Recent advances in electroconvulsive therapy in clinical practice and research.

Electroconvulsive therapy (ECT), the oldest somatic therapy still in use in psychiatry today, remains one of the most effective therapeutic interventions for a wide variety of psychiatric disorders. In this article, we review some of the recent advances in ECT that are currently being researched and implemented in clinical practice. We explore recent studies that point to the potential therapeutic benefit and safety of ECT in COVID-19-related neuropsychiatric complications and special populations (such as the elderly and pregnant persons) that are generally at higher risk of having adverse effects from psychotropic medications. We highlight studies that performed a head-to-head comparison of ECT and ketamine, which has shown promise for treatment-resistant depression and acute suicidality. Researchers continue to explore different ways of using ECT by modifying the treatment parameters to maintain efficacy and decrease side effects. Neurocognitive side effects remain one of the major drawbacks to its use and contribute to the negative stigma of this highly effective treatment. In this regard, we describe attempts to improve the safety of ECT by modifying dosing parameters, novel electrode placements, and the addition of augmenting agents with the aim of decreasing side effects and improving efficacy. This review identifies some of the recent advances in the last few years in ECT research while also highlighting areas where further research is needed.

Ocrelizumab extended-interval dosing in multiple sclerosis during SARS-CoV-2 pandemic: a real-world experience.

BACKGROUND AND PURPOSE: During the COVID-19 pandemic, ocrelizumab administration was frequently postponed because of a lack of safety information and to favour vaccination. The clinical implications of ocrelizumab administration delay in multiple sclerosis (MS) patients were assessed. METHODS: Relapsing (RMS) and primary progressive (PPMS) MS patients receiving ocrelizumab for at least 6 months at our centre were retrospectively classified, according to the possible occurrence of a delay (≥4 weeks) in treatment administration. Patients were categorized in the extended-interval dosing (EID) group in the presence of at least one delayed infusion; otherwise they were considered as part of the standard interval dosing (SID) cohort. MS history, magnetic resonance imaging examinations and B-cell counts were also retrospectively collected and analysed. RESULTS: A total of 213 RMS and 61 PPMS patients were enrolled; 115 RMS and 29 PPMS patients had been treated according to the SID regimen, whilst 98 RMS and 32 PPMS patients were included in the EID cohort. Average follow-up after delay was 1.28 ± 0.7 years in the EID cohort. In RMS, comparing SID and EID patients, no differences were found considering the occurrence of clinical relapses (9.6% vs. 16.3%, p = 0.338), magnetic resonance imaging activity (9.8% vs. 14.1%, p = 0.374) or disability progression (11.3% vs. 18.4%, p = 0.103). Similar findings were observed in PPMS patients. In the pooled EID group, treatment delay correlated with CD19-positive relative (r = 0.530, p < 0.001) and absolute (r = 0.491, p < 0.001) cell counts, without implications on disease activity. CONCLUSIONS: Sporadic ocrelizumab administration delay granted sustained treatment efficacy in our cohort. Prospective data should be obtained to confirm these observations and set up systematic extended-interval regimens.

Individualizing methadone treatment with split dosing: An underutilized tool.

Methadone's long half-life typically allows for once daily dosing. However, a growing body of evidence and clinical experience shows that some patients may benefit from twice-daily ("split") dosing to produce more stable symptoms and minimize side effects, independent of serum peak-to-trough levels. Concerns regarding split dosing typically center on diversion and poor adherence and must be taken seriously. However, policy changes during COVID-19 demonstrate that the rigidity historically applied to methadone may be unnecessarily stringent. Given clinical advances and policy updates, we believe clinicians should weigh the risks and benefits of this underutilized tool for select patients, as we await the evidence-based recommendations our patients deserve.

Frequent need for apixaban dose adjustment for atrial fibrillation in an unselected acute medical admission population during the COVID 19 pandemic

Background: During the COVID-19 pandemic, systematic switching patients of eligible patients with atrial fibrillation from warfarin to direct oral anticoagulants (DOACs) was encouraged to simplify drug dosing and obviate the need for regular monitoring. Regional exclusions to switching included mechanical heart valves, moderate to severe mitral stenosis and stage 5 chronic kidney disease (estimated glomerular filtration rate [eGFR]< 15ml/min/1.73m2). However, each DOAC requires dose adjustment depending on renal function and other patient factors. Purpose(s): Failure to dose reduce when indicated leads to excessive serum drug concentration and increased risk of major haemorrhage, particularly in patients who are acutely unwell. We thus quantified the likelihood of need for dose adjustment in an unselected acute medical admission population. Method(s): While on call, a single investigator prospectively identified all patients admitted on the acute medical or cardiology take-in between 1/ 12/21 and 1/2/22 who were taking apixaban for atrial fibrillation. Apixaban was selected as the study DOAC as it was the most commonly used DOAC but had the most complex dose adjustment algorithm and hence risk of dose error. In order to determine the appropriate drug dosage, patient age, weight, serum creatinine and eGFR were recorded. Dose reduction to 2.5mg was required if the patient meet 2 of the following 3 criteria of [age>80 years, weight <60kg, serum creatinine >133umol/l], or a single criterion, had an eGFR <30ml/min/1.73m2. Drug discontinuation was required if eGFR was <15ml/min/1.73m2. Result(s): All patients identified (n=50) had a CHA2DS2-VASc score of >=2. Patients with active COVID-19 infection were excluded. Mean age was 77.2 years (range 46-102). Mean weight was 78kg (range 52-101). Mean serum creatinine was 212umol/l (range 62-595). Mean eGFR was 33ml/min/1.73m2 (range 8 to >60). Of the 50 patients, 24 (48%) were taking the appropriate apixaban dose on admission which did not require dose adjustment (18 of whom were appropriately taking 5mg bd and 6 were taking 2.5mg bd). Dose reduction from 5mg bd to 2.5mg bd was required in 17 (34%) patients. Stopping treatment, at least temporarily due to eGFR<15ml/min/1.73m2, was indicated in 9 (18%) of patients. No patient required an increase in drug dose. (Graph 1) Conclusion(s): Over half of acute medical or cardiology patients admitted within a COVID-19 setting and taking apixaban for atrial fibrillation required at least temporary drug dose adjustment or discontinuation. Clinicians should expect that adjustment of apixaban dose may be required during acute admission.

Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV.

Introduction: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals. Methods: A total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis. Results: At 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron. Discussion: This study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges. Clinical trial registration: https://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.

The immunogenicity of an extended dosing interval of BNT162b2 against SARS-CoV-2 Omicron variant among healthy school-aged children, a randomized controlled trial.

OBJECTIVES: To evaluate the immunogenicity of an extended interval regimen of BNT162b2 among healthy school-age children. METHODS: A randomized-control trial conducted among healthy Thai children aged 5-11 years. Participants received two doses of BNT162b2 with an 8-week (extended dosing) vs 3-week interval. Immunogenicity was determined by neutralization test (NT) against the Omicron variant, surrogate virus NT (sVNT; BA.1, % inhibition), and pseudovirus NT (BA.2, the half-maximal inhibition dilution or ID50). The third dose was offered to participants who had sVNT <68% inhibition. The immunogenicity outcome was evaluated at 14 days after the second and third doses. RESULTS: During February to April 2022, 382 children with a median age (interquartile range) of 8.4 years (6.6-10.0) were enrolled. At 14 days, after two doses of BNT162b2, the geometric means of sVNT in 8-week vs 3-week interval groups were 49.6 (95% confidence interval [CI] 44.8-54.9) vs 16.5 (95% CI 13.0-20.9), with a geometric means ratio of 3.0 (95% CI 2.4-3.8). Among 102 participants who received the third dose at a median of 15 weeks from the second dose, the geometric means of sVNT increased to 73.3 (95% CI 69.0-77.8) and pseudovirus NT increased to 326 (95% CI 256-415). CONCLUSION: The extended 8-week interval regimen of BNT162b2 induced higher neutralizing antibodies than a standard 3-week interval regimen. The third dose induced high neutralizing antibodies against the Omicron variant.

Determining the Optimal SARS-CoV-2 mRNA Vaccine Dosing Interval for Maximum Immunogenicity.

OBJECTIVE: Emerging evidence indicates that longer SARS-CoV-2 vaccine dosing intervals results in an enhanced immune response. However, the optimal vaccine dosing interval for achieving maximum immunogenicity is unclear. METHODS: This study included samples from adult paramedics in Canada who received two doses of either BNT162b2 or mRNA-1273 vaccines and provided blood samples six months (170 to 190 days) after the first vaccine dose. The main exposure variable was vaccine dosing interval (days), categorized as "short" (first quartile), "moderate" (second quartile), "long" (third quartile), and "longest" interval (fourth quartile). The primary outcome was total spike antibody concentrations, measured using the Elecsys SARS-CoV-2 total antibody assay. Secondary outcomes included spike and receptor-binding domain (RBD) immunoglobulin G (IgG) antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to wild-type spike protein and several different Delta variant spike proteins. We fit a multiple log-linear regression model to investigate the association between vaccine dosing intervals and the antibody concentrations. RESULTS: A total of 564 adult paramedics (mean age 40 years, SD=10) were included. Compared to "short interval" (≤30 days), vaccine dosing intervals of the long (39-73 days) group (ß= 0.31, 95% Confidence interval (CI): 0.10-0.52) and the longest (≥74 days) group (ß = 0.82. 95% CI: 0.36-1.28) were associated with increased spike total antibody concentration. Compared to the short interval, the longest interval quartile was associated with higher spike IgG antibodies, while the long and longest intervals were associated with higher RBD IgG antibody concentrations. Similarly, the longest dosing intervals increased inhibition of ACE-2 binding to viral spike protein. CONCLUSION: Increased mRNA vaccine dosing intervals longer than 38 days result in higher levels of anti-spike antibodies and ACE-2 inhibition when assessed six months after the first COVID-19 vaccine.

Incremental expenditures attributable to daily dispensation and witnessed ingestion for opioid agonist treatment in British Columbia: 2014-20.

BACKGROUND AND AIM: While daily witnessed opioid agonist treatment (OAT) ingestion is common in British Columbia (BC), Canada, and elsewhere, sparse evidence supports this resource-intensive practice. Many settings across North America relaxed restrictions for take-home dosing during the COVID-19 pandemic and have reported consistent or improved patient outcomes. This study measured excess expenditures attributed to daily witnessed pharmacy dispensing compared with weekly or biweekly dispensation schedules. DESIGN, SETTING AND PARTICIPANTS: This study was a population-level retrospective analysis. We included all methadone, buprenorphine/naloxone and slow-release oral morphine dispensations in BC from 1 January 2014 to 30 December 2020. A total of 24 357 107 OAT dispensations among 51 195 unique individuals with 122 793 person-years of follow-up were included during the study period. MEASUREMENTS: Total expenditures for each person-week of OAT with an estimated expenditure under two scenarios are as follows: (1) a weekly dispensation scenario and (2) a biweekly dispensation scenario. FINDINGS: We estimated excess expenditures attributable to current dispensing practices of between $38 million (2014) and $47.4 million (2018) compared with a hypothetical weekly dispensing schedule, and $43.9 million (2014) to $54.9 million (2018) compared with biweekly dispensing. The majority of these expenditures (58-64%) were attributed to pharmacy dispensing fees ($23 million in 2014 to $30 million in 2018 compared with weekly dispensing; $26.6 million in 2014 to $34.7 million in 2018 compared with biweekly dispensing). CONCLUSION: Daily witnessed opioid agonist treatment ingestion results in more than $30 million in excess expenditures annually in the province of British Columbia, Canada compared with the costs of weekly or biweekly dispensation schedules.

Natalizumab wearing-off symptoms: effect of extend interval dosing during Sars-CoV-2 pandemic.

BACKGROUND: Many patients treated with Natalizumab experience wearing-off symptoms (WoS) towards the end of the administration cycle. During the pandemic we advised and asked patients undergoing treatment with Natalizumab if they wanted to be shifted from a standard interval dosing (StID of 4 weeks) to an extended interval dosing (ExID of 5-6 weeks), regardless of their JCV index. Our main objective was to study prevalence and incidence of WoS when ExID was adopted. METHODS: We enrolled 86 patients, from May 2020 to January 2021, evaluated at baseline and during a 6 months follow-up with a survey focused on WoS, Fatigue Severity Scale (FSS), Expanded Disability Status Scale (EDSS) and MRI. RESULTS: Among the 86 patients, 32 (37.2%) reported WoS. Most common one was fatigue (93.7%). Mean EDSS was higher in the group reporting WoS (3.8 WoS vs 3.1 non-WoS, p < 0.05). Sphincterial function was the EDSS item that significantly differed between the WoS group and the non-WoS group (1.4 WoS vs 0.6 non-WoS, p < 0.001). WoS correlate with the FSS scale (p < 0.001). CONCLUSION: Adopting an extended interval dosing does not result in significantly different occurrence of WoS between the ExID and the StID populations, in our cohort of patients. Interestingly, there is a strong correlation between WoS and a higher EDSS and FSS. Safety and efficacy of Natalizumab with ExID are relatively preserved in our study.

Correction of Anticoagulant Therapy in Patients with Severe COVID-19 Virus Infection Using a Thrombodynamics Coagulation Assay.

BACKGROUND: The average frequency of thrombosis in patients with COVID-19 is still high despite low molecular weight heparin (LMWH) prophylactic. Global hemostasis assays, particularly thrombodynamics (TD), known to be sensitive to both hypercoagulation and heparin effects, could potentially be useful for individual management of anticoagulant therapy. METHODS: A total of 74 patients with lung involvement >50% were randomized into two groups: Group A (44 patients) received weight-based dosing of LMWH, and Group B (30 patients) received the first LMWH dose by a weight-based dosing protocol and then received an adjusted dose based on TD daily results. The endpoints of the study were thrombosis and bleeding as well as discharge or death of the patient. RESULTS: The incidence of thrombosis was 3 times lower in Group B under TD control compared to Group A without TD control: 7% versus 23 respectively (p = .05). The relative risk of thrombosis if the average clot growth rate V in TD exceeded the threshold value of 25 µm/min was 14.3 (p = .0005, 95% confidence interval 3.2-63.7). There were no clinically significant bleeding episodes in Group B while there were 7% in unregulated Group A. Mortality in Group B under TD control was lower than that in Group A without control: 27% versus 36%, respectively (p = .13). CONCLUSIONS: The dosing LMWH under thrombodynamics control in severe patients with COVID-19 allows for a significant reduction in thrombotic complications. Long-term hypercoagulation revealed by thrombodynamics (3 and more days) is a strong predictor of thrombosis (AUC = 0.83).

Impact of COVID-19 Pandemic on Non-Small Cell Lung Cancer Care.

We assessed the impact of COVID-19 on healthcare visits, timing of stage IV NSCLC diagnosis and immunotherapy initiation, and rates of switching to extended dosing schedules of immunotherapies among patients with stage IV NSCLC. This retrospective study examined electronic health record data of adult patients receiving treatment for stage IV NSCLC within The US Oncology Network and Onmark. Endpoints were compared for February-July 2019 (before COVID) vs. February-July 2020 (during COVID). The study found rapid decreases in numbers of patients with clinic/vital visits, immunotherapy initiations, and new diagnoses of stage IV NSCLC during April-May 2020 vs. April-May 2019. The rate of delays of immunotherapy administrations and proportions of patients with such delays increased from February to March of 2020. These patterns may have resulted from the increase in COVID-19 cases during this period and the corresponding quarantine and lockdowns. However, when comparing pre COVID-19 and during COVID-19 for May and after, the differences in delay of immuno-oncology administrations became less marked, likely due to lifting of lockdowns. The rate of switching from shorter to longer dosing schedules increased from May-July 2020. This was mainly attributed to pembrolizumab, likely due to FDA approval of the pembrolizumab 6W dosing schedule in April 2020.

Altering the mRNA-1273 dosing interval impacts the kinetics, quality, and magnitude of immune responses in mice.

For a vaccine to achieve durable immunity and optimal efficacy, many require a multi-dose primary vaccination schedule that acts to first "prime" naive immune systems and then "boost" initial immune responses by repeated immunizations (ie, prime-boost regimens). In the context of the global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 2-dose primary vaccination regimens were often selected with short intervals between doses to provide rapid protection while still inducing robust immunity. However, emerging post-authorization evidence has suggested that longer intervals between doses 1 and 2 for SARS-CoV-2 vaccines may positively impact robustness and durability of immune responses. Here, the dosing interval for mRNA-1273, a messenger RNA based SARS-CoV-2 vaccine administered on a 2-dose primary schedule with 4 weeks between doses, was evaluated in mice by varying the dose interval between 1 and 8 weeks and examining immune responses through 24 weeks after dose 2. A dosing interval of 6 to 8 weeks generated the highest level of antigen-specific serum immunoglobulin G binding antibody titers. Differences in binding antibody titers between mRNA-1273 1 µg and 10 µg decreased over time for dosing intervals of ≥4 weeks, suggesting a potential dose-sparing effect. Longer intervals (≥4 weeks) also increased antibody-dependent cellular cytotoxicity activity and numbers of antibody-secreting cells (including long-lived plasma cells) after the second dose. An interval of 6 to 8 weeks elicited the strongest CD8+ T-cell responses, while an interval of 3 weeks elicited the strongest CD4+ T-cell response. Overall, these results suggest that in a non-pandemic setting, a longer interval (≥6 weeks) between the doses of the primary series for mRNA-1273 may induce more durable immune responses.

ACUTE PERICARDITIS CAUSED BY COVID-19 INFECTION AND ITS MANAGEMENT

SESSION TITLE: Extraordinary Cardiovascular Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: The incidence of acute pericarditis is 3.32 per 100,000 person-years (11). Patone et. Al, found that 0.001% had acute pericarditis after a dose of the COVID-19 vaccine, while 11.9% were COVID-19 positive (11). 1.5% of patients with COVID- 19 developed new onset pericarditis and six-month all-cause mortality was 15.5% (2). CASE PRESENTATION: 48-year-old male with no known past medical history who presented with acute onset of sharp, left-sided chest pain and associated with dyspnea on exertion. He was not vaccinated for COVID-19 and denied being around any sick contacts. On physical examination he was afebrile, normotensive and saturating 99% on room air. EKG initially showed diffuse ST elevations in leads II,III, aVF, V2-V6. Initial high sensitivity trop was <6. He was incidentally found to be COVID positive. Initial echocardiogram was not suggestive of wall motion abnormalities or pericardial effusions. He was not initiated on management for COVID-19 pneumonia as he was asymptomatic and on room air. He was started on colchicine 0.6 mg BID and ibuprofen 400 TID for pericarditis treatment and symptoms resolved on follow up. DISCUSSION: COVID-19 causing pericarditis is relatively rare and our patient presented with pericarditis and no associated respiratory symptoms. The clinical signs of pericarditis include: a pleuritic or sharp chest pain relieved by leaning forwards, a pericardial friction rub auscultated near the left sternal border and EKG changes including diffuse ST elevations or PR depressions seen in the leads I,II,III, aVL, aVF and the precordial leads V2-V6 (3). The common complications seen with pericarditis are pericardial effusion, cardiac tamponade, and constrictive pericarditis (1). A common etiology for pericarditis is a viral illness which can be seen to precede the cardiac symptoms and be seen as flu-like symptoms or as gastrointestinal symptoms. Treatment is with colchicine and NSAIDs. Aspirin has been the drug of choice in patient's who present with pericarditis following a myocardial infarction, solely because the other NSAIDs have been studied and shown to interfere with myocardial healing (3)(4). NSAIDs were believed to be harmful in patient's diagnosed with COVID, due to upregulation of ACE2 receptors in multiple sites which is used by SARS-COV-2 as a point of entry into cells (9). Drake et. Al, looked at patients with COVID-19 pneumonia, and found use of NSAIDs did not play any significant role in mortality (10). First-line therapy for pericarditis is NSAIDs and colchicine. Second line therapy can be with corticosteroids and refractory therapy is generally with intravenous human immunoglobulins, Azathioprine or anti-IL1 agents such as Anakinra (12). CONCLUSIONS: COVID 19 continues to present with varying levels of comorbidities. Timely diagnosis and intervention of pericarditis precipitated by COVID-19 can lead to near complete recovery and prevent fatal outcomes. Reference #1: Dababneh E, Siddique MS. Pericarditis. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431080/ Reference #2: Buckley BJR, Harrison SL, Fazio-Eynullayeva E, Underhill P, Lane DA, Lip GYH. Prevalence and clinical outcomes of myocarditis and pericarditis in 718,365 COVID-19 patients. Eur J Clin Invest. 2021 Nov;51(11):e13679. doi: 10.1111/eci.13679. Epub 2021 Sep 18. PMID: 34516657;PMCID: PMC8646627.1 Reference #3: Little WC, Freeman GL. Pericardial disease. Circulation. 2006 Mar 28;113(12):1622-32. doi: 10.1161/CIRCULATIONAHA.105.561514. Erratum in: Circulation. 2007 Apr 17;115(15):e406. Dosage error in article text. PMID: 16567581. DISCLOSURES: No relevant relationships by Atika Azhar No relevant relationships by Berty Baskaran No relevant relationships by Andres Cordova Sanchez No relevant relationships by Harvir Gambhir No relevant relationships by Hanish Jai

Is It Time for Ocrelizumab Extended Interval Dosing in Relapsing Remitting MS? Evidence from An Italian Multicenter Experience During the COVID-19 Pandemic.

In the COVID-19 pandemic era, safety concerns have been raised regarding the risk of severe infection following administration of ocrelizumab (OCR), a B-cell-depleting therapy. We enrolled all relapsing remitting multiple sclerosis (RRMS) patients who received maintenance doses of OCR from January 2020 to June 2021. Data were extracted in December 2021. Standard interval dosing (SID) was defined as a regular maintenance interval of OCR infusion every 6 months, whereas extended interval dosing (EID) was defined as an OCR infusion delay of at least 4 weeks. Three infusions were considered in defining SID vs. EID (infusions A, B, and C). Infusion A was the last infusion before January 2020. The primary study outcome was a comparison of disease activity during the A-C interval, which was defined as either clinical (new relapses) or radiological (new lesions on T1-gadolinium or T2-weighted magnetic resonance imaging (MRI) sequences). Second, we aimed to assess confirmed disability progression (CDP). A total cohort of 278 patients (174 on SID and 104 on EID) was enrolled. Patients who received OCR on EID had a longer disease duration and a higher rate of vaccination against severe acute respiratory syndrome-coronavirus 2 (p < 0.05). EID was associated with an increased risk of MRI activity during the A-C interval (OR 5.373, 95% CI 1.203-24.001, p = 0.028). Being on SID or EID did not influence CDP (V-Cramer 0.47, p = 0.342). EID seemed to be associated with a higher risk of MRI activity in our cohort. EID needs to be carefully considered for OCR-treated patients.

COVID-19 and antiepileptic drugs: an approach to guide practices when nirmatrelvir/ritonavir is co-prescribed.

Management and dose adjustment are a major concern for clinicians in the absence of specific clinical outcome data for patients on antiepileptic drugs (AEDs), in the event of short-term (5 days) nirmatrelvir/ritonavir co-exposure. Therefore, in this report, we identified drugs that require dose adjustment because of drug-drug interactions (DDIs) between nirmatrelvir/ritonavir and AEDs. We hereby used four databases (Micromedex Drug Interaction, Liverpool Drug Interaction Group for COVID-19 Therapies, Medscape Drug Interaction Checker, and Lexicomp Drug Interactions) and DDI-Predictor.In the light of applying the DDI-Predictor, for carbamazepine, clobazam, oxcarbazepine, eslicarbazepine, phenytoin, phenobarbital, pentobarbital, rufinamide, and valproate as CYP3A4 inducers, we recommend that a dose adjustment of short-term nirmatrelvir/ritonavir as a substrate (victim) drug would be more appropriate instead of these AEDs to avoid impending DDI-related threats in patients with epilepsy.

Coronavirus Disease 2019 Vaccine Dosage in Children, Adolescents, and Young Adults: Is Less More?

The lower efficacy of the COVID-19 mRNA vaccines in 5-11 year old children was unexpected. Neutralizing antibody titers elicited by the vaccines in children, adolescents, and young adults suggest that the lower efficacy is not due to the lower dosage. Confirming the efficacy of these vaccines in children, determining if mRNA vaccination strategies are less effective in younger children, as well as optimizing the dosage, dosing intervals, and number of doses needed in children, adolescents, and young adults are critical to improve vaccination strategies for these populations going forward.

COVID vaccines - therapeutic errors reported to the UK National Poisons Information Service (NPIS)

Objective: The first COVID-19 vaccine was administered in the UK on the 8 December 2020. Since then, the UK has authorised four vaccines for use against COVID-19 (Pfizer/BioNTech, Oxford/ AstraZeneca, Moderna and Janssen). Serious adverse effects, including fatalities, have been linked to COVID-19 vaccines [1]. We reviewed all enquiries to the UK National Poisons Information Service (NPIS) related to COVID-19 vaccines. Methods: We conducted a retrospective analysis of enquiries relating to COVID-19 vaccines to the NPIS from 1 March 2020 until 31 July 2021. Enquiries were identified from the UK Poisons Information Database (UKPID) and filtered to identify those relating specifically to COVID-19 vaccines. Results: The NPIS received 34 enquiries about COVID-19 vaccines during the study period (Oxford/AstraZeneca: 13, 38.2%;Pfizer/ BioNTech: 9, 26.5%;Moderna: 1, 2.9%). Two enquiries were seeking information about two different vaccines (Pfizer/BioNTech and Oxford/AstraZeneca) and in nine enquiries the manufacturer was unknown. Of these enquiries, 29 (85.3%) were specifically patient-related while five (14.7%) were for information only and were excluded from further analysis. The majority of patientrelated enquiries were from NHS 111 (17, 58.6%) with the remaining from hospitals (6, 20.7%) or primary care (6, 20.7%). All enquiries were regarding adult patients;21 enquiries were regarding female patients (72.4%) with 8 regarding male patients (27.6%). The most common enquiries were regarding patients who had received three doses instead of 2 (7, 24.1%), dosing errors due to incorrect dilution/reconstitution of the vaccine (5, 17.2%), doses administered outside the recommended timeframe of 8-12 weeks (5, 17.2%), adverse reactions (4, 13.8%) and patients receiving 2 doses in the same day (4, 13.8%). Nineteen patients (65.5%) were asymptomatic at the time of the enquiry. Four patients had symptoms (13.8%) but these were all deemed to be minor. In 6 enquiries (20.7%) it was unknown if the patient had symptoms. No moderate or severe symptoms were recorded and there were no fatalities. Conclusion: Serious adverse effects have been rarely associated with COVID-19 vaccines [1]. Enquiries to the NPIS regarding COVID-19 vaccines were generally related to administration or dosing errors. Reassuringly, in this patient population, most patients had no symptoms or mild symptoms only.

Real-world study of multiple naloxone administration for opioid overdose reversal among bystanders.

BACKGROUND: The increasing prevalence of highly potent, illicitly manufactured fentanyl and its analogues (IMF) in the USA is exacerbating the opioid epidemic which has worsened during the COVID-19 pandemic. Narcan® (naloxone HCl) Nasal Spray has been approved by the US Food and Drug Administration as a treatment for opioid-related overdoses. Due to the high potency of IMF, multiple naloxone administrations (MNA) may be needed per overdose event. It is essential to determine the patterns of naloxone use, including MNA, and preferences among bystanders who have used naloxone for opioid overdose reversal. METHODS: A cross-sectional web-based survey was administered to 125 adult US residents who administered 4 mg Narcan® Nasal Spray during an opioid overdose in the past year. The survey asked about the most recent overdose event, the use of Narcan® during the event and the associated withdrawal symptoms, and participant preferences regarding dosages of naloxone nasal spray. An open-ended voice survey was completed by 35 participants. RESULTS: Participants were mostly female (70%) and white (78%), while reported overdose events most frequently occurred in people who were males (54%) and white (86%). Most events (95%) were successfully reversed, with 78% using ≥ 2 doses and 30% using ≥ 3 doses of Narcan® Nasal Spray. Over 90% were worried that 1 Narcan® box may not be enough for a successful future reversal. Reported withdrawal symptoms were similar in overdose events where 1 versus ≥ 2 sprays were given. Eighty-six percent of participants reported more confidence in an 8 mg versus a 4 mg naloxone nasal spray and 77% reported a stronger preference for 8 mg over 4 mg. CONCLUSIONS: MNA occurred in most overdose events, often involving more sprays than are provided in one Narcan® nasal spray box, and participants predominantly expressed having a stronger preference for and confidence in an 8 mg compared to a 4 mg nasal spray. This suggests the need and desire for a higher dose naloxone nasal spray formulation option. Given that bystanders may be the first to administer naloxone to someone experiencing an opioid overdose, ensuring access to an adequate naloxone supply is critical in addressing the opioid overdose epidemic.