Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate

“The Original Journals of ‘Kitty’ Wilmot”: manufacturing women’s travel writing in the salon of Helen Maria Williams

This article discusses the implications of a previously unknown Romantic-period manuscript by Anglo-Irish traveler Katherine Wilmot (1773–1824). A later version of Wilmot’s epistolary travelogue of 1801–03 has been valued as an artifact of British experience abroad during the Peace of Amiens for its descriptions of Napoleonic Paris. Yet the newly discovered draft reveals a deeper assimilation within and sympathy towards the radical political and literary networks Wilmot documented, as well as a budding relationship with author and salonnière Helen Maria Williams that is occluded from the later narrative. This article examines the complex choices surrounding authorship for British women abroad in the period by considering a refused invitation that Wilmot submit writing to The English Press, the publishing venture of Williams and her companion John Hurford Stone. The article details Wilmot’s evolving writing in terms of Williams’s influence, outlining how British women travel writers reshaped their experiences to meet the expectations of readers at home while also considering the impact of sedition, gendered agency, and political affinity on the production and reception of their writing

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

An evaluation of owner expectation on apparent treatment effect in a blinded comparison of 2 homeopathic remedies for firework noise sensitivity in dogs.

A blinded and randomized study was carried out to investigate whether dog owners would report different treatment effects depending on whether they knew they might be administering a placebo, versus if they knew they were definitely administering a homeopathic remedy. A secondary aim was to determine the consistency of owner reports of treatment effect across multiple trial periods. A total of 73 dogs with a stable, predictable, and easily assessable response to firework noises were enrolled and randomly allocated to receive 1 of the 2 homeopathic preparations along with a basic behavior modification program. Treatment A was a homeopathic treatment formulated for firework noise sensitivity that had previously been tested in a placebo-controlled study by the authors, and Treatment B was a different formulation for the same condition. The same allocated treatment was trialed on 2 occasions by all participants to allow assessment of owner-report reliability. It was found that knowledge of participating in a placebo-controlled trial had no effect on the owners’ perception of treatment effect, and that their reports of effect were consistent across both trial periods. No specific effect of homeopathic treatment was found in this study; however, it was observed that the reported behavioral effects that followed each treatment were similar across the 2 firework periods, but that there was a consistently different pattern of behavioral effects reported between Treatment groups A and B. These results might be ascribed to either a treatment or population effect. We suggest that examination of the consistency of owner-reported effects within and between treatments may be used as part of the suite of methodologies available to investigate whether any specific effect can be ascribed to homeopathic intervention

Lung function in children in relation to ethnicity, physique and socioeconomic factors

QUESTION: Can ethnic differences in spirometry be attributed to differences in physique and socio-economic factors? METHODS: Assessments were undertaken in 2171 London primary school-children on two occasions a year apart whenever possible, as part of the Size and Lung function In Children study. MEASUREMENTS: included spirometry, detailed anthropometry, 3-D photonic scanning for regional body shape, body composition, information on ethnic ancestry, birth and respiratory history, socio-economic circumstances and tobacco smoke exposure. RESULTS: Technically acceptable spirometry was obtained from 1901 children (mean age: 8.3yrs (range: 5.2-11.8yrs), 46% boys, 35% White; 29% Black-African origin; 24% South-Asian; 12% Other/mixed) on 2767 test occasions. After adjusting for sex, age and height, FEV(1) was 1.32, 0.89 and 0.51 z-score units lower in Black, South-Asian and Other ethnicity children respectively, when compared with White children, with similar decrements for FVC (p<0.001 for all). Although further adjustment for sitting height and chest width reduced differences attributable to ethnicity by up to 16%, significant differences persisted after adjusting for all potential determinants including socio-economic circumstances. ANSWER: Ethnic differences in spirometric lung function persist despite adjusting for a wide range of potential determinants, including body physique and socio-economic circumstances, emphasising the need to use ethnic-specific equations when interpreting results