Validating the accuracy of deep learning for the diagnosis of pneumonia on chest x-ray against a robust multimodal reference diagnosis: a post hoc analysis of two prospective studies.

BACKGROUND: Artificial intelligence (AI) seems promising in diagnosing pneumonia on chest x-rays (CXR), but deep learning (DL) algorithms have primarily been compared with radiologists, whose diagnosis can be not completely accurate. Therefore, we evaluated the accuracy of DL in diagnosing pneumonia on CXR using a more robust reference diagnosis. METHODS: We trained a DL convolutional neural network model to diagnose pneumonia and evaluated its accuracy in two prospective pneumonia cohorts including 430 patients, for whom the reference diagnosis was determined a posteriori by a multidisciplinary expert panel using multimodal data. The performance of the DL model was compared with that of senior radiologists and emergency physicians reviewing CXRs and that of radiologists reviewing computed tomography (CT) performed concomitantly. RESULTS: Radiologists and DL showed a similar accuracy on CXR for both cohorts (p ≥ 0.269): cohort 1, radiologist 1 75.5% (95% confidence interval 69.1-80.9), radiologist 2 71.0% (64.4-76.8), DL 71.0% (64.4-76.8); cohort 2, radiologist 70.9% (64.7-76.4), DL 72.6% (66.5-78.0). The accuracy of radiologists and DL was significantly higher (p ≤ 0.022) than that of emergency physicians (cohort 1 64.0% [57.1-70.3], cohort 2 63.0% [55.6-69.0]). Accuracy was significantly higher for CT (cohort 1 79.0% [72.8-84.1], cohort 2 89.6% [84.9-92.9]) than for CXR readers including radiologists, clinicians, and DL (all p-values < 0.001). CONCLUSIONS: When compared with a robust reference diagnosis, the performance of AI models to identify pneumonia on CXRs was inferior than previously reported but similar to that of radiologists and better than that of emergency physicians. RELEVANCE STATEMENT: The clinical relevance of AI models for pneumonia diagnosis may have been overestimated. AI models should be benchmarked against robust reference multimodal diagnosis to avoid overestimating its performance. TRIAL REGISTRATION: NCT02467192 , and NCT01574066 . KEY POINT: • We evaluated an openly-access convolutional neural network (CNN) model to diagnose pneumonia on CXRs. • CNN was validated against a strong multimodal reference diagnosis. • In our study, the CNN performance (area under the receiver operating characteristics curve 0.74) was lower than that previously reported when validated against radiologists' diagnosis (0.99 in a recent meta-analysis). • The CNN performance was significantly higher than emergency physicians' (p ≤ 0.022) and comparable to that of board-certified radiologists (p ≥ 0.269).

Financial impact of medication reviews by clinical pharmacists to reduce in-hospital adverse drug events: a return-on-investment analysis.

BACKGROUND: Adverse drug events contribute to rising health care costs. Clinical pharmacists can reduce their risks by identifying and solving drug-related problems (DRPs) through medication review. AIM: To develop an economic model to determine whether medication reviews performed by clinical pharmacists could lead to a reduction in health care costs associated with the prevention of potential adverse drug events. METHOD: Two pharmacists performed medication reviews during ward rounds in an internal medicine setting over one year. Avoided costs were estimated by monetizing five categories of DRPs (improper drug selection, drug interactions, untreated indications, inadequate dosages, and drug use without an indication). An expert panel assessed potential adverse drug events and their probabilities of occurrence for 20 randomly selected DRPs in each category. The costs of adverse drug events were extracted from internal hospital financial data. A partial economic study from a hospital perspective then estimated the annual costs avoided by resolving DRPs identified by 3 part-time clinical pharmacists (0.9 full-time equivalent) from 2019 to 2020. The return on investment (ROI) of medication review was calculated. RESULTS: The estimated annual avoided costs associated with the potential adverse drug events induced by 676 DRPs detected was € 304,170. The cost of a 0.9 full-time equivalent clinical pharmacist was € 112,408. Extrapolated to 1 full-time equivalent, the annual net savings was € 213,069 or an ROI of 1-1.71. Sensitivity analyses showed that the economic model was robust. CONCLUSION: This economic model revealed the positive financial impact and favorable return on investment of a medication review intervention performed by clinical pharmacists. These findings should encourage the future deployment of a pharmacist-led adverse drug events prevention program.

[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.

PANDORA dyadic project: hope, spiritual well-being and quality of life of dyads of patients with chronic obstructive pulmonary disease in Switzerland - a multicentre longitudinal mixed-methods protocol study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is responsible for 2.9 million deaths annually in Europe. Symptom burden and functional decline rise as patients reach advanced stages of the disease enhancing risk of vulnerability and dependency on informal caregivers (ICs).Evidence shows that hope is an important psycho-social-spiritual construct that humans use to cope with symptom burden and adversity. Hope is associated with increased quality of life (QoL) comfort and well-being for patients and ICs. A better understanding of the meaning and experience of hope over time as patients transition through chronic illness may help healthcare professionals to plan and deliver care more appropriately. METHODS AND ANALYSIS: This is a longitudinal multicentre mixed-methods study with a convergent design. Quantitative and qualitative data will be collected from dyads of advanced COPD patients and their ICs in two university hospitals at two points in time. The Herth Hope Index, WHO Quality of Life BREF, Functional Assessment of Chronic Illness Therapy-Spiritual Well-being and the French version of the Edmonton Symptom Assessment Scale will be used to collect data. Dyadic interviews will be conducted using a semi-structured interview guide with five questions about hope and their relationship with QoL.Statistical analysis of data will be carried out using R V.4.1.0. To test whether our theoretical model as a whole is supported by the data, structural equation modelling will be used. The comparison between T1 and T2 for level of hope, symptom burden, QoL and spiritual well-being, will be carried out using paired t-tests. The association between symptom burden, QoL, spiritual well-being and hope will be tested using Pearson correlation. ETHICS AND DISSEMINATION: This study protocol received ethical approval on 24 May 2022 from the Commission cantonale d'éthique de la recherche sur l'être humain-Canton of Vaud. The identification number is 2021-02477.

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.

Validation of sham treatment in hyperbaric medicine: a randomised trial.

INTRODUCTION: This study aimed to determine the lowest possible atmospheric pressure in the 111-152 kPa (1.1-1.5 atmospheres absolute [atm abs]) range that would require the patients to equalise their ears, allowing an effective sham for a 203 kPa (2.0 atm abs) hyperbaric exposure. METHODS: We performed a randomised controlled study on 60 volunteers divided into 3 groups (compression to 111, 132 and 152 kPa (1.1, 1.3, 1.5 atm abs) to determine the minimum pressure to obtain blinding. Secondly, we applied additional blinding strategies (faster compression with ventilation during the fictitious compression time, heating at compression, cooling at decompression) on 25 new volunteers in order to enhance blinding. RESULTS: The number of participants who did not believe they had been compressed to 203 kPa was significantly higher in the 111 kPa compressed arm than in the other two arms (11/18 vs 5/19 and 4/18 respectively; P = 0.049 and P = 0.041, Fisher's exact test). There was no difference between compressions to 132 and 152 kPa. By applying additional blinding strategies, the number of participants who believed they had been compressed to 203 kPa increased to 86.5 %. CONCLUSIONS: A compression to 132 kPa, (1.3 atm abs, 3 metres of seawater equivalent) combined with the additional blinding strategies of forced ventilation, enclosure heating and compression in five minutes, simulates a therapeutic compression table and can be used as a hyperbaric placebo.

[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.

Electronic monitoring of potential adverse drug events related to lopinavir/ritonavir and hydroxychloroquine during the first wave of COVID-19.

During Switzerland's first wave of COVID-19, clinical pharmacy activities during medical rounds in Geneva University Hospitals were replaced by targeted remote interventions. We describe using the electronic PharmaCheck system to screen high-risk situations of adverse drug events (ADEs), particularly targeting prescriptions of lopinavir/ritonavir (LPVr) and hydroxychloroquine (HCQ) in the presence of contraindications or prescriptions outside institutional guidelines. Of 416 patients receiving LPVr and/or HCQ, 182 alerts were triggered for 164 (39.4%) patients. The main associated risk factors of ADEs were drug-drug interactions, QTc interval prolongation, electrolyte disorder and inadequate LPVr dosage. Therapeutic optimisation recommended by a pharmacist or proposals for additional monitoring were accepted in 80% (n=36) of cases. Combined with pharmacist contextualisation to the clinical context, PharmaCheck made it possible to successfully adapt clinical pharmacist activities by switching from a global to a targeted analysis mode in an emergency context.

[Thiamin: Simply a vitamin?] / Thiamine : une simple vitamine ?

Vitamin B1 also known as thiamin is an essential vitamin assuring body functioning and comes exclusively from food. Vitamin B1 deficiency is an under-diagnosed disease because it is less frequently suspected in high income countries. However, its risk factors, like alcohol and malnutrition, are common in the general population. Thiamin deficiency can lead to three clinical entities, Gayet-Wernicke encephalopathy, which can progress to Korsakoff encephalopathy, wet Beriberi and its dry form. These diseases are associated with high mortality and heavy long-term sequelae. Rapid diagnosis enables timely treatment.

La vitamine B1 ou thiamine est une vitamine essentielle au bon fonctionnement de l'organisme et provient exclusivement de l'alimentation. La carence en vitamine B1 est une maladie sous-diagnostiquée car sous-évoquée dans les pays à haut revenu. Pourtant, les facteurs de risque, tels que l'alcool et la malnutrition, sont répandus dans la population. Les conséquences d'une carence en thiamine se manifestent sous trois formes, l'encéphalopathie de Gayet-Wernicke, pouvant progresser en encéphalopathie de Korsakoff, le béribéri humide ou sa forme sèche. Ces maladies sont grevées d'une haute mortalité et peuvent entraîner à long terme de lourdes séquelles. Un diagnostic rapide permet d'instaurer un traitement substitutif simple et efficace.

Potential Role of Sphingolipidoses-Associated Lysosphingolipids in Cancer.

Sphingolipids play a key structural role in cellular membranes and/or act as signaling molecules. Inherited defects of their catabolism lead to lysosomal storage diseases called sphingolipidoses. Although progress has been made toward a better understanding of their pathophysiology, several issues still remain unsolved. In particular, whether lysosphingolipids, the deacylated form of sphingolipids, both of which accumulate in these diseases, are simple biomarkers or play an instrumental role is unclear. In the meanwhile, evidence has been provided for a high risk of developing malignancies in patients affected with Gaucher disease, the most common sphingolipidosis. This article aims at analyzing the potential involvement of lysosphingolipids in cancer. Knowledge about lysosphingolipids in the context of lysosomal storage diseases is summarized. Available data on the nature and prevalence of cancers in patients affected with sphingolipidoses are also reviewed. Then, studies investigating the biological effects of lysosphingolipids toward pro or antitumor pathways are discussed. Finally, original findings exploring the role of glucosylsphingosine in the development of melanoma are presented. While this lysosphingolipid may behave like a protumorigenic agent, further investigations in appropriate models are needed to elucidate the role of these peculiar lipids, not only in sphingolipidoses but also in malignant diseases in general.

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.

Abdominal pain patterns during COVID-19: an observational study.

Abdominal pain and liver injury have been frequently reported during coronavirus disease-2019 (COVID-19). Our aim was to investigate characteristics of abdominal pain in COVID-19 patients and their association with disease severity and liver injury.Data of all COVID-19 patients hospitalized during the first wave in one hospital were retrieved. Patients admitted exclusively for other pathologies and/or recovered from COVID-19, as well as pregnant women were excluded. Patients whose abdominal pain was related to alternative diagnosis were also excluded.Among the 1026 included patients, 200 (19.5%) exhibited spontaneous abdominal pain and 165 (16.2%) after abdomen palpation. Spontaneous pain was most frequently localized in the epigastric (42.7%) and right upper quadrant (25.5%) regions. Tenderness in the right upper region was associated with severe COVID-19 (hospital mortality and/or admission to intensive/intermediate care unit) with an adjusted odds ratio of 2.81 (95% CI 1.27-6.21, p = 0.010). Patients with history of lower abdomen pain experimented less frequently dyspnea compared to patients with history of upper abdominal pain (25.8 versus 63.0%, p < 0.001). Baseline transaminases elevation was associated with history of pain in epigastric and right upper region and AST elevation was strongly associated with severe COVID-19 with an odds ratio of 16.03 (95% CI 1.95-131.63 p = 0.010).More than one fifth of patients admitted for COVID-19 presented abdominal pain. Those with pain located in the upper abdomen were more at risk of dyspnea, demonstrated more altered transaminases, and presented a higher risk of adverse outcomes.

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.

Development and assessment of PharmaCheck: an electronic screening tool for the prevention of twenty major adverse drug events.

BACKGROUND: Adverse drug events (ADEs) can be prevented by deploying clinical decision support systems (CDSS) that directly assist physicians, via computerized order entry systems, and clinical pharmacists performing medication reviews as part of medical rounds. However, physicians using CDSS are known to be exposed to the alert-fatigue phenomenon. Our study aimed to assess the performance of PharmaCheck-a CDSS to help clinical pharmacists detect high-risk situations with the potential to lead to ADEs-and its impact on clinical pharmacists' activities. METHODS: Twenty clinical rules, divided into four risk classes, were set for the daily screening of high-risk situations in the electronic health records of patients admitted to our General Internal Medicine Department. Alerts to clinical pharmacists encouraged them to telephone prescribers and suggest any necessary treatment adjustments. PharmaCheck's performance was assessed using the intervention's positive predictive value (PPV), which characterizes the proportion of interventions for each alert triggered. PharmaCheck's impact was assessed by considering clinical pharmacists as a filter for ruling out futile alerts and by comparing the final clinical PPV with a pharmacist (the proportion of interventions that led to a change in the medical regimen) to the final clinical PPV without a pharmacist. RESULTS: Over 132 days, 447 alerts were triggered for 383 patients, leading to 90 interventions (overall intervention PPV = 20.1%). By risk class, intervention PPVs made up 26.9% (n = 65/242) of abnormal laboratory value alerts, 3.1% (4/127) of alerts for contraindicated medications or medications to be used with caution, 28.2% (20/71) of drug-drug interaction alerts, and 14.3% (1/7) of inadequate mode of administration alerts. Clinical PPVs reached 71.0% (64/90) when pharmacists filtered alerts and 14% (64/242) if they were not doing it. CONCLUSION: PharmaCheck enabled clinical pharmacists to improve their traditional processes and broaden their coverage by focusing on 20 high-risk situations. Alert management by pharmacists seemed to be a more effective way of preventing risky situations and alert-fatigue than a model addressing alerts to physicians exclusively. Some fine-tuning could enhance PharmaCheck's performance by considering the information quality of triggers, the variability of clinical settings, and the fact that some prescription processes are already highly secured.

Accuracy of a score predicting the presence of an atypical pathogen in hospitalized patients with moderately severe community-acquired pneumonia.

BACKGROUND: Atypical pathogens (AP), present in some patients with community-acquired pneumonia (CAP), are intrinsically resistant to betalactam drugs, the mainstay of empirical antibiotic treatment. Adding antibiotic coverage for AP increases the risk of adverse effects and antimicrobial selection pressure, while withholding such coverage may worsen the prognosis if an AP is causative. A clinical model predicting the presence of AP would allow targeting atypical coverage for patients most likely to benefit. METHODS: This is a secondary analysis of a multicentric randomized controlled trial that included 580 adults patients hospitalized for CAP. A predictive score was built using independent predictive factors for AP identified through multivariate analysis. Accuracy of the score was assessed using area under the receiver operating curve (AUROC), sensitivity, and specificity. RESULTS: Prevalence of AP was 5.3%. Age < 75 years (OR 2.7, 95% CI 1.2-6.2), heart failure (OR 2.6, 95% CI 1.1-6.1), absence of chest pain (OR 3.0, 95% CI 1.1-8.2), natremia < 135 mmol/L (OR 3.0, 95% CI 1.4-6.6) and contracting the disease in autumn (OR 2.7, 95% CI 1.3-5.9) were independently associated with AP. A predictive score using these factors had an AUROC of 0.78 (95% CI 0.71-0.85). A score of 0 or 1 (present in 33% of patients) had 100% sensitivity and 35% specificity. CONCLUSION: Use of a score built on easily obtained clinical and laboratory data would allow safe withholding of atypical antibiotic coverage in a significant number of patients, with an expected positive impact on bacterial resistance and drug adverse effects. TRIAL REGISTRATION: NCT00818610.

Kinetics of inflammatory biomarkers to predict one-year mortality in older patients hospitalized for pneumonia: a multivariable analysis.

OBJECTIVES: Long-term mortality is increased in older patients with pneumonia. We aimed to test whether residual inflammation is predictive of one-year mortality after pneumonia. METHODS: Inflammation biomarkers (C-reactive protein [CRP], interleukin [IL]-6 and IL-8, tumor necrosis factor-α, serum amyloid A, neopterin, myeloperoxidase, anti-apolipoprotein A-1, and anti-phosphorylcholine IgM) were measured at admission and discharge in older patients hospitalized for pneumonia in a prospective study. Univariate and multivariate analyses were conducted using absolute level at discharge and relative and absolute differences between admission and discharge for all biomarkers, along with usual prognostic factors. RESULTS: In the 133 included patients (median age, 83 years [interquartile range: 78-89]), one-year mortality was 26%. In univariate analysis, the relative difference of CRP levels had the highest area under the receiver operating characteristic curve (0.70; 95% confidence interval [CI] 0.60-0.80). A decrease of CRP levels of more than 67% between admission and discharge had 68% sensitivity and 68% specificity to predict survival. In multivariate analysis, lower body mass index (hazard ratio=0.87 [CI 95% 0.79-0.96], P-value=0.01), higher IL-8 (hazard ratio=1.02 [CI 95% 1.00-1.04], P-value=0.02), and higher CRP (1.01 [95% CI 1.00-1.02], P=0.01) at discharge were independently associated with mortality. CONCLUSION: Higher IL-8 and CRP levels at discharge were independently associated with one-year mortality. The relative CRP difference during hospitalization was the best individual biomarker for predicting one-year mortality.

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].

LOw-dose CT Or Lung UltraSonography versus standard of care based-strategies for the diagnosis of pneumonia in the elderly: protocol for a multicentre randomised controlled trial (OCTOPLUS).

INTRODUCTION: Pneumonia is a leading cause of mortality and a common indication for antibiotic in elderly patients. However, its diagnosis is often inaccurate. We aim to compare the diagnostic accuracy, the clinical and cost outcomes and the use of antibiotics associated with three imaging strategies in patients >65 years old with suspected pneumonia in the emergency room (ER): chest X-ray (CXR, standard of care), low-dose CT scan (LDCT) or lung ultrasonography (LUS). METHODS AND ANALYSIS: This is a multicentre randomised superiority clinical trial with three parallel arms. Patients will be allocated in the ER to a diagnostic strategy based on either CXR, LDCT or LUS. All three imaging modalities will be performed but the results of two of them will be masked during 5 days to the patients, the physicians in charge of the patients and the investigators according to random allocation. The primary objective is to compare the accuracy of LDCT versus CXR-based strategies. As secondary objectives, antibiotics prescription, clinical and cost outcomes will be compared, and the same analyses repeated to compare the LUS and CXR strategies. The reference diagnosis will be established a posteriori by a panel of experts. Based on a previous study, we expect an improvement of 16% of the accuracy of pneumonia diagnosis using LDCT instead of CXR. Under this assumption, and accounting for 10% of drop-out, the enrolment of 495 patients is needed to prove the superiority of LDCT over CRX (alpha error=0.05, beta error=0.10). ETHICS AND DISSEMINATION: Ethical approval: CER Geneva 2019-01288. TRIAL REGISTRATION NUMBER: NCT04978116.

Improving safety of unfractionated heparin: a retrospective, quasi-experimental, observational study of the impact of a pocket card and a computerised prescription aid tool in the University Hospitals of Geneva.

BACKGROUND: Despite the rapid rise of direct oral anticoagulants, unfractionated heparin (UFH) remains the mainstay anticoagulant in specific situations such as severe renal failure, perioperative setting or in critical care units. However, its titration is often challenging. OBJECTIVES: To investigate the effect of a pocket card and a computerised prescription aid tool (CPAT) on the quality of UFH anticoagulation. DESIGN: Monocentric retrospective, quasi-experimental, observational study. SETTING: Inpatient primary care centre between 1 January 2016 and 31 December 2019. PARTICIPANTS: >18 years-old treated with therapeutic UFH for more than 24 hours. There were 819 and 1169 anticoagulation episodes before and after intervention, respectively. INTERVENTION: In October 2017, we implemented a pocket card with evidence-based recommendation for therapeutic UFH initiation, monitoring and dosing adaptation. In October 2019, we implemented a CPAT in a group subset. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was the time needed to reach a therapeutic anti-Xa before and after the implementation of the pocket card. The secondary outcomes included a subgroup analysis assessing the effect of the CPAT. Other secondary outcomes were the anti-Xa status (infratherapeutic, therapeutic or supratherapeutic) at 7 and 24 hours of UFH treatment. RESULTS: We found a significant increase in the time to reach therapeutic dosing with pocket card-guided recommendations implementation (10.1 vs 14 hours, HR of 0.8, 95% CI: 0.70 to 0.93). However, the CPAT was associated with a significant decrease in the time needed to reach the therapeutic range (13.9 vs 7.1 hours, HR of 1.74, 95% CI: 1.17 to 2.60). CONCLUSION: Although we observed an increase in time to reach therapeutic anti-Xa with the pocket card, possibly due to a selection bias (use of activated partial thromboplastin time for monitoring before the pocket card), the implementation of CPAT significantly decreased the delay for effective therapy. Further studies are needed to confirm these findings, and to determine the optimal initial dose of UFH anticoagulation.

Eight versus 28-point lung ultrasonography in moderate acute heart failure: a prospective comparative study.

Lung ultrasonography (LUS) is an accurate method of estimating lung congestion but there is ongoing debate on the optimal number of scanning points. The aim of the present study was to compare the reproducibility (i.e. interobserver agreement) and the feasibility (i.e. time consumption) of the two most practiced protocols in patients hospitalized for acute heart failure (AHF). This prospective trial compared 8- and 28-point LUS protocols. Both were performed by an expert-novice pair of sonographers at admission and after 4 to 6 days on patients admitted for AHF. A structured bio-clinical evaluation was simultaneously carried out by the treating physician. The primary outcome was expert-novice interobserver agreement estimated by kappa statistics. Secondary outcomes included time spent on image acquisition and interpretation. During the study period, 43 patients underwent a total of 319 LUS exams. Expert-novice interobserver agreement was moderate at admission and substantial at follow-up for 8-point protocol (weighted kappa of 0.54 and 0.62, respectively) with no significant difference for 28-point protocol (weighted kappa of 0.51 and 0.41; P value for comparison 0.74 at admission and 0.13 at follow-up). The 8-point protocol required significantly less time for image acquisition at admission (mean time difference - 3.6 min for experts, - 5.1 min for novices) and interpretation (- 6.0 min for experts and - 6.3 min for novices; P value < 0.001 for all time comparisons). Similar differences were observed at follow-up. In conclusion, an 8-point LUS protocol was shown to be timesaving with similar reproducibility when compared with a 28-point protocol. It should be preferred for evaluating lung congestion in AHF inpatients.