SummaryBackgroundLimits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries.MethodsIn this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants.Findings45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups.InterpretationOver 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency.FundingNHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation.

There is an opportunity for state school boards associations, state public health nutrition directors, and school wellness advocates to build their own capacity to provide training and resources to districts on wellness issues, particularly physical education/activity, school-based wellness initiatives, and strategies for implementing and monitoring/evaluating wellness policies.

IMPORTANCEIn 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 MEASURESThe 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.

Summary. Three electrophoretic methods of typing methicillin-resistant Staphylococcus aureus (MRSA) strains-plasmid profiles (PP), whole-cell protein profiles (WCPP) and immunoblotting profiles (1P)-were evaluated and compared with phage typing. The results obtained with isolates from 12 outbreaks were compared both within the outbreaks, to determine the consistency of results, and between outbreaks. There was generally good agreement between the typing methods but in only six outbreaks did all four methods indicate the same relationship between isolates. WCPP comprised more than 50 bands; when differences occurred, they were seen in only a few bands. In contrast, IP comprised only one or two major bands and the differences were much easier to interpret. The PPs of many of the isolates were similar; many isolates contained a plasmid of mol. wt (18-25) x lo6. In several outbreaks both WCPP and IP showed minor differences between isolates that were not apparent with phage typing. When comparisons were made between the 12 index strains and an isolate representing the London epidemic MRSA strain, phage typing and WCPP were the most discriminatory methods ; both gave nine distinct patterns, whereas there were eight IPS and only six PPs amongst the 13 strains. It was concluded that both WCPP and IP could provide valuable epidemiological data on MRSA and that IP was the easiest of the three methods to interpret.

BackgroundMost schools have not fully implemented wellness policies, and those that have rarely incorporate meaningful student participation. The aim of the Fuel Up to Play 60 (FUTP60) program is to help schools implement wellness policies by engaging students in activities to improve access to healthful, good tasting food and drinks, and increase the number and type of opportunities for students to be physically active. The aim of this paper is to present initial student-level results from an implementation of FUTP60 in 72 schools, grades 6–9.MethodsThe study used a non-controlled pretest/posttest with serial cross-sectional data. School process data and student-level data were collected in fall 2009 (pre-intervention) and spring 2010 (post-intervention). School wellness practices were captured during a baseline needs assessment survey. Validated self-administered questionnaires assessing dietary and physical activity (PA) behaviors were administered to students in grades 6–9 in the 72 pilot schools. Mixed-effects logistic regression controlling for clustering of schools and demographics was used to calculate odds ratios and confidence intervals to evaluate changes pre- and post- intervention.ResultsAll 72 schools implemented FUTP60 during the 2009–2010 school year. Action strategies most frequently chosen by the schools included increasing breakfast participation and new activities before and after school. Positive and significant changes in students’ behaviors (n = 32,482 at pretest and 29,839 at post-test) were noted for dairy, whole grains, fruit, and vegetable consumption and PA levels pre- and post-intervention (OR 1.05 to 1.27). Students aware of the program at post-test were significantly more likely to report healthier eating and PA behaviors than students unaware of the program (OR 1.1 to 1.34).ConclusionsFUTP60 pilot findings indicate that a low intensity program focused on wellness policy implementation is associated with small positive changes in student behaviors, especially when students were aware of the program. Although these initial results are promising, a more rigorous controlled study is warranted as a next step.

We developed means to deliver multiple heterologous antigens on dual plasmids with non-antibiotic-resistance markers in a single recombinant attenuated vaccine strain of Salmonella enterica serotype Typhimurium. The first component of this delivery system is a strain of S. Typhimurium carrying genomic deletions in alr, dadB, and asd, resulting in obligate requirements for diaminopimelic acid (DAP) and D-alanine for growth. The second component is the Asd ؉ -DadB ؉ plasmid pair carrying wildtype copies of asdA and dadB, respectively, to complement the mutations. To evaluate the protection efficacy of the dual-plasmid vaccine, S. Typhimurium strain 9760 (a strain with multiple attenuating mutations: ⌬asd ⌬alr ⌬dadB ⌬recF) was transformed with Asd ؉ and DadB ؉ plasmids specifying pneumococcal antigens PspA and PspC, respectively. Both plasmids were stable in 9760 for 50 generations when grown in nonselective medium. This was significantly (P < 0.05) greater than the stability seen in its recF

Purpose:The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes.Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization.Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (V T ) was 7 (Interquartile range, IQR = 6.2-8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5-9) cmH 2 0, plateau pressure was 20 cmH 2 0 (IQR = 17-23), driving pressure was 12 cmH 2 0 (IQR = 10-15), mechanical power 16.2 J/min (IQR = 12.1-21.8), ventilatory ratio was 1.27 (IQR = 1.04-1.6), and respiratory rate was 17 breaths/minute (IQR = 14-20). Median partial pressure of oxygen was 87 mmHg (IQR = 75-105), and partial pressure of carbon dioxide was

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