Effect of early vs. delayed extubation on functional outcome among patients with acute ischemic stroke treated with endovascular thrombectomy under general anesthesia: the prospective, randomized controlled EDESTROKE trial study protocol.

BACKGROUND: Recent meta-analyses and randomized studies have shown that among patients with acute ischemic stroke undergoing endovascular thrombectomy, general anesthesia with mechanical ventilation is associated with better functional status compared to local anesthesia and sedation, and they recommend its use. But once the procedure is completed, when is the optimal moment for extubation? Currently, there are no guidelines recommending the optimal moment for extubation. Prolonged mechanical ventilation time could potentially be linked to increased complications such as pneumonia or disturbances in cerebral blood flow due to the vasodilatation produced by most anesthetic drugs. However, premature extubation in a patient who has suffered a stroke could led to complications such as agitation, disorientation, abolished reflexes, sudden fluctuations in blood pressure, alterations in cerebral blood flow, respiratory distress, bronchial aspiration, and the need for reintubation. We therefore designed a randomized study hypothesizing that early compared with delayed extubation is associated with a better functional outcome 3 months after endovascular thrombectomy treatment under general anesthesia for acute ischemic stroke. METHODS: This investigator-initiated, single-center, prospective, parallel, evaluated blinded, superiority, randomized controlled trial will include 178 patients with a proximal occlusion of the anterior circulation treated with successful endovascular thrombectomy (TICI 2b-3) under general anesthesia. Patients will be randomly allocated to receive early (< 6 h) or delayed (6-12 h) extubation after the procedure. The primary outcome measure is functional independence (mRS of 0-2) at 90 days, measured with the modified Rankin Score (mRS), ranging from 0 (no symptoms) to 6 (death). DISCUSSION: This will be the first trial to compare the effect of mechanical ventilation duration (early vs delayed extubation) after satisfactory endovascular thrombectomy for acute ischemic stroke under general anesthesia. TRIAL REGISTRATION: The study protocol was approved April 11, 2023, by the by the Santiago-Lugo Research Ethics Committee (CEI-SL), number 2023/127, and was registered into the clinicaltrials.gov clinical trials registry with No. NCT05847309. Informed consent is required. Participant recruitment begins on April 18, 2023. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

Impact of Universal Use of the McGrath Videolaryngoscope as a Device for All Intubations in the Cardiac Operating Room. A Prospective Before-After VIDEOLAR-CAR Study.

OBJECTIVE: Tracheal intubation in cardiac surgery patients has a higher incidence of difficult laryngoscopic views compared with patients undergoing other types of surgery. The authors hypothesized that using the McGrath Mac videolaryngoscope as the first intubation option for cardiac surgery patients improves the percentage of patients with "easy intubation" compared with using a direct Macintosh laryngoscope. DESIGN: A prospective, observational, before-after study. SETTING: At a tertiary-care hospital. PARTICIPANTS: One thousand one hundred nine patients undergoing cardiac surgery. INTERVENTION: Consecutive patients undergoing cardiac surgery were intubated using, as the first option, a Macintosh laryngoscope (preinterventional phase) or a McGrath Mac videolaryngoscope (interventional phase). MEASUREMENTS AND MAIN RESULTS: The main objective was to assess whether the use of the McGrath videolaryngoscope, as the first intubation option, improves the percentage of patients with "easy intubation," defined as successful intubation on the first attempt, modified Cormack-Lehane grades of I or IIa, and the absence of the need for adjuvant airway devices. A total of 1,109 patients were included, 801 in the noninterventional phase and 308 in the interventional phase. The incidence of "easy intubation" was 93% in the interventional phase versus 78% in the noninterventional phase (p < 0.001). First-success-rate intubation was higher in the interventional phase (304/308; 98.7%) compared with the noninterventional phase (754/801, 94.1%; p = 0.005). Intubation in the interventional phase showed decreases in the incidence of difficult laryngoscopy (12/308 [3.9%] v 157/801 [19.6%]; p < 0.001), as well as moderate or difficult intubation (5/308 [1.6%] v 57/801 [7.1%]; p < 0.001). CONCLUSIONS: The use of the McGrath videolaryngoscope as the first intubation option for tracheal intubation in cardiac surgery improves the percentage of patients with "easy" intubation," increasing glottic view and first-success-rate intubation and decreasing the incidence of moderate or difficult intubation.

Relationships between Patient-Reported Outcome Measures and Clinical Measures in Naïve Neovascular Age-Related Macular Degeneration Patients Treated with Intravitreal Ranibizumab.

Our objective was to evaluate changes in patient-reported outcome measures using the NEI-VFQ 25 questionnaire during a treat and extend regimen in naive neovascular Age-Related Macular Degeneration patients, and its correlation with anatomical and functional data. We conducted a prospective observational study. Patients underwent a treat and extend regimen with intravitreal ranibizumab for neovascular Age-Related Macular Degeneration. Initial response was evaluated at 4th month, and subsequently in every follow-up visit. If a clinical response was achieved, the injection interval was extended in two-week increments, up to a maximum of 12 weeks. Quality of life was assessed using the NEI-VFQ 25 questionnaire at baseline, 4th months, and 12th months. Patients were categorized as good or poor responders based on Best corrected visual acuity, central foveal thickness, intraretinal fluid, or subretinal fluid. Treatment with ranibizumab led to a significant improvement in quality of life, with a mean increase in NEI-VFQ 25 score of 4.27 points in the 12th month. No significant differences in improvement were observed between good and poor responders. Quality of life scores in neovascular Age-Related Macular Degeneration patients improved with intravitreal treatment regardless of the clinical response. The early response following the loading phase could indicate better quality of life after one year of treatment, with Best corrected visual acuity being the clinical parameter with the greatest influence on quality of life.

The Effect of Systemic Parameters and Baseline Characteristics in Short-Term Response Analysis with Intravitreal Ranibizumab in Treatment-Naive Patients with Neovascular Age-Related Macular Degeneration.

Anti-vascular endothelial growth factor drugs keep being the main therapy for neovascular age-related macular degeneration (AMD). Possible predictive parameters (demographic, biochemical and/or inflammatory) could anticipate short-term treatment response with ranibizumab. 46 treatment-naive patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD and the clinical examination was made at baseline and one month after the third injection. Demographic characteristics, co-morbidities and concomitant treatments were recorded at the baseline visit. Biochemical parameters, complete blood count and inflammation biomarkers were also measured at these times. Uric Acid was found to be statistically significant with a one-point difference between good and poor responders in both basal and treated patients, but only in basal parameters was statistical significance reached (p = 0.007 vs. p = 0.071 in treated patients). Cholesterol and inflammatory parameters such as white blood cell count and neutrophils were significantly reduced over time when treated with intravitreal ranibizumab. On the other hand, women seemed to have a worse prognosis for short-term response to intravitreal ranibizumab treatment. Uric acid may help identify possible non-responders before initial treatment with ranibizumab, and cholesterol and white blood cells could be good candidates to monitor short-term response to ranibizumab treatment.

Videolaryngoscope versus conventional technique for insertion of a transesophageal echocardiography probe in intubated ICU patients (VIDLARECO trial): A randomized clinical trial.

BACKGROUND: Transesophageal echocardiogram probe insertion in intubated critically ill patients can be difficult, leading to complications, such as gastric bleeding or lesions in the oropharyngeal mucosa. We hypothesised that the use of a videolaryngoscope would facilitate the first attempt at insertion of the transesophageal echocardiogram probe and would decrease the incidence of complications compared to the conventional insertion technique. METHODS: In this clinical trial, patients were randomly assigned the insertion of a transesophageal echocardiogram probe using a videolaryngoscope or conventional technique. The primary outcome was the successful transesophageal echocardiogram probe insertion on the first attempt. The secondary outcomes included total success rate, number of insertion attempts, and incidence of pharyngeal complications. RESULTS: A total of 100 intubated critically ill patients were enrolled. The success rate of transesophageal echocardiogram probe insertion on the first attempt was higher in the videolaryngoscope group than in the conventional group (90% vs. 58%; absolute difference, 32%; 95% CI 16%-48%; p < 0.001). The overall success rate was higher in the videolaryngoscope group than in the conventional group (100% vs. 72%; absolute difference, 28%; 95% CI 16%-40%; p < 0.001). The incidence of pharyngeal mucosal injury was smaller in the videolaryngoscope group than in the conventional group (14% vs. 52%; absolute difference, 38%; 95% CI 21%-55%; p < 0.001). CONCLUSIONS: Our study showed that in intubated critically ill patients required transesophageal echocardiogram, the use of videolaryngoscope resulted in higher successful insertion on the first attempt with lower rate of complications when compared with the conventional insertion technique. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04980976.

Influence of Genetic Polymorphisms on the Short-Term Response to Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration.

Purpose: To determine whether genetic risk single nucleotide polymorphisms (SNPs) for age-related macular degeneration (AMD) influence short-term response to intravitreal ranibizumab treatment. Methods: Forty-four treatment-naive AMD patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD. After an initial clinical examination (baseline measurement), a follow-up visit was performed to determine treatment response one month after the third injection (treatment evaluation). Patients were evaluated based on ophthalmoscopy, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography. Peripheral venous blood was collected for DNA analysis at baseline visit. Patients were genotyped for single-nucleotide polymorphisms within AMD-relevant genes and classified on good or poor responders based on visual acuity, central retinal thickness, intraretinal fluid, and subretinal fluid. Results: One hundred ten AMD-associated SNPs have been analyzed. Six were found to be relevant when associated to ranibizumab treatment response. The genetic variants rs890293 (CYP2J2), rs11200638 (HTRA1), rs405509 (APOE), rs9513070 (FLT1), and rs8135665 (SLC16A8) predisposed patients to a good response, whereas rs3093077 (CRP) was associated with a poor response. FTL1, SLC16A8, and APOE were the SNPs that showed significance (P < 0.05) but did not pass Bonferroni correction. Conclusions: This is the first study that links novel polymorphisms in genes such as CRP, SCL16A8, or CYP2J2 to treatment response to ranibizumab therapy. On the other hand, HTRA1, FLT1, and APOE are linked to a good ranibizumab response. These SNPs may be good candidates for short-term treatment response biomarkers in AMD patients. However, further studies will be necessary to confirm our findings.

Cognitive Function with PCSK9 Inhibitors: A 24-Month Follow-Up Observational Prospective Study in the Real World-MEMOGAL Study.

INTRODUCTION: The cognitive safety of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has been established in clinical trials, but not yet in real-world observational studies. We assessed the cognitive function in patients initiating PCSK9i, and differences in cognitive function domains, to analyze subgroups by the low-density lipoprotein cholesterol (LDL-C) achieved, and differences between alirocumab and evolocumab. METHODS: This has a multicenter, quasi-experimental design carried out in 12 Spanish hospitals from May 2020 to February 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). RESULTS: Among 158 patients followed for a median of 99 weeks, 52% were taking evolocumab and 48% alirocumab; the mean change from baseline in MoCA score at follow-up was + 0.28 [95% CI (- 0.17 to 0.73; p = 0.216)]. There were no significant differences in the secondary endpoints-the visuospatial/executive domain + 0.04 (p = 0.651), naming domain - 0.01 (p = 0.671), attention/memory domain + 0.01 (p = 0.945); language domain - 0.10 (p = 0.145), abstraction domain + 0.03 (p = 0.624), and orientation domain - 0.05 (p = 0.224)-but for delayed recall memory the mean change was statistically significant (improvement) + 0.44 (p = 0.001). Neither were there any differences in the three stratified subgroups according to lowest attained LDL-C level-0-54 mg/dL, 55-69 mg/dL and ≥ 70 mg/dL; p = 0.454-or between alirocumab and evolocumab arms. CONCLUSION: We did not find effect of monoclonal antibody PCSK9i on neurocognitive function over 24 months of treatment, either in global MoCA score or different cognitive domains. An improvement in delayed recall memory was shown. The study showed no differences in the cognitive function between the prespecified subgroups, even among patients who achieved very low levels of LDL-C. There were no differences between alirocumab and evolocumab. REGISTRATION: ClinicalTtrials.gov Identifier number NCT04319081.

Efficacy and Safety of Inhaled Ethanol in Early-Stage SARS-CoV-2 Infection in Older Adults: A Phase II Randomized Clinical Trial.

BACKGROUND: Inhaled ethanol in the early stages of SARS-CoV-2 infection may reduce the viral load, decreasing progression and improving prognosis. The ALCOVID-19 trial was designed to study the efficacy and safety of inhaled ethanol in older adults at initial phases of infection. METHODS: Randomized, triple-blind, placebo-controlled phase II clinical trial. Experimental group (n = 38) inhaled 65° ethanol through an oxygen flow, while in the control group (n = 37), water for injection was used. General endpoint was to evaluate disease progression according to the modified World Health Organization (WHO) Clinical Progression Scale. Specific effectiveness endpoints were body temperature, oxygen saturation, viral load assessed by cycle threshold (Ct) on real-time polymerase chain reaction (RT-PCR), analytical biomarkers and use of antibiotics or corticosteroids. Specific safety outcomes were the absence of ethanol in plasma, electrographic, analytical, or respiratory alterations. RESULTS: In the intention-to-treat population, no differences were found regarding disease progression. Mean Ct values increased over time in both groups, being numerically higher in the ethanol group, reaching a value above 33 only in the ethanol group on day 14, a value above which patients are considered non-infective. No differences were found in the other specific effectiveness endpoints. Inhaled ethanol was proven to be safe as no plasma ethanol was detected, and there were no electrocardiographic, analytical, or respiratory alterations. CONCLUSIONS: The efficacy of inhaled ethanol in terms of the progression of SARS-CoV-2 infection was not demonstrated in the present trial. However, it is positioned as a safe treatment for elderly patients with early-stage COVID-19.

Ansiedad y depresión en matronas del Área de Santiago de Compostela durante la pandemia de la COVID-19 / Anxiety and depression in midwives in the Santiago de Compostela Area during the COVID-19 pandemic

Objetivo: Identificar el nivel de ansiedad y depresión de las matronas del Área Sanitaria de Santiago de Compostela durante la pandemia de la COVID-19. Métodos: Estudio transversal observacional descriptivo. La población de estudio fueron las matronas que ejercen su profesión en el ámbito público en atención primaria o especializada del Área Sanitaria de Santiago de Compostela. En dicha área, un total de 20 matronas prestan servicio en atención especializada y 41 en atención primaria. Las principales variables fueron el nivel de ansiedad y depresión; para su medida se emplearon el Inventario de Ansiedad de Beck (BAI) y el Inventario de Depresión de Beck (BDI-II). Resultados: Se obtuvo una muestra de 42 matronas, lo cual supuso un 68,8 % de participación. De las matronas que respondieron el cuestionario, en cuanto al nivel de depresión, el 71,43 % (n= 30) presentó un nivel mínimo, el 21,43 % (n= 9) leve, el 4,76 %(n= 2) moderado y el 2,38 % (n= 1) grave. En lo referente a la ansiedad, el 88,09 % (n= 37) presentó un nivel bajo, el 9,52 % (n= 4) moderado y el 2,38 % (n= 1) severo. Además, el 88,10 % (n= 37) de las matronas percibió que el estrés aumentó en su lugar de trabajo y el 85,71 % (n= 36) estuvo preocupada por la posibilidad de contagiarse durante el desempeño de sus funciones. El 95,23 % (n= 40) declaró sentirse preocupada por el riesgo de contagiar a sus familiares. Conclusiones: Los niveles de ansiedad y depresión de las matronas del Área Sanitaria de Santiago de Compostela durante la pandemia de la COVID-19 fueron bajos. El miedo a contagiar a sus familiares ha sido la principal preocupación de dichas profesionales, siendo mayor que el miedo a contagiarse ellas mismas. Además, consideraban adecuado un plan de intervención por parte del Servicio Gallego de Salud (SERGAS) para minimizar el impacto psicológico que la pandemia ha generado en sus vidas. (AU)

Objective: Analyzing midwives’ anxiety and depression levels in the Health Area of Santiago de Compostela during the COVID-19 pandemic. Methods: A descriptive observational cross-sectional study was carried out, and midwives who work at hospitals and at primary health care centers in the Health Area of Santiago de Compostela were included in it. On that Health Area, 20 midwives provide specialized care and 41, primary care. The main variables were anxiety and depression levels. They were measured by the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI-II). Results: 42 midwives completed the test, which meant a 68.8% participation rate. From those midwives, 71.43% (n=30) showed a minimum level of depression, 21.43% (n=9) showed a minor level, 4.76% (n=2) a moderate level and 2.38% (n=1) a severe level. Regarding anxiety, 88.09% (n=37) registered a low level, 9.52% (n=4) a moderate level and 2.38% (n=1) a serious level. In addition, 88.10% (n=37) of midwives perceived that the stress increased in their workplace and 85.71% (n=36) of midwives were concerned about de possibility of being infected in their workplace and 95.23% (n=40) were worried about infecting their families. Conclusions: The COVID-19 pandemic is affecting physical and psychological health of healthcare workers, including midwives. The fear to infect their family members has been the main concern for these professionals being greater than the fear to get themselves infected. In addition, they consider that an intervention plan from Servicio Gallego de Salud (SERGAS) to reduce the psychological impact that pandemic has produced is needed. (AU)

Liver Brain Interactions: Focus on FGF21 a Systematic Review.

Fibroblast growth factor 21 is a pleiotropic hormone secreted mainly by the liver in response to metabolic and nutritional challenges. Physiologically, fibroblast growth factor 21 plays a key role in mediating the metabolic responses to fasting or starvation and acts as an important regulator of energy homeostasis, glucose and lipid metabolism, and insulin sensitivity, in part by its direct action on the central nervous system. Accordingly, pharmacological recombinant fibroblast growth factor 21 therapies have been shown to counteract obesity and its related metabolic disorders in both rodents and nonhuman primates. In this systematic review, we discuss how fibroblast growth factor 21 regulates metabolism and its interactions with the central nervous system. In addition, we also state our vision for possible therapeutic uses of this hepatic-brain axis.

Impact of the COVID-19 pandemic in the lipid control of the patients that start PCSK9 inhibitors. / Impacto de la pandemia por COVID-19 en el control lipídico de pacientes que inician inhibidores de la PCSK9.

OBJECTIVES: MEMOGAL study (NCT04319081) is aimed at evaluating changes in cognitive function in patients treated with PCSK9 inhibitors (PCSK9i). This is the first analysis: (1) discussion about the role of the Hospital Pharmacists during the pandemic, and also the assessment of the impact of COVID-19 in the lipid control; (2) descriptive analysis; (3) effectiveness in LDL cholesterol (LDL-c) reduction of alirocumab and evolocumab; (4) communicate PCSK9i safety. MATERIAL AND METHODS: It is a prospective Real-World Evidence analysis of patients that take PCSK9i for the first time in the usual clinical practice, and they are included after the first dispensation in the public pharmacy consultations of 12 Hospitals in Galicia from May 2020 to April 2021. Baseline values of LDL-c are the previous values before taking PCSK9 and the follow-up values are in 6 months time. RESULTS: 89 patients were included. 86.5% with cardiovascular disease and 53.9% with statin intolerances. 78.8% of the patients were treated with high intensity statins. Statins most used were rosuvastatin (34.1%) and atorvastatin (20.5%). Baseline value of LDL-c was 148mg/dL and the follow-up value was 71mg/dL. The baseline value of patients treated with alirocumab (N=43) was 144mg/dL and 73mg/dL in the follow-up. With evolocumab (N=46) was 151mg/dL in basaline and 69mg/dL in follow-up. The LDLc- reduction was 51.21% with evolocumab and 51.05% with alirocumab. 43.1% of the patients showed values >70mg/dL in six month time; 19.4% between 69mg/dl and 55mg/dL and 37.5% <55mg/dL. 58.3% of the patients achieved a reduction >50% of LDL-c. The adverse events were: injection point reaction (N=2), myalgias (N=1), flu-like symptoms (N=1) and neurocognitive worsening (N=1). CONCLUSIONS: (1) Despite the number of prescriptions was reduced because of the pandemic, the lipid control was not affected. (2) Half of the patients treated with PSCK9i is due to statins intolerance and the 86% is for secondary prevention. (2) The reduction results were similar to pivotal clinical trials. Despite this, 39% of the total of the patients and 60% of patients with dual teraphy did not reach the goal of ESC/EAS guidelines (<55mg/dL and/or reduction>50%). There were not significant differences between evolocumab and alirocumab: 51.21% vs 51.05% (P=.972). (3) There were not any adverse events of special interest. The possible neurocognitive worsening will be studied as the primary endpoint once the MEMOGAL study has been completed.

Synergism interaction between genetic polymorphisms in drug metabolizing enzymes and NSAIDs on upper gastrointestinal haemorrhage: a multicenter case-control study.

BACKGROUND: Interindividual genetic variations contribute to differences in patients' response to drugs as well as to the development of certain disorders. Patients who use non-steroidal anti-inflammatory drugs (NSAIDs) may develop serious gastrointestinal disorders, mainly upper gastrointestinal haemorrhage (UGIH). Studies about the interaction between NSAIDs and genetic variations on the risk of UGIH are scarce. Therefore, we investigated the effect of 16 single nucleotide polymorphisms (SNPs) involved in drug metabolism on the risk of NSAIDs-induced UGIH. MATERIALS AND METHODS: We conducted a multicenter case-control study of 326 cases and 748 controls. Participants were sub-grouped into four categories according to NSAID exposure and genetic profile. We estimated odds ratios (ORs) and their 95% confidence intervals (CI) using generalized linear mixed models for dependent binomial variables and then calculated the measures of interaction, synergism index (S), and relative excess risk due to interaction (RERI). We undertook stratified analyses by the type of NSAID (aspirin, non-aspirin). RESULTS: We observed an excess risk of UGIH due to an interaction between any NSAID, non-aspirin NSAIDs or aspirin and carrying certain SNPs. The greatest excess risk was observed for carriers of: rs2180314:C>G [any NSAID: S = 3.30 (95%CI: 1.24-8.80), RERI = 4.39 (95%CI: 0.70-8.07); non-aspirin NSAIDs: S = 3.42 (95%CI: 1.12-10.47), RERI = 3.97 (95%CI: 0.44-7.50)], and rs4809957:A>G [any NSAID: S = 2.11 (95%CI: 0.90-4.97), RERI = 3.46 (95%CI: -0.40-7.31)]. Aspirin use by carriers of rs6664:C>T is also associated with increased risk of UGIH [ORaspirin(+),wild-type: 2.22 (95%CI: 0.69-7.17) vs. ORaspirin(+),genetic-variation: 7.72 (95%CI: 2.75-21.68)], yet larger sample size is needed to confirm this observation. CONCLUSIONS: The joint effect of the SNPs s2180314:C>G and rs4809957:A>G and NSAIDs are more than three times higher than the sum of their individual effects. Personalized prescriptions based on genotyping would permit a better weighing of risks and benefits from NSAID consumption.KEY MESSAGESMulticenter case-control study of the effect of genetic variations involved in drug metabolism on upper gastrointestinal haemorrhage (UGIH) induced by NSAIDs (aspirin and non-aspirin).There is a statistically significant additive synergism interaction between certain genetic polymorphisms and NSAIDs on UGIH: rs2180314:C>G and rs4809957:A>G. The joint effect of each of these single nucleotide polymorphisms and NSAIDs on UGIH is more than three times higher than the sum of their individual effects.Genetic profiling and personalized prescriptions would be useful in managing the risks and benefits associated with NSAIDs.

Impact of the Coronavirus Disease 2019 Pandemic on Moral Distress Among Nurses and Physicians in Spanish ICUs.

OBJECTIVES: To assess the impact of COVID-19 pandemic on moral distress (MD) among healthcare professionals (HCPs) (physicians and nurses) in Spanish ICUs. DESIGN: Cross-sectional, prospective study. SETTING: ICUs in Spain. PARTICIPANTS: HCPs currently working in Spanish ICUs. INTERVENTIONS: Data were collected via electronic survey with the use of a 50-item questionnaire in two different periods: prepandemic (October-December 2019) and during the second wave of COVID-19 (September-November 2020). MEASUREMENTS AND MAIN RESULTS: During the prepandemic and pandemic periods, 1,065 (57.1% nurses) and 1,115 (58.5% nurses) HCPs completed the questionnaire, respectively. Higher MD levels were reported during COVID-19 pandemic, particularly among ICU nurses, when compared with the prepandemic period. Before COVID-19, physicians reported significantly higher levels of MD than ICU nurses (80.0 [interquartile range {IQR}, 40.0-135.0] vs 61.0 [IQR, 35.0-133.0]; p = 0.026). These differences disappeared during the pandemic period (81.0 [IQR, 39.0-138.5] vs 74.0 [IQR, 41.0-143.0]; p = 0.837). During the pandemic, younger and less experienced HCPs working in hospital areas that were converted in ICU or in ICUs with multiple occupancy rooms reported higher MD levels. In addition, HCPs who were off work for psychologic burden reported higher MD levels (108.0 [IQR, 66.0-139.0] vs 76.0 [IQR, 40.0-141.0]; p < 0.05). In the prepandemic period, patient-level root causes were the most morally distressing for nurses, whereas physicians reported higher MD on system-level root causes. During the pandemic, both groups reported higher MD on system-level root causes. During COVID-19, significantly more HCPs considered leaving their job due to MD. CONCLUSIONS: MD has increased among ICU HCPs in Spain during COVID-19 pandemic. Physicians reported higher MD levels than nurses in the prepandemic period, whereas both HCPs groups reported similar MD levels in the pandemic period. Strategies are needed and should be implemented to mitigate MD among HCPs.

Neurological Instability in Ischemic Stroke: Relation with Outcome, Latency Time, and Molecular Markers.

The National Institutes of Health Stroke Scale (NIHSS) is commonly used to evaluate stroke neurological deficits and to predict the patient's outcome. Neurological instability (NI), defined as the variation of the NIHSS in the first 48 h, is a simple clinical metric that reflects dynamic changes in the area of the brain affected by the ischemia. We hypothesize that NI may represent areas of cerebral instability known as penumbra, which could expand or reduce brain injury and its associated neurological sequels. In this work, our aim was to analyze the association of NI with the functional outcome at 3 months and to study clinical biomarkers associated to NI as surrogate biomarkers of ischemic and inflammatory penumbrae in ischemic stroke (IS) patients. We included 663 IS patients in a retrospective observational study. Neutral NI was defined as a variation in the NI scale between - 5 and 5% (37.1%). Positive NI is attributed to patients with an improvement of > 5% NI after 48 h (48.9%), while negative NI is assigned to patients values lower than - 5% (14.0%). Poor outcome was assigned to patients with mRS ≥ 3 at 3 months. We observed an inverse association of poor outcome with positive NI (OR, 0.35; 95%CI, 0.18-0.67; p = 0.002) and a direct association with negative NI (OR, 6.30; 95%CI, 2.12-18.65; p = 0.001). Negative NI showed a higher association with poor outcome than most clinical markers. Regarding good functional outcome, positive NI was the marker with the higher association (19.31; CI 95%, 9.03-41.28; p < 0.0001) and with the highest percentage of identified patients with good functional outcome (17.6%). Patients with negative NI have higher glutamate levels compared with patients with neutral and positive NI (p < 0.0001). IL6 levels are significantly lower in patients with positive NI compared with neutral NI (p < 0.0001), while patients with negative NI showed the highest IL6 values (p < 0.0001). High glutamate levels were associated with negative NI at short latency times, decreasing at higher latency times. An opposite trend was observed for inflammation, and IL6 levels were similar in patients with positive and negative NI in the first 6 h and then higher in patients with negative NI. These results support NI as a prognosis factor in IS and the hypothesis of the existence of a delayed inflammatory penumbra, opening up the possibility of extending the therapeutic window for IS.

Measuring family-centred care practices in adult intensive care units: The EMPATHIC-F questionnaire.

BACKGROUND: Engaging relatives in the care of critically ill patients is associated with better outcomes. It is crucial to empower relatives to provide feedback. Valid satisfaction instruments are essential to identify best practices and areas for improvement. AIM: The aim of the study was to adapt the Spanish version of the EMpowerment of PArents in The Intensive Care-30 (EMPATHIC-30) questionnaire in adult intensive care units (ICUs) and psychometrically test the EMpowerment of PAtients in The Intensive Care-Family (EMPATHIC-F) questionnaire to measure family satisfaction. DESIGN: This is a cross-sectional, prospective study conducted in two adult ICUs. Participants were relatives of patients who were discharged alive from the ICUs with an ICU length-of-stay >24 hours. The EMPATHIC-F questionnaire is divided into five domains that are related to the family-centred care principles. Responses are provided on a 6-point ordinal Likert scale, a score of >5 is considered acceptable. RESULTS: Patients' relatives confirmed the adaptation of the instrument. A total of 262 relatives responded to the EMPATHIC-F questionnaire (97% response rate). The empirical structure of the instrument was established by confirmatory factor analysis confirming 30 statements within five theoretically conceptualized domains: information, care and treatment, family participation, organization, and professional attitude. On item level, two statements scored a mean below 5.0. Cronbach's α at the domain level was between .64 and .75. Congruent validity was adequate between the five domains and four general satisfaction items (r's .26-.54). The non-differential validity was confirmed with no significant effect size between three patients' demographic characteristics and the domains. CONCLUSIONS: The EMPATHIC-F questionnaire is a reliable and valid quality performance indicator to measure the perceptions of family members in adult ICU settings. RELEVANCE TO CLINICAL PRACTICE: The EMPATHIC-F questionnaire can be used to benchmark and provides a framework for standardized quality improvement towards the development of a family-centred care philosophy within adult ICUs.

Effect of high versus low dose of dexamethasone on clinical worsening in patients hospitalised with moderate or severe COVID-19 pneumonia: an open-label, randomised clinical trial.

BACKGROUND: Low-dose dexamethasone demonstrated clinical improvement in patients with coronavirus disease 2019 (COVID-19) needing oxygen therapy; however, evidence on the efficacy of high-dose dexamethasone is limited. METHODS: We performed a randomised, open-label, controlled trial involving hospitalised patients with confirmed COVID-19 pneumonia needing oxygen therapy. Patients were randomly assigned in a 1:1 ratio to receive low-dose dexamethasone (6 mg once daily for 10 days) or high-dose dexamethasone (20 mg once daily for 5 days, followed by 10 mg once daily for an additional 5 days). The primary outcome was clinical worsening within 11 days since randomisation. Secondary outcomes included 28-day mortality, time to recovery and clinical status at day 5, 11, 14 and 28 on an ordinal scale ranging from 1 (discharged) to 7 (death). RESULTS: A total of 200 patients (mean±sd age 64±14 years; 62% male) were enrolled. 32 (31.4%) out of 102 patients enrolled in the low-dose group and 16 (16.3%) out of 98 in the high-dose group showed clinical worsening within 11 days since randomisation (rate ratio 0.427, 95% CI 0.216-0.842; p=0.014). The 28-day mortality was 5.9% in the low-dose group and 6.1% in the high-dose group (p=0.844). There was no significant difference in time to recovery, and in the seven-point ordinal scale at days 5, 11, 14 and 28. CONCLUSIONS: Among hospitalised COVID-19 patients needing oxygen therapy, high dose of dexamethasone reduced clinical worsening within 11 days after randomisation, compared with low dose.

[Effectiveness of smoking cessation programs of roll-your-own tobacco smokers in Galicia.] / Efectividad de los programas de cesación tabáquica en fumadores de tabaco de liar en Galicia.

OBJECTIVE: Currently in developed countries there is an increase in the consumption of roll your own tobacco, which is associated with a higher proportion of users of this form of tobacco who wish to make an attempt to quit. The objective of this study was to analyze the effectiveness of tobacco cessation interventions based on the type of tobacco consumed. METHODS: Longitudinal study of a cohort of 641 smokers recruited between 2015 and 2018 in a health area of Galicia included in smoking cessation programs, based on psychological counseling and pharmacological treatment. The characteristics and success of the intervention were evaluated in two groups: roll your own tobacco smokers (RYO) and manufactured tobacco smokers (MT). A logistic regression was performed to determine the probability of success in smoking cessation. The risk measure was the odds ratio (OR) with its 95% confidence interval. RESULTS: RYO users started at a younger age and had a lower sociocultural stratum than MT users. Interventions to quit smoking in RYO users were associated with less abstinence at 4 weeks (52% MT vs 38% LT) (OR: 0.5; 95% CI 0.35-0.99; p=0.045;) and at 3 months (42% TM vs 30% TL) (OR:0.6; 95% CI 0.33-0.98; p=0.04). CONCLUSIONS: Smoking cessation programs are less effective in short-term RYO users. There are no differences in long-term abstinence between the two groups.

OBJETIVO: Actualmente en los países desarrollados existe un aumento del consumo de tabaco de liar lo que se asocia a una mayor proporción de usuarios de esta forma de tabaco que desean realizar un intento de abandono. El objetivo de este estudio fue analizar la efectividad de las intervenciones de cesación tabáquica en función del tipo de tabaco consumido. METODOS: Estudio longitudinal de una cohorte de 641 fumadores reclutados entre 2015 y 2018 en un área sanitaria de Galicia incluidos en programas de deshabituación tabáquica, basados en el asesoramiento psicológico y en el tratamiento farmacológico. Se evaluaron las características y el éxito de la intervención en dos grupos: fumadores de tabaco de liar (TL) y fumadores de tabaco manufacturado (TM). Se realizó una regresión logística para determinar la probabilidad de éxito en la cesación tabáquica. La medida de riesgo fue el odds ratio (OR) con su intervalo de confianza al 95%. RESULTADOS: Los consumidores de TL se iniciaron a una edad más temprana y tenían un estrato sociocultural más bajo que los consumidores de TM. Las intervenciones para abandonar el tabaco en los consumidores de TL se asociaron a una menor abstinencia a las 4 semanas (52%TM vs 38% TL) (OR: 0,5; 95%IC 0,35-0,99; p=0,045;) y a los 3 meses (42%TM vs 30%TL) (OR:0,6; 95%IC 0,33-0,98; p=0,04). CONCLUSIONES: Los programas de cesación tabáquica son menos efectivas en los consumidores de TL a corto plazo. No se observan diferencias en la abstinencia a largo plazo entre ambos grupos.

Random forest-based prediction of stroke outcome.

We research into the clinical, biochemical and neuroimaging factors associated with the outcome of stroke patients to generate a predictive model using machine learning techniques for prediction of mortality and morbidity 3-months after admission. The dataset consisted of patients with ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH) admitted to Stroke Unit of a European Tertiary Hospital prospectively registered. We identified the main variables for machine learning Random Forest (RF), generating a predictive model that can estimate patient mortality/morbidity according to the following groups: (1) IS + ICH, (2) IS, and (3) ICH. A total of 6022 patients were included: 4922 (mean age 71.9 ± 13.8 years) with IS and 1100 (mean age 73.3 ± 13.1 years) with ICH. NIHSS at 24, 48 h and axillary temperature at admission were the most important variables to consider for evolution of patients at 3-months. IS + ICH group was the most stable for mortality prediction [0.904 ± 0.025 of area under the receiver operating characteristics curve (AUC)]. IS group presented similar results, although variability between experiments was slightly higher (0.909 ± 0.032 of AUC). ICH group was the one in which RF had more problems to make adequate predictions (0.9837 vs. 0.7104 of AUC). There were no major differences between IS and IS + ICH groups according to morbidity prediction (0.738 and 0.755 of AUC) but, after checking normality with a Shapiro Wilk test with the null hypothesis that the data follow a normal distribution, it was rejected with W = 0.93546 (p-value < 2.2e-16). Conditions required for a parametric test do not hold, and we performed a paired Wilcoxon Test assuming the null hypothesis that all the groups have the same performance. The null hypothesis was rejected with a value < 2.2e-16, so there are statistical differences between IS and ICH groups. In conclusion, machine learning algorithms RF can be effectively used in stroke patients for long-term outcome prediction of mortality and morbidity.

Observational multicentre prospective study to assess changes in cognitive function in patients treated with PCSK9i. Study protocol.

OBJECTIVE: PCSK9 inhibitors have been shown to reduce LDLc by up to about 60% and 85% when used with high doses of statins and ezetimibe (2019 ESC/EAS Guidelines). These therapies may lead to very low levels of LDLc and have been associated with possible cognitive deterioration. No significant differences were found in the only specific  study (EBBINGHAUS). The objective is to prospectively evaluate cognitive  deterioration and its repercussion on quality of life and changes in LDLc in  patients starting treatment with PCKS9 inhibitors. METHOD: It is a postauthorization, multicentre, non-randomized, prospective study. Patients starting treatment for the first time with PCSK9 inhibitors will be recruited in 11 Galician Hospitals over a period of 12 months and with 24 months of follow-up. The primary outcome will be to evaluate changes in cognitive function using the Montreal  Cognitive Assessment (MOCA) questionnaire. The secondary outcome will be to evaluate changes in quality of life using the EuroQol-5D. Changes in LDLc will be assessed. The sample size will be 275 patients, taking into account a loss to follow-up of no more than 10%. The primary outcome  will be studied through the dichotomous variable cognitive deterioration (0/1). Cognitive changes over the follow-up period will be analysed using  the McNemar test. In addition, an analytical approach using logistic regression will be followed to identify patients at risk of cognitive deterioration. As a result, this analysis will obtain a frequency measurement: the odds ratio (OR). The specific objectives will be studied  using bivariate analysis. Continuous contrast variables will be studied using the t-test or ANOVA and categorical variables will be studied using the chi- square test. CONCLUSIONS: The MEMOGAL study will provide information on safety in  terms of cognitive deterioration in patients starting treatment with PCSK9 inhibitors.

Objetivo: Los inhibidores de proproteína convertasa subtilisina/kexina de tipo 9 (PCSK9) han demostrado reducir hasta un 60% el colesterol  transportado por lipoproteínas de baja densidad (c-LDL) y hasta el 85%  asociado a estatinas de alta intensidad y ezetimibe (2019 ESC/EAS Guidelines). Estas terapias pueden dar lugar a muy bajos niveles de c-LDL y se ha especulado sobre su posible relación con deterioro cognitivo. En el  único estudio específico, EBBINGHAUS, no se encontraron diferencias  significativas. El objetivo es evaluar prospectivamente el deterioro  cognitivo y la repercusión en términos de calidad de vida y variaciones de  c-LDL en pacientes que inician tratamiento con inhibidores de PCSK9. Método: Se trata de un estudio postautorización, multicéntrico, no aleatorizado de seguimiento prospectivo. Se reclutarán pacientes que  inicien tratamiento por primera vez con iPCSK9 en 11 hospitales gallegos  durante un periodo de 12 meses y un seguimiento de 24 meses. El  endpoint primario será evaluar los cambios en la función cognitiva a través del cuestionario Montreal Cognitive Assessment (MOCA), y como endpoints secundarios se valorarán cambios en la calidad de vida a través del  EuroQol­5D y variación de los niveles de LDL. El tamaño muestral, teniendo en cuenta un porcentaje de pérdidas no superior al 10%, será de  275 individuos. El objetivo general se estudiará a través de la variable  dicotómica deterioro cognitivo (0/1). El estudio del deterioro cognitivo a lo  largo del seguimiento se realizará con el test McNemar. Además, se  pretende realizar un planteamiento analítico con una regresión logística que explore si existe algún perfil de paciente con riesgo de sufrir deterioro cognitivo. Este análisis obtendrá como resultado una medida de  frecuencia, la odds ratio (OR). Los objetivos específicos se estudiarán planteando análisis bivariados. Para las variables de contraste continuas se empleará el test T o el ANOVA, si las variables son de naturaleza  categórica se aplicará el test de chi cuadrado.Conclusiones: El estudio MEMOGAL intentará aportar información sobre  la seguridad en términos de deterioro cognitivo en pacientes que inicien  tratamiento con inhibidores de PCSK9 (real-world evidence).