Interventions in food business organisations to improve food safety culture: a rapid evidence assessment.

The European Commission recently adopted Commission Regulation (EU) 2021/382 requiring food businesses to establish and provide evidence of a food safety culture (FSC). FSC incorporates management systems, risk perceptions, leadership, communication, environment and commitment to ensure food safety. This review (n = 20) investigates food safety interventions in food businesses to identify effective strategies to improve food safety practices and FSC, and to provide recommendations for improving FSC. Results found that most interventions focused on knowledge training and that workplace practical demonstrations produced the best outcomes. Similar training topics were used evidencing the existence of common training needs. Frequent training over longer time periods was most successful for behavioral change, yet no sustained behavioral change was reported, indicating that single knowledge-based interventions are insufficient, reinforcing repeated experiential learning to be incorporated into training. We suggest that FSC training should focus on FSC more broadly, rather than solely on knowledge training, and that management leadership skills in particular are important to ensure sustained positive change. This study contributes to knowledge by providing a summative overview of food safety interventions and how components of these may be used to enhance FSC in food businesses.

Leukaemia, lymphoma, and multiple myeloma mortality after low-level exposure to ionising radiation in nuclear workers (INWORKS): updated findings from an international cohort study.

BACKGROUND: A major update to the International Nuclear Workers Study (INWORKS) was undertaken to strengthen understanding of associations between low-dose exposure to penetrating forms of ionising radiation and mortality. Here, we report on associations between radiation dose and mortality due to haematological malignancies. METHODS: We assembled a cohort of 309 932 radiation-monitored workers (269 487 [87%] males and 40 445 [13%] females) employed for at least 1 year by a nuclear facility in France (60 697 workers), the UK (147 872 workers), and the USA (101 363 workers). Workers were individually monitored for external radiation exposure and followed-up from Jan 1, 1944, to Dec 31, 2016, accruing 10·72 million person-years of follow-up. Radiation-mortality associations were quantified in terms of the excess relative rate (ERR) per Gy of radiation dose to red bone marrow for leukaemia excluding chronic lymphocytic leukaemia (CLL), as well as subtypes of leukaemia, myelodysplastic syndromes, non-Hodgkin and Hodgkin lymphomas, and multiple myeloma. Estimates of association were obtained using Poisson regression methods. FINDINGS: The association between cumulative dose to red bone marrow, lagged 2 years, and leukaemia (excluding CLL) mortality was well described by a linear model (ERR per Gy 2·68, 90% CI 1·13 to 4·55, n=771) and was not modified by neutron exposure, internal contamination monitoring status, or period of hire. Positive associations were also observed for chronic myeloid leukaemia (9·57, 4·00 to 17·91, n=122) and myelodysplastic syndromes alone (3·19, 0·35 to 7·33, n=163) or combined with acute myeloid leukaemia (1·55, 0·05 to 3·42, n=598). No significant association was observed for acute lymphoblastic leukaemia (4·25, -4·19 to 19·32, n=49) or CLL (0·20, -1·81 to 2·21, n=242). A positive association was observed between radiation dose and multiple myeloma (1·62, 0·06 to 3·64, n=527) whereas minimal evidence of association was observed between radiation dose and non-Hodgkin lymphoma (0·27, -0·61 to 1·39, n=1146) or Hodgkin lymphoma (0·60, -3·64 to 4·83, n=122) mortality. INTERPRETATION: This study reports a positive association between protracted low dose exposure to ionising radiation and mortality due to some haematological malignancies. Given the relatively low doses typically accrued by workers in this study (16 mGy average cumulative red bone marrow dose) the radiation attributable absolute risk of leukaemia mortality in this population is low (one excess death in 10 000 workers over a 35-year period). These results can inform radiation protection standards and will provide input for discussions on the radiation protection system. FUNDING: National Cancer Institute, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Institut de Radioprotection et de Sûreté Nucléaire, Orano, Electricité de France, UK Health Security Agency. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Site-specific cancer mortality after low level exposure to ionizing radiation: Findings from an update of the International Nuclear Workers Study (INWORKS).

A major update to the International Nuclear Workers Study was undertaken that allows us to report updated estimates of associations between radiation and site-specific solid cancer mortality. A cohort of 309,932 nuclear workers employed in France, the United Kingdom, and United States were monitored for external radiation exposure and associations with cancer mortality were quantified as the excess relative rate (ERR) per gray (Gy) using a maximum likelihood and a Markov chain Monte Carlo method (to stabilize estimates via a hierarchical regression). The analysis included 28,089 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using maximum likelihood, positive estimates of ERR per Gy were obtained for stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura/mesothelioma, bone and connective tissue, skin, prostate, testis, bladder, kidney, thyroid, and residual cancers; negative estimates of ERR per Gy were found cancers of oral cavity and pharynx, esophagus, and ovary. A hierarchical model stabilized site-specific estimates of association, including for lung (ERR per Gy=0.65; 95% credible interval [CrI]: 0.24, 1.07), prostate (ERR per Gy=0.44; 95% CrI: -0.06, 0.91), and colon cancer (ERR per Gy=0.53; 95% CrI: -0.07, 1.11). The results contribute evidence regarding associations between low dose radiation and cancer.

Shape of radiation dose response relationship for ischaemic heart disease mortality and its interpretation: analysis of the national registry for radiation workers (NRRW) cohort.

Statistically significant increases in ischemic heart disease (IHD) mortality with cumulative occupational external radiation dose were observed in the National Registry for Radiation Workers (NRRW) cohort. There were 174 541 subjects in the NRRW cohort. The start of follow up was 1955, and the end of the follow-up for each worker was chosen as the earliest date of death or emigration, their 85th birthday or 31 December 2011. The dose-response relationship showed a downward curvature at a higher dose level >0.4 Sv with the overall shape of the dose-response relationship best described by a linear-quadratic model. The smaller risk at dose >0.4 Sv appears to be primarily associated with workers who started employment at a younger age (<30 years old) and those who were employed for more than 30 years. We modelled the dose response by age-at-first exposure. For the age-at-first exposure of 30+ years old, a linear dose-response was the best fit. For age-at-first exposure <30 years old, there was no evidence of excess risk of IHD mortality for radiation doses below 0.1 Sv or above 0.4 Sv, excess risk was only observed for doses between 0.1-0.4 Sv. For this age-at-first exposure group, it was also found that the doses they received when they were less than 35 years old or greater than 50 years old did not contribute to any increased IHD risk.

The Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal Compared With Conventional Lung Protective Ventilation on Cardiac Function.

OBJECTIVES: Lower tidal volume ventilation (targeting 3 mL/kg predicted body weight, PBW) facilitated by extracorporeal carbon dioxide removal (ECCO2R) has been investigated as a potential therapy for acute hypoxemic respiratory failure (AHRF) in the pRotective vEntilation with veno-venouS lung assisT in respiratory failure (REST) trial. We investigated the effect of this strategy on cardiac function, and in particular the right ventricle. DESIGN: Substudy of the REST trial. SETTING: Nine U.K. ICUs. PATIENTS: Patients with AHRF (Pao2/Fio2 < 150 mm Hg [20 kPa]). INTERVENTION: Transthoracic echocardiography and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements were collected at baseline and postrandomization in patients randomized to ECCO2R or usual care. MEASUREMENTS: The primary outcome measures were a difference in tricuspid annular plane systolic excursion (TAPSE) on postrandomization echocardiogram and difference in NT-proBNP postrandomization. RESULTS: There were 21 patients included in the echocardiography cohort (ECCO2R, n = 13; usual care, n = 8). Patient characteristics were similar in both groups at baseline. Median (interquartile range) tidal volumes were lower in the ECCO2R group compared with the usual care group postrandomization; 3.6 (3.1-4.2) mL/kg PBW versus 5.2 (4.9-5.7) mL/kg PBW, respectively (p = 0.01). There was no difference in the primary outcome measure of mean (sd) TAPSE in the ECCO2R and usual care groups postrandomization; 21.3 (5.4) mm versus 20.1 (3.2) mm, respectively (p = 0.60). There were 75 patients included in the NT-proBNP cohort (ECCO2R, n = 36; usual care, n = 39). Patient characteristics were similar in both groups at baseline. Median (interquartile range [IQR]) tidal volumes were lower in the ECCO2R group than the usual care group postrandomization; 3.8 (3.3-4.2) mL/kg PBW versus 6.7 (5.8-8.1) mL/kg PBW, respectively (p < 0.0001). There was no difference in median (IQR) NT-proBNP postrandomization; 1121 (241-5370) pg/mL versus 1393 (723-4332) pg/mL in the ECCO2R and usual care groups, respectively (p = 0.30). CONCLUSIONS: In patients with AHRF, a reduction in tidal volume facilitated by ECCO2R, did not modify cardiac function.

Cancer mortality after low dose exposure to ionising radiation in workers in France, the United Kingdom, and the United States (INWORKS): cohort study.

OBJECTIVE: To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer. DESIGN: Multinational cohort study. SETTING: Cohorts of workers in the nuclear industry in France, the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS). PARTICIPANTS: 309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years. MAIN OUTCOME MEASURES: Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer. RESULTS: The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos. CONCLUSIONS: This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world's most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings.

Point-of-care echocardiography and thoracic ultrasound in the management of critically ill patients with COVID-19 infection: Experience in three regional UK intensive care units.

Introduction: Point-of-care ultrasound (POCUS) has an established role in the management of the critically ill. Information and experience of its use in those with COVID-19 disease is still evolving. We undertook a review of cardiac and thoracic ultrasound examinations in patients with COVID-19 on the intensive care unit (ICU). Our aim was to report key findings and their impact on patient management. Methods: A retrospective evaluation of critically ill patients with COVID-19 was undertaken in three adult ICUs, who received point-of-care cardiac and/or thoracic ultrasound during the 2019-2020 COVID-19 pandemic. We recorded baseline demographic data, principal findings, change in clinical management and outcome data. Results: A total of 55 transthoracic echocardiographic examinations scans were performed on 35 patients. 35/55 (64%) echocardiograms identified an abnormality, most commonly a dilated or impaired right ventricle (RV) and 39/55 (70%) scans resulted in a change in management. Nine patients (26%) were found to have pulmonary arterial thrombosis on CTPA or post-mortem. More than 50% of these patients showed evidence of right ventricular dilatation or impairment. Of the patients who were known to have pulmonary arterial thrombosis and died, 83% had evidence of right ventricular dilatation or impairment. 32 thoracic ultrasound scans were performed on 23 patients. Lung sliding and pleural thickening were present bilaterally in all studies. Multiple B-lines were present in all studies, and sub-pleural consolidation was present bilaterally in 72%. Conclusion: POCUS is able to provide useful and clinically relevant information in those critically ill with COVID-19 infection, resulting in change in management in a high proportion of patients. Common findings in this group are RV dysfunction, multiple B-lines and sub-pleural consolidation.

Effects of radiation on respiratory disease mortality: analysis of the national registry for radiation workers in United Kingdom.

PURPOSE: While some evidence of an effect of radiation exposure on respiratory disease at low dose levels has now emerged, there is heterogeneity in the risks between different studies and countries. In this paper, we aim to show the effect of radiation on three different sub-types of respiratory disease mortality through the analysis of the NRRW cohort in UK. MATERIALS AND METHODS: The NRRW cohort consisted of 174,541 radiation workers. Doses to the surface of the body were monitored using individual film badges. Most of the doses are associated with X-rays and gamma rays and to a less extent of beta and neutron particles. The overall mean 10-year lagged lifetime external dose was 23.2 mSv. Some workers were potentially exposed to alpha particles. However, doses from internal emitters were not available for the NRRW cohort. 25% of male workers and 17% of female workers were identified as being monitored for internal exposure. The Poisson regression methods for grouped survival data with a stratified baseline hazard function were used to describe the dependence of the risk on cumulative external radiation dose. The disease was analyzed by the following subgroups: Pneumonia (1066 cases including 17 cases of influenza), COPD and allied disease (1517 cases) and other remaining respiratory diseases (479 cases). RESULTS: There was very little radiation effect on pneumonia mortality, but evidence of a reduction in mortality risk for COPD and allied disease (ERR/Sv= -0.56, 95%CI: -0.94, -0.06; p = .02) and an increase in risk for other respiratory disease mortality (ERR/Sv = 2.30, 95%CI: 0.67, 4.62; p = .01) with increasing cumulative external dose were observed. The effects of radiation were more prominent amongst workers monitored for internal exposure. The reduction in mortality risk of COPD and allied disease per cumulative external dose was statistically significant for the radiation workers monitored for internal exposure (ERR/Sv= -0.59, 95%CI: -0.99, -0.05; p = .017) but not significant among the workers who were not monitored (ERR/Sv= -0.43, 95%CI: -1.20, 0.74; p = .42). A statistically significant increased risk was observed for other respiratory diseases among monitored radiation workers (ERR/Sv = 2.46, 95%CI: 0.69, 5.08; p = .019), but not among unmonitored workers (ERR/Sv = 1.70, 95%CI: -0.82, 5.65; p = .25). CONCLUSION: The effects of radiation exposure can be different depending on the type of respiratory disease. No effect was seen in pneumonia; a reduction in mortality risk of COPD, and increased mortality risk of other respiratory diseases were observed with cumulative external radiation dose. More studies are needed to verify these findings.

Liberal or restrictive antimicrobial prophylaxis for surgical site infection: systematic review and meta-analysis of randomised trials.

BACKGROUND: Antimicrobial prophylaxis is widely used to prevent surgical site infection. Amid growing concern about antimicrobial resistance, we determined the effectiveness of antimicrobial prophylaxis. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and WHO-ICTRP between January 1, 1990 and January 1, 2020 for trials randomising adults undergoing surgery to liberal (more doses) or restrictive (fewer or no doses) perioperative antimicrobial prophylaxis. Pairs of researchers reviewed articles and extracted data, and a senior author resolved discrepancies. The primary outcome measure was surgical site infection or bacteriuria for urological procedures. We calculated average risk difference (RD) with 95% confidence intervals and prediction intervals (PI) using random effects models, and present risk ratios (RR). We assessed evidence certainty using GRADE methodology, and risk of bias using the Cochrane Risk of Bias tool (PROSPERO: CRD42018116946). RESULTS: From 6593 records, we identified 294 trials including 86 146 patients. Surgical site infection occurred in 2237/44 113 (5.1%) patients receiving liberal prophylaxis vs 2889/42 033 (6.9%) receiving restrictive prophylaxis (RD -0.01 [-0.02 to -0.01]; relative risk 0.72 [0.67-0.77]; I2=52%, PI -0.05-0.02). There was a small benefit of prophylaxis in 161 trials comparing no prophylaxis with ≥1 dose (RD -0.02 [-0.03 to -0.02]; RR 0.58 [0.52-0.65]; I2=62%, PI -0.06-0.02). Treatment effect varied from a strong effect in urology to no benefit in 7/19 specialities. Tests for publication bias suggest 62 unreported trials and evidence certainty was very low. Treatment harms were reported in 43/294 trials. CONCLUSIONS: A systematic review and meta-analysis of randomised trials revealed that more liberal antimicrobial prophylaxis is associated with a small reduction in the risk of surgical site infection, although antimicrobial harms are poorly reported. Further evidence about the risks of antimicrobial prophylaxis to inform current widespread use is urgently needed.

Perioperative intravenous iron to treat patients with fractured hip surgery: A systematic review and meta-analysis.

Background: Treatment of preoperative anemia with intravenous iron is common within elective surgical care pathways. It is plausible that this treatment may improve care for people with hip fractures many of whom are anemic because of pre-existing conditions, fractures, and surgery. Objective: To review the evidence for intravenous iron administration on outcomes after hip fracture. Design: We followed a predefined protocol and conducted a systematic review and meta-analysis of the use of intravenous iron to treat anemia before and after emergency hip fracture surgery. The planned primary outcome was a difference in length of stay between those treated with intravenous iron and the control group. Other outcomes analyzed were 30-day mortality, requirement for blood transfusion, changes in quality of life, and hemoglobin concentration on discharge from the hospital. Data Sources: EMBASE, MEDLINE, The Cochrane Library (CENTRAL, DARE) databases, Clinicaltrials.gov, and ISRCTN trial registries. Date of final search March 2022. Eligibility Criteria: Adult patients undergoing urgent surgery for hip fracture. Studies considered patients who received intravenous iron and were compared with a control group. Results: Four randomized controlled trials (RCT, 732 patients) and nine cohort studies (2986 patients) were included. The RCTs were at low risk of bias, and the nonrandomized studies were at moderate risk of bias. After metanalysis of the RCTs there was no significant difference in the primary outcome, length of hospital stay, between the control group and patients receiving intravenous iron (mean difference: -0.59, 95% confidence interval [CI]; -1.20 to 0.03; I 2 = 30%, p = 0.23). Intravenous iron was not associated with a difference in 30-day mortality (n = 732, OR: 1.14, 95% CI: 0.62-2.1; I 2 = 0%, p = 0.50), nor with the requirement for transfusion (n = 732, OR: 0.85, 95% CI: 0.63-1.14; I 2 = 0%, p < 0.01) in the analyzed RCTs. Functional outcomes and quality of life were variably reported in three studies. Conclusion: The evidence on the use of intravenous iron in patients with hip fracture is low quality and shows no difference in length of acute hospital stay and transfusion requirements in this population. Improved large, multicentre, high-quality studies with patient-centered outcomes will be required to evaluate the clinical and cost-effectiveness of this treatment.

Changes in perioperative red cell transfusion practice over time in patients undergoing surgery for upper gastrointestinal and liver cancer: a retrospective cohort study at a single tertiary centre.

OBJECTIVES: Optimum transfusion trigger for adults undergoing cancer surgery is uncertain. Published guidelines recommend restrictive transfusion strategies in hospitalised adults. We aimed to measure the red cell transfusion rate and haemoglobin trigger in patients undergoing cancer surgery and how closely practice reflected published guidelines. DESIGN: Retrospective cohort study. SETTING: Single tertiary centre. PARTICIPANTS: Adult patients undergoing surgery for upper gastrointestinal or liver malignancy. EXPOSURE: Postguideline change (2015-2017) versus preguideline change (2011-2012). OUTCOME MEASURES: Primary: transfusion rate, secondary: transfusion trigger. Multivariable logistic regression was used to assess factors and adjust for confounders affecting our outcome measures. RESULTS: 1578 surgical records were identified for 1520 patients. 946/1530 (62%) patients had preoperative anaemia. The transfusion rate decreased from 23% in 2011-2012 to 14% in 2015-2017. This change remained significant after adjusting for other variables associated with transfusion rates. Mean pretransfusion haemoglobin in those who were transfused was 78±13 g/L in 2011-2012 and 80±15 g/L in 2015-2017. This change in haemoglobin transfusion triggers was not significant. CONCLUSION: Transfusion rate has decreased over the study period in patients undergoing surgery for malignancy and is consistent with a restrictive transfusion strategy.

Extended analysis of solid cancer incidence among the Nuclear Industry Workers in the UK: 1955-2011.

Radiation worker studies provide direct estimates of cancer risk after protracted low-dose exposures to external X-ray and gamma-ray irradiations. The National Registry for Radiation Workers (NRRW) started in 1976 and has become the largest epidemiological program of research on nuclear workers in the UK. Here, we report on the relationship between solid cancer incidence and external radiation at the low-dose levels in 172,452 NRRW cohort members of whom (90%) were men. This study is based on 5.25 million person-years of follow-up from 1955 through the end of 2011. In the range of accumulated low doses two-thirds of workers have doses of less than 10 mSv. This study is an updated analysis of solid cancer incidence data with an additional 10 years of follow-up over the previous analysis of the NRRW cohort (NRRW-3). A total of 18,310 cases of solid cancers based on a 10-year lag were registered and of these 43% of the solid cancer cases occurred during the latest 10 years. Poisson regression was used to investigate the relationship between solid cancers risk and protracted chronic low-dose radiation exposure. This study demonstrated for solid cancers a rapid decrease of risk at high external doses that appeared to be driven by the workers who were monitored for potential exposure to internal emitters and who had also received relatively high external doses. Among cohort members only exposed to external radiation, a strong association was found between external dose and solid cancers (ERR/Sv = 0.52, 95% CI: 0.11; 0.96, based on 13,199 cases). A similar pattern is also seen for lung cancer. Excluding lung cancer from the grouping of all solid cancers resulted in evidence of a linear association with external radiation dose (ERR/Sv = 0.24, 95% CI: 0.01; 0.49, based on 15,035 cases), so suggesting some degree of confounding by smoking. Statistically significantly increasing trends with dose were seen for cancers of the colorectal, bladder and pleura cancer. Some of these results should be treated with caution because of the limited corroborating evidence from other published studies. Information on internal doses as well as non-radiation factors such smoking would be helpful to make more definitive inferences.

Cerebrovascular Disease Mortality after occupational Radiation Exposure among the UK National Registry for Radiation Workers Cohort.

Exposure to ionizing radiation can damage the cerebrovascular system, however there is uncertainty regarding the effects after chronic exposure to low doses of radiation, such as that experienced by the public and those occupationally exposed. This study uses data from the UK National Registry for Radiation Workers cohort to assess the association between low-dose exposure to external radiation and cerebrovascular disease (CeVD) mortality. Poisson regression was used to estimate the Excess Relative Risk of CeVD mortality per Sievert (ERR/Sv) of radiation exposure. Estimates were obtained for all CeVD combined, ischemic stroke, hemorrhagic stroke and other/ill-defined CeVD. Results were adjusted for attained age, calendar period, sex, employer, industrial category and employment length. 166,812 nuclear workers (3,665,413 person-years) were included. By the end of 2011, 23% were dead including 3,219 deaths with an underlying cause of CeVD. The ERR/Sv for all CeVD deaths was 0.57 (95% CI: 0.00, 1.31; p = 0.05). Increased CeVD mortality rates were observed after doses as low as 10-20 mSv. However, a linear-exponential model fit the data significantly better than a linear model (p = 0.02). In the sub-type analyses, no evidence of linear associations were observed, however the patterns of response appeared to differ and there was some suggestion of an increased risk of hemorrhagic stroke at lower doses. These results are broadly consistent with other occupational cohort studies and suggest external radiation exposure may increase CeVD risk at lower doses than current ICRP protection guidelines suggest. Exploration of factors driving the observed dose-response shape, the potential impact of the healthy worker survivor effect, and further studies of cohorts with data on other potential confounders would be valuable.

Mortality and cancer incidence 1952-2017 in United Kingdom participants in the United Kingdom's atmospheric nuclear weapon tests and experimental programmes.

This study examines the mortality and cancer incidence experience among men who took part in the United Kingdom's atmospheric nuclear weapon tests between 1952-67. A cohort of 21 357 servicemen and male civilians from the UK who participated in the tests and a group of 22 312 controls were followed between 1952 and 2017. Analyses of mortality and cancer incidence were conducted. The overall mortality rate in the test participants was slightly higher relative risk (RR = 1.02, 90% CI 1.00-1.05,p= 0.04) than that in the control group. This difference was driven by similar increased risks for both all cancers combined (RR 1.03, 90% CI 1.00-1.07) and all non-cancer diseases (RR = 1.02, 90% CI 1.00-1.05). Leukaemia excluding chronic lymphatic incidence showed evidence of being raised relative to controls (RR = 1.38, 90% CI 1.10-1.75,p= 0.01). Leukaemia risks were driven by increased risks for chronic myeloid leukaemia (CML) (RR = 2.43, 90% CI 1.43-4.13,p= 0.003). Among non-cancer outcomes only cerebrovascular diseases showed increases in participants relative to controls. UK nuclear weapon tests participants have lower mortality rates compared to the national population although rates are slightly (2%) higher than in the study control group. Variation in background characteristics, that could not be accounted for in the analysis (e.g. smoking habits, diet), are a possible explanation for this difference. For leukaemia evidence of increased risk in the early years after the test has generally continued to diminish with time although for CML risks have persisted. There was some evidence that participants had higher mortality rates from cerebrovascular diseases than those in the control group. Assuming recorded radiation exposures (generally very low) are a true reflection of actual exposures then it is unlikely that any observed health effect will have been caused by radiation exposure.

Perioperative blood transfusion in major abdominal cancer surgery: a multi-centre service evaluation and national survey.

Background: Anaemia is associated with complications and death after surgery. Perioperative red-cell transfusion triggers are not well defined in patients having oncological surgery, or with cardiovascular disease. Methods: We carried out a prospective multicentre cohort study and a clinician survey of UK transfusion practice in adult patients undergoing surgery for abdominal malignancy. The primary outcome was red cell transfusion. Secondary outcomes were transfusion trigger haemoglobin, incidence of complications, length of hospital stay, and acute hospital mortality. Results: In this prospective cohort study, data were collected on 412 patients undergoing surgery for intrabdominal malignancy in 14 NHS hospitals. Twenty-two (5.2%) patients received preoperative, 42 (10.2%) intraoperative, and 52 (12.2%) postoperative red blood cell transfusion. The mean postoperative transfusion trigger was 75.3 g L-1, and the mean number of units of red blood cells transfused was 1.5 (standard deviation, 1.1). Seventeen (4.0%) patients had a documented postoperative troponin elevation. Five (1.2%) patients died within 30 days of surgery. In the survey, 117 clinicians submitted complete responses, of whom 62 (53%) indicated that a transfusion threshold of 70 g L-1 was appropriate: however, this decreased to six (5.1%) if there was evidence of recent cardiac ischaemia. There were 100 (86%) respondents who indicated equipoise for a trial of restrictive vs liberal transfusion, decreasing to 56% if there was coexisting cardiovascular disease. Conclusions: Many patients having oncological surgery receive red cell transfusion, the majority being given postoperatively. Restrictive transfusion practice is generally followed; however, variability exists especially in cardiovascular disease. Equipoise exists for a study of transfusion thresholds in this group.

Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial.

Importance: In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants: This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions: Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures: The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results: Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, -7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, -2.1 [95% CI, -3.8 to -0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02654327.

Risk of cancer associated with low-dose radiation exposure: comparison of results between the INWORKS nuclear workers study and the A-bomb survivors study.

The Life Span Study (LSS) of Japanese atomic bomb survivors has served as the primary basis for estimates of radiation-related disease risks that inform radiation protection standards. The long-term follow-up of radiation-monitored nuclear workers provides estimates of radiation-cancer associations that complement findings from the LSS. Here, a comparison of radiation-cancer mortality risk estimates derived from the LSS and INWORKS, a large international nuclear worker study, is presented. Restrictions were made, so that the two study populations were similar with respect to ages and periods of exposure, leading to selection of 45,625 A-bomb survivors and 259,350 nuclear workers. For solid cancer, excess relative rates (ERR) per gray (Gy) were 0.28 (90% CI 0.18; 0.38) in the LSS, and 0.29 (90% CI 0.07; 0.53) in INWORKS. A joint analysis of the data allowed for a formal assessment of heterogeneity of the ERR per Gy across the two studies (P = 0.909), with minimal evidence of curvature or of a modifying effect of attained age, age at exposure, or sex in either study. There was evidence in both cohorts of modification of the excess absolute risk (EAR) of solid cancer by attained age, with a trend of increasing EAR per Gy with attained age. For leukemia, under a simple linear model, the ERR per Gy was 2.75 (90% CI 1.73; 4.21) in the LSS and 3.15 (90% CI 1.12; 5.72) in INWORKS, with evidence of curvature in the association across the range of dose observed in the LSS but not in INWORKS; the EAR per Gy was 3.54 (90% CI 2.30; 5.05) in the LSS and 2.03 (90% CI 0.36; 4.07) in INWORKS. These findings from different study populations may help understanding of radiation risks, with INWORKS contributing information derived from cohorts of workers with protracted low dose-rate exposures.

A restrictive versus liberal transfusion strategy to prevent myocardial injury in patients undergoing surgery for fractured neck of femur: a feasibility randomised trial (RESULT-NOF).

BACKGROUND: The optimum transfusion strategy in patients with fractured neck of femur is uncertain, particularly if there is coexisting cardiovascular disease. METHODS: We conducted a prospective, single-centre, randomised feasibility trial of two transfusion strategies. We randomly assigned patients undergoing surgery for fractured neck of femur to a restrictive (haemoglobin, 70-90 g L-1) or liberal (haemoglobin, 90-110 g L-1) transfusion strategy throughout their hospitalisation. Feasibility outcomes included: enrolment rate, protocol compliance, difference in haemoglobin, and blood exposure. The primary clinical outcome was myocardial injury using troponin estimations. Secondary outcomes included major adverse cardiac events, postoperative complications, duration of hospitalisation, mortality, and quality of life. RESULTS: We enrolled 200 (22%) of 907 eligible patients, and 62 (31%) showed decreased haemoglobin (to 90 g L-1 or less) and were thus exposed to the intervention. The overall protocol compliance was 81% in the liberal group and 64% in the restrictive group. Haemoglobin concentrations were similar preoperatively and at postoperative day 1 but lower in the restrictive group on day 2 (mean difference [MD], 7.0 g L-1; 95% confidence interval [CI], 1.6-12.4). Lowest haemoglobin within 30 days/before discharge was lower in the restrictive group (MD, 5.3 g L-1; 95% CI, 1.7-9.0). Overall, 58% of patients in the restrictive group received no transfusion compared with 4% in the liberal group (difference in proportion, 54.5%; 95% CI, 36.8-72.2). The proportion with the primary clinical outcome was 14/26 (54%, liberal) vs 24/34 (71%, restrictive), and the difference in proportion was -16.7% (95% CI, -41.3 to 7.8; P=0.18). CONCLUSION: A clinical trial of two transfusion strategies in hip fracture with a clinically relevant cardiac outcome is feasible. CLINICAL TRIAL REGISTRATION: NCT03407573.

The PREVENNT randomised, double-blind, controlled trial of preoperative intravenous iron to treat anaemia before major abdominal surgery: an independent discussion.

Anaemia is a common finding in patients presenting for major elective surgery and is associated with poor outcomes including death and complications. Iron deficiency is the leading cause of perioperative anaemia. Intravenous (i.v.) iron is considered to be an effective and safe treatment for iron deficiency anaemia and is recommended by expert opinion for treatment of preoperative anaemia, although evidence from clinical trials is lacking. The PREVENTT trial was a large multicentre trial investigating the effects of i.v. iron on red cell transfusion, death, complications and quality of life in 487 patients undergoing major abdominal surgery. The principal finding of this multicentre randomised placebo controlled trial was that there was no difference in the co-primary outcomes of blood transfusion or death, or the number of transfusion episodes, within 30 days after surgery, in patients that received preoperative i.v. iron therapy compared to placebo. The major inferential differences in this independent discussion relate to the limitations of the PREVENTT trial and its implications for future practice. Although PREVENTT represents the best evidence available to guide perioperative use of i.v. iron, it is likely that the study was underpowered. In the context of already widespread adoption of preoperative i.v. iron therapy, many clinicians may have felt they lacked equipoise. In light of the PREVENTT study routine use of i.v. iron in patients undergoing elective abdominal surgery cannot be recommended. Further research should define the optimum red cell transfusion strategy for patients undergoing surgery and idenify other surgical groups who may benefit from this intervention.