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.

Survival for Nonshockable Cardiac Arrests Treated With Noninvasive Circulatory Adjuncts and Head/Thorax Elevation.

OBJECTIVES: Cardiac arrests remain a leading cause of death worldwide. Most patients have nonshockable electrocardiographic presentations (asystole/pulseless electrical activity). Despite well-performed basic and advanced cardiopulmonary resuscitation (CPR) interventions, patients with these presentations have always faced unlikely chances of survival. The primary objective was to determine if, in addition to conventional CPR (C-CPR), expeditious application of noninvasive circulation-enhancing adjuncts, and then gradual elevation of head and thorax, would be associated with higher likelihoods of survival following out-of-hospital cardiac arrest (OHCA) with nonshockable presentations. DESIGN: Using a prospective observational study design (ClinicalTrials.gov NCT05588024), patient data from the national registry of emergency medical services (EMS) agencies deploying the CPR-enhancing adjuncts and automated head/thorax-up positioning (AHUP-CPR) were compared with counterpart reference control patient data derived from the two National Institutes of Health clinical trials that closely monitored quality CPR performance. Beyond unadjusted comparisons, propensity score matching and matching of time to EMS-initiated CPR (TCPR) were used to assemble cohorts with corresponding best-fit distributions of the well-established characteristics associated with OHCA outcomes. SETTING: North American 9-1-1 EMS agencies. PATIENTS: Adult nontraumatic OHCA patients receiving 9-1-1 responses. INTERVENTIONS: In addition to C-CPR, study patients received the CPR adjuncts and AHUP (all U.S. Food and Drug Administration-cleared). MEASUREMENTS AND MAIN RESULTS: The median TCPR for both AHUP-CPR and C-CPR groups was 8 minutes. Median time to AHUP initiation was 11 minutes. Combining all patients irrespective of lengthier response intervals, the collective unadjusted likelihood of AHUP-CPR group survival to hospital discharge was 7.4% (28/380) vs. 3.1% (58/1,852) for C-CPR (odds ratio [OR], 2.46 [95% CI, 1.55-3.92]) and, after propensity score matching, 7.6% (27/353) vs. 2.8% (10/353) (OR, 2.84 [95% CI, 1.35-5.96]). Faster AHUP-CPR application markedly amplified odds of survival and neurologically favorable survival. CONCLUSIONS: These findings indicate that, compared with C-CPR, there are strong associations between rapid AHUP-CPR treatment and greater likelihood of patient survival, as well as survival with good neurological function, in cases of nonshockable OHCA.

Retinal vessel architecture and geometry are not impaired in normal-tension glaucoma.

To investigate the associations between retinal vessel parameters and normal-tension glaucoma (NTG). We conducted a case-control study with a prospective cohort, allowing to record 23 cases of NTG. We matched NTG patient with one primary open-angle glaucoma (POAG) and one control per case by age, systemic hypertension, diabetes, and refraction. Central retinal artery equivalent (CRAE), central retinal venule equivalent (CRVE), Arteriole-To-Venule ratio (AVR), Fractal Dimension and tortuosity of the vascular network were measured using VAMPIRE software. Our sample consisted of 23 NTG, 23 POAG, and 23 control individuals, with a median age of 65 years (25-75th percentile, 56-74). No significant differences were observed in median values for CRAE (130.6 µm (25-75th percentile, 122.8; 137.0) for NTG, 128.4 µm (124.0; 132.9) for POAG, and 135.3 µm (123.3; 144.8) for controls, P = .23), CRVE (172.1 µm (160.0; 188.3), 172.8 µm (163.3; 181.6), and 175.9 µm (167.6; 188.4), P = .43), AVR (0.76, 0.75, 0.74, P = .71), tortuosity and fractal parameters across study groups. Vascular morphological parameters were not significantly associated with retinal nerve fiber layer thickness or mean deviation for the NTG and POAG groups. Our results suggest that vascular dysregulation in NTG does not modify the architecture and geometry of the retinal vessel network.

Validity and reliability of standardized instruments measuring physician communication and interpersonal skills in video-recorded medical consultations - A systematic review.

OBJECTIVE: To identify standardized instruments measuring physician communication and interpersonal skills based on video-recorded consultations. METHODS: We searched electronic databases for primary studies published from 1950 to 2022. Eligible studies had to report the validation of standardized instruments dedicated to the assessment of physician interpersonal skills based on video-recorded consultations with adult patients. RESULTS: Of 7155 studies retrieved, 13 primary studies involving nine standardized instruments were included. The median number of physicians and participants was 23 (range, 1-200) and 71 (range, 1-950), respectively. Seven out of nine instruments were multidimensional and comprised a median number of 23 items (range, 7-95). The conceptual framework was reported for two instruments only. Content analysis identified 12 key behaviors with substantial overlap across instruments. The Four Habits Coding Scheme (4-HCS) yielded satisfactory validity and reliability while the evidence on psychometric properties was limited for other instruments. CONCLUSION: Limited evidence supports the psychometric attributes for most of the published standardized instruments dedicated to assessing physician communication and interpersonal skills. PRACTICE IMPLICATIONS: Although the decision to use a specific instrument depends on the study aims, the 4-HCS appears to be the most reliable instrument for assessing physician communication and interpersonal skills based on video-recorded consultations.

Lower fractal dimension of retinal vessel for patients with Birdshot chorioretinopathy.

PURPOSE: To identify the retinal vessel vasculature parameters associated with birdshot chorioretinopathy (BSCR). METHODS: This retrospective observational study included 28 prevalent cases of BSCR with a median time from diagnosis of 6 years and 28 controls matched for age, arterial hypertension, diabetes and refraction. Forty-five-degree fundus images of both dilated eyes were acquired with a fundus camera (Canon CR-2, Tokyo, Japan). The summary diameter of the arterial retinal vessels (central retinal artery equivalent, CRAE), venous retinal vessels (central retinal vein equivalent, CRVE), vascular tortuosity and fractal dimension (FD) were measured using VAMPIRE software. Retinal vasculitis was characterized using fluorescein angiography and active choroiditis using indocyanine green angiography. RESULTS: At baseline, BSCR was associated with lower FD compared with matched controls (mean difference, -0.04; 95% confidence interval [CI], -0.06 to -0.02, p < 0.001). No other VAMPIRE parameters (CRAE, CRVE, arterial and venous tortuosity) differed. Among BSCR patients, retinal vein vasculitis was associated with higher CRAE (mean difference, 21 µ; 95% CI, 2.6-40, p = 0.03), venous tortuosity (geometric mean ratio, 1.79; 95% CI, 1.18-2.72, p = 0.007) and FD (mean difference, -0.04; 95% CI, -0.06 to -0.01, p = 0.007). Resolution of retinal vein vasculitis during follow-up was paralleled by decrease in CRAE, CRVE and venous tortuosity values and increase in venous FD, respectively. CONCLUSION: BSCR is associated with lower FD value, suggesting that chronic retinal inflammation induces microvascular remodelling. Efficient treatment of retinal vasculitis may reverse changes in retinal vascular parameters. Changes in retinal vascular parameters could be potentially useful for assessing patients with BSCR disease.

Comparative diagnostic accuracy between simplified and original flow cytometric gating strategies for peripheral blood neutrophil myeloperoxidase expression in ruling out myelodysplastic syndromes.

BACKGROUND: Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression is accurate in ruling out myelodyplastic syndromes (MDS) but might not be suitable for implementation in busy clinical laboratories. We aimed to simplify the original gating strategy and examine its accuracy. METHODS: Using the individual data from 62 consecutive participants enrolled in a prospective validation study, we assessed the agreement in intra-individual robust coefficient of variation (RCV) of peripheral blood neutrophil myeloperoxidase expression and compared diagnostic accuracy between the simplified and original gating strategies. RESULTS: Cytomorphological evaluation of bone marrow aspirate confirmed MDS in 23 patients (prevalence, 37%), unconfirmed MDS in 32 patients (52%), and was uninterpretable in 7 patients (11%). Median intra-individual RCV for simplified and original gating strategies were 30.7% (range, 24.7-54.4) and 30.6% (range, 24.7-54.1), with intra-class correlation coefficient quantifying absolute agreement equal to 1.00 (95% confidence interval [CI], 0.99 to 1.00). The areas under the receiver operating characteristic (ROC) curves were 0.93 (95% CI, 0.82-0.98) and 0.92 (95% CI, 0.82-0.98), respectively (P = .32). Using simplified or original gating strategy, intra-individual RCV values lower than a pre-specified threshold of 30.0% ruled out MDS for 35% (19 of 55) patients, with both sensitivity and negative predictive value estimates of 100%. CONCLUSIONS: The simplified gating strategy performs as well as the original one for ruling out MDS and has the potential to save time and reduce resource utilization. Yet, prospective validation of the simplified gating strategy is warranted before its adoption in routine. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03363399 (First posted on December 6, 2017).

Flow cytometry lyophilised-reagent tube for quantifying peripheral blood neutrophil myeloperoxidase expression in myelodysplastic syndromes (MPO-MDS-Develop): protocol for a diagnostic accuracy study.

INTRODUCTION: Suspicion of myelodysplastic syndromes (MDS) is the most common reason for bone marrow aspirate in elderly patients. Peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis might rule out MDS for up to 35% of patients referred for suspected disease, without requiring bone marrow aspiration. Yet laboratory-developed liquid antibody cocktails have practical limitations, because of lack of standardisation and poor stability. This research project aims to estimate the level of agreement and comparative accuracy between a single-use flow cytometry tube of lyophilised reagents (BD Lyotube Stain 468) and its laboratory-developed liquid reagent counterpart in quantifying peripheral blood neutrophil myeloperoxidase expression, among adult patients referred for suspected MDS. METHODS AND ANALYSIS: The MPO-MDS-Develop project is a cross-sectional diagnostic accuracy study of two index tests by comparison with a reference standard in consecutive unselected adult patients conducted at a single university hospital. Flow cytometry analysis of peripheral blood samples will be performed by independent operators blinded to the reference diagnosis, using either Lyotube Stain 468 or laboratory-developed liquid reagent cocktail. The reference diagnosis of MDS will be established by cytomorphological evaluation of bone marrow aspirate by two independent haematopathologists blinded to the index test results. Morphologic assessment will be complemented by bone marrow flow cytometric score, karyotype and targeted next-generation sequencing panel of 43 genes, where relevant. The target sample size is 103 patients. ETHICS AND DISSEMINATION: An institutional review board (Comité de Protection des Personnes Sud Est III, Lyon, France) approved the protocol prior to study initiation (reference number: 2020-028-B). Participants will be recruited using an opt-out approach. Efforts will be made to release the primary results within 6 months of study completion. TRIAL REGISTRATION NUMBER: NCT04399018.

Head and thorax elevation during cardiopulmonary resuscitation using circulatory adjuncts is associated with improved survival.

BACKGROUND: Survival after out-of-hospital cardiac arrest (OHCA) remains poor. A physiologically distinct cardiopulmonary resuscitation (CPR) strategy consisting of (1) active compression-decompression CPR and/or automated CPR, (2) an impedance threshold device, and (3) automated controlled elevation of the head and thorax (ACE) has been shown to improve neurological survival significantly versus conventional (C) CPR in animal models. This resuscitation device combination, termed ACE-CPR, is now used clinically. OBJECTIVES: To assess the probability of OHCA survival to hospital discharge after ACE-CPR versus C-CPR. METHODS: As part of a prospective registry study, 227 ACE-CPR OHCA patients were enrolled 04/2019-07/2020 from 6 pre-hospital systems in the United States. Individual C-CPR patient data (n = 5196) were obtained from three large published OHCA randomized controlled trials from high-performing pre-hospital systems. The primary study outcome was survival to hospital discharge. Secondary endpoints included return of spontaneous circulation (ROSC) and favorable neurological survival. Propensity-score matching with a 1:4 ratio was performed to account for imbalances in baseline characteristics. RESULTS: Irrespective of initial rhythm, ACE-CPR (n = 222) was associated with higher adjusted odds ratios (OR) of survival to hospital discharge relative to C-CPR (n = 860), when initiated in <11 min (3.28, 95 % confidence interval [CI], 1.55-6.92) and < 18 min (1.88, 95 % CI, 1.03-3.44) after the emergency call, respectively. Rapid use of ACE-CPR was also associated with higher probabilities of ROSC and favorable neurological survival. CONCLUSIONS: Compared with C-CPR controls, rapid initiation of ACE-CPR was associated with a higher likelihood of survival to hospital discharge after OHCA.

Concordance between SIVA, IVAN, and VAMPIRE Software Tools for Semi-Automated Analysis of Retinal Vessel Caliber.

We aimed to compare measurements from three of the most widely used software packages in the literature and to generate conversion algorithms for measurement of the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) between SIVA and IVAN and between SIVA and VAMPIRE. We analyzed 223 retinal photographs from 133 human participants using both SIVA, VAMPIRE and IVAN independently for computing CRAE and CRVE. Agreement between measurements was assessed using Bland-Altman plots and intra-class correlation coefficients. A conversion algorithm between measurements was carried out using linear regression, and validated using bootstrapping and root-mean-square error. The agreement between VAMPIRE and IVAN was poor to moderate: The mean difference was 20.2 µm (95% limits of agreement, LOA, -12.2-52.6 µm) for CRAE and 21.0 µm (95% LOA, -17.5-59.5 µm) for CRVE. The agreement between VAMPIRE and SIVA was also poor to moderate: the mean difference was 36.6 µm (95% LOA, -12.8-60.4 µm) for CRAE, and 40.3 µm (95% LOA, 5.6-75.0 µm) for CRVE. The agreement between IVAN and SIVA was good to excellent: the mean difference was 16.4 µm (95% LOA, -4.25-37.0 µm) for CRAE, and 19.3 µm (95% LOA, 0.09-38.6 µm) for CRVE. We propose an algorithm converting IVAN and VAMPIRE measurements into SIVA-estimated measurements, which could be used to homogenize sets of vessel measurements obtained with different software packages.

Student characteristics associated with interpersonal skills in medical consultations.

BACKGROUND: The quality of medical care depends on effective physician-patient communication. Interpersonal skills can be improved through teaching, but the determinants are poorly understood. We therefore assessed the factors associated with the interpersonal skills of medical students during simulated medical consultations. METHODS: We conducted a cross-sectional study of fourth-year medical students participating in simulated consultations with standardized patients. Each video-recorded medical consultation was independently assessed by two raters, using a cross-cultural adaptation of the Four Habits Coding Scheme (4-HCS) into French. We then collected information on demographics and education-related characteristics. The relationship between the overall 4-HCS score and student characteristics was modeled using univariable and multivariable linear regression. RESULTS: Our analytical sample included 165 medical students for analysis. The factors significantly associated with 4-HCS score were gender (ß = - 4.8, p = 0.011) and completion of an international clinical placement (ß = 6.2, p = 0.002) or a research laboratory clerkship (ß = 6.5, p = 0.005). Education-related characteristics, multiple-choice examinations in the first to third preclinical years, and number of medicine or surgery clerkships were not significantly associated with 4-HCS score. CONCLUSIONS: Undergraduate students with higher level of interpersonal skills during video-recorded medical consultations with standardized patients are more likely to be female, to have completed international clinical placement as part of the ERASMUS exchange program or research laboratory clerkship.

Effectiveness of a multifaceted intervention to improve interpersonal skills of physicians in medical consultations (EPECREM): protocol for a randomised controlled trial.

INTRODUCTION: Interpersonal skills, encompassing communication and empathy, are key components of effective medical consultations. Although many organisations have implemented structured training programmes, limited evidence exists on their effectiveness in improving physician interpersonal skills. This study aims to evaluate the effectiveness of a standardised, multifaceted, interpersonal skills development programme for hospital physicians. METHODS AND ANALYSIS: This study is a prospective, randomised (with a 1:1 allocation ratio), controlled, open-label, two parallel arm, superiority trial conducted at a single university hospital. Physicians will be randomised to receive either a multifaceted training programme or no intervention. The experimental intervention combines two 4-hour training sessions, dissemination of interactive educational materials, review of video-recorded consultations and individual feedback. The primary outcome measure is the overall 4-Habits Coding Scheme score assessed by two independent raters blinded to the study arm, based on video-recorded consultations, before and after intervention. The secondary outcomes include patient satisfaction, therapeutic alliance, physician self-actualisation and the length of medical consultation. ETHICS AND DISSEMINATION: The study protocol was approved on 21 October 2020 by the CECIC Rhône-Alpes Auvergne, Clermont-Ferrand, France (IRB 5891). All participants will provide written informed consent. Efforts will be made to release the primary results within 6 to 9 months of study completion, regardless of whether they confirm or deny the research hypothesis. TRIAL REGISTRATION NUMBER: NCT04703816.

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.

Effectiveness of a Multifaceted Informational-Based and Text Message Reminders on Pneumococcal and Influenza Vaccinations in Hospital Emergency Departments: A Cluster-Randomized Controlled Trial.

OBJECTIVES: We aimed to evaluate the effectiveness of a multifaceted procedure in improving pneumococcal and influenza vaccinations 6 months after an emergency department (ED) visit among patients aged 65 years and older. METHODS: We conducted a cluster-randomized, controlled, parallel-group, open-label implementation trial in 18 EDs in France and Monaco. Participants were recruited from November 2015 to September 2016. EDs were randomly assigned with a 1:1 ratio to provide either a multifaceted procedure that combined structured information about pneumococcal and influenza vaccines and three text message reminders sent to patients every two weeks (intervention arm) or nonstructured information only (control arm). The outcomes were self-reported pneumococcal vaccination and influenza vaccination rates within 6 months of enrollment. RESULTS: A total of 9 EDs were randomized to the intervention arm (n = 780 patients) and 9 to the control arm (n = 695 patients). The median age for all enrolled patients was 74 years (25-75th percentiles, 69 to 82): 50.1% were male, 34.9% had at least one underlying condition, and 30.7% were at risk for invasive pneumococcal infection. In the intention-to-treat analysis, the multifaceted intervention did not alter the pneumococcal vaccination rate (6.4% versus 4.6%, absolute difference: 1.8; 95% CI: [-0.9 to 4.4]; p = 0.19), whereas it improved the influenza vaccination rate (52.1% versus 40.0%, absolute difference: 12.1; 95% CI: [2.4 to 21.8]; p = 0.01). At 12 months, mortality did not differ between the intervention (9.7%) and control (11.2%) arms (p = 0.35). CONCLUSIONS: A multifaceted intervention based on text message reminders provides an opportunity to increase anti-influenza vaccination among elderly patients visiting the ED. Efforts are warranted to provide better information on pneumococcal diseases and the benefits of pneumococcal vaccines, especially in the elderly.

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.

Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression for ruling out myelodysplastic syndromes: a prospective validation study.

Suspicion of myelodysplastic syndromes (MDS) is the most common reason for bone marrow aspirate in elderly patients. This study aimed to prospectively validate the accuracy for flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in ruling out MDS. We enrolled 62 consecutive patients who were referred for suspected MDS, based on medical history and peripheral blood cytopenia. The accuracy of intra-individual robust coefficient of variation (RCV) for peripheral blood neutrophil myeloperoxidase expression was assessed with a prespecified 30% threshold. Cytomorphological evaluation of bone marrow aspirate performed by experienced hematopathologists confirmed MDS in 23 patients (prevalence, 37%), unconfirmed MDS in 32 patients (52%, including 3 patients with idiopathic cytopenia of undetermined significance (ICUS)), and was uninterpretable in 7 patients (11%). The median intra-individual RCV values for neutrophil myeloperoxidase expression in peripheral blood were 37.4% (range, 30.7-54.1), 29.2% (range, 28.1-32.1), and 29.1% (range, 24.7-37.8) for patients with confirmed suspicion of MDS, ICUS, and unconfirmed suspicion of MDS, respectively (P<0.001). The area under the ROC curve was 0.92 (95% confidence interval, 0.86-0.99). An intra-individual RCV value lower than 30% ruled out MDS for 35% (i.e., 19/55) patients referred for suspected disease, with 100% sensitivity (95% CI, 85-100%) and 100% negative predictive value (95% CI, 82-100%) estimates. This study shows that flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression might obviate the need for bone marrow aspirate for 35% of patients with suspected MDS. Trial registration: ClinicalTrials.gov identifier: NCT03363399 (first posted on December 6, 2017).

Prognostic value of signs of life throughout cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest.

PURPOSE: Prognostication of refractory out-of-hospital cardiac arrest (OHCA) is essential for selecting the population that may benefit from extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to examine the prognostic value of signs of life before or throughout conventional CPR for individuals undergoing ECPR for refractory OHCA. METHODS: Pooling the original data from three cohort studies, we estimated the prevalence of signs of life, for individuals with refractory OHCA resuscitated with ECPR. We performed multivariable logistic regression to examine the independent associations between the occurrence of signs of life and 30-day survival with a CPC score ≤ 2. RESULTS: The analytical sample consisted of 434 ECPR recipients. The prevalence of any sign of life was 61%, including pupillary light reaction (48%), gasping (32%), or increased level of consciousness (13%). Thirty-day survival with favorable neurological outcome was 15% (63/434). In multivariable analysis, the adjusted odds ratios of 30-day survival with favorable neurological outcome were 7.35 (95% confidence interval [CI], 2.71-19.97), 5.86 (95% CI, 2.28-15.06), 4.79 (95% CI, 2.16-10.63), and 1.75 (95% CI, 0.95-3.21) for any sign of life, pupillary light reaction, increased level of consciousness, and gasping, respectively. CONCLUSION: The assessment of signs of life before or throughout CPR substantially improves the accuracy of a multivariable prognostic model in predicting 30-day survival with favorable neurological outcome. The lack of any sign of life might obviate the provision of ECPR for patients without shockable cardiac rhythm.