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.

Tricuspid regurgitation in ischemic mitral regurgitation patients: prevalence, predictors for outcome and long-term follow-up.

BACKGROUND: Functional tricuspid regurgitation (FTR) is common in left-sided heart pathology involving the mitral valve. The incidence, clinical impact, risk factors, and natural history of FTR in the setting of ischemic mitral regurgitation (IMR) are less known. METHOD: We conducted a cohort study based on data collected from January 2012 to December 2014. Patients diagnosed with IMR were eligible for the study. The median follow-up was 5 years. The primary outcome is defined as FTR developing at any stage. RESULTS: Among the 134 IMR patients eligible for the study, FTR was detected in 29.9% (N = 40, 20.0% mild, 62.5% moderate, and 17.5% severe). In the FTR group, the average age was 60.7 ± 9.2 years (25% females), the mean LV ejection fraction (LVEF) was 37.3 ± 6.45 [%], LA area 46.4 ± 8.06 (mm2), LV internal diastolic diameter (LVIDD) 59.6 ± 3.94 (mm), RV fractional area change 22.3 ± 4.36 (%), systolic pulmonary artery pressure (SPAP) 48.4 ± 9.45 (mmHg). Independent variables associated with FTR development were age ≥ 65y [OR 1.2], failed revascularization, LA area ≥ 42.5 (mm2) [OR 17.1], LVEF ≤ 24% [OR 32.5], MR of moderate and severe grade [OR 419.4], moderate RV dysfunction [OR 91.6] and pulmonary artery pressure of a moderate or severe grade [OR 33.6]. During follow-up, FTR progressed in 39 (97.5%) patients. Covariates independently associated with FTR progression were lower LVEF, RV dysfunction, and PHT of moderate severity. LA area and LVIDD were at the margin of statistical significance (p = 0.06 and p = 0.05, respectively). CONCLUSION: In our cohort study, FTR development and progression due to IMR was a common finding. Elderly patients with ischemic MR following unsuccessful PCI are at higher risk. FTR development and severity are directly proportional to LV ejection fraction, to the extent of mitral regurgitation, and SPAP. FTR tends to deteriorate in the majority of patients over a mean of 5-y follow-up.

[A mysterious pleural lesion: A case report]. / Une mystérieuse lésion pleurale : observation anatomoclinique.

A computed tomography scanner first, then a magnetic resonance imaging were performed for chest pain in a 24-year-old woman allowed to find out a 5-cm long and 2-cm large right pleural tumour close to the rachis (T9 and T10) and spindle-shaped. This patient was a smoker and reported a fall down the stairs a few weeks ago. A scan-guided biopsy was decided and microscopic examination revealed a fibrous tissue in which were entrapped regular and non-suspicious alveolar glands. After elimination of differential diagnosis, the most probable hypothesis was that this lesion was due to the traumatism reported by the patient.

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 randomized controlled trials (RCT) on patients hospitalized for CAP (pneumonia short treatment trial) comparing 3-day vs. 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). The choice of route and molecule was left to the physician in charge. The main outcome was a failure at 15 days after the 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 the route of administration was evaluated through logistic regression. Inverse probability treatment weighting with a propensity score model was used to adjust for non-randomization of treatment routes and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC vs. 3GC treatments, intravenous vs. 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. The failure rate at Day 15 was not significantly different among patients treated with initial intravenous vs. oral treatment [25/93 (26.9%) vs. 28/107 (26.2%), adjusted odds ratios (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. DISCUSSION: 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.

Profile trends of non-COVID patients admitted to the cardiac intensive care unit during the 2020 COVID pandemic.

BACKGROUND: During the COVID-19 outbreak, numerous reports indicated a higher mortality rate among cardiovascular patients. We investigated how this trend applied to patients admitted to the cardiac intensive care unit (CICU). METHODS: We retrospectively compared CICU patients admitted during the initial peak of the COVID outbreak between February and May 2020 (Covid Era, CE group) to a control group in pre-pandemic time in 2019. We interviewed patients to determine the symptom onset time and the time interval between symptomology and hospital arrival. RESULTS: The data of 292 patients were used in the analysis (119 patients in the CE group and 173 in the control group). CE patients had a higher incidence of ischemic heart disease (IHD) (p<.03), heart failure (p<.04), and psychiatric disorders (p<.001). During COVID time, more patients were hospitalized with myocarditis (OR: 26.45), arrhythmias (OR: 2.88), and new heart failure (HF) (p<.001) and less with STEMI (OR: 0.39; 95% CI: 0.24-0.63). Fewer PCIs were performed in the CE group (p<.001), with an overall lower success rate (p<.05) than reported in the control group. Patients in the CE group reported a longer period between symptom onset to hospital arrival (p<.001, χ2 = 12.42). The six-month survival rate was significantly lower in CE patients (χ2 = 7.01, P = 0.008). CONCLUSIONS: Among CICU patients admitted to our center during the initial period of the COVID pandemic, STEMI events were less frequent while cases of newly diagnosed HF sharply increased. Patients waited longer after symptom onset before seeking medical care during the pandemic. The delay may have resulted in clinical deterioration that could explain the high mortality rate and the new HF admission rate.

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.

[Diagnosis of pleurisy in an emergency setting]. / Epanchement pleural liquidien dans le contexte de l'urgence.

In a medical context, it is important to precise if the pleurisy is associated with signs of tamponnade, and/or clinical presentation of ominous organic distress (acute respiratory failure, septic, haemorragic, or cardiogenic shock) or pulmonary embolism. Presence of pleural tamponnade leads to immediate decompression pleural puncture which improves rapidly in general the clinical tolerance, and later permits etiologic treatment. In more severe conditions, pleural evacuation is done in parallel with cardiopulmonary resuscitation maneuvers. If hydropneumothorax is present, immediate drainage with a chest tube will be performed. In other situations, the presence of an abundant pleural effusion with clear fluid necessitates partial needle evacuation to authorize secondarily complementary investigations with pleural biopsy. If purulent pleurisy is discovered, immediate evacuation of pus is mandatory, with needle pleural lavage or chest tube. In all cases, the pleural fluid requires complete haematological, biochemical, and cytologic as well as bacteriological analysis. In the surgical emergency ward, if an opened wound is discovered (gun shot, blunt object or weapon), cardiocirculatory resuscitation is often mandatory, with immediate transfer to the operation ward for an exploratory thoracotomy. If a closed thoracic trauma is present, the problem is generally the management of an hemo(pneumo)thorax with chest tube drainage leading sometimes if the pleural bleeding persists to thoracotomy.

A Randomized Controlled Trial on the Effect of Needle Gauge on the Pain and Anxiety Experienced during Radial Arterial Puncture.

BACKGROUND: Arterial punctures for assessment of arterial blood-gases can be a painful procedure. Lidocaine can be used to reduce pain prior to needle insertion but it is not a widely accepted practice. The purpose of this study was to determine whether a large size needle induces more pain compared to a smaller size needle for radial arterial puncture and to assess the anxiety associated with radial arterial punctures. METHODS: We conducted a prospective, double-blind, randomized, controlled, monocentric study including all outpatients who had a planned assessment of arterial blood gas analysis. Patients were randomized to have the arterial puncture performed with a 23 or a 25 G needle. The main judgement criteria was pain during arterial puncture. Visual analogue scale for pain (VAS-P) and visual analogue scale for anxiety (VAS-A) were used to assess pain and anxiety during radial arterial puncture. RESULTS: Two hundred consecutive patients were randomized. The 25 G needle was as painful as the 23 G needle (6.63 mm [0-19 mm] vs. 5.21 mm [0-18.49 mm], respectively, p = 0.527). Time for arterial puncture was longer with the 25 G needle than with the 23 G needle (42 s [35-55 s] vs. 33 s [24.5-35 s], respectively, p = 0.002). There was a correlation between the level of anxiety prior to the arterial puncture and the pain experienced by the patients (p: 0.369, p<0.0001). There was a correlation between the pain experienced by patients and the anxiety experienced in anticipation of another arterial puncture (p: 0.5124, p<0.0001). CONCLUSIONS: The use of 23 G needle allows quicker arterial sampling and is not associated with increased pain and symptoms. Anxiety was correlated with the pain experienced by patients during arterial punctures. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02320916.

Refillable oxygen cylinders may be an alternative for ambulatory oxygen therapy in COPD.

STUDY OBJECTIVES: To compare, in clinical conditions, the efficacy of refilled oxygen cylinders (O2-HFs) in improving oxygenation and exercise capacity of patients with COPD during a 6-min walking test. DESIGN: Prospective randomized study with a cross-over design. SETTING: A university teaching hospital. PATIENTS: Ten patients with COPD, in a stable state and previously treated with long-term domiciliary oxygen therapy. Baseline characteristics were as follows: age, 65 +/- 7 years; PaO2 on room air, 55.4 +/- 6.3 mm Hg; PaCO2 on room air, 46.2 +/- 7.4 mm Hg; FEV1/vital capacity, 47 +/- 7%; and FEV1, 30 +/- 7% of predicted value (mean +/- SD). DESIGN: All patients performed three successive 6-min walking tests, the first test in room air and the other tests in a randomized order with either a conventional oxygen cylinder (O2-C) or an O2-HF. MEASUREMENTS AND RESULTS: The fraction of inspired oxygen (FIO2) delivered by O2-HFs was significantly lower than the FIO2 delivered by O2-Cs (94.2 +/- 2.6% vs 98.8 +/- 4.9%, p = 0.02). Mean O2-HF and O2-C weights before the walking tests were similar (3,510 +/- 251 g and 3,770 +/- 142 g, respectively; p = 0.09). Mean transcutaneous oxygen saturation was similarly improved with both oxygen delivery systems. Mean distances with O2-C (373.5 +/- 81 m) and O2-HF (375 +/- 97 m) were not different but significantly improved, as compared with room air (334.5 +/- 90 m; p = 0.03 and 0.02, respectively). Dyspnea sensations were similar for the three tests. CONCLUSION: O2-HFs are as efficient as O2-Cs for performing short-term exercises. Because of a lower cost, pressurizing units may be worthwhile for improving ambulatory oxygen therapy and pulmonary rehabilitation programs.

Dry powder ipratropium bromide is as safe and effective as metered-dose inhaler formulation: a cumulative dose-response study in chronic obstructive pulmonary disease patients.

A multi-center, open, randomized, 2-way crossover study was conducted with chronic obstructive pulmonary disease (COPD) patients to compare the safety and efficacy of cumulative doses of ipratropium bromide administered from a pressurized metered-dose inhaler (MDI) or from a breath-activated dry powder inhaler (DPI). Enrolled in the study were 39 patients with moderate to severe COPD and who showed a > or= 15% increase in baseline forced expiratory volume in the first second (FEV(1)) after 80 microg of ipratropium bromide. Thirty-six patients were evaluable for efficacy analysis, and 38 patients were included in the safety analysis group. A significant improvement in pulmonary function was observed following inhalation of cumulative doses of ipratropium bromide (from 20 to 320 microg), but no statistically significant difference was found between the 2 formulations. The dose-response curves were similar. There was no statistical difference in area-under-the-curve during the 180 min period after the last dose for any of the pulmonary function variables. Overall, effects on pulse rate, blood pressure, and QT interval on electrocardiogram were no different between the devices. Six mild adverse events occurred in 4 patients: ventricular ectopic beats on electrocardiogram at 270 min with MDI, bad taste with both MDI and DPI, slight transient increase in blood pressure in the same patient during each study day with both MDI and DPI. Two moderate adverse events occurred in 2 patients: transient ventricular ectopic beats on electrocardiograms with DPI at 270 min, moderate bronchospasm with MDI at 200 min. Patients expressed a preference for DPI, which was found to have a better acceptability and appeared to be easier to use than MDI. The new lactose powder formulation of ipratropium bromide inhaled via the breath-activated DPI is a safe and effective alternative to the chlorofluorocarbon-propelled MDI.

[Diagnosis of community acquired pneumonia in adults]. / Diagnostic des pneumonies aiguës communautaires de l'adulte.

In contrast with acute bronchitis, which is benign and very frequent, community acute pneumonia has to be considered as a serious illness with a mortality rate that can reach 10-15% in inpatients. In adult, pneumonia is usually due to bacteria and antibiotherapy is always required. Clinical diagnosis is based on presumption signs: fever, tachycardia, tachypnea, thoracic pain, localised rales and a global severity impression. A chest X-ray is required. The pathogens involved are usually Streptococcus pneumoniae or atypical organisms. In inpatients (severe pneumonia or presence of risk factors), other pathogens such as gram negative bacilli or anaerobes are possible. The accurate diagnosis is based on invasive methods, which are not justified in outpatients but indicated in severe pneumonia.