Exclusive Oral Antibiotic Treatment for Hospitalized Community-Acquired Pneumonia: A Post-Hoc Analysis of a Randomized Clinical Trial.

OBJECTIVES: In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). METHODS: In this post-hoc analysis of a RCT on patients hospitalized for CAP (PTC trial) comparing 3-day versus 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). Choice of route and molecule was left to the physician in charge. The main outcome was failure at 15 days after first antibiotic intake, defined as temperature>37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to route of administration was evaluated through logistic regression. Inverse probability treatment weighting (IPTW) with a propensity score model was used to adjust for non-randomization of treatment route and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC versus 3GC treatments, or intravenous versus oral AMC, patients with multi-lobar infection, patients aged ≥ 65 years old, and patients with CURB65 scores of 3-4). RESULTS: We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. Failure rate at Day 15 was not significantly different among patients treated with initial intravenous versus oral treatment (25/93 (26.9%) versus 28/107 (26.2%), aOR 0.973 (95%CI 0.519-1.823), p=0.932). Failure rates at Day 15 were not significantly different among the subgroup populations. CONCLUSIONS: Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT01963442.

In patients with OSA and CVD, CPAP did not reduce major adverse cardiac and cerebrovascular events.

SOURCE CITATION: Sanchez-de-la-Torre M, Gracia-Lavedan E, Benitez ID, et al. Adherence to CPAP treatment and the risk of recurrent cardiovascular events: a meta-analysis. JAMA. 2023;330:1255-1265. 37787793.

VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in long COVID patients.

BACKGROUND: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent clinical symptoms following COVID-19. OBJECTIVE: To correlate biomarkers of endothelial dysfunction with persistent clinical symptoms and pulmonary function defects at distance from COVID-19. METHODS: Consecutive patients with long COVID-19 suspicion were enrolled. A panel of endothelial biomarkers was measured in each patient during clinical evaluation and pulmonary function test (PFT). RESULTS: The study included 137 PASC patients, mostly male (68%), with a median age of 55 years. A total of 194 PFTs were performed between months 3 and 24 after an episode of SARS-CoV-2 infection. We compared biomarkers evaluated in PASC patients with 20 healthy volunteers (HVs) and acute hospitalized COVID-19 patients (n = 88). The study found that angiogenesis-related biomarkers and von Willebrand factor (VWF) levels were increased in PASC patients compared to HVs without increased inflammatory or platelet activation markers. Moreover, VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement. By employing a Cox proportional hazards model adjusted for age, sex, and body mass index, we further confirmed the accuracy of VEGF-A and VWF. Following adjustment, VEGF-A emerged as the most significant predictive factor associated with persistent lung CT scan lesions and impaired DLCO measurement. CONCLUSION: VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms.

Recovery of Endothelium-dependent vascular relaxation impairment in convalescent COVID-19 patients: Insight from a pilot study.

BACKGROUND: Endothelial dysfunction is a key-feature in acute COVID-19. However, follow-up data regarding endothelial dysfunction and injury after COVID-19 infection are lacking. We aimed to investigate the changes in endothelium-dependent vasorelaxation at baseline and four months after hospital discharge in COVID-19 patients. METHODS: Twenty COVID-19 patients were compared to 24 healthy controls. Clinical and morphological data were collected after hospital admission for SARS-CoV-2 infection and reactive hyperaemia index (RHI) measurement was performed with a delay between 24 and 48 h after hospital admission and four months after hospital discharge in the outpatient clinics. Blood tests including inflammatory markers and measurement of post-occlusive vasorelaxation by digital peripheral arterial tonometry were performed at both visits. RESULTS: At baseline, COVID-19 patients exhibited reduced RHI compared to controls (p < 0.001), in line with an endothelial dysfunction. At four months follow-up, there was a 51% increase in the RHI (1.69 ± 0.32 to 2.51 ± 0.91; p < 0.01) in favor of endothelium-dependent vascular relaxation recovery. RHI changes were positively correlated with baseline C-reactive protein (r = 0.68; p = 0.02). Compared to COVID-19 patients with a decrease in RHI, COVID-19 patients with an increase in RHI beyond the day-to-day variability (i.e. >11%) had less severe systemic inflammation at baseline. CONCLUSION: Convalescent COVID-19 patients showed a recovery of systemic artery endothelial dysfunction, in particular patients with lower inflammation at baseline. Further studies are needed to decipher the interplay between inflammation and endothelial dysfunction in COVID-19 patients.

Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Failure of treatment is the most serious complication in community-acquired pneumonia (CAP). Objective: To assess the potential risk factors for treatment failure in clinically stable patients with CAP. Design, Setting, and Participants: This secondary analysis assesses data from a randomized clinical trial on CAP (Pneumonia Short Treatment [PTC] trial) conducted from December 19, 2013, to February 1, 2018. Data analysis was performed from July 18, 2019, to February 15, 2020. Patients hospitalized at 1 of 16 centers in France for moderately severe CAP who were clinically stable at day 3 of antibiotic treatment were included in the PTC trial and analyzed in the per-protocol trial population. Interventions: Patients were randomly assigned (1:1) on day 3 of antibiotic treatment to receive ß-lactam (amoxicillin-clavulanate [1 g/125 mg] 3 times daily) or placebo for 5 extra days. Main Outcomes and Measures: The main outcome was failure at 15 days after first antibiotic intake, defined as a temperature greater than 37.9 °C and/or absence of resolution or improvement of respiratory symptoms and/or additional antibiotic treatment for any cause. The association among demographic characteristics, baseline clinical and biological variables available (ie, at the first day of ß-lactam treatment), and treatment failure at day 15 among the per-protocol trial population was assessed by univariate and multivariable logistic regressions. Results: Overall, 310 patients were included in the study; this secondary analysis comprised 291 patients (174 [59.8%] male; mean [SD] age, 69.6 [18.5] years). The failure rate was 26.8%. Male sex (odds ratio [OR], 1.74; 95% CI, 1.01-3.07), age per year (OR, 1.03; 95% CI, 1.01-1.05), Pneumonia Severe Index score (OR, 1.01; 95% CI, 1.00-1.02), the presence of chronic lung disease (OR, 1.85; 95% CI, 1.03-3.30), and creatinine clearance (OR, 0.99; 95% CI, 0.98-1.00) were significantly associated with failure in the univariate analysis. When the Pneumonia Severe Index score was excluded to avoid collinearity with age and sex in the regression model, only male sex (OR, 1.92; 95% CI, 1.08-3.49) and age (OR, 1.02; 95% CI, 1.00-1.05) were associated with failure in the multivariable analysis. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, among patients with CAP who reached clinical stability after 3 days of antibiotic treatment, only male sex and age were associated with higher risk of failure, independent of antibiotic treatment duration and biomarker levels. Another randomized clinical trial is needed to evaluate the impact of treatment duration in populations at higher risk for treatment failure.

Discontinuing ß-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial.

BACKGROUND: Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of ß-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. METHODS: We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with ß-lactam therapy were randomly assigned (1:1) to receive ß-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. FINDINGS: Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of ß-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or ß-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the ß-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0-84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the ß-lactam group (between-group difference of 9·42%, 95% CI -0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the ß-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI -0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the ß-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the ß-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the ß-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). INTERPRETATION: Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing ß-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. FUNDING: French Ministry of Health.

Antimicrobial Treatment of Human Plague: A Systematic Review of the Literature on Individual Cases, 1937-2019.

BACKGROUND: Yersinia pestis remains endemic in Africa, Asia, and the Americas and is a known bioterrorism agent. Treatment with aminoglycosides such as streptomycin or gentamicin is effective when initiated early in illness but can have serious side effects. Alternatives such as fluoroquinolones, tetracyclines, and sulfonamides are potentially safer but lack robust human data on efficacy. METHODS: We searched PubMed Central, Medline, Embase, and other databases for articles in any language with terms related to plague and antimicrobials. Articles that contained case-level information on antimicrobial treatment and patient outcome were included. We abstracted information related to patient demographics, clinical features, treatment, and fatality. RESULTS: Among 5837 articles screened, we found 762 published cases of treated plague reported from 1937 to 2019. Fifty-nine percent were male; median age was 22 years (range, 8 days-80 years). The case fatality rate was 20% overall. Most patients had primary bubonic (63%), pneumonic (21%), or septicemic (5%) plague, with associated case fatality rates of 17%, 27%, and 38%, respectively. Among those treated with an aminoglycoside (n = 407 [53%]), the case fatality rate was 13%. Among those treated with a sulfonamide (n = 322 [42%]), tetracycline (n = 171 [22%]), or fluoroquinolone (n = 61 [8%]), fatality was 23%, 10%, and 12%, respectively. Case fatality rate did not substantially differ between patients treated with 1 vs 2 classes of antimicrobials considered to be effective for plague. CONCLUSIONS: In addition to aminoglycosides, other classes of antimicrobials including tetracyclines, fluoroquinolones, and sulfonamides are effective for plague treatment, although publication bias and low numbers in certain treatment groups may limit interpretation.

Factors Influencing Atypical Clinical Presentations during the 2017 Madagascar Pneumonic Plague Outbreak: A Prospective Cohort Study.

In late 2017, Madagascar experienced a large urban outbreak of pneumonic plague, the largest outbreak to date this century. During the outbreak, there were widespread reports of plague patients presenting with atypical symptoms, such as prolonged duration of illness and upper respiratory tract symptoms. Reported mortality among plague cases was also substantially lower than that reported in the literature (25% versus 50% in treated patients). A prospective multicenter observational study was carried out to investigate potential reasons for these atypical presentations. Few subjects among our cohort had confirmed or probable plague, suggesting that, in part, there was overdiagnosis of plague cases by clinicians. However, 35% subjects reported using an antibiotic with anti-plague activity before hospital admission, whereas 55% had antibiotics with anti-plague activity detected in their serum at admission. Although there may have been overdiagnosis of plague by clinicians during the outbreak, the high frequency of community antibiotic may partly explain the relatively few culture-positive sputum samples during the outbreak. Community antibiotic use may have also altered the clinical presentation of plague patients. These issues make accurate detection of patients and the development of clinical case definitions and triage algorithms in urban pneumonic plague outbreaks difficult.

Multi-centre evaluation of recent troponin assays for the diagnosis of NSTEMI.

OBJECTIVES: We aimed to compare the use of nine different cardiac troponin (cTn) assays (2 cTnT and 7 cTnI) for the diagnosis of NSTEMI in a single multi-centre population. DESIGN AND METHODS: One hundred and fifty-eight patients were included (mean age 60 years, SD 17 years), including 23 patients (14%) with NSTEMI. RESULTS: The analytical comparison highlighted a large heterogeneity of cTn assays, as reflected by percentages of patients with detectable cTn, correlation coefficients, Passing-Bablok comparisons and concordance coefficients. Correlations within cTnI assays were good and correlation within cTnT assays was excellent. Diagnostic performances demonstrated that each cTn assay has specific threshold values. Furthermore, some assays (HS-cTnI and T, cTnI-Pathfast and cTnI-Centaur) indicated high sensitivity and negative predictive value using the limit of detection (LoD) diagnostic strategy. For the latter assays, a significant increase in specificity was found when using the 99th percentile or the H0-H3 strategies, in comparison to the LoD strategy. When applying the European Society of Cardiology H0-H3 algorithm, comparable diagnostic performances were obtained. CONCLUSION: All 9 cTn assays indicated overall good diagnostic performances for the diagnosis of NSTEMI in emergency departments when the recommended algorithm based on the variation of cTn value between two measurements at admission and 3 h later was used.

Management of chest pain in the French emergency healthcare system: the prospective observational EPIDOULTHO study.

OBJECTIVE: The aim of this paper was to describe the epidemiology, and diagnostic and therapeutic strategies that emergency physicians use to manage patients presenting with chest pain at all three levels of the French emergency medical system - that is, dispatch centres (SAMUs: the medical emergency system), which operate the mobile intensive care units (MICUs), and hospitals' emergency departments (EDs), with a focus on acute coronary syndrome (ACS). PATIENTS AND METHODS: All patients with chest pain who contacted a SAMU and/or were managed by a MICU and/or were admitted into an ED were included in a 1-day multicentre prospective study carried out in January 2013. Data on diagnostic and therapeutic management and disposition were collected. An in-hospital follow-up was performed. RESULTS: In total, 1339 patients were included: 537 from SAMU, 187 attended by a MICU and 615 in EDs. Diagnosing ACS was the main diagnostic strategy of the French emergency care system, diagnosed in 16% of SAMU patients, 25% of MICU patients and 10% of ED patients. Among patients calling the SAMU, 76 (14%) received only medical advice, 15 (8%) patients remained at home after being seen by a MICU and 454 (74%) were discharged from an ED. CONCLUSION: Management of chest pain at the three levels of the French medical emergency system is mainly oriented towards ruling out ACS. The strategy of diagnostic management is based on minimizing missed diagnoses of ACS.

Long-term mortality in older patients discharged after acute decompensated heart failure: a prospective cohort study.

BACKGROUND: Data are available on short- and intermediate-term mortality rates after discharge for acutely decompensated heart failure (ADHF). However, few studies specifically addressed ADHF outcomes in patients aged 75 years or over, who contribute more than half of all ADHF admissions. Our objectives here were to estimate the long-term mortality of patients aged 75 years or over who were discharged after admission for ADHF and to identify factors, especially geriatric findings, independently associated with 2-year mortality. METHODS: This prospective cohort study in five French hospitals included consecutive patients aged 75 years or older and discharged after emergency-department admission for ADHF meeting Framingham criteria (N = 478; median age, 85 years; 68% female). Kaplan-Meier 1-year and 2-year survival curves were plotted. Admission characteristics independently associated with overall 2-year mortality were identified using multivariable Cox proportional-hazards regression. RESULTS: Mortality was 41.7% (95% confidence interval [95% CI], 37.2%-53.5%) after 1 year and 56.0% (95% CI, 51.5%-60.7%) after 2 years. By multivariable analysis, independent predictors of 2-year mortality were male sex (hazard ratio [HR], 1.36; 95% CI, 1.00-1.82), age >85 years (HR, 1.57; 95% CI, 1.19-2.07), higher number of impaired activities of daily living (HR, 1.11 per impaired item; 95% CI, 1.05-1.17), recent weight loss (HR, 1.61; 95% CI, 1.14-2.28), and lower systolic blood pressure (HR, 0.86 per standard deviation increase; 95% CI, 0.74-0.99). Creatinine clearance ≤30 mL/min showed a trend toward an association with 2-year mortality (HR, 1.36; 95% CI, 0.97-2.00). CONCLUSION: Functional impairment before admission is associated with higher long-term mortality in patients ≥75 years admitted for ADHF. This study focused on geriatric markers not traditionally collected in heart-failure patients but did not analyse all cardiologic parameters associated with outcomes in other studies. Nevertheless, our findings may contribute to identify those patients admitted for ADHF who have the worst prognosis.

Score Predicting Acute Chest Syndrome During Vaso-occlusive Crises in Adult Sickle-cell Disease Patients.

BACKGROUND: Vaso-occlusive crisis (VOC), hallmark of sickle-cell disease (SCD), is the first cause of patients' Emergency-Room admissions and hospitalizations. Acute chest syndrome (ACS), a life-threatening complication, can occur during VOC, be fatal and prolong hospitalization. No predictive factor identifies VOC patients who will develop secondary ACS. METHODS: This prospective, monocenter, observational study on SS/S-ß0thalassemia SCD adults aimed to identify parameters predicting ACS at Emergency-Department arrival. The primary endpoint was ACS onset within 15days of admission. Secondary endpoints were hospitalization duration, morphine consumption, pain evaluation, blood transfusion(s) (BT(s)), requiring intensive care and mortality. FINDINGS: Among 250 VOCs included, 247 were analyzed. Forty-four (17.8%) ACSs occurred within 15 (median [IQR] 3 [2, 3]) days post-admission based on auscultation abnormalities; missing chest radiographs excluded three patients. Comparing ACS to VOC, respectively, median hospital stay was longer 9 [7-11] vs 4 [3-7] days (p<0.0001), 7/41 (17%) vs 1/203 (0.5%) required intensive care (p<0.0001), and 20/41 (48.7%) vs 6/203 (3%) required BTs (p<0.0001). No patient died. The multivariate model retained reticulocyte and leukocyte counts, and spine and/or pelvis pain as being independently associated with ACS; the resulting ACS-predictive score's area under the ROC was 0.840 [95% CI 0.780-0.900], 98.8% negative-predictive value and 39.5% positive-predictive value for the real ACS incidence. INTERPRETATION: The ACS-predictive score is simple, easily applied and could change VOC management and therapeutic perspectives. Assessed ACS risk could lead to earlier discharges or close monitoring and rapid medical intensification to prevent ACS.

Total liquid ventilation offers ultra-fast and whole-body cooling in large animals in physiological conditions and during cardiac arrest.

INTRODUCTION: Total liquid ventilation (TLV) can cool down the entire body within 10-15 min in small animals. Our goal was to determine whether it could also induce ultra-fast and whole-body cooling in large animals using a specifically dedicated liquid ventilator. Cooling efficiency was evaluated under physiological conditions (beating-heart) and during cardiac arrest with automated chest compressions (CC, intra-arrest). METHODS: In a first set of experiments, beating-heart pigs were randomly submitted to conventional mechanical ventilation or hypothermic TLV with perfluoro-N-octane (between 15 and 32 °C). In a second set of experiments, pigs were submitted to ventricular fibrillation and CC. One group underwent continuous CC with asynchronous conventional ventilation (Control group). The other group was switched to TLV while pursuing CC for the investigation of cooling capacities and potential effects on cardiac massage efficiency. RESULTS: Under physiological conditions, TLV significantly decreased the entire body temperatures below 34 °C within only 10 min. As examples, cooling rates averaged 0.54 and 0.94 °C/min in rectum and esophageous, respectively. During cardiac arrest, TLV did not alter CC efficiency and cooled the entire body below 34 °C within 20 min, the low-flow period slowing cooling during CC. CONCLUSION: Using a specifically designed liquid ventilator, TLV induced a very rapid cooling of the entire body in large animals. This was confirmed in both physiological conditions and during cardiac arrest with CC. TLV could be relevant for ultra-rapid cooling independently of body weight.

Functional status and co-morbidities are associated with in-hospital mortality among older patients with acute decompensated heart failure: a multicentre prospective cohort study.

BACKGROUND: Among patients admitted for acute decompensated heart failure (ADHF), half are aged 75 years or over. The high prevalence of co-morbidities and functional impairments in this age group may affect patient outcomes. OBJECTIVE: To assess the association between co-morbidities, functional status and in-hospital mortality in patients with ADHF aged ≥75 years. DESIGN: A prospective, multicentre cohort study. SETTING: Five French hospitals. SUBJECTS: Five hundred and fifty-five patients aged ≥75 years admitted to the emergency department with ADHF. METHODS: Baseline clinical data and co-morbidities were recorded at admission. Functional status and cognition were assessed using the Katz index and Mini-Mental Status Examination score, respectively. The primary outcome was in-hospital mortality. RESULTS: We found high prevalences of co-morbidities and functional impairments including hypertension (74.0%), atrial fibrillation (40.2%), prior acute coronary syndrome (32.3%) and diabetes (18.2%). The average creatinine clearance was 56.3 ml/min/1.73 m(2) (interquartile range, 39.2-77.0). In-hospital mortality was 67/555 (12.1%; 95% confidence interval, 9.4-14.8). In multivariate analysis, in-hospital mortality showed a statistically positive association with prior loss of self-sufficiency (Odds ratio [OR]: 5.85 [2.25-12.19]), hyperglycaemia (OR: 1.80 [1.26-2.54] per 1 SD increase), prior cerebral ischaemic event (OR: 3.56 [1.51-8.44]) and troponin I elevation above upper limit of normal (OR: 2.81 [1.37-5.77]). In addition, systolic blood pressure (OR: 0.98 [0.97-0.99] per 1 mmHg increase) and creatinine clearance (OR: 0.72 [0.51-1.00] per 1 SD increase) were negatively associated with in-hospital mortality. CONCLUSION: Co-morbidities and functional impairments are associated with a worse short-term prognosis in patients aged ≥75 years admitted for ADHF. Assessing these parameters at admission may improve patient management.

First evidence of subclinical renal tubular injury during sickle-cell crisis.

BACKGROUND: The pathophysiologic mechanisms classically involved in sickle-cell nephropathy include endothelial dysfunction and vascular occlusion. Arguments demonstrating that ischemia-reperfusion injury-related kidney damage might coincide with vaso-occlusive crisis (VOC) are lacking. METHODS: In this prospective study, we sought to determine whether tubular cells and glomerular permeability might be altered during VOC. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels and albumin-excretion rates (AER) of 25 patients were evaluated prospectively during 25 VOC episodes and compared to their steady state (ST) values. RESULTS: During VOC, white blood-cell counts (WBC) and C-reactive protein (CRP) were significantly higher than at ST but creatinine levels were comparable. Urine NGAL levels were significantly increased during VOC vs ST (P = 0.007) and remained significant when normalized to urine creatinine (P = 0.004), while AER did not change significantly. The higher urine NGAL concentration was not associated with subsequent (24-48 hour) acute kidney injury. Univariate analysis identified no significant correlations between urine NGAL levels and laboratory parameters during VOC. CONCLUSIONS: These results demonstrated that subclinical ischemia-reperfusion tubular injury is common during VOC and highlight the importance of hydroelectrolyte monitoring and correction during VOC.

How to derive and validate clinical prediction models for use in intensive care medicine.

BACKGROUND: Clinical prediction models are formal combinations of historical, physical examination and laboratory or radiographic test data elements designed to accurately estimate the probability that a specific illness is present (diagnostic model), will respond to a form of treatment (therapeutic model) or will have a well-defined outcome (prognostic model) in an individual patient. They are derived and validated using empirical data and used to assist physicians in their clinical decision-making that requires a quantitative assessment of diagnostic, therapeutic or prognostic probabilities at the bedside. PURPOSE: To provide intensivists with a comprehensive overview of the empirical development and testing phases that a clinical prediction model must satisfy before its implementation into clinical practice. RESULTS: The development of a clinical prediction model encompasses three consecutive phases, namely derivation, (external) validation and impact analysis. The derivation phase consists of building a multivariable model, estimating its apparent predictive performance in terms of both calibration and discrimination, and assessing the potential for statistical over-fitting using internal validation techniques (i.e. split-sampling, cross-validation or bootstrapping). External validation consists of testing the predictive performance of a model by assessing its calibration and discrimination in different but plausibly related patients. Impact analysis involves comparative research [i.e. (cluster) randomized trials] to determine whether clinical use of a prediction model affects physician practices, patient outcomes or the cost of healthcare delivery. CONCLUSIONS: This narrative review introduces a checklist of 19 items designed to help intensivists develop and transparently report valid clinical prediction models.

Frequency and severity of adverse drug reactions due to self-medication: a cross-sectional multicentre survey in emergency departments.

BACKGROUND: Little is known about the relation of adverse drug reactions (ADRs) to self-use of medications. OBJECTIVE: The aim of this study was to determine the frequency and severity of ADRs related to self-medication (ADR-SM) among emergency department (ED) patients and to describe their main characteristics. METHODS: A prospective, cross-sectional, observational study was conducted over a period of 8 weeks (1 March to 20 April 2010), in the ED of 11 French academic hospitals. Adult patients presenting to the ED during randomization periods were included, with the exception of cases of self-drug poisoning, inability to complete self-medication questionnaire, or refusal. Clinical outcomes were assessed as well as history of self-medication behaviours and all drugs taken. All doubtful files and those related to ADR-SM were systematically reviewed by an expert committee. RESULTS: A total of 3,027 of 4,661 patients presenting to the ED met the inclusion criteria. Of these, 84.4 % declared a self-medication behaviour, 63.7 % took at least one non-prescribed drug during the previous 2 weeks and 59.9 % took a prescribed medication. A total of 296 patients experienced an ADR (9.78 %), of which 52 (1.72 %) were related to self-medication. Those ADRs related to self-medication included prescribed drugs (n = 19), non-prescribed drugs (n = 17), treatment discontinuation (n = 14), and interactions between non-prescribed and prescribed drugs (n = 2). The ADRs attributed to non-prescribed drugs represented 1 % of all patients taking non-prescribed drugs (n = 1,927). ADR severity was significantly lower for those related to self-medication (p = .032). CONCLUSION: Self-medication is frequent; its potential toxicity should not be neglected, taking into account the rate of adverse drug reactions in about 1 % of ED patient.

Understanding providers' offering and patients' acceptance of HIV screening in emergency departments: a multilevel analysis. ANRS 95008, Paris, France.

OBJECTIVE: We assessed the EDs' characteristics associated with the offer and acceptance rates of a nontargeted HIV rapid-test screening in 29 Emergency Departments (EDs) in the metropolitan Paris region (11.7 million inhabitants), where half of France's new HIV cases are diagnosed annually. METHODS: EDs nurses offered testing to all patients 18-64-year-old, able to provide consent, either with or without supplemental staff (hybrid staff model or indigenous staff model). The EDS' characteristics collected included structural characteristics (location, type, size), daily workload (patients' number and severity, length of stay in hours), staff's participation (training, support to the intervention, leadership), type of week day (weekends vs weekdays) and time (in days). Associations between these variables and the staff model, the offer and acceptance rates were studied using multilevel modeling. RESULTS: Indigenous staff model was more frequent in EDs with a lower daily patient flow and a higher staff support score to the intervention. In indigenous-model EDs, the offer rate was associated with the patient flow (OR = 0.838, 95% CI = 0.773-0.908), was lower during weekends (OR = 0.623, 95% CI = 0.581-0.667) and decreased over time (OR = 0.978, 95% CI = 0.975-0.981). Similar results were found in hybrid-model EDs. Acceptance was poorly associated with EDs characteristics in indigenous-model EDs while in hybrid-model EDs it was lower during weekends (OR = 0.713, 95% CI = 0.623-0.816) and increased after the first positive test (OR = 1.526, 95% CI = 1.142-2.038). The EDs' characteristics explained respectively 38.5% and 15% of the total variance in the offer rate across indigenous model-EDs and hybrid model-EDs vs 12% and 1% for the acceptance rate. CONCLUSION: Our findings suggest the need for taking into account EDs' characteristics while considering the implementation of an ED-based HIV screening program. Strategies allowing the optimization of human resources' utilization such as HIV targeted screening in the EDs might be privileged.

Validation of a clinical prediction model for early admission to the intensive care unit of patients with pneumonia.

OBJECTIVES: The Risk of Early Admission to the Intensive Care Unit (REA-ICU) index is a clinical prediction model that was derived based on 4,593 patients with community-acquired pneumonia (CAP) for predicting early admission to the intensive care unit (ICU; i.e., within 3 days following emergency department [ED] presentation). This study aimed to validate the REA-ICU index in an independent sample. METHODS: The authors retrospectively stratified 850 CAP patients enrolled in a multicenter prospective randomized trial conducted in Switzerland, using the REA-ICU index, alternate clinical prediction models of severe pneumonia (SMART-COP, CURXO-80, and the 2007 IDSA/ATS minor severity criteria), and pneumonia severity assessment tools (the Pneumonia Severity Index [PSI] and CURB-65). RESULTS: The rate of early ICU admission did not differ between the validation and derivation samples within each risk class of the REA-ICU index, ranging from 1.1% to 1.8% in risk class I to 27.1% to 27.6% in risk class IV. The areas under the receiver operating characteristic (ROC) curve were 0.76 (95% confidence interval [CI] = 0.70 to 0.83) and 0.80 (95% CI = 0.77 to 0.83) in the validation and derivation samples, respectively. In the validation sample, the REA-ICU index performed better than the pneumonia severity assessment tools, but failed to demonstrate an accuracy advantage over alternate prediction models in predicting ICU admission. CONCLUSIONS: The REA-ICU index reliably stratifies CAP patients into four categories of increased risk for early ICU admission within 3 days following ED presentation. Further research is warranted to determine whether inflammatory biomarkers may improve the performance of this clinical prediction model.