Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 171 Records) |
Query Trace: Mehta P[original query] |
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Amyotrophic lateral sclerosis estimated prevalence cases from 2022 to 2030, data from the national ALS Registry
Mehta P , Raymond J , Nair T , Han M , Berry J , Punjani R , Larson T , Mohidul S , Horton DK . Amyotroph Lateral Scler Frontotemporal Degener 2025 1-6 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. |
Biodynamic modeling and analysis of human-exoskeleton interactions in simulated patient handling tasks
Chen Y , Yin W , Zheng L , Mehta R , Zhang X . Hum Factors 2025 187208241311271 OBJECTIVE: To investigate the biodynamics of human-exoskeleton interactions during patient handling tasks using a subject-specific modeling approach. BACKGROUND: Exoskeleton technology holds promise for mitigating musculoskeletal disorders caused by manual handling and most alarmingly by patient handling jobs. A deeper, more unified understanding of the biomechanical effects of exoskeleton use calls for advanced subject-specific models of complex, dynamic human-exoskeleton interactions. METHODS: Twelve sex-balanced healthy participants performed three simulated patient handling tasks along with a reference load-lifting task, with and without wearing the exoskeleton, while their full-body motion and ground reaction forces were measured. Subject-specific models were constructed using motion and force data. Biodynamic response variables derived from the models were analyzed to examine the effects of the exoskeleton. Model validation used load-lifting trials with known hand forces. RESULTS: The use of exoskeleton significantly reduced (19.7%-27.2%) the peak lumbar flexion moment but increased (26.4%-47.8%) the peak lumbar flexion motion, with greater moment percent reduction in more symmetric handling tasks; similarly affected the shoulder joint moments and motions but only during two more symmetric handling tasks; and significantly reduced the peak motions for the rest of the body joints. CONCLUSION: Subject-specific biodynamic models simulating exoskeleton-assisted patient handling were constructed and validated, demonstrating that the exoskeleton effectively lessened the peak loading to the lumbar and shoulder joints as prime movers while redistributing more motions to these joints and less to the remaining joints. APPLICATION: The findings offer new insights into biodynamic responses during exoskeleton-assisted patient handling, benefiting the development of more effective, possibly task- and individual-customized, exoskeletons. |
Contribution of malnutrition to infant and child deaths in Sub-Saharan Africa and South Asia
Madewell ZJ , Keita AM , Das PM , Mehta A , Akelo V , Oluoch OB , Omore R , Onyango D , Sagam CK , Cain CJ , Chukwuegbo C , Kaluma E , Luke R , Ogbuanu IU , Bassat Q , Kincardett M , Mandomando I , Rakislova N , Varo R , Xerinda EG , Dangor Z , du Toit J , Lala SG , Madhi SA , Mahtab S , Breines MR , Degefa K , Heluf H , Madrid L , Scott JAG , Sow SO , Tapia MD , El Arifeen S , Gurley ES , Hossain MZ , Islam KM , Rahman A , Mutevedzi PC , Whitney CG , Blau DM , Suchdev PS , Kotloff KL . BMJ Glob Health 2024 9 (12) INTRODUCTION: Malnutrition contributes to 45% of all childhood deaths globally, but these modelled estimates lack direct measurements in countries with high malnutrition and under-5 mortality rates. We investigated malnutrition's role in infant and child deaths in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. METHODS: We analysed CHAMPS data from seven sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone and South Africa) collected between 2016 and 2023. An expert panel assessed each death to determine whether malnutrition was an underlying, antecedent or immediate cause or other significant condition. Malnutrition was further classified based on postmortem anthropometry using WHO growth standards for underweight (z-scores for weight-for-age <-2), stunting (length-for-age <-2), and wasting (weight-for-length or MUAC Z-scores <-2). RESULTS: Of 1601 infant and child deaths, malnutrition was considered a causal or significant condition in 632 (39.5%) cases, including 85 (13.4%) with HIV infection. Postmortem measurements indicated 90.1%, 61.2% and 94.1% of these cases were underweight, stunted and wasted, respectively. Most malnutrition-related deaths (n=632) had an infectious cause (89.1%). The adjusted odds of having malnutrition as causal or significant condition were 2.4 (95% CI 1.7 to 3.2) times higher for deaths involving infectious diseases compared with other causes. Common pathogens in the causal pathway for malnutrition-related deaths included Klebsiella pneumoniae (30.4%), Streptococcus pneumoniae (21.5%), Plasmodium falciparum (18.7%) and Escherichia coli/Shigella (17.2%). CONCLUSION: Malnutrition was identified as a causal or significant factor in 39.5% of under-5 deaths in the CHAMPS network, often in combination with infectious diseases. These findings highlight the need for integrated interventions addressing both malnutrition and infectious diseases to effectively reduce under-5 mortality. |
Prevalence of amyotrophic lateral sclerosis - United States, 2010-2011
Mehta P . Am J Public Health 2015 105 (6) e7-9 This is the first population-based prevalence estimate and description of demographic characteristics of amyotrophic lateral sclerosis (ALS) for the United States. Data originated from the Agency for Toxic Substances and Disease’s National ALS Registry launched in 2009. Registry findings are consistent with estimates from long-established ALS registries in Europe and from smaller-scale epidemiologic studies conducted previously in the United States. | | The prevalence of ALS was calculated from the registry data. Demographic characteristics were described by sex, age, race, and ethnicity. The numerator was obtained by using the de-duplicated total number of persons with ALS identified through administrative data and those who self-identified through a secure web portal (Figure 1). The 2011 Census was used for the denominator. Although national incidence cannot be measured with registry data at this time, incidence is being measured in smaller geographic areas (3 states and 8 metropolitan areas) that have participated in ATSDR’s State and Metropolitan Area ALS surveillance projects. |
Assessing COVID-19 pandemic impacts on the health of PWID using a novel data sharing model
Bradley H , Luisi N , Carter A , Pigott TD , Abramovitz D , Allen ST , Asher A , Austin C , Bartholomew TS , Baum M , Board A , Boodram B , Borquez A , Brookmeyer KA , Buchacz K , Burnett J , Cooper HLF , Crepaz N , Debeck K , Feinberg J , Fong C , Freeman E , Furukawa NW , Genberg B , Gorbach P , Hagan H , Hayashi K , Huriaux E , Hurley H , Keruly J , Kristensen K , Lai S , Martin NK , Mateu-Gelabert P , McClain GM Jr , Mehta S , Mok WY , Reynoso M , Strathdee S , Torigian N , Weng CA , Westergaard R , Young A , Jarlais DCD . Aids 2024 OBJECTIVE: Using an innovative data sharing model, we assessed the impacts of the COVID-19 pandemic on the health of people who inject drugs (PWID). DESIGN: The PWID Data Collaborative was established in 2021 to promote data sharing across PWID studies in North America. Contributing studies submitted aggregate data on 23 standardized indicators during four time periods: pre-pandemic (Mar 2019 - Feb 2020), early-pandemic (Mar 2020 - Feb 2021), mid-pandemic (Mar 2021 - Feb 2022), and late pandemic (Mar 2022 - Feb 2023). METHODS: We present study-specific and meta-analyzed estimates for the percentage of PWID who took medications for opioid use disorder, received substance use treatment, shared syringes or injection equipment, had a mental health condition, had been incarcerated, or had experienced houselessness. To examine change over time across indicators, we fit a random effects meta-regression model to prevalence estimates using time as a moderator. RESULTS: Thirteen studies contributed estimates to the Data Collaborative on these indicators, representing 6,213 PWID interviews. We observed minimal change across prevalence of the six indicators between the pre-pandemic (March 2019 - February 2020) and three subsequent time periods, overall or within individual studies. Considerable heterogeneity was observed across study- and time-specific estimates. CONCLUSIONS: Limited pandemic-related change observed in indicators of PWID health is likely a result of policy and supportive service-related changes and may also reflect resilience among service providers and PWID themselves. The Data Collaborative is an unprecedented data sharing model with potential to greatly improve the quality and timeliness of data on the health of PWID. |
Characterization of population connectivity for enhanced cross-border surveillance of yellow fever at Mutukula and Namanga borders in Tanzania
Kakulu RK , Msuya MM , Makora SH , Lucas AM , Kapinga JV , Mwangoka NK , Mehta K , McIntyre E , Boos A , Lamb GS , Mponela M , Gatei W , Merrill R , Ward S , Seleman A , Massa K , Kimaro EG , Mpolya EA . IJID Regions 2024 13 Objectives: Yellow fever (YF) remains a public health threat in Sub-Saharan Africa and South America, with an estimated 200,000 cases and 30,000 deaths annually. Although the World Health Organization considers Tanzania to be at low risk for YF because no YF cases have been reported, the country remains at alert to importation of the virus due to ecological factors and high connectivity to high-risk YF areas in other countries. This study aimed to identify points of interest with connectivity to high-risk YF areas to guide preparedness efforts in Tanzania. Methods: Using the Population Connectivity Across Borders (PopCAB) toolkit, the Nelson Mandela African Institution of Science and Technology (Department of Health and Biomedical Sciences), in collaboration with the Tanzania Ministry of Health and the Centers for Disease Control and Prevention, implemented 12 focus group discussions with participatory mapping in two high-risk borders of Mutukula and Namanga. Results: Participants identified 147 and 90 points of interest with connectivity to YF risk areas in Kenya and Uganda, respectively. The identified locations are important for trade, fishing, pastoralism, tourism, health-seeking, agriculture, mining, religious activities, education, and cross-border marriages. Conclusions: The Tanzania Ministry of Health used the results to update cross-border surveillance and risk communication strategies and vaccination guidelines to prevent the importation of YF into Tanzania. © 2024 The Authors |
A randomized crossover trial of acceptability of quadruple-fortified salt in women and their households in Southern India
Guetterman HM , Rajagopalan K , Fox AM , Johnson CB , Fothergill A , George N , Krisher JT , Haas JD , Mehta S , Williams JL , Crider KS , Finkelstein JL . J Nutr 2024 BACKGROUND: Double-fortified salt (DFS; iron, iodine) improved iron status in randomized trials and was incorporated into India's social safety net programs, suggesting opportunities to address other micronutrient deficiencies. OBJECTIVES: To evaluate acceptability of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B(12)) in women and their households, using a randomized crossover trial design and triangle tests. METHODS: Women 18-49y (n=77) and their households were randomized to receive QFS or DFS in a randomized crossover design over a 3-week period (week 1: QFS/DFS, 2: iodized salt, 3: DFS/QFS). Each week, participants completed a 9-point hedonic questionnaire (1=dislike extremely to 9=like extremely) to evaluate five sensory domains (color, odor, taste, texture, overall acceptability) of the intervention, and remaining salt was weighed using a digital scale. Triangle tests were conducted among women to evaluate sensory discrimination of salt consumed in rice dishes prepared using standardized recipes. Mixed models were used to examine hedonic ratings and salt use; salt type, sequence, and period were included as fixed effects, and household was included as a random effect. Binomial tests were used to evaluate sensory discrimination of salt type in triangle tests. RESULTS: Mean hedonic ratings for most of the five sensory domains were ≥7 (like moderately) and did not differ by salt type (overall acceptability mean [SD]: QFS: 7.8 [0.7] vs. DFS: 7.7 [1.2]; p=0.68). Household salt use (weighed) did not differ by salt type. During the 3-week intervention period, weighed salt use and hedonic ratings significantly increased, indicating a period effect independent of salt type or sequence. In triangle tests, rice samples prepared with QFS, DFS, or iodized salt were not distinguishable. CONCLUSION: Acceptability of QFS was high, based on individual hedonic ratings and weighed household salt use. Rice dishes prepared with DFS, QFS, and iodized salt were not distinguishable. Findings informed the design of a randomized trial of QFS in this population. REGISTRATION NUMBERS: NCT03853304 and REF/2019/03/024479. |
The diabetes technology society error grid and trend accuracy matrix for glucose monitors
Klonoff DC , Freckmann G , Pleus S , Kovatchev BP , Kerr D , Tse CC , Li C , Agus MSD , Dungan K , Voglová Hagerf B , Krouwer JS , Lee WA , Misra S , Rhee SY , Sabharwal A , Seley JJ , Shah VN , Tran NK , Waki K , Worth C , Tian T , Aaron RE , Rutledge K , Ho CN , Ayers AT , Adler A , Ahn DT , Aktürk HK , Al-Sofiani ME , Bailey TS , Baker M , Bally L , Bannuru RR , Bauer EM , Bee YM , Blanchette JE , Cengiz E , Chase JG , YChen K , Cherñavvsky D , Clements M , Cote GL , Dhatariya KK , Drincic A , Ejskjaer N , Espinoza J , Fabris C , Fleming GA , Gabbay MAL , Galindo RJ , Gómez-Medina AM , Heinemann L , Hermanns N , Hoang T , Hussain S , Jacobs PG , Jendle J , Joshi SR , Koliwad SK , Lal RA , Leiter LA , Lind M , Mader JK , Maran A , Masharani U , Mathioudakis N , McShane M , Mehta C , Moon SJ , Nichols JH , O'Neal DN , Pasquel FJ , Peters AL , Pfützner A , Pop-Busui R , Ranjitkar P , Rhee CM , Sacks DB , Schmidt S , Schwaighofer SM , Sheng B , Simonson GD , Sode K , Spanakis EK , Spartano NL , Umpierrez GE , Vareth M , Vesper HW , Wang J , Wright E , Wu AHB , Yeshiwas S , Zilbermint M , Kohn MA . J Diabetes Sci Technol 2024 19322968241275701 INTRODUCTION: An error grid compares measured versus reference glucose concentrations to assign clinical risk values to observed errors. Widely used error grids for blood glucose monitors (BGMs) have limited value because they do not also reflect clinical accuracy of continuous glucose monitors (CGMs). METHODS: Diabetes Technology Society (DTS) convened 89 international experts in glucose monitoring to (1) smooth the borders of the Surveillance Error Grid (SEG) zones and create a user-friendly tool-the DTS Error Grid; (2) define five risk zones of clinical point accuracy (A-E) to be identical for BGMs and CGMs; (3) determine a relationship between DTS Error Grid percent in Zone A and mean absolute relative difference (MARD) from analyzing 22 BGM and nine CGM accuracy studies; and (4) create trend risk categories (1-5) for CGM trend accuracy. RESULTS: The DTS Error Grid for point accuracy contains five risk zones (A-E) with straight-line borders that can be applied to both BGM and CGM accuracy data. In a data set combining point accuracy data from 18 BGMs, 2.6% of total data pairs equally moved from Zones A to B and vice versa (SEG compared with DTS Error Grid). For every 1% increase in percent data in Zone A, the MARD decreased by approximately 0.33%. We also created a DTS Trend Accuracy Matrix with five trend risk categories (1-5) for CGM-reported trend indicators compared with reference trends calculated from reference glucose. CONCLUSION: The DTS Error Grid combines contemporary clinician input regarding clinical point accuracy for BGMs and CGMs. The DTS Trend Accuracy Matrix assesses accuracy of CGM trend indicators. |
Effects of COVID-19 on motor neuron disease mortality in the United States: a population-based cross-sectional study
Raymond J , Berry JD , Larson T , Horton DK , Mehta P . Amyotroph Lateral Scler Frontotemporal Degener 2024 1-8 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. |
A microRNA diagnostic biomarker for amyotrophic lateral sclerosis
Banack SA , Dunlop RA , Mehta P , Mitsumoto H , Wood SP , Han M , Cox PA . Brain Commun 2024 6 (5) fcae268 ![]() ![]() Blood-based diagnostic biomarkers for amyotrophic lateral sclerosis will improve patient outcomes and positively impact novel drug development. Critical to the development of such biomarkers is robust method validation, optimization and replication with adequate sample sizes and neurological disease comparative blood samples. We sought to test an amyotrophic lateral sclerosis biomarker derived from diverse samples to determine if it is disease specific. Extracellular vesicles were extracted from blood plasma obtained from individuals diagnosed with amyotrophic lateral sclerosis, primary lateral sclerosis, Parkinson's disease and healthy controls. Immunoaffinity purification was used to create a neural-enriched extracellular vesicle fraction. MicroRNAs were measured across sample cohorts using real-time polymerase chain reaction. A Kruskal-Wallis test was used to assess differences in plasma microRNAs followed by post hoc Mann-Whitney tests to compare disease groups. Diagnostic accuracy was determined using a machine learning algorithm and a logistic regression model. We identified an eight-microRNA diagnostic signature for blood samples from amyotrophic lateral sclerosis patients with high sensitivity and specificity and an area under the curve calculation of 98% with clear statistical separation from neurological controls. The eight identified microRNAs represent disease-related biological processes consistent with amyotrophic lateral sclerosis. The direction and magnitude of gene fold regulation are consistent across four separate patient cohorts with real-time polymerase chain reaction analyses conducted in two laboratories from diverse samples and sample collection procedures. We propose that this diagnostic signature could be an aid to neurologists to supplement current clinical metrics used to diagnose amyotrophic lateral sclerosis. |
Racial disparities in the diagnosis and prognosis of ALS patients in the United States
Raymond J , Nair T , Gwathmey KG , Larson T , Horton DK , Mehta P . J Racial Ethn Health Disparities 2024 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. |
Correction to: Comparison of demographics: National Amyotrophic Lateral Sclerosis Registry and Clinical Trials Data
Han M , Raymond J , Larson TC , Mehta P , Horton DK . J Racial Ethn Health Disparities 2024 |
Comparison of demographics: National Amyotrophic Lateral Sclerosis Registry and Clinical Trials Data
Han M , Raymond J , Larson TC , Mehta P , Horton DK . J Racial Ethn Health Disparities 2024 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. |
Prevalence of ALS in all 50 states in the United States, data from the National ALS Registry, 2011-2018
Mehta P , Raymond J , Nair T , Han M , Punjani R , Larson T , Berry J , Mohidul S , Horton DK . Amyotroph Lateral Scler Frontotemporal Degener 2024 1-7 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. |
Distinct features of ribonucleotides within genomic DNA in Aicardi-Goutières syndrome ortholog mutants of Saccharomyces cerevisiae
Kundnani DL , Yang T , Gombolay AL , Mukherjee K , Newnam G , Meers C , Verma I , Chhatlani K , Mehta ZH , Mouawad C , Storici F . iScience 2024 27 (6) Ribonucleoside monophosphates (rNMPs) are abundantly found within genomic DNA of cells. The embedded rNMPs alter DNA properties and impact genome stability. Mutations in ribonuclease (RNase) H2, a key enzyme for rNMP removal, are associated with the Aicardi-Goutières syndrome (AGS), a severe neurological disorder. Here, we engineered orthologs of the human RNASEH2A-G37S and RNASEH2C-R69W AGS mutations in yeast Saccharomyces cerevisiae: rnh201-G42S and rnh203-K46W. Using the ribose-seq technique and the Ribose-Map bioinformatics toolkit, we unveiled rNMP abundance, composition, hotspots, and sequence context in these AGS-ortholog mutants. We found a high rNMP presence in the nuclear genome of rnh201-G42S-mutant cells, and an elevated rCMP content in both mutants, reflecting preferential cleavage of RNase H2 at rGMP. We discovered unique rNMP patterns in each mutant, showing differential activity of the AGS mutants on the leading or lagging replication strands. This study guides future research on rNMP characteristics in human genomes with AGS mutations. © 2024 The Authors |
Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a)
Razavi AC , Richardson LC , Coronado F , Dzaye O , Bhatia HS , Mehta A , Quyyumi AA , Vaccarino V , Budoff MJ , Nasir K , Tsimikas S , Whelton SP , Blaha MJ , Blumenthal RS , Sperling LS . Am J Prev Cardiol 2024 18 100674 OBJECTIVE: Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). We assessed the association between regular aspirin use and ASCVD mortality among individuals with versus without elevated Lp(a) in a nationally representative US cohort. METHODS: Eligible participants were aged 40-70 years without clinical ASCVD, reported on aspirin use, and had Lp(a) measurements from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), the only cycle of this nationally representative US cohort to measure Lp(a). Regular aspirin use was defined as taking aspirin ≥30 times in the previous month. Using NHANES III linked mortality records and weighted Cox proportional hazards regression, the association between regular aspirin use and ASCVD mortality was observed in those with and without elevated Lp(a) (≥50 versus <50 mg/dL) over a median 26-year follow-up. RESULTS: Among 2,990 persons meeting inclusion criteria (∼73 million US adults), the mean age was 50 years, 86% were non-Hispanic White, 9% were non-Hispanic Black, 53% were female, and 7% reported regular aspirin use. The median Lp(a) was 14 mg/dL and the proportion with elevated Lp(a) was similar among those with versus without regular aspirin use (15.1% versus 21.9%, p = 0.16). Among individuals with elevated Lp(a), the incidence of ASCVD mortality per 1,000 person-years was lower for those with versus without regular aspirin use (1.2, 95% CI: 0.1-2.3 versus 3.9, 95% CI: 2.8-4.9). In multivariable modeling, regular aspirin use was associated with a 52% lower risk of ASCVD mortality among individuals with elevated Lp(a) (HR=0.48, 95% CI: 0.28-0.83), but not for those without elevated Lp(a) (HR=1.01, 95% CI: 0.81-1.25; p-interaction=0.001). CONCLUSION: Regular aspirin use was associated with significantly lower ASCVD mortality in adults without clinical ASCVD who had elevated Lp(a). These findings may have clinical and public health implications for aspirin utilization in primary prevention. |
What do you think caused your ALS? An analysis of the CDC national amyotrophic lateral sclerosis patient registry qualitative risk factor data using artificial intelligence and qualitative methodology
Boyce D , Raymond J , Larson TC , Kirkland E , Horton DK , Mehta P . Amyotroph Lateral Scler Frontotemporal Degener 2024 1-10 ![]() ![]() 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. |
Biodynamic modeling and analysis of human-exoskeleton interactions during assisted manual handling
Chen Y , Yin W , Zheng L , Mehta R , Zhang X . Proc Hum Factors Ergon Soc 2023 67 803-806 The objective of this study was to investigate the effects of a back exoskeleton on joint kinematics and kinetics during assisted manual handling tasks using subject-specific musculoskeletal biodynamic models and model-based analyses. We constructed these musculoskeletal models using OpenSim (Delp et al., 2007), incorporating optical motion capture, ground reaction forces (GRFs) measurements, and humanexoskeleton interactive force input. Our long-term goal is to enable digital modeling and simulation that can aid in the design and development of more effective exoskeletons and safer manual handling practices. © 2023 Human Factors and Ergonomics Society. |
Farmworker mobility and COVID-19 vaccination strategies: Yuma County, Arizona, 2021
Franc KA , Phippard AE , Ruedas P , Pinto SJ , Mehta K , Montiel S , Contreras S , Katz H , McIntyre E , Lopez B , Kreutzberg-Martinez M , Steiner D , Gomez D , Merrill R . Am J Trop Med Hyg 2024 Farmworkers, a group of essential workers, experience a disproportionately high burden of COVID-19 due to their living and working conditions. This project characterized farmworker mobility in and around Yuma County, Arizona, to identify opportunities to improve farmworker access to COVID-19 vaccination. We collected qualitative and geospatial data through a series of in-person and virtual focus group discussions, key informant interviews, and intercept interviews with participatory mapping. Participants included farmworkers, employers, and representatives of local institutions who serve or interact with farmworkers. We identified participants through purposive and referential sampling and grouped people by sociodemographic characteristics for interviews. We used qualitative and geospatial analyses to identify common themes and mobility patterns. The team interviewed 136 people from February 26 to April 2, 2021. Common themes emerged about how farmworkers have little or no access to COVID-19 vaccination unless offered at their workplaces or at locations where they congregate at convenient times. Further, farmworkers described how their demanding work schedules, long commute times, and caretaker commitments make it challenging to access vaccination services. Geospatial analyses identified three geographic areas in Yuma County where farmworkers reported living and working that did not have a COVID-19 vaccine clinic within walking distance. Coordination between local public health authorities and key partners, including employers and trusted representatives from local community-based organizations or the Mexican consulate, to offer vaccination at worksites or other locations where farmworkers congregate can help improve access to COVID-19 vaccines and booster doses for this population. |
Identifying delays in healthcare seeking and provision: The Three Delays-in-Healthcare and mortality among infants and children aged 1-59 months
Garcia Gomez E , Igunza KA , Madewell ZJ , Akelo V , Onyango D , El Arifeen S , Gurley ES , Hossain MZ , Chowdhury MAI , Islam KM , Assefa N , Scott JAG , Madrid L , Tilahun Y , Orlien S , Kotloff KL , Tapia MD , Keita AM , Mehta A , Magaço A , Torres-Fernandez D , Nhacolo A , Bassat Q , Mandomando I , Ogbuanu I , Cain CJ , Luke R , Kamara SIB , Legesse H , Madhi S , Dangor Z , Mahtab S , Wise A , Adam Y , Whitney CG , Mutevedzi PC , Blau DM , Breiman RF , Tippett Barr BA , Rees CA . PLOS Glob Public Health 2024 4 (2) e0002494 Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted. |
Mortality among children aged <5 years living with HIV who are receiving antiretroviral treatment - U.S. President's Emergency Plan for AIDS Relief, 28 supported countries and regions, October 2020-September 2022
Agathis NT , Faturiyele I , Agaba P , Fisher KA , Hackett S , Agyemang E , Mehta N , Kindra G , Morof DF , Mutisya I , Nyabiage L , Battey KA , Olotu E , Maphosa T , Motswere-Chirwa C , Ketlogetswe AT , Mafa-Setswalo J , Mazibuko S , de Deus MIT , Nhaguiombe HG , Machage EM , Mugisa B , Ogundehin DT , Mbelwa C , Birabwa E , Etima M , Adamu Y , Lawal I , Maswai J , Njeru D , Mwambona J , Nguhuni B , Mrina R , Hrapcak S , Siberry GK , Godfrey C , Wolf HT . MMWR Morb Mortal Wkly Rep 2023 72 (48) 1293-1299 Globally, children aged <5 years, including those living with HIV who are not receiving antiretroviral treatment (ART), experience disproportionately high mortality. Global mortality among children living with HIV aged <5 years receiving ART is not well described. This report compares mortality and related clinical measures among infants aged <1 year and children aged 1-4 years living with HIV with those among older persons aged 5-14, 15-49, and ≥50 years living with HIV receiving ART services at all clinical sites supported by the U.S. President's Emergency Plan for AIDS Relief. During October 2020-September 2022, an average of 11,980 infants aged <1 year and 105,510 children aged 1-4 years were receiving ART each quarter; among these infants and children receiving ART, 586 (4.9%) and 2,684 (2.5%), respectively, were reported to have died annually. These proportions of infants and children who died ranged from four to nine times higher in infants aged <1 year, and two to five times higher in children aged 1-4 years, than the proportions of older persons aged ≥5 years receiving ART. Compared with persons aged ≥5 years living with HIV, the proportions of children aged <5 years living with HIV who experienced interruptions in treatment were also higher, and the proportions who had a documented HIV viral load result or a suppressed viral load were lower. Prioritizing and optimizing HIV and general health services for children aged <5 years living with HIV receiving ART, including those recommended in the WHO STOP AIDS Package, might help address these disproportionately poorer outcomes. |
Endophthalmitis, cutaneous nodules, and brain lesions in stem cell transplant recipient
Axell-House DB , Nagarajan P , Bhatti MM , Mehta RS , Roy S , Ali IKM , John TM . Clin Infect Dis 2023 77 (8) 1212-1215 A 46-year-old man with relapsed acute myeloid leukemia underwent his second matched related donor stem cell transplant (SCT), after fludarabine and melphalan conditioning followed by post-transplant cyclophosphamide. He engrafted on day +20. On day +27, he developed fever, sinusitis, left eyelid swelling, and right eye subconjunctival swelling (Figure 1A). He required an urgent right vitrectomy for endophthalmitis. Seven days later, he developed skin nodules on his upper and lower extremities which progressively enlarged and became more diffuse (Figure 1Band 1C). Laboratory tests showed leukopenia (white blood cell count 3.1 × 109/L), anemia (Hb 7.2 g/dL), and severe thrombocytopenia (25 × 109/L) with normal electrolytes, and normal renal and hepatic function. Blood, urine, and sputum cultures were no growth, and infectious serologies, nucleic acid, and antigen tests were negative, including for human immunodeficiency virus, syphilis, Toxoplasma, tuberculosis, cytomegalovirus, and Strongyloides. Nasal endoscopy did not demonstrate necrosis of sinus tissue, and sinus swab cultures did not grow any organisms of clinical significance. Wide excisional skin biopsies of skin lesions demonstrated a lymphohistiocytic infiltrate and panniculitis (Figure 2A) and circular structures (Figure 2B). Vitrectomy was performed for endophthalmitis, and vitreous fluid cultures had no growth. Positron emission tomography (PET) demonstrated diffuse subcutaneous foci most numerous of the lower extremities, and a left occipitotemporal focus (Figure 3A). Shortly thereafter, he developed acute encephalopathy, drowsiness, and rhythmic movements of his right arm concerning for seizures. Brain magnetic resonance imaging (MRI) demonstrated abnormalities of the left frontal gyrus, occipital lobe, parieto-occipital sulcus, and cerebellum, concerning for embolic strokes (Figure 3B). He continued to have fever and progression of skin lesions despite treatment with meropenem, vancomycin, minocycline, and amphotericin. What is the likely diagnosis? |
A brief report on juvenile amyotrophic lateral sclerosis cases in the United States National ALS Registry: 2010-2018
Raymond J , Berry J , Kasarskis EJ , Larson T , Horton DK , Mehta P . Amyotroph Lateral Scler Frontotemporal Degener 2023 1-3 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. |
Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals
Otter AD , Jones S , Hicks B , Bailey D , Callaby H , Houlihan C , Rampling T , Gordon NC , Selman H , Satheshkumar PS , Townsend M , Mehta R , Pond M , Jones R , Wright D , Oeser C , Tonge S , Linley E , Hemingway G , Coleman T , Millward S , Lloyd A , Damon I , Brooks T , Vipond R , Rowe C , Hallis B . Nat Commun 2023 14 (1) 5948 In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design. |
Prevalence of amyotrophic lateral sclerosis in the United States, 2018
Mehta P , Raymond J , Zhang Y , Punjani R , Han M , Larson T , Muravov O , Lyles RH , Horton DK . Amyotroph Lateral Scler Frontotemporal Degener 2023 1-7 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. |
Folate and vitamin B12 status in women of reproductive age in rural Haryana, India: Estimating population-based prevalence for neural tube defects
Das R , Duggal M , Rosenthal J , Kankaria A , Senee HK , Jabbar S , Kaur M , Kumar V , Bhardwaj S , Singh N , Dhanjal GS , Kumar A , Rose CE , Bhatia R , Gupta R , Dalpath S , Crider KS , Zhang M , Pfeiffer CM , Gupta R , Mehta R , Raina N , Yeung LF . Birth Defects Res 2024 116 (8) e2390 ![]() BACKGROUND: Folate and vitamin B12 deficiencies in pregnant women are associated with increased risk for adverse maternal and infant health outcomes, including neural tube defects (NTDs). METHODS: A population-based cross-sectional survey was conducted in two rural areas in Ambala District, Haryana, India in 2017 to assess baseline folate and vitamin B12 status among women of reproductive age (WRA) and predict the prevalence of NTDs. We calculated the prevalence of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 775 non-pregnant, non-lactating WRA (18-49 years). Using red blood cell (RBC) folate distributions and an established Bayesian model, we predicted NTD prevalence. All analyses were conducted using SAS-callable SUDAAN Version 11.0.4 to account for complex survey design. RESULTS: Among WRA, 10.1% (95% CI: 7.9, 12.7) and 9.3% (95% CI: 7.4, 11.6) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The prevalence of RBC folate insufficiency (<748 nmol/L) was 78.3% (95% CI: 75.0, 81.3) and the predicted NTD prevalence was 21.0 (95% uncertainly interval: 16.9, 25.9) per 10,000 live births. Prevalences of vitamin B12 deficiency (<200 pg/mL) and marginal deficiency (≥200 pg/mL and ≤300 pg/mL) were 57.7% (95% CI: 53.9, 61.4) and 23.5% (95% CI: 20.4, 26.9), respectively. CONCLUSIONS: The magnitude of folate insufficiency and vitamin B12 deficiency in this Northern Indian population is a substantial public health concern. The findings from the survey help establish the baseline against which results from future post-fortification surveys can be compared. |
Comparing Amyotrophic lateral sclerosis (ALS) patient characteristics from the National ALS Registry and the Massachusetts ALS Registry, data through 2015
Raymond J , Punjani R , Larson T , Berry JD , Horton DK , Mehta P . Amyotroph Lateral Scler Frontotemporal Degener 2023 1-8 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. |
Effectiveness of 2 and 3 mRNA COVID-19 Vaccines Doses against Omicron and Delta-Related Outpatient Illness among Adults, October 2021 - February 2022 (preprint)
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Geffel KM , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M , Arroliga A , Beeram M , Dunnigan K , Ettlinger J , Graves A , Hoffman E , Jatla M , McKillop A , Murthy K , Mutnal M , Priest E , Raiyani C , Rao A , Requenez L , Settele N , Smith M , Stone K , Thomas J , Volz M , Walker K , Zayed M , Annan E , Daley P , Kniss K , Merced-Morales A , Ayala E , Amundsen B , Aragones M , Calderon R , Hong V , Jimenez G , Kim J , Ku J , Lewin B , McDaniel A , Reyes A , Shaw S , Takhar H , Torres A , Burganowski R , Kiniry E , Moser KA , Nguyen M , Park S , Wellwood S , Wickersham B , Alvarado-Batres J , Benz S , Berger H , Bissonnette A , Blake J , Boese K , Botten E , Boyer J , Braun M , Breu B , Burbey G , Cravillion C , Delgadillo C , Donnerbauer A , Dziedzic T , Eddy J , Edgren H , Ermeling A , Ewert K , Fehrenbach C , Fernandez R , Frome W , Guzinski S , Heeren L , Herda D , Hertel M , Heuer G , Higdon E , Ivacic L , Jepsen L , Kaiser S , Karl J , Keffer B , King J , Koepel TK , Kohl S , Kohn S , Kohnhorst D , Kronholm E , Le T , Lemieux A , Marcis C , Maronde M , McCready I , McGreevey K , Meece J , Mehta N , Miesbauer D , Moon V , Moran J , Nikolai C , Olson B , Olstadt J , Ott L , Pan N , Pike C , Polacek D , Presson M , Price N , Rayburn C , Reardon C , Rotar M , Rottscheit C , Salzwedel J , Saucedo J , Scheffen K , Schug C , Seyfert K , Shrestha R , Slenczka A , Stefanski E , Strupp M , Tichenor M , Watkins L , Zachow A , Zimmerman B , Bauer S , Beney K , Cheng CK , Faraj N , Getz A , Grissom M , Groesbeck M , Harrison S , Henson K , Jermanus K , Johnson E , Kaniclides A , Kimberly A , Lamerato LE , Lauring A , Lehmann-Wandell R , McSpadden EJ , Nabors L , Truscon R , Balasubramani GK , Bear T , Bobeck J , Bowser E , Clarke K , Clarke LG , Dauer K , Deluca C , Dierks B , Haynes L , Hickey R , Johnson M , Jonsson A , Luosang N , McKown L , Peterson A , Phaturos D , Rectenwald A , Sax TM , Stiegler M , Susick M , Suyama J , Taylor L , Walters S , Weissman A , Williams JV , Blair M , Carter J , Chappell J , Copen E , Denney M , Graes K , Halasa N , Lindsell C , Liu Z , Longmire S , McHenry R , Short L , Tan HN , Vargas D , Wrenn J , Wyatt D , Zhu Y . medRxiv 2022 10 Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Causes of death among infants and children in the Child Health and Mortality Prevention Surveillance (CHAMPS) Network
Bassat Q , Blau DM , Ogbuanu IU , Samura S , Kaluma E , Bassey IA , Sow S , Keita AM , Tapia MD , Mehta A , Kotloff KL , Rahman A , Islam KM , Alam M , El Arifeen S , Gurley ES , Baillie V , Mutevedzi P , Mahtab S , Thwala BN , Tippett Barr BA , Onyango D , Akelo V , Rogena E , Onyango P , Omore R , Mandomando I , Ajanovic S , Varo R , Sitoe A , Duran-Frigola M , Assefa N , Scott JAG , Madrid L , Tesfaye T , Dessie Y , Madewell ZJ , Breiman RF , Whitney CG , Madhi SA . JAMA Netw Open 2023 6 (7) e2322494 IMPORTANCE: The number of deaths of children younger than 5 years has been steadily decreasing worldwide, from more than 17 million annual deaths in the 1970s to an estimated 5.3 million in 2019 (with 2.8 million deaths occurring in those aged 1-59 months [53% of all deaths in children aged <5 years]). More detailed characterization of childhood deaths could inform interventions to improve child survival. OBJECTIVE: To describe causes of postneonatal child deaths across 7 mortality surveillance sentinel sites in Africa and Asia. DESIGN, SETTING, AND PARTICIPANTS: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network conducts childhood mortality surveillance in sub-Saharan Africa and South Asia using innovative postmortem minimally invasive tissue sampling (MITS). In this cross-sectional study, MITS was conducted in deceased children aged 1 to 59 months at 7 sites in sub-Saharan Africa and South Asia from December 3, 2016, to December 3, 2020. Data analysis was conducted between October and November 2021. MAIN OUTCOMES AND MEASURES: The expert panel attributed underlying, intermediate, and immediate conditions in the chain of events leading to death, based on histopathologic analysis, microbiological diagnostics, clinical data, and verbal autopsies. RESULTS: In this study, MITS was performed in 632 deceased children (mean [SD] age at death, 1.3 [0.3] years; 342 [54.1%] male). The 6 most common underlying causes of death were malnutrition (104 [16.5%]), HIV (75 [11.9%]), malaria (71 [11.2%]), congenital birth defects (64 [10.1%]), lower respiratory tract infections (LRTIs; 53 [8.4%]), and diarrheal diseases (46 [7.2%]). When considering immediate causes only, sepsis (191 [36.7%]) and LRTI (129 [24.8%]) were the 2 dominant causes. An infection was present in the causal chain in 549 of 632 deaths (86.9%); pathogens most frequently contributing to infectious deaths included Klebsiella pneumoniae (155 of 549 infectious deaths [28.2%]; 127 [81.9%] considered nosocomial), Plasmodium falciparum (122 of 549 [22.2%]), and Streptococcus pneumoniae (109 of 549 [19.9%]). Other organisms, such as cytomegalovirus (57 [10.4%]) and Acinetobacter baumannii (39 [7.1%]; 35 of 39 [89.7%] considered nosocomial), also played important roles. For the top underlying causes of death, the median number of conditions in the chain of events leading to death was 3 for malnutrition, 3 for HIV, 1 for malaria, 3 for congenital birth defects, and 1 for LRTI. Expert panels considered 494 of 632 deaths (78.2%) preventable and 26 of 632 deaths (4.1%) preventable under certain conditions. CONCLUSIONS AND RELEVANCE: In this cross-sectional study investigating causes of child mortality in the CHAMPS Network, results indicate that, in these high-mortality settings, infectious diseases continue to cause most deaths in infants and children, often in conjunction with malnutrition. These results also highlight opportunities for action to prevent deaths and reveal common interaction of various causes in the path toward death. |
Evaluating demographic representation in clinical trials: Use of the adaptive coronavirus disease 2019 treatment trial (ACTT) as a test case
Ortega-Villa AM , Hynes NA , Levine CB , Yang K , Wiley Z , Jilg N , Wang J , Whitaker JA , Colombo CJ , Nayak SU , Kim HJ , Iovine NM , Ince D , Cohen SH , Langer AJ , Wortham JM , Atmar RL , El Sahly HM , Jain MK , Mehta AK , Wolfe CR , Gomez CA , Beresnev T , Mularski RA , Paules CI , Kalil AC , Branche AR , Luetkemeyer A , Zingman BS , Voell J , Whitaker M , Harkins MS , Davey RT Jr , Grossberg R , George SL , Tapson V , Short WR , Ghazaryan V , Benson CA , Dodd LE , Sweeney DA , Tomashek KM . Open Forum Infect Dis 2023 10 (6) ofad290 BACKGROUND: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. METHODS: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. RESULTS: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. CONCLUSIONS: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease. |
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