Precision medicine approaches that target patients on the basis of disease subtype have transformed treatment approaches to cancer, asthma, and other heterogeneous syndromes. Two distinct ...subphenotypes of acute respiratory distress syndrome (ARDS) have been identified in three US-based clinical trials, and these subphenotypes respond differently to positive end-expiratory pressure and fluid management. We aimed to investigate whether these subphenotypes exist in non-US patient populations and respond differently to pharmacotherapies.
HARP-2 was a multicentre, randomised controlled trial of simvastatin (80 mg) versus placebo done in general intensive care units (ICUs) at 40 hospitals in the UK and Ireland within 48 h of onset of ARDS. The primary outcome was ventilator-free days, and secondary outcomes included non-pulmonary organ failure-free days and mortality. In a secondary analysis of HARP-2, we applied latent class analysis to baseline data without consideration of outcomes to identify subphenotypes, and we compared clinical outcomes across subphenotypes and treatment groups.
540 patients were recruited to HARP-2. One patient withdrew consent for the use of their data, so data from 539 patients were analysed. In our secondary analysis, a two-class (two subphenotype) model was an improvement over a one-class model (p<0·0001), with 353 (65%) patients in the hypoinflammatory subphenotype group and 186 (35%) in the hyperinflammatory subphenotype group. Additional classes did not improve model fit. Clinical and biological characteristics of the two subphenotypes were similar to previous studies. Patients with the hyperinflammatory subphenotype had fewer ventilator-free days (median 2 days IQR 0-17 vs 18 IQR 0-23; p<0·0001), fewer non-pulmonary organ failure-free days (15 0-25 vs 27 21-28; p<0·0001), and higher 28-day mortality (73 39% vs 59 17%; p<0·0001) than did those with the hypoinflammatory subphenotype. Although HARP-2 found no difference in 28-day survival between placebo and simvastatin, significantly different survival was identified across patients stratified by treatment and subphenotype (p<0·0001). Specifically, within the hyperinflammatory subphenotype, patients treated with simvastatin had significantly higher 28-day survival than did those given placebo (p=0·008). A similar pattern was observed for 90-day survival.
Two subphenotypes of ARDS were identified in the HARP-2 cohort, with distinct clinical and biological features and disparate clinical outcomes. The hyperinflammatory subphenotype had improved survival with simvastatin compared with placebo. These findings support further pursuit of predictive enrichment strategies in critical care clinical trials.
UK Efficacy and Mechanism Evaluation Programme and National Institutes of Health.
As the chancellor stated in his reply, the monetary policy committee is expected to "set Bank rate to keep inflation on track to meet the 2 per cent target in the medium term". But, there is a ...fundamental problem with the chancellor's chosen measure of inflation (the consumer prices index). Virtually everyone is experiencing actual inflation a good deal higher than the reported 3.1 per cent rise in the March CPI. For example, the old retail prices index is now rising at an annual rate of 4.8 per cent.
The conversion factor between centigrade and fahrenheit is fixed. The same cannot be said for the relationship between RPIX and CPI, where the current difference is 1.3 per cent compared with an ...average difference over the past 15 years of 0.75 per cent (according to the Bank's own estimates).
The origin of the Polynesian bottle gourd (Lagenaria siceraria), an important crop species in prehistoric Polynesia, has remained elusive. Most recently, a South American origin has been favored as ...the bottle gourd could have been introduced from this continent with the sweet potato by Polynesian voyagers around A.D. 1,000. To test the hypothesis of an American origin for the Polynesian bottle gourd, we developed seven markers specific to bottle gourd (two chloroplast and five nuclear). The nuclear markers were developed using a new technique where polymorphic inter simple sequence repeat (ISSR) markers are converted into single-locus polymerase chain reaction and sequencing markers-an approach that will be useful for developing markers in other taxa. All seven markers were sequenced in 36 cultivars of bottle gourd from Asia, the Americas, and Polynesia. The results support a dual origin for the Polynesian bottle gourd: the chloroplast markers are exclusively of Asian origin, but the nuclear markers show alleles originating in both the Americas and Asia. Because hybridization of Polynesian bottle gourds with post-European introductions cannot be excluded, ancient DNA from archaeological material will be useful for further elucidating the prehistoric movements of this species in Polynesia. This work has implications not only for the dispersal of the Polynesian bottle gourd but also for the domestication and dispersal of the species as a whole.
Northeast Pacific blue whales seasonally migrate, ranging from the waters off Central America to the Gulf of Alaska. Using acoustic and satellite remote sensing, we have continuously monitored the ...acoustic activity and habitat of blue whales during 1994–2000. Calling blue whales primarily aggregate off the coast of southern and central California in the late summer, coinciding with the timing of the peak euphausiid biomass, their preferred prey. The northward bloom of primary production along the coast and subsequent northbound movements of the blue whales are apparent in the satellite and acoustic records, respectively, with the calling blue whales moving north along the Oregon and Washington coasts to a secondary foraging area with high primary productivity off Vancouver Island in the late fall. El Ni
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concentrations, are apparent in the satellite records, particularly in the Southern California Bight during 1997/1998. These conditions disrupt biological production and alter the presence of calling blue whales in primary feeding locations. Remote sensing using acoustics is well suited to characterizing the seasonal movements and relative abundance of the northeast Pacific blue whales, and remote sensing using satellites allows for monitoring their habitat. These technologies are invaluable because of their ability to provide continuous large-scale spatial and temporal coverage of the blue whale migration.
We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (≥80 years; VIP). ...Predictors of mortality, with special emphasis on frailty, were assessed.
In total, 5063 VIPs were included in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.
Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 ± 5 vs 7 ± 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).
VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
Trial registration: NCT03134807. Registered 1st May 2017.
•We evaluated differences in outcome between VIPs admitted to ICU after elective versus acute intervention•VIPs after elective intervention evidenced favorable outcome after correction for relevant confounders•Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
This article reviews the lessons that can be learned by the health sector, in particular, and the public sector, more generally, from the governmental response to pandemic (H1N1) 2009 influenza A ...(pH1N1) in Australia during 2009. It covers the period from the emergence of the epidemic to the release of the vaccine, and describes a range of impacts on the Western Australian health system, the government sector and the community. There are three main themes considered from a State government agency perspective: how decisions were influenced by prior planning; how the decision making and communication processes were intimately linked; and the interdependent roles of States and the Commonwealth Government in national programs. We conclude that: (a) communications were generally effective, but need to be improved and better coordinated between the Australian Government, States and general practice; (b) decision making was appropriately flexible, but there needs to be better alignment with expert advice, and consideration of the need for a national disease control agency in Australia; and (c) national funding arrangements need to fit with the model of state-based service delivery and to support critical workforce needs for surge capacity, as well as stockpile and infrastructure requirements.
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