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The proceedings contain 109 papers. The topics discussed include: dose intensity of palbociclib and initial body weight dosage: implications on progression free survival in 220 patients with ER+/HER2-negative metastatic breast cancer;characteristics of Nirmatrelvir/Ritonavir (Paxlovid) recipients and clinical interventions by oncology pharmacists at a tertiary outpatient cancer center;safe handling of non-carcinogenic drugs in the Ghent University Hospital: development, implementation and communication of hospital-specific guidelines;case series: use of olaparib in uncommon locations in patients with impaired homologous recombination;real-world data evaluation of medicines used in special situations in oncohematology: a retrospective study from a comprehensive cancer institution;Dostarlimab in the treatment of recurrent endometrial cancer: real life experience;medication-related osteonecrosis of the jaws and CDK4/6 inhibitors in breast cancer;and efficacy and safety outcomes of generic imatinib in adults with chronic myeloid leukemia (CML) following the switch from branded imatinib.
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Objectives: To evaluate how payers utilize Institute for Clinical and Economic Review (ICER) assessments to inform coverage or formulary decisions. Method(s): Double-blinded, web-based survey was fielded through Xcenda's research panel, the Managed Care Network, from June to July 2022. Result(s): A total of 51 payers from health plans (n=27), integrated delivery networks (n=12), and pharmacy benefit managers (n=12) participated in the survey. When assessing the usefulness of ICER's value assessment framework (VAF) to inform formulary decisions within their organizations, 57% of payers indicated it was extremely/very useful, 33% indicated somewhat useful, and 10% indicated not at all/not very useful. Most respondents (73%) agreed that ICER assessments are aligned with their organization's internal assessment. Utilization of ICER's VAF was most prevalent in high-cost drug or disease states (78%), rare/orphan disease states (71%), and oncology/hematology disease states (67%). Payers reported less use in primary care disease states (29%), COVID-19 (8%), and digital therapeutics (4%). In the last 24 months, 20% of payers reported ICER's recommendations often influenced coverage decisions, 59% indicated occasional influence, and 22% indicated no influence. In the last 24 months, payers indicated the top 5 ICER assessments that influenced their coverage decisions included high cholesterol (38%), Alzheimer's disease (36%), atopic dermatitis (33%), multiple myeloma (31%), and chemotherapy-induced neutropenia (28%). ICER assessments that were less impactful included beta thalassemia (3%), digital health technologies (3%), and supervised injection facilities (3%). Payers reported using ICER assessments to inform both expanded and restricted coverage decisions. Conclusion(s): Payers find ICER's VAF useful to inform their organization's formulary decisions. ICER's assessments often align with payers' internal assessments and are most frequently utilized for high-cost drugs or disease states. Payers indicate ICER assessments have affected both expansion and restriction in their coverage policies.Copyright © 2023
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In novel coronavirus disease 2019 (COVID-19), liver injury was found at a high rate, and reports from outside Japan revealed that such injury was related to severity. We examined the characteristics of liver injury in 15 cases of COVID-19. Thirteen of these patients received antiviral therapy, such as favipiravir, remdesivir, and hydroxychloroquine. Liver injury was observed in eight cases at admission for COVID-19. The hepatic CT attenuation values at admission were significantly lower in nine patients who developed liver damage or showed its exacerbation during the treatment than in the remaining patients. Drug-induced liver injury due to antiviral drug was suspected in six cases. Liver injury due to COVID-19 may be related to low hepatic CT attenuation values and be modified by antiviral drugs.Copyright © 2021 The Japan Society of Hepatology.
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Objectives: Cases of fulminant myocarditis after mRNA COVID-19 vaccination have been reported. The most severe may need venoarterial extracorporeal membrane oxygenation (V-A ECMO) support. Here we report two cases successfully rescued with V-A ECMO. Method(s): We included all the cases supported with V-A ECMO for refractory cardiogenic shock due to myocarditis secondary to a mRNA SARS-COV2 vaccine in the high-volume adult ECMO Program in Vall Hebron University Hospital since January 2020. Result(s): We identified two cases (table). One of them was admitted for out-of-hospital cardiac arrest. In both, a peripheral V-A ECMO was implanted in the cath lab. An intra-aortic balloon pump was needed in one case for left ventricle unloading. Support could be successfully withdrawn in a mean of five days. No major bleeding or thrombosis complications occurred. Definite microscopic diagnosis could be reached in one case (Image, 3). Treatment was the same, using 1000mg of methylprednisolone/day for 3 days. A cardiac magnetic resonance 10 days after admission showed a significant improvement in systolic function and diffuse oedema and subepicardial contrast intake in different segments (Image, 1-2). Both patients were discharged fully recovered. Conclusion(s): V-A ECMO should be established in cases of COVID-19 vaccine-associated myocarditis with refractory cardiogenic shock during the acute phase. (Table Presented).
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Background: Coronavirus disease-2019 (COVID-19) poses expectant mothers to a higher risk of serious complications and mortality. Following a risk-benefit review, a number of governmental and professional bodies from across the globe recently approved the COVID-19 vaccination during pregnancy. Aim(s): This study aimed to investigate knowledge, actual acceptance, and concerns about the COVID-19 vaccine among the obstetric population. Material(s) and Method(s): Participants were selected from among the expecting women who came for antenatal checkup during the study period (October 1, 2021-November 30, 2021). About 150 pregnant women who met the inclusion criteria and consented were recruited into the study. Data related to socio-demographic and clinical characteristics as well as knowledge, actual acceptance, and concerns about COVID-19 vaccine were collected through in-person interviews using a prestructured questionnaire. The SPSS version 23 was used to analyze data. The association between the attitude (acceptance and hesitance) of participants toward the COVID-19 vaccine and their sociodemographic and clinical profile was found by Fisher's exact test. Result(s): The actual acceptance of the COVID-19 vaccine among expecting women was 52.0%. The primary motive for accepting COVID-19 immunization was to protect the fetus, followed by the protection of one's own health. A significant association was found between COVID-19 vaccine acceptance and the level of education, socio-economic status, and presence of comorbidities. The leading causes for vaccine reluctance were concerns about the efficacy and safety of the vaccines and lack of awareness about their usage during pregnancy. Conclusion(s): Multifaceted activities are required to promote the effectiveness and safety profile of the COVID-19 vaccine as well as disseminate knowledge about its usage during pregnancy. Clinical significance: Unlike numerous other studies that have investigated the accepting attitude only, the present one has investigated the actual COVID-19 vaccine uptake among the obstetric population.Copyright © The Author(s).
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This study compares the serological antibody level post-COVID-19 vaccine among healthy subjects and psychiatric patients on antidepressant therapy. It also examines the difference in antidepressants' side effects experienced by psychiatric patients following the completion of two vaccine doses. A comparative posttest quasi-experimental study was conducted among healthy subjects and psychiatric patients on antidepressant medication in a teaching hospital in Malaysia. Elecsys Anti-SARS-CoV-2 assay was used to detect the antibody titre between weeks 4 and 12 post vaccination. The antidepressant side-effect checklist (ASEC) was used to monitor the occurrence of antidepressant-related side effects pre-and post-vaccination. 24 psychiatric patients and 26 healthy subjects were included. There was no significant difference in the antibody level between the patients (median = 1509 u/ml) and the healthy subjects (median = 995 u/ml). There was no significant worsening in the antidepressant-related side effects. The antibody level post-COVID-19 vaccine did not differ significantly between patients on antidepressant therapy and healthy subjects. Additionally, there was no change in the antidepressant side effects experienced by the patients following the completion of the vaccine.Copyright © 2022, Research Trends (P) LTD.. All rights reserved.
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Objective: To assess the course of COVID-19 infections and the tolerability of the mRNA vaccines of Moderna and Pfizer/BioNTech and the viral vector vaccines from Astra Zeneca and Johnson & Johnson in adult patients with epilepsy (PWE). Method(s): From July 2020 to July 2021, we consecutively included adult outpatients with confirmed epilepsy. These PWE were interviewed about COVID-19 infections and vaccinations. Results of follow-up visits were added until the cut-off date (December 31, 2021). The data of COVID-19-infected without vaccinations or fully vaccinated PWE without COVID-19 infections were analyzed. Full vaccination was defined as a double vaccination with the Pfizer/BionTech, Moderna, or Astra Zeneca vaccines or a single Johnson & Johnson vaccination. Result(s): At cut-off, 612 of 1152 PWE fulfilled the inclusion criteria: 51 PWE had been infected without vaccination and 561 had full vaccination without infection. Among the infected PWE, 76.5% presented with symptoms;9.8% had a severe course (one death). The leading symptoms were influenza-like disorders (48.7% of infected PWE with symptoms), anosmia (28.2%), and ageusia (20.5%). Seizure increases or relapses after sustained seizure freedom occurred in 7.8%. Adverse events (AEs) were reported by 113 vaccinated PWE (20.1% of all vaccinated PWE). The leading AEs were fatigue, fever, and headache. The AE rate per vaccine was 14.0% for Pfizer/BionTech, 32.7% for Moderna, 25.8% for Astra Zeneca, and 46.2% for Johnson & Johnson. Of the AEs, 93.3% lasted <=1 week. Seizure increase or relapse occurred in 1.4% and was significantly less frequent than in the infected group (p= 0.0016). Conclusion(s): The course of COVID-19 infections and the tolerability of the vaccines were similar as in the general population, yet, seizure worsening occurred more often after the infection than after the vaccination.Copyright © 2023, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, part of Springer Nature.
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Introduction: Macrophage activation syndrome (MAS) is a severe hyper inflammatory condition caused by the over-activation and proliferation of T cells, NK cells and macrophages. It is often associated with complications of rheumatic/immune diseases. We present a case of a 15-year-old female who experiences recurrent episodes of MAS without any known definitive underlying etiology. Case Presentation: A 15-year-old previously healthy female developed fatigue, fevers, myalgia, chest pain, splenomegaly and lymphadenopathy 10 days after receiving her first Pfizer COVID-19 vaccine. Her symptoms recurred 10 days after receiving the second dose. Her myocarditis, MIS-C, and infectious work up was negative except for positive EBV IgG. Laboratory studies revealed anemia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. She initially responded to decadron;however, her symptoms recurred with steroid taper. Bone marrow biopsy revealed hemophagocytosis. Whole exome sequencing (WES) revealed a heterozygous variant of uncertain significance in UNC13D c.962C>A (p.Thr321Asn). She had multiple re-admissions with significantly elevated inflammatory markers, including extremely high IL2-R, IL-18 and CXCL9. Each episode was complicated by an acute viral infection. She responds to high dose steroids, anti-IL-1, and JAK inhibitors. Nonetheless, it has been difficult to wean decadron without triggering a flare. She continues to require increasing doses of baricitinib. Discussion(s): MAS may be seen as a complication of rheumatic diseases, as well as inborn errors of immunity. However, none of these conditions have been diagnosed in this patient despite extensive testing, including WES. The degree of her immune dysregulation has been very severe making her disease process unpredictable and extremely difficult to control. She has frequent flares precipitated by viral infections or attempts at adjusting her immunomodulators. Weaning her medications has been challenging as she continues to require increasing doses of baricitinib and corticosteroids. The UNC13D gene is associated with autosomal recessive familial hemophagocytic lymphohistiocytosis type 3 (FHL3). Our patient is heterozygous for an UNC13D variant of uncertain significance. Additional genetic inquiries with whole genome sequencing to help elucidate the underlying etiology of her severe condition is being conducted. We hypothesize she developed MAS due to a combination of genetic predisposition, prior EBV infection, and immune stress associated with the COVID-19 vaccine. [Formula presented] [Formula presented] [Formula presented]Copyright © 2023 Elsevier Inc.
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The patient presented with nausea, appetite loss, and fatigue. She had received two doses of Pfizer/BioN-Tech BNT162b2 mRNA vaccine (COMIRNATY) for coronavirus disease 2019 (COVID-19). Acute liver injury was noted 14 days after the first dose of the vaccine. Re-exposure through the second dose worsened the liver injury. After liver biopsy on the third day of admission, methylprednisolone (1000 mg) was administered. Liver histology showed acute hepatitis with diffuse lobular inflammation/necrosis and lymphocyte-dominant infiltra-tion in the portal areas. The patient was diagnosed with drug-induced liver injury due to the COVID-19 vaccine based on the Digestive Disease Week Japan 2004 (DDW-J) scale, which assesses the temporal relationship, liver biopsy, and laboratory findings. With improvements in the blood test parameters, prednisolone was gradually tapered and stopped. One month later, no biochemical signs of relapse were noted. To our knowledge, this is the first report describing liver injury after the administration of the Pfizer COVID-19 vaccine in Japan.Copyright © 2022 The Japan Society of Hepatology.
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Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.
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Bruton tyrosine kinase inhibitors (BTKis) were approved for use at the end of 2013 and have since been used for indications including chronic lymphocytic leukaemia (CLL), Waldenstrom's macroglobulinaemia and mantle cell lymphoma. The use of BTKis has increased significantly in the UK since they achieved NICE (National Institute for Health and Care Excellence) approval for frontline treatment of CLL in 2021. However, they are associated with significant adverse cardiovascular events. In September 2021 the British Journal of Haematology published good practice guidelines for the management of cardiovascular complications of BTKis. Our aim was to see whether these guidelines had been adhered to for patients taking BTKis. Method(s): Data was collected for all patients being prescribed BTKis (ibrutinib and acalabrutinib) in the South Tees NHS Trust in July 2022. Patients' medical records were used to assess whether their management adhered to the good practice guidelines. Data was collated for 67 patients in total. Result(s): The data showed that although all patients were consented for the risk of atrial fibrillation only 6% were consented for hypertension and only 1.5% for ventricular arrhythmias and sudden cardiac death. The guidelines recommend a baseline ECG (electrocardiogram) on commencement of treatment;however, only 7% had this completed and 0% had the minimum monitoring recommendation of 6-monthly ECGs. Thirty patients (45%) had an indication for a baseline echocardiogram;however, only one had this completed. For patients reporting symptoms of syncope, dizziness or palpitations only 50% had an ECG completed. Three patients developed worsening heart failure. The recommendations suggest referral to a cardio-oncologist;however, due to lack of availability of this service the referrals were instead made to the usual cardiologist. Conclusion(s): Although there was a lack of compliance with guideline recommendations, it should be considered that most usual checks were affected by COVID-19 outbreaks and a drop in face-to- face clinics, which were replaced by phone clinics and home delivery of medications. However, the premade consent forms for BTKis need to be updated to include consent for ventricular arrhythmias and sudden cardiac death. There also needs to be routine procedures in place to ensure that regular blood pressure testing and ECG monitoring occurs and that there is prompt recognition of cardiovascular complications. Action and implementation: To ensure improved compliance with these guidelines we plan to update our consent forms and create a proforma for clinic use to ensure that clinicians are aware of the various monitoring criteria required.
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The TG6002.03 trial is a dose-escalation phase 1 clinical trial of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion). TG6002 infusion was performed over 30 minutes via selective catheterization of the hepatic artery proper. 5-FC oral dosing was 50mg/kg x4 daily. Blood was sampled for TG6002 pharmacokinetics and 5-FC and 5-FU measurements. Sampling of liver metastases was performed at screening and on day 4 or day 8 for virus detection and 5-FC and 5-FU quantification. In total, 15 patients (median age 61 years, range 37-78) were treated in 1 UK centre and 2 centres in France and received a dose of TG6002 of 1 x 106 (n=3), 1 x 107 (n=3), 1 x 108 (n=3), or 1 x 109 pfu (n=6). Fourteen of the 15 patients received a single cycle of treatment, including one patient who did not received 5-FC, and one patient received two cycles. TG6002 was transiently detected in plasma following administration, suggesting a strong tissue selectivity for viral replication. In the highest dose cohort, a virus rebound was observed on day 8, concordant with replication time of the virus. In serum samples, 5-FU was present on day 8 in all patients with a high variability ranging from 0.8 to 1072 ng/mL and was measurable over several days after initiation of therapy. Seven of the 9 patients evaluable showed the biodistribution of the virus in liver lesions by PCR testing on day 4 or day 8. Translational blood samples showed evidence for T-cell activation and immune checkpoint receptor-ligand expression. At 1 x 109 pfu, there was evidence for T-cell proliferation and activation against tumour-associated antigens by ELISpot and for immunogenic cell death. In terms of safety, a total of 34 TG6002-related adverse events were reported, of which 32 were grade 1-2 and 2 were grade 3. The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively localized and replicated in the tumor tissues, expressed its therapeutic payload and showed anti-tumoral immunological activity.
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Timely, effective, and safe antiviral therapy in COVID-19 patients reduces complications, disability and mortality rates. The greatest concern with remdesivir is the risk of drug-induced liver injury, including in patients whose liver function is compromised by COVID-19. The aim of the study was to investigate the efficacy and safety of remdesivir in patients with confirmed SARSCoV-2 infection who had been admitted to an infectious diseases hospital in the Volgograd region in March 2022. Material(s) and Method(s): the authors carried out an open, non-randomised, single-arm study using medical records of 234 patients who had been diagnosed with "U07.1 COVID-19, virus identified" and prescribed remdesivir upon admission. The effectiveness of therapy was evaluated using two criteria: the need for oxygen supplementation or ventilatory support, or mortality. The authors conducted the evaluation on days 7, 14, and 28 using the six-point ordinal severity scale by Y. Wang et al. The safety of therapy was assessed on the basis of complaints and changes in laboratory findings. Result(s): for the patients prescribed remdesivir at admission, the 7-day mortality rate was 3.0%, the 14-day mortality rate was 5.6%, and the 28-day mortality rate was 7.3%. With the exception of a patient with myocardial infarction, all the patients who had been hospitalised with mild COVID-19 and prescribed remdesivir did not require oxygen therapy and/or transfer to intensive care and were discharged following recovery. The patients with moderate to severe COVID-19 had the 14-day mortality rate of 6.4% and the 28-day mortality rate of 8.6%. 17 patients (7.2%) discontinued remdesivir prematurely for various reasons, including adverse drug reactions. Remdesivir therapy of 5-10 days was associated with an increase in ALT activity by 2.7 +/- 0.8 times in 15.9% of patients with mild COVID-19, by 3.8 +/- 1.8 times in 20.4% of patients with moderately severe COVID-19, and by 4.8 +/- 2.7 times in 24% (12/50) of patients with severe COVID-19. In two patients (0.9%), the increase exceeded 10-fold the upper limit of normal. Conclusion(s): the obtained results support recommending remdesivir to patients with mild, moderate and severe COVID-19, including those with moderately elevated baseline activity of hepatic transaminases.Copyright © NEICON ISP LLC. All rights reserved.
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Objectives: Varenox is the first locally manufactured and approved biosimilar in Algeria. It is an enoxaparin sodium (ES) with established good analytical characterization and manufacturing quality control. The aim of the PROPHYVAR study was to generate real-life data in routine practices and to assess the safety and tolerability in the prophylaxis of venous thromboembolism (VTE). Method(s): This is an observational, prospective, multicenter study, conducted between April 2021 and May 2022. The primary safety outcome was the incidence of Adverse Events (AEs) related to the study drug. A sample size of 500 patients was calculated to estimate the proportion of patients with AEs. Assuming that approximately 10% will be lost to follow-up or not evaluable, 550 patients were needed to describe the impact of Varenox use. Result(s): The study was conducted in 25 different sites in Algeria, in 4 therapeutic areas: ICU, orthopedic surgery, obstetrics and nephrology;550 patients were included and received at least one injection of Varenox. The mean age was 47 years, women in majority (62.5%). The patients were overweight or obese (53%), with a history of arterial hypertension (25%), diabetes (7.5%) and renal failure (6.4%). Reasons for hospitalization were mainly fracture (15.5%), pregnancy (8.3%), COVID-19 (7%) or cancer (7%). The majority of patients were treated at prophylactic dose of 0.4ml (80%) or 0.6ml (10%). The median duration of follow-up was 24 days. A total of 38 patients experienced at least one AE (6.9%, CI95=[4.9%;9.4%]). Related AEs were reported in 10 patients (1.8%), mainly in nephrology (N=7 arterio-venous fistula). VTE events were reported in 6 patients (1.1%, CI95=[0.2%;2%]). Conclusion(s): This study suggests that Varenox is safe in the prophylaxis of VTE. To our knowledge this is the first large study describing the use of ES in current medical practice in Algeria.Copyright © 2023
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Objectives: Several populations are at greater risk of severe COVID-19 due to inadequate responses to COVID-19 vaccines. Many of these individuals, and their caregivers, continue practicing varying degrees of social isolation to avoid SARS-CoV-2 infection. Following the end of lockdowns, the behaviors and impacts of continued isolation on the quality-of-life of high-risk populations remain poorly understood. This study describes the main avoidance and protective behaviors and ongoing impacts experienced by adults and caregivers of adults at high-risk of severe COVID-19. Method(s): Four virtual focus groups (April-July 2022) were conducted with individuals at high-risk of severe COVID-19, or caregivers, recruited via a convenience sample from patient panels. A discussion guide of open-ended questions was prepared based on COVID-19 guidance documents and a literature review. For qualitative analyses, an inductive approach was used for behaviors, deductive for impacts. A pre-defined codebook was updated throughout as needed. Salient concepts were defined as those mentioned by >=30% of participants or in every focus-group session. Result(s): Fourteen participants were interviewed (12 patients, 2 caregivers). Participants highlighted continued behaviors greatly impacting their quality-of-life. Avoidance behaviors (staying home, avoiding bystanders, avoiding shopping facilities and gatherings, using delivery services, family protection [43%-64%]) and protective behaviors (masking [79%], vaccination [57%]) were reported. Negative impacts included family relationship impacts (71%), collapse of social relationships (57%), difficulties accessing healthcare (43%), anxiety, fear, loneliness and depression (36%-50%), and impacts on employment/finances (36%). Positive impacts included the advent of telehealth (57%) and recognizing family importance (36%). Lack of trust in authority (57%) and hoarding of medications (36%) were negative general impacts of the COVID-19 pandemic highlighted. Concepts reported by patients and caregivers were similar. Conclusion(s): Individuals at high-risk of severe COVID-19 and their caregivers maintained avoidance and protective behaviors similar to those reported during lockdowns. This study highlights the continued burden experienced by high-risk populations.Copyright © 2023
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Surgical care in a mono-hospital for patients with COVID-19 leads to a number of organisational problems due to the lack of specialised departments. The article presents the experience of surgical treatment in a mono-hospital obtained from one and a half years of work in this mode. In total, approximately 400 surgeries were performed. The experience of treatment of 7 patients with acute intestinal obstruction has been summarised. In the abdominal cavity, a significant number of hematomas of varied localisation were found under the parietal and visceral peritoneum, as well as in the subcutaneous fat. This is possibly associated with anticoagulant therapy included in the treatment regimen for patients with COVID-19 according to the methodical recommendations by the Ministry of Health of the Russian Federation. As an illustration, a successful case of treating COVID-19 patient with strangulated hernia of the abdominal white line complicated by acute intestinal obstruction is presented.Copyright © 2022, Krasnoyarsk State Medical University. All rights reserved.
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Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.
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Objective: A new generation of vaccine technology platform has been developed to combat the COVID- 19 pandemic, the mRNA vaccine. The EMA granted the Pfizer- BioNTech COVID-19 vaccine an emergency use authorization in December 2020 with limited clinical experience, especially in the pediatric population. Method(s): Here, we present a case-report of a 17-yearold girl, who was vaccinated with the mRNA-COVID vaccine in October 2021, and developed a gross hematuria and proteinuria the day after the vaccination. Result(s): The patient presented at our outpatient clinic three days after the vaccination with new-onset hematuria and proteinuria. Up to this date, she had no former known medical conditions and the family history was negative regarding kidney diseases. We excluded nephrolithiasis, autoimmune glomerulonephritis and urinary tract infection as causes. The laboratory chemistry of the kidney was within normal range. The proteinuria dissolved spontaneously, and a microhematuria persisted. One day after the second dose of Cominarty in November 2021, the gross hematuria with proteinuria relapsed. A treatment with an ACE-inhibitor did not have any effect on the proteinuria. At this point, only a few casereports of patients with a comparable clinical course, especially from Japan, were published. In suspicion of a vaccine-triggered nephritis we started a prednisolon therapy which dissolved the proteinuria and induced a regression of the haematuria to a minimal stage. Conclusion(s): Within the last year, the medical community has gained more insights concerning mRNA vaccines. There is growing evidence, that mRNA vaccines can trigger de novo or relapse IgA nephropathy. But more systematic research and long-term evaluation is desirable to elucidate the underling pathophysiology as well as the influence on kidney survival of affected patients in the future. Furthermore, patient education should incorporate the risk of hematuria and proteinuria in children when applying mRNA vaccines.
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The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.