Erlotinib or Gefitinib for Treating Advanced Epidermal Growth Factor Receptor Mutation-Positive Lung Cancer in Aotearoa New Zealand: Protocol for a National Whole-of-Patient-Population Retrospective Cohort Study and Results of a Validation Substudy.

BACKGROUND: Starting in 2010, the epidermal growth factor receptor (EGFR) kinase inhibitors erlotinib and gefitinib were introduced into routine use in Aotearoa New Zealand (NZ) for treating advanced lung cancer, but their impact in this setting is unknown. OBJECTIVE: The study described in this protocol aims to understand the effectiveness and safety of these new personalized lung cancer treatments and the contributions made by concomitant medicines and other factors to adverse outcomes in the general NZ patient population. A substudy aimed to validate national electronic health databases as the data source and the methods for determining patient eligibility and identifying outcomes and variables. METHODS: This study will include all NZ patients with advanced EGFR mutation-positive lung cancer who were first dispensed erlotinib or gefitinib before October 1, 2020, and followed until death or for at least 1 year. Routinely collected health administrative and clinical data will be collated from national electronic cancer registration, hospital discharge, mortality registration, and pharmaceutical dispensing databases by deterministic data linkage using National Health Index numbers. The primary effectiveness and safety outcomes will be time to treatment discontinuation and serious adverse events, respectively. The primary variable will be high-risk concomitant medicines use with erlotinib or gefitinib. For the validation substudy (n=100), data from clinical records were compared to those from national electronic health databases and analyzed by agreement analysis for categorical data and by paired 2-tailed t tests for numerical data. RESULTS: In the validation substudy, national electronic health databases and clinical records agreed in determining patient eligibility and for identifying serious adverse events, high-risk concomitant medicines use, and other categorical data with overall agreement and κ statistic of >90% and >0.8000, respectively; for example, for the determination of patient eligibility, the comparison of proxy and standard eligibility criteria applied to national electronic health databases and clinical records, respectively, showed overall agreement and κ statistic of 96% and 0.8936, respectively. Dates for estimating time to treatment discontinuation and other numerical variables and outcomes showed small differences, mostly with nonsignificant P values and 95% CIs overlapping with zero difference; for example, for the dates of the first dispensing of erlotinib or gefitinib, national electronic health databases and clinical records differed on average by approximately 4 days with a nonsignificant P value of .33 and 95% CIs overlapping with zero difference. As of May 2024, the main study is ongoing. CONCLUSIONS: A protocol is presented for a national whole-of-patient-population retrospective cohort study designed to describe the safety and effectiveness of erlotinib and gefitinib during their first decade of routine use in NZ for treating EGFR mutation-positive lung cancer. The validation substudy demonstrated the feasibility and validity of using national electronic health databases and the methods for determining patient eligibility and identifying the study outcomes and variables proposed in the study protocol. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000998549; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368928. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51381.

Exploring the Use of Traditional Medicines, Natural Health Products and Conventional Medicines: Development and Testing of the New Zealand 'All-Medicines' Questionnaire.

INTRODUCTION: Traditional, complementary and alternative medicine (TCAM) are popular healthcare choices among consumers globally. The latest national data on the use of TCAM practitioners in New Zealand (NZ) were collected over a decade ago. Robust data on the use of natural health products (NHPs) and TCAM practices alongside conventional medicines are not yet available in NZ. OBJECTIVES: This study aimed to develop and test a bespoke questionnaire (All-MedsNZ) that included comprehensive data collection elements exploring NHPs' and conventional medicines' use. METHODS: This was a questionnaire design study involving expert panel feedback, and engagement with TCAM users, in the development process. This work comprised questionnaire development (stage 1) followed by a questionnaire-testing study (stage 2). The questionnaire was developed on the basis of literature review findings and the research team's expertise. The questionnaire content was then validated by an expert panel comprising practitioners in TCAM and conventional medicine. Then, a two-phase study was utilised to test the questionnaire. Phase 1 involved participants (NHP users) completing the web-based questionnaire and providing feedback by answering probing questions added throughout the questionnaire to evaluate users' comprehension of the questions and to identify issues with the questionnaire. In phase 2, selected participants were interviewed online to gain in-depth insights into issues identified in phase one. Based on these findings, the questionnaire was revised. RESULTS: The expert panel (n = 9) confirmed the questionnaire had high face and content validity; most original questions were retained. In the questionnaire-testing study, 95 and 27 participants completed the phase 1 and 2 studies, respectively. Most questions achieved a high response rate of ≥ 90%, and participants had no major issues understanding and answering the questionnaire. Problematic questions were those relating to providing product barcodes and photographs, and information on product costs. Most of the NHPs data entered by participants included the brand/generic name, manufacturer/company name, main ingredient(s) and dose form. Generally, these NHP-related data were of acceptable quality. However, information on the main ingredient(s) of products entered by participants was less satisfactory: approximately one-third of the 143 NHPs recorded in the study had the main ingredient(s) missing or incorrectly stated. Interviews with participants reiterated the issues identified in the phase 1 study. The low response rates for some of the questions were partly due to participants' unpreparedness (i.e. not having NHPs/medicines on hand) to complete the questionnaire. In addition, a lack of clarity for the term 'natural health practitioner' led to confusion among some participants. CONCLUSION: Overall, no major design-, method- or questionnaire-related issues were identified in this development and testing work. The questionnaire demonstrated adequate face and content validity and acceptability among participants. The data collected were reasonably complete and of sufficient quality for analysis. Future studies should pilot the revised All-MedsNZ questionnaire with a larger, nationally representative sample to ascertain its feasibility and utility.

Effectiveness of nicotine salt vapes, cytisine, and a combination of these products, for smoking cessation in New Zealand: protocol for a three-arm, pragmatic, community-based randomised controlled trial.

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.

Prevalence of Use of Traditional, Complementary and Alternative Medicine by the General Population: A Systematic Review of National Studies Published from 2010 to 2019.

INTRODUCTION: Traditional, complementary and alternative medicine (TCAM) refers to a broad range of health practices and products typically not part of the 'conventional medicine' system, and its use is substantial among the general population. TCAM products and therapies may be used in addition to, or instead of, conventional medicine approaches, and some have been associated with adverse reactions or other harms. OBJECTIVES: The aims of this systematic review were to identify and examine recently published national studies globally on the prevalence of TCAM use in the general population, to review the research methods used in these studies and to propose best practices for future studies exploring prevalence of use of TCAM. METHODS: MEDLINE, Embase, CINAHL, PsycINFO and AMED were searched to identify relevant studies published since 2010. Articles/reports describing the prevalence of TCAM use in a national study among the general population were included. The quality of included studies was assessed using a risk of bias tool developed by Hoy et al. Relevant data were extracted and summarised. RESULTS: Forty studies from 14 countries, comprising 21 national surveys and one cross-national survey, were included. Studies explored the use of TCAM products (e.g. herbal medicines), TCAM practitioners/therapies, or both. Included studies used different TCAM definitions, prevalence time frames and data collection tools, methods and analyses, thereby limiting comparability across studies. The reported prevalence of use of TCAM (products and/or practitioners/therapies) over the previous 12 months was 24-71.3%. CONCLUSION: The reported prevalence of use of TCAM (products and/or practitioners/therapies) is high, but may underestimate use. Published prevalence data varied considerably, at least in part because studies utilise different data collection tools, methods and operational definitions, limiting cross-study comparisons and study reproducibility. For best practice, comprehensive, detailed data on TCAM exposures are needed, and studies should report an operational definition (including the context of TCAM use, products/practices/therapies included and excluded), publish survey questions and describe the data-coding criteria and analysis approach used.

Traditional, complementary and alternative medicine (TCAM) includes products (e.g. herbal medicines, dietary supplements) and therapies/practices (e.g. chiropractic, acupuncture), and is a popular healthcare choice for many people. This study systematically reviewed national surveys of TCAM use around the world. We identified studies carried out in 14 different countries and one continent (Europe) on the extent of use of TCAM in the general population. TCAM use was found to be substantial, ranging from 24 to 71.3% in different countries. National surveys use different methods and different survey questionnaires. Some studies did not publish the survey questionnaire that they used and/or did not describe the types of TCAM included in the study. This means that it is not possible to compare the results between countries or to do further data analysis. For example, the survey questions from different countries asked people if they had 'used' or 'seen a practitioner' for a specific therapy, such as homeopathy. These questions look similar, but could elicit different answers from people. This means that the answers to these questions cannot be pooled together or compared directly. Also, some studies collected information on use of a category of TCAM products, such as herbal medicines, but other studies collected information on use of specific herbal medicines, such as St John's wort. New surveys of the extent of use of TCAM should provide full information on the types of TCAM products, practices and therapies included in the study and consider collecting comprehensive information on use of specific TCAM products, practices and therapies.

Mapping prevalence and patterns of use of, and expenditure on, traditional, complementary and alternative medicine in New Zealand: a scoping review of qualitative and quantitative studies.

AIM: Traditional, complementary and alternative medicine (TCAM) is a popular healthcare choice worldwide. The extent of data available on TCAM, including prevalence and patterns of use in New Zealand, is unknown. This scoping review aims to map the existing research describing the use of TCAM (including prevalence, access, expenditure and concurrent use with conventional medicines) in New Zealand. METHOD: Research databases (MEDLINE, EMBASE, AMED, IPA (International Pharmaceutical Abstracts), CINAHL, PsycINFO and Scopus) and grey literature (Google Scholar and New Zealand government and relevant organisations' websites) were searched for studies published before 7 June 2019. Studies reporting on the prevalence and/or exploring aspects of TCAM use were included in this review. RESULTS: In total, 72 studies were reviewed. Available data suggest that TCAM use is widespread among New Zealanders, and some consumers pay large sums of money out-of-pocket. A wide range of TCAM practices and products is used by people of all ages and ethnicities and with various health conditions. There is some evidence of consumers using TCAM concurrently with conventional medicines. Studies were generally small, localised and conducted in sub-populations (e.g., specific age groups, health conditions). Different TCAM definitions, data collection tools, methods and prevalence measurement were used across studies, thereby limiting the comparability of data locally and internationally. CONCLUSION: A considerable number of studies/reports on TCAM use are available. Still, there is a lack of comprehensive, nationally representative data on prevalence and patterns of use of TCAM, including its use in relation to conventional medicine(s) in New Zealand.

Study of Natural Products Adverse Reactions (SONAR) in Adults with Mental Health Conditions: A Cross-Sectional Study.

INTRODUCTION: Mental illness is a leading cause of non-fatal disease burden worldwide. Natural health products (NHPs) are sought by patients with mental health conditions as a safer and more 'natural' option than conventional pharmacotherapy; however, the possible adverse events (AE) and interactions between NHPs and prescription medicines are not fully known. OBJECTIVES: The aim of this study was to determine (i) the prevalence of adult patients with mental health conditions taking prescription medications only, NHPs only, NHPs and prescription medications concurrently, or neither, (ii) which prescription medications and NHPs are most commonly used, (iii) AEs (serious and non-serious) experienced in the last 30 days for each product use group. METHODS: Mental health clinics in Alberta and Ontario, Canada, were included in an active surveillance study investigating NHP-drug interactions. On their first clinic visit, adult mental health patients were provided with a form inquiring about prescription drug use, NHP use, and any undesirable health events experienced in the last month. Healthcare professionals were also asked to report AEs. RESULTS: A total of 3079 patients were screened at 11 mental health clinics in Alberta and Ontario. In total, 620 AEs were reported in 447 patients (14.9%). The majority of adverse events were seen in patients using both NHPs and prescription medicines (58.8%), followed by patients taking only prescription medicines (37.1%), NHPs only (3.4%) and neither (0.67%). Combining NHPs and prescription medications increases the likelihood of experiencing AEs (OR 2.1; p < 0.001; 95% CI 1.7-2.6). CONCLUSIONS: Adult patients with mental health conditions who are taking both prescription medications and NHPs are more likely to report an adverse event than patients taking prescription drugs or NHPs alone. Polypharmacy increases the likelihood of an adverse event. Active surveillance is feasible and could contribute to enhanced pharmacovigilance.

Cytisine versus varenicline for smoking cessation in New Zealand indigenous Maori: a randomized controlled trial.

AIM: To determine whether cytisine was at least as effective as varenicline in supporting smoking abstinence for ≥ 6 months in New Zealand indigenous Maori or whanau (extended-family) of Maori, given the high smoking prevalence in this population. DESIGN: Pragmatic, open-label, randomized, community-based non-inferiority trial. SETTING: Bay of Plenty, Tokoroa and Lakes District Health Board regions of New Zealand. PARTICIPANTS: Adult daily smokers who identified as Maori or whanau of Maori, were motivated to quit in the next 2 weeks, were aged ≥ 18 years and were eligible for subsidized varenicline. Recruitment used multi-media advertising. INTERVENTIONS: A total of 679 people were randomly assigned (1 : 1) to receive a prescription for 12 weeks of cytisine or varenicline, plus low-intensity cessation behavioural support from the prescribing doctor and community stop-smoking services or a research assistant. Day 5 of treatment was the designated quit date. MEASUREMENTS: The primary outcome was carbon monoxide-verified continuous abstinence at 6 months, analysed as intention-to-treat (with multiple imputation for missing data). Secondary outcomes measured at 1, 3, 6 and 12 months post-quit date included: self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance and acceptability, nicotine withdrawal/urge to smoke and health-care utilization/health-related quality of life. FINDINGS: Verified continuous abstinence rates at 6 months post-quit date were 12.1% (41 of 337) for cytisine versus 7.9% (27 of 342) for varenicline [risk difference 4.29%, 95% confidence interval (CI) = -0.22 to 8.79; relative risk 1.55; 95% CI = 0.97-2.46]. Sensitivity analyses confirmed that the findings were robust. Self-reported adverse events over 6 months occurred significantly more frequently in the varenicline group (cytisine: 313 events in 111 participants; varenicline: 509 events in 138 participants, incidence rate ratio 0.56, 95% CI = 0.49-0.65, P < 0.001) compared with the cytisine group. Common adverse events were headache, nausea and difficulty sleeping. CONCLUSION: A randomized controlled trial found that cytisine was at least as effective as varenicline at supporting smoking abstinence in New Zealand indigenous Maori or whanau (extended-family) of Maori, with significantly fewer adverse events.

Study of Natural products Adverse Reactions (SONAR) in children seen in mental health clinics: a cross-sectional study.

BACKGROUND: Paediatric mental health patients frequently use natural health products (NHP) in addition to prescription medications, but very little is known about adverse events and possible NHP-drug interactions. OBJECTIVE: To determine: (1) the prevalence of paediatric mental health patients taking prescription medications only, NHP only, both NHP and prescription medications concurrently or neither; (2) which prescription medications and NHP are most commonly used in paediatric mental health populations and (3) adverse events experienced in the last 30 days (serious and non-serious). DESIGN: Cross-sectional surveillance study. SETTING: Paediatric mental health clinics. POPULATION/INTERVENTION: On their first clinic visit, paediatric mental health patients were provided with a form inquiring about prescription drug use, NHP use and any undesirable event experienced in the last month. RESULTS: Of the 536 patients included in this study, 23% (n=120) reported taking only prescription medication(s), 21% (n=109) reported only NHP use, 21% (n=112) reported using both NHP and prescription drugs concurrently, and 36% (n=191) reported using neither. Overall, there were 23 adverse events reported; this represents 6.3%, 2.8%, 10.8% and 0.6% of each population, respectively. The majority of patients who experienced an adverse event reported taking more than one NHP or prescription drug. No serious adverse events were reported. CONCLUSION: Nearly half of the paediatric mental health patients in this study were taking NHPs alone or in addition to prescription medications. Active surveillance identified multiple adverse events associated with NHP and prescription drug use; none were serious. Healthcare professionals were encouraged to initiate conversations regarding NHP use.

Community Pharmacists' Views and Experiences with ADR Reporting for Complementary Medicines: A Qualitative Study in New Zealand.

INTRODUCTION: Detecting signals of safety concerns associated with complementary medicines (CMs) relies on spontaneous reports submitted by health professionals and patients/consumers. Community pharmacists are well placed to identify and report suspected adverse drug reactions (ADRs) associated with CMs, but pharmacists submit few CMs ADR reports. OBJECTIVES: The aim of this study was to explore New Zealand community pharmacists' views and experiences with ADR reporting for CMs. METHODS: Qualitative, in-depth, semi-structured interviews were undertaken with 27 practising community pharmacists identified through purposive and convenience sampling. Data were analysed using a general inductive approach. RESULTS: Participants were familiar with systems for reporting ADRs, believed ADR reporting for CMs important, and that pharmacists should contribute. However, few submitted reports of CMs ADRs and none encouraged patients/consumers to do so. Participants explained this was because they had never been informed by patients about ADRs associated with CMs. Participants said they would report serious ADRs; time pressures, lack of certainty around causality, lack of awareness of mechanisms for reporting CMs ADRs, and lack of remuneration were deterrents to reporting. Participants were aware of intensive-monitoring studies for prescription medicines, understood the rationale for considering this approach for CMs and recognised there would be potential practical difficulties. CONCLUSIONS: Participants used their knowledge of CMs safety concerns to minimise risk of harms to consumers from CMs use, but most had a passive approach to identifying and reporting ADRs for CMs. There is substantial potential for pharmacists to adopt proactive strategies in pharmacovigilance for CMs, particularly in recognising and reporting ADRs, and empowering CMs users to do the same.

Community pharmacists' professional practices for complementary medicines: a qualitative study in New Zealand.

Background Complementary medicines are a popular healthcare choice among patients/consumers, and most pharmacies sell these products. Pharmacists are well-placed to advise on complementary medicines, but their training and practices for these products are not optimal. Pharmacists' professional practices for complementary medicines ought to be influenced by professional codes of ethics and standards. Objective To examine community pharmacists' perspectives on complementary medicines in New Zealand, including motivations and justifications for selling these products, and professional and ethical issues complementary medicines raise for pharmacists. Setting Community pharmacists in New Zealand. Method Qualitative, semi-structured interviews with 27 New Zealand practising community pharmacists identified through purposive and convenience sampling. Main outcome measure Participants' views, experiences, and professional practices for complementary medicines. Results Participants struggled to clearly describe products they considered complementary medicines. Perspectives towards these products ranged from strongly supportive to somewhat sceptical; none was strongly opposed. Participants had several motivations for selling complementary medicines, particularly consumer demand and profits. Participants acknowledged ethical issues concerning complementary medicines, including lack of evidence of efficacy and pharmacists' limited training/knowledge. Few referred explicitly to complementary-medicines-related statements in the Pharmacy Council of New Zealand's Code of Ethics, or indicated these guided their practice. Conclusion Participants sold complementary medicines despite having limited knowledge on these products and concerns about efficacy; participants justified this as they believe they are providing an holistic option for patients, and/or ensuring complementary medicines do no harm. Participants were mindful of ethical/professional issues regarding complementary medicines, but were not necessarily aware of, or guided by, explicit statements in the Pharmacy Council of New Zealand's Code of Ethics.

Evaluation of a Web-Based, 'Purchase Event' Intensive Monitoring Method for Pharmacovigilance of Natural Health Products: Lessons and Insights from Development Work in New Zealand.

INTRODUCTION: Intensive monitoring methods are used in pharmacovigilance for prescription medicines but have not yet been implemented for natural health products (NHPs). OBJECTIVES: Our objective was to assess feasibility issues with a new 'purchase event' intensive monitoring method for pharmacovigilance of NHPs, including pharmacy and NHP purchaser recruitment rates, collection of NHP purchaser key patient identifier information for data linkage and quality and completeness of data. METHODS: For the Ginkgo study, 213 community pharmacies in the Auckland (Aotearoa New Zealand) District Health Board area were invited to participate. Staff in participating pharmacies (n = 3 [1.4%]) recorded ginkgo product sales and gave purchasers a study invitation card (October 2015-January 2016). Ginkgo purchaser participants were emailed links to web-based baseline and follow-up questionnaires about adverse events occurring during/after taking ginkgo. Participating pharmacists and consumers were invited to provide qualitative feedback about the study. For the NHP-Lite study, all NHPs were included for monitoring. Community pharmacies in the Green Cross Health network were invited to participate. Participating pharmacy staff gave all NHP purchasers a study invitation card over a 2-week period (May 2016). NHP purchaser participants were emailed links to web-based baseline, follow-up and feedback questionnaires. RESULTS: Few community pharmacists (Ginkgo study, n = 3; NHP-Lite study, n = 18) and NHP purchasers (Ginkgo study, n = 0; NHP-Lite study, n = 4) participated. Pharmacists (Ginkgo study, 3/3; NHP-Lite study, 11/18) described several reasons for participating and suggested ways to increase consumer recruitment, including simplifying study procedures. CONCLUSIONS: These web-based, purchase event, intensive monitoring studies, with cohorts built through NHP purchases in pharmacies, identified substantial issues with recruiting pharmacists/pharmacies and NHP purchasers that, at present, render such studies unfeasible. Future studies need to consider other methods of recruiting NHP purchasers and develop a simple method for recording NHP purchases.

Analysis of Hepatobiliary Disorder Reports Associated With the Use of Herbal Medicines in the Global Suspected ADR Database Vigibase.

Introduction: Use of herbal medicines (HMs) is widespread across the world, with many people relying on HMs for their primary healthcare or using HMs in the context of a healthy life style. HMs originate from plant material and, as such, are often seen as "natural" and believed to be (relatively) safe by patients. Hepatobiliary disorders have been associated with numerous HMs. Aim: This paper aims to analyze reporting patterns for hepatobiliary disorders associated with HMs use from reports submitted to the WHO global database of individual case safety reports (ICSRs) VigiBase. Methods: A data extraction in VigiBase, the WHO international database of ICSR reports, was performed by the Uppsala Monitoring Centre on 2019-01-16. The dataset contained all ICSRs where an HM was identified with the UMC-assigned ATC code "V90: unspecified herbal and traditional medicine" and where the HM was classified as being either the suspected drug or an interacting drug, and containing at least one adverse reaction in the MedDRA® System Organ Class (SOC) Hepatobiliary Disorders (HBD). Descriptive analyses in Excel 2013® were used to determine general characteristics of the reports in the broad data set, including total number of reports, reporting country and patient characteristics. For single suspect herbal reports, reports categorized as "serious" according to CIOMS criteria (CIOMS), 2001) were extracted. Results: In total, 2,483 reports describing with at least one ADR in the SOC HBD were extracted from VigiBase. In total, 780 (31.4%) reports concern only one suspect HM. However, for 188 reports of these reports (24.1%), the single suspect herbal preparation contains more than one herbal ingredient. The 592 reports for single suspect herbal preparations described a total of 764 ADRs in the SOC HBD. Jaundice was the most reported ADR for these reports. Conclusion: Almost 2,500 reports for HMs and with at least one ADR coded to the MedDRA® SOC HBD were retrieved from VigiBase. Of the HBD SOC HM reports, around 25% concerned a single herbal species as the suspect "drug." Substantial issues with coding of the suspect herbal drugs were found. In-depth causality assessment of the cases is needed to draw conclusions on the strength of the relationships.

Hypnotherapy for smoking cessation.

BACKGROUND: Hypnotherapy is widely promoted as a method for aiding smoking cessation. It is intended to act on underlying impulses to weaken the desire to smoke, or strengthen the will to stop. OBJECTIVES: To evaluate the effect and safety of hypnotherapy for smoking cessation. SEARCH METHODS: For this update we searched the Cochrane Tobacco Addiction Group Specialized Register, and trial registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform), using the terms "smoking cessation" and "hypnotherapy" or "hypnosis", with no restrictions on language or publication date. The most recent search was performed on 18 July 2018. SELECTION CRITERIA: We considered randomized controlled trials that recruited people who smoked and implemented a hypnotherapy intervention for smoking cessation compared with no treatment, or with any other therapeutic interventions. Trials were required to report smoking cessation rates at least six months after the beginning of treatment. Study eligibility was determined by at least two review authors, independently. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data on participant characteristics, the type and duration of hypnotherapy, the nature of the control group, smoking status, method of randomization, and completeness of follow-up. These authors also independently assessed the quality of the included studies. In undertaking this work, we used standard methodological procedures expected by Cochrane.The main outcome measure was abstinence from smoking after at least six months' follow-up. We used the most rigorous definition of abstinence in each trial, and biochemically validated abstinence rates where available. Those lost to follow-up were considered to still be smoking. We summarized effects as risk ratios (RRs) and 95% confidence intervals (CIs). Where possible, we performed meta-analysis using a fixed-effect model. We also noted any adverse events reported. MAIN RESULTS: We included three new trials in this update, which brings the total to 14 included studies that compared hypnotherapy with 22 different control interventions. The studies included a total of 1926 participants. Studies were diverse and a single meta-analysis was not possible. We judged only one study to be at low risk of bias overall; we judged 10 studies to be at high risk of bias and three at unclear risk. Studies did not provide reliable evidence of a greater benefit from hypnotherapy compared with other interventions or no treatment for smoking cessation. Most individual studies did not find statistically significant differences in quit rates after six months or longer, and studies that did detect differences typically had methodological limitations.Pooling small groups of relatively comparable studies did not provide reliable evidence for a specific effect of hypnotherapy relative to controls. There was low certainty evidence, limited by imprecision and risk of bias, that showed no statistically significant difference between hypnotherapy and attention-matched behavioural treatments (RR 1.21, 95% CI 0.91 to 1.61; I2 = 36%; 6 studies, 957 participants). Results were similarly imprecise, and also limited by risk of bias, when comparing hypnotherapy to intensive behavioural interventions (not matched for contact time) (RR 0.93, 95% CI 0.47 to 1.82; I2 = 0%; 2 studies, 211 participants; very low certainty evidence). Results from one small study (40 participants) detected a statistically significant benefit of hypnotherapy compared to no intervention (RR 19.00, 95% CI 1.18 to 305.88), but this evidence was judged to be of very low certainty due to high risk of bias and imprecision. No significant differences were detected in comparisons of hypnotherapy with brief behavioural interventions (RR 0.98, 95% CI 0.57 to 1.69; I² = 0%; 2 studies, 269 participants), rapid/focused smoking (RR 1.00, 95% CI 0.43 to 2.33; I2 = 65%; 2 studies, 54 participants), and pharmacotherapies (RR 1.68, 95% CI 0.88 to 3.20; I2 = 5%; 2 studies, 197 participants). When hypnotherapy was evaluated as an adjunct to other treatments, the pooled result from five studies showed a statistically significant benefit in favour of hypnotherapy (RR 2.10, 95% CI 1.31 to 3.35; I² = 62%; 224 participants); however, this result should be interpreted with caution due to the high risk of bias across studies (four had a high risk or bias, one had an unclear risk), and substantial statistical heterogeneity.Most studies did not provide information on whether data specifically relating to adverse events were collected, and whether or not any adverse events occurred. One study that did collect such data did not find a statistically significant difference in the adverse event 'index' between hypnotherapy and relaxation. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether hypnotherapy is more effective for smoking cessation than other forms of behavioural support or unassisted quitting. If a benefit is present, current evidence suggests the benefit is small at most. There is very little evidence on whether hypnotherapy causes adverse effects, but the existing data show no evidence that it does. Further large, high-quality randomized controlled trials, and more comprehensive assessments of safety, are needed on this topic.

Suspected Hepatotoxicity With a Supercritical Carbon Dioxide Extract of Artemisia annua in Grapeseed Oil Used in New Zealand.

A case series of hepatotoxicity associated with an extract of Artemisia annua L. was identified through the New Zealand spontaneous adverse drug reaction reporting system. A. annua extract, produced using a supercritical carbon dioxide extraction method and formulated with grapeseed oil, has been marketed in New Zealand as a natural product for joint health. As of 31 January 2019, the New Zealand Pharmacovigilance Centre had received 29 reports of hepatic adverse reactions occurring in patients taking A. annua extract in grapeseed oil. The case reports were assessed for patient and adverse reaction characteristics, patterns of A. annua extract use and causality (based on the WHO-UMC system for standardized case causality assessment). Patients were aged 47 to 93 years (median 67). Time to onset of hepatotoxicity from starting A. annua extract was 7 days to approximately 12 months in the 23 reports with this information. Nineteen of these reports indicated onset within 12 weeks. A. annua extract was the sole suspect medicine in 27 reports. A few patients had possible predisposing conditions. Twenty-seven patients were reported to have recovered or improved on stopping A. annua extract. Nine patients required hospital admission. The pattern of hepatic injury varied. Jaundice, often with pruritus and dark urine, was experienced by 16 patients. There was considerable consistency across case reports from various reporters. We assessed the case reports as a series using the Bradford Hill guidelines for causal inference and concluded that there was a safety signal of a causal association between the A. annua extract and hepatotoxicity sufficient to be communicated and investigated further.

Cytisine versus varenicline for smoking cessation for Maori (the indigenous people of New Zealand) and their extended family: protocol for a randomized non-inferiority trial.

BACKGROUND AND AIMS: Cytisine, a nicotinic acetylcholine receptor partial agonist (like varenicline) found in some plants, is a low-cost, effective smoking cessation medication that may appeal to Maori [the indigenous people of New Zealand (NZ)]. The RAUORA trial aims to determine the effectiveness, safety and cost-effectiveness of cytisine (Tabex® ) versus varenicline (Champix® ) for smoking cessation in Maori and the whanau (extended family) of Maori. DESIGN: Pragmatic, community-based, open-label randomized non-inferiority trial. SETTING: Lakes District Health Board region, NZ. PARTICIPANTS: Daily smokers (n = 2140) who self-identify as Maori or whanau of Maori, and are: aged ≥ 18 years, motivated to quit smoking in the next 2 weeks, eligible for subsidized varenicline, able to provide verbal consent and have daily access to a mobile phone/internet. Recruitment uses multi-media advertising. INTERVENTION AND COMPARATOR: Participants are randomized (1 : 1 ratio) to receive a prescription for 12 weeks of cytisine tablets [following the manufacturer's dosing regimen for 25 days, then one 1.5-mg tablet every 6 hours (two per day) until 12 weeks] or varenicline tablets (following the manufacturer's dosing regimen). Both groups receive brief stop-smoking advice from the prescribing doctor and withdrawal-orientated behavioural support via community-based stop-smoking counselling services (frequency, duration and mode of delivery tailored for participants) or a research assistant (six weekly 10-15-minute calls). Participants are advised to reduce their smoking over the first 4 days of treatment, with day 5 as their designated quit-date. MEASUREMENTS: The primary outcome is carbon monoxide-verified continuous abstinence at 6 months post-quit date. Secondary outcomes at 1, 3, 6 and 12 months post-quit date include: self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance, treatment acceptability, nicotine withdrawal/urge to smoke and health-care utilization/health-related quality of life. COMMENTS: This trial compares cytisine and varenicline when used by the indigenous people of NZ and their extended family for smoking cessation.

Community pharmacists' views on the regulation of complementary medicines and complementary-medicines practitioners: a qualitative study in New Zealand.

OBJECTIVES: To examine community pharmacists' perspectives on CMs regulation in New Zealand, where proposals for CMs regulations had recently been suspended and where, currently, CMs are only weakly regulated. METHODS: Qualitative, in-depth, semi-structured interviews with New Zealand practising community pharmacists are identified through purposive and convenience sampling. Data were analysed using a general inductive approach. KEY FINDINGS: Participants held mixed views regarding harmonisation of CMs regulations across Australia and NZ; some supported an NZ national regulatory framework for CMs, based on the Australian system. Participants recognised the current CMs regulatory framework in NZ as inadequate, that regulation was required to some extent, and that mandatory regulation was not necessarily required. A key reason given in support of CMs regulations was the need for greater assurances around quality of CMs. Participants also supported a regulatory framework that incorporated assessment of the safety of CMs, but were less convinced of the need for, or feasibility of, requiring evidence of efficacy from clinical trials. Participants believed that regulation of CMs practitioners, such as herbalists, and CMs retailers was important, although there were mixed views as to whether regulation should be statutory or whether self-regulation would be adequate. CONCLUSIONS: On the basis of these findings, pharmacists would be expected to welcome proposals for national regulations for CMs in NZ: such regulations should address concerns regarding product quality, inappropriate health claims and supporting evidence, and therefore should support pharmacists in meeting their obligations under the NZ Pharmacy Council's Code of Ethics.