aimed to assess whether AEDs reduce the likelihood of seizures in people who have a stroke but do not have a seizure. For secondary prevention, we aimed to assess whether AEDs reduce the likelihood of further seizures in people who have a stroke and at least one post-stroke seizure. SEARCH METHODS: We searched the following databases on 9 March 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to March 08, 2021). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organisation International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy and Stroke. We also checked the reference lists of articles retrieved from these searches. SELECTION CRITERIA: We selected randomised and quasi-randomised controlled studies that recruited participants with a clinical diagnosis of stroke, either ischaemic or haemorrhagic. We excluded studies that only recruited participants with subarachnoid haemorrhage, subdural haemorrhage, extradural haemorrhage, or other non-stroke diagnoses such as tumour- or infection-related infarction or haemorrhage. We also excluded studies that recruited only participants who had undergone neurosurgery. We included participants of all ages suffering any seizure type who were assigned to AEDs or placebo groups. DATA COLLECTION AND ANALYSIS: In accordance with standard methodological procedures expected by The Cochrane Collaboration, two review authors independently assessed trials for inclusion before evaluating trial risk of bias and extracting relevant data. The primary outcome assessed was the proportion of participants who experienced seizures in the follow-up period. We presented results as summary risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. Where we had sufficient data, we calculated random-effects (Mantel-Haenszel) meta-analyses for dichotomous outcomes; otherwise, we reported results narratively. We used the I2 statistic to analyse statistical heterogeneity. We planned to use funnel plots to assess publication bias in meta-analyses with at least 10 included studies. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: Two studies with a total of 856 subjects were included. AEDs were not shown to be effective in primary prophylaxis of post-stroke seizure (RR 0.65, 95% CI 0.34 to 1.26; 2 studies, 856 participants; moderate-certainty evidence). The first study was a randomised double-blind study comparing valproic acid with placebo for primary seizure prevention up to one year after stroke. The study included 72 adults with intracerebral haemorrhage. There was no difference in the risk of post-stroke seizures (RR 0.88, 95% CI 0.35 to 2.16) or of death (RR 1.20, 95% CI 0.40 to 3.58). The second study was a substudy on the use of diazepam in acute stroke. It was a randomised double-blind study, comparing a three-day diazepam treatment versus placebo for primary seizure prevention up to three months after stroke in 784 adults with acute stroke. There was no evidence of a difference in the risk of post-stroke seizures for all stroke or subgroups of haemorrhagic or ischaemic stroke (RR for all stroke 0.47, 95% CI 0.18 to 1.22). In a subgroup analysis of anterior circulation cortical infarcts, primary prophylaxis with diazepam was associated with a reduced risk of post-stroke seizures (RR 0.21, 95% CI 0.05 to 0.95). Risks of mortality did not differ between the diazepam and the placebo group at two weeks (RR 0.84, 95% CI 0.56 to 1.26) and three months follow-up (RR 0.95, 95% CI 0.72 to 1.26). We assessed both studies to be at a low overall risk of bias. Using the GRADE approach, we assessed the overall certainty of the evidence as low to moderate. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of AEDs on the primary and secondary prevention of seizures after stroke. Further well-conducted studies are warranted for this important clinical problem.

Generating political priority for skin cancer primary prevention: A case study from Aotearoa New Zealand.

ISSUES ADDRESSED: Skin cancer is highly prevalent but preventable, yet little research has been done on the challenges in generating political priority for skin cancer prevention. This qualitative study aimed to identify the political challenges to, facilitators of, and strategies to strengthen skin cancer prevention. The focus was on the case of Aotearoa New Zealand (NZ): a country with high skin cancer rates, but limited investment in primary prevention. METHODS: Data sources included 18 national key informant interviews and documentary analysis. Data were analysed inductively for emerging themes and framed using a conceptual framework of political priority. RESULTS: Challenges to advocates for skin cancer primary prevention include limited resources and competing priorities. Political-level challenges include a lack of quick results compared with other initiatives vying for political attention, lack of negative externalities and, in NZ, misalignment with health system priorities. Challenges in the evidence base include the perceived conflict of sun protection with Vitamin D and physical activity, the lack of data on the financial burden of skin cancer and relatively low temperatures in NZ. Facilitators include strong policy community cohesion and issue framing, and weak opposition. Promising strategies to strengthen skin cancer prevention in NZ could include network building, using framing that resonates with policy makers and addressing key knowledge gaps in NZ, such as the financial burden of skin cancer. CONCLUSION: Advocacy for skin cancer prevention faces challenges due to advocates' limited resources, political challenges such as lack of quick results and gaps in evidence. Nonetheless, the initiative encounters little opposition and can be framed in ways that resonate with policy makers. SO WHAT?: Skin cancer is highly preventable, but advocates for prevention initiatives have struggled to gain political traction. This study identifies several strategies that could help raise the political profile for skin cancer prevention.

Clinical and cost-effectiveness of an online-delivered group-based pain management programme in improving pain-related disability for people with persistent pain-protocol for a non-inferiority randomised controlled trial (iSelf-help trial).

INTRODUCTION: Persistent non-cancer pain affects one in five adults and is more common in Maori-the Indigenous population of New Zealand (NZ), adults over 65 years, and people living in areas of high deprivation. Despite the evidence supporting multidisciplinary pain management programmes (PMPs), access to PMPs is poor due to long waiting lists. Although online-delivered PMPs enhance access, none have been codesigned with patients or compared with group-based, in-person PMPs. This non-inferiority trial aims to evaluate the clinical and cost-effectiveness of a cocreated, culturally appropriate, online-delivered PMP (iSelf-help) compared with in-person PMP in reducing pain-related disability. METHODS AND ANALYSIS: Mixed-methods, using a modified participatory action research (PAR) framework, involving three phases. Phase I involved cocreation and cultural appropriateness of iSelf-help by PAR team members. Phase II: The proposed iSelf-help trial is a pragmatic, multicentred, assessor-blinded, two-arm, parallel group, non-inferiority randomised controlled trial. Adults (n=180, age ≥18 years) with persistent non-cancer pain eligible for a PMP will be recruited and block randomised (with equal probabilities) to intervention (iSelf-help) and control groups (in-person PMP). The iSelf-help participants will participate in two 60-minute video-conferencing sessions weekly for 12 weeks with access to cocreated resources via smartphone application and a password-protected website. The control participants will receive group-based, in-person delivered PMP. Primary outcome is pain-related disability assessed via modified Roland Morris Disability Questionnaire at 6 months post intervention. Secondary outcomes include anxiety, depression, stress, pain severity, quality of life, acceptance, self-efficacy, catastrophising and fear avoidance. Data will be collected at baseline, after the 12-week intervention, and at 3 and 6 months post intervention. We will conduct economic analyses and mixed-method process evaluations (Phase IIA). ETHICS AND DISSEMINATION: The Health and Disability Ethics Committee approved the study protocol (HDEC18/CEN/162). Phase III involves dissemination of findings guided by the PAR team as outcomes become apparent. TRIAL REGISTRATION NUMBER: ACTRN 12619000771156.

Prospective community programme versus parent-driven care to prevent respiratory morbidity in children following hospitalisation with severe bronchiolitis or pneumonia.

BACKGROUND: Hospitalisation with severe lower respiratory tract infection (LRTI) in early childhood is associated with ongoing respiratory symptoms and possible later development of bronchiectasis. We aimed to reduce this intermediate respiratory morbidity with a community intervention programme at time of discharge. METHODS: This randomised, controlled, single-blind trial enrolled children aged <2 years hospitalised for severe LRTI to 'intervention' or 'control'. Intervention was three monthly community clinics treating wet cough with prolonged antibiotics referring non-responders. All other health issues were addressed, and health resilience behaviours were encouraged, with referrals for housing or smoking concerns. Controls followed the usual pathway of parent-initiated healthcare access. After 24 months, all children were assessed by a paediatrician blinded to randomisation for primary outcomes of wet cough, abnormal examination (crackles or clubbing) or chest X-ray Brasfield score ≤22. FINDINGS: 400 children (203 intervention, 197 control) were enrolled in 2011-2012; mean age 6.9 months, 230 boys, 87% Maori/Pasifika ethnicity and 83% from the most deprived quintile. Final assessment of 321/400 (80.3%) showed no differences in presence of wet cough (33.9% intervention, 36.5% controls, relative risk (RR) 0.93, 95% CI 0.69 to 1.25), abnormal examination (21.7% intervention, 23.9% controls, RR 0.92, 95% CI 0.61 to 1.38) or Brasfield score ≤22 (32.4% intervention, 37.9% control, RR 0.85, 95% CI 0.63 to 1.17). Twelve (all intervention) were diagnosed with bronchiectasis within this timeframe. INTERPRETATION: We have identified children at high risk of ongoing respiratory disease following hospital admission with severe LRTI in whom this intervention programme did not change outcomes over 2 years. TRIAL REGISTRATION NUMBER: ACTRN12610001095055.

Mass media promotion of a smartphone smoking cessation app: modelled health and cost-saving impacts.

BACKGROUND: Smartphones are increasingly available and some high quality apps are available for smoking cessation. However, the cost-effectiveness of promoting such apps has never been studied. We therefore aimed to estimate the health gain, inequality impacts and cost-utility from a five-year promotion campaign of a smoking cessation smartphone app compared to business-as-usual (no app use for quitting). METHODS: A well-established Markov macro-simulation model utilising a multi-state life-table was adapted to the intervention (lifetime horizon, 3% discount rate). The setting was the New Zealand (NZ) population (N = 4.4 million). The intervention effect size was from a multi-country randomised trial: relative risk for quitting at 6 months = 2.23 (95%CI: 1.08 to 4.77), albeit subsequently adjusted to consider long-term relapse. Intervention costs were based on NZ mass media promotion data and the NZ cost of attracting a smoker to smoking cessation services (NZ$64 per person). RESULTS: The five-year intervention was estimated to generate 6760 QALYs (95%UI: 5420 to 8420) over the remaining lifetime of the population. For Maori (Indigenous population) there was 2.8 times the per capita age-standardised QALY gain relative to non-Maori. The intervention was also estimated to be cost-saving to the health system (saving NZ$115 million [m], 95%UI: 72.5m to 171m; US$81.8m). The cost-saving aspect of the intervention was maintained in scenario and sensitivity analyses where the discount rate was doubled to 6%, the effect size halved, and the intervention run for just 1 year. CONCLUSIONS: This study provides modelling-level evidence that mass-media promotion of a smartphone app for smoking cessation could generate health gain, reduce ethnic inequalities in health and save health system costs. Nevertheless, there are other tobacco control measures which generate considerably larger health gains and cost-savings such as raising tobacco taxes.

Studying third-parties and environments: New Zealand sun-safety research.

Wearable cameras have been used to study health behaviours, but their utility in assessing third-party behaviours and the built environment is uncertain. This paper reports on the feasibility of using wearable cameras for this purpose in a study of sun-protective behaviours and shade availability during school lunch-breaks. The Kids'Cam study provided 168 children (aged 11-13 years), recruited from 16 randomly selected schools in the Wellington region of New Zealand, with wearable cameras. The devices automatically captured images every 7 s from the child's perspective. Images captured during school lunch-breaks by a random sample of 15 children who took part during terms 4 and 1 (October 2014-April 2015) were selected and assessed for usability. The feasibility of studying third-party sun-protective behaviours and school shade availability was assessed for a subset of 320 images. Of the 3492 eligible lunch-break images, 96.4% were useable; the remainders were excluded due to obstruction, blurriness or unsuitable camera position. Overall, 1278 children and 108 shade structures were observed in the sample images. The use of shade, hats, sleeves, collars and sunglasses could be determined for 97.0%, 77.2%, 74.4%, 47.6% and 54.9% of children, respectively. All shade structures could be classified according to type, and canopy composition could be assessed for 95.4% of structures. Wearable cameras are a feasible tool for assessing sun-safety, particularly shade availability, hat wearing and shade use. This methodology could be used to objectively study other third-party health-related behaviours, and other features of the built environment.

Sun protection and shade availability in New Zealand's outdoor recreation spaces.

AIMS: We aimed to investigate sun protection behaviours and shade availability in outdoor recreation spaces using images captured by children who, in 2014/15, wore wearable cameras for four consecutive days. METHODS: The 168 participants visited 16 outdoor recreation spaces between 10am and 4pm, capturing 378 images, on average, in each setting. People observed in the images (n=2,635) were coded for age, sex, clothing worn (38 clothing types) and shade used. Mean temperature and ultraviolet index (UVI) values were linked with the time-stamped and geo-referenced images. RESULTS: The UVI in most settings was high enough to warrant sun protection, but only 4.3% of people wore sun-protective hats (broad-brim, bucket and legionnaire styles) and 10.7% used shade. Areas most popular with children, including playground equipment, beach sand and pool areas, had little or no shade available. CONCLUSIONS: Despite New Zealand having the highest incidence of melanoma skin cancer in the world, the results indicate that few New Zealanders wear hats and seek shade in outdoor recreation settings. The findings highlight the need to improve policy and environmental support for skin cancer prevention activities.

Sun Protection Among New Zealand Primary School Children.

Schools are an important setting for raising skin cancer prevention awareness and encouraging sun protection. We assessed the clothes worn and shade used by 1,278 children in eight schools in the Wellington region of New Zealand. These children were photographed for the Kids'Cam project between September 2014 and March 2015 during school lunch breaks. Children's mean clothing coverage (expressed as a percentage of body area covered) was calculated. Data on school sun-safety policies were obtained via telephone. Mean total body clothing coverage was 70.3% (95% confidence interval = 66.3%, 73.8%). Body regions with the lowest mean coverage were the head (15.4% coverage), neck (36.1% coverage), lower arms (46.1% coverage), hands (5.3% coverage), and calves (30.1% coverage). Children from schools with hats as part of the school uniform were significantly more likely to wear a hat (52.2%) than children from schools without a school hat (2.7%). Most children (78.4%) were not under the cover of shade. Our findings suggest that New Zealand children are not sufficiently protected from the sun at school. Schools should consider comprehensive approaches to improve sun protection, such as the provision of school hats, sun-protective uniforms, and the construction of effective shade.

A national quitline service and its promotion in the mass media: modelling the health gain, health equity and cost-utility.

BACKGROUND: Mass media campaigns and quitlines are both important distinct components of tobacco control programmes around the world. But when used as an integrated package, the effectiveness and cost-effectiveness are not well described. We therefore aimed to estimate the health gain, health equity impacts and cost-utility of the package of a national quitline service and its promotion in the mass media. METHODS: We adapted an established Markov and multistate life-table macro-simulation model. The population was all New Zealand adults in 2011. Effect sizes and intervention costs were based on past New Zealand quitline data. Health system costs were from a national data set linking individual health events to costs. RESULTS: The 1-year operation of the existing intervention package of mass media promotion and quitline service was found to be net cost saving to the health sector for all age groups, sexes and ethnic groups (saving $NZ84 million; 95%uncertainty interval 60-115 million in the base-case model). It also produced greater per capita health gains for Maori (indigenous) than non-Maori (2.2 vs 0.73 quality-adjusted life-years (QALYs) per 1000 population, respectively). The net cost saving of the intervention was maintained in all sensitivity and scenario analyses for example at a discount rate of 6% and when the intervention effect size was quartered (given the possibility of residual confounding in our estimates of smoking cessation). Running the intervention for 20 years would generate an estimated 54 000 QALYs and $NZ1.10 billion (US$0.74 billion) in cost savings. CONCLUSIONS: The package of a quitline service and its promotion in the mass media appears to be an effective means to generate health gain, address health inequalities and save health system costs. Nevertheless, the role of this intervention needs to be compared with other tobacco control and health sector interventions, some of which may be even more cost saving.

Clothing Protection from Ultraviolet Radiation: A New Method for Assessment.

Clothing modifies ultraviolet radiation (UVR) exposure from the sun and has an impact on skin cancer risk and the endogenous synthesis of vitamin D. There is no standardized method available for assessing body surface area (BSA) covered by clothing, which limits generalizability between study findings. We calculated the body cover provided by 38 clothing items using diagrams of BSA, adjusting the values to account for differences in BSA by age. Diagrams displaying each clothing item were developed and incorporated into a coverage assessment procedure (CAP). Five assessors used the CAP and Lund & Browder chart, an existing method for estimating BSA, to calculate the clothing coverage of an image sample of 100 schoolchildren. Values of clothing coverage, inter-rater reliability and assessment time were compared between CAP and Lund & Browder methods. Both methods had excellent inter-rater reliability (>0.90) and returned comparable results, although the CAP method was significantly faster in determining a person's clothing coverage. On balance, the CAP method appears to be a feasible method for calculating clothing coverage. Its use could improve comparability between sun-safety studies and aid in quantifying the health effects of UVR exposure.

Economic evaluation of an exercise-counselling intervention to enhance smoking cessation outcomes: The Fit2Quit trial.

BACKGROUND: In the Fit2Quit randomised controlled trial, insufficiently-active adult cigarette smokers who contacted Quitline for support to quit smoking were randomised to usual Quitline support or to also receive ≤10 face-to-face and telephone exercise-support sessions delivered by trained exercise facilitators over the 24-week trial. This paper aims to determine the cost-effectiveness of an exercise-counselling intervention added to Quitline compared to Quitline alone in the Fit2Quit trial. METHODS: Within-trial and lifetime cost-effectiveness were assessed. A published Markov model was adapted, with smokers facing increased risks of lung cancer and cardiovascular disease. RESULTS: Over 24 weeks, the incremental programme cost per participant in the intervention was NZ$428 (US$289 or €226; purchasing power parity-adjusted [PPP]). The incremental cost-effectiveness ratio (ICER) for seven-day point prevalence measured at 24-week follow-up was NZ$31,733 (US$21,432 or €16,737 PPP-adjusted) per smoker abstaining. However, for the 52% who adhered to the intervention (≥7 contacts), the ICER for point prevalence was NZ$3,991 (US$2,695 or €2,105 PPP-adjusted). In this adherent subgroup, the Markov model estimated 0.057 and 0.068 discounted quality-adjusted life-year gains over the lifetime of 40-year-old males (ICER: NZ$4,431; US$2,993 or €2,337 PPP-adjusted) and females (ICER: NZ$2,909; US$1,965 or €1,534 PPP-adjusted). CONCLUSIONS: The exercise-counselling intervention will only be cost-effective if adherence is a minimum of ≥7 intervention calls, which in turn leads to a sufficient number of quitters for health gains. TRIAL REGISTRATION: Australasian Clinical Trials Registry Number ACTRN12609000637246.

Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer by Age and Hormone Receptor Status: A Cost-Utility Analysis.

BACKGROUND: The anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab improves outcomes in patients with node-positive HER2+ early breast cancer. Given trastuzumab's high cost, we aimed to estimate its cost-effectiveness by heterogeneity in age and estrogen receptor (ER) and progesterone receptor (PR) status, which has previously been unexplored, to assist prioritisation. METHODS AND FINDINGS: A cost-utility analysis was performed using a Markov macro-simulation model, with a lifetime horizon, comparing a 12-mo regimen of trastuzumab with chemotherapy alone using the latest (2014) effectiveness measures from landmark randomised trials. A New Zealand (NZ) health system perspective was adopted, employing high-quality national administrative data. Incremental quality-adjusted life-years for trastuzumab versus chemotherapy alone are two times higher (2.33 times for the age group 50-54 y; 95% CI 2.29-2.37) for the worst prognosis (ER-/PR-) subtype compared to the best prognosis (ER+/PR+) subtype, causing incremental cost-effectiveness ratios (ICERs) for the former to be less than half those of the latter for the age groups from 25-29 to 90-94 y (0.44 times for the age group 50-54 y; 95% CI 0.43-0.45). If we were to strictly apply an arbitrary cost-effectiveness threshold equal to the NZ gross domestic product per capita (2011 purchasing power parity [PPP]-adjusted: US$30,300; €23,700; £21,200), our study suggests that trastuzumab (2011 PPP-adjusted US$45,400/€35,900/£21,900 for 1 y at formulary prices) may not be cost-effective for ER+ (which are 61% of all) node-positive HER2+ early breast cancer patients but cost-effective for ER-/PR- subtypes (37% of all cases) to age 69 y. Market entry of trastuzumab biosimilars will likely reduce the ICER to below this threshold for premenopausal ER+/PR- cancer but not for ER+/PR+ cancer. Sensitivity analysis using the best-case effectiveness measure for ER+ cancer had the same result. A key limitation was a lack of treatment-effect data by hormone receptor subtype. Heterogeneity was restricted to age and hormone receptor status; tumour size/grade heterogeneity could be explored in future work. CONCLUSIONS: This study highlights how cost-effectiveness can vary greatly by heterogeneity in age and hormone receptor subtype. Resource allocation and licensing of subsidised therapies such as trastuzumab should consider demographic and clinical heterogeneity; there is currently a profound disconnect between how funding decisions are made (largely agnostic to heterogeneity) and the principles of personalised medicine.

Decision-making in an era of cancer prevention via aspirin: New Zealand needs updated guidelines and risk calculators.

Based on new systematic reviews of the evidence, the US Preventive Services Task Force has drafted updated guidelines on the use of low-dose aspirin for the primary prevention of both cardiovascular disease (CVD) and cancer. The Task Force generally recommends consideration of aspirin in adults aged 50-69 years with 10-year CVD risk of at least 10%, in who absolute health gain (reduction of CVD and cancer) is estimated to exceed absolute health loss (increase in bleeds). With the ongoing decline in CVD, current risk calculators for New Zealand are probably outdated, so it is difficult to be precise about what proportion of the population is in this risk category (roughly equivalent to 5-year CVD risk ≥5%). Nevertheless, we suspect that most smokers aged 50-69 years, and some non-smokers, would probably meet the new threshold for taking low-dose aspirin. The country therefore needs updated guidelines and risk calculators that are ideally informed by estimates of absolute net health gain (in quality-adjusted life-years (QALYs) per person) and cost-effectiveness. Other improvements to risk calculators include: epidemiological rigour (eg, by addressing competing mortality); providing enhanced graphical display of risk to enhance risk communication; and possibly capturing the issues of medication disutility and comparison with lifestyle changes.

Alternatives to colonoscopy for population-wide colorectal cancer screening.

Colorectal cancer is one of the top three cancers in the world in terms of incidence. Colonoscopy, which many regard as the gold standard in diagnosis of colonic polyps and neoplasm, is costly, invasive and labour-intensive, and deemed an unsuitable population-wide index screening tool. Alternative modalities, including guaiac and immunohistochemical faecal occult blood tests, computed tomographic colonography, colon capsule endoscopy, flexible sigmoidoscopy, and double-contrast barium enema are available. The procedures, test characteristics, and their implications are reviewed. Immunohistochemical faecal occult blood testing appears to be the most suitable population-wide screening test for an average-risk population, with flexible sigmoidoscopy as an alternative. More evidence is needed to determine the role of computed tomographic colonography and colon capsule endoscopy in colorectal cancer screening.