Escalation to Anti-CD20 Treatment for Multiple Sclerosis Following Natalizumab-Associated Progressive Multifocal Leukoencephalopathy.

Objectives: Disease-modifying therapy (DMT) for multiple sclerosis (MS) after natalizumab-associated progressive multifocal leukoencephalopathy (PML) is controversial due to concern for recurrent PML. We describe DMT utilization for over a decade in a patient with MS who survived PML. Methods: Case report. Results: A 36-year-old woman was diagnosed with MS in 2002 and treated with interferon beta-1a until 2006, when she transitioned to natalizumab due to relapses. She presented in 2012 with 2 months of progressive cognitive and gait concerns and was diagnosed with PML by positive CSF JC virus testing with concordant clinical and MRI findings. She was treated with plasma exchange and then corticosteroids for PML immune reconstitution inflammatory syndrome before starting glatiramer acetate for DMT. She transitioned to dimethyl fumarate in 2013 after MS activity on MRI with negative CSF JC virus testing. Owing to worsening footdrop consistent with progression, she transitioned to ocrelizumab in 2017 and then to ofatumumab in 2020 due to logistics of medication administration. There has been no clinicoradiographic or CSF evidence of recurrent PML. Discussion: DMT selection is challenging for patients with MS who survive PML. We used an escalation approach extending to ocrelizumab and ofatumumab due to MS progression. Anti-CD20 DMTs are a high-efficacy option post-PML. Classification of Evidence: This provides Class IV evidence. It is a single observational study without controls.

Screening for lung cancer: 2023 guideline update from the American Cancer Society.

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.

Mycobacterium abscessus Meningitis Associated with Stem Cell Treatment During Medical Tourism.

Mycobacterium abscessus infections have been reported as adverse events related to medical tourism. We report M. abscessus meningitis in a patient who traveled from Colorado, USA, to Mexico to receive intrathecal stem cell injections as treatment for multiple sclerosis. We also review the management of this challenging central nervous system infection.

Challenging Cases in Neuroimmunology.

Neuroimmunology is rapidly evolving field extending from well-known, but incompletely understood conditions like multiple sclerosis, to novel antibody-mediated disorders, of which dozens have been described in the past 10 years. The ongoing expansion in knowledge needed to effectively diagnose and treat these patients presents myriad challenges for clinicians. Here, we discuss six informative cases from our institution. By highlighting these challenging cases, we hope to instill fundamental points on the nuances of diagnosis and management for conditions including tumefactive multiple sclerosis, antibody-mediated encephalitis, antiphospholipid antibody syndrome, neuromyelitis optica, and myelin oligodendrocyte glycoprotein IgG-associated disease.

COVID and the Risky Immigrant Workplace: How Declining Employment Standards Socialized Risk and Made the COVID-19 Pandemic Worse.

This article investigates the impacts of the COVID-19 pandemic in NYC as they were concentrated on immigrant workers and their communities, studying one group of immigrant workers, namely taxi drivers. Based on two years of ethnographic research with the New York Taxi Workers Alliance, a union of 24,000 taxi and app-based drivers in NYC, conducted before and during the pandemic, as well as formal interviews and an original survey of 1,002 union members, my research shows how drivers' precarious existence in the work-citizenship nexus informed their experiences of sustaining their families during the pandemic. COVID highlighted how the welfare state's increasing privatization of risk, the fissuring of the workplace, and the rise in employment precarity have generated an immigrant underclass. This manifested in immigrant drivers experiencing the pandemic through the lens of specific uncertainties-health, economic, bureaucratic, and immigration-that shaped their unequal access to pandemic support. This process in turn produced a boomerang effect, as immigrant drivers' weaker connection to state and social institutions made it harder to contain the virus in their communities, a development which ultimately puts society writ large at greater risk. This article advances our knowledge of precious employment by introducing the concept of uncertainties to explain the socio-cultural aspects of how crises of social reproduction are generated. It also extends our understanding of the decline of the welfare and regulatory state by showing how this process interacts with immigrant status.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

Comparison of analytical techniques to quantitate the capsid content of adeno-associated viral vectors.

Adeno-associated virus (AAV) vectors, which contain a DNA transgene packaged into a protein capsid, have shown tremendous therapeutic potential in recent years. An inherent characteristic of the manufacturing process is production of empty capsids that lack the transgene and are therefore unable to provide the intended therapeutic benefit. The effect of empty capsids on clinical outcomes is not well understood, but there are immunogenicity and efficacy concerns, and these empty capsids are considered a product-related impurity. Therefore, empty capsids should be controlled during the manufacturing process and monitored through analytical testing, but there are limited techniques available that are capable of quantifying capsid content and even fewer that are amenable to validation and implementation as registered release tests in a regulated environment. In addition, there is currently not a widely accepted gold standard technique for quantifying capsid content, and the understanding of how the results compare between different orthogonal technologies is limited. The current study utilizes a comprehensive assessment to evaluate diverse analytical techniques for their ability to quantitate capsid content.

COVID-19 Vaccination in Patients With Multiple Sclerosis on Disease-Modifying Therapy.

The COVID-19 pandemic has resulted in challenges for the practice of neurology. One major concern is how to best manage patients with multiple sclerosis (MS) who are on disease-modifying therapies (DMTs). DMTs frequently have immunosuppressive properties that both increase the risk for COVID-19 and potentially reduce the immunologic response to vaccination in a group already vulnerable to infection due to neurologic deficits. Here, we review early data on COVID-19 outcomes in patients with MS and discuss what is known about vaccine effectiveness in those on anti-CD20 and sphingosine-1-phosphate receptor agents, which are proposed to have attenuating effects based on their mechanisms of action. In addition, we provide recommendations to best use novel COVID-19 vaccines in this population and highlight what information may better inform vaccine strategies in the future.

Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis.

BACKGROUND: Strategies for sequencing disease modifying therapies (DMTs) in multiple sclerosis (MS) patients include escalation, high efficacy early, induction, and de-escalation. OBJECTIVE: To provide a perspective on de-escalation, which aims to match the ratio of DMT benefit/risk in aging patients. METHODS: We reanalyzed data from a retrospective, real-world cohort of MS patients to model disease activity for oral (dimethyl fumarate and fingolimod) and higher efficacy infusible (natalizumab and rituximab) DMTs by age. For patients with relapsing MS, we conducted a controlled, stratified analysis examining odds of disease activity for oral vs. infusible DMTs in patients <45 or ≥45 years. We reviewed the literature to identify DMT risks and predictors of safe discontinuation. RESULTS: Younger patients had lower probability of disease activity on infusible vs. oral DMTs. There was no statistical difference after age 54.2 years. When dichotomized, patients <45 years on oral DMTs had greater odds of disease activity compared to patients on infusible DMTs, while among those ≥45 years, there was no difference. Literature review noted that adverse events increase with aging, notably infections in patients with higher disability and longer DMT duration. Additionally, we identified factors predictive of disease reactivation including age, clinical stability, and MRI activity. CONCLUSION: In a real-world cohort of relapsing MS patients, high efficacy DMTs had less benefit with aging but were associated with increased risks. This cohort helps overcome some limitations of trials where older patients were excluded. To better balance benefits/risks, we propose a DMT de-escalation approach for aging MS patients.

Increasing Cancer Screening Rates in Primary Care.

Screening for cancer has contributed to substantial reductions in death from several cancers and is one of the most cost-effective preventive interventions in all of health care. In the United States, primary care clinicians, their clinical teams, and the systems in which they work are primarily responsible for ensuring that screening occurs. In order to achieve the highest possible population-wide screening rates, primary care clinicians must embrace the responsibility to screen their entire enrolled patient population, institute several overarching general approaches to screening, and implement a combination of evidence-based interventions.

Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society.

The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation). The ACS recommends that individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening (qualified recommendation). These new screening recommendations differ in 4 important respects compared with the 2012 recommendations: 1) The preferred screening strategy is primary HPV testing every 5 years, with cotesting and cytology alone acceptable where access to US Food and Drug Administration-approved primary HPV testing is not yet available; 2) the recommended age to start screening is 25 years rather than 21 years; 3) primary HPV testing, as well as cotesting or cytology alone when primary testing is not available, is recommended starting at age 25 years rather than age 30 years; and 4) the guideline is transitional, ie, options for screening with cotesting or cytology alone are provided but should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers. Evidence related to other relevant issues was reviewed, and no changes were made to recommendations for screening intervals, age or criteria for screening cessation, screening based on vaccination status, or screening after hysterectomy. Follow-up for individuals who screen positive for HPV and/or cytology should be in accordance with the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors.

Rituximab-induced serum sickness in multiple sclerosis patients.

Rituximab is a chimeric anti-CD20 monoclonal antibody that is an effective therapy for multiple sclerosis. Rituximab has been associated with the development of serum sickness (type III hypersensitivity) characterized by arthralgia, fever, and rash during the treatment of other conditions, such as rheumatoid arthritis. Here we describe serum sickness associated with rituximab in multiple sclerosis patients and discuss both the management of serum sickness itself and implications for utilizing alternative anti-CD20 monoclonal antibodies for disease management in this patient population.

The Impact of Web-Based Video Lectures on Learning in Nursing Education: An Integrative Review.

AIM: The purpose of this review was to explore what is known about the efficacy of web-based video lectures (WBVLs). BACKGROUND: Nurse educators have embraced innovations such as online, flipped, and blended learning. Such innovations are enhanced by WBVLs, but there has been limited research on effective design. METHOD: A systematic search was conducted to identify studies of the efficacy of WBVL in nursing education between 2005 and 2017. An established framework was used to analyze the quality of studies. RESULTS: Findings from 11 studies revealed that students were satisfied with WBVL as supplement to or replacement for in-person lectures. Studies were hampered by lack of theory, methodological concerns, and an absence of experimental trials. CONCLUSION: Findings suggest that the efficacy of WBVL may be equivalent to or better than in-person lectures. Future studies should be guided by pedagogical theory and focus on comparing design practices for WBVL.

A Novel Decision Aid to Encourage Smoking Cessation Among Patients at an Urban Safety Net Clinic.

INTRODUCTION: Decision aids are not readily available to individualize the benefits of smoking cessation but could help health care providers engage in meaningful conversations with their patients to explore and encourage an attempt to quit smoking. We conducted a pilot study of a novel decision aid among an underserved population to assess its effectiveness in increasing readiness to quit and quit attempts. METHODS: We designed a decision aid that used images of birthday cakes to highlight the number of years of life that could be gained from smoking cessation and tested it in an urban safety net clinic. Active adult smokers were randomized to receive smoking cessation counseling, either with motivational interviewing techniques alone (control) or with motivational interviewing and the decision aid (intervention). The primary outcome assessed was readiness to quit, measured by using a previously validated contemplation ladder. The secondary outcome assessed was making a quit attempt. RESULTS: Immediately following the interview, 21.1% of patients rose on the readiness-to-quit ladder; at 1 month, 40.6%; and at 3 months, 46.6%. We saw no significant difference between the control and intervention groups immediately after the interview (P = .79), at 1 month (P = .92), or at 3 months (P = .79). Over the 3-month follow-up period, 25% of patients in the control group made a quit attempt, and 15.4% of patients in the intervention group made a quit attempt (P = .30). Patients found the decision aid useful and easy to understand. CONCLUSION: Patients from an underserved population were highly receptive to a visual and personalized decision aid that highlighted the positive impact of smoking cessation. However, we found no difference in readiness to quit between patients who received motivational interviewing with the decision aid or without it.

Colorectal cancer screening for average­risk adults: 2018 guideline update from the American Cancer Society

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model­recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high­sensitivity stool­based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average­risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high­sensitivity, guaiac­based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;000:000­000. © 2018 American Cancer Society.