A joint analysis of influenza-associated hospitalizations and mortality in Hong Kong, 1998-2013.

Influenza viruses may cause severe human infections leading to hospitalization or death. Linear regression models were fitted to population-based data on hospitalizations and deaths. Surveillance data on influenza virus activity permitted inference on influenza-associated hospitalizations and deaths. The ratios of these estimates were used as a potential indicator of severity. Influenza was associated with 431 (95% CrI: 358-503) respiratory deaths and 12,700 (95% CrI: 11,700-13,700) respiratory hospitalizations per year. Majority of the excess deaths occurred in persons ≥65 y of age. The ratios of deaths to hospitalizations in adults ≥65 y were significantly higher for influenza A(H1N1) and A(H1N1)pdm09 compared to A(H3N2) and B. Substantial disease burden associated with influenza viruses were estimated in Hong Kong particularly among children and elderly in 1998-2013. Infections with influenza A(H1N1) was suggested to be more serious than A(H3N2) in older adults

Pain Squad+ smartphone app to support real-time pain treatment for adolescents with cancer: protocol for a randomised controlled trial.

INTRODUCTION: Pain negatively affects the health-related quality of life (HRQL) of adolescents with cancer. The Pain Squad+ smartphone-based application (app), has been developed to provide adolescents with real-time pain self-management support. The app uses a validated pain assessment and personalised pain treatment advice with centralised decision support via a registered nurse to enable real-time pain treatment in all settings. The algorithm informing pain treatment advice is evidence-based and expert-vetted. This trial will longitudinally evaluate the impact of Pain Squad+, with or without the addition of nurse support, on adolescent health and cost outcomes. METHODS AND ANALYSIS: This will be a pragmatic, multicentre, waitlist controlled, 3-arm parallel-group superiority randomised trial with 1:1:1 allocation enrolling 74 adolescents with cancer per arm from nine cancer centres. Participants will be 12 to 18 years, English-speaking and with ≥3/10 pain. Exclusion criteria are significant comorbidities, end-of-life status or enrolment in a concurrent pain study. The primary aim is to determine the effect of Pain Squad+, with and without nurse support, on pain intensity in adolescents with cancer, when compared with a waitlist control group. The secondary aims are to determine the immediate and sustained effect over time of using Pain Squad+, with and without nurse support, as per prospective outcome measurements of pain interference, HRQL, pain self-efficacy and cost. Linear mixed models with baseline scores as a covariate will be used. Qualitative interviews with adolescents from all trial arms will be conducted and analysed. ETHICS AND DISSEMINATION: This trial is approved by the Hospital for Sick Children Research Ethics Board. Results will provide data to guide adolescents with cancer and healthcare teams in treating pain. Dissemination will occur through partnerships with stakeholder groups, scientific meetings, publications, mass media releases and consumer detailing. TRIAL REGISTRATION NUMBER: NCT03632343

Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1)

<p>Abstract</p> <p>Background</p> <p>After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission.</p> <p>Methods</p> <p>We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case.</p> <p>Results</p> <p>Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays.</p> <p>Conclusions</p> <p>Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.</p

HBO1 is required for the maintenance of leukaemia stem cells.

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcriptional dysregulation that results in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, but most show only modest efficacy owing to an inability to effectively eradicate leukaemia stem cells (LSCs)1. Here, to specifically identify novel dependencies in LSCs, we screened a bespoke library of small hairpin RNAs that target chromatin regulators in a unique ex vivo mouse model of LSCs. We identify the MYST acetyltransferase HBO1 (also known as KAT7 or MYST2) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance. Using CRISPR domain screening and quantitative mass spectrometry, we identified the histone acetyltransferase domain of HBO1 as being essential in the acetylation of histone H3 at K14. H3 acetylated at K14 (H3K14ac) facilitates the processivity of RNA polymerase II to maintain the high expression of key genes (including Hoxa9 and Hoxa10) that help to sustain the functional properties of LSCs. To leverage this dependency therapeutically, we developed a highly potent small-molecule inhibitor of HBO1 and demonstrate its mode of activity as a competitive analogue of acetyl-CoA. Inhibition of HBO1 phenocopied our genetic data and showed efficacy in a broad range of human cell lines and primary AML cells from patients. These biological, structural and chemical insights into a therapeutic target in AML will enable the clinical translation of these findings

Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households

Background: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. Methodology/Principal Findings: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomised to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contact at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios old not significantly differ across the intervention arms. Adherence to interventions was variable. Conclusions/Significance: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learn from this pilot have informed changes for the main study in 2008.published_or_final_versio

Pravastatin for early-onset pre-eclampsia:a randomised, blinded, placebo-controlled trial

Objective: Women with pre-eclampsia have elevated circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1). Statins can reduce sFlt-1 from cultured cells and improve pregnancy outcome in animals with a pre-eclampsia-like syndrome. We investigated the effect of pravastatin on plasma sFlt-1 levels during pre-eclampsia. Design: Blinded (clinician and participant), proof of principle, placebo-controlled trial. Setting: Fifteen UK maternity units. Population: We used a minimisation algorithm to assign 62 women with early-onset pre-eclampsia (24 +0–31 +6 weeks of gestation) to receive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32), from randomisation to childbirth. Primary outcome: Difference in mean plasma sFlt-1 levels over the first 3 days following randomisation. Results: The difference in the mean maternal plasma sFlt-1 levels over the first 3 days after randomisation between the pravastatin (n = 27) and placebo (n = 29) groups was 292 pg/ml (95% CI −1175 to 592; P = 0.5), and over days 1–14 was 48 pg/ml (95% CI −1009 to 913; P = 0.9). Women who received pravastatin had a similar length of pregnancy following randomisation compared with those who received placebo (hazard ratio 0.84; 95% CI 0.50–1.40; P = 0.6). The median time from randomisation to childbirth was 9 days [interquartile range (IQR) 5–14 days] for the pravastatin group and 7 days (IQR 4–11 days) for the placebo group. There were three perinatal deaths in the placebo-treated group and no deaths or serious adverse events attributable to pravastatin. Conclusions: We found no evidence that pravastatin lowered maternal plasma sFlt-1 levels once early-onset pre-eclampsia had developed. Pravastatin appears to have no adverse perinatal effects. Tweetable abstract: Pravastatin does not improve maternal plasma sFlt-1 or placental growth factor levels following a diagnosis of early preterm pre-eclampsia #clinicaltrial finds

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries