Fixed vs weight-based dosing of pembrolizumab for patients under 80 kg, based on observed ADRs in one cancer setting

Background and ImportanceMonoclonal antibodies are usually dosed by the kilogramme of the patient's weight, due to perceived contribution of body size in pharmacokinetic variability. Lately, especially during the COVID pandemic, a lot of monoclonal antibodies, including pembrolizumab, were switched to fixed dosing. Pembrolizumab was initially dosed at 2 mg/kg, fixed dosing includes 200 mg every three weeks or 400 mg every six weeks (Freshwater, 2017). The fixed dosing is more convenient, eliminates the waste, might improve patient's compliance and reduces dosing errors. However, for the patients that weight less than 80 kg, fixed dose is associated with almost maximum exposure, which is also associated with greater occurrence of toxicity (CADTH, 2020).Aim and ObjectivesThe aim of this retrospective study was to determine whether it is better to use fixed or weight-based dosing of pembrolizumab for patients under 80 kg in order to avoid serious ADRs.Material and MethodsWe observed ADRs that occurred with 391 patients receiving pembrolizumab in 2021, regardless the diagnosis. We collected the data, by reviewing patients' documentation. The patients were distributed across oncology indications, including NSCLC, melanoma, breast cancer, urothelial carcinoma, cervical cancer, Hodgkin's lymphoma, head and neck squamous cell carcinoma, oesophageal cancer and renal cell carcinoma.ResultsThe patients were split into two subgroups, under and over 80 kg in weight (group 1 and 2). For 29 patients, data about weight was not available. 198 patients were in group 1, whereas in group 2 there were 164 patients. The ADRs occurred in 69 patients (34,8%) from group 1 and 46 patients from group 2 (26%). The most common ADRs occurred were skin toxicities, hypothyreosis, muscle and joint pain, diarrhoea and fatigue. There were no significant differences in the occurred ADRs between group 1 and 2.Conclusion and RelevanceThe results indicated that for patients under 80 kg, weight-based dose would not only be better in terms of less toxicity, but it would also be more cost effective. The adaptation of fixed dosing regimens would lead to the estimated 26% of additional cost (e.g. 50 kg patient would receive 100 mg dose, which means half price of the fixed dose) (Monirul et al, 2020).References and/or AcknowledgementsConflict of InterestNo conflict of interest.

Challenges and Sources of Advertising in Agritourism during the Covid-19 Pandemic

With the emergence of the COV1D-19 pandemic, the tourism market faces many challenges, including the Agritourism business. Because of the necessary measures introduced to reduce the spread of the virus, travel and tourist movements have been reduced. Therefore, agritourism is forced to focus its advertising methods on online sources to attract tourist demand for its facilities, products, and services. This paper explores the challenges agritourism has faced in promoting and advertising and how they have adapted to new digital and online advertising opportunities. The paper aims to identify new advertising challenges during the pandemic and analyze the importance of internet sales and security as the most significant attractive factor caused by the pandemic outbreak. The survey was conducted on a sample of 83 holders/owners of Agritourism in the Republic of Croatia. Through empirical research, respondents were offered questions in three thematic units: general data of objects, advertising methods, and content of posts. In order to meet the objectives of the paper, three hypotheses were given. The validation of hypotheses is processed using the statistical method of measurement known as the McNemar's test and descriptive statistics and analysis. The research results indicate the presence of advertising challenges in the new business conditions, the weaker representation of the use of traditional sources of advertising (while online advertising remains without significant changes), the under-representation of internet sales, and security, whose importance is recognized but under-promoted. The contribution of the work is reflected in the presentation of the trend of online advertising as an indispensable tool for attracting more visitors and tourists. At the same time, this topic notices the emergence of new requirements and ways of communication with tourists during the COVID-19 pandemic outbreak.

The Chloroquine Story in the First Year of the COVID-19 Pandemic

The emergence of COVID-19 has caused worldwide concern due to its high infectivity and mortality. Research groups around the world have prioritised drug development against COVID-19. Repurposing of already approved drugs, including the antimalarial drug chloroquine, has attracted considerable attention. The aim of this article is to (i) provide an overview of the recent chemical methods used to synthesise chloroquine and hydroxychloroquine, and (ii) provide insight into the data collected in 2020 on their efficacy against COVID-19. Unfortunately, the promising early results have not been confirmed and a clear and unambiguous conclusion on their clinical efficacy has not yet been drawn. (English) [ FROM AUTHOR] Pojava COVIDA-19 uzrokovala je globalnu zabrinutost zbog visoke zaraznosti i mortaliteta. Stoga je razvoj lijekova protiv COVIDA-19 postao prioritet istraživačkim skupinama diljem svijeta. Pri tom je posebnu pozornost privukla moguća prenamjena prethodno odobrenih lijekova, uključujući i antimalarijski lijek klorokin. Cilj ovog rada je (i) prikazati pregled recentnih kemijskih metoda primijenjenih za sintezu klorokina i hidroksiklorokina te (ii) dati uvid u podatke o njihovoj učinkovitosti protiv COVIDA-19 prikupljene tijekom 2020. Nažalost, početni obećavajući rezultati nisu potvrđeni, a jasni i nedvosmisleni zaključci o kliničkoj učinkovitosti klorokina i hidroksiklorokina još nisu postignuti. (Croatian) [ FROM AUTHOR] Copyright of Kemija u Industriji is the property of Croatian Society of Chemical Engineers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Novel protocol for selection of SARS-CoV-2 convalescent plasma donors

Background/Aim. Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) 2019 infection represents a global problem. At this moment, in October 2020, there is no vaccine or efficient treatment for infected patients. Treatment with blood plasma rich with anti-SARS-CoV-2 specific antibodies might be a safe, and effective therapy for COVID-19 patients. Methods. A total of 768 patients were analyzed in this study, whose samples were collected in a time interval from May 1, 2020, till August 15, 2020. Patients were enrolled in the study from COVID-19 hospitals and out-clinics. In-house ELISA tests were developed to measure the concentration of anti-S1S2 spike and anti-nucleoprotein (np) (IgG, IgA, IgM) SARS-CoV-2 antibodies. Blood convalescent plasma was selectively collected from recovered patients according to specific antibodies concentration. Results. The highest concentrations of anti-S1S2 spike or anti-np specific IgG antibodies were detected in patients with the moderate/heavy clinical form of the infection. An extremely high concentration of anti-S1S2 spike IgG and anti-np IgG was demonstrated in 3% and 6% of patients who recovered from severe COVID-19, respectively. Of tested hospitalized patients, 63% and 51% had modest levels of anti-S1S2 spike and anti-np, respectively. After 60 days, in our selected donors, concentrations of antiS1S2 spike IgG and anti-np IgG antibodies increased in 67% and 58% of donors, respectively. Conclusion. In-house developed ELISA tests enable a novel protocol for selecting convalescent blood plasma donors recovered from SARS-CoV-2 infection.

Evaluation of rocuronium in critically ill patients during the COVID-19 pandemic

INTRODUCTION: Limited data exist to support the use of rocuronium continuous infusions in the intensive care unit (ICU). Due to a shortage of cisatracurium, our Pharmacy and Therapeutics committee approved the use of rocuronium as a therapeutic alternative. The objective of this study was to evaluate the dosing and monitoring of adult patients who received rocuronium for hypoxemic respiratory failure during the COVID-19 pandemic. METHODS: This was a prospective, single-center study from March 1, 2020 to May 31, 2020. We identified all adult patients admitted to any ICU who received rocuronium via continuous infusion. Patients were excluded if they received rocuronium for < 6 hours. Study subjects could have multiple paralysis infusions during the same admission. Each rocuronium infusion was separated by at least 24 hours. The main outcome of this study was the relationship between the hourly administration rate of rocuronium and TOF assessment by using Pearson correlation coefficient. Secondary outcomes of this study included median rocuronium dose at initiation, duration of infusion, and median rate of infusion. TOF results were classified as over-paralyzed (TOF = 0), wellparalyzed (TOF = 1-2), or under-paralyzed (TOF = 3-4). RESULTS: Seventy-one patients and 97 paralysis infusions were included. Fifty-nine patients (83%) were positive for SARS CoV-2. There was a negligible correlation between the dose of rocuronium and the TOF results (r = 0.04). Of the 97 paralysis infusions, the median dose at initiation was 3 [3-5] mcg/kg/min and duration of infusion was 45 [23.6-92.5] hours. The median rate of infusion was 4.3 [2.8-7.2] mcg/kg/ min. A total of 1775 TOFs were assessed, of which 46.2% were over-paralyzed, 35.7% well-paralyzed, and 18.1% under-paralyzed. CONCLUSIONS: We found no correlation between rocuronium dose and TOF assessments. The initial and maintenance infusion doses in our analysis were lower than what have been previously referenced. As TOF is unpredictable, patients initiated on continuous infusion rocuronium may be started at lower doses while being titrated to ventilator synchrony to avoid over-paralysis.

Evaluation of hypertriglyceridemia in critically ill patients with COVID-19 receiving propofol

INTRODUCTION: Propofol 1%, available as an oilin- water emulsion, is an attractive sedative option in patients with COVID-19 since it is rapid acting and easily titratable. Previous studies have shown approximately 18% to 45% of patients who receive propofol in the ICU develop hypertriglyceridemia, depending on the definition. Additionally, various reports have recently described hypertriglyceridemia without a clear etiology in patients infected with SARS-CoV-2. The objective of this analysis was to report the incidence of, and evaluate risk factors for, hypertriglyceridemia in patients with COVID-19 who received propofol. METHODS: This was a retrospective, observational analysis in SARS-CoV-2 positive patients who received propofol for at least four hours from March 1, 2020 to April 20, 2020. Patients were excluded if transferred from an outside hospital with propofol administered for > 24 hours, had zero triglyceride levels drawn during admission, or had acute pancreatitis on admission. Hypertriglyceridemia was defined as any triglyceride level ≥ 400 mg/dL. Univariate and multivariate analyses were performed to evaluate risk factors for hypertriglyceridemia. RESULTS: A total of 128 patients were screened, of which 106 patients were included in the analysis. Sixty patients (56.6%) met criteria for hypertriglyceridemia, with a median time to development of 46 hours. A total of five patients had clinical suspicion of acute pancreatitis, with one patient having confirmatory imaging. There was no difference in the dose (8.1 g vs. 6.8 g;p = 0.2) or duration (171 hr vs. 162 hr;p = 0.7) of propofol in patients who developed hypertriglyceridemia. Patients who developed hypertriglyceridemia had significantly increased levels of ferritin, CRP, and d-dimer compared to those who did not develop hypertriglyceridemia. CONCLUSIONS: Hypertriglyceridemia was commonly observed in critically ill patients with COVID-19 who received propofol. Neither the cumulative dose nor duration of propofol were identified as a risk factor for the development of hypertriglyceridemia. Due to the incidence of hypertriglyceridemia in this patient population, monitoring of serum triglyceride levels should be done frequently in patients who require more than 24 hours of propofol.

Impact of COVID-19 outbreak on hospital admissions and outcome of acute coronary syndromes in a single high-volume centre in southeastern Europe.

BACKGROUND: As coronavirus disease 2019 (COVID-19) has reached pandemic status, authors from the most severely affected countries have reported reduced rates of hospital admissions for patients with acute coronary syndrome (ACS). AIM: The aim of the present study was to investigate the influence of the COVID-19 outbreak on hospital admissions and outcomes in ACS patients in a single high-volume centre in southeastern Europe. METHODS: This retrospective observational study aimed to investigate the number of hospital admissions for ACS, clinical findings at admission, length of hospitalisation, major complications and in-hospital mortality during the COVID-19 outbreak and to compare the data with the same parameters during an equivalent time frame in 2019. For the ST-elevated myocardial infarction (STEMI) subgroup of patients, changes in ischaemic times were analysed as well. RESULTS: There was a significant reduction of 44.3% in the number of patients admitted for ACS during the COVID-19 outbreak when compared with the same period in 2019 (151 vs 271; 95% confidence interval 38.4-50.2, p < 0.01) with a higher mortality rate (13.2% vs 7.2%, p = 0.03). In 2020, patients with non-ST-elevated myocardial infarction presented more often with acute heart failure (3.3% vs 0.7%, p = 0.04). During the COVID-19 outbreak, we observed increases in the total ischaemic time (303 ± 163.4 vs 200.8 ± 156.8 min, p < 0.05) and door-to-balloon time (69.2 ± 58.4 vs 50.5 ± 31.3 min, p < 0.01) in STEMI patients. CONCLUSIONS: These findings should increase the awareness of morbidity and mortality related to missed or delayed treatment of ACS among the public and the healthcare services.

Pathological lung changes in COVID-19 deceased patients

Background: COVID-19 disease causes diffuse alveolar damage associated with a high mortality rate. The aim of the analysis of deceased patients with SARS-CoV-2 virus infection is to assess histopathological changes in the lungs as the key target organ in this infection. Methods: We performed partial autopsies on patients with COVID-19 treated at the University Hospital of Respiratory and Allergic Diseases Golnik. We assessed various histopathological changes in the lungs of deceased patients with COVID-19 disease. We performed immunohisto-chemical stainings to prove the presence of SARS-CoV-2 virus in lung samples. Results: The main histopathological finding was diffuse alveolar damage with hyaline membrane formation, interstitial and alveolar oedema and fibrinous exudation in the alveoli. Interstitial inflammatory infiltration was mild to moderate. In some patients, alveolar damage was partly organized, but without the presence of fibrosis. We found cytopathic changes of the alveolar epithelium consistent with viral infection in all patients. We found the presence of virus in lung samples of all patients. Conclusion: COVID-19 disease affects the lungs, causing diffuse alveolar damage, which can lead to death. Autopsy still plays an important role in modern medicine, giving a contribution to the understanding of new diseases.