Start2quit: a randomised clinical controlled trial to evaluate the effectiveness and cost-effectiveness of using personal tailored risk information and taster sessions to increase the uptake of the NHS Stop Smoking Services.

BACKGROUND: The NHS Stop Smoking Services (SSSs) offer help to smokers who want to quit. However, the proportion of smokers attending the SSSs is low and current figures show a continuing downward trend. This research addressed the problem of how to motivate more smokers to accept help to quit. OBJECTIVES: To assess the relative effectiveness, and cost-effectiveness, of an intervention consisting of proactive recruitment by a brief computer-tailored personal risk letter and an invitation to a 'Come and Try it' taster session to provide information about the SSSs, compared with a standard generic letter advertising the service, in terms of attendance at the SSSs of at least one session and validated 7-day point prevalent abstinence at the 6-month follow-up. DESIGN: Randomised controlled trial of a complex intervention with follow-up 6 months after the date of randomisation. SETTING: SSSs and general practices in England. PARTICIPANTS: All smokers aged ≥ 16 years identified from medical records in participating practices who were motivated to quit and who had not attended the SSS in the previous 12 months. Participants were randomised in the ratio 3 : 2 (intervention to control) by a computer program. INTERVENTIONS: Intervention - brief personalised and tailored letter sent from the general practitioner using information obtained from the screening questionnaire and from medical records, and an invitation to attend a taster session, run by the local SSS. Control - standard generic letter from the general practice advertising the local SSS and the therapies available, and asking the smoker to contact the service to make an appointment. MAIN OUTCOME MEASURES: (1) Proportion of people attending the first session of a 6-week course over a period of 6 months from the receipt of the invitation letter, measured by records of attendance at the SSSs; (2) 7-day point prevalent abstinence at the 6-month follow-up, validated by salivary cotinine analysis; and (3) cost-effectiveness of the intervention. RESULTS: Eighteen SSSs and 99 practices within the SSS areas participated; 4384 participants were randomised to the intervention (n = 2636) or control (n = 1748). One participant withdrew and 4383 were analysed. The proportion of people attending the first session of a SSS course was significantly higher in the intervention group than in the control group [17.4% vs. 9.0%; unadjusted odds ratio (OR) 2.12, 95% confidence interval (CI) 1.75 to 2.57; p  86% over a lifetime horizon. LIMITATIONS: Participating SSSs may not be representative of all SSSs in England. Recruitment was low, at 4%. CONCLUSIONS: The Start2quit trial added to evidence that a proactive approach with an intensive intervention to deliver personalised risk information and offer a no-commitment introductory session can be successful in reaching more smokers and increasing the uptake of the SSS and quit rates. The intervention appears less likely to be cost-effective in the short term, but is highly likely to be cost-effective over a lifetime horizon. FUTURE WORK: Further research could assess the separate effects of these components. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76561916. FUNDING DETAILS: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 3. See the NIHR Journals Library website for further project information

Measurements of the branching fractions for B→K∗γB \to K^{*}\gamma decays at Belle II

This paper reports a study of $B \to K^{*}\gamma$ decays using $62.8\pm 0.6$ fb$^{-1}$ of data collected during 2019--2020 by the Belle II experiment at the SuperKEKB $e^{+}e^{-}$ asymmetric-energy collider, corresponding to $(68.2 \pm 0.8) \times 10^6$ $B\overline{B}$ events. We find $454 \pm 28$, $50 \pm 10$, $169 \pm 18$, and $160 \pm 17$ signal events in the decay modes $B^{0} \to K^{*0}[K^{+}\pi^{-}]\gamma$, $B^{0} \to K^{*0}[K^0_{\rm S}\pi^{0}]\gamma$, $B^{+} \to K^{*+}[K^{+}\pi^{0}]\gamma$, and $B^{+} \to K^{*+}[K^{+}\pi^{0}]\gamma$, respectively. The uncertainties quoted for the signal yield are statistical only. We report the branching fractions of these decays: $$\mathcal{B} [B^{0} \to K^{*0}[K^{+}\pi^{-}]\gamma] = (4.5 \pm 0.3 \pm 0.2) \times 10^{-5},$$ $$\mathcal{B} [B^{0} \to K^{*0}[K^0_{\rm S}\pi^{0}]\gamma] = (4.4 \pm 0.9 \pm 0.6) \times 10^{-5},$$ $$\mathcal{B} [B^{+} \to K^{*+}[K^{+}\pi^{0}]\gamma] = (5.0 \pm 0.5 \pm 0.4)\times 10^{-5},\text{ and}$$ $$\mathcal{B} [B^{+} \to K^{*+}[K^0_{\rm S}\pi^{+}]\gamma] = (5.4 \pm 0.6 \pm 0.4) \times 10^{-5},$$ where the first uncertainty is statistical, and the second is systematic. The results are consistent with world-average values

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study.

BACKGROUND: Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden. METHODS: Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006-11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable. FINDINGS: Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16-22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13-34), suggesting most influenza infections are asymptomatic. 25% (18-35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10-26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2. INTERPRETATION: Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2. FUNDING: Medical Research Council and the Wellcome Trust

Combinations of favipiravir and peramivir for the treatment of pandemic influenza A/California/04/2009 (H1N1) virus infections in mice

Favipiravir, an influenza virus RNA polymerase inhibitor, and peramivir, an influenza virus neuraminidase inhibitor, were evaluated alone and in combination against pandemic influenza A/California/04/2009 (H1N1) virus infections in mice. Infected mice were treated twice daily for 5 d starting 4 h after virus challenge. Favipiravir was 40%, 70%, and 100% protective at 20, 40, and 100 mg/kg/d. Peramivir was 30% protective at 0.5 mg/kg/d, but ineffective at lower doses when used as monotherapy. Combinations of favipiravir and peramivir increased the numbers of survivors by 10–50% when the 0.025, 0.05, and 0.1 mg/kg/d doses of peramivir were combined with 20 mg/kg/d favipiravir and when all doses of peramivir were combined with 40 mg/kg/d favipiravir. Three-dimensional analysis of drug interactions using the MacSynergy method indicates strong synergy for these drug combinations. In addition, an increase in lifespan for groups of mice treated with drug combinations, compared to the most effective monotherapy group, was observed for the 0.025, 0.05, and 0.1 mg/kg/d doses of peramivir combined with favipiravir at the 20 mg dose level. Therefore, the 20 mg/kg/d dose of favipiravir was selected for further combination studies. Increased survival was exhibited when this dose was combined with peramivir doses of 0.1, 0.25 and 0.5 mg/kg/d (1 mg/kg/d of peramivir alone was 100% protective in this experiment). Improved body weight relative to either compound alone was evident using 0.25, 0.5, and 1 mg/kg/d of peramivir. Significant reductions in lung hemorrhage score and lung weight were evident on day 6 post-infection. In addition, virus titers were reduced significantly on day 4 post-infection by combination therapy containing favipiravir combined with peramivir at 0.25 and 0.5 mg/kg/d. These data demonstrate that combinations of favipiravir and peramivir perform better than suboptimal doses of each compound alone for the treatment of influenza virus infections in mice