Adverse event potentially due to an interaction between ibrutinib and verapamil: a case report.

WHAT IS KNOWN AND OBJECTIVE: Ibrutinib is a recently approved oral anticancer agent with pharmacokinetics that is very sensitive to metabolic inhibition. We report a serious side effect of ibrutinib potentially attributable to interaction with the moderate CYP3A4 inhibitor verapamil. CASE DESCRIPTION: A patient with mantle cell lymphoma was admitted to our emergency department with severe diarrhoea. During a prescription review, the clinical pharmacist identified a potential drug interaction between ibrutinib and verapamil present in a branded combination product also containing trandolapril. Ibrutinib was discontinued for 5 days, and verapamil was stopped. Lercanidipine 10 mg daily was prescribed as an alternative antihypertensive drug. The patient was discharged after 3 days with symptomatic treatment for his diarrhoea. Three months later, the patient maintained control with ibrutinib and olmesartan, but without verapamil. WHAT IS NEW AND CONCLUSION: This is the first description of a serious side effect of ibrutinib likely due to an interaction with the CYP3A4 inhibitor verapamil. Prescriptions of ibrutinib must be carefully checked to identify possible interactions with CYP3A4 inhibitors and patients monitored accordingly.

[Emergency overcrowding and hospital organization: Causes and solutions]. / La saturation de la structure des urgences et le rôle de l'organisation hospitalière : réflexions sur les causes et les solutions.

Emergency Department (ED) overcrowding is a silent killer. Thus, several studies in different countries have described an increase in mortality, a decrease in the quality of care and prolonged hospital stays associated with ED overcrowding. Causes are multiple: input and in particular lack of access to lab test and imaging for general practitioners, throughput and unnecessary or time-consuming tasks, and output, in particular the availability of hospital beds for unscheduled patients. The main cause of overcrowding is waiting time for available beds in hospital wards, also known as boarding. Solutions to resolve the boarding problem are mostly organisational and require the cooperation of all department and administrative levels through efficient bed management. Elderly and polypathological patients wait longer time in ED. Internal Medicine, is the ideal specialty for these complex patients who require time for observation and evaluation. A strong partnership between the ED and the internal medicine department could help to reduce ED overcrowding by improving care pathways.

A common gesture with a rare but potentially severe complication: Re-expansion pulmonary edema following chest tube drainage.

BACKGROUND: Primary Spontaneous Pneumothorax (PSP) is usually considered as a benign pathology occurring in young people. In about half of cases, observation only is purposed. In case of intervention, chest tube drainage remains the preponderant strategy even if no studies conclude about superiority of drainage or aspiration. Re-expansion pulmonary edema (REPE) is a rare but potentially severe complication of chest tube drainage. Risk factors are not well identified, but REPE is more frequent for patients with diabetes, younger than 40 years, with large pneumothorax, lung collapse more than one week and fast re-expansion. CASE REPORT: We report a case of a 19-year old male presenting to the Emergency Department with a first episode of PSP. He was treated by chest tube drainage with immediate suction. He developed a REPE 3 hours after chest tube drainage with suction. Conservative management and oxygen therapy led to withdrawing the chest tube 9 days later. CONCLUSION: For the initial management of PSP, prevention of this complication is essential. In case of risk factors, prevention consist of absence of immediate suction after chest tube drainage and suction should be reserved in case of failure of initial treatment after 24 hours. Even if chest tube drainage is a common gesture, clinical presentation of REPE must alert physicians taking care of these patients.

Increased risk and severity of unprovoked venous thromboembolism with clustering cardiovascular risk factors for atherosclerosis: Results of the REMOTEV registry.

BACKGROUND: The role of cardiovascular risk factors (CVRF) for atherosclerosis in venous thromboembolic disease (VTE) is controversial. The aim of this study was to evaluate the impact of CVRF and their cumulative effects on the occurrence of unprovoked VTE, severity, recurrence and survival. METHODS AND RESULTS: This is a prospective cohort from the REMOTEV registry including all consecutively hospitalized patients for acute symptomatic VTE. From November 2013 to December 2016, 515 patients with 6months follow-up (FU) were selected for the analysis. Events were classified as unprovoked or provoked VTE. In univariate analysis, hypertension (OR 1.44, [95% CI 1.01-2.06]), diabetes (OR 2.07, [95% CI: 1.25-3.55]) and age (OR 1.94, [95% CI: 1.31-2.88]) were significantly associated with the risk of unprovoked VTE. After adjustment, diabetes (OR 1.82, [95% CI: 1.07-3.18]) and age (OR 1.79, [95% CI: 1.15-2.8]) remained associated with the risk of unprovoked VTE. The proportion of unprovoked VTE increased significantly with the number of CVRF adjusted for thrombophilia (1 CVRF: OR 3 [95% CI: 1.44-6.52]) 2 CVRF: OR 4.33 [95% CI: 2.07-9.49] and ≥3 CVRF: OR 4.58 [95% CI: 2.27-9.7]). The severity of pulmonary embolism was significantly associated with CVRF clustering. There were more VTE recurrences and deaths during the 6months of FU with cumulative CVRF. CONCLUSION: The risks of unprovoked VTE and PE severity are associated with clustering CVRF. The role of cumulative CVRF predominates rather than the specific burden of each of the CVRF in the risk of VTE occurrence.

Cardio protective effect of glucose-insulin infusion on acute digoxin toxicity in rat.

UNLABELLED: We recently observed a case of digoxin and insulin self-poisoning without cardiac repercussion. We raised the hypothesis that insulin may have a cardio-protective effect in case of digoxin toxicity. We have therefore evaluated the effect of glucose-insulin infusion on mortality and ECG abnormalities during acute digoxin toxicity in rats. Before and after a hyperinsulinemia-euglycemia clamp, rats in glucose-insulin-digoxin (GID) group (n=10) received an intravenous infusion of 12ml/h or 2,5ml/h digoxin (0.25mg/ml) respectively until death occured. Animals receiving digoxin or saline solution intravenously served as control (n=10). ECG recording was performed in all animals over the entire period. Serum insulin and digoxin concentrations were measured by ELISA method after digoxin administration. When digoxin was administered after the clamp, all animals in GID group were alive, whereas 80% of animals in the digoxin group were dead (p<0.001) after 30min. The administration of Digoxin provoked rapid death of rats in the digoxin group in 15+/-12min whereas in GID group the survival period was significantly increased to 38+/-3min (p<0.001). Twenty minutes after digoxin administration, P waves disappeared for 78% of animals in digoxin group while they were present in all rats of GID group (p<0.001). Animal death occurred after a digoxin infusion volume of 7.7+/-0.6ml and 3.0+/-2.4ml in GID and digoxin group respectively (p<0.001). Five minutes after digoxin administration, potassium plasmatic level increased significantly in digoxin group as compared to GID group: 7.1+/-2mmol/l versus 4.4+/-0.4mmol/l (p<0.001). When digoxin was infused before the clamp, 40% of animals in GID group were alive after 180min and the other 60% died after 137+/-40min whereas death of rats in the digoxin group occurred within 80+/-10min (p<0.001). The death of animals was preceded by the P waves disappearing. Thirty minutes after digoxin administration, the potassium plasmatic level increased significantly in the digoxin group as compared to the GID group: 6.9+/-0.5mmol/l versus 4.9+/-0.3mmol/l (p<0.001). At the time of death, both volume of digoxin infusion and serum digoxin concentration were increased in GID group as compared to digoxin group: 5.7+/-1.6ml versus 3.3+/-0.4ml (p<0.001) and 10.7+/-8.3mg/l versus 8.5+/-4.6mg/l. CONCLUSION: Glucose-insulin infusion delayed the abnormalities in cardiac conduction and improved rat survival after acute digoxin toxicity. These results suggest a cardioprotective effect of insulin in case of acute digoxin toxicity.

[Relevance of eosinopenia as marker of sepsis in the Emergency Department]. / Intérêt de l'éosinopénie dans le diagnostic de sepsis aux urgences.

BACKGROUND: Several studies in internal medicine departments and in intensive care units have shown the interest of eosinopenia in the diagnosis of infected patients. The aim of the present study was to test the value of this marker in the Emergency Department (ED), either alone or associated with other common sepsis markers. METHODS: We report on a retrospective and monocentric study. We reviewed the complete blood count (CBC) of all patients visiting the ED during one-week duration (in February 2014). Every element of the CBC and other inflammation markers (such as CRP) were analyzed. RESULTS: During the week of our study, 725 patients had a CBC (33 exclusions) and 692 patients were included for analysis. The median age was 59 years (IQR: 16-100). One hundred and twenty-five patients (18.1%) had a sepsis. The ROC curve demonstrated a cut off level of 10/mm3 eosinophils for which the specificity for sepsis was 91%. The association of eosinopenia (< 10/mm3) and white blood cells (WBC) or CRP elevation also showed a good specificity in patients with sepsis. CONCLUSION: In the ED, with a "simple" CBC, a profound eosinopenia appears to be very specific for sepsis, alone or in association with other markers of inflammation. Eosinopenia may become a helpful tool in our daily practice in the ED. Further studies are needed to further evaluate this marker.

Plasma cyclic guanosine 3'-5' monophosphate concentrations and low vascular resistance in human septic shock.

OBJECTIVE: To investigate the increase in plasma cyclic GMP (cGMP) concentrations in humans with hyperkinetic septic shock (SS) and to evaluate its relationship to low systemic vascular resistance (SVR). DESIGN: Prospective clinical investigation. SETTING: Medical intensive care unit of a university hospital. PATIENTS: 22 patients with documented SS requiring hemodynamic resuscitation, respiratory support and--in some cases--hemodialysis. MEASUREMENTS AND RESULTS: Hemodynamic data were recorded at admission time and then twice a-day during the following 72 h. We simultaneously measured cyclic GMP, atrial natriuretic peptides (ANP), creatininemia and platelet counts. At admission time, higher plasma cGMP concentrations were observed in patients with SS (11.84 +/- 1.52 pmol.ml-1) than in healthy controls (1.77 +/- 0.18 pmol.ml-1, p < 0.0001), in septicemia patients without circulatory failure (3.28 +/- 0.36 pmol.ml-1, p < 0.005) or in patients with hyperkinetic non-septic shock (3.6 +/- 0.7 pmol.ml-1, p < 0.02). In contrast, there was no significant difference between patients with SS and controls with anuria from non-septic origin. Also ANP concentrations were higher in patients with SS than in others. In addition, cGMP levels correlated negatively with SVR during the first 48 h of the study, and positively with creatininemia later when renal function worsened. However, they did not correlate significantly with ANP. CONCLUSION: These data demonstrate that a significant increase in plasma cGMP concentrations occurs during human SS and that it correlates with the decline in peripheral vascular resistance in the absence, but not in the presence, of severe renal failure. Furthermore, the increase in cGMP levels cannot be ascribed solely to enhanced ANP-induced particulate guanylyl cyclase activity. Thus, our results suggest the occurrence of another endogenous source of cGMP during hyperkinetic SS.

[Spontaneous anaerobic osteomyelitis with necrotizing fasciitis of femur: two reasons for the use of hyperbaric oxygenotherapy]. / Ostéomyélite auguë gazogène non traumatique associée à une myonécrose de la cuisse: deux raisons d'utiliser l'oxygénothérapie hyperbare.

This is a case report of a 50-year-old male patient who had septic shock with anaerobic bacterial septicaemia coming from a spontaneous left femoral osteomyelitis. The combined treatment with antibiotics, surgery and hyperbaric oxygenotherapy restored normal mobility of the lower limb. Two years later, there was no recurrence. Despite many efforts the aetiology of the disease is unknown. The authors, discuss the relevance of hyperbaric oxygenotherapy in such cases.

[Propacetamol: from basic action to clinical utilization]. / Le propacétamol: des données fondamentales à l'utilisation clinique.

OBJECTIVE: To review pharmacology and therapeutic use of propacetamol, an injectable prodrug of acetaminophen (paracetamol). DATA SOURCES: Extraction from the Medline database of French and English articles on pharmacology and clinical use of propacetamol. STUDY SELECTION: Articles providing new data into the mechanisms of the analgesic action of paracetamol. Selection of controlled studies (original articles and abstracts of oral communications on therapeutic trials with propacetamol as a single agent or part of balanced analgesia protocols). Case reports and letters to the editor were not considered in this analysis. DATA EXTRACTION: Clinical articles were selected for advantages and adverse effects of propacetamol. Articles dealing with mechanisms of action of propacetamol and paracetamol were selected for the more recent data, excluding those reporting outdated theories not confirmed or abandoned. DATA SYNTHESIS AND CONCLUSION: Mechanisms of action of paracetamol differ from those of NSAIDs, giving account of a low risk of adverse renal, gastrointestinal and haematological effects. Thanks to their high therapeutic index, prescription of propacetamol and paracetamol is quite simple and safe. Main indications of both drugs are painful conditions, especially but not exclusively in the postoperative period, not requiring opioids and also in combination with other analgesic drug and/or techniques (balanced or multimodal analgesia). Because of cost, IV propacetamol is changed for oral paracetamol as soon as possible.

[Effect of the association propofol-alfentanil on bronchial resistances in asthmatic patients]. / Influence de l'association propofol-alfentanil sur les résistances bronchiques du sujet asthmatique.

The bronchial resistances in 17 patients scheduled for ENT surgery were studied during general anaesthesia carried out with propofol and alfentanil. There were nine controls, all free from any allergic pathology. The other eight had bronchial hyperreactivity, with clinical asthma (one or two crises a month) treated with bronchodilators. Two had a complete Fernand-Widal syndrome, and the remaining six documented allergic asthma. All the patients were premedicated with hydroxyzine 2 mg.kg-1 orally on the eve of surgery, and two hours beforehand. Those patients who were on bronchodilators were given their drugs as usual with the premedication. Because bronchial resistances were measured with the patient breathing spontaneously (forced oscillation technique), induction was carried out in two steps, first with propofol 1.5 mg.kg-1, followed, two minutes later, by alfentanil 7 micrograms.kg-1. Once the bronchial resistances had been assessed the patient was given a further 2 mg.kg-1 dose of propofol, and alfentanil 40 micrograms.kg-1. The patient was then intubated, and anaesthesia maintained with propofol 9 mg.kg-1.h-1, and alfentanil 15 micrograms.kg-1 every fifteen minutes. In all, bronchial resistances were measured on the day before surgery, after premedication but before the patient had been given any anaesthetic drug, two minutes after the first injection of propofol, two minutes after the first injection of alfentanil, and after extubation. There were no significant differences between the two groups. Despite the small number of patients included in this study, it would seem that hydroxyzine, propofol and alfentanil may be used safely in patients with hyperreactive bronchi.

[Herpes simplex hepatitis with macrophage activation syndrome in an immunocompetent patient]. / Hépatite herpétique avec syndrome d'activation macrophagique chez un patient immunocompétent.

INTRODUCTION: Herpes simplex hepatitis is a rare cause of acute hepatitis in immunocompetent patients. The triad of fever, increase in liver enzymes and leucopenia is suggestive of herpes simplex hepatitis. Delayed diagnosis without antiviral therapy contributes significantly to an unfavorable outcome. OBSERVATION: We report a 50-year old immunocompetent male patient, who presented with acute severe hepatitis due to a reactivation of a herpes simplex infection with a complicated course including macrophage activation syndrome and severe coagulopathy. Outcome was finally favorable with early acyclovir therapy. CONCLUSION: Despite its relatively low occurrence rate, diagnosis of herpetic hepatitis should be discussed in immunocompetent patients with acute liver failure. The benefit of an early acyclovir treatment should lead clinicians to consider this uncommon diagnosis in unexplained cases of hepatitis and to test rapidly HSV DNA levels by PCR in plasma.