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Background. Spain is the country with the highest number of health care workers affected by COVID-19 disease in the world. The aim of this study was to describe the epidemiology of SARS-COV-2 infection in HCW at the Gómez Ulla Military Hospital. Methods. A case-control study was conducted during the first outbreak of COVID 19 at GUMH. The study was extended to the total number of HCW in the hospital who met the inclusion criteria. HCW of the GUMH were civilian and military personnel that included Nursing and Medicine students of Spanish Military Academy, Medicine specialty residents and Nursing residents of Medical Surgical Specialty in Operations (EMQO). An ad hoc questionnaire of 33 items was made up. The questionnaire was sent by e-mail to the entire population of study. With this questionnaire personnel were classified into sick (cases) or healthy (controls). Results and Conclusions. 150 professionals answered the questionnaire. Cases were defined as those who tested positive in the diagnostic tests (n=28, 20.7 %) and controls were those who tested negative (n=107, 79.3 %). Therefore, the prevalence of SARS-CoV-2 in the GUMH was 20.7 %. Of the total number of cases, 64.3 % were men (p

Purpose We aimed to elucidate the influence on analgesic effect of genetic polymorphisms in enzymes responsible for biotransformation of tramadol and ibuprofen or other possible genes involved in their mechanism of action. Methods The study population comprised 118 patients from a multicenter, randomized, double-blind, placebo-controlled, Phase III clinical trial that assessed the analgesic efficacy and tolerability of a single dose of ibuprofen (arginine)/tramadol 400/37.5 mg compared with ibuprofen arginine 400 mg alone, tramadol 50 mg alone, and placebo in patients with moderate to severe pain after dental surgery. We analyzed 32 polymorphisms in the cytochrome P450 (CYP) enzymes COMT, ABCB1, SLC22A1, OPRM1, and SLC22A1. Findings We did not find any statistically significant difference among CYP2C9 phenotypes related to ibuprofen response, although CYP2C9 poor metabolizers had a longer effect (higher pain relief at 6 hours). Likewise, we did not find any statistically significant difference among PTGS2 genotypes, contradicting previously publications. Implications There was not a clear effect of CYP2D6 phenotype on tramadol response, although CYP2D6 poor metabolizers had a slower analgesic effect. Concerning the transport of CYP2D6, we observed a better response in individuals carrying ABCB1 mutated alleles, which might correlate with higher tramadol plasma levels. Finally, we found a statistically significant better response in patients carrying the OPRM1 A118G G allele, which contradicts the previous reports. Measuring the active metabolite O-desmethyl-tramadol formation would be of great importance to better evaluate this association because O-desmethyl-tramadol has a higher μ-opioid receptor affinity compared with the parent drug. EudraCT.ema.europa.eu identifier: 2013-004637-33 (Clin Ther. 2021;XX:XXX-XXX) © 2021 Elsevier HS Journals, Inc.

[Background] Concerns have been raised about the possibility that inhibitors of the renin–angiotensin–aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19., [Methods] In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437., [Findings] We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39·0%) were female and the mean age was 69·1 years (SD 15·4), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1·98, 95% CI 1·62–2·41) and risk factors (1·46, 1·23–1·73) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0·94 (95% CI 0·77–1·15). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0·80, 0·64–1·00) or angiotensin-receptor blockers (1·10, 0·88–1·37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0·53, 95% CI 0·34–0·80). The adjusted ORs were similar across severity degrees of COVID-19., [Interpretation] RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19., This study was funded by a research grant from the Institute of Health Carlos III (COV20/00027).

Objective: To determine whether an educational programme could reduce the inappropriate use of albumin. Study design and setting: A hospital albumin working group (San Carlos Clinical Hospital, Madrid, Spain) developed local guidelines for albumin prescribing. After the guidelines were disseminated, all albumin prescriptions were analysed according to these guidelines. Physicians who prescribed albumin for indications other than those in the guidelines were selected for a personalised face-to-face educational programme with a clinical pharmacologists. Adherence to the guidelines was then evaluated compared with an observational period with success being measured in terms of quality of prescribing and economic consequences. The effects of the intervention were assessed again during the intervention (7 months) and after the intervention (in the first 5-month period and in the subsequent year). Main outcomes measures and results: In the observational period, consumption was centralised in medical services and nearly 76% of prescriptions for albumin were inappropriate. During the intervention, the percentage of inappropriate albumin prescribing decreased to 38.8%. Albumin consumption decreased from 444 vials/month during the observational period to 249 vials/month during the intervention, and although the average monthly consumption increased slightly during the 17 months following the intervention, it was similar to that immediately after the intervention. Differences in albumin consumption and quality improvement between the observational period and during the intervention were statistically significant (p < 0.00001). These results led to cost savings of nearly 30% during the intervention and in the follow-up period. Conclusions: This educational programme improved the quality of albumin prescribing and controlled local expenses related to albumin use in a general hospital.

1. 1. Increase of Ca 2+ concentration in the bath solution diminishes the contractile response of isolated rabbit aorta rings to α 1 -adrenoceptor agonists and KCI. 2. 2. In intact preparations the contractions of methoxamine and phenylephrine were maximal when a 0.3- to 0.6-mM Ca 2+ bath solution was used, and those of KCI were maximal with a 2.5-mM Ca 2+ concentration. 3. 3. The contractions of methoxamine and phenylephrine also were decreased by increasing the Ca 2+ concentration above 1.25 mM in disrupted endothelium preparations and in those incubated in indomethacin (10 −5 M), N ω -nitro-L-arginine methyl ester (10 −4 M), or methylene blue (10 −6 M). 4. 4. High organ bath Ca 2+ concentrations also caused a decrease in KCI contractions using endotheliumdenuded and the treated preparations, the responses being similar with 1.25 mM and 2.5-mM Ca 2+ in the methylene blue-treated preparations, whereas they were greater with 1.25 mM Ca 2+ in the others.

Objective: To evaluate the characteristics of using intravenous omeprazole in a university hospital. Method: A prospective follow-up of all patients (n = 108) treated with intravenous omeprazole in our hospital was done from October 1994 through May 1995. Based on requests sent to the pharmacy service, patients receiving this drug were located and their charts were reviewed. The patients were visited daily throughout the duration of their treatment to evaluate any change in dosage, addition of new drugs to the regimen, and the final date of treatment. Results: Only 52% of the patients received omeprazole for indications in which its usefulness is clearly demonstrated. The dosages used frequently exceeded those recommended by the pharmaceutical manufacturer and in the literature. In fact, more than 50% of the patients were treated with dosages over 40 mg/d. It would have been possible to administer omeprazole orally instead of intravenously in 17% of the patients. Twenty-three percent of the patients were treated simultaneously with omeprazole and histamine2-antagonists. Conclusions: The use of intravenous omeprazole in our hospital is not optimal; thus, it seems that a strategy to improve this situation should be designed.

1. 1. TMB-8 (10 −6 M–10 −4 M) depresses the contractile effect of the selective α 1 -adrenoceptor agonists methoxamine and phenylephrine in the isolated rabbit aorta. 2. 2. TMB-8 also depresses contractions evoked by 80 mM KCl in this tissue when used at similar concentrations. 3. 3. The calcium antagonist nifedipine potentiates the inhibitory effect of TMB-8 on the α 1 -contractions. 4. 4. In preparations mounted in Ca-free solution containing 0.5 mM EGTA, 10 −4 M TMB-8 markedly depressed the contractions caused by both α 1 -adrenoceptor agonists. 5. 5. The Ca 2+ agonist BAY K 8644 (10 −6 M) partially prevented the inhibitory effect of TMB-8 on 80 mM KCl contractions.

Background: Paracetamol is often the analgesic or antipyretic of choice, especially for patients for whom salicylates or other nonsteroidal anti-inflammatory drugs are contraindicated. Objective: The aim of this study was to compare the absorption rate of a new tablet formulation of paracetamol (500 mg) with a reference formulation of paracetamol at the same dose. Methods: This was a single-center, Phase I, open-label, randomized, 2-period, crossover, single-dose, comparative bioavailability clinical trial. During both study periods, healthy volunteers were given a single oral dose of a more hydrophilic test formulation of paracetamol, or a reference formulation. Fifteen plasma samples were obtained to determine paracetamol concentrations and to calculate kinetic parameters. Results: The study participants comprised 24 healthy volunteers (12 men, 12 women; mean [SD] age, 22.8 [1.5] years). The pharmacokinetic parameters calculated for the test versus the reference formulation were as follows: median time to maximum concentration (Tmax), 0.42 versus 0.75 hour; mean (SD) maximum plasma drug concentration (Cmax), 9.85 (2.40) μg/mL versus 8.33 (2.22) μg/mL; and mean (SD) area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞), 30.16 (8.87) μg·h/mL versus 28.49 (8.57) μg · h/mL. The 90% CIs of the ratios were as follows: base e logarithm (Ln)-transformed Cmax, 105.08% to 137.59%; Ln-AUC0–∞, 102.02% to 110.43%; and the difference in Tmax, −0.375 to −0.085 hours. Conclusions: The speed of release and absorption was statistically significantly higher with the test formulation compared with the reference one (evaluated using Tmax, Cmax, and Cmax/AUC parameters). This speed is especially important for a rapid analgesic or antipyretic effect.

TMB-8 has been characterized as an inhibitor of the release of Ca2+ from intracellular pools. We have studied the modification of the pressor responses to selective alpha 1-adrenoceptor agonists (methoxamine and phenylephrine), and to selective alpha 2-adrenoceptor agonists (B-HT 920 and B-HT 933) in pithed rats, produced by TMB-8. We have compared this modification with that produced by the calcium antagonist nifedipine. Nifedipine (100 micrograms/kg, 300 micrograms/kg, and 1000 micrograms/kg) inhibited in a dose-dependent manner the pressor responses to the alpha 1- and alpha 2-adrenoceptor agonists, the dose-response curves to the alpha 2-adrenoceptor agonists being shifted further to the right. TMB-8 at a dose of 3000 micrograms/kg did not modify the pressor effects of the alpha 1-adrenoceptor agonists, and neither did it reinforce the inhibition of such responses produced by nifedipine. By contrast, TMB-8 pretreatment (0.03 micrograms/kg, 0.3 micrograms/kg, 3 micrograms/kg, 30 micrograms/kg, 300 micrograms/kg and 3000 micrograms/kg) inhibited the responses to both alpha 2-adrenoceptor agonists, the inhibition being more pronounced with B-HT 920. A similar effect was obtained with 0.03 micrograms/kg TMB-8 and 0.3 microgram/kg TMB-8, particularly in the case of B-HT 920. It was stronger with higher doses, but similar for all doses over 3 micrograms/kg. The inhibition of the pressor responses mediated by the stimulation of alpha 2-adrenoceptors by TMB-8 was less in rats treated with the Ca2+ entry promoter BAY K 8644 (300 micrograms/kg), and could also be reduced by the continuous infusion of CaCl2 (0.25 microgram/min).(ABSTRACT TRUNCATED AT 250 WORDS)

We tested the effect of the selective alpha 2-adrenoceptor agonists B-HT 920 and B-HT 933 on the rabbit aorta. These drugs had weak contractile effects in the tissue, which were inhibited by the selective alpha 1-adrenoceptor antagonist prazosin (10(-5) M). Their contractile effects were potentiated by the Ca2+ channel facilitator BAY K 8644 (10(-6) M). The selective alpha 2-adrenoceptor antagonist yohimbine (10(-5) M) reduced the contractions elicited by B-HT 920 and B-HT 933 in the presence of BAY K 8644 (10(-6) M), but did not alter the control effect of these drugs. In the rabbit aorta, the contractile effect of B-HT 920 and B-HT 933 in the presence of BAY K 8644 (10(-6) M) was partly caused by alpha 1-adrenoceptor stimulation, because prazosin (10(-5) M) relaxed the contractions elicited under these conditions. In the aorta preincubated with BAY K 8644 (10(-6) M) and prazosin (10(-5) M), B-HT 920 (3 x 10(-4) M) elicited non-sustained phasic contractions (1-5 g), which were probably due to alpha 2-adrenoceptor stimulation, as they were inhibited by yohimbine (10(-5) M). In similar experiments B-HT 933 (3 x 10(-4) M) caused inconsistent and slight contractions (0.5 g developed tension).