New Zealand COPD Guidelines: Quick Reference Guide.

The purpose of the Asthma and Respiratory Foundation of New Zealand's COPD Guidelines: Quick Reference Guide is to provide simple, practical, evidence-based recommendations for the diagnosis, assessment, and management of chronic obstructive pulmonary disease (COPD) in clinical practice. The intended users are health professionals responsible for delivering acute and chronic COPD care in community and hospital settings, and those responsible for the training of such health professionals.

Asthma and Respiratory Foundation NZ Adolescent and Adult Asthma Guidelines 2020: a quick reference guide.

The purpose of the 2020 Asthma and Respiratory Foundation NZ Adolescent and Adult Asthma Guidelines is to provide simple, practical and evidence-based recommendations for the diagnosis, assessment and management of asthma in adolescents and adults (aged 12 and over) in a quick reference format. The intended users are health professionals responsible for delivering asthma care in the community and hospital settings, and those responsible for the training of such health professionals. The main changes in the 2020 update are: 1) combining the recommendations for both adolescents and adults in a single document, 2) the recommendation to avoid SABA-only treatment in the long-term management of asthma, 3) the use of budesonide/formoterol reliever, with or without maintenance budesonide/formoterol, is preferred to SABA reliever, with or without maintenance ICS or ICS/LABA, across the spectrum of asthma severity, 4) introduction of the terminology 'anti-inflammatory reliever (AIR)' therapy to describe the use of budesonide/formoterol as a reliever medication, with or without maintenance budesonide/ formoterol therapy. This approach encompasses and extends the 'Single combination ICS/LABA inhaler Maintenance And Reliever Therapy' (SMART) approach recommended in the previous guideline, 5) the inclusion of two stepwise management algorithms, 6) a clinical allergy section, 7) the role of LAMA therapy in severe asthma, 8) the role of omalizumab in severe allergic asthma and mepolizumab in severe eosinophilic asthma, 9) an appendix detailing educational materials.

Patient preferences for symptom-driven or regular preventer treatment in mild to moderate asthma: findings from the PRACTICAL study, a randomised clinical trial.

Symptom-driven low-dose inhaled corticosteroid-formoterol is safe and effective in mild asthma and has been recommended as one of the preferred treatment regimens at steps 1 and 2 in the 2019 update of the Global Initiative for Asthma. However, there are no data on patient preferences for this regimen.A subgroup of participants in the PRACTICAL study (ACTRN12616000377437), a randomised controlled trial comparing symptom-driven budesonide-formoterol with maintenance budesonide plus as-needed terbutaline completed a survey on treatment preferences, satisfaction, beliefs and experience at their final study visit.306 (75%) out of 407 eligible participants completed the survey. Regimen preference was strongly associated with randomised treatment, as were preferences for and beliefs about preventer inhaler use. Combination preventer and reliever as-needed therapy was preferred by 135 (90%, 95% CI 85.2-94.8%) out of 150 who were randomised to as-needed budesonide-formoterol, and by 63 (40%, 95% CI 32.7-48.1%) out of 156 who were randomised to maintenance budesonide. By contrast, twice-daily preventer inhaler with a reliever inhaler as required was preferred by 15 (10%) out of 150 of those randomised to as-needed budesonide-formoterol and 93 (60%) out of 156 of those randomised to maintenance budesonide. Satisfaction with all study inhalers was high. Of patients randomised to as-needed budesonide-formoterol 92% (n=138) were confident using it as a reliever at the end of the study.Although most participants preferred the regimen to which they had been randomised, this association was much stronger for those randomised to budesonide-formoterol as needed, indicating that most patients preferred as-needed corticosteroid-formoterol therapy if they had experienced it.

ß-Blockers in COPD: A Cohort Study From the TONADO Research Program.

BACKGROUND: Cardiovascular disease is a frequent comorbidity in patients with COPD. Many physicians, particularly pulmonologists, are reluctant to use ß-adrenoceptor blocking agents (ß-blockers) in patients with COPD, despite their proven effectiveness in preventing cardiovascular events. METHODS: The large (5,162 patients) phase III TONADO 1 and 2 studies assessed lung function and patient-reported outcomes in patients with moderate to very severe COPD receiving long-acting bronchodilator treatment across 1 year. This post hoc analysis characterized lung-function changes, patient-reported outcomes, and safety in the subgroup of patients receiving ß-blockers in the studies. RESULTS: In total, 557 of 5,162 patients (11%) received ß-blockers at baseline. Postbronchodilator FEV1 at baseline was higher in the ß-blocker group (1.470 L) compared with that in the no ß-blocker group (1.362 L). As expected, patients receiving ß-blockers had a more frequent history of cardiovascular comorbidities and medications. Lung function improved from baseline in patients with or those without ß-blocker treatment, and no relevant between-group differences were observed in trough FEV1 or trough FVC at 24 or 52 weeks. No relevant differences were observed for St. George's Respiratory Questionnaire results and Transition Dyspnea Index in patients with ß-blockers compared with those in patients without. Safety findings were comparable between groups. CONCLUSIONS: Lung function, overall respiratory status, and safety of tiotropium/olodaterol were not influenced by baseline ß-blocker treatment in patients with moderate to very severe COPD. Results from this large patient cohort support the cautious and appropriate use of ß-blockers in patients with COPD and cardiovascular comorbidity. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01431274 and No. NCT01431287; URL: www.clinicaltrials.gov.

Asthma and Respiratory Foundation NZ child and adolescent asthma guidelines: a quick reference guide.

The purpose of the New Zealand Child and adolescent asthma guidelines: a quick reference guide is to provide simple, practical, evidence-based recommendations for the diagnosis, assessment and management of asthma in children and adolescents in New Zealand, with the aim of improving outcomes and reducing inequities. The intended users are health professionals responsible for delivering asthma care in the community and hospital emergency department settings, and those responsible for the training of such health professionals.

Asthma and Respiratory Foundation NZ adult asthma guidelines: a quick reference guide.

The purpose of the Asthma and Respiratory Foundation NZ Adult Asthma Guidelines is to provide simple, practical and evidence-based recommendations for the diagnosis, assessment and management of asthma in adults (aged 16 and over) in a quick reference format. The intended users are health professionals responsible for delivering asthma care in the community and hospital Emergency Department settings, and those responsible for the training of such health professionals.

Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: A randomized, placebo-controlled trial.

BACKGROUND: Before pandemic H1N1 vaccines were available, the potential benefit of existing seasonal trivalent inactivated influenza vaccines (IIV3s) against influenza due to the 2009 pandemic H1N1 influenza strain was investigated, with conflicting results. This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain. METHODS: This observer-blind, randomized, placebo-controlled study enrolled adults aged 18-64years during 2008 and 2009 in Australia and New Zealand. Participants were randomized 2:1 to receive IIV3 or placebo. The primary objective was to demonstrate the efficacy of IIV3 against laboratory-confirmed influenza. Participants reporting an influenza-like illness during the period from 14days after vaccination until 30 November of each study year were tested for influenza by real-time reverse transcription polymerase chain reaction. RESULTS: Over a study period of 2years, 15,044 participants were enrolled (mean age±standard deviation: 35.5±14.7years; 54.4% female). Vaccine efficacy of the 2008 and 2009 IIV3s against influenza due to any strain was 42% (95% confidence interval [CI]: 30%, 52%), whereas vaccine efficacy against influenza due to the vaccine-matched strains was 60% (95% CI: 44%, 72%). Vaccine efficacy of the 2009 IIV3 against influenza due to the 2009 pandemic H1N1 strain was 38% (95% CI: 19%, 53%). No vaccine-related deaths or serious adverse events were reported. Solicited local and systemic adverse events were more frequent in IIV3 recipients than placebo recipients (local: IIV3 74.6% vs placebo 20.4%, p<0.001; systemic: IIV3 46.6% vs placebo 39.1%, p<0.001). CONCLUSIONS: The 2008 and 2009 IIV3s were efficacious against influenza due to seasonal influenza strains and the 2009 IIV3 demonstrated moderate efficacy against influenza due to the 2009 pandemic H1N1 strain. Funded by CSL Limited, ClinicalTrials.gov identifier NCT00562484.

Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4).

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials. Patients received tiotropium+olodaterol FDC 2.5/5 µg or 5/5 µg, tiotropium 2.5 µg or 5 µg, or olodaterol 5 µg delivered once-daily via Respimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks. In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment. Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies. Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 µg. Incidence of adverse events was comparable between the FDCs and the mono-components. These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.

On the histone lysine methyltransferase activity of fungal metabolite chaetocin.

Histone lysine methyltransferases (HKMTs) are an important class of targets for epigenetic therapy. 1 (chaetocin), an epidithiodiketopiperazine (ETP) natural product, has been reported to be a specific inhibitor of the SU(VAR)3-9 class of HKMTs. We have studied the inhibition of the HKMT G9a by 1 and functionally related analogues. Our results reveal that only the structurally unique ETP core is required for inhibition, and such inhibition is time-dependent and irreversible (in the absence of DTT), ultimately resulting in protein denaturation. Mass spectrometric data provide a molecular basis for this effect, demonstrating covalent adduct formation between 1 and the protein. This provides a potential rationale for the selectivity observed in the inhibition of a variety of HKMTs by 1 in vitro and has implications for the activity of ETPs against these important epigenetic targets.

Company profile: Sistemic Ltd.

Founded in 2009 and headquartered in Glasgow, Scotland, UK, Sistemic Ltd has developed from a thought in the minds of four scientists into a company working globally to play its part in delivering the exciting opportunities for improvements in human health presented by cell therapies and regenerative medicine products (jointly referred to as the CT industry). Sistemic is now working in all corners of the world with some of the industry's leading companies to ensure that the products that they are developing, which will undoubtedly change the way we treat some of the major diseases and conditions currently placing a large burden on healthcare systems, including diabetes, dementia and cardiovascular disease, are as safe and efficacious as possible. Sistemic is also working to ensure that these products can be produced at a cost that will not lead to potentially transformational treatments being an additional financial burden on our already overburdened healthcare systems. Sistemic is using its revolutionary and IP-protected SistemQC™ (UK) technology to enhance understanding of characterization, process optimization and potency of CT products. The company is using the diagnostic power of miRNAs, a set of approximately 2000 ncRNAs that regulate a large percentage of the total gene expression of a cell. miRNAs are often present in a cell- and tissue-specific way that, at least in some cases, accounts for the phenotypic differences between cell types. These differences in miRNA expression can be interpreted by the miRNA profile and it is interpreting the instructive power of these profiles that underpin Sistemic's knowledge bases, giving CT companies a more comprehensive understanding of their cell populations with respect to their identity and functional capabilities. This knowledge is being used by companies to characterize, process, optimize and assess the efficacy of cell products.

Monitor tumor burden with circulating tumor DNA.

There is a need to identify better biomarkers to monitor diseases and/or assess therapeutic responses. For those with cancer, one can identify DNA fragments that contain somatic mutations originating in the tumor DNA in plasma or serum. There have been several early studies suggesting that advances in sequencing technologies will allow identification of somatic genomic alterations that can be used to monitor tumor dynamics. Dawson et.al. investigated circulating cell-free DNA carrying tumor specific alterations in patients with breast cancer. The authors compared CT imaging from 30 women with metastatic breast cancer receiving treatment, using two assays for circulating tumor DNA, CA 15-3, and CTCs. Taken the two methods together circulating tumor DNA was detected in 29 or 30 women (97%) and 115 of 141 plasma samples (82%). Circulating tumor DNA levels showed a greater dynamic range and greater correlation with changes in tumor burden than did CA 15-3 or CTC. The relatively small study showed that circulating tumor DNA has a superior sensitivity to other circulating biomarkers and a dynamic range that correlates with tumor burden.