Highlights Dexamethasone, or alternative steroids, are recommended in severe COVID-19. The use of tocilizumab in COVID-19, with or without steroids, is still controversial. Risk for mortality was assessed in 186 COVID-19 patients receiving tocilizumab. Mortality was associated with older age, chronic heart failure and liver disease. In tocilizumab-treated patients, the additional use of steroids was beneficial.

Introduction: On the basis of the preliminary report from the RECOVERY trial, the use of dexamethasone or alternative corticosteroids (CS) is currently recommended in severe COVID-19 patients requiring supplemental oxygen. However, last updated recommendations have not taken a position either for or against the use of other immunomodulators such as tocilizumab (TCZ), with or without CS, since results are still limited. Methods: From March 17 to April 7, 2020, a real-world observational retrospective analysis was conducted at our 750-bed university hospital to study the characteristics and risk factors for mortality in patients with severe COVID-19 treated with TCZ, with or without CS, in addition to standard of care (SOC). Data were obtained from routine clinical practice, stored in electronic medical records. The main outcome was all-cause in-hospital mortality. Results: A total of 1,092 COVID-19 patients were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186, 155 (83.3 %) patients were receiving non-invasive ventilation when TCZ, with or without CS was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (SD 4.3) and 4.3 days (SD 3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR=1.09, p<0.001), chronic heart failure (HR=4.4, p=0.003), and chronic liver disease (HR=4.69, p=0.004). The use of CS, in combination with TCZ, was the main protective factor against mortality (HR=0.26, p<0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. Conclusions: In severe COVID-19 patients receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in combined therapy with TCZ, was the main protective factor against in-hospital mortality.

Low-dose VPA was a highly effective treatment for the majority of those with JME and GTCS only. The seizures in JAE tended to be more resistant to treatment, usually requiring higher doses of VPA or polytherapy.

Background Therapeutic drug monitoring (TDM) of total valproic acid (TVPA) concentrations is challenging because of its variable pharmacokinetics. In our department The authors normalise the total VPA (NTVPA) according to serum albumin (Hermida et al). The accepted serum concentration range is 50-150 mg/L. Higher concentrations could be useful in complicated seizures such as status epilepticus (SE). Purpose The aim of this study was to evaluate the safety of high NTVPA levels. Materials and methods Retrospective observational study in patients treated with VPA included in TDM program with a minimum of two NTVPA levels over 150 mg/L separated by at least 7 days. Parameters recorded: sex, age, ward admitted to, indication for VPA, dose administered, concomitant antiepileptic therapy, TVPA, albumin, efficacy variables (seizures, electroencephalogram (EEG)) and adverse effects. Results 24 patients were included (13 men) with 140 TVPA analyses (5.8 analyses/patient (2-13)). Mean age was 61.9 years (29-86). 16 patients were admitted to intensive care units. Patients were followed for a mean of 31.4 days (7-156). Mean VPA dose was 27.6 mg/kg/day. 14 (58.3%) were treated for SE. 6 patients died. Mean TVPA and NTVPA (mg/L) were 65.6 (31.6-140) and 214.7 (151-377) respectively and a mean albuminaemia was 25 g/L. Median NTVPA was 203.5 mg/L and the 75th percentile was 245.2 mg/L. Most of the patients (n=13) received combined treatment with one or more of the following antiepileptic drugs: phenytoin, levetiracetam, oxcarbazepine, carbamazepine, clonazepam, phenobarbital and lacosamide. 2 patients had clinical seizures despite high levels of NTVPA, both confirmed by EEG. Side effects due to VPA were: diarrhoea (n=1) and sedation (n=2). However, 15 patients were pharmacologically sedated. 7 patients had alanine-aminotransferase levels over twofold the normal range (>1.4 ukat/L) and 12 patients had platelet count <135x10E9/L. Conclusions Expanded therapeutic range NTVPA levels may be a safe option to treat complicated seizures. In the light of our results, The authors suggest 245 mg/L as an upper level of the therapeutic range of NTVPA.

Background Gastrointestinal tract resection (GIR) results in a range of physiological changes that affect the absorption of nutrients, water, and electrolytes. These changes may also affect the absorption of orally medication reducing its effect. The highly heterogeneous of GIR patients makes individual monitoring necessary to ensure an optimal clinical effect. Purpose To determinate the incidence of patients with GIR and the proportion of patients with oral medication, which absorption may be affected after GIR. Materials and methods Observational prospective study of patients undergoing gastrointestinal surgery in a third-level hospital. All patients undergoing general surgery during October 2010 were collected, selecting those with GIR. Demographics (age, sex), before and after admission pharmacological treatment (drug, dosage, drug formulation) and surgery information (site of resection) were collected. A bibliographic research was made to establish how GIR could affect the clinical efficacy of drugs. Results Out of 249 patients undergoing surgery (106 women, 57,6 years (16-90)), 35 (14%) had GIR (mean age 58 years (24-84)). 15 (42,8%) had total/partial colectomy, 14 (40%) partial gastrectomy, 3 (8,6%) rectum resection, 2(5,7%) small bowel resection and 1 (2,9%) oesophagectomy. 7 (20%) patients were treated with oral medication which pharmacological effect may be reduced after GIR: 1(14.7%) had small bowel resection and received hydrochlorothiazide, 6(85.7%) had gastrectomy: one received Metformin which decreases B12 levels and 2 received enalapril and cotrimoxazole respectively which absorption may be decreased. Other 3 patients received drugs formulations which couldn't be absorbed because of the gastrectomy. To avoid a decrease in pharmacological effect patients medication was switched to a correct formulation or to an active substance with an appropriate absorption site. Conclusions There were few patients treated with drugs affected by GIR, however, they should be closely monitored. There is limited and scarce updated literature regarding clinical outcome of drug efficacy in these patients. The authors should keep in mind those patients with GIR and poor pharmacological response.