The First Domestic Original Drug for the Treatment of COVID-19: Azvudine

OBJECTIVE To summarize the basic information, mechanism of action, pharmacokinetics, efficacy, safety, interactions, and precautions of azvudine, to provide references for its clinical use. METHODS Literatures related to azvudine from the official website of Chinese clinical trial regi stry, clinicaltrials.gov, Pubmed, CNKI and Wanfang were systematically searched and summarized. RESULTS Azvudine is an oral small-molecule corona virus disease(COVID-19) treatment drug independently developed by China. As a nucleoside analogue targeting to viral RNA-dependent RNA polymerases (RdRp), it can inhibit RNA virus reverse transcription process and replication process. The results of phase III clinical trials showed that azvudine could significantly shorten the time of nucleic acid conversion in patients with mild to moderate corona virus disease (COVID-19). Compared with the control group, the azvudine group can significantly shorten the improvement time of pneumonia. For moderate and severe patients, azvudine treatment also showed significant therapeutic effects in the time of nucleic acid conversion, discharge, and rehabilitation. CONCLUSION The drug possesses good safety and tolerability in patients, which provide a choice for the clinical treatment of COVID-19.

The Effect of Carriage of CYP3A5*3 and CYP3A4*22 Polymorphic Variants on the Safety of Remdesivir Therapy in Patients with COVID-19

The aim of the study was to assess the association of polymorphic variants CYP3A5*3 6986 A>G rs776746 and CYP3A4*22 rs35599367 C>T with the safety parameters of remdesivir therapy in patients with COVID-19. Material and methods. The study included 156 patients admitted to the City Clinical Hospital No. 15 of the Moscow Health Department with COVID-19 diagnosis, who received remdesivir as an antiviral drug. The frequency of adverse reactions (bradycardia, dyspeptic disorders), as well as various laboratory parameters (ALT, AST, creatinine, ferritin, interleukin-6, and d-dimer levels) were compared between the carriers of wild-type and polymorphic variants of the studied genes. Results. Carriers of CYP3A5*3 polymorphic variants (GA+AA) had higher ALT levels after the treatment with remdesivir than carriers of the wild variant (GG). When comparing the level of interleukin-6 after therapy with remdesivir, carriers of the polymorphic variant of the CYP3A4*22 (CT) gene had a significantly higher level of this cytokine. Conclusion. An association between the carriage of polymorphic variants of CYP3A5*3 and an increase in the level of liver enzymes was found. Polymorphic variants of CYP3A4*22 were associated with higher levels of interleukin-6. Additional pharmacogenetic studies are required to assess the possibilities of personalizing antiviral therapy for COVID-19.

Tixagevimab/ Cilgavimab Outcomes Among Patients with Immunodeficiency

Rationale: The FDA granted an emergency use authorization for tixagevimab/ cilgavimab in December 2021 for COVID-19 pre-exposure prophylaxis for individuals that are moderate to severely immunocompromised and has since recommended repeat dosing every 6 months. Given its novelty and resultant hesitation for use among some physicians and patients, our study aimed to observe safety and efficacy of tixagevimab/ cilgavimab, including against one of the newest variants, Omicron BA.5, among our patient population with immunodeficiencies 6 months post-administration via a telephone survey. We hypothesized that adverse outcomes would be minimal and COVID-19 incidence and severity would lessen following tixagevimab/cilgavimab administration. Methods: The Atrium Health Wake Forest Baptist Allergy, Asthma, and Immunology department recruited 15 patients with immunodeficiencies receiving immunoglobulin replacement and tixagevimab/ cilgavimab in March 2022 for a prospective cohort study. A telephone survey was conducted 6 months later regarding tixagevimab/ cilgavimab adverse effects and incidence/severity of COVID infection before and after administration. Results: Two patients experienced minor adverse effects (fatigue, bruising) following tixagevimab/ cilgavimab administration. No severe reactions were reported. Two patients required hospitalization for severe COVID-19 infection prior to tixagevimab/cilgavimab administration, whereas 0 patients required hospitalization for COVID-19 in the 6 months following administration. Four of 5 patients that had COVID-19 following administration had not yet received the bivalent Omicron booster vaccine and 2 had received no COVID-19 vaccines. Conclusions: Tixagevimab/ cilgavimab is associated with minor adverse effects and reduction of COVID-19 severity, albeit perhaps not associated with diminished incidence of newest COVID-19 strains, in a prospective, population-based cohort.

Aspects and issues of marketing authorisation and use of medicinal products for COVID-19 prevention during the pandemic

At the end of 2019, an outbreak of a new coronavirus began in the city of Wuhan (Hubei Province) in the People's Republic of China. The outbreak turned into a pandemic. In the shortest possible time, national and international manufacturers developed preventive COVID-19 vaccines, and the population was vaccinated. During pandemics, accelerated approval of vaccines is an important factor that shortens the time to market with the aim of mass vaccination. The experience of rapidly developing and introducing vaccines into routine practice is not only important for managing the current pandemic, but also valuable in case of extremely likely future ones. The aim of this study was to analyse the main issues associated with assessing the safety and efficacy of vaccines for COVID-19 prevention during their registration and widespread use amid the pandemic and ongoing SARS-CoV-2 evolution. The vaccines for COVID-19 prevention were developed and introduced into healthcare practice very rapidly and under the circumstances of the pandemic, and the use of these vaccines has surfaced a number of concerns requiring further research. The most important issues identified in the performed analysis include, but are not limited to the need for accelerated assessment of the safety and immunogenicity of new vaccines;the lack of immune correlates of protection against SARS-CoV-2;the waning of antibody immunity over time, motivating the need to determine revaccination and post-recovery vaccination timelines;and the emergence of mutant SARS-CoV-2 variants. One of noteworthy aspects is the need to develop recommendations for updating the strain composition of registered COVID-19 vaccines. According to the conclusions, the level of herd immunity, including vaccine-induced protection, plays a certain role in virus evolution during the pandemic. If COVID-19 becomes seasonal, which is a probable scenario, regular revaccination can be essential.

Safety of and antibody response to the BNT162b2 COVID-19 vaccine in adolescents and young adults with underlying disease

Background: Data are limited regarding the safety of and antibody response to the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid vaccine in adolescents and young adults with underlying disease. Methods: This prospective observational study enrolled patients age 12–25 years with chronic underlying disease who received 2 doses of BNT162b2. A 18-item questionnaire was used to assess adverse events within 7 days post-vaccination, and data regarding severe adverse events were collected from electronic medical records. An antibody titer for the receptor-binding domain of the spike protein in SARS-CoV-2 was used to assess antibody response after the second vaccine dose. Results: Study participants were 429 patients (241 [56.2%] age 12–15 years;188 [43.8%] age 16–25 years). The most common underlying diseases were genetic or chromosomal abnormalities and/or congenital anomalies, followed by endocrine or metabolic diseases;32% of participants were immunocompromised. Severe adverse events were observed after the second dose in 1 (0.4%) patient age 12–15 years and in 2 (1.1%) patients age 16–25 years;all patients recovered. Seropositivity after the second vaccine dose was 99.0%. The geometric mean antibody titer was higher in patients age 12–15 years versus 16–25 years (1603.3 [1321.8–1944.7] U/mL vs. 949.4 [744.2–1211.0] U/mL). Compared with immunocompetent patients, immunocompromised patients had a lower antibody titer (2106.8 [1917.5–2314.7] U/mL vs. 467.9 [324.4–674.8] U/mL). Conclusions: Vaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases

Challenges and strategies with international recruitment in early phase gene therapy trials

The Children's NIHR Clinical Research Facility at Royal Manchester Children's Hospital has been involved in numerous early phase gene therapy trials for diseases such as GM1 gangliosidosis, Gaucher disease, MPSIIIA and MPSII. These trials have necessitated international recruitment which brings challenges for both site and families. In addition, we also actively recruited participants during the Covid-19 global pandemic, amplifying these challenges. A typical patient journey on one of these trials would involve being approached soon after diagnosis due to the rapid progression of these diseases and the need for early intervention. The family would then relocate to the UK with relatively short notice and commence an intensive period of screening involving a lot of extensive information for them to retain and invasive procedures for the patient. Some of these families will speak no English at all which is an additional barrier to managing the parental anxiety and expectations of the trial and its outcome. Once eligibility is confirmed the families are then faced with an extended stay in the UK without the support of their extended family/community. This impacts parent's employment and other siblings who may or may not be with them and who may also be affected by the same disease. Following administration of the gene therapy, participants then commence intensive follow up often associated with immunosuppressants. Close working with the local clinicians is essential for patient safety and trial integrity. Good engagement with families once they have returned to their home country is vital in obtaining continuing trial data and ensuring retention and compliance with attending future visits. Follow up visits are essential for safety and efficacy data for the progression of gene therapy trials. Travel restrictions brought about by the covid 19 pandemic exacerbated these challenges but with good communication and engagement we have mostly overcome them.

Experience of Using Remdesivir in Patients with Novel Coronavirus Infection

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. Materials and methods: 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. Results: 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. Conclusions: 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.

MAINTAINING AN ACTIVE RESEARCH CAREER DURING COVID-19 LOCKDOWNS

Maintaining an active medical research career is a multifaceted undertaking, and many challenges arise, even under normal circumstances. Therefore, the Australian government mandated COVID19 lockdowns and worksite restrictions from 2020 2021 inflicted an additional layer of complexity to an already complicated career for most researchers. A critical issue I faced during these COVID19 lockdowns was to establish whether our research focus was considered an essential service during a period of time when the public health advice was to restrict the movement of research staff and students by enacting new laws to ensure they stay at home. My research team members were also rightfully worried about contracting COVID19 during a period when a viable vaccine was not available. In this presentation, I will be covering some of the adaptive changes I implemented during the COVID19 lockdowns to ensure the continuity of our research program, which includes: 1) Proactive engagement with our medical institute and university COVID-19 taskforces to formulate a joint vision of which research areas should be prioritised during these lockdowns in pursuit of both treatments and vaccines;2) Continuous communication with my research team to encourage, motivate and energise staff and students to allow them to contribute to the research program meaningfully;3) Provide flexible working hours for research team members to work within the confinements of a reduced worksite footprint with an appreciation for social distancing;and 4) Contingency planning to ensure if one research team member contracts COVID-19, there are others with the cross-functional skillset to take over their responsibilities. Taking such steps ensured the rapid development of a new treatment regime that was showing impressive results in reversing multi-organ dysfunction in another clinically challenging area in intensive care units (sepsis). Following the preclinical assessment of safety and efficacy of this new treatment regime, we were able to compassionately treat a critically ill COVID19 patient receiving intensive care at Austin Health. In a short period of time, we saw improved regulation of blood pressure, arterial blood oxygen levels and kidney function. The patient was able to be taken off machine ventilation 12 days after starting sodium ascorbate treatment and discharged from hospital without any complications 22 days later. This research has now informed the design and commencement of multi-centre randomised controlled clinical trials at four hospital intensive care units in Australia.

Safety of Gam-COVID-Vac (Sputnik V) Combined Vector Vaccine in Patients With Immunoinflammatory Rheumatic Diseases: Preliminary Data

Background. Patients with autoimmune and inflammatory rheumatic diseases (AIRDs) are at high risk of developing COVID-19. Vaccination is an effective method of preventing this disease, which may be unsafe for patients with AIRDs. The aim of the study is to assess the safety of Gam-COVID-Vac in patients with IVRD in real clinical practice. Material and methods. A cross-sectional study was carried out. The main group consisted of patients with AIRDs, the control group consisted of individuals without AIRDs. All participants were interviewed by the research physician using a unified questionnaire, additional information was obtained from medical records. Results. The study included 222 patients with AIRDs (119 with rheumatoid arthritis, 36 with ankylosing spondylitis, 17 with psoriatic arthritis, 17 with Sjögren's disease, 10 with undifferentiated spondyloarthritis, 8 with systemic lupus erythematosus, 4 with metabolic arthritis, 3 with systemic scleroderma, 3 with systemic vasculitis, 2 with polymyalgia rheumatica, 2 with undifferentiated systemic connective tissue disease, 1 with adult Still's disease) and 111 patients without AIRDs. The number of patients with AIRDs who had a combination of local and systemic adverse events (AE) on the introduction of the first component of the vaccine was significantly less than in the control group (22.1 and 44.1%, respectively, P<0.001). Similar differences were also noted after the introduction of the second component (14.0 and 29.7%, respectively, P<0.001). AEs such as pain at the injection site without restriction of movement, weakness, fever, arthralgia/myalgia, headache, and chills were significantly more common in the control group after the introduction of the first component of the vaccine. After complete immunization, AEs were absent in 35.6% of patients with AIRDs and in 21.6% of control group patients (P=0.01). Exacerbations of AIRDs and new autoimmune phenomena were not registered in any cases. Conclusions. According to preliminary data, immunization of patients with AIRDs with the Gam-COVID-Vac combined vector vaccine appears to be quite safe.

Ambroxol therapy for patients with Gaucher disease type 1, either poor responders to enzyme replacement therapy/substrate reduction therapy (ERT/SRT) or untreated

Ambroxol hydrochloride is an oral mucolytic drug, available over-the-counter for many years as cough medicine, which was found to also act as a pharmacological chaperone for mutant glucocerebrosidase, albeit in a several-fold higher dose. Proof-of-concept reports have been published over the past decade in all three forms of Gaucher disease (GD). The current study aimed to assess the safety and efficacy of 12-months ambroxol 600 mg/day in 3 groups of type 1 GD patients with sub-optimal response, after a minimum of 3 years, to enzyme replacement therapy (ERT)/substrate reduction therapy (SRT) defined as lumbar spine bone density <−2.0 t-score, or platelet count<100 × 10−3/L, or LysoGb1 > 200 ng/ml, and for a group of naïve patients, i.e., never treated or stopped therapy >12 months prior to enrollment, who had abnormal values in 2 of the 3 above-mentioned parameters. Forty patients were enrolled: 28 ERT/SRT treated and 12 naïve;21 (52%) males, mean age 52 years (range 24–84). Safety aspects included several adverse effects (mainly gastrointestinal, excessive saliva, and vertigo) all mild and transient in nature, but led to drug discontinuation in 14 patients, additional dropouts were 7 patients due to COVID19 pandemic and 3 due to personal reasons. Of the remaining 16 patients, 14 have completed 12 months, and 2 are ongoing. Of the 14 completers, 5 (~36%) achieved significant improvement in at least one of the three parameters, and nine did not demonstrate any improvement nor deterioration. The interpretation of the results must take into account the fact that most of the enrolled patients have had poor response to ERT/SRT (including 10 of the 12 naïve patients) and therefore may not represent the majority of the patients. Further studies are needed in never-treated patients as well as an oral, less expensive, alternative to unselected stable patients currently treated with ERT/SRT with a favorable response.

Treatment of children with COVID-19

Currently, there is not any specific effective treatment for COVID-19. There are many studies published and ongoing especially on adult patients. Treatment options in pediatric patients are determined according to the agents used in adult patients. Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Supportive therapy forms the basis of the treatment as the symptoms and disease course in children are mild. There are currently no randomized controlled trials of drugs that can be used to treat COVID-19 in children. However, in severe clinical cases, the drugs used in adults are evaluated and used on a case-by-case basis. There is a growing need for well-designed controlled clinical trials to better define the safety and efficacy of potential treatments for COVID-19 in children.

Comparison Of The Efficacy And Safety Of Secukinumab, Ustekinumab And Guselkumab For The Treatment Of Moderate To Severe Plaque Psoriasis: A Systematic Review

Psoriasis is a chronic inflammatory skin condition characterized by scaly erythematous patches or plaques affecting the extensor surfaces that are prominent but spreading to all areas of the body, including the flexor surfaces. Psoriasis occurs when the body's immune system attacks the skin;the interleukin (IL)-12 and IL-17/23 axes play a major role in its pathogenesis. Biologic therapies targeting IL-17 or IL-23 have emerged as an important treatment option for psoriasis and have led to substantial improvements in patients' quality of life. This systematic review aimed to evaluate the comparative efficacy and safety of secukinumab, ustekinumab and guselkumab for the treatment of moderate to severe plaque psoriasis. Based on the final analysis, there were 10 articles, namely 5 RCTs and 5 observational. We found that patients who were given secukinumab showed a rapid response, whereas guselkumab was superior in terms of long-term response (approximately 1 year) and complete remission compared to other biologics. Among all the biologics assessed, ustekinumab showed relatively low efficacy.

Safety and immunogenicity of booster dose in patients with chronic liver disease

Background/Aims: Several studies showed that patients with liver cirrhosis have an immune dysregulation leading to poor immunological response to vaccination. However, in literature there are few data about the response to SARS-CoV-2 vaccination in patients with chronic liver disease (CLD). Aims of the study are (is) the evaluation of safety and immunogenicity of booster dose in patients with CLD. Methods: From September 2021 to April 2022, all consecutive outpatients with CLD who completed the primary vaccination course and the booster dose for anti-SARS-CoV-2 vaccination were enrolled. Blood samples were collected 12-16 weeks after second dose and after booster dose. Collected samples were analyzed for detecting anti-Spike protein IgG using LIAISON TrimericS IgG chemiluminescent assay (Diasorin, Italy). Results: We enrolled 340 patients (187 Males, mean age:64.32±17.34years). Stratified by the presence of cirrhosis, 249 had CLD and 91 were cirrhotic whose 57 (62.24%) had portal hypertension. At the end of the primary vaccination course, 60 patients (17.65%) did not develop a protective antibody titer, with no statistically significant differences between the two groups (19.7% in cirrhotic vs 16.8% in non-cirrhotic;p=0.076). The majority of them (53/60 patients;88.3%) developed a protective titer after booster dose, without differences between cirrhotics and non-cirrhotics (p=0.089). At multivariate analysis, factors associated with a higher humoral response after booster dose were young age (p=0.0098);porto-sinusoidal vascular disorder (p=0.005), none or a single comorbidity rather than two or more (p=0.05) and Spikevax booster dose compared with Comirnaty (p=0.001). Moreover, the antibody titer is inversely related to age (p=0.000). Conclusions: In a large cohort of patients with CLD booster dose of anti-Sars-CoV-2 vaccine has an excellent immunogenicity and leads to an adequate antibody response even in those who had not produced a protective titer after the primary vaccination course. Cirrhosis is not associated with a reduced humoral response.

Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

Background & Aims: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Methods: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited;35 females;median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Results: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases;seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. Conclusion: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition. Impact and implications: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition. © 2022 The Author(s)

Immunogenicity of Vaccines Against SARS-CoV-2 In Patients With Rheumatic Diseases

The problem of coronavirus disease 2019 (COVID-19) still remains relevant even now, after two years. As one of the methods of combating the current COVID-19 pandemic, most experts suggest the widespread use of vaccination. The use of anticovid vaccines in patients with rheumatic diseases raises a number of questions related to efficacy, immunogenicity (especially in patients receiving immunosuppressive therapy), as well as safety of immunization. With that in mind, it is very important to analyze the data on the above-mentioned aspects in real time. This review presents the results of studies on COVID-19 vaccination immunogenicity in rheumatology conducted over the past two years. The ability of a number of antirheumatic drugs to have a negative effect (to varying degrees) on the post-vaccination response has been demonstrated. Interpretation and comparison of the results of vaccine immunogenicity studies are complicated by a number of factors usually associated with the design of works. Within the framework of the problem under consideration, there are still a sufficient number of questions, the answers to which should be found in further research.

The impact of telesensors on neurosurgical service demand: A cohort cost-effectiveness analysis from institutional and patient perspectives

Introduction: Implantable telemetric intracranial pressure sensors (telesensors) enable routine, non-invasive ICP feedback which can assist with clinical decision-making and attribution of pressure-related symptoms in patients with CSF shunt systems. Here, we aim to characterise telesensor cost-effectiveness and impact on service demand. Methods: A single-centre, retrospective, cohort study and costeffectiveness analysis of 80 patients (78% Female;30% IIH, 22% Chiari malformation, 48% other) with MScio® (Christoph Miethke) telemetric ICP monitors. Service demand in the two years before and after implantation were retrieved from the centre's electronic patient record system. Intentionally, data did not overlap with the COVID-19 pandemic period. The frequencies of hydrocephalusrelated neurosurgical admissions, outpatient clinics, and scans were recorded along with A&E, neurology, and ophthalmology encounters. Tariffs were used to compare expenditure before and after implantation. Results: Significant reductions were seen in the frequencies of neurosurgical admissions (1.9/year to 0.6;p < 0.001), ICP monitoring (0.4 to 0.01;p < 0.001), and CT scans (0.5 to 0.3;p = 0.013) following implantation. There were also significant reductions in the proportion of patients requiring admissions (91% to 45%;p < 0.001) and ICP monitoring (30% to 3%;p < 0.001). There were non-significant reductions in other invasive procedures, neurology encounters, and A&E admissions. Overall, there was a £341 (SD = 1069) per patient per year saving (22% reduction in included costs). Conclusions: From an institutional perspective, the implantation of telesensors contributes to a reduction in service demand and a net financial saving. From a patient perspective, fewer appointments, invasive procedures, and radiation exposures suggest an improvement in patient experience and safety.

Peripheral facial palsy post SARS-CoV-2 vaccine: A regional pharmacovigilance cases series.

Peripheral facial palsy (PFP) is a rare adverse reaction identified from clinical trials of coronavirus disease 2019 (COVID-19) vaccines (messenger ribonucleic acid [mRNA] and viral vector). Few data are available on their onset patterns and risk of recurrence after re-injection of a COVID-19 vaccine; the objective of this study was to describe PFP cases attributed to COVID-19 vaccines. All cases of facial paralysis reported to the Regional Pharmacovigilance Center of Centre-Val de Loire area between January and October 2021, in which the role of a COVID-19 vaccine was suspected, were selected. Based on initial data and following additional information requested, each case was reviewed and analyzed to include only confirmed cases of PFP for which the role of the vaccine could be retained. From the 38 cases reported, 23 were included (15 excluded because of diagnosis not retained). They occurred in 12 men and 11 women (median age of 51 years). The first clinical manifestations occurred with a median time of 9 days after COVID-19 vaccine injection, and the paralysis was homolateral to the vaccinated arm in 70%. The etiological workup, always negative, included brain imaging (48%), infectious serologies (74%) and Covid-19 PCR (52%). Corticosteroid therapy was prescribed for 20 (87%) patients, combined with aciclovir in 12 (52%). At 4-month follow-up, clinical manifestations had regressed completely or partially in 20 (87%) of the 23 patients (median time of 30 days). From them 12 (60%) received another dose of COVID-19 vaccine and none had a recurrence and the PFP regressed despite the second dose in 2 of the 3 patients not fully recovered at 4 months. The potential mechanism of PFP after COVID-19 vaccine, which don't have a specific profile, is probably the interferon-γ. Moreover, the risk of recurrence after a new injection appears to be very low, which makes it possible to continue the vaccination.

Systemic lupus erythematosus cutaneous flare following COVID-19 vaccination: A case report

Objective: To present a case of a SLE cutaneous flare following COVID-19 vaccination in a patient with low disease activity Background: Disease flare in a patient with underlying autoimmune rheumatic disease (AIRD) after vaccination had already been experienced with other vaccines, such as influenza, hepatitis B, and HPV vaccines. Given the relatively unknown safety profile of the COVID-19 vaccine among patients with AIRD, the probability of a disease flare is not a remote possibility. Several case reports available had already reported few cases of AIRD disease flare following vaccination, some of which requiring escalation of the treatment regimen. Molecular mimicry, as had been described with other vaccines, is still implicated as the possible explanation for such a phenomenon. Case: A 57 year old female with systemic lupus erythematosus with nephritis since 1994 with low disease activity, maintained on hydroxychloroquine and low dose methylprednisolone daily who developed multiple well-defined elevated erythematous and pruritic plaques on both thighs, spreading to the face, scalp, trunk, and extremities 3 weeks after receiving her first dose of viral vector vaccine. Work-ups included eosinophilia on CBC, elevated ESR, anti-dsDNA, ferritin, and LDH, with low C3, with proteinuria and hematuria on urinalysis. She was admitted and her glucocorticoid was increased and tapered accordingly. Skin punch biopsy with alcian blue staining was also done which revealed interface dermatitis consistent with lupus erythematosus. Few days after increasing her glucocorticoid, cutaneous lesions gradually resolved and she was discharged improved. She received her second dose of vaccine 2 months after her first dose with no reported incidents of adverse events. Conclusion(s): This is one of the few cases of a reported SLE flare confirmed by disease activity index and biopsy-confirmed skin rashes. The development of such an adverse reaction to a vaccine may be relatively low but still possible due to intricate interaction of the immune system and vaccine.

Adverse events of COVID-19 vaccines in patients with rheumatic and musculoskeletal disease (RMD)

Background: COVID-19 has severely influenced all aspects of life since its emergence and one of the strategies to end this pandemic rest on the vaccination to achieve herd immunity. While vaccinations are usually a safe and effective tool, the abbreviated development process of the available COVID -19 vaccines has increased uncertainties about the safety among the general population especially among patients with immune-mediated diseases (IMD) such as RMD. Method(s): This was a cross sectional study looking at the incidence of adverse events within a month following COVID-19 vaccination among the RMD patients attended rheumatology clinic at the Hospital Tuanku Ja'afar Seremban (HTJS) from 1 May 2021 to 31 September 2021. Result(s): 549 patients were recruited with mean age of 51.5 years. Majority (n = 417, 76%) were females. 414 (75.4%) received Pfizer/ BioNTech, 127 (23.1%) received Sinovac, 7 (1.3%) received Oxford/ AstraZeneca and 1 (0.2%) received Moderna. 35 (6.3%) patients had COVID-19 infection with half of them contracted the infection after at last 1 dose of vaccine. The underlying RMD included RA (n = 217, 39.5%), SLE (n = 122, 22.2%), gout (n = 65, 11.8%), osteoarthritis (n = 41, 7.5%) and psoriatic arthritis (n = 30, 5.5%). 288 (52.4%) patients did not report any side effects following the vaccination. Pain at the site of the injection (n = 169, 30.8%) was the most common side effects, followed by muscle pain (n = 91, 16.4%), fever (n = 90, 16.4%), joint pain (n = 55, 10%) and tiredness (n = 43, 7.7%). 30 (5.4%) cases of RMD flares were reported following the vaccination. 25 were arthritis flare, 3 were SLE flare (2 renal and 1 mucocutaneous involvement) and 2 were psoriasis flare. There were no serious adverse events that required hospitalization. Conclusion(s): This study supports the overall safety of COVID-19 vaccines in patients with RMD. This information can help to overcome vaccine hesitancy among this population.