Explore the vast range of titles available.

Background Combining short-acting nicotine replacement therapy with varenicline increases smoking cessation rates compared with varenicline alone, but not all people tolerate these medications or find them helpful. We aim to investigate the therapeutic potential of an analogous combination, by evaluating the effectiveness, safety, and acceptability of combining nicotine salt e-cigarettes with cytisine, compared to nicotine salt e-cigarettes or cytisine only, on smoking abstinence at six months. Methods A pragmatic, community-based, investigator-blinded, randomised superiority trial design will be utilised. Eligible participants will be people who smoke daily ( N  = 800, 90% power) from throughout New Zealand, who are: aged ≥ 18 years, motivated to quit in the next two weeks, able to provide online consent, willing to use e-cigarettes and/or cytisine, and have daily access to a mobile phone. Recruitment will utilise multi-media advertising. Participants will be randomised (3:3:2 ratio) to 12 weeks of: 1) e-cigarettes (closed pod system, 3% nicotine salt, tobacco flavour) plus cytisine; 2) e-cigarettes alone, or 3) cytisine alone. All groups will receive a six-month, text-message-based behavioural support programme. The primary outcome is self-reported, biochemically verified, continuous abstinence at six months post-quit date. Secondary outcomes, measured at quit date, then one, three, six, and 12 months post-quit date, include self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes smoked per day, withdrawal and urge to smoke, time to (re)lapse, treatment use and compliance, treatment crossover, dual-use, use of other cessation products, change in e-cigarette products, continuation of product use, acceptability, change in health state, health-related quality of life, change in body mass index, adverse events, and cost per quitter. Discussion Pragmatic trials are of particular value as they reflect the ‘real world’ impact of interventions. The trial will provide some of the first evidence on the effectiveness of combining nicotine salt e-cigarettes with cytisine for smoking cessation, in a country with strong tobacco control policy. Findings will be incorporated into relevant systematic reviews, informing practice and policy. Trial registration NCT05311085 ClinicalTrials.gov. Registered 5th April, 2022.

Molecular testing is fundamental to the modern precision oncology toolkit. However, set on a backdrop of inconsistent use of the term ‘value’ in healthcare literature, evidentiary limitations in what determines ‘high-value’ molecular testing have contributed to its variable adoption in the clinic. Key to an improved understanding of value in this setting is eliciting what outcomes (health and non-health) and costs of molecular testing are important to the relevant stakeholders and what contextual considerations influence this. This protocol describes the first stage of a multi-staged mixed methods study to elicit preferences and views on the value of molecular testing among the stakeholders relevant to an Aotearoa New Zealand societal perspective. Semi-structured interviews, focus groups, and questionnaires will elicit the elements that determine the value of molecular testing for patients and family | whānau (Māori and non-Māori), clinicians, testing providers, molecular medicine researchers, industry (pharmaceutical and diagnostic) members, and decision-makers. Interviews and focus groups will be analysed using thematic analysis and questionnaire data will be analysed using descriptive statistics. Identifying the elements of molecular testing in cancer that warrant consideration in value assessment discussion is a prerequisite to modernizing and improving health technology assessment and funding decision-making processes. Findings from this qualitative study will inform the second stage (presented in a subsequent paper) of this multi-staged mixed-methods study, which will use the identified elements in a discrete choice experiment to understand different stakeholders’ preferences and tradeoffs.

Abstract Sporadically occurring malignant peripheral nerve sheath tumours (MPNSTs) can have a variety of genomic alterations including altered NF1, leading to activation of the RAS-RAF-MEK-ERK signalling pathway. Trametinib is an inhibitor of MEK1 and MEK2. Here we present a case of a patient diagnosed with sporadic MPNST with an identified NF1 gene treated successfully with trametinib.

In February 2023, Severe Tropical Cyclone Gabrielle devastated the North Island of Aotearoa New Zealand with loss of life, extreme flooding, damage to homes, roads and infrastructure particularly in the regions of Te Tairāwhiti (Gisborne) and the Te Matau-a-Māui (Hawke's Bay). This paper presents key findings from a qualitative study of the impacts of Cyclone Gabrielle on community health and wellbeing in these two communities. Drawing upon interviews and focus groups with 143 residents of these two regions, we present five high-level findings, specifically the impacts on: (1) physical health, (2) mental wellbeing, (3) the most at-risk groups (i.e. residents with a disability, chronic illness, elderly), (4) rural and remote communities, and (5) communities of care. This paper contributes to Critical Disaster Studies, with a focus on the uneven health and wellbeing impacts of extreme weather events. It also highlights how communities come together to support one another, grieve and recover in relational and connected ways. Additionally, it underscores the value of trauma-informed, place-based methodologies for conducting ethical and responsible research within, by and for affected communities.

Background Smoking rates are higher in New Zealand (NZ) adults with mental illnesses and alcohol and other drug (AOD) addictions, compared to the overall population. Quit attempts using “gold standard” smoking cessation treatments often fail in people with these conditions, so more flexible treatment regimens that adapt to a person’s responsiveness to treatment are worth investigating. The STATUS trial aims to evaluate the effectiveness and safety of combining varenicline with nicotine e-cigarettes for smoking cessation among varenicline non-responders in treatment for mental health illnesses and/or AOD addictions. Methods This is a pragmatic two-arm, open-label, randomised trial. Participants will be daily smokers using mental health and/or addiction services in Auckland, aged ≥18 years, motivated to quit smoking, and eligible to access varenicline through the NZ special authority process. After 2 weeks of using varenicline plus behavioural support, participants who have not reduced their daily smoking by ≥50% will be randomised (1:1) to either 10 weeks of continued varenicline use or 10 weeks of varenicline plus an 18 mg/mL nicotine e-cigarette. All participants will receive weekly withdrawal-orientated behavioural support calls for 6 weeks post-randomisation. The primary outcome is self-reported biochemically-verified (exhaled carbon monoxide) continuous abstinence at 24 weeks post-randomisation. Secondary outcomes, measured at six, 12 and 24 weeks post-randomisation include: self-reported continuous abstinence, 7-day point prevalence abstinence, smoking reduction, time to relapse, cross-over, use of other smoking cessation support, serious adverse events, treatment adherence, compliance, acceptability, dual use, continuation of treatment use, mental illness symptoms and AOD use, health-related quality of life, and cost-analysis. A sample size of 338 will confer 80% power ( p  = 0.05) to detect a 15% absolute difference between the varenicline alone and varenicline plus e-cigarette groups. Discussion People with mental illness and/or AOD addictions are just as motivated as others to quit smoking, but are less likely to succeed. Adapting smoking cessation medication after a lack of responsiveness in the first 2 weeks of initial treatment in this priority population by adding a nicotine e-cigarette may be one way to increase long-term quit rates. Trial Registration Australian NZ Clinical Trial Registry: ACTRN12616001355460 (29 September 2016).

IntroductionCompression is the mainstay of treatment for venous leg ulcers (VLUs) and there are few effective adjuvant treatments. There is only observational evidence supporting the use of hypochlorous acid (HOCl) as a topical wound solution on VLU and some limited randomised evidence for the effect of a prescribed regimen of exercise.Methods and analysisThe Factorial4VLU trial is a pragmatic, blinded, factorial randomised controlled trial, with 380 participants receiving either a prescribed exercise regimen compared with usual care and either active HOCl wound solution or placebo wound solution at each dressing change for up to 24 weeks. All participants will receive compression therapy. The primary outcome is the proportion of participants with healed VLU at 12 weeks after randomisation as adjudicated by blinded review of ulcer photographs. Secondary outcomes are proportion healed at 24 weeks, time to healing, estimated change in ulcer area, change in 2-Minute Walk Test, change in health-related quality of life, incidence of infection and incidence of all-cause adverse events. If either of the interventions shows a statistically significant positive difference on healing outcomes, cost-effectiveness will be modelled using a health service perspective.Ethics and disseminationThe Factorial4VLU trial received ethical approval from the Northern B Health and Disability Ethics Committee. We plan to publish the results within 1 year of trial completion and will include the results on the trial registration page.Trial registration numbersAustralia and New Zealand Clinical Trials Register (http://www.anzctr.org.au) (ACTRN12620000116921); Universal Trial Number (WHO) (U1111-1236-2997).

Over the last 10 years there has been an explosion of information about the molecular biology of cancer. A challenge in oncology is to translate this information into advances in patient care. While there are well-formed routes for translating new molecular information into drug therapy, the routes for translating new information into sensitive and specific diagnostic, prognostic and predictive tests are still being developed. Similarly, the science of using tumor molecular profiles to select clinical trial participants or to optimize therapy for individual patients is still in its infancy. This review will summarize the current technologies for predicting treatment response and prognosis in cancer medicine, and outline what the future may hold. It will also highlight the potential importance of methods that can integrate molecular, histopathological and clinical information into a synergistic understanding of tumor progression. While these possibilities are without doubt exciting, significant challenges remain if we are to implement them with a strong evidence base in a widely available and cost-effective manner.

Tobacco has been known to contain radioactive polonium and lead for 50 years but the literature is divided as to the public health significance. I review the data on tobacco radioactivity and its internalization by smokers. Data sources: Reports of lead-210 and polonium-210 content of tobacco leaf, cigarettes, cigarette smoke, and human respiratory tissues, published between 1964 and September 2017. Study selection: Any identified study that reported values for lead-210 and polonium-210 content. Data extraction: Data quality was addressed by comparative review of analytic methods. The data about radiation content of tobacco and smoke are robust. Early reports suggesting microsievert lifetime doses of inhaled radioactivity to smokers were not borne out. The results remain sensitive to pharmacological assumptions around absorption and redistribution of inhaled radionuclides, and radiobiological assumptions about interaction with human tissues. Literature on tobacco radioactivity has not fully contended with pharmacological and radiobiological uncertainty, and is therefore divided as to health significance. This does much to explain regulatory inaction over the last half century. Before radiation safety law can offer a vehicle for tobacco control, more must be learnt about the pharmacology and radiobiology of inhaled radionuclides in tobacco smoke. This work makes it apparent that the study of tobacco smoke radioactivity has been scientifically stagnant for the last 40 years. The field cannot advance until we improve understanding of the pharmacology and radiobiology of inhaled radionuclides in tobacco smoke. Despite this, a subset of contemporary authors is still suggesting individual health risks about 1000 times higher than can be supported by internationally accepted models.

Health care system-wide outcomes from routine treatment with erlotinib and gefitinib are incompletely understood. The aim of the study is to describe the effectiveness of erlotinib and gefitinib during the first decade of their routine use for treating advanced epidermal growth factor receptor (EGFR) mutation-positive nonsquamous non-small cell lung cancer in the entire cohort of patients treated in Aotearoa New Zealand. Patients were identified, and data collated from national pharmaceutical dispensing, cancer registration, and mortality registration electronic databases by deterministic data linkage using National Health Index numbers. Time-to-treatment discontinuation and overall survival were measured from the date of first dispensing of erlotinib or gefitinib and analyzed by Kaplan-Meier curves. Associations of treatment outcomes with baseline factors were evaluated using univariable and multivariable Cox regressions. Overall, 752 patients were included who started treatment with erlotinib (n=418) or gefitinib (n=334) before October 2020. Median time-to-treatment discontinuation was 11.6 (95% CI 10.8-12.4) months, and median overall survival was 20.1 (95% CI 18.1-21.6) months. Shorter time-to-treatment discontinuation was independently associated with high socioeconomic deprivation (hazard ratio [HR] 1.3, 95% CI 1.1-1.5 compared to the New Zealand Index of Deprivation 1-4 group), EGFR L858R mutations (HR 1.3, 95% CI 1.1-1.6 compared to exon 19 deletion), and distant disease at cancer diagnosis (HR 1.4, 95% CI 1.2-1.7 compared to localized or regional disease). The same factors were independently associated with shorter overall survival. Outcome estimates and predictors remained unchanged in sensitivity analyses. Outcomes from routine treatment with erlotinib and gefitinib in New Zealand patients with advanced EGFR-mutant nonsquamous non-small cell lung cancer are comparable with those reported in randomized trials and other health care system-wide retrospective cohort studies. Socioeconomic status, EGFR mutation subtype, and disease extent at cancer diagnosis were independent predictors of treatment outcomes in that setting.