[Selected novelties for hospital based internal medicine]. / Nouveautés en médecine interne hospitalière.

In this selective overview of articles, we describe new concepts, therapeutic measures and pharmacological agents that may modify current practice in clinical internal medicine. Novelties for the management of cardiovascular disease, such as heart failure, hypoxemic respiratory failure, nosocomial pneumonia and certain allergies are discussed.

À travers quelques articles et études choisis, cet article décrit de nouveaux concepts, mesures thérapeutiques et agents pharmacologiques pouvant modifier les pratiques courantes en médecine interne. Des notions concernant la gestion de maladies cardiovasculaires telles que l'insuffisance cardiaque, les décompensations respiratoires hypoxémiques, les pneumonies nosocomiales et la gestion d'allergies y figurent au premier plan.

Reliability and Accuracy of the Pediatric Swiss Emergency Triage Scale-the SETSped Study.

BACKGROUND AND IMPORTANCE: The Swiss Emergency Triage Scale (SETS) is an adult triage tool used in several emergency departments. It has been recently adapted to the pediatric population but, before advocating for its use, performance assessment of this tool is needed. OBJECTIVES: The purpose of this study was to assess the reliability and the accuracy of the pediatric version of the SETS for the triage of pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This study was a cross-sectional study among a sample of emergency triage nurses (ETNs) exposed to 17 clinical scenarios using a computerized simulator. OUTCOME MEASURES AND ANALYSIS: The primary outcome was the reliability of the triage level performed by the ETNs. It was assessed using an intraclass correlation coefficient.Secondary outcomes included accuracy of triage compared with expert-based triage levels and factors associated with accurate triage. MAIN RESULTS: Eighteen ETNs participated in the study and completed the evaluation of all scenarios, for a total of 306 triage decisions. The intraclass correlation coefficient was 0.80 (95% confidence interval, 0.69-0.91), with an agreement by scenario ranging from 61.1% to 100%. The overall accuracy was 85.8%, and nurses were more likely to undertriage (16.0%) than to overtriage (4.3%). No factor for accurate triage was identified. CONCLUSIONS: This simulator-based study showed that the SETS is reliable and accurate among a pediatric population. Future research is needed to confirm these results, compare this triage scale head-to-head with other recognized international tools, and study the SETSped in real-life setting.

[Duration of antibiotic therapy in febrile neutropenia]. / Durée du traitement antibiotique lors de neutropénie fébrile.

Febrile neutropenia is a frequent complication of cancer treatment and is associated with an increased risk of morbidity and mortality. However, standardization in the management of neutropenic fever has led to a reduction in its complications. The duration and type of antibiotic therapy differ according to guidelines, particularly in cases of febrile neutropenia of unknown origin. Continuation of antibiotic treatment until resolution of neutropenia has historically been recommended but exposes patients to prolonged periods of broad-spectrum antibiotic therapy. In a context of growing resistance to antibiotics, optimization of antibiotic use is necessary, particularly in this frail patient population, faced with the consequences of repeated exposure to broad-spectrum antibiotic therapy.

La neutropénie fébrile est une complication fréquente du traitement des maladies hémato-oncologiques et est associée à un risque accru de morbidité et de mortalité. La standardisation de sa prise en charge a toutefois permis une diminution de ses complications. La durée et le type d'antibiothérapie diffèrent selon les recommandations en particulier lors de neutropénie fébrile d'origine indéterminée. La poursuite du traitement antibiotique jusqu'à la résolution de la neutropénie a été historiquement préconisée mais expose les patients à des durées d'antibiothérapie prolongées. Dans un contexte de résistance croissante aux antibiotiques, une optimisation de leur utilisation est nécessaire, en particulier pour cette population fragile confrontée aux conséquences d'une exposition répétée à une antibiothérapie à large spectre.

[POCUS : diagnosis of pneumonia by lung ultrasonography]. / POCUS : diagnostiquer la pneumonie par l'échographie pleuropulmonaire.

Point-Of-Care Ultrasonography (POCUS) has emerged to support the diagnosis process and management strategies. Its use for the diagnosis of pneumonia has been shown to be reliable and effective over the past decade. Various ultrasonography patterns exist, none of which are pathognomonic for pneumonia. Therefore, POCUS findings must be interpreted in association with the clinical setting. POCUS enables early identification of complications such as parapneumonic effusion and pulmonary abscess. It also provides guidance for invasive procedure such as thoracocentesis and pleural drainage. The forthcoming results of the Swiss OCTOPLUS study will provide data on the clinical and economic impact of a diagnostic strategy based on targeted lung ultrasonography.

L'échographie ciblée, aussi connue sous le terme de Point-Of-Care Ultrasonography (POCUS), a émergé comme outil essentiel dans la démarche diagnostique et la stratégie de prise en charge des patients. Son utilisation pour le diagnostic de la pneumonie a été démontrée comme fiable et performante depuis plus d'une décennie. Plusieurs profils échographiques existent mais aucun n'est pathognomonique de la pneumonie. L'examen échographique est ainsi indissociable du contexte clinique. Le POCUS permet en outre la recherche précoce de complications (épanchement parapneumonique et abcès pulmonaire) et le guidage des gestes invasifs (thoracocentèse et drainage thoracique). Les résultats à venir de l'étude suisse OCTOPLUS permettront d'en savoir plus sur l'impact clinique et économique d'une stratégie diagnostique basée sur l'échographie pleuropulmonaire.

Trends in management and outcomes of COVID patients admitted to a Swiss tertiary care hospital.

Two successive COVID-19 flares occurred in Switzerland in spring and autumn 2020. During these periods, therapeutic strategies have been constantly adapted based on emerging evidence. We aimed to describe these adaptations and evaluate their association with patient outcomes in a cohort of COVID-19 patients admitted to the hospital. Consecutive patients admitted to the Geneva Hospitals during two successive COVID-19 flares were included. Characteristics of patients admitted during these two periods were compared as well as therapeutic management including medications, respiratory support strategies and admission to the ICU and intermediate care unit (IMCU). A mutivariable model was computed to compare outcomes across the two successive waves adjusted for demographic characteristics, co-morbidities and severity at baseline. The main outcome was in-hospital mortality. Secondary outcomes included ICU admission, Intermediate care (IMCU) admission, and length of hospital stay. A total of 2'983 patients were included. Of these, 165 patients (16.3%, n = 1014) died during the first wave and 314 (16.0%, n = 1969) during the second (p = 0.819). The proportion of patients admitted to the ICU was lower in second wave compared to first (7.4 vs. 13.9%, p < 0.001) but their mortality was increased (33.6% vs. 25.5%, p < 0.001). Conversely, a greater proportion of patients was admitted to the IMCU in second wave compared to first (26.6% vs. 22.3%, p = 0.011). A third of patients received lopinavir (30.7%) or hydroxychloroquine (33.1%) during the first wave and none during second wave, while corticosteroids were mainly prescribed during second wave (58.1% vs. 9.1%, p < 0.001). In the multivariable analysis, a 25% reduction of mortality was observed during the second wave (HR 0.75; 95% confidence interval 0.59 to 0.96). Among deceased patients, 82.3% (78.2% during first wave and 84.4% during second wave) died without beeing admitted to the ICU. The proportion of patients with therapeutic limitations regarding ICU admission increased during the second wave (48.6% vs. 38.7%, p < 0.001). Adaptation of therapeutic strategies including corticosteroids therapy and higher admission to the IMCU to receive non-invasive respiratory support was associated with a reduction of hospital mortality in multivariable analysis, ICU admission and LOS during the second wave of COVID-19 despite an increased number of admitted patients. More patients had medical decisions restraining ICU admission during the second wave which may reflect better patient selection or implicit triaging.

[Advances in hospital based internal medicine]. / Nouveautés en médecine interne hospitalière.

Hospital based internal medicine has been strongly solicited for over two years with the SARS-CoV-2 epidemic. This epidemic continues to evolve and represents a strain for public health. Numerous studies have addressed issues concerning this epidemic, and multiple novelties concerning other frequent pathologies have also been published. Management strategies of cardiovascular, pulmonary, gastro-intestinal and metabolic diseases are discussed.

La médecine interne hospitalière a été fortement sollicitée depuis 2 ans avec l'épidémie de SARS-CoV-2. Celle-ci continue d'évoluer et reste une épreuve pour la santé publique. Une pléthore d'études a tenté de résoudre les multiples défis que représente cette épidémie, mais de multiples nouveautés concernant d'autres pathologies fréquentes sont également apparues. La prise en charge des maladies cardiovasculaires, pulmonaires, gastro-intestinales et métaboliques est évoquée.

Development and retrospective evaluation of a clinical decision support system for the efficient detection of drug-related problems by clinical pharmacists.

BACKGROUND: Clinical decision support systems (CDSS) can help identify drug-related problems (DRPs). However, the alert specificity remains variable. Defining more relevant alerts for detecting DRPs would improve CDSS. AIM: Develop electronic queries that assist pharmacists in conducting medication reviews and an assessment of the performance of this model to detect DRPs. METHOD: Electronic queries were set up in CDSS using "triggers" from electronic health records: drug prescriptions, laboratory values, medical problems, vital signs, demographics. They were based on a previous study where 315 patients admitted in internal medicine benefited from a multidisciplinary medication review (gold-standard) to highlight potential DRPs. Electronic queries were retrospectively tested to assess performance in detecting DRPs revealed with gold-standard. For each electronic query, sensitivity, specificity, positive and negative predictive value were computed. RESULTS: Of 909 DRPs, 700 (77.8%) were used to create 366 electronic queries. Electronic queries correctly detected 77.1% of DRPs, median sensitivity and specificity reached 100.0% (IQRs, 100.0%-100.0%) and 99.7% (IQRs, 97.0%-100.0%); median positive predictive value and negative predictive value reached 50.0% (IQRs, 12.5%-100.0%) and 100.0% (IQRs, 100.0%-100.0%). Performances varied according to "triggers" (p < 0.001, best performance in terms of predictive positive value when exclusively involving drug prescriptions). CONCLUSION: Electronic queries based on electronic heath records had high sensitivity and negative predictive value and acceptable specificity and positive predictive value and may contribute to facilitate medication review. Implementing some of these electronic queries (the most effective and clinically relevant) in current practice will allow a better assessment of their impact on the efficiency of the clinical pharmacist.

Atypical Pathogens in Adult Community-Acquired Pneumonia and Implications for Empiric Antibiotic Treatment: A Narrative Review.

Atypical pathogens are intracellular bacteria causing community-acquired pneumonia (CAP) in a significant minority of patients. Legionella spp., Chlamydia pneumoniae and psittaci, Mycoplasma pneumoniae, and Coxiella burnetii are commonly included in this category. M. pneumoniae is present in 5-8% of CAP, being the second most frequent pathogen after Streptococcus pneumoniae. Legionella pneumophila is found in 3-5% of inpatients. Chlamydia spp. and Coxiella burnetii are present in less than 1% of patients. Legionella longbeachae is relatively frequent in New Zealand and Australia and might also be present in other parts of the world. Uncertainty remains on the prevalence of atypical pathogens, due to limitations in diagnostic means and methodological issues in epidemiological studies. Despite differences between CAP caused by typical and atypical pathogens, the clinical presentation alone does not allow accurate discrimination. Hence, antibiotics active against atypical pathogens (macrolides, tetracyclines and fluoroquinolones) should be included in the empiric antibiotic treatment of all patients with severe CAP. For patients with milder disease, evidence is lacking and recommendations differ between guidelines. Use of clinical prediction rules to identify patients most likely to be infected with atypical pathogens, and strategies of narrowing the antibiotic spectrum according to initial microbiologic investigations, should be the focus of future investigations.

High-flow nasal oxygen in acute hypoxemic respiratory failure: A narrative review of the evidence before and after the COVID-19 pandemic.

High-flow nasal oxygen (HFNO) is a type of non-invasive advanced respiratory support that allows the delivery of high-flow and humidified air through a nasal cannula. It can deliver a higher inspired oxygen fraction than conventional oxygen therapy (COT), improves secretion clearance, has a small positive end-expiratory pressure, and exhibits a washout effect on the upper air space that diminishes dead space ventilation. HFNO has been shown to reduce the work of breathing in acute hypoxemic respiratory failure (AHRF) and has become an interesting option for non-invasive respiratory support. Evidence published before the COVID-19 pandemic suggested a possible reduction of the need for invasive mechanical ventilation compared to COT. The COVID-19 pandemic has resulted in a substantial increase in AHRF worldwide, overwhelming both acute and intensive care unit capacity in most countries. This triggered new trials, adding to the body of evidence on HFNO in AHRF and its possible benefits compared to COT or non-invasive ventilation. We have summarized and discussed this recent evidence to inform the best supportive strategy in AHRF both related and unrelated to COVID-19.

[Osmotic demyelination syndrome and overly rapid correction of hyponatremia]. / Syndrome de démyélinisation osmotique : quelle vitesse de correction de la natrémie ?

Hyponatremia is a frequent condition in hospitalized patients and is associated with significant morbidity and mortality. An association between rapid correction of hyponatremia and the occurrence of osmotic demyelination syndrome has been reported. Osmotic demyelination syndrome may present with severe neurologic symptoms, including in rare cases locked-in. Therefore, rapid correction of hyponatremia is recommended only in the presence of severe symptoms. In those cases, hypertonic saline (NaCl 3% 2 ml/Kg over 20 minutes) is recommended with close plasma sodium monitoring. After symptoms improvement, increases in sodium concentration should not exceed 8 mmol/l/24h. In cases without severe neurologic symptoms, the use of 3% NaCl solution should be avoided, and management should target the underlying causes of hyponatremia.

L'hyponatrémie est fréquente à l'hôpital avec une morbimortalité significative. Une association entre la vitesse de correction d'une hyponatrémie et la survenue d'un syndrome de démyélinisation osmotique (SDO) a été mise en évidence dans des études observationnelles. Dès lors, une correction rapide d'une hyponatrémie doit être réservée aux patients avec des symptômes sévères d'hyponatrémie. Dans ces situations, l'utilisation de NaCl 3 % (2 ml/kg) en bolus est recommandée avec des contrôles rapprochés de la natrémie. Après l'amélioration des symptômes, une vitesse de correction inférieure à 8 mmol/24 heures est indiquée. En l'absence de symptômes sévères, il est préférable d'éviter l'utilisation du NaCl 3 % et de traiter selon le mécanisme sous-jacent.

[Interprofessional simulation in emergency medicine]. / Simulation interprofessionnelle en médecine d'urgence.

Teamwork is essential in emergency medicine, but in practice it can be polluted by communication difficulties, a lack of understanding of everyone's roles and responsibilities, and a discordant definition of operating methods and objectives. Today, there is a strong awareness of the need to train medical and healthcare teams in interprofessional collaborative practice to learn how to work as a team, reduce medical errors and improve patient safety. Simulation is a recognized and effective pedagogical modality for achieving these objectives. It is now permanently established in pre- and postgraduate medical-nursing training courses in emergency medicine.

Le travail en équipe est indispensable en médecine d'urgence mais, dans la pratique, il peut être pollué par des difficultés de communication, une méconnaissance des rôles et responsabilités de chacun, et une définition discordante des modes de fonctionnement et des objectifs. Aujourd'hui, il y a une forte prise de conscience de la nécessité de former les équipes médico­soignantes à la pratique collaborative interprofessionnelle pour apprendre à travailler en équipe, réduire les erreurs médicales et améliorer la sécurité des patient-e-s. La simulation est une modalité pédagogique reconnue et efficace pour atteindre ces objectifs. Elle est désormais implantée de façon pérenne dans les cursus de formation médico-soignante pré et postgraduée en médecine d'urgence.

Comparison of prognostic scores for inpatients with COVID-19: a retrospective monocentric cohort study.

BACKGROUND: The SARS-CoV-2 pandemic led to a steep increase in hospital and intensive care unit (ICU) admissions for acute respiratory failure worldwide. Early identification of patients at risk of clinical deterioration is crucial in terms of appropriate care delivery and resource allocation. We aimed to evaluate and compare the prognostic performance of Sequential Organ Failure Assessment (SOFA), Quick Sequential Organ Failure Assessment (qSOFA), Confusion, Uraemia, Respiratory Rate, Blood Pressure and Age ≥65 (CURB-65), Respiratory Rate and Oxygenation (ROX) index and Coronavirus Clinical Characterisation Consortium (4C) score to predict death and ICU admission among patients admitted to the hospital for acute COVID-19 infection. METHODS AND ANALYSIS: Consecutive adult patients admitted to the Geneva University Hospitals during two successive COVID-19 flares in spring and autumn 2020 were included. Discriminative performance of these prediction rules, obtained during the first 24 hours of hospital admission, were computed to predict death or ICU admission. We further exluded patients with therapeutic limitations and reported areas under the curve (AUCs) for 30-day mortality and ICU admission in sensitivity analyses. RESULTS: A total of 2122 patients were included. 216 patients (10.2%) required ICU admission and 303 (14.3%) died within 30 days post admission. 4C score had the best discriminatory performance to predict 30-day mortality (AUC 0.82, 95% CI 0.80 to 0.85), compared with SOFA (AUC 0.75, 95% CI 0.72 to 0.78), qSOFA (AUC 0.59, 95% CI 0.56 to 0.62), CURB-65 (AUC 0.75, 95% CI 0.72 to 0.78) and ROX index (AUC 0.68, 95% CI 0.65 to 0.72). ROX index had the greatest discriminatory performance (AUC 0.79, 95% CI 0.76 to 0.83) to predict ICU admission compared with 4C score (AUC 0.62, 95% CI 0.59 to 0.66), CURB-65 (AUC 0.60, 95% CI 0.56 to 0.64), SOFA (AUC 0.74, 95% CI 0.71 to 0.77) and qSOFA (AUC 0.59, 95% CI 0.55 to 0.62). CONCLUSION: Scores including age and/or comorbidities (4C and CURB-65) have the best discriminatory performance to predict mortality among inpatients with COVID-19, while scores including quantitative assessment of hypoxaemia (SOFA and ROX index) perform best to predict ICU admission. Exclusion of patients with therapeutic limitations improved the discriminatory performance of prognostic scores relying on age and/or comorbidities to predict ICU admission.

Impact of interactive computerised decision support for hospital antibiotic use (COMPASS): an open-label, cluster-randomised trial in three Swiss hospitals.

BACKGROUND: Computerised decision-support systems (CDSSs) for antibiotic stewardship could help to assist physicians in the appropriate prescribing of antibiotics. However, high-quality evidence for their effect on the quantity and quality of antibiotic use remains scarce. The aim of our study was to assess whether a computerised decision support for antimicrobial stewardship combined with feedback on prescribing indicators can reduce antimicrobial prescriptions for adults admitted to hospital. METHODS: The Computerised Antibiotic Stewardship Study (COMPASS) was a multicentre, cluster-randomised, parallel-group, open-label superiority trial that aimed to assess whether a multimodal computerised antibiotic-stewardship intervention is effective in reducing antibiotic use for adults admitted to hospital. After pairwise matching, 24 wards in three Swiss tertiary-care and secondary-care hospitals were randomised (1:1) to the CDSS intervention or to standard antibiotic stewardship measures using an online random sequence generator. The multimodal intervention consisted of a CDSS providing support for choice, duration, and re-evaluation of antimicrobial therapy, and feedback on antimicrobial prescribing quality. The primary outcome was overall systemic antibiotic use measured in days of therapy per admission, using adjusted-hurdle negative-binomial mixed-effects models. The analysis was done by intention to treat and per protocol. The study was registered with ClinicalTrials.gov (identifier NCT03120975). FINDINGS: 24 clusters (16 at Geneva University Hospitals and eight at Ticino Regional Hospitals) were eligible and randomly assigned to control or intervention between Oct 1, 2018, and Dec 31, 2019. Overall, 4578 (40·2%) of 11 384 admissions received antibiotic therapy in the intervention group and 4142 (42·8%) of 9673 in the control group. The unadjusted overall mean days of therapy per admission was slightly lower in the intervention group than in the control group (3·2 days of therapy per admission, SD 6·2, vs 3·5 days of therapy per admission, SD 6·8; p<0·0001), and was similar among patients receiving antibiotics (7·9 days of therapy per admission, SD 7·6, vs 8·1 days of therapy per admission, SD 8·4; p=0·50). After adjusting for confounders, there was no statistically significant difference between groups for the odds of an admission receiving antibiotics (odds ratio [OR] for intervention vs control 1·12, 95% CI 0·94-1·33). For admissions with antibiotic exposure, days of therapy per admission were also similar (incidence rate ratio 0·98, 95% CI 0·90-1·07). Overall, the CDSS was used at least once in 3466 (75·7%) of 4578 admissions with any antibiotic prescription, but from the first day of antibiotic treatment for only 1602 (58·9%) of 2721 admissions in Geneva. For those for whom the CDSS was not used from the first day, mean time to use of CDSS was 8·9 days. Based on the manual review of 1195 randomly selected charts, transition from intravenous to oral therapy was significantly more frequent in the intervention group after adjusting for confounders (154 [76·6%] of 201 vs 187 [87%] of 215, +10·4%; OR 1·9, 95% CI 1·1-3·3). Consultations by infectious disease specialists were less frequent in the intervention group (388 [13·4%] of 2889) versus the control group (405 [16·9%] of 2390; OR 0·84, 95% CI 0·59-1·25). INTERPRETATION: An integrated multimodal computerised antibiotic stewardship intervention did not significantly reduce overall antibiotic use, the primary outcome of the study. Contributing factors were probably insufficient uptake, a setting with relatively low antibiotic use at baseline, and delays between ward admission and first CDSS use. FUNDING: Swiss National Science Foundation. TRANSLATIONS: For the French and Italian translations of the abstract see Supplementary Materials section.

Effect of body position on the redistribution of regional lung aeration during invasive and non-invasive ventilation of COVID-19 patients.

Severe COVID-19-related acute respiratory distress syndrome (C-ARDS) requires mechanical ventilation. While this intervention is often performed in the prone position to improve oxygenation, the underlying mechanisms responsible for the improvement in respiratory function during invasive ventilation and awake prone positioning in C-ARDS have not yet been elucidated. In this prospective observational trial, we evaluated the respiratory function of C-ARDS patients while in the supine and prone positions during invasive (n = 13) or non-invasive ventilation (n = 15). The primary endpoint was the positional change in lung regional aeration, assessed with electrical impedance tomography. Secondary endpoints included parameters of ventilation and oxygenation, volumetric capnography, respiratory system mechanics and intrapulmonary shunt fraction. In comparison to the supine position, the prone position significantly increased ventilation distribution in dorsal lung zones for patients under invasive ventilation (53.3 ± 18.3% vs. 43.8 ± 12.3%, percentage of dorsal lung aeration ± standard deviation in prone and supine positions, respectively; p = 0.014); whereas, regional aeration in both positions did not change during non-invasive ventilation (36.4 ± 11.4% vs. 33.7 ± 10.1%; p = 0.43). Prone positioning significantly improved the oxygenation both during invasive and non-invasive ventilation. For invasively ventilated patients reduced intrapulmonary shunt fraction, ventilation dead space and respiratory resistance were observed in the prone position. Oxygenation is improved during non-invasive and invasive ventilation with prone positioning in patients with C-ARDS. Different mechanisms may underly this benefit during these two ventilation modalities, driven by improved distribution of lung regional aeration, intrapulmonary shunt fraction and ventilation-perfusion matching. However, the differences in the severity of C-ARDS may have biased the sensitivity of electrical impedance tomography when comparing positional changes between the protocol groups.Trial registration: ClinicalTrials.gov (NCT04359407) and Registered 24 April 2020, https://clinicaltrials.gov/ct2/show/NCT04359407 .

A COVID-19-Related Retinopathy Case Report.

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 has been declared a worldwide pandemic by the WHO. Within various multi-organ involvements, several ocular manifestations have been described. We report the case of a patient diagnosed with COVID-19 who presented with a progressive increase of bilateral cotton wool spots over a 1-week period, despite quick and complete recovery of systemic signs of the disease and no ocular symptoms. We followed the evolution of such lesions over a 3-month period. Here, we underline the importance of retinal screening even if no ocular symptom is reported. Furthermore, we demonstrate the essential role of fundus examination as a reflection of systemic vascular changes.

Therapeutic drug monitoring and clinical outcomes in severely ill patients receiving amoxicillin: a single-centre prospective cohort study.

Therapeutic drug monitoring (TDM) of ß-lactam antibiotics is increasingly used to overcome rising antimicrobial resistance and improve antibiotic exposure. However, there is little guidance on target amoxicillin plasma concentrations. We aimed to define these by evaluating associations between amoxicillin concentrations and clinical outcomes. This single-centre prospective cohort study enrolled severely ill and/or immunosuppressed adult patients receiving amoxicillin for suspected or confirmed bacterial infection. TDM with ≥1 intermediate and ≥1 trough level was performed 24 h after therapy initiation. Primary and secondary outcomes were incidence of adverse events (AEs) and clinical failure through Day 30, respectively. A total of 156 patients were included. Important variations were observed both for intermediate (mean 13 mg/L, S.D. 13) and trough (mean 7 mg/L, S.D. 9) amoxicillin levels. Of 111 patients, 33 (30%) had trough levels below the non-species-related breakpoint (2 mg/L). AEs occurred in 27/156 patients (17%); no intermediate- or trough-level threshold predicting toxicity could be established. Patients with the highest-quartile trough levels (9.07-51.5 mg/L) did not experience significantly increased AEs [6/28 (21%) vs. 13/83 (16%); P = 0.6]. Nearly one-third (48/156; 31%) experienced clinical failure; low trough levels did not correlate with failure. There were few amoxicillin AEs yet a relatively high incidence of clinical failure. While no toxicity threshold could be established, the absence of increased AEs among patients with the highest trough concentrations suggests that trough levels up to 40 mg/L may be safe, at least for limited durations. Larger trials must further define optimal amoxicillin concentrations. [ClinicalTrials.gov ID: NCT03790631].

Risk Stratification in Patients with Acute Pulmonary Embolism: Current Evidence and Perspectives.

Risk stratification is one of the cornerstones of the management of acute pulmonary embolism (PE) and determines the choice of both diagnostic and therapeutic strategies. The first step is the identification of patent circulatory failure, as it is associated with a high risk of immediate mortality and requires a rapid diagnosis and prompt reperfusion. The second step is the estimation of 30-day mortality based on clinical parameters (e.g., original and simplified version of the pulmonary embolism severity index): low-risk patients without right ventricular dysfunction are safely managed with ambulatory anticoagulation. The remaining group of hemodynamically stable patients, labeled intermediate-risk PE, requires hospital admission, even if most of them will heal without complications. In recent decades, efforts have been made to identify a subgroup of patients at an increased risk of adverse outcomes (intermediate-high-risk PE), who might benefit from a more aggressive approach, including reperfusion therapies and admission to a monitored unit. The cur-rent approach, combining markers of right ventricular dysfunction and myocardial injury, has an insufficient positive predictive value to guide primary thrombolysis. Sensitive markers of circulatory failure, such as plasma lactate, have shown interesting prognostic accuracy and may play a central role in the future. Furthermore, the improved security of reduced-dose thrombolysis may enlarge the indication of this treatment to selected intermediate-high-risk PE.