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Objective: To evaluate ifthe COVID-19vaccine produces changes in the menstrual pattern, type ofchange anddysmenorrhea. Methods: Observational and cross-sectional study. 6616 digital surveys were carried out on women who received a vaccine against COVID-19. Asurvey was applied via networks and in gynecological consultations. Percentages and 95 %confidence intervals were calculated from 2x2 tables, menstrual changes were analyzed in the sample and in subgroups according to type of vaccine, number of doses, age, and residence. Results: 86.5 % (3535/4087) reported menstrual changes, the most frequent being: menstrual delay (40.4 %) and heavier menstrual bleeding (37.7 %). Dysmenorrhea presented in 39 % accompanying menstrual changes, but 2.1 % as the only symptom. A statistically significant difference was observed: 1) more menstrual changes with mechanism of action chimpanzee viral vector when compared to inactivated virus, 2) human viral vector and inactivated virus more menstrual changes 18-34 years compared to 35-50 years and less changes when compared to chimpanzee viral vector in 35-50 years 3) mRNA was the least associated with menstrual absence when compared to human viral vector 53 % and chimpanzee 50 % more frequent. Conclusion: Menstrual changes are very common after vaccination against COVID-19, this being related to the type of vaccine administered. Some mechanisms of action seem to be related to a greater or lesser risk of specific menstrual changes. © 2023 Sociedad de Obstetricia y Ginecologia de Venezuela. All rights reserved.
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Background: Completion of advance directives can help to ensure consistency with people's preferences at the end of life. However, disparities in access to advance care planning is common among Hispanic population and little is known about their end-of life wishes. Although in Mexico, advance directives were legalized in 2008, only 21% of people know about it. Objective(s): To describe end-of-life wishes among patients with advanced cancer planning in a third level hospital in Mexico City. Method(s): We conducted a cross-sectional analysis of advance directives planning from patients with advanced cancer included in a multidisciplinary patient navigator-led supportive care program in Mexico City (Te Acompanamos). Patients with a life expectancy of 6 months or less were invited to complete advance directives (AD). Life expectancy was calculated using the palliative performance scale (PPS). Descriptive statistics were used for this analysis. Result(s): From September 2017 to November 2021, a total of 238 patients were invited to complete AD and 55 (23.1%) completed it, 14.5% in 2017, 29% in 2018, 34.5% in 2019, 9% in 2020 and 12.7% in 2021. The mean age among those who completed AD was 65.8 years (range 38-91), 52.7% were women and 61.8% had gastrointestinal cancer. Fortythree (78.1%) patients stated their wish to die at home, 18.1% to have cardiopulmonary reanimation, 9% invasive mechanical ventilation, 24.4% tube feeding, 90.9% pain medications, 10.9% organ donation, 40% cremation, 38.1% a funeral and 50.9% a death ritual. At median follow up of 5 months (0-39), 43 (78.1%) patients have died, and their endo-of-life wishes were respected in 77.5 % of them concerning the place of death and in 96.7% regarding cardiopulmonary reanimation and invasive mechanical ventilation. Conclusion(s): In our patient navigator-led supportive program approximately a quarter of patients with advanced cancer and a life expectancy of 6 month or less completed AD and end-of-life wishes were respected in a significant proportion of them. Telemedicine methods used to invite patients during COVID-19 pandemic decreased the proportion of AD completion. Although, advanced care planning is associated with improved in quality of care at the end of life, several barriers and disparities exist among Hispanics and strategies to improve their completion are needed.
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Background: Immunogenicity and safety of SARS-CoV-2 vaccines have been widely investigated in patients (pts) with cancer. However, their effectiveness against Coronavirus disease 2019 (COVID-19) and the additional protective effect of a booster dose in this population are yet to be defined. Methods: Using OnCovid study data (NCT04393974), a European registry enrolling consecutive pts with cancer and COVID-19, we evaluated morbidity and 14 days case fatality rates (CFR14) from COVID-19 in pts who were unvaccinated, vaccinated (either partially/full vaccinated but not boosted) and those who had received a third dose. Analyses were restricted to pts diagnosed between 17/11/2021 (first breakthrough infection in a boosted pt) and the 31/01/2022. Pts with unknown vaccination status were excluded. Results: By the data lock of 22/02/2022, out of 3820 consecutive pts from 36 institutions, 415 pts from 3 countries (UK, Spain, Italy) were eligible for analysis. Among them, 51 (12.3%) were unvaccinated, 178 (42.9%) were vaccinated and 186 (44.8%) were boosted. Among vaccinated pts, 26 (14.6%) were partially vaccinated (1 dose). Pts with haematological malignancies had more likely received a booster dose prior to infection (25.4% vs 13.6% and 11.8%, p = 0.02). We found no other associations between vaccination status and pts' characteristics including sex, age, comorbidities, smoking history, tumour stage, tumour status and receipt of systemic anticancer therapy. Compared to unvaccinated pts, boosted and vaccinated pts achieved improved CFR14 (6.8% and 7.0% vs 22.4%, p = 0.01), COVID-19-related hospitalization rates (26.1% and 20.6% vs 41.2%, p = 0.01) and COVID-19-related complications rates (14.5% and 15.7% vs 31.4%). Using multivariable Inverse Probability of Treatment Weighting (IPTW) models adjusted for sex, comorbidities, tumour status and country of origin we confirmed that boosted (OR 0.21, 95%CI: 0.05-0.89) and vaccinated pts (OR 0.19, 95%CI: 0.04-0.81) achieved improved CFR14 compared to unvaccinated pts, whilst a significantly reduced risk of COVID-19 complications (OR 0.26, 95%CI: 0.07-0.93) was reported for vaccinated pts only. Conclusions: SARS-CoV-2 vaccines protect from COVID-19 morbidity and mortality in pts with cancer. Accounting for the enrichment of haematologic pts in the boosted group, the observation of comparable mortality outcomes between boosted and vaccinated pts is reassuring and suggests boosting to be associated with reduced mortality in more vulnerable subjects, despite evidence of adverse features in this group.
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Since the first outbreak of coronavirus disease (COVID-19) reported in Wuhan (China) on December 31, 2019, countries all over the world have decreed different security measures such as lockdowns and confinement, resulting in reduced levels of air pollution. The present study explores the correlation of the levels of nitrogen dioxide (NO2) measured using two different source data as Sentinel - 5P images and the on-site database of three monitoring stations belonging to the Environmental Monitoring Network in the Metropolitan District of Quito, within three periods of time during the progression of COVID-19. The result of this analysis shows an overall correlation of ninety-three percent of the levels of NO2 for both measurements in the period January to June 2020. During the lockdown and confinement measures from March to April 2020 a reduction of forty-nine percent was found, but when confinement measures were reduced within the period May to June 2020, an increase in NO2 concentration was again observed and the reduction was only thirteen percent;thus, the reduction in NO2 concentrations may be attributed partly due to the significant reduction in vehicle exhaust gas emissions. From the correlation of the results obtained, it can be concluded that this methodology, using Sentinel-5P image analysis may be used to measure the NO2 concentrations in the atmosphere in cities where there is no on-site air quality monitoring network. © 2022. International Journal on Advanced Science, Engineering and Information Technology.All Rights Reserved
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The Yellowstone Volcano Observatory (YVO) monitors volcanic and hydrothermal activity associated with the Yellowstone magmatic system, carries out research into magmatic processes occurring beneath Yellowstone Caldera, and issues timely warnings and guidance related to potential future geologic hazards (see sidebar on volcanic hazards on p. 2). YVO is a collaborative consortium made up of the U.S. Geological Survey (USGS), Yellowstone National Park, University of Utah, University of Wyoming, Montana State University, UNAVCO, Wyoming State Geological Survey, Montana Bureau of Mines and Geology, and Idaho Geological Survey (see sidebar on YVO on p. 3). The USGS arm of YVO also has the operational responsibility for monitoring volcanic activity in the Intermountain West of the United States, including Arizona, New Mexico, Utah, and Colorado. Despite the decrease in activity compared to the previous 3 years, Steamboat Geyser continued to impress visitors with 20 major water eruptions in 2021. This episodic activity is typical of many geysers in Yellowstone National Park, as demonstrated once again in 2021, when Sawmill Geyser returned to its usual pattern of multiple eruptions per day after about 4.5 years of quiescence. Monitoring measurements indicate background levels of seismicity, deformation, and thermal emissions. The number of located earthquakes (2,773) was the most since 2017, when 3,427 earthquakes were located, but the 2021 value was still not significantly different from the average number of annual located events. GPS measurements indicated no significant deformation at Norris Geyser Basin throughout the year, and Yellowstone Caldera continued to subside at rates of a few centimeters (about 1 inch) per year, as it has since 2015. One noteworthy change in deformation style was detected by satellite radar, which documented about 1 centimeter (0.4 inch) of uplift centered on the north side of the caldera, south of Norris Geyser Basin, between late 2020 and late 2021. The deformation strongly resembles that which occurred during 1996-2004 but is yet too small to be strongly apparent in nearby continuous GPS stations. Heat flux estimates from both satellite imagery and river chemistry indicate no major changes with respect to previous years. The COVID-19 pandemic limited field work in 2021, although critical equipment maintenance and deployments and several scientific studies were still carried out. Temporary deployments of seismometers in Norris and Upper Geyser Basins collected information that will be used to better understand geyser plumbing systems, and a new continuous gas-monitoring station-the first of its kind in Yellowstone National Park-was deployed near Mud Volcano in July. Geologic investigations focused on better understanding the age and history of hydrothermal explosion craters in the Lower Geyser Basin, revising geologic maps in the areas around Mount Everts and the Sour Creek resurgent dome, improving age constraints on post-caldera rhyolite lava flows, and investigating the sources of hydrothermal travertine within Yellowstone Caldera. Additional sedimentary cores were collected from Yellowstone Lake to better constrain the characteristics and extent of lake-bottom hydrothermal activity and triggers for hydrothermal explosions. New research results will be highlighted in future editions of YVO's weekly series of online articles, Yellowstone Caldera Chronicles, which can be accessed at https://www.usgs.gov/volcanoes/yellowstone/caldera-chronicles, as well as in annual reports, monthly updates and videos, and public presentations. © 2021 US Geological Survey. All Rights Reserved.
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The exponential growth of technology has caused changes in all areas of knowledge, and education has not been an exception. This paper shows the methodology used in a public university in northeastern Mexico for the transformation of the face-to-face modality to the digital modality based on the health contingency of COVID 19. The methodology used for the development of this proposal was design thinking. The suggested technologies are the Microsoft Teams, Forms, and Turnitin platforms, and the proposed teaching strategies are the flipped classroom, active learning, and inquiry-based learning. The proposed methodology consists of 6 steps that are the framing of the course, the exposure to the contents of the subject, the asynchronous seminar-type session for the discussion of the exposed topics, the elaboration of the integrative PIA learning product divided into advances with their respective feedback. synchronous and the dissemination of the products in magazines, congresses, or seminars. The case shows the experience of implementing the digital strategy. © 2022 IMCIC 2022 - 13th International Multi-Conference on Complexity, Informatics and Cybernetics, Proceedings. All rights reserved.
ABSTRACT
We sought to determine parameters of the acute phase response, a feature of innate immunity activated by infectious noxae and cancer, deranged by Covid-19 and establish oncological indices' prognostic potential for patients with concomitant cancer and Covid-19. Between 27/02 and 23/06/2020, OnCovid retrospectively accrued 1,318 consecutive referrals of patients with cancer and Covid-19 aged 18 from the U.K., Spain, Italy, Belgium, and Germany. Patients with myeloma, leukemia, or insufficient data were excluded. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and prognostic index (PI) were evaluated for their prognostic potential, with the NLR, PLR, and PNI risk stratifications dichotomized around median values and the pre-established risk categorizations from literature utilized for the mGPS and PI. 1,071 eligible patients were randomly assorted into a training set (TS, n=529) and validation set (VS, n=542) matched for age (67.9±13.3 TS, 68.5±13.5 VS), presence of 1 comorbidity (52.1% TS, 49.8% VS), development of 1 Covid-19 complication (27% TS, 25.9% VS), and active malignancy at Covid-19 diagnosis (66.7% TS, 61.6% VS). Among all 1,071 patients, deceased patients tended to categorize into poor risk groups for the NLR, PNI, mGPS, and PI (P<0.0001) with a return to pre-Covid-19 diagnosis NLR, PNI, and mGPS categorizations following recovery (P<0.01). In the TS, higher mortality rates were associated with NLR>6 (44.6% vs 28%, P<0.0001), PNI<40 (46.6% vs 20.9%, P<0.0001), mGPS (50.6% for mGPS2 vs 30.4% and 11.4% for mGPS1 and 0, P<0.0001), and PI (50% for PI2 vs 40% for PI1 and 9.1% for PI0, P<0.0001). Findings were confirmed in the VS (P<0.001 for all comparisons). Patients in poor risk categories had shorter median overall survival [OS], (NLR>6 30 days 95%CI 1-63, PNI<40 23 days 95%CI 10-35, mGPS2 20 days 95%CI 8-32, PI2 23 days 95%CI 1-56) compared to patients in good risk categories, for whom median OS was not reached (P<0.001 for all comparisons). The PLR was not associated with survival. Analyses of survival in the VS confirmed the NLR (P<0.0001), PNI (P<0.0001), PI (P<0.01), and mGPS (P<0.001) as predictors of survival. In a multivariable Cox regression model including all inflammatory indices and pre-established prognostic factors for severe Covid-19 including sex, age, comorbid burden, malignancy status, and receipt of anti-cancer therapy at Covid-19 diagnosis, the PNI was the only factor to emerge with a significant hazard ratio [HR] in both TS and VS analysis (TS HR 1.97, 95%CI 1.19-3.26, P=0.008;VS HR 2.48, 95%CI 1.47- 4.20, P=0.001). We conclude that systemic inflammation drives mortality from Covid-19 through hypoalbuminemia and lymphocytopenia as measured by the PNI and propose the PNI as the OnCovid Inflammatory Score (OIS) in this context.
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Background: Early reports from registry studies demonstrated high vulnerability of cancer patients from COVID-19, with case-fatality rates (CFR) >30% at the onset of the pandemic. With advances in disease management and increased testing capacity, the lethality of COVID-19 in cancer patients may have improved over time. Methods: The OnCovid registry lists European cancer patients consecutively diagnosed with COVID-19 in 35 centres from Jan 2020 to Feb 2021. We analysed clinical characteristics and outcomes stratified in 5 trimesters (Jan-Mar, Apr-Jun, Jul-Sep, Oct-Dec 2020 and Jan-Feb 2021) and studied predictors of mortality across 2 semesters (Jan-Jun 2020 and Jul 2020-Feb 2021). Results: At data cut-off, the 2634 eligible patients demonstrated significant time-dependant improvement in 14-days CFR with trimestral estimates of 29.8%, 20.3%, 12.5%, 17.2% and 14.5% (p<0.0001). Compared to the 2nd semester, patients diagnosed in the Jan-Jun 2020 time period were ≥65 (60.3% vs 56.1%, p=0.031) had ≥2 comorbidities (48.8% vs 42.4%, p=0.001) and non-advanced tumours (46.4% vs 56.1%, p<0.001). COVID-19 was more likely to be complicated in Jan-Jun 2020 (45.4% vs 33.9%, p<0.001), requiring hospitalization (59.8% vs 42.1%, p<0.001) and anti-COVID-19 therapy (61.7% vs 49.7%, p<0.001). The 14-days CFR for the 1st and 2nd semester was 25.6% vs 16.2% (p<0.0001), respectively. After adjusting for gender, age, comorbidities, tumour features, COVID-19 and anti-cancer therapy and COVID-19 complications, patients diagnosed in the 1st semester had an increased risk of death at 14 days (HR 1.68 [95%CI: 1.35-2.09]), but not at 3 months (HR 1.10 [95%CI: 0.94-1.29]) compared to those from the 2nd semester. Conclusions: We report a time-dependent improvement in the mortality from COVID-19 in European cancer patients. This may be explained by expanding testing capacity, improved healthcare resources and dynamic changes in community transmission over time. These findings are informative for clinical practice and policy making in the context of an unresolved pandemic. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding. Disclosure: D.J. Pinato: Financial Interests, Personal, Speaker’s Bureau: ViiV Healthcare;Financial Interests, Personal, Speaker’s Bureau: Bayer;Financial Interests, Personal, Advisory Board: EISAI;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.
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Background: There is uncertainty as to the contribution of cancer patients' features on severity and mortality from Covid-19 and little guidance as to the role of anti-cancer and anti-Covid-19 therapy in this population. Method(s): OnCovid is a retrospective observational study conducted across 19 European centers that recruited cancer patients aged >18 and diagnosed with Covid-19 between 26/02 and 01/04/2020. Uni- and multivariable regression models were used to evaluate predictors of Covid-19 severity and mortality. Result(s): We identified 890 patients from UK (n=218, 24%), Italy (n=343, 37%), Spain (n=323, 36%) and Germany (n=6, 1%). Most patients were male (n=503, 56%) had a diagnosis of solid malignancy (n=753, 84%) and 556 (62%) had active disease. Mean (+/-SD) patient age was 68+/-13 years, and 670 (75%) had >1 co-morbidity, most commonly hypertension (n=386, 43%). Commonest presenting symptoms were fever (n=569, 63%) and cough (n=448, 50%), beginning 6.3 (+/-9.5 SD) days before diagnosis. Most patients (n=565, 63%) had >1 complication from Covid-19, including respiratory failure (n=527, 59%) and acute respiratory distress syndrome (n=127, 22%). In total, 110 patients (14%) were escalated to high-dependency or intensive care. At time of analysis, 299 patients had died (33%). Multi-variate logistic regression identified male gender, age>65 (p<0.0001) presence of >2 comorbidities (p=0.001) active malignancy (p=0.07) as predictors of complicated Covid-19. Mortality was associated with active malignancy (p<0.0001), age>65 and co-morbid burden (p=0.002). Provision of chemotherapy, targeted therapy or immunotherapy was not associated with higher mortality. Exposure to anti-malarials alone (chloroquine/hydroxychloroquine, n=182, p<0.001) or in combination with anti-virals (n=195, p<0.001) or tocilizumab (n=51, p=0.004) was associated with improved mortality compared to patients who did not receive any of these therapies (n=446) independent of patients' gender, age, tumour stage and severity of Covid-19. Conclusion(s): This study highlights the clinical utility of demographic factors for individualized risk-stratification of patients and supports further research into emerging anti Covid-19 therapeutics in SARS-Cov-2 infected cancer patients. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding(s): Has not received any funding. Disclosure: D.J. Pinato: Speaker Bureau/Expert testimony: ViiV Healthcare;Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy: MiNa Therapeutics;Advisory/Consultancy: Eisai;Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: AstraZeneca;Research grant/Funding (institution): MSD. All other authors have declared no conflicts of interest.Copyright © 2020 European Society for Medical Oncology
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Case Report A 2yo girl presented with 7 days of fever as high as 103F. 5 days prior she was dx'd with OM and given amoxicillin, but fevers persisted. On day of presentation she had a new rash and eye redness without discharge. Prior to the illness she was exposed to her MGM who tested positive for COVID-19. Mom works as a nurse who interacts with COVID patients but was asymptomatic. PE: fussy but nontoxic appearing, T 98.1, HR 132, RR 38, BP 102/60 and O2 98% RA, HEENT: dry, cracked lips, injected conjunctivae, no cervical lymphadenopathy, lungs clear, heart RRR without murmurs, no hand or foot swelling but there was a desquamating rash on both LE. Labs: CRP 5.2, ESR >80, ferritin 66, Pro-BNP 182, WBC 14k, lymphs 15%, platelets of 677k. Patient was diagnosed with incomplete Kawasaki disease (IKD) with suspicion for COVID related MIS-C. She was treated with IVIG and aspirin. She started showing improvement and was discharged a couple of days later. Follow up echo showed slight dilatation of one coronary artery. Her COVID-19 test came back negative. Discussion In 2020, with COVID-19 spreading across the world, IKD and MIS-C can be challenging to differentiate. Patients with IKD must have fever for at least 5 days while only 24 hours are required to be diagnosed with MIS-C. IKD patients must have 2-3 of the following 5 findings: bilateral conjunctival injection, changes in lips and oral cavity, cervical lymphadenopathy, swelling of the hands or feet and a polymorphous rash. IKD also requires positive coronary artery dilation on echocardiogram or elevated inflammatory lab values. Some MIS-C patients look very similar to IKD with a desquamating rash, mucous membrane involvement, and increased inflammatory markers. Even coronary artery dilation and aneurysms have been seen in MIS-C. MIS-C patients are generally older (2-15yo), compared to those with IKD (1-4yo). MIS-C patients may have respiratory distress, vomiting and diarrhea or neurologic symptoms like headache and encephalopathy. They can also present with shock or an acute abdomen, which is uncommon in IKD. MIS-C patients tend to have far higher levels of Pro-BNP, CRP and D-Dimer compared to IKD. In the end, IKD and MIS-C can both be successfully treated with IVIG which makes the need to accurately differentiate between the two diseases less urgent.
ABSTRACT
OBJECTIVES: Baricitinib is supposed to have a double effect on SARS-CoV2 infection. Firstly, it reduces the inflammatory response through the inhibition of the Januse-Kinase signalling transducer and activator of transcription (JAK-STAT) pathway. Moreover, it reduces the receptor mediated viral endocytosis by AP2-associated protein kinase 1 (AAK1) inhibition. We propose the use of baricinitib to prevent the progression of the respiratory insufficiency in SARS-CoV2 pneumonia in onco-haematological patients. In this phase Ib/II study, the primary objective in the safety cohort is to describe the incidence of severe adverse events associated with baricitinib administration. The primary objective of the randomized phase (baricitinib cohort versus standard of care cohort) is to evaluate the number of patients who did not require mechanical oxygen support since start of therapy until day +14 or discharge (whichever it comes first). The secondary objectives of the study (only randomized phase of the study) are represented by the comparison between the two arms of the study in terms of mortality and toxicity at day+30. Moreover, a description of the immunological related changes between the two arms of the study will be reported. TRIAL DESIGN: The trial is a phase I/II study with a safety run-in cohort (phase 1) followed by an open label phase II randomized controlled trial with an experimental arm compared to a standard of care arm. PARTICIPANTS: The study will be performed at the Institut Català d'Oncologia, a tertiary level oncological referral center in the Catalonia region (Spain). The eligibility criteria are: patients > 18 years affected by oncological diseases; ECOG performance status < 2 (Karnofsky score > 60%); a laboratory confirmed infection with SARS-CoV-2 by means of real -time PCR; radiological signs of low respiratory tract disease; absence of organ dysfunction (a total bilirubin within normal institutional limits, AST/ALT≤2.5 X institutional upper limit of normal, alkaline phosphatase ≤2.5 X institutional upper limit of normal, coagulation within normal institutional limits, creatinine clearance >30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal); absence of HIV infection; no active or latent HBV or HCV infection. The exclusion criteria are: patients with oncological diseases who are not candidates to receive any active oncological treatment; hemodynamic instability at time of study enrollment; impossibility to receive oral medication; medical history of recent or active pulmonary embolism or deep venous thrombosis or patients at high-risk of suffering them (surgical intervention, immobilization); multi organ failure, rapid worsening of respiratory function with requirement of fraction of inspired oxygen (FiO2) > 50% or high-flow nasal cannula before initiation of study treatment; uncontrolled intercurrent illness (ongoing or severe active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements); allergy to one or more of study treatments; pregnant or breastfeeding women; positive pregnancy test in a pre-dose examination. Patients should have the ability to understand, and the willingness to sign, a written informed consent document; the willingness to accept randomization to any assigned treatment arm; and must agree not to enroll in another study of an investigational agent prior to completion of Day +28 of study. An electronic Case Report Form in the Research Electronic Data Capture (REDCap) platform will be used to collect the data of the trial. Removal from the study will apply in case of unacceptable adverse event(s), development of an intercurrent illness, condition or procedural complication, which could interfere with the patient's continued participation and voluntary patient withdrawal from study treatment (all patients are free to withdraw from participation in this study at any time, for any reasons, specified or unspecified, and without prejudice). INTERVENTION AND COMPARATOR: Treatment will be administered on an inpatient basis. We will compare the experimental treatment with baricitinib plus the institutional standard of care compared with the standard of care alone. During the phase I, we will define the dose-limiting toxicity of baricitinib and the dose to be used in the phase 2 part of the study. The starting baricitinib dose will be an oral tablet 4 mg-once daily which can be reduced to 2 mg depending on the observed toxicity. The minimum duration of therapy will be 5 days and it can be extended to 7 days. The standard of care will include the following therapies. Antibiotics will be individualized based on clinical suspicion, including the management of febrile neutropenia. Prophylaxis of thromboembolic disease will be administered to all participants. Remdesivir administration will be considered only in patients with severe pneumonia (SatO2 <94%) with less than 7 days of onset of symptoms and with supplemental oxygen requirements but not using high-flow nasal cannula, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). In the randomized phase, tocilizumab or interferon will not be allowed in the experimental arm. Tocilizumab can be used in patients in the standard of care arm at the discretion of the investigator. If it is prescribed it will be used according to the following criteria: patients who, according to his baseline clinical condition, would be an ICU tributary, interstitial pneumonia with severe respiratory failure, patients who are not on mechanical ventilation or ECMO and who are still progressing with corticoid treatment or if they are not candidates for corticosteroids. Mild ARDS (PAFI <300 mmHg) with radiological or blood gases deterioration that meets at least one of the following criteria: CRP >100mg/L D-Dimer >1,000µg/L LDH >400U/L Ferritin >700ng/ml Interleukin 6 ≥40ng/L. The use of tocilizumab is not recommended if there are AST/ALT values greater than 10 times the upper limit of normal, neutrophils <500 cells/mm3, sepsis due to other pathogens other than SARS-CoV-2, presence of comorbidity that can lead to a poor prognosis, complicated diverticulitis or intestinal perforation, ongoing skin infection. The dose will be that recommended by the Spanish Medicine Agency in patients ≥75Kg: 600mg dose whereas in patients <75kg: 400mg dose. Exceptionally, a second infusion can be assessed 12 hours after the first in those patients who experience a worsening of laboratory parameters after a first favourable response. The use of corticosteroids will be recommended in patients who have had symptoms for more than 7 days and who meet all the following criteria: need for oxygen support, non-invasive or invasive mechanical ventilation, acute respiratory failure or rapid deterioration of gas exchange, appearance or worsening of bilateral alveolar-interstitial infiltrates at the radiological level. In case of indication, it is recommended: dexamethasone 6mg/d p.o. or iv for 10 days or methylprednisolone 32mg/d orally or 30mg iv for 10 days or prednisone 40mg day p.o. for 10 days. MAIN OUTCOMES: Phase 1 part: to describe the toxicity profile of baricitinib in COVID19 oncological patients during the 5-7 day treatment period and until day +14 or discharge (whichever it comes first). Phase 2 part: to describe the number of patients in the experimental arm that will not require mechanical oxygen support compared to the standard of care arm until day +14 or discharge (whichever it comes first). RANDOMISATION: For the phase 2 of the study, the allocation ratio will be 1:1. Randomization process will be carried out electronically through the REDcap platform ( https://www.project-redcap.org/ ) BLINDING (MASKING): This is an open label study. No blinding will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The first part of the study (safety run-in cohort) will consist in the enrollment of 6 to 12 patients. In this population, we will test the toxicity of the experimental treatment. An incidence of severe adverse events grade 3-4 (graded by Common Terminology Criteria for Adverse Events v.5.0) inferior than 33% will be considered sufficient to follow with the next part of the study. The second part of the study we will perform an interim analysis of efficacy at first 64 assessed patients and a definitive one will analyze 128 assessed patients. Interim and definitive tests will be performed considering in both cases an alpha error of 0.05. We consider for the control arm this rate is expected to be 0.60 and for the experimental arm of 0.80. Considering this data, a superiority test to prove a difference of 0.20 with an overall alpha error of 0.10 and a beta error of 0.2 will be performed. Considering a 5% of dropout rate, it is expected that a total of 136 patients, 68 for each study arm, will be required to complete study accrual. TRIAL STATUS: Version 5.0. 14th October 2020 Recruitment started on the 16th of December 2020. Expected end of recruitment is June 2021. TRIAL REGISTRATION: AEMPs: 20-0356 EudraCT: 2020-001789-12, https://www.clinicaltrialsregister.eu/ctr-search/search (Not publically available as Phase I trial) Clinical trials: BARCOVID19, https://www.clinicaltrials.gov/ (In progress) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol."
Subject(s)
Antiviral Agents/adverse effects , Azetidines/adverse effects , COVID-19 Drug Treatment , Hematologic Neoplasms/complications , Purines/adverse effects , Pyrazoles/adverse effects , Respiratory Insufficiency/prevention & control , SARS-CoV-2/genetics , Sulfonamides/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Cohort Studies , Female , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/mortality , Humans , Male , Middle Aged , Oxygen Inhalation Therapy , Randomized Controlled Trials as Topic , Real-Time Polymerase Chain Reaction , Respiratory Insufficiency/epidemiology , Spain/epidemiology , Treatment Outcome , Young AdultABSTRACT
Introduction: The rapid expansion of COVID-19 caused the World Health Organization, on January 30, 2020, to declare it a health emergency and recognized it as a pandemic on March 11 of the same year. Objective: To describe the clinical evolution of a hypertensive patient, affected by COVID-19. Clinical case: This is a 49-year-old patient, hypertensive, affected by COVID-19, treated at the Dr. “Joaquín Castillo Duany” Military Hospital, who during his stay in the intensive care unit, suffered serious complications such as: Acute respiratory distress syndrome, pneumonia associated with mechanical artificial ventilation, and pulmonary thromboembolism. The delay in going to the hospital, arterial hypertension, and previous treatment with angiotensin-converting enzyme inhibitors, were among the variables present in this patient, which possibly had a negative impact on his evolution. Conclusion: With intensive treatment, the ventilatory and anticoagulation strategy used, evolved favorably until his hospital discharge. © 2020, Editorial Ciencias Medicas. All rights reserved.