Screen-detected colorectal cancers are associated with an improved outcome compared with stage-matched interval cancers

Background: Colorectal cancers (CRCs) detected through the NHS Bowel Cancer Screening Programme (BCSP) have been shown to have a more favourable outcome compared to non-screen-detected cancers. The aim was to identify whether this was solely due to the earlier stage shift of these cancers, or whether other factors were involved. Methods: A combination of a regional CRC registry (Northern Colorectal Cancer Audit Group) and the BCSP database were used to identify screen-detected and interval cancers (diagnosed after a negative faecal occult blood test, before the next screening round), diagnosed between April 2007 and March 2010, within the North East of England. For each Dukes' stage, patient demographics, tumour characteristics, and survival rates were compared between these two groups. Results: Overall, 322 screen-detected cancers were compared against 192 interval cancers. Screen-detected Dukes' C and D CRCs had a superior survival rate compared with interval cancers (P=0.014 and P=0.04, respectively). Cox proportional hazards regression showed that Dukes' stage, tumour location, and diagnostic group (HR 0.45, 95% CI 0.29-0.69, P<0.001 for screen-detected CRCs) were all found to have a significant impact on the survival of patients. Conclusions: The improved survival of screen-detected over interval cancers for stages C and D suggest that there may be a biological difference in the cancers in each group. Although lead-time bias may have a role, this may be related to a tumour's propensity to bleed and therefore may reflect detection through current screening tests

Dexmedetomidine sedation in ICU

Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is the newest agent introduced for sedation in intensive care unit (ICU). The sedation strategy for critically ill patients has stressed light sedation with daily awakening and assessment for neurologic, cognitive, and respiratory functions, since Society of Critical Care Medicine (SCCM) guidelines were presented in 2002. The traditional GABAergic agents, including benzodiazepines and propofol, have some limitations for safe sedatives in this setting, due to an unfavorable pharmacokinetic profile and to detrimental adverse effects (such as lorazepam associated propylene glycol intoxication and propofol infusion syndrome). DEX produces it's sedative, analgesic and cardiovascular effects through α2 receptors on the locus ceruleus (LC). Activities of LC, the tuberomammillary nucleus (TMN) are depressed and activity of the ventrolateral preoptic nucleus (VLPO) is increased during DEX sedation, which is similar in features to normal non-REM (NREM) sleep. At the same time, perifornical orexinergic activity is maintained, which might be associated with attention. This mechanism of action produces a normal sleep-like, cooperative sedation. The characteristic feature of sedation, together with a concomitant opioid sparing effect, may decrease the length of time spent on a ventilator, length of stay in ICU, and prevalence and duration of delirium, as the evidence shown from several comparative studies. In addition, DEX has an excellent safety profile. In conclusion, DEX is considered as a promising agent optimized for sedation in ICU

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky

Representativeness of Eddy-Covariance flux footprints for areas surrounding AmeriFlux sites

Large datasets of greenhouse gas and energy surface-atmosphere fluxes measured with the eddy-covariance technique (e.g., FLUXNET2015, AmeriFlux BASE) are widely used to benchmark models and remote-sensing products. This study addresses one of the major challenges facing model-data integration: To what spatial extent do flux measurements taken at individual eddy-covariance sites reflect model- or satellite-based grid cells? We evaluate flux footprints—the temporally dynamic source areas that contribute to measured fluxes—and the representativeness of these footprints for target areas (e.g., within 250–3000 m radii around flux towers) that are often used in flux-data synthesis and modeling studies. We examine the land-cover composition and vegetation characteristics, represented here by the Enhanced Vegetation Index (EVI), in the flux footprints and target areas across 214 AmeriFlux sites, and evaluate potential biases as a consequence of the footprint-to-target-area mismatch. Monthly 80% footprint climatologies vary across sites and through time ranging four orders of magnitude from 103 to 107 m2 due to the measurement heights, underlying vegetation- and ground-surface characteristics, wind directions, and turbulent state of the atmosphere. Few eddy-covariance sites are located in a truly homogeneous landscape. Thus, the common model-data integration approaches that use a fixed-extent target area across sites introduce biases on the order of 4%–20% for EVI and 6%–20% for the dominant land cover percentage. These biases are site-specific functions of measurement heights, target area extents, and land-surface characteristics. We advocate that flux datasets need to be used with footprint awareness, especially in research and applications that benchmark against models and data products with explicit spatial information. We propose a simple representativeness index based on our evaluations that can be used as a guide to identify site-periods suitable for specific applications and to provide general guidance for data use

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society

Enhancing physical activity in older adults receiving hospital based rehabilitation: a phase II feasibility study

<p>Abstract</p> <p>Background</p> <p>Older adults receiving inpatient rehabilitation have low activity levels and poor mobility outcomes. Increased physical activity may improve mobility. The objective of this Phase II study was to evaluate the feasibility of a randomized controlled trial (RCT) of enhanced physical activity in older adults receiving rehabilitation.</p> <p>Methods</p> <p>Patients admitted to aged care rehabilitation with reduced mobility were randomized to receive usual care or usual care plus additional physical activity, which was delivered by a physiotherapist or physiotherapy assistant. The feasibility and safety of the proposed RCT protocol was evaluated. The primary clinical outcome was mobility, which was assessed on hospital admission and discharge by an assessor blinded to group assignment. To determine the most appropriate measure of mobility, three measures were trialled; the Timed Up and Go, the Elderly Mobility Scale and the de Morton Mobility Index.</p> <p>Results</p> <p>The protocol was feasible. Thirty-four percent of people admitted to the ward were recruited, with 47 participants randomised to a control (n = 25) or intervention group (n = 22). The rates of adverse events (death, falls and readmission to an acute service) did not differ between the groups. Usual care therapists remained blind to group allocation, with no change in usual practice. Physical activity targets were met on weekdays but not weekends and the intervention was acceptable to participants. The de Morton Mobility Index was the most appropriate measure of mobility.</p> <p>Conclusions</p> <p>The proposed RCT of enhanced physical activity in older adults receiving rehabilitation was feasible. A larger multi-centre RCT to establish whether this intervention is cost effective and improves mobility is warranted.</p> <p>Trial registration</p> <p>The trial was registered with the ANZTCR (ACTRN12608000427370).</p

Postoperative Pain Control Following Craniotomy: A Systematic Review of Recent Clinical Literature

Background: Pain intensity after craniotomy is considered to be moderate to severe during the first 2 postoperative days. The ideal pain treatment to facilitate a rapid postoperative recovery and optimize outcome is unknown.Objectives: This systematic review aims to report current clinical evidence related to pharmacological and adjuvant analgesic modalities for postcraniotomy pain control.Design: Systematic review of randomized controlled trials (RCTs).Data Sources: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (January 2011 to April 2016).Eligibility Criteria: Original research involving the use of any analgesic drug, analgesic method, or nonpharmacological intervention for postcraniotomy pain relief, as assessed by pain scores up to 48 hours postoperatively, supplemental analgesic requirements, or occurence of adverse events.Results: Nineteen RCTs enrolling a total of 1,805 patients were included. Most of the retrieved studies were of moderate- to-good methodological quality. Systemic pharmacological intervention was assessed in 14 RCTs. Opioids (5 RCTs) provided superior pain relief to other analgesics with no significant side effects, but the quality of studies was low. Diclofenac (3 RCTs) presented adequate craniotomy pain control without any adverse effects, while the use of parecoxib is not supported. Dexmedetomidine (3 RCTs) provided adequate transitional analgesia, but further research is needed. Data on the analgesic efficacy of gabapentin, pregabalin, and intravenous lidocaine are very limited (1 RCT for each). Scalp infiltration/block (3 RCTs) provided adequate analgesia in the early postoperative period, while more studies are needed to verify the analgesic benefit obtained from nonpharmacological interventions, such as multipoint electro-acupuncture, in craniotomy surgery (2 RCTs).Conclusions: No definite recommendations can be made based on this systematic review of pharamacological interventions following craniotomy due to significant divergence in the methodology of available studies. Limited evidence on scalp infiltration/block suggests an adequate analgesic effect in the early postoperative period. Analgesic efficacy of dexmedetomidine and multipoint electro-acupuncture needs further evaluation