Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data.

BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche

Planck intermediate results. II. Comparison of Sunyaev-Zeldovich measurements from Planck and from the Arcminute Microkelvin Imager for 11 galaxy clusters

A comparison is presented of Sunyaev-Zeldovich measurements for 11 galaxy clusters as obtained by Planck and by the ground-based interferometer, the Arcminute Microkelvin Imager. Assuming a universal spherically-symmetric Generalised Navarro, Frenk and White (GNFW) model for the cluster gas pressure profile, we jointly constrain the integrated Compton-Y parameter (Y500) and the scale radius (\u3b8500) of each cluster. Our resulting constraints in the Y500 - \u3b8500 2D parameter space derived from the two instruments overlap significantly for eight of the clusters, although, overall, there is a tendency for AMI to find the Sunyaev-Zeldovich signal to be smaller in angular size and fainter than Planck. Significant discrepancies exist for the three remaining clusters in the sample, namely A1413, A1914, and the newly-discovered Planck cluster PLCKESZ G139.59+24.18. The robustness of the analysis of both the Planck and AMI data is demonstrated through the use of detailed simulations, which also discount confusion from residual point (radio) sources and from diffuse astrophysical foregrounds as possible explanations for the discrepancies found. For a subset of our cluster sample, we have investigated the dependence of our results on the assumed pressure profile by repeating the analysis adopting the best-fitting GNFW profile shape which best matches X-ray observations. Adopting the best-fitting profile shape from the X-ray data does not, in general, resolve the discrepancies found in this subset of five clusters. Though based on a small sample, our results suggest that the adopted GNFW model may not be sufficiently flexible to describe clusters universally

Evaluating the incidence of pathological complete response in current international rectal cancer practice: the barriers to widespread safe deferral of surgery

This is the peer reviewed version of the following article: , which has been published in final form at https://doi.org/10.1111/codi.14361. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland Introduction: The mainstay of management for locally advanced rectal cancer is chemoradiotherapy followed by surgical resection. Following chemoradiotherapy, a complete response may be detected clinically and radiologically (cCR) prior to surgery or pathologically after surgery (pCR). We aim to report the overall complete pathological response (pCR) rate and the reliability of detecting a cCR by conventional pre-operative imaging. Methods: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients treated by elective rectal resection were included. A pCR was defined as a ypT0 N0 EMVI negative primary tumour; a partial response represented any regression from baseline staging following chemoradiotherapy. The primary endpoint was the pCR rate. The secondary endpoint was agreement between post-treatment MRI restaging (yMRI) and final pathological staging. Results: Of 2572 patients undergoing rectal cancer surgery in 277 participating centres across 44 countries, 673 (26.2%) underwent chemoradiotherapy and surgery. The pCR rate was 10.3% (67/649), with a partial response in 35.9% (233/649) patients. Comparison of AJCC stage determined by post-treatment yMRI with final pathology showed understaging in 13% (55/429) and overstaging in 34% (148/429). Agreement between yMRI and final pathology for T-stage, N-stage, or AJCC status were each graded as ‘fair’ only (n = 429, Kappa 0.25, 0.26 and 0.35 respectively). Conclusion: The reported pCR rate of 10% highlights the potential for non-operative management in selected cases. The limited strength of agreement between basic conventional post-chemoradiotherapy imaging assessment techniques and pathology suggest alternative markers of response should be considered, in the context of controlled clinical trials

State of the climate in 2015

In 2015, the dominant greenhouse gases released into Earth\u2019s atmosphere\u2014carbon dioxide, methane, and nitrous oxide\u2014all continued to reach new high levels. At Mauna Loa, Hawaii, the annual CO2 concentration increased by a record 3.1 ppm, exceeding 400 ppm for the first time on record. The 2015 global CO2 average neared this threshold, at 399.4 ppm. Additionally, one of the strongest El Ni\uf1o events since at least 1950 developed in spring 2015 and continued to evolve through the year. The phenomenon was far reaching, impacting many regions across the globe and affecting most aspects of the climate system. Owing to the combination of El Ni\uf1o and a long-term upward trend, Earth observed record warmth for the second consecutive year, with the 2015 annual global surface temperature surpassing the previous record by more than 0.1\ub0C and exceeding the average for the mid- to late 19th century\u2014commonly considered representative of preindustrial conditions\u2014by more than 1\ub0C for the first time. Above Earth\u2019s surface, lower troposphere temperatures were near-record high. Across land surfaces, record to near-record warmth was reported across every inhabited continent. Twelve countries, including Russia and China, reported record high annual temperatures. In June, one of the most severe heat waves since 1980 affected Karachi, Pakistan, claiming over 1000 lives. On 27 October, Vredendal, South Africa, reached 48.4\ub0C, a new global high temperature record for this month. In the Arctic, the 2015 land surface temperature was 1.2\ub0C above the 1981\u20132010 average, tying 2007 and 2011 for the highest annual temperature and representing a 2.8\ub0C increase since the record began in 1900. Increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 25 February 2015, the lowest maximum sea ice extent in the 37-year satellite record was observed, 7% below the 1981\u20132010 average. Mean sea surface temperatures across the Arctic Ocean during August in ice-free regions, representative of Arctic Ocean summer anomalies, ranged from ~0\ub0C to 8\ub0C above average. As a consequence of sea ice retreat and warming oceans, vast walrus herds in the Pacific Arctic are hauling out on land rather than on sea ice, raising concern about the energetics of females and young animals. Increasing temperatures in the Barents Sea are linked to a community-wide shift in fish populations: boreal communities are now farther north, and long-standing Arctic species have been almost pushed out of the area. Above average sea surface temperatures are not confined to the Arctic. Sea surface temperature for 2015 was record high at the global scale; however, the North Atlantic southeast of Greenland remained colder than average and colder than 2014. Global annual ocean heat content and mean sea level also reached new record highs. The Greenland Ice Sheet, with the capacity to contribute ~7 m to sea level rise, experienced melting over more than 50% of its surface for the first time since the record melt of 2012. Other aspects of the cryosphere were remarkable. Alpine glacier retreat continued, and preliminary data indicate that 2015 is the 36th consecutive year of negative annual mass balance. Across the Northern Hemisphere, late-spring snow cover extent continued its trend of decline, with June the second lowest in the 49-year satellite record. Below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska, increasing by up to 0.66\ub0C decade\u20131 since 2000. In the Antarctic, surface pressure and temperatures were lower than the 1981\u20132010 average for most of the year, consistent with the primarily positive southern annular mode, which saw a record high index value of +4.92 in February. Antarctic sea ice extent and area had large intra-annual variability, with a shift from record high levels in May to record low levels in August. Springtime ozone depletion resulted in one of the largest and most persistent Antarctic ozone holes observed since the 1990s. Closer to the equator, 101 named tropical storms were observed in 2015, well above the 1981\u20132010 average of 82. The eastern/central Pacific had 26 named storms, the most since 1992. The western north Pacific and north and south Indian Ocean basins also saw high activity. Globally, eight tropical cyclones reached the Saffir\u2013Simpson Category 5 intensity level. Overlaying a general increase in the hydrologic cycle, the strong El Ni\uf1o enhanced precipitation variability around the world. An above-normal rainy season led to major floods in Paraguay, Bolivia, and southern Brazil. In May, the United States recorded its all-time wettest month in its 121-year national record. Denmark and Norway reported their second and third wettest year on record, respectively, but globally soil moisture was below average, terrestrial groundwater storage was the lowest in the 14-year record, and areas in \u201csevere\u201d drought rose from 8% in 2014 to 14% in 2015. Drought conditions prevailed across many Caribbean island nations, Colombia, Venezuela, and northeast Brazil for most of the year. Several South Pacific countries also experienced drought. Lack of rainfall across Ethiopia led to its worst drought in decades and affected millions of people, while prolonged drought in South Africa severely affected agricultural production. Indian summer monsoon rainfall was just 86% of average. Extremely dry conditions in Indonesia resulted in intense and widespread fires during August\u2013November that produced abundant carbonaceous aerosols, carbon monoxide, and ozone. Overall, emissions from tropical Asian biomass burning in 2015 were almost three times the 2001\u201314 average

Outcomes from elective colorectal cancer surgery during the SARS‐CoV‐2 pandemic

Aim This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic. Method This was an international cohort study of patients undergoing elective resection of colon or rectal cancer without preoperative suspicion of SARS-CoV-2. Centres entered data from their first recorded case of COVID-19 until 19 April 2020. The primary outcome was 30-day mortality. Secondary outcomes included anastomotic leak, postoperative SARS-CoV-2 and a comparison with prepandemic European Society of Coloproctology cohort data. Results From 2073 patients in 40 countries, 1.3% (27/2073) had a defunctioning stoma and 3.0% (63/2073) had an end stoma instead of an anastomosis only. Thirty-day mortality was 1.8% (38/2073), the incidence of postoperative SARS-CoV-2 was 3.8% (78/2073) and the anastomotic leak rate was 4.9% (86/1738). Mortality was lowest in patients without a leak or SARS-CoV-2 (14/1601, 0.9%) and highest in patients with both a leak and SARS-CoV-2 (5/13, 38.5%). Mortality was independently associated with anastomotic leak (adjusted odds ratio 6.01, 95% confidence interval 2.58–14.06), postoperative SARS-CoV-2 (16.90, 7.86–36.38), male sex (2.46, 1.01–5.93), age >70 years (2.87, 1.32–6.20) and advanced cancer stage (3.43, 1.16–10.21). Compared with prepandemic data, there were fewer anastomotic leaks (4.9% versus 7.7%) and an overall shorter length of stay (6 versus 7 days) but higher mortality (1.7% versus 1.1%). Conclusion Surgeons need to further mitigate against both SARS-CoV-2 and anastomotic leak when offering surgery during current and future COVID-19 waves based on patient, operative and organizational risks

Energy calibration and resolution of the CMS electromagnetic calorimeter in pp collisions at s\sqrt{s} = 7 TeV

The energy calibration and resolution of the electromagnetic calorimeter (ECAL) of the CMS detector have been determined using proton-proton collision data from LHC operation in 2010 and 2011 at a centre-of-mass energy of sqrt(s)=7 TeV with integrated luminosities of about 5 inverse femtobarns. Crucial aspects of detector operation, such as the environmental stability, alignment, and synchronization, are presented. The in-situ calibration procedures are discussed in detail and include the maintenance of the calibration in the challenging radiation environment inside the CMS detector. The energy resolution for electrons from Z-boson decays is better than 2% in the central region of the ECAL barrel (for pseudorapidity abs(eta)<0.8) and is 2-5% elsewhere. The derived energy resolution for photons from 125 GeV Higgs boson decays varies across the barrel from 1.1% to 2.6% and from 2.2% to 5% in the entraps. The calibration of the absolute energy is determined from Z to e+e- decays to a precision of 0.4% in the barrel and 0.8% in the endcaps

Search for heavy resonances in the W/Z-tagged dijet mass spectrum in pp collisions at 7 TeV

A search has been made for massive resonances decaying into a quark and a vector boson, qW or qZ, or a pair of vector bosons, WW, WZ, or ZZ, where each vector boson decays to hadronic final states. This search is based on a data sample corresponding to an integrated luminosity of 5.0 fb 121 of proton\u2013proton collisions collected in the CMS experiment at the LHC in 2011 at a center-of-mass energy of 7 TeV. For sufficiently heavy resonances the decay products of each vector boson are merged into a single jet, and the event effectively has a dijet topology. The background from QCD dijet events is reduced using recently developed techniques that resolve jet substructure. A 95% CL lower limit is set on the mass of excited quark resonances decaying into qW (qZ) at 2.38 TeV (2.15 TeV) and upper limits are set on the cross section for resonances decaying to qW, qZ, WW, WZ, or ZZ final states

Search for long-lived particles in events with photons and missing energy in proton\u2013proton collisions at sqrt(s)=7 TeV

Results are presented from a search for long-lived neutralinos decaying into a photon and an invisible particle, a signature associated with gauge-mediated supersymmetry breaking in supersymmetric models. The analysis is based on a 4.9 inverse femtobarn sample of proton-proton collisions at 1as = 7 TeV, collected with the CMS detector at the LHC. The missing transverse energy and the time of arrival of the photon at the electromagnetic calorimeter are used to search for an excess of events over the expected background. No significant excess is observed, and lower limits at the 95% confidence level are obtained on the mass of the lightest neutralino, m(neutralino) > 220 GeV (for c tau 6000 mm (for m(neutralino) < 150 GeV)