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.

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.

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.

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.

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.

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.

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.

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.

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.

Mortality from heart diseases following occupational radiation exposure: analysis of the National Registry for Radiation Workers (NRRW) in the United Kingdom.

Statistically significant increases in heart disease (HD) mortality with cumulative recorded occupational radiation dose from external sources were observed among 174 541 subjects, who were predominately exposed to protracted low doses over a number of years, and were followed up until the end of 2011 in the UK National Registry for Radiation Workers (NRRW) cohort. Amongst the subtypes of HD, the increasing trends with cumulative dose arose for ischaemic heart disease (IHD) and other HD (which includes pulmonary HD, valve disorders, cardiomyopathy, cardiac dysrhythmias, carditis, conduction disorder and ill-defined HD). For IHD, the increased mortality appears to be at least 20 years after first exposure and the excess risk peaked between 30 and 40 years after the first exposure. There was no evidence of excess risk of IHD mortality for cumulative radiation doses below 0.1 Sv. A categorical analysis also showed that the risk falls below the expected value based on a linear trend, for cumulative doses greater than 0.4 Sv; this smaller risk appears to be primarily associated with workers who started employment at a younger age and who were employed for longer than 30 years, reflecting possible healthy worker survivor effect. This analysis provided further evidence that low doses of radiation exposure may be associated with increased risk of IHD. For other HD, the data suggest an increased risk starting around 40 years after the first exposure. The risk was statistically significant raised only for cumulative doses above 0.4 Sv. However, the number of deaths in this group was small and the results need to be interpreted with caution.

Cancer mortality and incidence following external occupational radiation exposure: an update of the 3rd analysis of the UK national registry for radiation workers.

BACKGROUND: This study provides direct evidence of cancer risk from low dose and dose rate occupational external radiation exposures. METHODS: Cancer mortality and incidence were studied in relation to external radiation exposure in the National Registry for Radiation Workers. A cohort of 167,003 workers followed for an average of 32 years was analysed using Poisson regression methods. RESULTS: Mortality and incidence risks were significantly raised for the group of all malignant neoplasms excluding leukaemia (ERR/Sv mortality = 0.28; 90%CI: 0.06, 0.53, ERR/Sv incidence = 0.28; 90%CI: 0.10, 0.48) but with narrower confidence bounds compared with the previous analysis of this cohort reflecting the increased statistical power from the additional 10 years of follow-up information. The linear trends in relative risk for both mortality and incidence of these cancers remained statistically significantly raised when information relating to cumulative doses above 100 mSv was excluded (ERR/Sv mortality = 1.42; 90%CI: 0.51, 2.38 and ERR/Sv incidence = 1.18; 90%CI: 0.47, 1.92). CONCLUSIONS: This study improved the precision of the cancer risk estimates seen in the third analysis of the NRRW cohort. The overall results remain consistent with the risk estimates from the Life Span Study and those adopted in the current ICRP recommendations.

Site-specific Solid Cancer Mortality After Exposure to Ionizing Radiation: A Cohort Study of Workers (INWORKS).

BACKGROUND: There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer. METHODS: Associations between ionizing radiation and site-specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation-mortality associations were estimated using a maximum-likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association. RESULTS: The analysis included 17,957 deaths attributable to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum-likelihood method to quantify associations between radiation dose- and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types, the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization. CONCLUSIONS: The results provide further evidence regarding associations between low-dose radiation exposure and cancer.

Examining temporal effects on cancer risk in the international nuclear workers' study.

The paper continues the series of publications from the International Nuclear Workers Study cohort that comprises 308,297 workers from France, the United Kingdom and the United States, providing 8.2 million person-years of observation from a combined follow-up period (at earliest 1944 to at latest 2005). These workers' external radiation exposures were primarily to photons, resulting in an estimated average career absorbed dose to the colon of 17.4 milligray. The association between cumulative ionizing radiation dose and cancer mortality was evaluated in general relative risk models that describe modification of the excess relative risk (ERR) per gray (Gy) by time since exposure and age at exposure. Methods analogous to a nested-case control study using conditional logistic regression of sampled risks sets were used. Outcomes included: all solid cancers, lung cancer, leukemias excluding chronic lymphocytic, acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma, Hodgkin lymphoma and non-Hodgkin lymphoma. Significant risk heterogeneity was evident in chronic myeloid leukemia with time since exposure, where we observed increased ERR per Gy estimates shortly after exposure (2-10 year) and again later (20-30 years). We observed delayed effects for acute myeloid leukemia although estimates were not statistically significant. Solid cancer excess risk was restricted to exposure at age 35+ years and also diminished for exposure 30 years prior to attained age. Persistent or late effects suggest additional follow-up may inform on lifetime risks. However, cautious interpretation of results is needed due to analytical limitations and a lack of confirmatory results from other studies.

The Effect of High-Flow Nasal Cannula Oxygen Therapy on Mortality and Intubation Rate in Acute Respiratory Failure: A Systematic Review and Meta-Analysis.

OBJECTIVE: High-flow nasal cannulae are used in adults with or at risk of acute respiratory failure. We conducted a systematic review and meta-analysis to evaluate the evidence for their use in this setting. DATA SOURCES: Ovid Medline, Embase, and Cochrane Database of Systematic Reviews. STUDY SELECTION: Databases were searched for randomized controlled trials comparing administration of high-flow nasal cannulae with usual care (i.e., conventional oxygen therapy or noninvasive ventilation) in adults with respiratory failure. The primary outcome was hospital mortality; the rate of intubation and assessment of delirium and comfort were secondary outcomes. DATA EXTRACTION: One hundred forty-seven nonduplicate citations were screened, 32 underwent full screening and data extraction, and 14 trials were eligible for inclusion in the review. Nine trials were used in the meta-analysis, including a total of 2,507 subjects. DATA SYNTHESIS: When high-flow nasal cannulae were compared with usual care, there was no difference in mortality (high-flow nasal cannulae, 60/1,006 [6%] vs usual care, 90/1,106 [8.1%]) (n = 2,112; p = 0.29; I, 25%; fixed effect model: odds ratio, 0.83; 95% CI, 0.58-1.17) or rate of intubation (high-flow nasal cannulae, 119/1,207 [9.9%] vs usual care, 204/1,300 [15.7%]) (n = 2,507; p = 0.08; I, 53%; random effect model: odds ratio, 0.63; 95% CI, 0.37-1.06). A qualitative analysis of 13 studies on tolerability and comfort suggested that high-flow nasal cannulae are associated with improved patient comfort and dyspnea scores. Trial sequential analyses on primary and secondary outcomes suggested that required information size was not reached. CONCLUSIONS: No difference in mortality or intubation was detected in patients with acute respiratory failure treated with high-flow nasal cannulae compared with usual care. High-flow nasal cannulae seem well tolerated by patients. Further large randomized controlled trials are required to evaluate their utility in this setting.

ICU admission after surgery: who benefits?

PURPOSE OF REVIEW: Death following surgery remains a major cause of death worldwide, and ICU admission following major surgery is considered a standard of care in many healthcare systems. However, ICU resources are finite and expensive, thus identifying those most likely to benefit is of great importance. RECENT FINDINGS: Advances in surgical and perioperative management have moved the focus of postoperative care to preventing complications and reducing duration of hospitalisation. Recent health services research has failed to find association between ICU admission and improved outcome in many types of elective major noncardiac surgery. Use of alternatives to ICU such as post anaesthesia care units (PACUs), high dependency units (HDUs) or specialist wards with enhanced nursing care are able to perform some elements of ICU monitoring in a less intensive environment, and may provide a better alternative to the traditional model of ICU admission for many patients having major surgery. ICU admission should still be considered for very high-risk patients and those having complex or emergency surgery. Improved triage tools are required to identify those at the highest risk of death or complications. SUMMARY: Identifying those most at risk of death and complications following surgery and preventing them is the major challenge of perioperative care in the coming decades. Future research should focus on how postoperative care can best be structured to provide optimum care to patients within available resources. Incidence of complications or failure to rescue (FtR) may provide useful metrics in future research.

Five-Year Mortality and Hospital Costs Associated with Surviving Intensive Care.

RATIONALE: Survivors of critical illness experience significant morbidity, but the impact of surviving the intensive care unit (ICU) has not been quantified comprehensively at a population level. OBJECTIVES: To identify factors associated with increased hospital resource use and to ascertain whether ICU admission was associated with increased mortality and resource use. METHODS: Matched cohort study and pre/post-analysis using national linked data registries with complete population coverage. The population consisted of patients admitted to all adult general ICUs during 2005 and surviving to hospital discharge, identified from the Scottish Intensive Care Society Audit Group registry, matched (1:1) with similar hospital control subjects. Five-year outcomes included mortality and hospital resource use. Confounder adjustment was based on multivariable regression and pre/post within-individual analyses. MEASUREMENTS AND MAIN RESULTS: Of 7,656 ICU patients, 5,259 survived to hospital discharge (5,215 [99.2%] matched to hospital control subjects). Factors present before ICU admission (comorbidities/pre-ICU hospitalizations) were stronger predictors of hospital resource use than acute illness factors. In the 5 years after the initial hospital discharge, compared with hospital control subjects, the ICU cohort had higher mortality (32.3% vs. 22.7%; hazard ratio, 1.33; 95% confidence interval, 1.22-1.46; P < 0.001), used more hospital resources (mean hospital admission rate, 4.8 vs. 3.3/person/5 yr), and had 51% higher mean 5-year hospital costs ($25,608 vs. $16,913/patient). Increased resource use persisted after confounder adjustment (P < 0.001) and using pre/post-analyses (P < 0.001). Excess resource use and mortality were greatest for younger patients without significant comorbidity. CONCLUSIONS: This complete, national study demonstrates that ICU survivorship is associated with higher 5-year mortality and hospital resource use than hospital control subjects, representing a substantial burden on individuals, caregivers, and society.

Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure.

The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation.

Which intravenous fluid for the surgical patient?

PURPOSE OF REVIEW: This review appraises recent evidence and provides clinical guidance on optimal perioperative fluid therapy. RECENT FINDINGS: Choice of perioperative intravenous fluid continues to be the source of much debate. Not all crystalloids are equivalent, and there is growing evidence that balanced solutions are superior to 0.9% saline in many situations. Recent evidence from the critical care population has highlighted risks associated with synthetic colloids; this and the absence of demonstrable benefit in the surgical population make it difficult to recommend their use in the perioperative period. Giving the correct amount of fluid may be as important as the choice of the fluid used. There is increasing evidence that excessive positive fluid balance is harmful to patients but there have been no randomized trials comparing maintenance fluid strategy. A knowledge of the physiology and accurate estimation of fluid balance is important for water and electrolyte homeostasis until the patient is able to resume adequate enteral nutrition. SUMMARY: Balanced crystalloids are the fluid of choice for perioperative resuscitation and optimization in patients not requiring blood products. Avoidance of a grossly positive sodium and water balance during the maintenance phase is likely to be important, but has not been assessed in randomized trials.

Fenoldopam to prevent acute kidney injury after major surgery-a systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) after surgery is associated with increased mortality and healthcare costs. Fenoldopam is a selective dopamine-1 receptor agonist with renoprotective properties. We conducted a systematic review and meta-analysis of randomised controlled trials comparing fenoldopam with placebo to prevent AKI after major surgery. METHODS: We searched EMBASE, PubMed, meta-Register of randomised controlled trials and Cochrane CENTRAL databases for trials comparing fenoldopam with placebo in patients undergoing major surgery. The primary outcome was incidence of new AKI. Secondary outcomes were requirement for renal replacement therapy and hospital mortality. RESULTS: Eighty-three publications were screened; 23 studies underwent full data extraction and scoring. Six trials were suitable for inclusion in the data synthesis (total of 507 subjects undergoing cardiovascular surgery, partial nephrectomy, liver transplant surgery). Five studies were rated at high risk of bias. Data on post-operative incidence of AKI were available in five of the six trials (total of 471 patients) but definitions of AKI varied between studies. Of the 238 patients receiving fenoldopam, 45 (18.9%) developed AKI compared to 62 (26.6%) of the 233 patients who received placebo (p = 0.004, I (2) = 0 %; random-effects model odds ratio 0.46, 95% confidence interval 0.27-0.79). In patients treated with fenoldopam, there was no difference in renal replacement therapy (n = 478; p = 0.11, I (2) = 47%; fixed-effect model odds ratio 0.27, 95% confidence interval 0.06-1.19) or hospital mortality (p = 0.60, I (2) = 0 %; fixed-effect model odds ratio 1.0, 95% confidence interval 0.14-7.37). CONCLUSIONS: In this analysis, peri-operative treatment with fenoldopam was associated with a significant reduction in post-operative AKI but it had no impact on renal replacement therapy or hospital mortality. Equipoise remains for further large trials in this area since the studies were conducted in three types of surgery, the majority of studies were rated at high risk of bias and the criteria for AKI varied between trials.