Safety of Drugs Used during the First Wave of COVID-19: A Hospital-Registry-Based Study

COVID-19; Adverse drug reactions; HydroxychloroquineCOVID-19; Reaccions adverses als medicaments; HidroxicloroquinaCOVID-19; Reacciones adversas a los medicamentos; HidroxicloroquinaThe emergency of the coronavirus disease 2019 (COVID-19) pandemic led to the off-label use of drugs without data on their toxicity profiles in patients with COVID-19, or on their concomitant use. Patients included in the COVID-19 Patient Registry of a tertiary hospital during the first wave were analyzed to evaluate the adverse drug reactions (ADRs) with the selected treatments. Twenty-one percent of patients (197 out of 933) had at least one ADR, with a total of 240 ADRs. Patients with ADRs were more commonly treated with multiple drugs for COVID-19 infection than patients without ADRs (p < 0.001). They were younger (median 62 years vs. 70.1 years; p < 0.001) and took less medication regularly (69.5% vs. 75.7%; p = 0.031). The most frequent ADRs were gastrointestinal (67.1%), hepatobiliary (10.8%), and cardiac disorders (3.3%). Drugs more frequently involved included lopinavir/ritonavir (82.2%), hydroxychloroquine (72.1%), and azithromycin (66.5%). Although most ADRs recovered without sequelae, fatal cases were described, even though the role of the disease could not be completely ruled out. In similar situations, efforts should be made to use the drugs in the context of clinical trials, and to limit off-label use to those drugs with a better benefit/risk profile in specific situations and for patients at high risk of poor disease prognosis

Tesi doctoral: factors pronòstics en la pèrdua visual en l’arteritis de cèl·lules gegants

L’arteritis de cèl·lules gegants és la vasculitis més freqüent en persones majors de 50 anys. Es classifica segons els criteris de Hunder (1990), essent la cefalea el símptoma més freqüent. L’afectació vascular s’ha estudiat de forma extensa amb diferents proves d’imatge i amb la biòpsia de l’artèria temporal, havent-se suggerit que existeixen dos subtipus de la malaltia. Es coneix que una proporció elevada de pacients presenta aortitis i que aquesta s’associa a una major dosi acumulada de corticoides i a un major risc d’aneurisma d’aorta toràcica. Per altra banda, l’afectació ocular constitueix la complicació més temuda en l’actualitat, ja que un cop instaurada no és reversible. L’objectiu d’aquest treball va ser identificar quins són els patrons de captació per PET/TC en el moment del diagnòstic de l’ACG d’acord amb la presència o absència de clínica isquèmica, incloent l’afectació ocular. A més, s’estudià quins eren els patrons clínics i histològics en aquesta cohort de pacients d’acord a la presència o absència d’aortitis en el PET/TC. En el primer estudi, realitzat amb una cohort de pacients amb ACG de nou diagnòstic, s’inclogueren 30 pacients i s’objectivà que els pacients amb clínica isquèmica presentaven una major proporció d’afectació d’artèries vertebrals (OR 5.0, IC 95%: 0.99 – 24.86, p=0.051). Aquests pacients, en canvi, presentaven una menor proporció d’afectació d’artèries de gran cabal, essent l’aortitis un factor protector tant per la clínica isquèmica, en global (OR 19.0, IC 95%: 2.79 – 127.97, p=0.001), com per la pèrdua de visió permanent (OR 10.67, IC 95%: 1.12 – 101.34, p=0.04). En aquesta cohort, la presència de símptomes isquèmics s’associà a patrons de PET/TC diferenciats (p=0.001). En el segon estudi es demostrà que els pacients amb aortitis eren més joves (69.9 anys vs. 83.7 anys, p=0.04) i presentaven menys freqüentment clínica isquèmica, incloent clínica ocular (25.0% en els pacients amb aortitis vs. 84.2% en els pacients sense aortitis, p=0.006). La presència de cèl·lules gegants multinucleades en la biòpsia de l’artèria temporal s’associà de forma independent a la presència d’aortitis en el PET/TC (OR 12.23, p=0.046). En el grup de pacients amb aortitis no s’objectivà halo en el Doppler d’artèria temporal en cap cas. Així, podem concloure que el PET/TC és una eina útil en el diagnòstic de l’ACG, que permet identificar dos patrons de captació vascular diferents d’acord a la presència o absència de clínica isquèmica al diagnòstic de l’ACG. Així mateix, la presència d’aortitis en el PET/TC s’associa amb la presencia de cèl·lules gegants multinucleades en la biòpsia.Giant cell arteritis is the most frequently diagnose vasculitis among patients older than 50 years. Classification is done by Hunder criteria (1990). Headache is the most frequent symptom. Vascular involvement has been extensively studied by imaging techniques, including temporal artery biopsy, suggesting the existence of two different clinical subsets of the disease. Evidence suggests that a high proportion of patients present with aortitis and that this situation is associated to a higher corticosteroid dose requirement and a higher risk of developing aortic aneurisms. Moreover, ocular involvement is the most feared complication nowadays as it is usually irreversible. The objective of this study was to identify different patterns of vascular involvement on PET/CT at GCA diagnosis according to the presence or absence of ischaemic manifestations at disease onset, including ocular involvement. Furthermore, we sought to describe clinical and histological patterns on TAB according to the presence or absence of aortitis in PET/CT. In the first study, performed with a cohort that comprised 30 patients with a newly diagnosed GCA, patients with ischaemic symptoms showed a higher proportion of vertebral involvement when compared to those patients without these symptoms (OR 5.0, CI 95%: 0.99 – 24.86, p=0.051). Patients with ischaemic manifestations showed a lower proportion of large vessel vasculitis, being aortitis a protector factor against ischaemic manifestations (OR 19.0, CI 95%: 2.79 – 127.97, p=0.001) and against permanent visual loss (OR 10.67, CI 95%: 1.12 – 101.34, p=0.04). In this cohort, the presence or absence of ischaemic symptoms was associated to different vascular patterns of PET/TC (p=0.001). In the second study we showed that patients with aortitis were younger (69.9 years vs. 83.7 years, p=0.04) and had less frequently ischaemic manifestations, including ocular involvement (25.0% of patients with aortitis vs. 84.2% of patients without aortitis, p=0.006). The presence of giant multinucleated cells on TAB was an independent risk factor for the presence of aortitis on PET/CT (OR 12.23, p=0.046). The halo sign was absent in patients with aortitis. We can conclude that PET/CT is a useful technique at GCA diagnosis that allows identifying two patterns of vascular involvement according to the presence or absence of ischaemic symptoms. When we compared PET/CT and TAB findings, we identified that aortitis was related to the presence of giant multinucleated cells

Tesi doctoral : factors pronòstics en la pèrdua visual en l'arteritis de cèl·lules gegants

L'arteritis de cèl·lules gegants és la vasculitis més freqüent en persones majors de 50 anys. Es classifica segons els criteris de Hunder (1990), essent la cefalea el símptoma més freqüent. L'afectació vascular s'ha estudiat de forma extensa amb diferents proves d'imatge i amb la biòpsia de l'artèria temporal, havent-se suggerit que existeixen dos subtipus de la malaltia. Es coneix que una proporció elevada de pacients presenta aortitis i que aquesta s'associa a una major dosi acumulada de corticoides i a un major risc d'aneurisma d'aorta toràcica. Per altra banda, l'afectació ocular constitueix la complicació més temuda en l'actualitat, ja que un cop instaurada no és reversible. L'objectiu d'aquest treball va ser identificar quins són els patrons de captació per PET/TC en el moment del diagnòstic de l'ACG d'acord amb la presència o absència de clínica isquèmica, incloent l'afectació ocular. A més, s'estudià quins eren els patrons clínics i histològics en aquesta cohort de pacients d'acord a la presència o absència d'aortitis en el PET/TC. En el primer estudi, realitzat amb una cohort de pacients amb ACG de nou diagnòstic, s'inclogueren 30 pacients i s'objectivà que els pacients amb clínica isquèmica presentaven una major proporció d'afectació d'artèries vertebrals (OR 5.0, IC 95%: 0.99 - 24.86, p=0.051). Aquests pacients, en canvi, presentaven una menor proporció d'afectació d'artèries de gran cabal, essent l'aortitis un factor protector tant per la clínica isquèmica, en global (OR 19.0, IC 95%: 2.79 - 127.97, p=0.001), com per la pèrdua de visió permanent (OR 10.67, IC 95%: 1.12 - 101.34, p=0.04). En aquesta cohort, la presència de símptomes isquèmics s'associà a patrons de PET/TC diferenciats (p=0.001). En el segon estudi es demostrà que els pacients amb aortitis eren més joves (69.9 anys vs. 83.7 anys, p=0.04) i presentaven menys freqüentment clínica isquèmica, incloent clínica ocular (25.0% en els pacients amb aortitis vs. 84.2% en els pacients sense aortitis, p=0.006). La presència de cèl·lules gegants multinucleades en la biòpsia de l'artèria temporal s'associà de forma independent a la presència d'aortitis en el PET/TC (OR 12.23, p=0.046). En el grup de pacients amb aortitis no s'objectivà halo en el Doppler d'artèria temporal en cap cas. Així, podem concloure que el PET/TC és una eina útil en el diagnòstic de l'ACG, que permet identificar dos patrons de captació vascular diferents d'acord a la presència o absència de clínica isquèmica al diagnòstic de l'ACG. Així mateix, la presència d'aortitis en el PET/TC s'associa amb la presencia de cèl·lules gegants multinucleades en la biòpsia.Giant cell arteritis is the most frequently diagnose vasculitis among patients older than 50 years. Classification is done by Hunder criteria (1990). Headache is the most frequent symptom. Vascular involvement has been extensively studied by imaging techniques, including temporal artery biopsy, suggesting the existence of two different clinical subsets of the disease. Evidence suggests that a high proportion of patients present with aortitis and that this situation is associated to a higher corticosteroid dose requirement and a higher risk of developing aortic aneurisms. Moreover, ocular involvement is the most feared complication nowadays as it is usually irreversible. The objective of this study was to identify different patterns of vascular involvement on PET/CT at GCA diagnosis according to the presence or absence of ischaemic manifestations at disease onset, including ocular involvement. Furthermore, we sought to describe clinical and histological patterns on TAB according to the presence or absence of aortitis in PET/CT. In the first study, performed with a cohort that comprised 30 patients with a newly diagnosed GCA, patients with ischaemic symptoms showed a higher proportion of vertebral involvement when compared to those patients without these symptoms (OR 5.0, CI 95%: 0.99 - 24.86, p=0.051). Patients with ischaemic manifestations showed a lower proportion of large vessel vasculitis, being aortitis a protector factor against ischaemic manifestations (OR 19.0, CI 95%: 2.79 - 127.97, p=0.001) and against permanent visual loss (OR 10.67, CI 95%: 1.12 - 101.34, p=0.04). In this cohort, the presence or absence of ischaemic symptoms was associated to different vascular patterns of PET/TC (p=0.001). In the second study we showed that patients with aortitis were younger (69.9 years vs. 83.7 years, p=0.04) and had less frequently ischaemic manifestations, including ocular involvement (25.0% of patients with aortitis vs. 84.2% of patients without aortitis, p=0.006). The presence of giant multinucleated cells on TAB was an independent risk factor for the presence of aortitis on PET/CT (OR 12.23, p=0.046). The halo sign was absent in patients with aortitis. We can conclude that PET/CT is a useful technique at GCA diagnosis that allows identifying two patterns of vascular involvement according to the presence or absence of ischaemic symptoms. When we compared PET/CT and TAB findings, we identified that aortitis was related to the presence of giant multinucleated cells

Effectiveness of a multidisciplinary educational intervention in patients with hip fracture : SWEET HOME study Efectividad de una intervención educativa multidisciplinar en pacientes con fractura de fémur: estudio SWEET HOME

Background and objective: Hip fracture is a common injury among elderly patients. The main goal of our study was to assess the effectiveness of a multidisciplinary educational intervention aimed at hip fracture patients to promote home discharges and reduce in-hospital complications. Material and method: A quasi-experimental study was performed by taking repeated measurements at hospital admission, at hospital discharge, and at both 30 days and one year of discharge. Patients aged ≥ 65 years with hip fracture who were admitted to the Orthogeriatric Service between February 2016 and January 2017 were included in the study. The educational intervention consisted in two coordinated actions: patient education administered during their hospitalization and multimodal support provided during their discharge home. Results: A total of 67 patients were included in the study (77.6% of whom were women; 84.19 ± 7,78 years old). Of these, 70.1% were discharged home, which doubles the figures recorded in the 2014-2015 period. The rate of readmission at 30 days and one year of the discharge was 8.5%. At the one-year follow-up, the patient's dependence to perform basic activities of daily living was nearer to the pre-fracture level (Barthel: 86.67 ± 19.31; 94.33 ± 14.66), their mobility had improved in comparison with the time of discharge (Parker: 4.73 ± 1.84; 6.73 ± 2.76; Timed Up and Go Test: 38.29 ± 21.27; 21.91 ± 10.97), and their cognitive function had not worsened significantly. The patient education measures improved the patients' autonomy as perceived by the patients, the caregivers, and the healthcare providers. Satisfaction with the healthcare received was high. Conclusions: As a novelty to the already described benefits in orthogeriatric care models, this study would contribute by proving an increase of the number of patients discharged home in a safe condition

Generic Entry into the Regulated Spanish Pharmaceutical Market

Generic entry, Pharmaceutical industry, Reference pricing, I11, L11, L65,

Chasing Gravitational Waves with the Chereknov Telescope Array

Presented at the 38th International Cosmic Ray Conference (ICRC 2023), 2023 (arXiv:2309.08219)2310.07413International audienceThe detection of gravitational waves from a binary neutron star merger by Advanced LIGO and Advanced Virgo (GW170817), along with the discovery of the electromagnetic counterparts of this gravitational wave event, ushered in a new era of multimessenger astronomy, providing the first direct evidence that BNS mergers are progenitors of short gamma-ray bursts (GRBs). Such events may also produce very-high-energy (VHE, > 100GeV) photons which have yet to be detected in coincidence with a gravitational wave signal. The Cherenkov Telescope Array (CTA) is a next-generation VHE observatory which aims to be indispensable in this search, with an unparalleled sensitivity and ability to slew anywhere on the sky within a few tens of seconds. New observing modes and follow-up strategies are being developed for CTA to rapidly cover localization areas of gravitational wave events that are typically larger than the CTA field of view. This work will evaluate and provide estimations on the expected number of of gravitational wave events that will be observable with CTA, considering both on- and off-axis emission. In addition, we will present and discuss the prospects of potential follow-up strategies with CTA

Performance of a proposed event-type based analysis for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) will be the next-generation observatory in the field of very-high-energy (20 GeV to 300 TeV) gamma-ray astroparticle physics. Classically, data analysis in the field maximizes sensitivity by applying quality cuts on the data acquired. These cuts, optimized using Monte Carlo simulations, select higher quality events from the initial dataset. Subsequent steps of the analysis typically use the surviving events to calculate one set of instrument response functions (IRFs). An alternative approach is the use of event types, as implemented in experiments such as the Fermi-LAT. In this approach, events are divided into sub-samples based on their reconstruction quality, and a set of IRFs is calculated for each sub-sample. The sub-samples are then combined in a joint analysis, treating them as independent observations. This leads to an improvement in performance parameters such as sensitivity, angular and energy resolution. Data loss is reduced since lower quality events are included in the analysis as well, rather than discarded. In this study, machine learning methods will be used to classify events according to their expected angular reconstruction quality. We will report the impact on CTA high-level performance when applying such an event-type classification, compared to the classical procedure