Treatment Patterns and Unmet Need for Patients with Progressive Multiple Sclerosis in the United States: Survey Results from 2016 to 2021.

INTRODUCTION: Much of the current literature on treatment patterns and disability progression in multiple sclerosis (MS) does not distinguish between the relapsing-remitting and progressive subtypes (including primary [PPMS] and secondary progressive MS [SPMS]), or between active/nonactive disease. Current treatment options for progressive MS are limited, with only one approved product for PPMS and none specifically for nonactive SPMS. Here we report treatment patterns, disability progression, and unmet needs among patients with active and nonactive PPMS and SPMS. METHODS: The annual, cross-sectional survey from the Adelphi Disease Specific Program was used to collect physician-reported data on US adult patients with PPMS and SPMS, including active and nonactive disease. Treatment patterns (including the proportion of patients who were untreated with a disease-modifying therapy [DMT]), disability progression, and unmet need are described from 2016 to 2021. RESULTS: Data were collected for 2067 patients with progressive MS (PPMS, 1583; SPMS, 484). A substantial proportion of patients were untreated across all groups, and this was highest for nonactive PPMS (~ 43%). The proportion of untreated patients generally declined over time but remained high in 2018-2021 (~ 10-38%). Among treated patients, the proportion receiving infusions increased over time to ~ 34-46%, largely driven by ocrelizumab use after approval. Disability progression was reported for most patients (> 50%), including many who were receiving a DMT. Across all disease subtypes, when physicians were asked about the greatest unmet need with current DMTs, they most frequently cited effectiveness (~ 63-87%), and specifically slowing disease progression (~ 32-59%). CONCLUSIONS: This analysis of physician-reported data reveals that patients with progressive MS, particularly those with nonactive disease, frequently remain untreated or continue to decline despite treatment with available DMTs. Thus there is an enduring need for safe and effective treatments for this underserved population.

Anti-Black racism in the early years: the experiences of Black families and early childhood educators in Nova Scotia. / Le racisme envers les personnes noires durant la petite enfance : l'expérience de familles noires et d'éducateurs de la petite enfance en Nouvelle-Écosse.

INTRODUCTION: Anti-Black racism is a social determinant of health that has significantly impacted Black children and families. Limited research has examined anti-Black racism during the early years-a critical period of development. In this study, we sought to understand the manifestations of anti-Black racism in early childhood and explore its impact on Black children and families. METHODS: This qualitative research project was informed by critical race theory, Black Critical Theory and interpretive description. Early childhood educators (ECEs) and parents with Black children between the ages of 18 months and 5 years (n = 15) participated in virtual, semistructured interviews. RESULTS: Awareness of and protection against anti-Black racism was a constant in Black families' lives. Parents felt as though they had to remain hypervigilant and overprotective of their Black children, knowing they were liable to encounter racial violence. The early learning environment was a source of heightened stress for families, given the significant amount of time young children spend in child care. Black children were often "othered" in predominately White spaces and had been objectified by White ECE staff and children. Parents worked to instill a strong sense of self-confidence in their children to counteract the negative impacts of racial discrimination. CONCLUSION: Results from this study suggest that children as young as 18 months are experiencing racial violence and adverse childhood experiences. Findings may contribute to antiracist policy development and a focus on more inclusive early childhood education for Black children and families.

Results of genetic analysis of 11 341 participants enrolled in the My Life, Our Future hemophilia genotyping initiative in the United States.

BACKGROUND: Hemophilia A (HA) and hemophilia B (HB) are rare inherited bleeding disorders. Although causative genetic variants are clinically relevant, in 2012 only 20% of US patients had been genotyped. OBJECTIVES: My Life, Our Future (MLOF) was a multisector cross-sectional US initiative to improve our understanding of hemophilia through widespread genotyping. METHODS: Subjects and potential genetic carriers were enrolled at US hemophilia treatment centers (HTCs). Bloodworks performed genotyping and returned results to providers. Clinical data were abstracted from the American Thrombosis and Hemostasis Network dataset. Community education was provided by the National Hemophilia Foundation. RESULTS: From 2013 to 2017, 107 HTCs enrolled 11 341 subjects (68.8% male, 31.2% female) for testing for HA (n = 8976), HB (n = 2358), HA/HB (n = 3), and hemophilia not otherwise specified (n = 4). Variants were detected in most male patients (98.2%% HA, 98.1% HB). 1914 unique variants were found (1482 F8, 431 F9); 744 were novel (610 F8, 134 F9). Inhibitor data were available for 6986 subjects (5583 HA; 1403 HB). In severe HA, genotypes with the highest inhibitor rates were large deletions (77/80), complex intron 22 inversions (9/17), and no variant found (7/14). In severe HB, the highest rates were large deletions (24/42). Inhibitors were reported in 27.3% of Black versus 16.2% of White patients. CONCLUSIONS: The findings of MLOF are reported, the largest hemophilia genotyping project performed to date. The results support the need for comprehensive genetic approaches in hemophilia. This effort has contributed significantly towards better understanding variation in the F8 and F9 genes in hemophilia and risks of inhibitor formation.

A review of the risks of long-term consequences associated with components of the CHOP chemotherapy regimen.

A common chemotherapy regimen in post-transplant lymphoproliferative disease (PTLD) following solid organ transplants (SOT) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). This study reviews the quantitative evidence for long-term consequences associated with components of CHOP identified from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cited references were screened using prespecified criteria (English, systematic review, randomized controlled trial n > 100, observation study n > 100, case series n > 20). Relevant data were extracted and synthesized. Of 61 studies, 66% were retrospective cohort studies, 28% were in the US, and 95% enrolled pediatric patients. No study focused specifically on the CHOP regimen. Long-term consequences for CHOP components observed in >3 studies included cardiac toxicity (n = 14), hormone deficiencies/infertility (n = 14), secondary leukemia (n = 7), osteonecrosis (n = 6), and bladder cancer (n = 4). These effects are significant, impact a high percentage of patients, and occur as early as one year after treatment. Although none of the studies focused specifically on the CHOP regimen, 30%, 23%, and 15% evaluated alkylating agents (e.g. cyclophosphamide), anthracyclines (e.g. doxorubicin), and corticosteroids (e.g. prednisone), respectively. All three product classes had a dose-dependent risk of long-term consequences with up to 13.2-fold, 27-fold, 16-fold, 14.5-fold, and 6.2-fold increase in risk of heart failure, early menopause, secondary leukemia, bladder cancer, and osteonecrosis, respectively. Lymphoma patients had significantly elevated risks of cardiac toxicity (up to 12.2-fold), ovarian failure (up to 3.8-fold), and osteonecrosis (up to 6.7-fold). No studies were found in PTLD or SOT. Safe and effective PTLD treatments that potentially avoid these long-term consequences are urgently needed.

Results from Patient Interviews on Fatigue in Progressive Multiple Sclerosis and Evaluation of Fatigue Patient-Reported Outcome (PRO) Instruments.

INTRODUCTION: Fatigue is one of the most common and debilitating symptoms of multiple sclerosis (MS) but is challenging to assess and has not been comprehensively characterized in patients with progressive MS. This study aimed to (1) obtain qualitative evidence from patients with progressive MS to characterize MS-related fatigue concepts and their impacts on health-related quality of life (HRQoL), and (2) evaluate the conceptual frameworks of existing MS-specific fatigue patient-reported outcome (PRO) instruments using study data to determine the most suitable PRO instrument in this population. METHODS: Qualitative interviews were conducted with 30 US participants with confirmed progressive MS and fatigue in the last 6 months to assess their MS-related fatigue. Data were compared with concepts in existing PRO instruments to evaluate their relevance in progressive MS. RESULTS: Physical and mental concepts of fatigue were identified and characterized distinctly from patients with progressive MS. Most patients characterized fatigue as occurring daily and lasting several hours, with negative impacts on HRQoL. Concept mapping to existing MS-specific fatigue PRO instruments supported the Fatigue Severity Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) as the most suitable existing option for assessing fatigue in patients with progressive MS, as it separates physical and mental aspects of fatigue and includes every highly endorsed concept reported by the interviewed patients. CONCLUSIONS: This qualitative study identified meaningful physical and mental fatigue concepts in patients with progressive MS and preliminarily supports the use of the FSIQ-RMS for this population. More research is needed to fully validate this instrument for progressive MS.

Mean lifetime survival estimates following solid organ transplantation in the US and UK.

AIMS: Accurately estimating mean survival after solid organ transplant (SOT) is crucial for efficient healthcare resource allocation decisions. However, registry-based post-transplant recipient survival estimates vary greatly and are incomplete. Often, the methods used in lifetime survival extrapolation may not fit complex transplant data and therefore alternative methods are required. We aimed to explore the flexible cubic spline methodology as a meaningful alternative for estimating lifetime survival following SOT. METHODS: Survival analyses were conducted in kidney, liver, heart, and lung transplant recipients. Mean survival was estimated using flexible cubic splines on the hazard scale fitted with three knots, based on where hazards changed direction, clinical advice, and best-fit curve using Akaike and Bayesian information criterion. The tail was extrapolated when data were no longer available. Extrapolation tails were compared with general population mortality, using age-matched life table hazards, and the highest hazards were taken at all times. RESULTS: We found that mean survival post-transplant was longest for kidney transplants (US: 22.79 years; UK: 26.58 years), followed by liver (US: 20.90 years; UK: 20.38 years), heart (US: 14.82 years; UK: 15.85 years), and lung (US: 9.28 years; UK: 9.21 years). A sensitivity analysis using two knots found differences in survival ranging from -1.30 to +4.83 years across SOTs examined. LIMITATIONS: This study does not represent individual patient survival, survival by age groups, multiple-organ transplants, or assess factors that may impact overall or organ survival. CONCLUSIONS: Our study estimates reflect real-world survival following SOTs and demonstrate the importance of including long-term hazards in survival estimations. These lifetime survival estimates can be used by decision-makers in situations where means are preferred over medians (e.g. population projections, budgetary estimates, and cost-effectiveness models) and can thus offer a meaningful alternative to the estimates used and accepted in current practice.

Risk and the Republican National Convention: Application of the Novel COVID-19 Operational Risk Assessment.

The United States Centers for Disease Control and Prevention and the World Health Organization broadly categorize mass gathering events as high risk for amplification of coronavirus disease 2019 (COVID-19) spread in a community due to the nature of respiratory diseases and the transmission dynamics. However, various measures and modifications can be put in place to limit or reduce the risk of further spread of COVID-19 for the mass gathering. During this pandemic, the Johns Hopkins University Center for Health Security produced a risk assessment and mitigation tool for decision-makers to assess SARS-CoV-2 transmission risks that may arise as organizations and businesses hold mass gatherings or increase business operations: The JHU Operational Toolkit for Businesses Considering Reopening or Expanding Operations in COVID-19 (Toolkit). This article describes the deployment of a data-informed, risk-reduction strategy that protects local communities, preserves local health-care capacity, and supports democratic processes through the safe execution of the Republican National Convention in Charlotte, North Carolina. The successful use of the Toolkit and the lessons learned from this experience are applicable in a wide range of public health settings, including school reopening, expansion of public services, and even resumption of health-care delivery.

Using prediction polling to harness collective intelligence for disease forecasting.

BACKGROUND: The global spread of COVID-19 has shown that reliable forecasting of public health related outcomes is important but lacking. METHODS: We report the results of the first large-scale, long-term experiment in crowd-forecasting of infectious-disease outbreaks, where a total of 562 volunteer participants competed over 15 months to make forecasts on 61 questions with a total of 217 possible answers regarding 19 diseases. RESULTS: Consistent with the "wisdom of crowds" phenomenon, we found that crowd forecasts aggregated using best-practice adaptive algorithms are well-calibrated, accurate, timely, and outperform all individual forecasters. CONCLUSIONS: Crowd forecasting efforts in public health may be a useful addition to traditional disease surveillance, modeling, and other approaches to evidence-based decision making for infectious disease outbreaks.

Cost burden of post-transplant lymphoproliferative disease following kidney transplants in Medicare-eligible patients by survival status.

AIMS AND OBJECTIVES: Patients diagnosed with post-transplant lymphoproliferative disease (PTLD) experience high mortality within the first 2 years of diagnosis; however, few data exist on the economic burden of PTLD in these patients. We determined the healthcare resource utilization (HRU) and cost burden of post-kidney transplant PTLD and evaluated how these differ by survival status. MATERIALS AND METHODS: Utilizing data from the United States Renal Data System and the Scientific Registry of Transplant Recipients, we identified 83,818 Medicare-covered kidney transplant recipients between 2007 and 2016, of which 347 had at least one Medicare claim during the first year after diagnosis of PTLD. We tabulated Medicare Part A and Part B and calculated per patient-year (PPY) costs. RESULTS: Patients diagnosed with PTLD in the first year post-transplant had Part A + B costs of $222,336 PPY, in contrast with $83,546 PPY in all kidney transplants. Post-transplant costs in the first year of PTLD diagnosis were similar regardless of the year of diagnosis. Cost burden for PTLD patients who died within 2 years of diagnosis was >3.3 times higher than PTLD patients still alive after 2 years. Of those who died within 2 years, the majority died within 6 months and costs were highest for these patients, with almost 7 times higher costs than PTLD patients who were still alive after 2 years. LIMITATIONS: Medicare costs were the only costs examined in this study and may not be representative of other costs incurred, nor be generalizable to other insured populations. Patients were only Medicare eligible for 3 years after transplant unless aged ≥62 years, therefore any costs after this cut-off were not included. CONCLUSIONS: PTLD represents a considerable HRU and cost burden following kidney transplant, and the burden is most pronounced in patients who die within 6 months.

Qualitative Findings on the Impact of Disease in Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disease Patients, as Measured by EQ-5D, SF-36, and the FACT-LYM.

INTRODUCTION: There are no validated patient-reported outcome (PRO) instruments for Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV+ PTLD). The aim of this study was to assess the content applicability for three frequently used PRO instruments from the perspective of patients with EBV+ PTLD. METHODS: A moderated focus group comprising adult patients with EBV+ PTLD was conducted using a concept confirmation and an open-ended concept elicitation approach. The domains of the EuroQoL Group-5 Dimension (EQ-5D) instrument, Short Form Health Survey-Version 2 (SF-36v2) questionnaire, and Functional Assessment of Chronic Illness Therapy-Lymphoma (FACT-LYM) questionnaire were discussed. The concept elicitation portion was a general discussion of symptoms and patient burden of EBV+ PTLD. RESULTS: Six patients participated in this study: five women and one man. Most participants reported acute pain in the location of their EBV+ PTLD. All participants reported significant physical fatigue and experienced productivity loss. Patients reported emotional fatigue, feelings of dissociation, lack of motivation, and persistent fear of disease progression, including mortality. Patients described their social functioning as disjointed, behaving differently with loved ones/caregivers than when alone. The EQ-5D was relevant for the pain/discomfort and anxiety/depression domains; most SF-36v2 domains were relevant, with the exception of the general health perception domain, which was not applicable; all domains in the FACT-LYM were relevant. The open-ended portion drew no new content. CONCLUSIONS: This qualitative research identified meaningful concepts in patients with EBV+ PTLD, with physical, emotional, and social functioning being impacted. The FACT-LYM questionnaire was the most relevant of the three PROs studied, with all domains relevant to this population. It is important to properly analyze PRO data in patients with EBV+ PTLD.

Retrospective database analysis of healthcare resource utilization and costs in patients who develop post-transplant lymphoproliferative disease within the first year following allogeneic hematopoietic stem cell transplants.

AIMS: Healthcare resource utilization (HRU) and costs in post-transplant lymphoproliferative disease (PTLD) patients following allogeneic hematopoietic stem cell transplant (HCT) were evaluated in the USA. METHODS: MarketScan Commercial and Medicare Supplemental database claims from 01 July 2010 to 31 December 2017 were analyzed. Patients eligible for analysis received allogeneic HCT between 01 January 2011 to 31 December 2015, had ≥6 months of continuous enrollment before HCT, and had ≥1 claim for PTLD or ≥1 inpatient or ≥2 outpatient claims for a clinically-relevant lymphoma within 1 year following HCT (PTLD index = first claim of diagnosis). Patients with clinically-relevant lymphomas within 6 months before HCT were excluded. HRU and total paid amounts were assessed from the week before the HCT through 1-day pre-PTLD index (HCT to PTLD) and monthly from PTLD index through 1-year post-PTLD index. HRU is reported as mean (SD). Results were also provided by survival status. RESULTS: Overall, 92 patients were eligible for analysis. From HCT to PTLD, 98.9% of patients were hospitalized, with 1.7 (1.2) hospitalizations/patient. The average length of stay was 25.3 (22.2) days/patient. From HCT to PTLD, 98.9% of patients had outpatient services with 233.7 (261.1) services/patient and 91.3% of patients had a prescription fill with 32.9 (26.0) prescriptions/patient. In the first month post-PTLD index, 51.2% of patients were hospitalized. Mean paid amounts were $399,470/patient (range $7542-$1.7 M) from HCT to PTLD. Cumulative mean paid amounts 1-year post-PTLD were $429,043/patient. Total cost/patient/month was ∼7 times higher in patients who died (n = 49; $232,591) than those who lived (n = 43; $33,677). Costs were mainly driven by hospitalizations. LIMITATIONS: Limitations include those inherent to retrospective analyses (i.e. miscoding, lack of clinical detail). CONCLUSIONS: HRU and costs from HCT to PTLD were high and more than doubled within 1-year post-PTLD. PTLD patients who died had ∼7 times higher costs than those who lived, driven by hospitalizations. Effective treatments are needed to reduce the burden of PTLD.

Zika Inquiries Made to the CDC-INFO System, December 2015-September 2017.

We examined Zika-related inquiries to CDC-INFO, the national contact center for the Centers for Disease Control and Prevention, to identify potential communication gaps. The most frequently asked questions related to travel or geographic location of Zika (42% of all inquiries), information about laboratory testing (13%), or acquiring a Zika test (11%).

A Public Health Systems View of Risk Communication About Zika.

OBJECTIVES: The spread of Zika virus throughout Latin America and parts of the United States in 2016 and 2017 presented a challenge to public health communicators. The objective of our study was to describe emergency risk communication practices during the 2016-2017 Zika outbreak to inform future infectious disease communication efforts. METHODS: We conducted semi-structured telephone interviews with 13 public health policy makers and practitioners, 10 public information officers, and 5 vector-control officials from May through August 2017. RESULTS: Within the public health macro-environment, extended outbreak timeframe, government trust, US residence status, and economic insecurity set the backdrop for Zika communication efforts. Limited resources, staffing, and partnerships negatively affected public health structural capacity for communication efforts. Public health communicators and practitioners used a range of processes and practices to engage in education and outreach, including fieldwork, community meetings, and contact with health care providers. Overall, public health agencies' primary goals were to prevent Zika infection, reduce transmission, and prevent adverse birth outcomes. CONCLUSIONS: Lessons learned from this disease response included understanding the macro-environment, developing partnerships across agencies and the community, and valuing diverse message platforms. These lessons can be used to improve communication approaches for health officials at the local, state, and federal levels during future infectious disease outbreaks.

Vector control in Zika-affected communities: Local views on community engagement and public health ethics during outbreaks.

Aerial spraying of products to kill larvae or adult mosquitoes is a public health measure used to control vector-borne diseases. In some outbreaks, the intervention has evoked controversy and community resistance. This study evaluated how local opinion leaders in US localities affected by Zika think about community engagement in public health policies for outbreak response. In December 2017 through March 2018, 4 focus groups were convened in Houston, TX, New Orleans, LA, Miami, FL, and Brooklyn, NY. They discussed a hypothetical scenario that featured vector control by aerial spraying. Participants (N = 20) more readily accepted this vector control method under 4 conditions: They were informed of alternatives, benefits, and risks for human health and the environment. Public health claims were backed by objective evidence and an authority figure genuinely working in the community's interests. They received timely notice about how to mitigate toxin exposure. And, aerial spraying helped to protect vulnerable individuals. The community engagement requirements of the local opinion leaders resonate with core principles of recent public health ethics frameworks: namely, personal autonomy, transparency, reasonableness, and solidarity. Participants foresaw problems with community consent in an era of growing social media use and mistrust in governmental and scientific authority. They also debated whether health authorities should use moral-based arguments, in addition to science-based ones, to communicate aerial spraying's risks and benefits.