ABSTRACT
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.
ABSTRACT
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 148 mg/dL and the follow-up value was 71 mg/dL. The baseline value of patients treated with alirocumab (N = 43) was 144 mg/dL and 73 mg/dL in the follow-up. With evolocumab (N = 46) was 151 mg/dL in basaline and 69 mg/dL in follow-up. The LDLc- reduction was 51.21% with evolocumab and 51.05% with alirocumab. 43.1% of the patients showed values >70 mg/dL in six month time;19.4% between 69 mg/dl and 55 mg/dL and 37.5% <55 mg/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 (< 55 mg/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.
ABSTRACT
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 148 mg/dL and the follow-up value was 71 mg/dL. The baseline value of patients treated with alirocumab (N = 43) was 144 mg/dL and 73 mg/dL in the follow-up. With evolocumab (N = 46) was 151 mg/dL in basaline and 69 mg/dL in follow-up. The LDLc- reduction was 51.21% with evolocumab and 51.05% with alirocumab. 43.1% of the patients showed values >70 mg/dL in six month time;19.4% between 69 mg/dl and 55 mg/dL and 37.5% <55 mg/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 (< 55 mg/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. Resumen Objetivos El estudio MEMOGAL (NCT04319081) está dirigido a evaluar cambios en la función cognitiva en pacientes tratados con inhibidores de la PCSK9 (iPCSK9). Se realiza primer análisis: 1) discutir el papel de los farmacéuticos hospitalarios durante de la pandemia, así como evaluar el impacto de la misma en el control lipídico;2) análisis descriptivo;3) eficacia en reducción de colesterol-LDL (c-LDL) de alirocumab y v;y 4) reportar seguridad de los iPCSK9. Material y métodos Se trata de un análisis prospectivo en vida real de pacientes tratados por primera vez con iPCSK9 en la práctica clínica habitual e incluidos en su primera dispensación en las consultas de farmacia de 12 hospitales de Galicia desde mayo de 2020-abril de 2021. Los valores basales de c-LDL son los previos al inicio del tratamiento con iPCSK9 y como seguimiento los valores a los 6 meses. Resultados Se incluyeron 89 pacientes. El 86,5% con enfermedad cardiovascular y un 53,9% intolerancia a las estatinas. Un 78,8% de los pacientes fueron tratados con estatinas de alta intensidad. Las estatinas más usadas fueron rosuvastatina (34,1%) y atorvastatina (20,5%). El nivel basal de c-LDL fue 148 mg/dl y de 71 mg/dl al seguimiento. Los pacientes tratados con alirocumab (n = 43) presentaban valores basales de 144 mg/dl y de 73 mg/dl al seguimiento y con evolocumab (n = 46) de 151 mg/dl basal y 69 mg/dl al seguimiento. La reducción de c-LDL fue para evolocumab 51,21% y alirocumab 51,05%. El 43,1% presentaba a los 6 meses valores > 70 mg/dl, el 19,4% entre 55 y 69 mg/dl y el 37,5% < 55 mg/dl. Los pacientes que obtuvieron una reducción > 50% de c-LDL fueron el 58,3%. Los eventos adversos presentados fueron: reacción en el lugar de inyección (n = 2), mialgias (n = 1), síntomas pseudogripales (n = 1) y deterioro neurocognitivo (n = 1). Conclusiones 1) A pesar de haber disminuido el número de prescripciones de iPCSK9 durante la pandemia, el control lipídico de estos pacientes no se ha visto afectado;2) la mitad de los pacientes tratados con iPSCK9 se debe a intolerancia a estatinas y el 86% es en prevención secundaria;3) se presentaron valores de reducción similares a los ensayos clínicos pivotales. A pesar de esto, un 39% del total y un 60% en doble terapia no alcanzaron las recomendaciones de las guías ESC/EAS (< 55 mg/dl y/o reducción > 50%). No hubo diferencias significativas entre evolocumab y alirocumab: 51,21% vs. 51,05% (p = 0,972);y 4) no se observaron eventos de especial interés con el uso de estos fármacos. El posible deterioro cognitivo será analizado como variable principal una vez completado el estudio MEMOGAL.
ABSTRACT
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.
Subject(s)
Anticholesteremic Agents , COVID-19 Drug Treatment , COVID-19 , PCSK9 Inhibitors , Anticholesteremic Agents/adverse effects , COVID-19/epidemiology , Cholesterol, LDL , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , PCSK9 Inhibitors/adverse effects , Pandemics , Proprotein Convertase 9 , Prospective StudiesABSTRACT
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 (6â mg once daily for 10â days) or high-dose dexamethasone (20â mg once daily for 5â days, followed by 10â mg once daily for an additional 5â days). The primary outcome was clinical worsening within 11â 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±14â 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 11â 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 11â days after randomisation, compared with low dose.
Subject(s)
COVID-19 Drug Treatment , Aged , Dexamethasone , Female , Humans , Male , Middle Aged , Oxygen , SARS-CoV-2 , Treatment OutcomeABSTRACT
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.