Suspected adverse events following immunization against SARS-CoV2 in a university hospital in 2021: Observational study

Aim: Vaccination against SARS-CoV2 has been proposed as a fundamental element for the control of the pandemic. This study aimed to describe the suspected adverse reactions (ADR) reported by vaccinated hospital workers. Methods: A descriptive study of suspected ADR was conducted between January and March 2021. The suspected ADR were identified using a specifically designed electronic form and spontaneous reporting. Data were also collected regarding the characteristics of the professionals, vaccine administered, severity, and outcome of ADR. Results: 8169 professionals received 2 doses of SARS-CoV2 vaccine (6672 Comirnaty (R) and 1497 Spikevax (R)) and 894 reports of suspected ADR were reported (762 for Comirnaty (R) and 132 for Spikevax (R)), resulting in a cumulative ADR incidence of 10.94% (95%CI: 10.27-11.62). The majority of ADR were reported only after the second dose, 497 (56.2%), while 211 (23.6%) were reported only after the first dose and 186 (21%) after both doses. The symptoms were mostly mild, did not require medical assistance, and disappeared within approximately 3 days. One hundred and seventeen professionals had a history of COVID-19 infection. These studies reported, statistically significant, more suspected ADR after the first dose (42.7%) than those with no history of COVID-19 (20.7%). Among professionals, more ADR occurred after the first dose with the Spikevax (R) vaccine (41.6%) than with the Comirnaty (R) vaccine (20.5%). Conclusion: The majority of suspected ADR reported were described in the summary of product characteristics (SmPC). Professionals with a history of COVID-19 reported more suspected ADR after the first dose than did those without a history

Clinical consequences of BRCA2 hypomorphism

Altres ajuts: Asociación Española contra el Cáncer (LABAE16020PORTT)Altres ajuts: Asociación Española contra el Cáncer (ERAPERMED2019-215)The tumor suppressor FANCD1/BRCA2 is crucial for DNA homologous recombination repair (HRR). BRCA2 biallelic pathogenic variants result in a severe form of Fanconi anemia (FA) syndrome, whereas monoallelic pathogenic variants cause mainly hereditary breast and ovarian cancer predisposition. For decades, the co-occurrence in trans with a clearly pathogenic variant led to assume that the other allele was benign. However, here we show a patient with biallelic BRCA2 (c.1813dup and c.7796 A > G) diagnosed at age 33 with FA after a hypertoxic reaction to chemotherapy during breast cancer treatment. After DNA damage, patient cells displayed intermediate chromosome fragility, reduced survival, cell cycle defects, and significantly decreased RAD51 foci formation. With a newly developed cell-based flow cytometric assay, we measured single BRCA2 allele contributions to HRR, and found that expression of the missense allele in a BRCA2 KO cellular background partially recovered HRR activity. Our data suggest that a hypomorphic BRCA2 allele retaining 37-54% of normal HRR function can prevent FA clinical phenotype, but not the early onset of breast cancer and severe hypersensitivity to chemotherapy

Efficacy and safety clinical trial with efavirenz in patients diagnosed with adult Niemann-pick type C with cognitive impairment

Background:Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca (R)) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46. Methods:This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters. Discussion:NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz's capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression

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

Ús dels sistemes d’informació essencial en terapèutica

JUSTIFICACIÓ La informació sobre medicaments i terapèutica és un element central generador de coneixement i indispensable en el procés de prescripció raonada. El metge necessita disposar de les eines adequades per a gestionar el coneixement en la presa de decisions clíniques. La gestió de la informació científica implica identificar, seleccionar, analitzar, i difondre aquella que es pot considerar més rellevant. En una època d’excés d’informació, cal prioritzar i seleccionar aquella més rellevant i oferir les eines que permetin al metge la millor gestió de la informació i el coneixement. OBJECTIU I MÈTODE Els objectius d’aquest treball han estat examinar el contingut de la base de dades SIETES i l’evolució en el període 2000-2014. S’ha analitzat el contingut a partir de les paraules clau de la base, les publicacions utilitzades i l’ús per part dels usuaris (període 2013-2015) Per a cada grup s’ha dut a terme una anàlisi global del contingut i de l’evolució temporal, i s’ha comparat el global amb les cites qualificades com a notables o excel·lents. RESULTATS En el període d’estudi es van incloure 45.242 cites de les quals un 51% amb resum o comentari. Un total de 3.868 es van considerar notables o excel·lents (90% amb resum). La paraula clau més utilitzada va ser Ensayo clínico seguida de Efectos Indeseados. El terme Estudios observacionales va ser el tercer descriptor més freqüent. Això reflecteix un interès per la Medicina basada en proves i en basar el raonament causal en terapèutica en els seus principis. La cardiologia va ser l’especialitat més citada. En l’anàlisi de l’evolució temporal, les infeccioses van mostrar l’augment més marcat, probablement associat a l’aparició els darrers anys dels nous tractaments per a l’hepatitis C. Els antidepressius i els hipocolesterolemiants es van citar en un 25% dels articles introduïts. Els fàrmacs més esmentats van ser l’AAS, rofecoxib i warfarina. Un 90% de les fonts utilitzades per seleccionar els articles van ser revistes. No obstant, entre el 2000 i el 2014 es va veure un augment important de les revistes electròniques i els butlletins com a fonts d’informació. La nova web de SIETES, ha permès augmentar la visibilitat del seu contingut Actualment, prop d’un 70% dels accessos provenen de Google, bé a través d’una cita concreta o un vincle compartit. L’anàlisi del comportament dels usuaris de SIETES va mostrar una certa discordança amb les prioritats dels continguts de la base. En els tres anys de l’anàlisi de l’utilització, l’ús del mòbil com a dispositiu es va triplicar. CONCLUSIONS La tesi proporciona informació sobre el que s’ha considerat essencial en terapèutica durant els darrers 15 anys. En aquest sentit, la principal aportació de SIETES és haver estat un observatori crític de les principals novetats en terapèutica i una eina de selecció de la informació. Els resultats confirmen el valor de SIETES com a sistema de suport a la individualització del tractament i per a promoure una prescripció raonada i reforcen la importància d’aquest i altres sistemes com a activitats prioritàries de la farmacologia clínica. No obstant, l’hegemonia progressiva d’internet i les xarxes socials com a medi d’intercanvi d’informació mostren un nou escenari i plantegen la necessitat d’una evolució en la manera de transmetre i compartir la informació.RATIONALE Information about drugs and therapeutics is a central part of knowledge process and rational prescribing. Doctor needs to have the best tools to manage knowledge in clinical decision making. Scientific information management involves identifying, selecting, analyzing, and disseminating that can be considered essential. In an era of information overload, it’s important to prioritize and select those most relevant and provide the tools that allow the physician to better manage information and knowledge. OBJECTIVES AND METHOD The objectives of this study were to examine the contents of SIETES database and its evolution between years 2000 to 2014. We have analyzed its content based on keywords included and publications used to select the articles. We also analyzed users behaviour (period 2013-2015). For each group of keywords, it has been compared overall content with those references qualified as remarkable or excellent. RESULTS During the study period there were included 45.242 citations of which 51% with summary or comment. A total of 3.868 were considered remarkable or excellent (90% with a summary). The keywords “clinical trial” and “adverse effects” were most used. The term “observational study” was the third most common descriptor. This reflected an interest in evidence-based medicine and causal reasoning based on their therapeutic principles. Cardiology as a specialty was the most cited. Regarding the analysis of temporal evolution, infectious showed more marked increase, probably associated with new treatments for hepatitis C. Antidepressants and hypolipemiants were cited by 25% of the items included. The drugs most frequently mentioned were acetylsalicylic acid, rofecoxib and warfarin. About 90% of the sources used to select the articles were medical journals. However, between 2000 and 2014 there was a significant increase of electronic journals and drug bulletins as sources of information. From 2013, SIETES new website, has allowed to increase contents visibility. Currently, about 70% of accesses of users come from Google, either through a specific item or a shared link. The analysis of user’s behaviour also showed some disagreement with priorities reflected in database contents. Mobile use as a device has tripled between 2013 and 2015. CONCLUSIONS This work provides information about what has been considered essential in therapy over the last 15 years. In this sense, the main contribution of SIETES database has been to represent a critical watchdog of the major therapeutic innovations in tool selection and therapeutic information. The results confirm the value of SIETES as a support system for individualization of treatment, to promote rational prescribing and to reinforce the value as priority activities in clinical pharmacology. However, the gradual hegemony of the Internet and social networks as a means of information exchange shows a new stage and raised the need for an evolution in the way of transmitting and sharing information

Supportive and palliative care: Experience at the Institut Jules Bordet

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Ús dels sistemes d'informació essencial en terapèutica

JUSTIFICACIÓ La informació sobre medicaments i terapèutica és un element central generador de coneixement i indispensable en el procés de prescripció raonada. El metge necessita disposar de les eines adequades per a gestionar el coneixement en la presa de decisions clíniques. La gestió de la informació científica implica identificar, seleccionar, analitzar, i difondre aquella que es pot considerar més rellevant. En una època d'excés d'informació, cal prioritzar i seleccionar aquella més rellevant i oferir les eines que permetin al metge la millor gestió de la informació i el coneixement. OBJECTIU I MÈTODE Els objectius d'aquest treball han estat examinar el contingut de la base de dades SIETES i l'evolució en el període 2000-2014. S'ha analitzat el contingut a partir de les paraules clau de la base, les publicacions utilitzades i l'ús per part dels usuaris (període 2013-2015) Per a cada grup s'ha dut a terme una anàlisi global del contingut i de l'evolució temporal, i s'ha comparat el global amb les cites qualificades com a notables o excel·lents. RESULTATS En el període d'estudi es van incloure 45.242 cites de les quals un 51% amb resum o comentari. Un total de 3.868 es van considerar notables o excel·lents (90% amb resum). La paraula clau més utilitzada va ser Ensayo clínico seguida de Efectos Indeseados. El terme Estudios observacionales va ser el tercer descriptor més freqüent. Això reflecteix un interès per la Medicina basada en proves i en basar el raonament causal en terapèutica en els seus principis. La cardiologia va ser l'especialitat més citada. En l'anàlisi de l'evolució temporal, les infeccioses van mostrar l'augment més marcat, probablement associat a l'aparició els darrers anys dels nous tractaments per a l'hepatitis C. Els antidepressius i els hipocolesterolemiants es van citar en un 25% dels articles introduïts. Els fàrmacs més esmentats van ser l'16S, rofecoxib i warfarina. Un 90% de les fonts utilitzades per seleccionar els articles van ser revistes. No obstant, entre el 2000 i el 2014 es va veure un augment important de les revistes electròniques i els butlletins com a fonts d'informació. La nova web de SIETES, ha permès augmentar la visibilitat del seu contingut Actualment, prop d'un 70% dels accessos provenen de Google, bé a través d'una cita concreta o un vincle compartit. L'anàlisi del comportament dels usuaris de SIETES va mostrar una certa discordança amb les prioritats dels continguts de la base. En els tres anys de l'anàlisi de l'utilització, l'ús del mòbil com a dispositiu es va triplicar. CONCLUSIONS La tesi proporciona informació sobre el que s'ha considerat essencial en terapèutica durant els darrers 15 anys. En aquest sentit, la principal aportació de SIETES és haver estat un observatori crític de les principals novetats en terapèutica i una eina de selecció de la informació. Els resultats confirmen el valor de SIETES com a sistema de suport a la individualització del tractament i per a promoure una prescripció raonada i reforcen la importància d'aquest i altres sistemes com a activitats prioritàries de la farmacologia clínica. No obstant, l'hegemonia progressiva d'internet i les xarxes socials com a medi d'intercanvi d'informació mostren un nou escenari i plantegen la necessitat d'una evolució en la manera de transmetre i compartir la informació.RATIONALE Information about drugs and therapeutics is a central part of knowledge process and rational prescribing. Doctor needs to have the best tools to manage knowledge in clinical decision making. Scientific information management involves identifying, selecting, analyzing, and disseminating that can be considered essential. In an era of information overload, it's important to prioritize and select those most relevant and provide the tools that allow the physician to better manage information and knowledge. OBJECTIVES AND METHOD The objectives of this study were to examine the contents of SIETES database and its evolution between years 2000 to 2014. We have analyzed its content based on keywords included and publications used to select the articles. We also analyzed users behaviour (period 2013-2015). For each group of keywords, it has been compared overall content with those references qualified as remarkable or excellent. RESULTS During the study period there were included 45.242 citations of which 51% with summary or comment. A total of 3.868 were considered remarkable or excellent (90% with a summary). The keywords "clinical trial" and "adverse effects" were most used. The term "observational study" was the third most common descriptor. This reflected an interest in evidence-based medicine and causal reasoning based on their therapeutic principles. Cardiology as a specialty was the most cited. Regarding the analysis of temporal evolution, infectious showed more marked increase, probably associated with new treatments for hepatitis C. Antidepressants and hypolipemiants were cited by 25% of the items included. The drugs most frequently mentioned were acetylsalicylic acid, rofecoxib and warfarin. About 90% of the sources used to select the articles were medical journals. However, between 2000 and 2014 there was a significant increase of electronic journals and drug bulletins as sources of information. From 2013, SIETES new website, has allowed to increase contents visibility. Currently, about 70% of accesses of users come from Google, either through a specific item or a shared link. The analysis of user's behaviour also showed some disagreement with priorities reflected in database contents. Mobile use as a device has tripled between 2013 and 2015. CONCLUSIONS This work provides information about what has been considered essential in therapy over the last 15 years. In this sense, the main contribution of SIETES database has been to represent a critical watchdog of the major therapeutic innovations in tool selection and therapeutic information. The results confirm the value of SIETES as a support system for individualization of treatment, to promote rational prescribing and to reinforce the value as priority activities in clinical pharmacology. However, the gradual hegemony of the Internet and social networks as a means of information exchange shows a new stage and raised the need for an evolution in the way of transmitting and sharing information

Protein production from recombinant protein bodies

In this study, we describe a process for protein expression and purification from plants and insect cells based on the accumulation of recombinant proteins in protein bodies. This technology is using Zera®, which sequence has the capacity to trigger in vivo the formation of dense, non-secretory storage protein body-like organelles derived from the endoplasmic reticulum (ER). With this method, recombinant human growth hormone (hGH) was expressed and purified from protein bodies accumulated in plants (Nicotiana benthamiana) and in insect cells (Spodoptera frugiperda). We found that recombinant Zera-hGH are stored in large quantity inside those proteins bodies and can be easily recovered during a one-step process from plant and insect cell biomass. After solubilization of recombinant protein bodies and cleavage of Zera tag from the fusion protein, active hGH was finally purified by a single chromatography step. These results indicate that recombinant proteins derived from Zera-fusion could provide both an efficient protein production system and eased purification downstream process.ILL and FW are recipient of a Torres Quevedo postdoctoral grant (Ministerio de Ciencia e Innovación), and RP is a recipient of an AGAUR grant (2006FI02015). This work was supported by the CIDEM and CeRBA-SGR00182 (Generalitat de Catalunya) and ERA Biotech.Peer reviewe

Efficacy and safety clinical trial with efavirenz in patients diagnosed with adult Niemann-pick type C with cognitive impairment

Background: Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca®) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46. Methods: This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters. Discussion: NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz’s capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression