Extended Interval Dosing of Ocrelizumab Reduces Risk of Developing Hypogammaglobulinaemia

Introduction Disruption to clinical services, triggered by the COVID-19 pandemic, led to extended intervals between ocrelizumab treatments for some patients. Objectives To assess the rates of developing low immunoglobulin levels and timing of CD19+ B-cell count repopulation in a real-world clinical population. To assess for evidence of clinical or radiological MS disease activity with extended interval dosing of ocrelizumab. Methods We audited 712 patients given ocrelizumab by our seven clinical services. All monitoring of immunoglobulin levels and CD19+ cell counts were recorded. Disease activity was defined as on treatment clinical relapse, radiological activity, and EDSS progression. Results Low immunoglobulin levels developed in 102 patients, the odds ratio for developing hypogam- maglobulinaemia comparing extended to standard interval dosing was 0.42 (CI 0.22-0.81). Disease activity included 20 participants with clinical relapses and 72 with new MRI lesions. There was no evidence of excess clinical or radiological disease activity on switching to extended interval dosing. 38 had EDSS progression, giving an odds ratio comparing extended to standard interval dosing of 0.77 (CI 0.38-1.56). Conclusions This real-world data of extended interval dosing of ocrelizumab indicates lower rates of hypogammaglobulinaemia and no detrimental effect on short-term treatment efficacy.

Short-course remdesivir for healthcare-associated COVID-19: Case series from a non-acute care hospital

Healthcare-associated COVID-19 among vulnerable patients leads to disproportionate morbidity and mortality. Early pharmacologic intervention may reduce negative sequelae and improve survival in such settings. This study aimed to describe outcome of patients with healthcare-associated COVID-19 who received early short-course remdesivir therapy. We reviewed the characteristics and outcome of hospitalized patients who developed COVID-19 during an outbreak that involved two wards at a non-acute care hospital in Japan and received short-course remdesivir. Forty-nine patients were diagnosed with COVID-19, 34 on a comprehensive inpatient rehabilitation ward and 15 on a combined palliative care and internal medicine ward. Forty-seven were symptomatic and 46 of them received remdesivir. The median age was 75, and the median Charlson comorbidity index was 6 among those who received it. Forty-one patients had received one or two doses of mRNA vaccines, while none had received a third dose. Most patients received 3 days of remdesivir. Of the patients followed up to 14 and 28 days from onset, 41/44 (95.3%) and 35/41(85.4%) were alive, respectively. Six deaths occurred by 28 days in the palliative care/internal medicine ward and two of them were possibly related to COVID-19. Among those who survived, the performance status was unchanged between the time of onset and at 28 days. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases

Early Short-Term Use of Different Doses of Corticosteroid in Hospitalized Pediatric Patients with Coronavirus Disease 2019 Pneumonia

Objective Encouraged by reports of favorable outcomes following the use of corticosteroids in patients with moderate-to-severe coronavirus 2019 (COVID-19) pneumonia, we aimed to present our experience with early short-term corticosteroid use at our center in pediatric patients with COVID-19 pneumonia. Methods One hundred and twenty-nine pediatric patients were included in the study. Patients were divided into four groups according to the type and dose of corticosteroids given: Group 1 (those receiving dexamethasone 0.15 mg/kg/d);Group 2 (those receiving methylprednisolone 1 mg/kg/d);Group 3 (those receiving methylprednisolone 2 mg/kg/d);and Group 4 (those receiving pulse methylprednisolone 10-30 mg/kg/d). Results Of 129 patients, 19 (14.7%) patients were assigned to Group 1, 30 (23.3%) patients to Group 2, 30 (23.3%) patients to Group 3, and 50 (38.8%) patients to Group 4. Thirty-two (24.8%) patients were followed in the pediatric intensive care unit (PICU), of whom 13 (10%) required mechanical ventilation, and 7 (%5.4) died. In Group 4, the hospitalization length was significantly longer than in other groups (p < 0.001, p < 0.001). No significant difference was found among the groups in terms of mortality (p = 0.15). The most common comorbidity was obesity (33%). A significant association was found between the presence of comorbidity and mortality (p < 0.001). All patients who died had an underlying disease. Cerebral palsy was the most common underlying disease among the patients who died. Worsening of lymphopenia was significant in patients with severe COVID-19 pneumonia at the time of transfer to the PICU (p = 0.011). Conclusion Although children usually have a milder course of COVID-19 than adults, underlying diseases and obesity increase the severity of disease manifestations also in children. Further studies are needed to define the exact role of corticosteroids in COVID-19 patients. © 2022. Thieme. All rights reserved.

REGRESSIVE BONE MINERAL DENSITY TRENDS SEEN with DELAY in FOLLOW UP of DENOSUMAB TREATMENT DUE to the PANDEMIC INDUCED LOCKDOWN-A SINGLE CENTRE INDIAN EXPERIENCE

Background: Denosumab (Dmab), a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-β ligand (RANKL), which selectively inhibits osteoclastogenesis can be used for a long period unlike the relatively short period with Teriparatide.1-2 However the effects of Dmab can quickly regress if the treatment is delayed.3 Objectives: The pandemic led to multiple prolonged lockdowns since March 2020 to Jan 2022 in India. This resulted in follow up Dmab treatment delays. The retrospective study was aimed to look for the effect of the delays. Methods: The bone mineral density (BMD) trends from the central dual-energy X-ray absorptiometry (DXA) at our centre were studied. The trends of patients under Dmab for one year and delay in follow up for 10-12 months for the forth dose were evaluated. 21 postmenopausal women who had been under treatment with Dmab 60 mg subcutaneous injection at 6 monthly interval for one year followed up with such delays. 6 were excluded because of history of sars-cov-2 infection and glucocorticoid use. In the study group of 15 (n=15), the mean BMD at L2, L3 & L4 (sp BMD) and Right and Left Hip (hip BMD) were studied from before treatment (a BMD), 6 months after 1st and at the time of 2nd injection (b BMD), 6 months of the 2nd and at the time of 3 rd injection of Dmab (c BMD), and that due to delay in follow up of 10-12 months (d BMD). The mean percentage trend change between a-b, b-c, and c-d BMDs was evaluated. The least signifcant change (LSC) 4 from a single centre DXA was used to validate the fndings. Results: The mean percentage change after the treatment for the 1st 6 months of Dmab (a-b BMD) was 4.08% and 3.60% and the second injection resulted in a further change (b-c BMD) of 5.98% and 4.52% in the sp BMD & hip BMD respectively. The delay in follow up of 10-12 months resulted in a change (c-d BMD) of-7.81% in the sp BMD and-2.96% in the hip BMD. The LSC from a single centre DXA is 2.6% and 3.6% for sp BMD and hip BMD respectively. A p>0.05 was considered statistically signifcant. Table 1 shows the BMD changes. Conclusion: These fndings suggest that regressive trend in BMD are seen when the treatment with Dmab is delayed even as early as 10 to 12 months. It was seen much faster in the spine compared to the hip. It is therefore advised that short term treatment with Dmab without follow up could lead to loss of all gains and may also worsen the osteoporosis.

BEHAVIORAL SELF-CONTROL TRAINING VERSUS MOTIVATIONAL ENHANCEMENT THERAPY FOR INDIVIDUALS WITH ALCOHOL USE DISORDER WHO AIM FOR CONTROLLED DRINKING: A RANDOMIZED CONTROL

Background: Controlled drinking is an attractive treatment goal among a large proportion of individuals with alcohol use disorder (AUD), with Behavioral Self-control Training (BSCT) as the most established treatment intervention, for this purpose. Yet, few controlled trials have aimed at investigating the efficacy of interventions with controlled drinking as treatment goal, and the implementation of these treatments in addiction care is scarce. Methods: A multi-site randomized controlled parallel superiority trial compared the efficacy of BSCT (5 sessions) to the active comparator Motivational Enhancement Therapy (MET) (4 sessions). A sample of 250 patients fulfilling criteria for AUD (DSM 5) with a goal of controlled drinking were included. As a result of the covid pandemic, a total of 76 participants received treatment via video meeting instead of face-to-face. Follow-ups were conducted at 12- and 26 weeks after inclusion. Primary outcome measure was mean weekly alcohol consumption. Treatment effects were analyzed by linear mixed-models. Results: Both treatment arms showed significant treatment effects for the primary outcome as well as binge drinking days (BDD) and measures of alcohol-related harm at 26 weeks after inclusion. There were no significant differences between treatment groups for the primary outcome. A total of 41,6 % of the patients obtained a level of low-risk drinking at the 26-week follow-up (9/14 standard drinks of 12 g of alcohol for women/men). No significant differences based on how the treatment was delivered i.e., between the face-to-face or video based intervention were detected. A subgroup of individuals (n = 25) with 75% or more of BDD before inclusion, reduced their drinking to 29% BDD at the 26-week follow-up. Conclusions: These results suggest that BSCT and MET designed as short-term treatments, are efficacious for a wide range of patients with AUD. This is evident in that a substantial proportion of patients obtained low-risk drinking levels, and individuals with more heavy consumption patterns, also significantly reduced their consumption. These results highlight a need for a more diverse approach within health care services to recovery from AUD with possibility of offering psychological treatments with controlled drinking as a treatment goal.