The REDS score: a new scoring system to risk-stratify emergency department suspected sepsis: a derivation and validation study.

OBJECTIVE: To derive and validate a new clinical prediction rule to risk-stratify emergency department (ED) patients admitted with suspected sepsis. DESIGN: Retrospective prognostic study of prospectively collected data. SETTING: ED. PARTICIPANTS: Patients aged ≥18 years who met two Systemic Inflammatory Response Syndrome criteria or one Red Flag sepsis criteria on arrival, received intravenous antibiotics for a suspected infection and admitted. PRIMARY OUTCOME MEASURE: In-hospital all-cause mortality. METHOD: The data were divided into derivation and validation cohorts. The simplified-Mortality in Severe Sepsis in the ED score and quick-SOFA scores, refractory hypotension and lactate were collectively termed 'component scores' and cumulatively termed the 'Risk-stratification of ED suspected Sepsis (REDS) score'. Each patient in the derivation cohort received a score (0-3) for each component score. The REDS score ranged from 0 to 12. The component scores were subject to univariate and multivariate logistic regression analyses. The receiver operator characteristic (ROC) curves for the REDS and the components scores were constructed and their cut-off points identified. Scores above the cut-off points were deemed high-risk. The area under the ROC (AUROC) curves and sensitivity for mortality of the high-risk category of the REDS score and component scores were compared. The REDS score was internally validated. RESULTS: 2115 patients of whom 282 (13.3%) died in hospital. Derivation cohort: 1078 patients with 140 deaths (13%). The AUROC curve with 95% CI, cut-off point and sensitivity for mortality (95% CI) of the high-risk category of the REDS score were: derivation: 0.78 (0.75 to 0.80); ≥3; 85.0 (78 to 90.5). VALIDATION: 0.74 (0.71 to 0.76); ≥3; 84.5 (77.5 to 90.0). The AUROC curve and the sensitivity for mortality of the REDS score was better than that of the component scores. Specificity and mortality rates for REDS scores of ≥3, ≥5 and ≥7 were 54.8%, 88.8% and 96.9% and 21.8%, 36.0% and 49.1%, respectively. CONCLUSION: The REDS score is a simple and objective score to risk-stratify ED patients with suspected sepsis

(Un)Becoming Queer/(Un)Becoming LGBTIC

This article is one result of an ongoing dialogue among a number of members of the LGBTIC/Queer Caucus. The dialogue has taken place primarily through a torrent of e-mails, but also through a number of emotionally charged telephone calls. It began as a friendly, (perhaps naively) simple idea -to turn members\u27 viewpoints about changing the name of our caucus, from Lesbian, Gay, Bisexual and Transgendered Issues Caucus to Queer Issues Caucus into an article. What began with good will and a fervent hope for understanding, at times turned into vitriol and contention -volleys of world views, personal identities, and philosophies. Although tempers flared occasionally, we feel each of us came to better understandings of the others\u27 points of view. Editors Debbie and Kim have attempted to distill a bubbling pot of various points of view into an imaginary roundtable dialogue: respecting all stances, without silencing anyone, without hurting anyone\u27s feelings, and without privileging anyone viewpoint. All actors in this drama are named above and identified in the text by their initials. We apologize in advance

Methods to Recruit Hard-to-Reach Groups: Comparing Two Chain Referral Sampling Methods of Recruiting Injecting Drug Users Across Nine Studies in Russia and Estonia

Evidence suggests rapid diffusion of injecting drug use and associated outbreaks of HIV among injecting drug users (IDUs) in the Russian Federation and Eastern Europe. There remains a need for research among non-treatment and community-recruited samples of IDUs to better estimate the dynamics of HIV transmission and to improve treatment and health services access. We compare two sampling methodologies “respondent-driven sampling” (RDS) and chain referral sampling using “indigenous field workers” (IFS) to investigate the relative effectiveness of RDS to reach more marginal and hard-to-reach groups and perhaps to include those with the riskiest behaviour around HIV transmission. We evaluate the relative efficiency of RDS to recruit a lower cost sample in comparison to IFS. We also provide a theoretical comparison of the two approaches. We draw upon nine community-recruited surveys of IDUs undertaken in the Russian Federation and Estonia between 2001 and 2005 that used either IFS or RDS. Sampling effects on the demographic composition and injecting risk behaviours of the samples generated are compared using multivariate analysis. Our findings suggest that RDS does not appear to recruit more marginalised sections of the IDU community nor those engaging in riskier injecting behaviours in comparison with IFS. RDS appears to have practical advantages over IFS in the implementation of fieldwork in terms of greater recruitment efficiency and safety of field workers, but at a greater cost. Further research is needed to assess how the practicalities of implementing RDS in the field compromises the requirements mandated by the theoretical guidelines of RDS for adjusting the sample estimates to obtain estimates of the wider IDU population

The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice.

RATIONALE Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice. OBJECTIVE We test the ability of GSK1521498 to reduce alcohol consumption and compare its intrinsic efficacy to that of naltrexone by comparing the two drugs at doses matched for equivalent receptor occupancy. METHODS Thirty-six C57BL/6J mice were tested in a DID procedure. In 2-day cycles, animals experienced one baseline, injection-free session, and one test session when they received two injections, one of test drug and one placebo. All animals received GSK1521498 (0, 0.1, 1 and 3 mg/kg, i.p., 30 min pre-treatment) and naltrexone (0, 0.1, 1 and 3 mg/kg, s.c. 10 min pre-treatment) in a cross-over design. Receptor occupancies following the same doses were determined ex vivo in separate groups by autoradiography, using [3H]DAMGO. Binding in the region of interest was measured integrally by computer-assisted microdensitometry and corrected for non-specific binding. RESULTS Both GSK1521498 and naltrexone dose-dependently decreased ethanol consumption. When drug doses were matched for 70-75 % receptor occupancy, GSK1521498 3 mg/kg, i.p., caused a 2.5-fold greater reduction in alcohol consumption than naltrexone 0.1 mg/kg, s.c. Both GSK1521498 and naltrexone significantly reduced sucrose consumption at a dose of 1 mg/kg but not 0.1 mg/kg. In a test of conditioned taste aversion, GSK1521498 (3 mg/kg) reduced sucrose consumption 24 h following exposure to a conditioning injection. CONCLUSIONS Both opioid receptor antagonists reduced alcohol consumption but GK1521498 has higher intrinsic efficacy than naltrexone

Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers

Introduction Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents. Methods Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed. Results By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator. Conclusions These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC

How do you say ‘hello’? Personality impressions from brief novel voices

On hearing a novel voice, listeners readily form personality impressions of that speaker. Accurate or not, these impressions are known to affect subsequent interactions; yet the underlying psychological and acoustical bases remain poorly understood. Furthermore, hitherto studies have focussed on extended speech as opposed to analysing the instantaneous impressions we obtain from first experience. In this paper, through a mass online rating experiment, 320 participants rated 64 sub-second vocal utterances of the word ‘hello’ on one of 10 personality traits. We show that: (1) personality judgements of brief utterances from unfamiliar speakers are consistent across listeners; (2) a two-dimensional ‘social voice space’ with axes mapping Valence (Trust, Likeability) and Dominance, each driven by differing combinations of vocal acoustics, adequately summarises ratings in both male and female voices; and (3) a positive combination of Valence and Dominance results in increased perceived male vocal Attractiveness, whereas perceived female vocal Attractiveness is largely controlled by increasing Valence. Results are discussed in relation to the rapid evaluation of personality and, in turn, the intent of others, as being driven by survival mechanisms via approach or avoidance behaviours. These findings provide empirical bases for predicting personality impressions from acoustical analyses of short utterances and for generating desired personality impressions in artificial voices

Treatment variables associated with outcome in emergency department patients with suspected sepsis.

BACKGROUND: Early treatment is advocated in the management of patients with suspected sepsis in the emergency department (ED). We sought to understand the association between the ED treatments and outcome in patients admitted with suspected sepsis. The treatments studied were: (i) the time to antibiotics, where time zero is the time the patient was booked in which is also the triage time; (ii) the volume of intravenous fluid (IVF); (iii) mean arterial pressure (MAP) after 2000 ml of IVF and (iv) the final MAP in the ED. METHODS: We performed a retrospective analysis of the ED database of patients aged ≥ 18 year who met two SIRS criteria or one red flag sepsis criteria on arrival, received intravenous antibiotics for a suspected infection and admitted between 8th February 2016 and 31st August 2017. The primary outcome measure was all-cause in-hospital mortality. The four treatments stated above were controlled for severity of illness and subject to multivariate logistic regression and Cox proportional-hazard regression to identify independent predictors of mortality. RESULTS: Of the 2,066 patients studied 272 (13.2%) died in hospital. The median time to antibiotics was 48 (interquartile range 30-82) minutes. The time to antibiotics was an independent predictor of mortality only in those who developed refractory hypotension (RH); antibiotics administered more than 55 mins after arrival was associated with an odds ratio (OR) for mortality of 2.75 [95% confidence interval (CI) 1.22-6.14]. The number-needed-to-treat was 4. IVF > 2000 ml (95% CI > 500- > 2100), except in RH, and a MAP ≤ 66 mmHg after 2000 ml of IVF were also independent predictors of mortality. The OR for mortality of IVF > 2,000 ml in non-RH was 1.80 (95% CI 1.15-2.82); Number-needed-to-harm was 14. The OR for morality for a MAP ≤ 66 mmHg after 2000 ml of IVF was 3.42 (95% CI 2.10-5.57). A final MAP  2000 ml (except in RH) and a MAP ≤ 66 mmHg after 2000 ml of IVF were also independent predictors of mortality

A pilot Internet "Value of Health" Panel: recruitment, participation and compliance

Objectives To pilot using a panel of members of the public to provide preference data via the Internet Methods A stratified random sample of members of the general public was recruited and familiarised with the standard gamble procedure using an Internet based tool. Health states were perdiodically presented in "sets" corresponding to different conditions, during the study. The following were described: Recruitment (proportion of people approached who were trained); Participation (a) the proportion of people trained who provided any preferences and (b) the proportion of panel members who contributed to each "set" of values; and Compliance (the proportion, per participant, of preference tasks which were completed). The influence of covariates on these outcomes was investigated using univariate and multivariate analyses. Results A panel of 112 people was recruited. 23% of those approached (n = 5,320) responded to the invitation, and 24% of respondents (n = 1,215) were willing to participate (net = 5.5%). However, eventual recruitment rates, following training, were low (2.1% of those approached). Recruitment from areas of high socioeconomic deprivation and among ethnic minority communities was low. Eighteen sets of health state descriptions were considered over 14 months. 74% of panel members carried out at least one valuation task. People from areas of higher socioeconomic deprivation and unmarried people were less likely to participate. An average of 41% of panel members expressed preferences on each set of descriptions. Compliance ranged from 3% to 100%. Conclusion It is feasible to establish a panel of members of the general public to express preferences on a wide range of health state descriptions using the Internet, although differential recruitment and attrition are important challenges. Particular attention to recruitment and retention in areas of high socioeconomic deprivation and among ethnic minority communities is necessary. Nevertheless, the panel approach to preference measurement using the Internet offers the potential to provide specific utility data in a responsive manner for use in economic evaluations and to address some of the outstanding methodological uncertainties in this field

Disclosing intimate partner violence to health care clinicians - What a difference the setting makes: A qualitative study

<p>Abstract</p> <p>Background</p> <p>Despite endorsement by national organizations, the impact of screening for intimate partner violence (IPV) is understudied, particularly as it occurs in different clinical settings. We analyzed interviews of IPV survivors to understand the risks and benefits of disclosing IPV to clinicians across specialties.</p> <p>Methods</p> <p>Participants were English-speaking female IPV survivors recruited through IPV programs in Massachusetts. In-depth interviews describing medical encounters related to abuse were analyzed for common themes using Grounded Theory qualitative research methods. Encounters with health care clinicians were categorized by outcome (IPV disclosure by patient, discovery evidenced by discussion of IPV by clinician without patient disclosure, or non-disclosure), attribute (beneficial, unhelpful, harmful), and specialty (emergency department (ED), primary care (PC), obstetrics/gynecology (OB/GYN)).</p> <p>Results</p> <p>Of 27 participants aged 18–56, 5 were white, 10 Latina, and 12 black. Of 59 relevant health care encounters, 23 were in ED, 17 in OB/GYN, and 19 in PC. Seven of 9 ED disclosures were characterized as unhelpful; the majority of disclosures in PC and OB/GYN were characterized as beneficial. There were no harmful disclosures in any setting. Unhelpful disclosures resulted in emotional distress and alienation from health care. Regardless of whether disclosure occurred, beneficial encounters were characterized by familiarity with the clinician, acknowledgement of the abuse, respect and relevant referrals.</p> <p>Conclusion</p> <p>While no harms resulted from IPV disclosure, survivor satisfaction with disclosure is shaped by the setting of the encounter. Clinicians should aim to build a therapeutic relationship with IPV survivors that empowers and educates patients and does not demand disclosure.</p