Multiple adverse drug reactions and genetic polymorphism testing: a case report with negative result

FUNDAMENTO: Los defectos en las vías metabólicas de los medicamentos podrían explicar por qué algunos pacientes tienen antecedentes de múltiples reacciones adversas a los medicamentos (ADR); por lo tanto, nuestro objetivo fue analizar los polimorfismos genéticos en un paciente con ADR múltiple relacionado con fármacos con una vía metabólica hepática común a través de CYP2D6. PREOCUPACIONES DEL PACIENTE: informamos a un paciente con psicosis e hipertensión relacionada con amitriptilina, tramadol y duloxetina en un período de 2 años. INTERVENCIONES Y RESULTADOS: Se realizó una prueba farmacogenética para evaluar el papel causante de la enzima CYP2D6, pero no demostró una deficiencia metabólica. LECCIONES: Aunque resultados negativos en el caso reportado; la tipificación para los polimorfismos de isoenzimas del citocromo P450 podría ser una herramienta de diagnóstico útil en algunos pacientes con antecedentes de ADR múltiple.RATIONALE: Defects in drug metabolic pathways could explain why some patients have a history of multiple adverse drug reactions (ADR); therefore we aimed to analyze genetic polymorphisms in a patient with multiple ADR related to drugs with a common hepatic metabolic pathway through CYP2D6. PATIENT CONCERNS: We report a patient with psychosis and hypertension related to amitriptyline, tramadol, and duloxetine within a 2-year period. INTERVENTIONS AND OUTCOMES: A pharmacogenetic test was performed to assess the causative role of the CYP2D6 enzyme, but did not demonstrate a metabolic deficiency. LESSONS: Although negative results in the reported case; typing for cytochrome P450 isoenzyme polymorphisms could be a useful diagnostic tool in some patients with a history of multiple ADR.peerReviewe

Seguiment d'una cohort d'embarassades exposades a fàrmacs

Objectiu: Analitzar el resultat de la gestació en embarassades exposades a fàrmacs

Medical Students' Opinion of Their Learning Process

The opinion of students is of utmost importance to identify areas of improvement in undergraduate studies. Medical schools would use this information to plan actions to ensure that the students achieve the necessary medical knowledge. The aim of this study was to analyse the opinion of medical students about their learning process and to analyse the influence of their experience according to their year of medical degree. A questionnaire including 21 items, divided into four sections (motivation, theory lectures, hospital internships, and research) and two overall questions, was distributed among eligible 246 students. Each item was scored from 1 (strongly disagree) to 5 (strongly agree). The opinions of intermediate-year students of medical degree (3rd and 4th) were compared to late-year students (5th and 6th). A total of 148 students answered the questionnaire (60.2% response rate). The mean scores for overall student motivation and teaching quality were 6.15 and 7.10, respectively. The student-teacher interaction and new learning technological tools were considered important for student motivation. The only differences found between the two groups of students were that late-year students wished to become part of a medical team and to learn writing scientific papers more than the intermediate-year students. This questionnaire revealed that the year of career had little influence on the medical students' opinion on their learning process during their undergraduate studies. Late-year students rated highest on being more interested in being part of a medical team and their knowledge on writing scientific articles. The use of new technologies and the student-teacher interaction is key to motivate students

Assaig Clínic aleatoritzat de fase I en voluntaris sans per avaluar la seguretat de la vacuna terapèutica antituberculosa RUTI

Es va avaluar la seguretat de quatre dosis diferents (5, 25, 100 i 200 µg de FCMtb) d'una nova vacuna anti-tuberculosa (RUTI) en voluntaris sans comparant-la amb placebo amb un assaig clínic de fase I (n=24), unicèntric, doble cec, emmascarat, aleatoritzat (2:1), controlat amb placebo, seqüencial, d'escalada de dosi, administrant dues dosis de vacuna separades per 28 dies. Noranta-nou % dels esdeveniments adversos van ser lleus. Cefalea, dolor al lloc d'inoculació i fasciculacions van ser els esdeveniments locals més freqüents. Els grups de dosi de 5 i 25 µg de FCMtb van presentar la millor relació benefici/risc, sent d'elecció per a futurs estudis de fase II

Reporting randomised clinical trials of analgesics after traumatic or orthopaedic surgery is inadequate: a systematic review

Background Several randomised clinical trials (RCTs) of analgesics in postoperative pain after traumatic or orthopaedic surgery (TOS) have been published, but no studies have assessed the quality of these reports. We aimed to examine the quality of reporting RCTs on analgesics for postoperative pain after TOS. Methods Reports of RCTs assessing analgesics in postoperative pain after TOS were systematically searched from electronic databases. The quality of reports was assessed using the CONSORT checklist (scoring range from 0 to 22). The quality was considered poor when scoring was 12 or lesser. The publication year and the impact factor of journals were recorded. Results A total of 92 reports of RCTs were identified and 69 (75%) scored 12 or lesser in CONSORT checklist (range 5-17). The mean (SD) CONSORT score of all reports was 10.6 (2.7). Missing CONSORT items included primary and secondary outcome measures (11%), the specific objectives and hypothesis definition (12%), the sample size calculation (12%), the dates defining the periods of recruitment (12%), the discussion of external validity of findings (14%), the allocation sequence generation (24%), and the interpretation of potential bias or imprecision of results (25%). There was a little improvement in CONSORT scores over time (r = 0.62; p < 0.001) and with impact factor of journals (r = 0.30; p < 0.001). Conclusion Quality of reporting RCTs on analgesics after TOS is poor. Reporting of those RCTs should be improved according to methodological standard checklists in the next years

Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection : A Spanish, Multicenter, Cohort Study

We aimed to determine the impact of tocilizumab use on severe COVID-19 (coronavirus disease 19) pneumonia mortality. We performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by inverse probability of the treatment weights (IPTW). Tocilizumab's effect in patients receiving steroids during the 48 h following inclusion was analysed. During the study period, 506 patients with severe COVID-19 fulfilled the inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days [interquartile range (IQR) 8-14]. Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls: 16.8% versus 31.5%, hazard ratio (HR) 0.514 [95% confidence interval (95% CI) 0.355-0.744], p < 0.001; weighted HR 0.741 (95% CI 0.619-0.887), p = 0.001. Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment [relative risk reduction (RRR) 46.7%]. We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in those treated with tocilizumab than in those treated with steroids alone [10.9% versus 40.2%, HR 0.511 (95% CI 0.352-0.741), p = 0.036; weighted HR 0.6 (95% CI 0.449-0.804), p < 0.001] (interaction p = 0.094). These results show that survival of patients with severe COVID-19 is higher in those treated with tocilizumab than in those not treated and that tocilizumab's effect adds to that of steroids administered to non-intubated patients with COVID-19 during the first 48 h of presenting with respiratory failure despite oxygen therapy. Randomised controlled studies are needed to confirm these results. European Union electronic Register of Post-Authorization Studies (EU PAS Register) identifier, EUPAS34415 The online version of this article (10.1007/s40121-020-00373-8) contains supplementary material, which is available to authorized users

Safety and effectiveness of CIMAvax-EGF administered in community polyclinics

In spite of the advances in immunotherapy and targeted therapies, lung cancer continues to be the leading cause of cancer-related death. The epidermal growth factor receptor is an established target for non-small cell lung cancer (NSCLC), and its overactivation by the ligands can induce accelerated proliferation, angiogenesis, and metastasis as well as proinflammatory or immunosuppressive signals. CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy that is approved for the treatment of NSCLC patients in Cuba. The study was designed as a phase IV trial to characterize the safety and effectiveness of CIMAvax-EGF in advanced NSCLC patients treated in 119 community polyclinics and 24 hospitals. CIMAvax-EGF treatment consisted of four bi-weekly doses followed by monthly boosters. Overall, 741 NSCLC patients ineligible for further cancer-specific treatment were enrolled. CIMAvax-EGF was safe, and the most common adverse events consisted of mild-to-moderate injection site reactions, fever, chills, tremors, and headache. For patients completing the loading doses, the median survival was 9.9 months. For individuals achieving at least stable disease to the frontline and completing vaccination induction, the median survival was 12 months. Most of the functional activities and symptoms evaluated through the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire improved over time. In conclusion, this real-world trial demonstrated that CIMAvax-EGF was safe and effective in patients who were vaccinated in the maintenance scenario. A larger effect was seen in subjects with poor prognosis like those with squamous tumors and high EGF levels. Remarkably, this community-based intervention was very important because it demonstrated the feasibility of treating advanced lung cancer patients with active immunotherapy in primary care institutions. In addition to CIMAvax-EGF, patients received supportive care at the community clinic. Vaccine administration by the family doctors at the polyclinics reduced the patients’ burden on the medical oncology services that continued providing chemotherapy and other complex therapies. We conclude that community polyclinics constitute the optimal scenario for administering those cancer vaccines that are safe and require prolonged maintenance in patients with advanced cancer, despite the continuous deterioration of their general condition.Clinical trial registrationhttps://rpcec.sld.cu/trials/RPCEC00000205-En, identifier RPCEC00000205

Pharmacoepidemiology : An Overview

The aims of this review are to provide a comprehensive overview of the definition and scope of pharmacoepidemiology, to summarize the study designs and methodologies used in the field, to discuss the future trends in the field and new methodologies to address bias and confounding, and finally to give some recommendations to clinicians interested in pharmacoepidemiologic research. Because drug efficacy and safety from randomized clinical trials do not reflect the real-world situation, pharmacoepidemiological studies on drug safety monitoring and drug effectiveness in large numbers of people are needed by healthcare professionals and regulatory institutions. We aim to highlight the importance of pharmacoepidemiologic research in informing evidence-based medicine and public health policy. The development of new designs and methodologies for the generation of valid evidence, as well as new initiatives to provide guidance and recommendations on how to incorporate real-world evidence into the drug development process, are reported on. In addition, we have touched on the implication of artificial intelligence in the management of real-world data. This overview aims to summarize all important aspects to consider when conducting or interpreting a pharmacoepidemiologic study

Evidència científica del tractament farmacològic del dolor postoperaori en cirurgia ortopèdica i/o traumatològica i de l'espasticitat per malaltia neurològica no progressiva

S'han realitzat dues revisions sistemàtiques de dos símptomes molt freqüents i ben caracteritzats en l'àrea de Traumatologia i Rehabilitació que són el dolor postoperatori, secundari a cirurgia ortopèdica i/o traumatològica (COT), i l'espasticitat, relacionada amb la malaltia neurològica no progressiva (MNNP).-Revisió sistemàtica del tractament amb analgèsics en el dolor postoperatori per COT:Objectiu: avaluar els fàrmacs analgèsics en el tractament del dolor postoperatori per COTDisseny: revisió sistemàtica d'assaigs clínics (AC) aleatoritzats Font de les dades: PubMed, EMBASE, The Cochrane Library i cerques manualsSelecció dels estudis: AC aleatoritzats d'analgèsics administrats per via oral, intramuscular, cubcutània o rectal, comparats amb altres analgèsics o placebo, en pacients sotmesos a COT. Es van avaluar els dissenys dels estudis, les característiques de la població en estudi, els fàrmacs analgèsics avaluats, les puntuacions de la intensitat del dolor i de la milloria del dolor i els esdeveniments adversos.Resultats: es van incloure 92 AC aleatoritzats (9.596 pacients). Quaranta dos (46%) van ser controlats amb placebo i 50 (54%) eren comparacions directes entre no opiacis, opiacis i/o combinacions d'ambdós. La mitjana d'edat dels pacients (de) va ser de 49 anys (18). En la majoria dels AC l'ulcus gastro-intestinal i les malalties del hepàtiques i renals van ser criteris d'exclusió. Només en 30 AC (33%) el cegament va se doble i es van descriure resultats de les variables d'intensitat i milloria del dolor; 19 d'aquests van ser de dosi única, i el seguiment de l'efecte analgèsic no va ser superior a 12 hores en 23 (77%). En general, només 9 AC (10%) van ser amb cegament doble, van descriure les pèrdues i/o retirades, van realitzar anàlisis per intenció de tractar i van descriure la magnitud de l'efecte.Conclusió: l'evidència dels AC aleatoritzats en el tractament del dolor postoperatori per COT per a la presa de decisions clínicques és inadequada. L'avaluació dels analgèsics en el dolor postoperatori per COT s'ha de basar en variables clínicament rellevants, en pacients representatius i amb períodes d'observació més llargs. A més a més, cal incloure comparacions directes entre el fàrmac d'estudi amb diferents fàrmacs i pautes d'administració. -Revisió sistemàtica dels fàrmacs oral pel tractament de l'espasticitat en pacients amb MNNP:Objectiu: Avaluar l'eficàcia dels fàrmacs orals en el tractament de l'espasticitat en pacients amb MNNPDisseny: revisió sistemàtica d'assaigs clínics (AC) aleatoritzats i amb cegament dobleFont de les dades: PubMed, EMBASE, The Cochrane Library i cerques manualsResultats: es van incloure 12 estudis (469 pacients), 6 en ictus, 3 en lesió medul·lar i 3 en paràlisi cerebral. La tizanidina es va avaluar en 4 AC (276 pacients, 142 exposats), el dantrolè en 4 (103, 93), el baclofèn en 3 (70, 55), el diazepam en 2 (127, 76) i la gabapentina en un (28, tots exposats). La majoria dels AC eren fets amb pocs pacients, durant un curt període de temps i llur qualitat metodològica inadequada. Deu AC van ser controlats amb placebo i només 2 eren comparacions directes entre els fàrmacs. Les variables d'eficàcia avaluades van ser heterogènies. Només 4 articles van descriure la magnitud de l'efecte antiespàstic. La incidència d'esdeveniments adversos (mareig, sedació i debilitat muscular) va ser alta.Conclusió: l'evidència en l'eficàcia dels fàrmacs orals pel tractament de l'espasticitat en la MNNP és dèbil i no inclou l'avaluació de la qualitat de vida dels pacients. En cas de que hi hagi alguna eficàcia, aquesta és marginal. Els esdeveniments adversos van ser freqüents. Calen millors instruments metodològics per a l'avaluació del tractament de l'espasticitat.Two systematic review have been done about two very usual symptoms treated in the Traumatology and Rehabilitation area. Those symptoms are the postoperative pain after traumatic and orthopaedic surgery (TOS), and the spasticity in patients with non-progressive neurological disease.-Systematic review of analgesic drugs in the treatment of the postoperative pain after TOSObjective: To assess analgesic drugs in the treatment of postoperative pain after TOS.Design: Systematic review of randomised clinical trials (RCTs). Data sources: Electronic PubMed, EMBASE, The Cochrane Library, and hand searches.Study selection: RCTs of analgesics administered by oral, intramuscular, intravenous, subcutaneous or rectal route, compared to other analgesics or placebo, in patients under TOS. Study design, characteristics of the study population, analgesic drugs tested, pain intensity and pain relief scores, and adverse effects were assessed. Results: 92 RCTs (9,596 patients) met our inclusion criteria. Forty-two (46%) were placebo-controlled, and 50 (54%) were direct comparisons between non-opioid, opioid, and/or combinations of both. Patients' mean age (SD) was 49 years (18). In most trials, gastrointestinal ulcer, liver and renal diseases were exclusion criteria. Only 30 trials (33%) were double-blind and reported standardised outcomes of pain intensity and pain relief; 19 of these were single-dose, and follow up of analgesic effects lasted no more than 12 hours in 23 (77%). Globally, only nine trials (10%) were double blind, described dropouts or withdrawals, performed analysis by intention to treat, and reported the effects magnitude. Conclusion: Evidence from RCTs on the treatment of postoperative pain after TOS is inadequate for clinical decision making. Assessment of analgesics in pain after TOS should be based on agreed clinically relevant outcomes, in representative patients, and for longer observation periods. In addition, it should include direct comparisons between candidate drugs or their combinations and between various drug administration schedules.-Systematic review of oral antispastic drugs in the treatment of spasticity in patients with non-progressive neurological disease.Objective: To assess the efficacy of oral drugs in the treatment of spasticity in patients with non-progressive neurological disease (NPND). Design: Systematic review of double-blind randomised controlled trials.Data sources: electronic MEDLINE, PubMed, Cochrane Library and hand searches. Results: Twelve studies (469 patients) were included (6 on stroke, 3 on spinal cord diseases, and 3 on cerebral palsy). Tizanidine was assessed in four trials (276 patients, 142 exposed), dantrolene in four (103, 93), baclofen in three (70, 55), diazepam in two (127, 76), and gabapentin in one (28, all exposed). Most trials were of small size, of short duration and their methodological quality was inadequate. Ten trials were controlled with placebo and only two were direct comparisons between drugs. Efficacy outcome variables were heterogeneous. Only four reports described the magnitude of the anti-spastic effect. The incidence of adverse drug effects (drowsiness, sedation and muscle weakness) was high. Conclusion: Evidence on the efficacy of oral anti-spastic drugs in NPND is weak and does not include evaluation of patients' quality of life. If any, efficacy is marginal. Adverse drug reactions were common. Better methodological instruments are needed for the evaluation of anti-spastic treatment

Pharmacoepidemiology: An Overview

The aims of this review are to provide a comprehensive overview of the definition and scope of pharmacoepidemiology, to summarize the study designs and methodologies used in the field, to discuss the future trends in the field and new methodologies to address bias and confounding, and finally to give some recommendations to clinicians interested in pharmacoepidemiologic research. Because drug efficacy and safety from randomized clinical trials do not reflect the real-world situation, pharmacoepidemiological studies on drug safety monitoring and drug effectiveness in large numbers of people are needed by healthcare professionals and regulatory institutions. We aim to highlight the importance of pharmacoepidemiologic research in informing evidence-based medicine and public health policy. The development of new designs and methodologies for the generation of valid evidence, as well as new initiatives to provide guidance and recommendations on how to incorporate real-world evidence into the drug development process, are reported on. In addition, we have touched on the implication of artificial intelligence in the management of real-world data. This overview aims to summarize all important aspects to consider when conducting or interpreting a pharmacoepidemiologic study