Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients.

BACKGROUND: Antifibrinolytics reduce death from bleeding in trauma and post-partum haemorrhage. We examined the effect of treatment delay on the effectiveness of antifibrinolytics. METHODS: We did an individual patient-level data meta-analysis of randomised trials done with more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials done between Jan 1, 1946, and April 7, 2017, from MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PubMed, Popline, and the WHO International Clinical Trials Registry Platform. The primary measure of treatment benefit was absence of death from bleeding. We examined the effect of treatment delay on treatment effectiveness using logistic regression models. We investigated the effect of measurement error (misclassification) in sensitivity analyses. This study is registered with PROSPERO, number 42016052155. FINDINGS: We obtained data for 40 138 patients from two randomised trials of tranexamic acid in acute severe bleeding (traumatic and post-partum haemorrhage). Overall, there were 3558 deaths, of which 1408 (40%) were from bleeding. Most (884 [63%] of 1408) bleeding deaths occurred within 12 h of onset. Deaths from post-partum haemorrhage peaked 2-3 h after childbirth. Tranexamic acid significantly increased overall survival from bleeding (odds ratio [OR] 1·20, 95% CI 1·08-1·33; p=0·001), with no heterogeneity by site of bleeding (interaction p=0·7243). Treatment delay reduced the treatment benefit (p<0·0001). Immediate treatment improved survival by more than 70% (OR 1·72, 95% CI 1·42-2·10; p<0·0001). Thereafter, the survival benefit decreased by 10% for every 15 min of treatment delay until 3 h, after which there was no benefit. There was no increase in vascular occlusive events with tranexamic acid, with no heterogeneity by site of bleeding (p=0·5956). Treatment delay did not modify the effect of tranexamic acid on vascular occlusive events. INTERPRETATION: Death from bleeding occurs soon after onset and even a short delay in treatment reduces the benefit of tranexamic acid administration. Patients must be treated immediately. Further research is needed to deepen our understanding of the mechanism of action of tranexamic acid. FUNDING: UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation (CRASH-2 trial). London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation (WOMAN trial)

Self-rated health: analysis of distances and transitions between response options

Purpose: We explored health differences between population groups who describe their health as excellent, very good, good, fair, or poor. Methods: We used data from a population-based survey which included self-rated health (SRH) and three global measures of health: the SF36 general health score (computed from the 4 items other than SRH), the EQ-5D health utility, and a visual analogue health thermometer. We compared health characteristics of respondents across the five health ratings. Results: Survey respondents (N=1.844, 49.2% response) rated their health as excellent (12.2%), very good (39.1%), good (41.9%), fair (6.0%), or poor (0.9%). The means of global health assessments were not equidistant across these five groups, for example, means of the health thermometer were 95.8 (SRH excellent), 88.8 (SRH very good), 76.6 (SRH good), 49.7 (SRH fair), and 33.5 (SRH poor, p<0.001). Recoding the SRH to reflect these mean values substantially improved the variance explained by the SRH, for example, the linear r 2 increased from 0.50 to 0.56 for the health thermometer if the SRH was coded as poor=1, fair=2, good=3.7, very good=4.5, and excellent=5. Furthermore, transitions between response options were not explained by the same health-related characteristics of the respondents. Conclusions: The adjectival SRH is not an evenly spaced interval scale. However, it can be turned into an interval variable if the ratings are recoded in proportion to the underlying construct of health. Possible improvements include the addition of a rating option between good and fair or the use of a numerical scale instead of the classic adjectival scal

Self-rated health: analysis of distances and transitions between response options

Purpose: We explored health differences between population groups who describe their health as excellent, very good, good, fair, or poor. Methods: We used data from a population-based survey which included self-rated health (SRH) and three global measures of health: the SF36 general health score (computed from the 4 items other than SRH), the EQ-5D health utility, and a visual analogue health thermometer. We compared health characteristics of respondents across the five health ratings. Results: Survey respondents (N=1.844, 49.2% response) rated their health as excellent (12.2%), very good (39.1%), good (41.9%), fair (6.0%), or poor (0.9%). The means of global health assessments were not equidistant across these five groups, for example, means of the health thermometer were 95.8 (SRH excellent), 88.8 (SRH very good), 76.6 (SRH good), 49.7 (SRH fair), and 33.5 (SRH poor, p<0.001). Recoding the SRH to reflect these mean values substantially improved the variance explained by the SRH, for example, the linear r 2 increased from 0.50 to 0.56 for the health thermometer if the SRH was coded as poor=1, fair=2, good=3.7, very good=4.5, and excellent=5. Furthermore, transitions between response options were not explained by the same health-related characteristics of the respondents. Conclusions: The adjectival SRH is not an evenly spaced interval scale. However, it can be turned into an interval variable if the ratings are recoded in proportion to the underlying construct of health. Possible improvements include the addition of a rating option between good and fair or the use of a numerical scale instead of the classic adjectival scal

Rilpivirine use in the Swiss HIV cohort study: a prospective cohort study.

Rilpivirine is safe and effective in HIV-naïve patients with low baseline HIV-RNA or in switch strategy. It offers the advantages of few drug-drug interactions and a favourable toxicity profile. We aimed to determine the reasons for prescribing the rilpivirine (RPV)/tenofovir disoproxil (TDF)/emtricitabine (FTC) co-formulation within the Swiss HIV Cohort Study and to assess its effectiveness and safety over a 24 months period. All individuals enrolled in the Swiss HIV Cohort Study who initiated a RPV/TDF/FTC co-formulation between April 2013 and March 2014 were included. Primary outcomes were the HIV-RNA viral load (copies/mL) and CD4 cell count (cells/mm(3)) at 6, 12 and 24 months. Reasons for a switch to RPV/TDF/FTC were evaluated through a standardized questionnaire. We also assessed discontinuation and reasons for discontinuation of RPV/TDF/FTC until October 30, 2015. Of 644 individuals who started the RPV/TDF/FTC co-formulation, only 7.5% were treatment-naïve. At 24 months, viral suppression (HIV-RNA &lt;50 copies/mL) was achieved in 100% and 96.7% of cART-naïve and cART-experienced patients respectively. The switch to RPV was mainly done for simplification (44.6%) and to overcome central nervous system toxicity symptoms due to efavirenz (24%). Six months after switch, 74.8% of patients reported an improvement of psycho-neurological symptoms with continued improvement at 12 months for almost 80%. However, one quarter of patients reported a discontinuation of RPV/TDF/FTC on October 30, 2015 after a median time of 18.4 months. Reasons for discontinuation included physician decision (5.3%) and side-effects (3.9%) mainly related to the central nervous system and to renal toxicity. The RPV/TDF/FTC co-formulation was safe and effective throughout 24 months of follow-up but barely prescribed for HIV-naïve patients. Despite excellent virological suppression among both treatment-naïve and -experienced patients, we observed a high rate of treatment discontinuation

Efficacy of a New Educational Tool to Improve Handrubbing Technique amongst Healthcare Workers: A Controlled, Before-After Study

Introduction: Hand hygiene is a key component of infection control in healthcare. WHO recommends that healthcare workers perform six specific poses during each hand hygiene action. SureWash (Glanta Ltd, Dublin, Ireland) is a novel device that uses video-measurement technology and immediate feedback to teach this technique. We assessed the impact of self-directed SureWash use on healthcare worker hand hygiene technique and evaluated the device's diagnostic capacity. Methods: A controlled before-after study: subjects in Group A were exposed to the SureWash for four weeks followed by Group B for 12 weeks. Each subject's hand hygiene technique was assessed by blinded observers at baseline (T0) and following intervention periods (T1 and T2). Primary outcome was performance of a complete hand hygiene action, requiring all six poses during an action lasting ≥20 seconds. The number of poses per hand hygiene action (maximum 6) was assessed in a post-hoc analysis. SureWash's diagnostic capacity compared to human observers was assessed using ROC curve analysis. Results: Thirty-four and 29 healthcare workers were recruited to groups A and B, respectively. No participants performed a complete action at baseline. At T1, one Group A participant and no Group B participants performed a complete action. At baseline, the median number of poses performed per action was 2.0 and 1.0 in Groups A and B, respectively (p = 0.12). At T1, the number of poses per action was greater in Group A (post-intervention) than Group B (control): median 3.8 and 2.0, respectively (p<0.001). In Group A, the number of poses performed twelve weeks post-intervention (median 3.0) remained higher than baseline (p<0.001). The area under the ROC curves for the 6 poses ranged from 0.59 to 0.88. Discussion: While no impact on complete actions was demonstrated, SureWash significantly increased the number of poses per hand hygiene action and demonstrated good diagnostic capacity

Risk factors for noma disease: a 6-year, prospective, matched case-control study in Niger

Background Noma is a poorly studied disease that leads to severe facial tissue destruction in children in developing countries, but the cause remains unknown. We aimed to identify the epidemiological and microbiological risk factors associated with noma disease. Methods We did a prospective, matched, case-control study in Niger between Aug 1, 2001, and Oct 31, 2006, in children younger than 12 years to assess risk factors for acute noma. All acute noma cases were included and four controls for each case were matched by age and home village. Epidemiological and clinical data were obtained at study inclusion. We undertook matched-paired analyses with conditional logistic regression models. Findings We included 82 cases and 327 controls. Independent risk factors associated with noma were: severe stunting (odds ratio [OR] 4·87, 95% CI 2·35–10·09) or wasting (2·45, 1·25–4·83); a high number of previous pregnancies in the mother (1·16, 1·04–1·31); the presence of respiratory disease, diarrhoea, or fever in the past 3 months (2·70, 1·35–5·40); and the absence of chickens at home (1·90, 0·93–3·88). After inclusion of microbiological data, a reduced proportion of Fusobacterium (4·63, 1·61–13·35), Capnocytophaga (3·69, 1·48–9·17), Neisseria (3·24, 1·10–9·55), and Spirochaeta in the mouth (7·77, 2·12–28·42), and an increased proportion of Prevotella (2·53, 1·07–5·98), were associated with noma. We identifi ed no specifi c single bacterial or viral pathogen in cases. Interpretation Noma is associated with indicators of severe poverty and altered oral microbiota. The predominance of specifi c bacterial commensals is indicative of a modifi cation of the oral microbiota associated with reduced bacterial diversity.Funding Gertrude Hirzel Foundation

Gram and acridine orange staining for diagnosis of septic arthritis in different patient populations

Purpose: The sensitivity of Gram staining is known to be suboptimal for the diagnosis of native joint septic arthritis. We lack information about the accuracy of Gram compared to other microscopic staining techniques for predicting infection in different patient populations. Methods: This was a cohort study with cost evaluations at the Orthopaedic Service of Geneva University Hospitals (January 1996-October 2012). Results: Among 500 episodes of arthritis (196 with immunosuppression, 227 with underlying arthroplasties and 69 with gout or other crystals in synovial fluid), Gram staining revealed pathogens in 146 episodes (146/500, 29%) or in 146 of the 400 culture-positive episodes (37%). Correlation between the Gram and acridine staining of the same sample was good (Spearman 0.85). Overall, the sensitivity, specificity, positive predictive value and negative predictive value of Gram stain for rapid diagnosis of septic arthritis was 0.37, 0.99, 0.99 and 0.28, respectively, compared to microbiological cultures. Quite similar values were recorded across the different patient subpopulations, in particular for sensitivity values that were 0.33 for patients with prosthetic joint infections, 0.40 for immunosuppressed patients, 0.36 for patients under antibiotic administration and 0.52 for patients with concomitant crystalline disease. Conclusions: The sensitivity of Gram or acridine orange staining for a rapid diagnosis of episodes of septic arthritis is suboptimal compared to microbiological culture, regardless of underlying conditions, immunosuppression or antibiotic therapy. The sensitivity in the presence of synovial fluid crystals is moderate. Acridine orange and Gram stains are equivalent