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Background: The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort. Objective: To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort. Design: This multi-centre cohort study analysed relapse and disability outcomes post-COVID-19 infection after balancing covariates using a propensity score matching method. The study period was from the 11th of September 2019 to the 16th of February 2023. The mean follow-up period was 1.7 years. Methods: Data were retrieved from the MSBase Registry. Propensity scores were obtained based on age, sex, disease duration, baseline Expanded Disability Status Scale (EDSS), MS course, relapses pre-baseline, disease-modifying therapy (DMT) class and country. Primary outcomes were time to first relapse, annualised relapse rate (ARR) and time to confirm EDSS progression. Secondary outcomes were time to EDSS of 3, 4 or 6. Sensitivity analyses with baseline DMT classes were performed. Results: The study included 2253 cases and 6441 controls. After matching, there were 2161 cases and an equal number of matched controls. Cases had a significantly higher ARR (ARR = 0.10 [95% CI 0.09–0.11]) compared to controls (ARR = 0.07 [95% CI 0.06–0.08]). Cases had a significantly greater hazard of time to first relapse compared to controls (hazard ratio (HR) = 1.54 [95% CI 1.29–1.84]). There was no association between COVID-19 infection and 24-week EDSS progression (HR = 1.18 [95% CI 0.92–1.52]), or time to EDSS of 3, 4 or 6. For patients on interferons and glatiramer acetate (BRACE), COVID-19 infection was associated with a greater hazard of time to first relapse (HR = 1.83 [95% CI 1.25–2.68]) and greater hazard of time to EDSS of 3 (HR = 2.04 [95% CI 1.06–3.90]) compared to patients on BRACE therapy without COVID-19 infection. Conclusion: COVID-19 infection was associated with a significantly increased MS relapse rate and a shorter time to first relapse. There was no effect on confirmed EDSS progression over the short term. These results support ongoing COVID-19 risk minimisation strategies to protect patients with MS.

The Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) risk stratification model, developed to predict ≥10% abnormal plasma cells in the bone marrow in monoclonal gammopathy of undetermined significance (MGUS) patients, was developed in a predominantly White and genetically homogeneous Icelandic population, lacking external validation. Our study aimed to externally validate this model in a racially and ethnically diverse Bronx population. The medical records of patients at Montefiore Medical Center (2002–2023) were searched to identify patients with MGUS who had undergone a bone marrow biopsy. For each patient, the iStopMM variables were entered into the iStopMM prediction model, and predicted, and actual plasma cell percentages were recorded. The area under the receiver operating characteristic (AUROC) curve assessed the iStopMM model’s performance in predicting ≥10% plasma cells, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Of the initial 663 patients, 190 were included in the final cohort, of whom 52.6% were African-Americans, and 23.2% identified themselves as Hispanic/Latino, remarkably different from the homogenous population of the iStopMM study. The iStopMM predictive model was able to predict greater than or equal to 10% plasma cells on bone marrow biopsy with an AUROC of 0.78 (CI 0.71, 0.85). When set at a 10% threshold for predicting SMM or worse, the iStopMM model had a 93.3% sensitivity, 33.7% specificity, 55.3% PPV, and 85.0% NPV. This AUROC value of 0.778 suggests a reasonable discriminatory performance of the model in our racially and ethnically diverse Bronx population.

Patients with cancer often face significant financial challenges, known as financial toxicity (FT), which is associated with reduced quality of life. Patients with hematologic malignancies (HMs) are especially vulnerable due to intensive and prolonged treatments, frequent hospital visits, and a high risk of complications. While FT affects many in the general population, it is particularly severe among racial and ethnic minorities, especially those below the poverty line. To our knowledge, no studies have specifically examined FT in this vulnerable group in the United States. This study aimed to evaluate the severity of FT in patients receiving treatment for HMs in a socioeconomically underserved population, explore sociodemographic factors that may predict the severity of FT, and evaluate the subjective experiences of these patients as they relate to FT. We conducted a prospective, observational, longitudinal study at the Montefiore Cancer Center's outpatient department in the Bronx, New York, from October 1, 2022, to October 30, 2023. Participants included either adult patients newly diagnosed (ND) with HMs or those already diagnosed, undergoing cellular therapy (CT). The severity of FT was assessed using the validated Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) questionnaire. Additionally, an investigator-designed questionnaire was developed to gather sociodemographic data and evaluate the subjective effects of financial burden on patient care. Patients in both the ND and CT groups were followed for 90 days. Data collection occurred at their initial presentation, as well as on days 30 and 90. Ninety patients participated in the study (ND=52 and CT=38). The median age was 59 (IQR 44-66) years, with 27% (n=24) African American and 55% (n=48) Hispanic. Overall, 75% (n=67) of participants experienced some degree of FT, most with mild FT at baseline (day 0, median COST-FACIT score=19.4). In the CT group, FT worsened significantly over time, with a decline in median COST-FACIT scores from 19.9 at day 0 to 15.5 on day 90 (P=.02). In a multivariable linear regression model, race and ethnicity were a significant predictor of FT burden: identifying as African American or Hispanic was associated with a significantly lower COST-FACIT score (ie, higher FT) compared to non-Hispanic White participants (B=-3.08, P=.04, 95% CI -6.05 to -0.12). Additionally, over half of ND and CT participants reported difficulty affording basic necessities (ND: 28/52, 54%; CT: 23/38, 61%) and concerns regarding transportation access and costs (ND: 26/50, 52%; CT: n=18/38, 47%). FT is prevalent among patients with HMs receiving care in underserved populations, and the burden is significantly higher among African American and Hispanic populations.

In many developing nations, cervical cancer screening is done by visual inspection with acetic acid (VIA). Monitoring and evaluation (M&E) of such screening programs is challenging. An enhanced visual assessment (EVA) system was developed to augment VIA procedures in low-resource settings. The EVA System consists of a mobile colposcope built around a smartphone, and an online image portal for storing and annotating images. A smartphone app is used to control the mobile colposcope, and upload pictures to the image portal. In this paper, a new app feature that documents clinical decisions using an integrated job aid was deployed in a cervical cancer screening camp in Kenya. Six organizations conducting VIA used the EVA System to screen 824 patients over the course of a week, and providers recorded their diagnoses and treatments in the application. Real-time aggregated statistics were broadcast on a public website. Screening organizations were able to assess the number of patients screened, alongside treatment rates, and the patients who tested positive and required treatment in real time, which allowed them to make adjustments as needed. The real-time M&E enabled by “smart” diagnostic medical devices holds promise for broader use in screening programs in low-resource settings.

Background The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset. Methods A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018–March 10 2020) and post-pandemic onset (March 11 2020–11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use. Results Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39–2.13; switching: OR 1.66, 95% CI 1.40–1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09–1.87; switching: OR 1.67, 95% CI 1.41–1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06–1.49; Switching: OR 1.15, 95% CI 1.02–1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41–0.73; switching: OR 0.49, 95% CI 0.41–0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41–0.57; switching: OR 0.78, 95% CI 0.62–0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15–0.48; switching: OR 0.27, 95% CI 0.17–0.44)]. Conclusions Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges.

BackgroundISB 2001 is a trispecific T-cell engager antibody that targets BCMA and CD38 on myeloma cells, with binder affinity tuning and distal positioning of the CD38 vs CD3 to drive potent tumor killing while minimizing CD38-related off-tumor adverse events. We report PK/PD results from the dose escalation part of the FIH Phase 1 study of ISB 2001.MethodsISB 2001 was administered weekly by subcutaneous injection, with step-up doses on days 1 and 4 followed by target dose from day 8. ISB 2001 and 28 biomarkers were measured in serum, and T-cell activation markers in whole blood, to characterize PK/PD properties of ISB 2001.ResultsAs of 8 May, 2025, 42 patients received ISB 2001 across 9 dose levels between 5-2700 μg/kg with no dose-limiting toxicity observed. ORR across effective dose levels (50–2700 µg/kg) was 79% (n=33), and 73% in the 15 patients treated with prior BCMA-directed therapies. PK was dose proportional with a median half-life of approximately 17 days, supporting the potential for less frequent dosing of ISB 2001. Serum soluble BCMA levels and circulating B-cell counts were reduced by ISB 2001 (figure 1), an effect that was rapid and sustained, and there were gradual increases in BCMA ligands APRIL and BAFF (figure 2). These effects are consistent with strong cytotoxicity from co-targeting BCMA and CD38 on MM and normal plasma cells, whereas CD38+BCMA- NK cells and monocytes demonstrated relatively limited and/or transient reductions or increases, respectively. Transient increases in serum levels of soluble biomarkers were observed in some patients following initial doses of ISB 2001, including most frequently IL-6, IL-8, IL-10, IL-2RA, CXCL11, CCL17, MCP-1 and MIP-3β. These effects generally coincided with CRS events which were grade 1 (n=20) or 2 (n=4), and generally occurred following the first or second doses of ISB 2001. Transient increases in cell surface expression of multiple T-cell activation/proliferation markers were also observed following initial doses of ISB 2001, including Ki-67, PD-1, CD25, HLA-DR, CD137, TIM-3 and LAG-3.ConclusionsISB 2001 demonstrated dose proportional PK, a high ORR and acceptable safety profile across a wide range of dose levels (50-2700 μg/kg) in patients with heavily pre-treated RRMM. Biomarker changes at these dose levels were consistent with T-cell engaging activity and reduced tumor burden, while sparing CD38+BCMA- normal immune cells. PK/PD data support the exploration of multiple doses and schedules in the ongoing dose expansion part of the study.Trial RegistrationNCT05862012Ethics ApprovalThe study was approved by the institutional review board at each site and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines of the International Conference on Harmonization. All patients provided written informed consent.Abstract 554 Figure 1Reduced serum soluble BCMA and peripheral blood B-cell counts following ISB 2001 treatment. Serum soluble BCMA (sBCMA) was determined by immunocapture-mass spectrometry (left); peripheral blood B-cell counts were determined by flow cytometry prior to ISB 2001 (right). Plots represent data from patients who achieved an objective response[Image Omitted. See PDF.]Abstract 554 Figure 2Increased BCMA ligands APRIL and BAFF following ISB 2001 treatment. Serum levels of APRIL (left) and BAFF (right) were determined by bead-based immunoassay; Tmax data represents the highest measured value for each patient. Plots represent data from patients who achieved an objective response[Image Omitted. See PDF.]

Background/ObjectivesThe COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapy (DMT), particularly anti-CD20 monoclonal antibodies (mAB) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic.MethodsA multi-centre longitudinal study with 8,771 participants was conducted using data from the MSBase COVID-19 sub-study. Trends in DMT prescribing between 2018–2022 were analysed using multivariable mixed-effects logistic regression. DMT-initiation referred to the first prescription of any DMT in that timeframe, DMT-switches denoted a change in DMT regimen within 6 months of last DMT use.ResultsPost-pandemic, there was a significant increase in DMT initiation/switching to natalizumab and cladribine ([Natalizumab-Initiation:OR 1.72, 95% CI 1.39–2.13;Switching:OR 1.66, 95% CI 1.40–1.98],[Cladribine-Initiation:OR 1.43, 95% CI 1.09–1.87;Switching:OR 1.67, 95% CI 1.41–1.98]). Anti-CD20 mABs initiation decreased during-pandemic but recovered post-pandemic. Overall, anti-CD20 mABs initiation/switching increased, however less than other high-efficacy DMTs(Initiation:OR 1.26, 95% CI 1.06–1.49;Switching:OR 1.15, 95% CI 1.02–1.29). Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased([Fingolimod-Initiation:OR 0.55, 95% CI 0.41–0.73;Switching:OR 0.49, 95% CI 0.41–0.58],[Interferon-Initiation:OR 0.48, 95% CI 0.41–0.57; Switching:OR 0.78, 95% CI 0.62–0.99],[Alemtuzumab-Initiation:OR 0.27, 95% CI 0.15–0.48;Switching:OR 0.27, 95% CI 0.17–0.44]). Dimethyl fumarate initiation increased, while switching decreased(Initiation: OR 1.76, 95% CI 1.49–2.09;Switching:OR 0.85, 95% CI 0.69–1.05).ConclusionPost-pandemic, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mABs and fingolimod, likely to preserve efficacy but reduce perceived risk of immunosuppression. This has clinical implications for disease progression and highlights the importance of equitable access to DMTs and COVID-19 treatment in a pandemic to ensure continued use of high-efficacy DMTs.

When having conversations with your clients, it is always a good idea to remind them of the value of offering a strong benefit program. For employers, strong benefits give employers an edge when it comes to attracting and retaining employees, and reducing recruitment and training costs. Benefits can encourage employees to work harder and perform better, which has an impact on the bottom line. As a consultant, you can recommend solutions to your clients to help them make benefit decisions that work for both their businesses and their employees. What follows are four ways to accomplish this. These are: 1. Cover core needs and allow additional coverage. 2. Use voluntary benefits. 3. Make benefit design changes. 4. Educate employees. While the economy is pressuring employers to look at their business expenses, remind them of the importance of employee benefits.