ObjectiveMotor neuron disease (MND) is a progressive neurological disorder with no known cure that damages motor neurons. The purpose of this analysis is to examine the place of death for MND patients in the United States during the coronavirus disease 2019 (COVID-19) pandemic and to investigate the extent of specific comorbidities.MethodsWe obtained death certificate and associated comorbidities data for all U.S. MND deaths from 2018 to 2021 and conducted a population-based cross-sectional analysis of the deaths pre-COVID-19 (2018-2019) and during COVID-19 (2020-2021). We hypothesized that place of death and comorbidities associated with place of death for MND patients in the United States were altered during the COVID-19 pandemic in comparison to the 2 years period before the pandemic.ResultsWe analyzed 30 066 MND deaths (14 562 pre-COVID-19 and 15 504 during COVID-19) aged 20 years and older. During COVID-19, MND deaths at home increased (54.4% vs 45.5% pre-COVID). Hispanic individuals had an increased likelihood of dying at home compared to a nursing home or hospice (OR = 1.57, 95%CI: 1.22-2.02), but a decreased likelihood compared to a hospital (OR = 0.61, 95% CI: 0.51-0.72). Among the top comorbidities listed, there was a 27.8% increase in diabetes mellitus and a 20.2% increase in essential hypertension during COVID-19. During COVID-19, diabetes mellitus was more commonly reported as a comorbidity for deaths occurring in hospitals (OR = 1.40, 95%CI: 1.03-1.89) or at home (OR = 1.26, 95%CI: 1.03-1.55), while essential hypertension was more commonly reported with deaths at home (OR = 1.17, 95%CI: 1.01-1.36).ConclusionOur analysis showed an increase in at-home MND deaths as well as certain comorbidities during the COVID-19 pandemic, suggesting MND patients had a higher likelihood of death from non-COVID-19 comorbidities.

Background/Objectives: To examine if head injury (HI) is associated with age at ALS diagnosis in the United States. Methods: In this cross-sectional populationf-based analysis, we identified patients with ALS who were registered from 2015 to 2023 who completed the Registry's head trauma survey module. The association between HI and age at ALS diagnosis was assessed using multivariate analysis. Results: Of the 3424 respondents, 56.6% had experienced a HI. The adjusted odds ratio (aOR) for an ALS diagnosis before age 60 years for patients with a HI was 1.24 (95% CI, 1.07-1.45). One or two HIs had an aOR of 1.15 (95% CI, 0.97-1.36), and five or more HIs had an aOR of 1.58 (95% CI, 1.19-2.09). HI before age 18 years yielded an aOR of 2.03 (95% CI, 1.53-2.70) as well as HI between the ages of 18 and 30 years (aOR = 1.48, 95% CI: 1.06-2.06)). When narrowing the analysis to patients with HI before age 18 compared with patients with no HI, we found an association with HI that led to an emergency department or hospital visit (aOR = 1.50 (95% CI: 1.21-1.86)). Conclusions: In this cross-sectional analysis of ALS patients, HIs occurring in childhood and early adulthood and the number of HIs increased the odds of being diagnosed before age 60 years. These results suggest that HI continues to be a risk factor for ALS and could be associated with a younger age of diagnosis.

Objective: To estimate the projected number of ALS cases in the United States from 2022 to 2030. Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease with no known cure. Because ALS is not a notifiable disease in the United States, the accurate ascertainment of prevalent ALS cases continues to be a challenge. To overcome this, the National ALS Registry (Registry) uses novel methods to estimate newly diagnosed and existing cases in the United States. Methods: We estimated ALS prevalence retrospectively from 2022 to 2024 and prospectively from 2025 to 2030 using prevalence obtained through previous CRC analyses on 2018 Registry data (the most current data available) to generate projected observed, missing, and total cases. Projected prevalent cases were then stratified by age, race, and sex. Results: The number of estimated ALS cases in 2022 was 32,893. By 2030, projected cases increase more than 10%, to 36,308. The largest increase occurs for the population ages 66 years and older, with a 25% increase (from 16,349 cases in 2022 to 20,438 cases in 2030). The projected number of cases classified as "other race" will increase by 15% (from 2,473 cases in 2022 to 2,854 cases in 2030). Conclusions: These estimates of projected ALS cases reflect anticipated changes in the underlying demographics of the United States. Our projections are likely an underestimation because emerging therapeutics and improved healthcare will improve survivability in this vulnerable population. These results should inform policy to more efficiently allocate resources for ALS patients and programs.

BACKGROUND: In March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) to be a pandemic, stating that those with underlying health conditions are most susceptible, including motor neuron disease (MND). OBJECTIVE: To examine the effect the COVID-19 pandemic had on deaths from MND in the United States. METHODS: Death certificate data for all MND deaths aged 20 years and older were analyzed from 2017 to 2019 (pre-COVID), then expanded to include 2020 and 2021 (COVID) deaths to evaluate if COVID-19 impacted MND deaths. RESULTS: The average number of MND deaths documented during the COVID-19 years was 8009, up from 7485 MND deaths pre-COVID. The age-adjusted mortality rate among the non-Hispanic population increased during COVID to 2.78 per 100,000 persons (95% CI = 2.73-2.82) from 1.81 (95% CI = 1.78-1.84). The Hispanic population also saw an increase in mortality rate during COVID (1.61, 95% CI = 1.51-1.71) compared with pre-COVID (1.10, 95% CI = 1.03-1.17). Decedent's home as a place of death also saw a mortality rate increase during COVID (1.51, 95% CI = 1.48-1.54) compared with pre-COVID (1.30, 95% CI = 1.27-1.32). For the Hispanic population, the rate peaked at 80-84 years pre-COVID, but for the COVID years, the rate peaked earlier, at 75-79 years. CONCLUSION: The total number of MND deaths was greater during COVID than in the preceding years. The analysis suggests there might have been a consequence of circumstances surrounding the global pandemic and the associated restrictions.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a highly effective pharmaceutical intervention that prevents HIV infection, but PrEP uptake across the US has been slow among men who have sex with men (MSM), especially among Black/African American (B/AA) and Hispanic /Latino (H/L) MSM. This study investigates the acceptability and essential components of a peer-driven intervention (PDI) for promoting PrEP uptake among MSM, with a specific focus on B/AA and H/L communities. METHODS: We conducted 28 semi-structured, qualitative interviews with MSM in southern New England to explore the components of a PDI, including attitudes, content, and effective communication methods. A purposive sampling strategy was used to recruit diverse participants who reflect the communities with the highest burden of HIV infection. RESULTS: Of 28 study participants, the median age was 28 years (interquartile range [IQR]: 25, 35). The sample comprised B/AA (39%, n = 11) and H/L (50%, n = 14) individuals. Notably, nearly half of the participants (46%) were current PrEP users. We found that many participants were in favor of using a PDI approach for promoting PrEP. Additionally, several participants showed interest in becoming peer educators themselves. They emphasized the need for strong communication skills to effectively teach others about PrEP. Moreover, participants noted that peer education should cover key topics like how PrEP works, how effective it is, and any possible side effects. CONCLUSIONS: Our study shows that effective PDIs, facilitated by well-trained peers knowledgeable about PrEP, could enhance PrEP uptake among MSM, addressing health disparities and potentially reducing HIV transmission in B/AA and H/L communities.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with largely unknown etiology. This study compares racial differences in clinical characteristics of ALS patients enrolled in the National ALS Registry (Registry). METHODS: Data from ALS patients who completed the Registry's online clinical survey during 2013-2022 were analyzed to determine characteristics such as site of onset, associated symptoms, time of symptom onset to diagnosis, and pharmacological and non-pharmacological interventions for White, Black, and other race patients. RESULTS: Surveys were completed by 4242 participants. Findings revealed that Black ALS patients were more likely to be diagnosed at a younger age, to have arm or hand initial site of onset, and to experience pneumonia than were White ALS patients. ALS patients of other races were more likely than White ALS patients to be diagnosed at a younger age and to experience twitching. The mean interval between the first sign of weakness and an ALS diagnosis for Black patients was almost 24 months, statistically greater than that of White (p = 0.0374; 16 months) and other race patients (p = 0.0518; 15.8 months). The mean interval between problems with speech until diagnosis was shorter for White patients (6.3 months) than for Black patients (17.7 months) and other race patients (14.8 months). CONCLUSIONS AND RELEVANCE: Registry data shows racial disparities still exist in the diagnosis and clinical characteristics of ALS patients. Increased recruitment of non-White ALS patients and better characterization of symptom onset between races might aid clinicians in diagnosing ALS sooner, leading to earlier therapeutic interventions.

OBJECTIVE: To characterize the participant demographics in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database compared with the web-portal National Amyotrophic Lateral Sclerosis (ALS) Registry (the Registry). METHODS: Demographics and ALS symptom information were compared between the self-reported registrant data in the Registry web portal (2010-2021) and the latest available PRO-ACT data (updated August 2022), which is a collection of clinical trials data. RESULTS: Greater percentages of younger (≤ 59 years old) but smaller percentages of older (60 + years old) participants were represented in PRO-ACT compared to Registry. Enrollment for minority race groups was greater in the Registry portal data, but race information was largely missing/unknown in PRO-ACT database. Median age at the time of diagnosis and age at the time of symptom onset were significantly higher for Registry enrollees compared to the participants of PRO-ACT. Symptom onset sites were similarly reported, but duration between self-noted symptom onset and diagnosis was slight, but significantly longer for the Registry enrollees (11 vs. 9 months). Hispanic were as likely as non-Hispanic to participate in research studies, based on the Registry data. CONCLUSION: There was a notable difference in the age distribution and minority representation of enrollees between the PRO-ACT and Registry study populations. Age distribution in the PRO-ACT database skewed to a younger and less diverse cohort. Despite the clinical heterogeneity and complex disease mechanism of ALS, identifying the underrepresented demographic niche in the PRO-ACT and Registry study populations can help improve patient participation and criteria for patient selection to enhance generalizability.

Objective: To summarize the prevalence of ALS in all 50 states and Washington, DC in the United States from 2011 to 2018 using data collected and analyzed by the National ALS Registry. In October 2010, the federal Agency for Toxic Substances and Disease Registry (ATSDR) launched the congressionally mandated Registry to determine the incidence and prevalence of ALS within the USA, characterize the demographics of persons with ALS, and identify the potential risk factors for the disease. This is the first analysis of state-level ALS prevalence estimates. Methods: ALS is not a notifiable disease in the USA, so the Registry uses a two-pronged approach to identify cases. The first approach uses existing national administrative databases (Medicare, Veterans Health Administration, and Veterans Benefits Administration). The second method uses a secure web portal to gather voluntary participant data and identify cases not included in the national administrative databases. Results: State-level age-adjusted average prevalence from 2011-2018 ranged from 2.6 per 100,000 persons (Hawaii) to 7.8 per 100,000 persons (Vermont), with an average of 4.4 per 100,000 persons in the US. New England and Midwest regions had higher prevalence rates than the national average. Conclusions: These findings summarize the prevalence of ALS for all 50 states from 2011 to 2018. This is a continuing effort to identify ALS cases on a national population basis. The establishment of the National ALS Registry has allowed for epidemiological trends of this disease and the assessment of potential risk factors that could cause ALS.

Objective: Amyotrophic lateral sclerosis (ALS) is an incurable, progressive neurodegenerative disease with a significant health burden and poorly understood etiology. This analysis assessed the narrative responses from 3,061 participants in the Centers for Disease Control and Prevention's National ALS Registry who answered the question, "What do you think caused your ALS?" Methods: Data analysis used qualitative methods and artificial intelligence (AI) using natural language processing (NLP), specifically, Bidirectional Encoder Representations from Transformers (BERT) to explore responses regarding participants' perceptions of the cause of their disease. Results: Both qualitative and AI analysis methods revealed several, often aligned themes, which pointed to perceived causes including genetic, environmental, and military exposures. However, the qualitative analysis revealed detailed themes and subthemes, providing a more comprehensive understanding of participants' perceptions. Although there were areas of alignment between AI and qualitative analysis, AI's broader categories did not capture the nuances discovered using the more traditional, qualitative approach. The qualitative analysis also revealed that the potential causes of ALS were described within narratives that sometimes indicate self-blame and other maladaptive coping mechanisms. Conclusions: This analysis highlights the diverse range of factors that individuals with ALS consider as perceived causes for their disease. Understanding these perceptions can help clinicians to better support people living with ALS (PLWALS). The analysis highlights the benefits of using traditional qualitative methods to supplement or improve upon AI-based approaches. This rapidly evolving area of data science has the potential to remove barriers to accessing the rich narratives of people with lived experience.

Genetics has become a critical component of medicine over the past five to six decades. Alongside genetics, a relatively new discipline, dysmorphology, has also begun to play an important role in providing critically important diagnoses to individuals and families. Both have become indispensable to unraveling rare diseases. Almost every medical specialty relies on individuals experienced in these specialties to provide diagnoses for patients who present themselves to other doctors. Additionally, both specialties have become reliant on molecular geneticists to identify genes associated with human disorders. Many of the medical geneticists, dysmorphologists, and molecular geneticists traveled a circuitous route before arriving at the position they occupied. The purpose of collecting the memoirs contained in this article was to convey to the reader that many of the individuals who contributed to the advancement of genetics and dysmorphology since the late 1960s/early 1970s traveled along a journey based on many chances taken, replying to the necessities they faced along the way before finding full enjoyment in the practice of medical and human genetics or dysmorphology. Additionally, and of equal importance, all exhibited an ability to evolve with their field of expertise as human genetics became human genomics with the development of novel technologies.

Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of human populations for centuries(1). A previous genomic study concluded that Shigella dysenteriae type 1 (Sd1), the epidemic dysentery bacillus, emerged and spread worldwide after the First World War, with no clear pattern of transmission(2). This is not consistent with the massive cyclic dysentery epidemics reported in Europe during the eighteenth and nineteenth centuries(1,3,4) and the first isolation of Sd1 in Japan in 1897(5). Here, we report a whole-genome analysis of 331 Sd1 isolates from around the world, collected between 1915 and 2011, providing us with unprecedented insight into the historical spread of this pathogen. We show here that Sd1 has existed since at least the eighteenth century and that it swept the globe at the end of the nineteenth century, diversifying into distinct lineages associated with the First World War, Second World War and various conflicts or natural disasters across Africa, Asia and Central America. We also provide a unique historical perspective on the evolution of antibiotic resistance over a 100-year period, beginning decades before the antibiotic era, and identify a prevalent multiple antibiotic-resistant lineage in South Asia that was transmitted in several waves to Africa, where it caused severe outbreaks of disease.

After the hurricanes in 2017 in the U.S. Caribbean, it was essential to rebuild, strengthen, and sustain essential environmental health (EH) services and systems. The National Environmental Health Association, in partnership with the Centers for Disease Control and Prevention, developed an online mentorship program for newly hired and existing EH staff and health department leadership in Caribbean health departments. Participants were provided with both practical and didactic learning and were allowed to evaluate the program. Both mentors and mentees were highly satisfied with the knowledge and skills acquired, and mentees expressed it was relevant to their daily work. Based on the findings, we recommend both an online and a hybrid mentorship program for leadership- and inspector-level workforces in EH and potentially in other fields.

Juvenile ALS (jALS) is a rare form of ALS, defined as symptom onset before age 25. This report describes the demographic characteristics of confirmed and likely jALS cases in a large cohort of ALS patients ascertained in the National ALS Registry (Registry) from 2010 to 2018. Patients in the Registry must be at least 18 years of age. Of the 44 identified patients, 37.8% were diagnosed at age 24, were more likely to be nonwhite (54.5%), male (79.5%), and live in the Midwest or Northeast regions (54.5%) of the US. Some 68.9% of the jALS cases were received from federal administrative databases, and 16% came from the web portal only. Demographic characteristics for jALS cases in the Registry differed from previous publications examining ALS cases for all adults. More research is needed to better understand risk factors contributing to jALS, which could lead to earlier diagnosis and therapeutic interventions.

OBJECTIVE: To estimate prevalent ALS cases in the United States for calendar year 2018. METHODS: The National ALS Registry (Registry) compiled data from national administrative databases (from the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration) and enrollment data voluntarily submitted through a web portal (www.cdc.gov/als). We used log-linear capture-recapture (CRC) model-based methodology to estimate the number of cases not ascertained by the Registry. RESULTS: The Registry identified 21,655 cases of ALS in 2018, with an age-adjusted prevalence of 6.6 per 100,000 U.S. population. When CRC methods were used, an estimated 29,824 cases were identified, for an adjusted prevalence of 9.1 per 100,000 U.S. population. The demographics of cases of ALS did not change from previous year's reports. ALS continues to impact Whites, males, and persons over 50 years of age more so than other comparison groups. The results from the present report suggest case ascertainment for the Registry has improved, with the estimate of missing prevalent cases decreasing from 44% in 2017 to 27% in in 2018. DISCUSSION: Consistent with previous estimates that used CRC, ALS prevalence in the United States is about 29,824 cases per year.

OBJECTIVE: To compare, for completeness, ALS patients identified in the National ALS Registry (National Registry) from MA to those in the Massachusetts ALS Registry (MA Registry) through 2015. METHODS: Sensitivity analyses were conducted to determine the completeness among patients reported in both registries. Patients were matched on first and last name, month and year of birth, sex, as well as Soundex name matching. Demographics for matching and nonmatching ALS patients were also examined using bivariate analyses and logistic regression. RESULTS: There were 1,042 ALS patients in the MA Registry, and 642 patients matched (61.6%) in the National Registry. Sensitivity analyses found the National Registry had a sensitivity of 87.7% and specificity of 60%. For these matched patients, 522 (81.2%) came from Medicare. Of the 400 patients in the MA Registry not matched to the National Registry, 11.1% were nonwhite, compared to 6.0% in the matched group) (p = 0.0091) and 59.2% were diagnosed before age 60, compared to 28.6% in the matched group (p < 0.0001). Multivariate logistic regression analysis showed being an ALS case (p < 0.0001) and having an ALS diagnosis at age 60 or later (p < 0.0001) were associated with being more likely to match between the two registries. CONCLUSIONS: These findings show that ALS's non-notifiable condition status at the national level continues to pose a challenge in identifying all ALS patients. This analysis also showed missing cases at the state level even with a reporting statute. Additional strategies are needed for better patient-ascertainment to quantify all ALS patients in the U.S.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) persistence and adherence are critical to ending the HIV epidemic in the United States. SETTING: In 2017 National HIV Behavioral Surveillance, HIV-negative men who have sex with men (MSM) in 4 U.S. cities completed a survey, HIV testing, and dried blood spots (DBS) at recruitment. METHODS: We assessed three PrEP outcomes: persistence (self-reported PrEP use at any time in the past 12 months and had tenofovir, emtricitabine, or tenofovir diphosphate (TFV-DP) detected in DBS), adherence at ≥4 doses/week (self-reported past-month PrEP use and TFV-DP concentration ≥700 fmol/punch), and adherence at 7 doses/week (self-reported past-month PrEP use and TFV-DP concentration ≥1250 fmol/punch). Associations with key characteristics were examined using log-linked Poisson regression models with generalized estimating equations. RESULTS: Among 391 MSM who took PrEP in the past year, persistence was 80% and was lower among MSM who were younger, had lower education, and had fewer sex partners. Of 302 MSM who took PrEP in the past month, adherence at ≥4 doses/week was 80% and adherence at 7 doses/week was 66%. Adherence was lower among MSM who were younger, were Black, and had fewer sex partners. CONCLUSIONS: Although persistence and adherence among MSM were high, 1 in 5 past-year PrEP users were not persistent and 1 in 5 past-month PrEP users were not adherent at levels that would effectively protect them from acquiring HIV (i.e., ≥4 doses/week). Efforts to support PrEP persistence and adherence should include MSM who are young, are Black, and have less education.

OBJECTIVE: This research aims to examine the impact of the National Amyotrophic Lateral Sclerosis (ALS) Registry-funded research activities. METHODS: Registry-funded research and related publications were identified through the National ALS Registry website, the National Institutes of Health (NIH) Reporter website, and verified by Principal Investigators. Key study characteristics (e.g., study population, sample size) and key impact features (e.g., risk factors) were abstracted and recorded on study abstraction forms. Descriptive statistics were used to analyze the volume, productivity, and findings of the Registry-funded research. RESULTS: Since 2012, the National ALS Registry funded 21 research projects. Of these, 14 were through extramural research grants and included in the analysis. These studies are often related to environmental, medical conditions, and genetic risk factors. On average, the funded grants produced 1 to 2 publications which were cited 114 times by other researchers. The relative citation ratio averaged 1.81 with a weighted relative citation ratio of 16.28. These studies supported the identification and confirmation of candidate risk factors. Environmental and occupational risk factors typically related to heavy metal exposure (e.g., lead, mercury) and agricultural chemicals (e.g., pesticides, herbicides), and the occupations associated with exposure to these substances were most frequently explored. INTERPRETATION: The National ALS Registry is a multifaceted research platform, one component of which is funded research. This Registry-funded research fills an essential gap in the overall ALS scientific community as it is difficult to prevent and treat a disease without a deeper understanding of its causes.

Objective: To evaluate the impact of 1) updating the existing algorithm to improve case-finding sensitivity and 2) reclassifying the Registry's diagnostic status nomenclature into four new categories ("confirmed ALS," "likely ALS," "undetermined ALS," or "not ALS") versus the current three ("definite ALS," "possible ALS," or "not ALS") to be more inclusive and descriptive of cases and individuals. Methods: A retrospective analysis of Registry data from 2011-2017 was conducted to follow "possible ALS" individuals over time to determine what qualifier caused them to convert, if at all and when, to Registry-eligible cases (i.e. "confirmed ALS" or "likely ALS"). Results: In 2011, 720 individuals were classified by the Registry algorithm as having "possible ALS". By 2017, 42% of these had converted to Registry-eligible ALS cases. Approximately 14% of those who were identified solely based on an ALS prescription drug never converted to Registry-eligible cases. This analysis indicates that "possible ALS" individuals with a single prescription for an ALS drug should be converted to Registry-eligible cases which would add between 300-500 cases per year on average. Conclusions: The Registry's existing algorithm likely results in the under-ascertainment of ALS cases. However, updating the algorithm with the inclusion of patients having been prescribed ALS-specific drugs, even with a single prescription, leads to improved epidemiologic estimates of ALS in the US. This and future algorithmic updates will help the Registry more accurately depict the true disease burden of ALS in the US.

We previously reported on a series of patients diagnosed with ALS whom had an extraordinary course defined by substantial and sustained improvement in weakness and function. For this study, twenty-five of these "ALS Reversals" completed extensive environmental exposure questionnaires. These responses were then compared to a large database of prior responses from patients with typically progressive ALS (n = 6187). The results demonstrated that the "Reversal" participants have had a diverse number of exposures with substantial heterogeneity. In general, this was similar to the control group; however, there were a few specific differences that could be further explored in future research.

INTRODUCTION: The Centers for Disease Control and Prevention (CDC) National Amyotrophic Lateral Sclerosis (ALS) Registry is the first national registry for a chronic neurologic disease in the USA and uses a combination of case-finding methods including administrative healthcare data and patient self-registration. METHODS: We applied capture-recapture methodology to estimate the completeness of the Registry for ascertaining patients with ALS for the first full year and the fourth year of the Registry (2011, 2014). The Registry uses the combination of two national administrative claims databases (Medicare and Veterans Affairs) with a self-register option at the registry portal. We conducted descriptive analyses of the demographic and clinical characteristics of the ALS cases identified by each of the sources and estimated the completeness of case ascertainment for each of the three ALS Registry sources individually, pairwise, and in all combinations. RESULTS: Case-finding completeness was 54% in 2011 and improved to 56% in 2014. A smaller proportion of ALS patients under age 65 were ascertained than those 65 or older, and ascertainment was also lower for nonwhite than white patients. The uncorrected ALS prevalence was 4.3/100,000 in 2011 (in 2014, 5.0/100,000), but after correction for underascertainment, annual prevalence in 2011 was 7.9/100,000 (95% CI: 7.6-8.2) (in 2014 was 8.9/100,000 [95% CI: 8.7-9.2]). DISCUSSION/CONCLUSION: Our findings indicate that administrative healthcare databases are a very efficient method for identifying the majority of ALS prevalent cases in the National ALS Registry and that the inclusion of a web registry portal for patients to self-register is important to ensure a more representative population for estimating ALS prevalence. Nonetheless, more than 40% of ALS cases were not ascertained by the Registry, with individuals younger than age 65 and people of color underrepresented. Recommendations are provided for additional methods that can be considered to improve the completeness of case ascertainment.

Objective:To estimate the prevalence of amyotrophic lateral sclerosis (ALS) in the United States for 2017 using data from the National ALS Registry (Registry) as well as capture-recapture methodology to account for under-ascertainment. Established in 2010, the Registry collects and examines data on ALS patients in the US to better describe the epidemiology of ALS (i.e. risk factor exposures, demographics).Methods: The Registry compiled data from national administrative databases (from the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration) and a voluntary enrollment data through a web portal (www.cdc.gov/als). To estimate the number of missing cases, capture-recapture methodology was utilized.Results: The Registry conservatively identified 17,800 adult persons (lower-bound estimate) who met the Registry definition of ALS for an age-adjusted prevalence of 5.5 per 100,000 US population. Using capture-recapture methodology, we obtained a "mean case count" of 24,821 ALS cases (prevalence of 7.7 per 100,000 U.S. population) and estimated the upper-bound estimate to be 31,843 cases (prevalence of 9.9 per 100,000 U.S. population). The pattern of patient characteristics (e.g. age, sex, and race/ethnicity) remained unchanged from previous Registry reports. Overall, ALS was most common among whites, males, and persons aged 60-69 years. The age groups with the lowest number of cases were persons aged 18-39 years. Males had a higher prevalence than females overall and across all data sources.Conclusions: Existing Registry methodology, along with capture-recapture methodology, are being used to better describe the epidemiology and demographics of ALS in the US.

Objective: To estimate the incidence of amyotrophic lateral sclerosis (ALS) in the United States for calendar years 2014-2016 using data from the National ALS Registry (Registry). The Registry collects data on ALS patients in the United States to better describe the epidemiology of ALS, examine risk factors such as environmental and occupational exposures, and characterize the demographics of those living with the disease. Methods: To identify adult incident cases of ALS, the Registry compiles data from three national administrative databases (maintained by the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration). For cases that are not included in these databases, the Registry includes data collected from patients who voluntarily enroll via a secure web portal. Results: The Registry identified 5695 ALS cases in 2014; 6045 cases in 2015; and 4861 cases in 2016 for age-adjusted incidence rates of 1.7 (2014), 1.5 (2015), and 1.5 (2016) per 100,000 U.S. population, respectively. ALS was more common among whites, males, and persons aged 60-79 years. Conclusions: This is the first time administrative and self-reported databases have been used to describe the incidence of ALS for the United States resulting in a better estimate of disease demographics.

BACKGROUND: Researchers face challenges in patient recruitment, especially for rare, fatal diseases such as amyotrophic lateral sclerosis (ALS). These challenges include obtaining sufficient statistical power as well as meeting eligibility requirements such as age, sex, and study proximity. Similarly, persons with ALS (PALS) face difficulty finding and enrolling in research studies for which they are eligible. OBJECTIVE: The aim of this study was to describe how the federal Agency for Toxic Substances and Disease Registry's (ATSDR) National ALS Registry is linking PALS to scientists who are conducting research, clinical trials, and epidemiological studies. METHODS: Through the Registry's online research notification mechanism (RNM), PALS can elect to be notified about new research opportunities. This mechanism allows researchers to upload a standardized application outlining their study design and objectives, and proof of Institutional Review Board approval. If the application is approved, ATSDR queries the Registry for PALS meeting the study's specific eligibility criteria, and then distributes the researcher's study material and contact information to PALS via email. PALS then need to contact the researcher directly to take part in any research. Such an approach allows ATSDR to protect the confidentiality of Registry enrollees. RESULTS: From 2013 to 2019, a total of 46 institutions around the United States and abroad have leveraged this tool and over 600,000 emails have been sent, resulting in over 2000 patients conservatively recruited for clinical trials and epidemiological studies. Patients between the ages of 60 and 69 had the highest level of participation, whereas those between the ages of 18 and 39 and aged over 80 had the lowest. More males participated (4170/7030, 59.32%) than females (2860/7030, 40.68%). CONCLUSIONS: The National ALS Registry's RNM benefits PALS by connecting them to appropriate ALS research. Simultaneously, the system benefits researchers by expediting recruitment, increasing sample size, and efficiently identifying PALS meeting specific eligibility requirements. As more researchers learn about and use this mechanism, both PALS and researchers can hasten research and expand trial options for PALS.

Objective: To estimate the prevalence of amyotrophic lateral sclerosis (ALS) in the United States for 2016 using data from the National ALS Registry (Registry). Established in 2009, the Registry collects data on ALS patients in the U.S. to better describe the epidemiology of ALS, examine risk factors such as environmental and occupational exposures, and characterize the demographics of those living with the disease. Methods: To identify adult prevalent cases of ALS, the Registry compiles data from three national administrative databases (maintained by the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration). To ascertain cases not necessarily included in these databases and to better understand risk-factors associated with ALS and disease progression, the Registry also includes data collected from patients who voluntarily enroll via a web portal to complete online surveys. Results: In 2016, the Registry conservatively identified 16,424 adult persons who met the Registry definition of ALS for an age-adjusted prevalence rate of 5.2 per 100,000 U.S. population. The pattern of patient characteristics (e.g., age, sex, and race/ethnicity) has not changed from previous Registry reports. Overall, ALS was more common among whites, males, and persons aged 60-69 years. The age groups with the lowest number of ALS cases were persons aged 18-39 years. Males had a higher prevalence rate of ALS than females overall and across all data sources. Conclusions: Data collected by the National ALS Registry are being used to better describe the epidemiology and demographics of ALS in the U.S.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurological disease of largely unknown etiology with no cure. The National ALS Registry is a voluntary online system that collects demographic and reproductive history (females only) data from patients with ALS. We will examine the association between demographic and reproductive history among female patients aged >18 years and various ages of onset for ALS. METHODS: Data from a cross-sectional study were collected and examined for 1,018 female ALS patients. Patient characteristics examined were demographics including race, BMI, and familial history of ALS. Among patients, information on reproductive history, including age at menopause, ever pregnant, and age at first pregnancy was collected. Unadjusted and adjusted logistic regression models were used to estimate OR and 95% CI in this study. RESULTS: Women were more likely to be diagnosed with ALS before age 60 if they were nonwhite (p = 0.015), had attended college (p = 0.0012), had a normal BMI at age 40 (p < 0.0001), completed menopause before age 50 (p < 0.0001), and had never been pregnant (p = 0.046) in the univariate analysis. Women diagnosed with ALS before age 60 were also more likely to have limb site of onset (p < 0.0001). In the multivariate analysis, those who completed menopause before age 50 were more likely to be diagnosed with ALS before age 60 (OR = 1.8, 95% CI: 1.4-2.3) compared with women who completed menopause at or after age 50, after controlling for race, ever pregnant, age at first pregnancy, family history of ALS, education status, smoking history, and BMI at age 40. For women who were diagnosed with ALS before age 50, the odds of them entering menopause before age 50 climb to 48.7 (95% CI: 11.8, 200.9). The mean age of ALS diagnosis for women who completed menopause before age 50 was 58 years and 64 years for women who entered menopause after age 50 (p < 0.0001). CONCLUSION: Women who reported completing menopause before age 50 were significantly more likely to be diagnosed with ALS before age 60 compared with those who reported entering menopause after age 50. More research is needed to determine the relationship between female reproductive history, especially regarding endogenous estrogen exposure and early-onset ALS.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) precore (PC) and dual basal core promoter (BCP) mutations halt and down-regulate hepatitis B e antigen (HBeAg) production respectively. PC mutation is rarely associated with HBV genotype A. We sought to examine the association of these variants with HBV genotypes, age, and HBeAg status in a racially diverse population in North America. Prospective study included 1,036 (808 adults, 228 children) participants in the Hepatitis B Research Network. PC and BCP variants were determined by Sanger sequencing, and dominant HBV species (>50%) were reported. APPROACH AND RESULTS: Median age was 36.3 years (range, 2-80), 44.6% HBeAg(+), 74.2% Asians, 13.3% black, and 9.7% white. The dominant PC variant was present in 29.4% participants, including 20 with subgenotype A1 or A2. Seventeen of 20 participants with genotype A and PC had a compensatory C1858T mutation. In the HBeAg(+) cohort, the prevalence of PC and/or BCP variants increased from 14.4% in the first two decades to 51% after 40 years of age. Among those aged 2-18, 52% and 83% with dominant PC and BCP variants were HBeAg(+) compared to 3.8% and 29% in the >40 years age group. HBeAg clearance rates were significantly higher for those with dominant PC or BCP variants: 24.4 and 15.0 per 100 person-years compared to 6.0 in wild-type HBV (P < 0.0001). CONCLUSIONS: PC variants can be present in HBV genotype A and are usually associated with C1858T, which preserves the pregenome encapsidation sequence. Selection of PC and BCP variants occurred at a young age, with increasing prevalence across age groups. HBeAg(+) participants with dominant PC and BCP variants progressed to the HBeAg(-) phase of chronic HBV infection significantly faster. This finding has potential clinical and therapeutic implications.

Background: Previous research has suggested that vigorous physical activity (VPA) during adolescence and early adulthood is associated with ALS. The National ALS Registry (Registry) collects physical activity data from persons with ALS. Objective: To examine the association between vigorous VPA and early onset ALS, defined as a diagnosis before age 60, among patients enrolled in the Registry. VPA was defined as engaging in dynamic exercise for at least 10 minutes in a session that caused heavy sweating or large increases in breathing or heart rate. Methods: A cross-sectional study was conducted of 5463 ALS patients with VPA history and 956 ALS patients who never engaged in VPA. Patient characteristics were collected via online surveys in the following areas: demographic, lifetime VPA history, and initial onset of symptoms. General linear modeling was used to estimate mean age of diagnosis and to compute 95% confidence intervals. Results: Patients who reported engaging in VPA at least moderately (three times a week) during early adulthood were more likely to have an ALS diagnosis earlier compared to patients who did not (p < 0.0001). After controlling for year of birth, statistically significant associations between those reporting VPA at age 15-24 and 25-34 and diagnosis of ALS earlier (p = 0.0009, p = 0.0144 respectively). Conclusion: Patients with ALS who had a history of VPA before age 35, were significantly more likely to be diagnosed with ALS before age 60 compared to patients with ALS who never engaged vigorously. More research is needed in the relationship between VPA and early onset ALS.

INTRODUCTION: A study was conducted in three districts in Hai Phong province, Vietnam to estimate the population size of the Female Sex Workers (FSW) in June-July 2019. METHODS: The procedures included selection of three districts, compilation of a list of accessible venues where FSW congregate, distribution of first unique objects (first capture) and second unique objects (second capture) to FSW in randomly selected venues and implementation of a Mini-Respondent Driven Sampling (mRDS) Survey (third capture). Population size of the FSW was calculated based on the number of FSW in each round, number of FSW 'recaptured' during the second and the third captures. Additionally, personal network size data captured in the mRDS was used to measure the population of FSW within the three districts using Successive Sampling Population Size Estimates (SS-PSE). RESULTS: The total estimated FSWs in the three selected districts, using Three Source Capture-Recapture (3S-CRC) was 958, which is slightly lower than that estimated using SS-PSE - 1192. The 3S-CRC method yielded a provincial estimate of 1911 while the SS-PSE method resulted in a total of 2379 FSW for the province. CONCLUSION: Two techniques produced different PSE at both the district and the province levels and resulted in estimates lower than ones produced using programmatic data. For planning HIV prevention and care service needs among all FSWs, additional studies are needed to estimate the number of sex workers who are not venue-based and use social media platforms to sell services.

BACKGROUND: People who inject drugs (PWID) lag behind other key populations in HIV care continuum outcomes. The impacts of criminal justice reform and increasing drug treatment access on HIV have been underexplored. METHODS: We developed agent-based models (ABM) of sexual partnerships among PWID and non-PWID, and injection equipment-sharing partnerships among PWID in five US cities (Baltimore, Boston, Miami, New York City, San Francisco) over 3 years. The first set of ABM projected changes in partnership discordance among PWID as a function of decreasing ZIP code-level incarceration rates. The second set projected discordance as a function of increasing ZIP code-level drug treatment access. ABM were parameterized and validated overall, and by city and PWID race/ethnicity (Black, Latino, White) using National HIV Behavioral Surveillance data, administrative ZIP code-level data, surveillance reports and prior literature. Informed by research on prisoner release and community-level HIV prevalence, reductions in incarceration rates were fixed at 5% and 30% and respectively projected to increase ZIP code-level HIV prevalence by 2% and 12%. Increases in drug treatment access were fixed at 30% and 58%. RESULTS: In each city, a 30% reduction in ZIP code-level incarceration rates and 12% increase in ZIP code-level HIV prevalence significantly increased sero-discordance among at least one racial/ethnic group of PWID by 1-3 percentage points. A 5% reduction in incarceration rates, and 30% and 58% increases in drug treatment access, led to isolated significant changes in sero-discordance among Black and White PWID that were less than 1 percentage point. CONCLUSION: Reductions in incarceration rates may lead to short-term increases in sero-discordant partnerships among some PWID by increasing community-level HIV prevalence. Efforts to increase HIV testing, engagement in care and community reintegration post release, should be strengthened in the wake of incarceration reform. Additional research should confirm these findings and explore the lack of widespread impacts of drug treatment in this study.