Treatment of distal third humeral shaft fractures with posterior minimally invasive plate osteosynthesis (MIPO) with segmental isolation of the radial nerve: minimum one-year follow-up.

Background: Open reduction and internal fixation with plate is one of the most widely used treatments for distal third humeral shaft fractures. The purpose of this study was to report the outcomes of the treatment of distal third humeral shaft fractures with posterior minimally invasive plate osteosynthesis (MIPO) with segmental isolation of the radial nerve. Methods: We performed an observational, retrospective, consecutive, monocentric, continuous multioperator study. We reviewed 22 distal third humeral shaft fractures treated with posterior MIPO in our institution with an extra-articular distal humerus plate from 2018 to 2021. Inclusion was limited to functionally independent patients with displaced fractures involving the junction of the middle and distal thirds of the humerus and minimum 12-month follow-up for implant removal. We assessed clinical outcomes including range of motion; QuickDASH score; Mayo Elbow Performance Score; and Constant-Murley score. Results: The average follow-up period of the sample was 31.7 ± 11.6 months (range, 15.7-51.3 months). The average elbow flexion and extension were 146.4° ± 7.3° (range, 120°-150°) and -0.7° ± 3.3° (range, -15° to 0°), respectively. The average shoulder anterior flexion, elevation, and abduction were 178.6° ± 3.6° (range, 170°-180°), 179.1° ± 2.9° (range, 170°-180°), and 140.9° ± 14.8° (range, 110°-160°), respectively. The average external rotation was 88.6° ± 6.4 (range, 65°-90°). The mean visual analog scale score for pain was 1.0 ± 1.6 (range, 0-5) and the mean Mayo Elbow Performance Score was 90.5 ± 9.9 (range, 70-100). The mean QuickDASH and Constant-Murley scores were 4.7 ± 6.8 (range, 0-20.5) and 95.5 ± 5.1 (range, 81-100), respectively. Two patients presented with relevant compromise of radial nerve motor function postoperatively (M3 and M2; the more compromised was preoperative injury). All patients recovered radial nerve neuropraxia within six weeks postoperatively. All fractures achieved union. The average anteroposterior and lateral axis were 175.0 ± 3.6 (168.0°-180.0°) and 177.5 ± 2.0 (173.0°-180.0°), respectively. No superficial or deep infection was reported. No cases of re-displacement of fracture, implant failure, or any other implant-related complication in follow-up were reported. No patient required plate withdrawal. Conclusion: The results of this study demonstrate that the posterior MIPO technique is a reliable option for treating distal third shaft humeral fractures. The radial nerve must be identified and protected in all cases to prevent palsy.

Long-term outcomes of an educational paediatric antimicrobial stewardship programme: a quality improvement study.

BACKGROUND AND OBJECTIVES: Antimicrobial stewardship programmes (ASPs) have resulted in antimicrobial consumption (AMC) reduction and quality of prescription (QOP) improvement. However, evidence of ASP impact in paediatrics is still limited. This study aims to assess a paediatric ASP long-term outcomes. METHODS: A quality improvement study assessed by a interrupted time series analysis was conducted in a paediatric tertiary hospital. QOP expressed as proportion of adequate prescriptions, AMC measured by defined daily dose incidence per 1000 occupied bed days, incidence density of bloodstream infections (BSIs) and its related all-cause crude death rate (CDR) were compared between pre (from January 2013 to December 2015) and post (from January 2016 to December 2019) ASP activities intensification, which included a dedicated paediatric infectious diseases physician to actively perform educational interviews with prescribers. RESULTS: Inappropriate prescribing showed a significant downward shift associated to the intervention with a -51.4% (-61.2% to -41.8%) reduction with respect to the expected values. Overall AMC showed no trend change after the intervention. For neonatology a28.8% (-36.8% to -20.9%) reduction was observed. Overall anti-pseudomonal cephalosporin use showed a -51.2% (-57.0% to -45.4%) reduction. Decreasing trends were observed for carbapenem use, with a quarterly per cent change (QPC) of -2.4% (-4.3% to -0.4%) and BSI-related CDR (QPC=-3.6%; -5.4% to -1.7%) through the study period. Healthcare-associated multi-drug-resistant BSI remained stable (QPC=2.1; -0.6 to 4.9). CONCLUSIONS: Intensification of counselling educational activities within an ASP suggests to improve QOP and to partially reduce AMC in paediatric patients. The decreasing trends in mortality remained unchanged.

Antidepressant- and anxiolytic-like activities and acute toxicity evaluation of the Psilocybe cubensis mushroom in experimental models in mice.

ETHNOPHARMACOLOGY RELEVANCE: Central nervous system (CNS) diseases can be diverse and usually present with comorbidity, as in the case of depression and anxiety. Despite alternatives like Psilocybe mushrooms for mental health there is no basic research to evidence their CNS benefits. AIM OF THE STUDY: To evaluate the anxiolytic- and antidepressant-like effects, as well as the acute toxicity of P. cubensis mushroom. MATERIAL AND METHODS: First, the acute toxicity (LD50) of P. cubensis (2000 mg/kg) was determined after the esophageal (p.o.) and intraperitoneal (i.p.) route of administration. The rota-rod test and electroencephalogram (EEG) were included to assess CNS toxicity in free moving mice. Anxiolytic (ambulatory or exploratory and rearing behaviors) and antidepressant behavioral responses were assayed in the open-field, plus-maze, and forced swimming test, respectively, after administration of 1000 mg/kg, p.o., of the whole P. cubensis mushroom or the polar aqueous (AQ) or methanolic (MeOH) extractions (1, 10, and/or 100 mg/kg, i.p.) in comparison to the reference drugs buspirone (4 mg/kg, i.p.), fluoxetine and/or imipramine (10 mg/kg, s.c. and i.p., respectively). A chemical analysis of the AQ and MeOH extractions was performed to detect psilocybin and/or psilocin by using UHPLC. RESULTS: Neurotoxic effects of P. cubensis mushroom administered at high doses were absent in mice assessed in the rota-rod test or for EEG activity. A LD50 > 2000 mg/kg was calculated by p.o. or i.p. administration. While significant and/or dose-response antidepressant-like effects were produced with the whole P. cubensis mushroom, p.o., and after parenteral administration of the AQ or MeOH extractions resembling the effects of the reference drugs. Behavioral responses were associated with an anxiolytic-like effect in the open-field as corroborated in the plus-maze tests. The presence of psilocybin and psilocin was mainly characterized in the AQ extraction. CONCLUSION: Our results provide preclinical evidence of the anxiolytic- and antidepressant-like effects of the P. cubensis mushroom without producing neurotoxicity after enteral or parenteral administration, where psilocybin and psilocin were identified mainly after AQ extraction. This study reinforces the benefits of the P. cubensis mushroom in mental health and therapy for anxiety and depression.

Implementation of a PCR-based strategy to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit.

OBJECTIVES: To evaluate the clinical and epidemiological impact of a new molecular surveillance strategy based on qPCR to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit (NICU). METHODS: We design a specific qPCR for the detection of S. marcescens in rectal swabs of patients admitted to a NICU. We divided the surveillance study into two periods: (a) the pre-PCR, from the outbreak declaration to the qPCR introduction, and (b) the PCR period, from the introduction of the qPCR until the outbreak was solved. In all cases, S. marcescens isolates were recovered and their clonal relationship was analysed by PFGE. Control measures were implemented during the outbreak. Finally, the number of bloodstream infections (BSI) was investigated in order to evaluate the clinical impact of this molecular strategy. RESULTS: Nineteen patients colonized/infected by S. marcescens were detected in the pre-PCR period (October 2020-April 2021). On the contrary, after the PCR implementation, 16 new patients were detected. The PFGE revealed 24 different pulsotypes belonging to 7 different clonal groups, that were not overlapping at the same time. Regarding the clinical impact, 18 months after the qPCR implementation, no more outbreaks by S. marcescens have been declared in the NICU of our hospital, and only 1 episode of BSI has occurred, compared with 11 BSI episodes declared previously to the outbreak control. CONCLUSIONS: The implementation of this qPCR strategy has proved to be a useful tool to control the nosocomial spread of S. marcescens in the NICU.

Recomendaciones SER sobre la gestión de riesgo del tratamiento con FAME biológicos o sintéticos dirigidos en pacientes con artritis reumatoide / Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis

Objetivo: Elaborar recomendaciones basadas en la evidencia disponible y el consenso de expertos, para la gestión del riesgo del tratamiento biológico y los inhibidores de las JAK en pacientes con artritis reumatoide. Métodos: Se identificaron preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO (paciente, intervención, comparación, outcome o desenlace) por un panel de expertos, seleccionados en base a su experiencia en el área. Se realizó una revisión sistemática de la evidencia, graduándose de acuerdo a los criterios GRADE (Grading of Recommendations Assessment, Development, and Evaluation). A continuación, se formularon las recomendaciones específicas. Resultados: Se propusieron por el panel de expertos 6preguntas PICO en base a su relevancia clínica y a la existencia de información reciente referentes al riesgo de aparición de infecciones graves, el riesgo de reactivación del virus de la hepatitisB, el riesgo de reactivación del virus varicela-zoster, el riesgo de aparición de cáncer de piel (melanoma y no melanoma) o hematológico, el riesgo de aparición de enfermedad tromboembólica y el riesgo de progresión del virus del papiloma humano. Se formularon un total de 29 recomendaciones, estructuradas por pregunta, basadas en la evidencia encontrada y el consenso de los expertos. Conclusiones: Se presentan las recomendaciones SER sobre la gestión del riesgo del tratamiento con terapias biológicas e inhibidores de las JAK en la artritis reumatoide.(AU)

Objective: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. Methods: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. Results: Six PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitisB virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or hematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 29 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. Conclusions: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.(AU)

Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis.

OBJECTIVE: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. METHODS: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome or outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. RESULTS: 6 PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitis B virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or haematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 28 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. CONCLUSIONS: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.

Three double-dose reinforced hepatitis B revaccination scheme for patients with cirrhosis unresponsive to the standard regimen: an open-label randomised clinical trial.

OBJECTIVE: We aimed to compare the response rates between two different hepatitis B virus vaccination schedules for cirrhotic subjects who were non-responders to the first three 40 µg doses (month 0-1-2), and identify factors associated with the final response. DESIGN: A total of 120 cirrhotic patients (72.5% decompensated) were randomised at a 1:1 ratio to receive a single 40 µg booster vaccination at month 6 (classical arm) versus an additional round of three new 40 µg doses administered at monthly intervals (experimental arm). The main outcome was the rate of postvaccinal anti-hepatitis B surface antibodies levels ≥10 mIU/mL. RESULTS: Efficacy by ITT analysis was higher in the experimental arm (46.7%) than in the classical one (25%); OR 2.63, p=0.013. The experimental arm increased response rates compared with the classical one from 31% to 68% (OR 4.72; p=0.007), from 24.4% to 50% (OR 3.09; p=0.012) and from 24.4% to 53.8% (OR 3.62; p=0.007), in Child A, Model for End-Stage Liver Disease (MELD) <15 and MELD-Na<15 patients, respectively. Patients with more advanced liver disease did not benefit from the reinforced scheme. Both regimens showed similar safety profiles. Multivariable analysis showed that the experimental treatment was independently response associated when adjusted across three logistic regression models indicating equivalent cirrhosis severity. CONCLUSION: For cirrhotic patients, the revaccination of non-responders to the first three dose cycle, with three additional 40 µg doses, achieved significantly better response rates to those obtained with an isolated 40 µg booster dose. TRIAL REGISTRATION NUMBER: NCT01884415.

Adverse events: an expensive and avoidable hospital problem.

INTRODUCTION: Adverse healthcare-related events (AE) entail reduced patient safety. Estimating their frequency, characteristics, avoidability and impact is a means to identify targets for improvement in the quality of care. METHODS: This was a descriptive observational study conducted within the Patient Safety Incident Study in Hospitals in the Community of Madrid (ESHMAD). The study was conducted in a high-complexity hospital in May 2019 through a two-phase electronic medical record review: (1) AE screening and epidemiological and clinical data collection and (2) AE review and classification and analysis of their impact, avoidability, and associated costs. RESULTS: A total of 636 patients were studied. The prevalence of AE was 12.4%. Death during the stay was associated with the presence of AE (OR [CI95%]: 2.15 [1.07 to 4.52]) versus absence and emergency admission (OR [CI95%]: 17.11[6.63 to 46.26]) versus scheduled. A total of 70.2% of the AEs were avoidable. Avoidable AEs were associated with the presence of pressure ulcers (OR [CI95%]: 2.77 [1.39 to 5.51]), central venous catheter (OR [CI95%]: 2.58 [1.33 to 5.00]) and impaired mobility (OR [CI95%]: 2.24[1.35 to 3.71]), versus absences. They were associated too with the stays in the intensive care unit (OR [CI95%]: 2.75 [1.07 to 7.06]) versus medical service. AEs were responsible for additional costs of €909,716.8 for extra days of stay and €12,461.9 per patient with AE. CONCLUSIONS: The prevalence of AEs was similar to that found in other studies. AEs led to worse patient outcomes and were associated with the patient's death. Although avoidable AEs were less severe, their higher frequency produced a greater impact on the patient and healthcare system.Key messagesAdverse events are one of the main problems in healthcare delivery and patients who suffer from at least one AE are double as likely to die during hospitalization.Avoidable adverse events are the most frequent in health care and they are a good target where achieve improvement areas that allow getting optimal patient safety and quality of care levels.Patients hospitalized in the ICU, with the previous presence of pressure ulcers, central venous catheter, or impaired mobility were associated with the development of avoidable AE, so optimal management of these patients would reduce the impact of AE.

Prevalence, characteristics, and impact of Adverse Events in 34 Madrid hospitals. The ESHMAD study.

INTRODUCTION: Adverse Events (AE) are one of the main problems in healthcare. Therefore, many policies have been developed worldwide to mitigate their impact. The Patient Safety Incident Study in Hospitals in the Community of Madrid (ESHMAD) measures the results of them in the region. METHODS: Cross-sectional study, conducted in May 2019, in hospitalised patients in 34 public hospitals using the Harvard Medical Practice Study methodology. A logistic regression model was carried out to study the association of the variables with the presence of AE, calibrated and adjusted by patient. RESULTS: A total of 9,975 patients were included, estimating a prevalence of AE of 11.9%. A higher risk of AE was observed in patients with surgical procedures (OR[CI95%]: 2.15[1.79 to 2.57], vs. absence), in Intensive Care Units (OR[CI95%]: 1.60[1.17 to 2.17], vs. Medical), and in hospitals of medium complexity (OR[CI95%]: 1.45[1.12 to 1.87], vs. low complexity). A 62.6% of AE increased the length of the stay or it was the cause of admission, and 46.9% of AE were considered preventable. In 11.5% of patients with AE, they had contributed to their death. CONCLUSIONS: The prevalence of AE remains similar to the previously estimated in studies developed with the same methodology. AE keep leading to longer hospital stays, contributing to patient's death, showing that it is necessary to put focus on patient safety again. A detailed analysis of these events has enabled the detection of specific areas for improvement according to the type of care, centre, and patient.

Surgical Error Compensation Claims as a Patient Safety Indicator: Causes and Economic Consequences in the Murcia Health System, 2002 to 2018.

OBJECTIVES: Compensation claims are a useful source of information on patient safety research. The purpose of this study was to determine the main causes of surgical compensation claims and their financial impact on the health system. METHODS: A descriptive observational study with analytical components was carried out on compensation claims brought against the surgical area of the Murcia Health System between 2002 and 2018. We analyzed the frequency, causes, consequences, locations and surgical settings of these claims, the time of judicial procedure, and compensation adjusted to the Consumer Price Index. RESULTS: There were 1172 compensation claims. "orthopedic surgery and traumatology" (27.4%), "gynecology and obstetrics" (25.7%), and "general surgery" (17.2%) were the main surgical settings involved. The most frequent causes were surgical error (42.4%) and treatment error (30.9%). The main sequelae were musculoskeletal (20.0%), neurological (17.7%), and obstetric (17.7%). The average time from incident to resolution of claims was 6.3 years. A total of 20.1% of these claims were successful, particularly those involving retained surgical foreign bodies (71.4% successful claims; P < 0.001). The total compensation paid was €56,338,247 (an average of €17,207 per claim). Compensation was higher in cases with respiratory sequelae (median, 131,600; P = 0.033), death (75,916; P < 0.001), and neurological (60,000; P = 0.024). CONCLUSIONS: Compensation claims associated with surgical procedures are made on a variety of grounds. They are drawn-out proceedings, and patients are only successful in 20% of cases.

Resveratrol-Based MTDLs to Stimulate Defensive and Regenerative Pathways and Block Early Events in Neurodegenerative Cascades.

By replacing a phenolic ring of (E)-resveratrol with an 1,3,4-oxadiazol-2(3H)-one heterocycle, new resveratrol-based multitarget-directed ligands (MTDLs) were obtained. They were evaluated in several assays related to oxidative stress and inflammation (monoamine oxidases, nuclear erythroid 2-related factor, quinone reductase-2, and oxygen radical trapping) and then in experiments of increasing complexity (neurogenic properties and neuroprotection vs okadaic acid). 5-[(E)-2-(4-Methoxyphenyl)ethenyl]-3-(prop-2-yn-1-yl)-1,3,4-oxadiazol-2(3H)-one (4e) showed a well-balanced MTDL profile: cellular activation of the NRF2-ARE pathway (CD = 9.83 µM), selective inhibition of both hMAO-B and QR2 (IC50s = 8.05 and 0.57 µM), and the best ability to promote hippocampal neurogenesis. It showed a good drug-like profile (positive in vitro central nervous system permeability, good physiological solubility, no glutathione conjugation, and lack of PAINS or Lipinski alerts) and exerted neuroprotective and antioxidant actions in both acute and chronic Alzheimer models using hippocampal tissues. Thus, 4e is an interesting MTDL that could stimulate defensive and regenerative pathways and block early events in neurodegenerative cascades.

Recommendations for prevention of infection in systemic autoimmune rheumatic diseases.

OBJECTIVES: To develop recommendations for the prevention of infection in adult patients with systemic autoimmune rheumatic diseases (SARD). METHODS: Clinical research questions relevant to the objective of the document were identified by a panel of experts selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network criteria. Specific recommendations were made. RESULTS: Five questions were selected, referring to prevention of infection by Pneumocystis jirovecii with trimethoprim/sulfamethoxazole, primary and secondary prophylactic measures against hepatitis B virus, vaccination against human papillomavirus, vaccination against Streptococcus pneumoniae and vaccination against influenza virus, making a total of 18 recommendations, structured by question, based on the evidence found for the different SARD and/or expert consensus. CONCLUSIONS: There is enough evidence on the safety and efficacy of vaccinations and other prophylactic measures against the microorganisms reviewed in this document to specifically recommend them for patients with SARD.

Synthesis and Biological Assessment of 4,1-Benzothiazepines with Neuroprotective Activity on the Ca2+ Overload for the Treatment of Neurodegenerative Diseases and Stroke.

In excitable cells, mitochondria play a key role in the regulation of the cytosolic Ca2+ levels. A dysregulation of the mitochondrial Ca2+ buffering machinery derives in serious pathologies, where neurodegenerative diseases highlight. Since the mitochondrial Na+/Ca2+ exchanger (NCLX) is the principal efflux pathway of Ca2+ to the cytosol, drugs capable of blocking NCLX have been proposed to act as neuroprotectants in neuronal damage scenarios exacerbated by Ca2+ overload. In our search of optimized NCLX blockers with augmented drug-likeness, we herein describe the synthesis and pharmacological characterization of new benzothiazepines analogues to the first-in-class NCLX blocker CGP37157 and its further derivative ITH12575, synthesized by our research group. As a result, we found two new compounds with an increased neuroprotective activity, neuronal Ca2+ regulatory activity and improved drug-likeness and pharmacokinetic properties, such as clog p or brain permeability, measured by PAMPA experiments.

Recommendations for prevention of infection in systemic autoimmune rheumatic diseases. / Recomendaciones SER sobre prevención de infección en enfermedades reumáticas autoinmunes sistémicas.

OBJECTIVES: To develop recommendations for the prevention of infection in adult patients with systemic autoimmune rheumatic diseases (SARD). METHODS: Clinical research questions relevant to the objective of the document were identified by a panel of experts selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network criteria. Specific recommendations were made. RESULTS: Five questions were selected, referring to prevention of infection by Pneumocystis jirovecii with trimethoprim/sulfamethoxazole, primary and secondary prophylactic measures against hepatitis B virus, vaccination against human papillomavirus, vaccination against Streptococcus pneumoniae and vaccination against influenza virus, making a total of 18 recommendations, structured by question, based on the evidence found for the different SARD and/or expert consensus. CONCLUSIONS: There is enough evidence on the safety and efficacy of vaccinations and other prophylactic measures against the microorganisms reviewed in this document to specifically recommend them for patients with SARD.

The Study on Safety in Hospitals in the Region of Madrid (ESHMAD) design: Screening and analysis of incidents and adverse events.

BACKGROUND: A Study related to Safety in Hospitals in the Region of Madrid (ESHMAD) was carried out in order to determine the prevalence, magnitude and characteristics of adverse events in public hospitals. This work aims to define a useful methodology for the multicenter study of adverse events in the Region of Madrid, to set out the preliminary results of the hospital enrollment and to establish a model of a strategy of training of trainers for its implementation. METHODS: ESHMAD was a multicenter, double phase study for the estimation of adverse events and incidents prevalence across the Region of Madrid. First phase comprehended a 1-day cross-sectional prevalence study, in which it was collected, through a screening guide, information about admission, patient characteristics, intrinsic and extrinsic risk factors, and the possibility of an adverse event or incident had happened during the hospitalization. Second phase was a retrospective nested cohort study, in which it was used a Modular Review Form for reviewing the positive screenings of the first phase, identifying in each possible adverse event or incident the classification of the patient safety event, clinical onset, root, and associated causes and factors, impact, and preventability. A pilot study was performed in an Internal Medicine Unit of a tertiary hospital. RESULTS: 34 public hospitals participated, belonging to 6 healthcare categories and with more than 10,000 hospitalisations aggregate capacity. 72 coordinators were enrolled in the strategy of training of trainers, which was performed through five on-site training workshops. In the pilot study, 45.2% patients were identified with at least one positive event of the screening. Of them, 48.1% (25 positive events) were identified as truly AE, with a result of 0.29 EA per analyzed patient. CONCLUSIONS: The ESHMAD protocol allows to estimate the prevalence of adverse events, and the strategy of training of trainers facilitated the spread of the research methodology among the participants.

Estimation of the Overuse of Preoperative Chest X-rays According to "Choosing Wisely", "No Hacer", and "Essencial" Initiatives: Are They Equally Applicable and Comparable?

BACKGROUND: Overuse reduces the efficiency of healthcare systems and compromises patient safety. Different institutions have issued recommendations on the indication of preoperative chest X-rays, but the degree of compliance with these recommendations is unknown. This study investigates the frequency and characteristics of the inappropriateness of this practice. METHODS: This is a descriptive observational study with analytical components, performed in a tertiary hospital in the Community of Madrid (Spain) between July 2018 and June 2019. The inappropriateness of preoperative chest X-ray tests was analyzed according to "Choosing Wisely", "No Hacer" and "Essencial" initiatives and the cost associated with this practice was estimated in Relative Value and Monetary Units. RESULTS: A total of 3449 preoperative chest X-ray tests were performed during the period of study. In total, 5.4% of them were unjustified according to the "No Hacer" recommendation and 73.3% according to "Choosing Wisely" and "Essencial" criteria, which would be equivalent to 5.6% and 11.8% of the interventions in which this test was unnecessary, respectively. One or more preoperative chest X-ray(s) were indicated in more than 20% of the interventions in which another chest X-ray had already been performed in the previous 3 months. A higher inappropriateness score was also recorded for interventions with an American Society of Anesthesiologists (ASA) grade ≥ III (16.5%). The Anesthesiology service obtained a lower inappropriateness score than other Petitioning Surgical Services (57.5% according to "Choosing Wisely" and "Essencial"; 4.1% according to "No Hacer"). Inappropriate indication of chest X-rays represents an annual cost of EUR 52,122.69 (170.1 Relative Value Units) according to "No Hacer" and EUR 3895.29 (2276.1 Relative Value Units) according to "Choosing Wisely" or "Essencial" criteria. CONCLUSIONS: There was wide variability between the recommendations that directly affected the degree of inappropriateness found, with the main reasons for inappropriateness being duplication of preoperative chest X-rays and the lack of consideration of the particularities of thoracic interventions. This inappropriateness implies a significant expense according to the applicable recommendations and therefore a high opportunity cost.

[Binge drinking: the challenges of definition and its impact on health.] / Episodios de consumo intensivo de alcohol "Binge drinking": retos en su definición e impacto en salud.

Heavy episodic drinking, or binge drinking, is a drinking pattern characterized by the intake of large amounts of alcohol in a short period of time, which often leads to alcohol intoxication. There is no consensus on its operational definition, finding large methodological differences between studies in estimating the amount of alcohol consumed, as well as in defining the occasion of drinking and the reference time period. Keep in mind that most drinkers with this pattern have a low risk total average alcohol consumption. Therefore, actively detecting binge drinking is essential to be able to identify and classify all risk drinkers and characterize the global impact of alcohol consumption on health, society or the economy. Its negative effects affect the drinker himself (intoxication, cardiovascular diseases, dependence, neurocognitive and developmental disorders, among others), but also causes harm to others (accidents, violence, harmful effects on fetal and perinatal neuronal development). These effects can be acute or chronic, even among those who adopt binge drinking sporadically. Different thresholds or ways of characterizing this pattern of alcohol consumption could more adequately predict each of the associated acute and chronic effects, especially if we consider the intensity and frequency of the episodes. However, the absence of a safe threshold for alcohol consumption, both regularly and occasionally, is clear; Any intake with a binge drinking pattern, regardless of the threshold we establish, carries significant risks, not only for the health of the drinker, but also for the people around them.

El patrón de episodios de consumo intensivo de alcohol o binge drinking, se caracteriza por la ingesta de grandes cantidades de alcohol concentrada en un corto espacio de tiempo, que comporta con frecuencia una intoxicación alcohólica. No existe consenso en su definición operativa, hallando entre los estudios grandes diferencias metodológicas en la estimación de la cantidad de alcohol consumido, así como en la definición de la ocasión de bebida y el periodo temporal de referencia. Hay que tener en cuenta que una mayoría de los bebedores con este patrón tienen un consumo de alcohol promedio total de bajo riesgo. Por ello, detectar de forma activa el patrón de consumo intensivo episódico, resulta fundamental para poder identificar y clasificar a todos los bebedores de riesgo y caracterizar el impacto global del consumo de alcohol en la salud, la sociedad o la economía. Sus efectos negativos afectan al propio bebedor (intoxicación, enfermedades cardiovasculares, dependencia, alteraciones neurocognitivas y de maduración entre otros), pero también potencialmente a terceras personas (accidentes, violencia, efectos perjudiciales en el desarrollo neuronal fetal y perinatal). Estos efectos se pueden manifestar de forma aguda, pero también crónica, incluso entre los que adoptan el binge drinking de forma esporádica. Distintos umbrales o formas de caracterizar este patrón de consumo de alcohol podrían predecir de forma más adecuada cada uno de los efectos agudos y crónicos asociados, especialmente si consideramos la intensidad y la frecuencia con que se adopta. No obstante, resulta clara la ausencia de un umbral seguro de consumo de alcohol, tanto de forma regular como puntual; cualquier ingesta con un patrón binge drinking, con independencia del umbral que establezcamos, comporta riesgos importantes, no solo para la salud del bebedor, sino también para las personas de su entorno.

Mascarillas como equipo de protección individual durante la pandemia de COVID-19: cómo, cuándo y cuáles deben utilizarse / Masks as personal protective equipment in the COVID-19 pandemic: How, when and which should be used

ANTECEDENTES Y OBJETIVO: Durante la pandemia COVID-19 se ha producido un aumento de la demanda de mascarillas por parte de profesionales sanitarios y de la población general. En este contexto, se hace necesario sintetizar las características y las indicaciones de uso de los distintos tipos de mascarillas existentes. MATERIAL Y MÉTODOS: Se consultaron y recopilaron las diferentes recomendaciones difundidas por instituciones de reconocido prestigio, como la Organización Mundial de la Salud, The European Centre for Disease Prevention, The Centre for Evidence-Based Medicine o el Ministerio de Sanidad del Gobierno de España. RESULTADOS: Las instituciones consultadas aconsejan reservar las mascarillas filtering face piece (FFP) para el personal sanitario, especialmente en la realización de procedimientos generadores de aerosoles (PGA) (protección mínima de FFP2), y plantean posibles sistemas de reutilización durante épocas de escasez. Asimismo, se recomienda el uso de mascarillas quirúrgicas en profesionales que no realicen PGA y en población sintomática, existiendo variación en las indicaciones de uso para población general sana. CONCLUSIÓN: En situaciones de escasez de equipos de protección individual por pandemia de COVID-19 se debe establecer una priorización y racionalización de uso de cada tipo de mascarilla en función del usuario y de la actividad a realizar

BACKGROUND AND OBJECTIVE: In the COVID-19 pandemic, the demand of masks has been increased by health professionals and the general population. In this context, it is necessary to summarize the features and indications of the different types of masks. MATERIAL AND METHODS: To consult and to compile the different recommendations disseminated by prestigious institutions such as the World Health Organization, the European Center for Disease Prevention, the Center for Evidence-Based Medicine, or the Ministry of Health of the Government of Spain has been reviewed. RESULTS: The institutions consulted recommend reserving FFP respirators for healthcare workers, especially when carrying out aerosol-generating procedures (AGPs) (minimum FFP2 protection) and consider some reutilization systems during times of scarcity. The use of surgical masks is recommended to professionals who do not perform AGPs and to the symptomatic population but exist variations in its indications intended for the general healthy population. CONCLUSION: In the context of shortage of personal protective equipment due to the COVID-19 pandemic, a prioritization and rationalization of the use of each type of mask should be established according to the user and the activity performed

[Masks as personal protective equipment in the COVID-19 pandemic: How, when and which should be used]. / Mascarillas como equipo de protección individual durante la pandemia de COVID-19: cómo, cuándo y cuáles deben utilizarse.

BACKGROUND AND OBJECTIVE: In the COVID-19 pandemic, the demand of masks has been increased by health professionals and the general population. In this context, it is necessary to summarize the features and indications of the different types of masks. MATERIAL AND METHODS: To consult and to compile the different recommendations disseminated by prestigious institutions such as the World Health Organization, the European Center for Disease Prevention, the Center for Evidence-Based Medicine, or the Ministry of Health of the Government of Spain has been reviewed. RESULTS: The institutions consulted recommend reserving FFP respirators for healthcare workers, especially when carrying out aerosol-generating procedures (AGPs) (minimum FFP2 protection) and consider some reutilization systems during times of scarcity. The use of surgical masks is recommended to professionals who do not perform AGPs and to the symptomatic population but exist variations in its indications intended for the general healthy population. CONCLUSION: In the context of shortage of personal protective equipment due to the COVID-19 pandemic, a prioritization and rationalization of the use of each type of mask should be established according to the user and the activity performed.

Optical control of muscular nicotinic channels with azocuroniums, photoswitchable azobenzenes bearing two N-methyl-N-carbocyclic quaternary ammonium groups.

By linking two N-methyl-N-carbocyclic quaternary ammonium groups to an azobenzene scaffold in meta- or para-positions we generated a series of photoswitchable neuromuscular ligands for which we coined the term "azocuroniums". These compounds switched between the (E)- and (Z)-isomers by light irradiation at 400-450 nm and 335-340 nm, respectively. Meta-azocuroniums were potent nicotinic ligands with a clear selectivity for the muscular nAChRs compared to neuronal α7 and α4ß2 subtypes, showed good solubility in physiologic media, negligible cell toxicity, and would not reach the CNS. Electrophysiological studies in muscle-type nAChRs expressed in Xenopus laevis oocytes showed that (E)-isomers were more potent than (Z)-forms. All meta-azocuroniums were neuromuscular blockers, with the exception of the pyrrolidine derivative that was an agonist. These new meta-azocuroniums, which can be modulated ad libitum by light, could be employed as photoswitchable muscle relaxants with fewer side effects for surgical interventions and as tools to better understand the pharmacology of muscle-type nAChRs.