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1.
Ann Neurol ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38924596

ABSTRACT

OBJECTIVE: Alzheimer's disease (AD) is believed to be more common in African Americans (AA), but biomarker studies in AA populations are limited. This report represents the largest study to date examining cerebrospinal fluid AD biomarkers in AA individuals. METHODS: We analyzed 3,006 cerebrospinal fluid samples from controls, AD cases, and non-AD cases, including 495 (16.5%) self-identified black/AA and 2,456 (81.7%) white/European individuals using cutoffs derived from the Alzheimer's Disease Neuroimaging Initiative, and using a data-driven multivariate Gaussian mixture of regressions. RESULTS: Distinct effects of race were found in different groups. Total Tauand phospho181-Tau were lower among AA individuals in all groups (p < 0.0001), and Aß42 was markedly lower in AA controls compared with white controls (p < 0.0001). Gaussian mixture of regressions modeling of cerebrospinal fluid distributions incorporating adjustments for covariates revealed coefficient estimates for AA race comparable with 2-decade change in age. Using Alzheimer's Disease Neuroimaging Initiative cutoffs, fewer AA controls were classified as biomarker-positive asymptomatic AD (8.0% vs 13.4%). After adjusting for covariates, our Gaussian mixture of regressions model reduced this difference, but continued to predict lower prevalence of asymptomatic AD among AA controls (9.3% vs 13.5%). INTERPRETATION: Although the risk of dementia is higher, data-driven modeling indicates lower frequency of asymptomatic AD in AA controls, suggesting that dementia among AA populations may not be driven by higher rates of AD. ANN NEUROL 2024.

2.
J Biol Chem ; 298(12): 102625, 2022 12.
Article in English | MEDLINE | ID: mdl-36306823

ABSTRACT

Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused by N-sulfoglucosamine sulfohydrolase (SGSH) deficiency. SGSH removes the sulfate from N-sulfoglucosamine residues on the nonreducing end of heparan sulfate (HS-NRE) within lysosomes. Enzyme deficiency results in accumulation of partially degraded HS within lysosomes throughout the body, leading to a progressive severe neurological disease. Enzyme replacement therapy has been proposed, but further evaluation of the treatment strategy is needed. Here, we used Chinese hamster ovary cells to produce a highly soluble and fully active recombinant human sulfamidase (rhSGSH). We discovered that rhSGSH utilizes both the CI-MPR and LRP1 receptors for uptake into patient fibroblasts. A single intracerebroventricular (ICV) injection of rhSGSH in MPS IIIA mice resulted in a tissue half-life of 9 days and widespread distribution throughout the brain. Following a single ICV dose, both total HS and the MPS IIIA disease-specific HS-NRE were dramatically reduced, reaching a nadir 2 weeks post dose. The durability of effect for reduction of both substrate and protein markers of lysosomal dysfunction and a neuroimmune response lasted through the 56 days tested. Furthermore, seven weekly 148 µg doses ICV reduced those markers to near normal and produced a 99.5% reduction in HS-NRE levels. A pilot study utilizing every other week dosing in two animals supports further evaluation of less frequent dosing. Finally, our dose-response study also suggests lower doses may be efficacious. Our findings show that rhSGSH can normalize lysosomal HS storage and markers of a neuroimmune response when delivered ICV.


Subject(s)
Brain Diseases , Mucopolysaccharidosis III , Cricetinae , Animals , Humans , Mice , Mucopolysaccharidosis III/drug therapy , Mucopolysaccharidosis III/metabolism , CHO Cells , Pilot Projects , Cricetulus , Hydrolases/metabolism , Brain/metabolism , Heparitin Sulfate/metabolism , Brain Diseases/metabolism , Lysosomes/metabolism , Disease Models, Animal
3.
J Viral Hepat ; 29(11): 994-1003, 2022 11.
Article in English | MEDLINE | ID: mdl-35925950

ABSTRACT

Persons who inject drugs (PWID) have been experiencing a higher burden of new hepatitis C (HCV) due to the opioid epidemic. The greatest increases in injection have been in rural communities. However, less is known about the prevalence of HCV or its risk factors in rural compared to non-rural communities. This study compared HCV infection history, current infection, and associated behavioural and sociodemographic correlates among PWID recruited from rural and non-rural communities from Upstate New York (NY). This cross-sectional study recruited 309 PWID, using respondent-driven sampling. Blood samples were collected through finger stick for HCV antibody and RNA tests. A survey was also self-administered for HCV infection history, sociodemographics and behavioural correlates to compare by setting rurality. HCV seropositivity was significantly higher among PWID from rural than non-rural communities (71.0% vs. 46.8%), as was current infection (41.4% vs. 25.9%). High levels of past year syringe (44.4%) and equipment (62.2%) sharing were reported. Factors associated with infection history include syringe service program utilization, non-Hispanic white race, sharing needles and methamphetamine injection, which was higher in rural vs. non-rural communities (38.5% vs. 15.5%). HCV burden among PWID appears higher in rural than non-rural communities and may be increasing possibly due to greater levels of methamphetamine injection. On-going systematic surveillance of HCV prevalence and correlates is crucial to respond to the changing opioid epidemic landscape. Additionally, improving access to harm reduction services, especially with special focus on stimulants, may be important to reduce HCV prevalence among PWID in rural settings.


Subject(s)
Drug Users , HIV Infections , Hepatitis C , Methamphetamine , Substance Abuse, Intravenous , Cross-Sectional Studies , HIV Infections/epidemiology , Hepacivirus , Hepatitis C/epidemiology , Humans , Prevalence , RNA , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/epidemiology
4.
Plant Dis ; 106(6): 1736-1742, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34962417

ABSTRACT

Ralstonia solanacearum is a pathogen causing bacterial wilt disease of potato, resulting in 70% potato production losses in Kenya. A study was conducted to determine the diversity of R. solanacearum species complex strains within the main potato-growing regions of Kenya. Potato tubers were collected in different potato-growing regions of Kenya from visibly wilted potato plants as well as samples of tomato, irrigation water, and cultures for pathogen isolation. Genomic DNA was isolated from 135 purified cultures of RSSC isolates and PCR-amplified using multiplex and sequevar primers targeting the endoglucanase (egl) partial gene sequences. Pathogenicity tests using R. solanacearum strain (phylotype II sequevar I) were done on the cultivars Kenya Karibu, Shangi, Chulu, Wanjiku, and MoneyMaker. Phylogenetic analysis of the partial egl gene identified two genospecies, R. pseudosolanacearum sp. nov. (1.5%) and R. solanacearum (98.5%). All R. solanacearum strains clustered in sequevar I and were distributed in all the potato-growing regions surveyed. The cultivars were grown in a greenhouse for two cycles in a randomized complete block design and inoculated with R. solanacearum strain. The severity scores were assessed and the area under the disease progress curve (AUDPC) was determined. All the cultivars tested for pathogenicity exhibited wilting symptoms at varying intervals after infection, with none showing complete resistance to R. solanacearum. Cultivar Shangi exhibited minimum disease severity and progression of 41.14% and AUDPC of 1041.7, respectively, while 'Kenya Karibu' was the most susceptible with a high progression rate of 68.24% and AUDPC of 1897.5, respectively. 'MoneyMaker', 'Chulu', and 'Wanjiku' showed no significant difference in disease severity, depicting a simultaneous rate of infection among them. These findings provide valuable information to better understand the pathogen genetic diversity in Kenya and how it spreads.


Subject(s)
Phylogeny , Plant Diseases , Ralstonia solanacearum , Solanum tuberosum , Kenya , Plant Diseases/microbiology , Ralstonia solanacearum/genetics , Solanum tuberosum/microbiology
5.
J Infect Dis ; 223(5): 743-751, 2021 03 03.
Article in English | MEDLINE | ID: mdl-33417696

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) received an Emergency Use Authorization by the US Food and Drug Administration (FDA). CCP with a signal-to-cutoff ratio of ≥12 using the Ortho VITROS severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) test (OVSARS2IgG) is permitted to be labeled "high titer." Little is known about the relationship between OVSARS2IgG ratio and neutralizing capacity of plasma/sera against genuine SARS-CoV-2. METHODS: Nine hundred eighty-one samples from 196 repeat CCP donors 0-119 days post-initial donation (DPID) were analyzed. Neutralizing capacity was assessed for 50% (PRNT50) and 90% (PRNT90) reduction of infectious virus using the gold standard plaque reduction neutralization test (PRNT). A subset of 91 donations was evaluated by OVSARS2IgG and compared to PRNT titers for diagnostic accuracy. RESULTS: Of donations, 32.7%/79.5% (PRNT90/PRNT50) met a 1:80 titer initially but only 14.0%/48.8% (PRNT90/PRNT50) met this cutoff ≥85 DPID. Correlation of OVSARS2IgG results to neutralizing capacity allowed extrapolation to CCP therapy results. CCP with OVSARS2IgG ratios equivalent to a therapeutically beneficial group had neutralizing titers of ≥1:640 (PRNT50) and/or ≥1:80 (PRNT90). Specificity and positive predictive value of the OVSARS2IgG for qualifying highly neutralizing CCP was optimal using ratios significantly greater than the FDA cutoff. CONCLUSIONS: This information provides a basis for refining the recommended properties of CCP used to treat COVID-19.


Subject(s)
COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Cohort Studies , Female , Humans , Immunization, Passive/standards , Male , Middle Aged , Neutralization Tests , Retrospective Studies , Sensitivity and Specificity , Time Factors , COVID-19 Serotherapy
6.
Plant Dis ; 105(4): 770-779, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32720880

ABSTRACT

Bacterial wilt (BW), caused by Ralstonia solanacearum species complex (RSSC), leads to substantial potato yield losses in Rwanda. Studies were conducted to (i) determine the molecular diversity of RSSC strains associated with BW of potato, (ii) generate an RSSC distribution map for epidemiological inferences, and (iii) test the pathogenicity of predominant RSSC phylotypes on six commercial potato cultivars. In surveys conducted in 2018 and 2019, tubers from wilting potato plants were collected for pathogen isolation. DNA was extracted from 95 presumptive RSSC strain colonies. The pathogen was phylotyped by multiplex PCR and typed at sequevar level. Phylotype II sequevar 1 strains were then haplotyped using multilocus tandem repeat sequence typing (TRST) schemes. Pathogenicity of one phylotype II strain and two phylotype III strains were tested on cultivars Kinigi, Kirundo, Victoria, Kazeneza, Twihaze, and Cruza. Two RSSC phylotypes were identified, phylotype II (95.79%, n = 91) and phylotype III (4.21%, n = 4). This is the first report of phylotype III strains from Rwanda. Phylotype II strains were identified as sequevar 1 and distributed across potato growing regions in the country. The TRST scheme identified 14 TRST haplotypes within the phylotype II sequevar 1 strains with moderate diversity index (HGDI = 0.55). Mapping of TRST haplotypes revealed that a single TRST '8-5-12-7-5' haplotype plays an important epidemiological role in BW of potato in Rwanda. None of the cultivars had complete resistance to the tested phylotypes; the level of susceptibility varied among cultivars. Cultivar Cruza, which is less susceptible to phylotype II and III strains, is recommended when planting potatoes in the fields with history of BW.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Subject(s)
Ralstonia solanacearum , Solanum tuberosum , Phylogeny , Plant Diseases , Ralstonia solanacearum/genetics , Rwanda , Virulence/genetics
7.
Ann Neurol ; 86(3): 407-418, 2019 09.
Article in English | MEDLINE | ID: mdl-31271450

ABSTRACT

OBJECTIVE: Compared to older Caucasians, older African Americans have higher risks of developing Alzheimer disease (AD) and lower cerebrospinal fluid (CSF) tau biomarker levels. It is not known whether tau-related differences begin earlier in life or whether race modifies other AD-related biomarkers such as inflammatory proteins. METHODS: We performed multiplex cytokine analysis in a healthy middle-aged cohort with family history of AD (n = 68) and an older cohort (n = 125) with normal cognition (NC), mild cognitive impairment, or AD dementia. After determining baseline interleukin (IL)-9 level and AD-associated IL-9 change to differ according to race, we performed immunohistochemical analysis for proteins mechanistically linked to IL-9 in brains of African Americans and Caucasians (n = 38), and analyzed postmortem IL-9-related gene expression profiles in the publicly available Mount Sinai cohort (26 African Americans and 180 Caucasians). RESULTS: Compared to Caucasians with NC, African Americans with NC had lower CSF tau, p-Tau181 , and IL-9 levels in both living cohorts. Conversely, AD was only correlated with increased CSF IL-9 levels in African Americans but not Caucasians. Immunohistochemical analysis revealed perivascular, neuronal, and glial cells immunoreactive to IL-9, and quantitative analysis in independent US cohorts showed AD to correlate with molecular changes (upstream differentiation marker and downstream effector cell marker) of IL-9 upregulation only in African Americans but not Caucasians. INTERPRETATION: Baseline and AD-associated IL-9 differences between African Americans and Caucasians point to distinct molecular phenotypes for AD according to ancestry. Genetic and nongenetic factors need to be considered in future AD research involving unique populations. ANN NEUROL 2019;86:407-418.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Black or African American , Brain/metabolism , Cognitive Dysfunction/cerebrospinal fluid , Interleukin-9/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , Aged , Biomarkers/cerebrospinal fluid , Female , Humans , Male , Middle Aged , White People
8.
Bioscience ; 70(9): 744-758, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32973407

ABSTRACT

The geographic pattern of cropland is an important risk factor for invasion and saturation by crop-specific pathogens and arthropods. Understanding cropland networks supports smart pest sampling and mitigation strategies. We evaluate global networks of cropland connectivity for key vegetatively propagated crops (banana and plantain, cassava, potato, sweet potato, and yam) important for food security in the tropics. For each crop, potential movement between geographic location pairs was evaluated using a gravity model, with associated uncertainty quantification. The highly linked hub and bridge locations in cropland connectivity risk maps are likely priorities for surveillance and management, and for tracing intraregion movement of pathogens and pests. Important locations are identified beyond those locations that simply have high crop density. Cropland connectivity risk maps provide a new risk component for integration with other factors-such as climatic suitability, genetic resistance, and global trade routes-to inform pest risk assessment and mitigation.

9.
Sex Transm Dis ; 47(5S Suppl 1): S8-S12, 2020 05.
Article in English | MEDLINE | ID: mdl-31876868

ABSTRACT

BACKGROUND: In 2016, HIV-2 nucleic acid testing (NAT) was added to a shared service program that conducts HIV-1 NAT for public health laboratories performing the recommended algorithm for diagnosing HIV. Here, we evaluate the usefulness of HIV-2 NAT in this program as compared with HIV-1 NAT. METHODS: Specimens eligible for HIV-1 NAT were reactive on an HIV-1/2 antibody or antigen/antibody initial test and nonreactive or indeterminate on a supplemental antibody test or were reactive for HIV-1 antigen-only on an HIV-1/2 antigen/antibody initial test. Specimens eligible for HIV-2 NAT were reactive on an initial test, HIV-2 indeterminate or HIV indeterminate on a supplemental antibody test and had no detectable HIV-1 RNA or were reactive for HIV-2 antibody on an HIV-1/2 antigen/antibody test, and this reactivity was not confirmed with a supplemental antibody assay. All specimens were tested in a reference laboratory using APTIMA HIV-1 qualitative RNA and/or a validated qualitative HIV-2 RNA real-time PCR assay. RESULTS: During 2016 to 2019, HIV-1 RNA was detected in 234 (14%) of 1731 specimens tested. HIV-2 RNA was not detected in 52 specimens tested. Median time from specimen collection to reporting of HIV-1 and HIV-2 NAT results by year ranged from 9 to 10 days and from 22 to 27 days, respectively. Two specimens with HIV-2 indeterminate results on a supplemental antibody test had detectable HIV-1 RNA. CONCLUSIONS: A shared service model for HIV-1 NAT is both feasible and beneficial for public health laboratories. However, because no HIV-2 infections were detected, our data suggest that this program should reconsider the usefulness of HIV-2 NAT testing.


Subject(s)
Diagnostic Tests, Routine/methods , HIV Infections/diagnosis , HIV-1/genetics , HIV-2/genetics , Nucleic Acid Amplification Techniques/methods , RNA, Viral/blood , Algorithms , HIV-1/isolation & purification , HIV-2/isolation & purification , Humans , Laboratories , Mass Screening , Public Health , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Virology/methods
10.
Alzheimer Dis Assoc Disord ; 34(3): 191-197, 2020.
Article in English | MEDLINE | ID: mdl-32483017

ABSTRACT

BACKGROUND: Norms for the Uniform Data Set Version 3 Neuropsychological Battery are available for cognitively normal individuals based on age, education, and sex; however, these norms do not include race. We provide expanded norms for African Americans and whites. METHODS: Data from 32 Alzheimer's Disease Centers (ADCs) and ADC affiliated cohorts with global Clinical Dementia Rating Scale (CDR) Dementia Staging Instrument scores of 0 were included. Descriptive statistics for each test were calculated by age, sex, race, and education. Multiple linear regressions were conducted to estimate the effect of each demographic variable; squared semipartial correlation coefficients measured the relative importance of variables. RESULTS: There were 8313 participants (16% African American) with complete demographic information, ranging from 6600 to 7885 depending on the test. Lower scores were found for older and less educated groups, and African Americans versus whites. Education was the strongest predictor for most tests, followed in order by age, race, and sex. Quadratic terms were significant for age and education, indicating some nonlinearity, but did not substantially increase R. CONCLUSIONS: Although race-based norms represent incomplete proxies for other sociocultural variables, the appropriate application of these norms is important given the potential to improve diagnostic accuracy and to reduce misclassification bias in cognitive disorders of aging such as Alzheimer disease.


Subject(s)
Aging , Black or African American/statistics & numerical data , Healthy Volunteers , Neuropsychological Tests , White People/statistics & numerical data , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Databases, Factual , Female , Humans , Male , Middle Aged , Neuropsychological Tests/standards , Neuropsychological Tests/statistics & numerical data , United States
11.
Phytopathology ; 109(11): 1922-1931, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31272278

ABSTRACT

Bacterial wilt (BW) caused by the Ralstonia solanacearum species complex (RSSC) is a serious threat to potato production in Uganda. However, little is known about the extent of the disease and the type of the pathogen strains involved. A nationwide survey was conducted to study BW prevalence and incidence in potato, and potato tuber and stem samples of potential alternative hosts were collected for pathogen isolation. DNA was extracted from pure cultures for genetic diversity studies. The pathogen was phylotyped by multiplex PCR; then, a subset of isolates was typed at sequevar level. Isolates of the same sequevar were then haplotyped using multilocus tandem repeat sequence typing (TRST) schemes. BW prevalence and incidence in potato farms were 81.4 and 1.7%, respectively. Three RSSC phylotypes were identified, with the majority of the strains belonging to Phylotype II (80%) followed by Phylotype I (18.5%) and III (1.5%). Phylotype I strains belonged to Sequevar 31, and Phylotype II strains belonged to Sequevar 1. Potato-associated Phylotype II Sequevar 1 strains were more diverse (27 TRST haplotypes) than nonpotato Phylotype I (5 TRST haplotypes). Mapping of TRST haplotypes revealed that three TRST haplotypes of Phylotype II Sequevar 1 strains play an important epidemiological role in BW of potato in Uganda being disseminated via latently infected seed.[Formula: see text]Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Subject(s)
Molecular Epidemiology , Ralstonia solanacearum , Solanum tuberosum , Molecular Typing , Phylogeny , Plant Diseases/microbiology , Ralstonia solanacearum/classification , Ralstonia solanacearum/genetics , Solanum tuberosum/microbiology , Uganda
12.
Health Expect ; 22(3): 465-474, 2019 06.
Article in English | MEDLINE | ID: mdl-30770609

ABSTRACT

Patient and public involvement in research includes non-academics working with researchers, on activities from consultative tasks, to joint working, and on user-led initiatives. Health and social care funding bodies require involvement in research projects. A current debate focuses on a perceived lack of empirical "proof" to demonstrate the impact of involvement upon the quality of research. It is also argued that the working relationships between researchers and those becoming involved need to be understood more fully. These areas are beginning to be reported upon but there are few studies of young people involved in health research. This study describes the experiences of adult academics and young people, working together on a large-scale, UK health research programme. Using qualitative interview and focus group methods, the aim was to explore participants' perceptions about the process and outcomes of their work together. The importance of cyclical, dynamic and flexible approaches is suggested. Enablers include having clear mechanisms for negotiation and facilitation, stakeholders having a vision of "the art of the possible," and centrally, opportunities for face-to-face working. What is needed is a continuing discourse about the challenges and benefits of working with young people, as distinct from younger children and adults, understanding the value of this work, without young people having to somehow "prove" themselves. Involvement relies on complex social processes. This work supports the view that an improved understanding of how key processes are enabled, as well as what involvement achieves, is now needed.


Subject(s)
Health Services Research , Patient Participation , Research Subjects/psychology , Adolescent , Age Factors , Decision Making , Female , Focus Groups , Humans , Informed Consent , Male , Qualitative Research , United Kingdom , Young Adult
13.
Plant Dis ; 103(5): 959-965, 2019 May.
Article in English | MEDLINE | ID: mdl-30895864

ABSTRACT

Bacterial wilt caused by Ralstonia solanacearum is considered among the most damaging diseases of potato in Sub-Saharan Africa and the most significant biotic constraint of potato production alongside late blight. Unlike late blight, which can be managed by chemical means, R. solanacearum can only be managed through cultural methods and clean seed. Laboratory testing to certify seed before planting is required to confirm the absence of the pathogen in Kenya. A loop-mediated isothermal amplification (LAMP) assay was developed using the UDP-(3-O-acyl)-N-acetylglucosamine deacetylase gene (IpxC) to screen seed potato for R. solanacearum strains. The assay was assessed using DNA extracted from R. solanacearum and other soil and potato pathogens to demonstrate specificity and sensitivity. The LAMP assay was validated using field samples from different potato growing regions of Kenya collected over two growing seasons and compared with established nucleic acid and protein-based assays. The IpxC LAMP assay was found to be specific and sensitive to R. solanacearum, detecting as low as 2.5 pg/µl of R. solanacearum DNA. Of the 47 potentially infected field samples collected, both IpxC LAMP and quantitative polymerase chain reaction (PCR) detected R. solanacearum DNA in 90% of the samples, followed by conventional PCR (86%) and ELISA (75%). This IpxC LAMP assay is a promising diagnostic tool to rapidly screen for R. solanacearum in seed potato with high sensitivity in Kenya. Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .


Subject(s)
Agriculture/methods , Enzyme-Linked Immunosorbent Assay , Nucleic Acid Amplification Techniques , Ralstonia solanacearum , Solanum tuberosum , Enzyme-Linked Immunosorbent Assay/standards , Kenya , Nucleic Acid Amplification Techniques/standards , Plant Diseases/microbiology , Ralstonia solanacearum/genetics , Ralstonia solanacearum/isolation & purification , Solanum tuberosum/microbiology
14.
Alzheimers Dement ; 13(10): 1168-1173, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28926722

ABSTRACT

There is now an unprecedented opportunity to improve the care of the over 5 million people who are living with Alzheimer's disease and related dementias and many more with cognitive impairment due to brain injury, systemic diseases, and other causes. The introduction of a new Medicare care planning benefit-long sought openly by advocacy organizations and clinicians and badly needed by patients and families-could greatly improve health care quality, but only if widely and fully implemented. We describe the components of this new benefit and its promise of better clinical care, as well as its potential to create a new platform for clinical and health outcomes research. We highlight external factors-and some that are internal to the benefit structure itself-that challenge the full realization of its value, and we call for broad public and professional engagement to ensure that it will not fail.


Subject(s)
Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/therapy , Medicare , Quality of Health Care , Reimbursement Mechanisms , Humans , Reimbursement Mechanisms/legislation & jurisprudence , United States
15.
Transfusion ; 56(6 Pt 2): 1560-8, 2016 06.
Article in English | MEDLINE | ID: mdl-27079968

ABSTRACT

BACKGROUND: Blood donation screening for human immunodeficiency virus Type 2 (HIV-2) has been in place in the United States since 1992. However, only three HIV-2 antibody-positive donors have been reported to date, all detected via HIV-1 cross-reactivity. STUDY DESIGN AND METHODS: Here we identify two additional HIV-2-positive donors by routine anti-HIV-1 and anti-HIV-2 screening, including a first-time male donor living in Georgia having recently immigrated to the United States from West Africa (from a 1998 donation) and a Taiwanese female repeat donor (nurse) living in California with no travel outside of Taiwan or apparent connections to West Africa (from a 2015 donation). Neither donor acknowledged any risk factors, and both remained asymptomatic through follow-up. The second donor was further investigated by serologic, molecular, and genomic assays because of her unusual demographics. She was documented to harbor HIV-2 RNA, albeit sporadically by HIV-2-specific nucleic acid tests (35%-100% of replicates) and at very low levels (<9.6 IU/mL). Metagenomic next-generation sequencing (mNGS) confirmed the identification of a Group B HIV-2 strain, with recovered reads covering 46.9% of the predicted genome. CONCLUSIONS: The estimated frequency of an HIV-2-positive blood donor in the United States is one in 57 million donations. Due to the low frequency and low pathogenicity of HIV-2, public health and blood donation screening efforts must focus on HIV-1 detection and prevention. However, detection of HIV-2 infection in a donor with no apparent link to West Africa suggests that the United States must remain vigilant for HIV-2 virus infections. Ultradeep mNGS may be useful in the future for comprehensive identification of rare transfusion-transmissible agents.


Subject(s)
Blood Donors , HIV-2/immunology , Transfusion Reaction , Adult , Africa, Western/ethnology , Female , HIV Antibodies/blood , HIV Infections/diagnosis , HIV Infections/transmission , HIV-1/pathogenicity , HIV-2/genetics , HIV-2/pathogenicity , Humans , Male , Middle Aged , Risk Factors , Taiwan/ethnology , United States/epidemiology
16.
J Health Commun ; 21(5): 527-33, 2016 05.
Article in English | MEDLINE | ID: mdl-27077665

ABSTRACT

This study examined the effect of message framing on African American women's intention to participate in health-related research and actual registration in ResearchMatch (RM), a disease-neutral, national volunteer research registry. A community-engaged approach was used involving collaboration between an academic medical center and a volunteer service organization formed by professional women of color. A self-administered survey that contained an embedded message framing manipulation was distributed to more than 2,000 African American women attending the 2012 national assembly of The Links, Incorporated. A total of 391 surveys were completed (381 after exclusion: 187 containing the gain-framed message and 194 containing the loss-framed message). The majority (57%) of women expressed favorable intentions to participate in health-related research, and 21% subsequently enrolled in RM. The effect of message framing on intention was moderated by self-efficacy. There was no effect of message framing on RM registration; however, those with high self-efficacy were more than 2 times as likely as those with low self-efficacy to register as a potential study volunteer in RM (odds ratio = 2.62, 95% confidence interval [1.29, 5.33]). This investigation makes theoretical and practical contributions to the field of health communication and informs future strategies to meaningfully and effectively include women and minorities in health-related research.


Subject(s)
Biomedical Research , Black or African American/psychology , Health Communication/methods , Intention , Research Subjects/psychology , Black or African American/statistics & numerical data , Aged , Cross-Sectional Studies , Female , Humans , Middle Aged , Research Subjects/statistics & numerical data , Self Efficacy , Surveys and Questionnaires
17.
Pediatr Emerg Care ; 32(10): 675-681, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26011806

ABSTRACT

OBJECTIVES: This study aimed to develop a performance assessment tool for the history-taking components of the medical evaluation of physical abuse in young children by (1) determining the consensus-based injury history and social components for documentation, (2) identifying preliminary performance standards, (3) assessing current level-specific performance using the created tools, and (4) evaluating reliability and validity of the created tools. METHODS: The Physical Abuse Assessment Tool (PHAAT) was developed in 2 steps: (1) a modified Delphi survey was used to identify the injury history and social components for documentation in a medical evaluation for physical abuse, and (2) level-specific ("novice," "competent," "expert") practice standards (minimum passing scores) were created using the identified components via the Angoff method. To evaluate validity, reliability, and level-specific performance of the PHAAT, a chart review of 50 consecutive cases from each of the 3 levels was performed. RESULTS: Seventy-one child abuse pediatricians and 39 social workers participated in the modified Delphi survey, and 67 child abuse pediatricians and 27 social workers participated in the Angoff method. The resulting PHAAT included 2 checklists for use based on presence or absence of a history of an injurious event. One-way analysis of variance shows significant differences in performance based on team level (P < 0.001), indicating construct validity. Intrarater and interrater reliability evaluations showed strong (rs = 0.64-0.92) and moderate to strong (intraclass correlation coefficient = 0.81-0.98) correlations, respectively. CONCLUSIONS: Initial evaluation suggests the PHAAT may be a reliable and valid practice assessment tool for the medical evaluation of physical abuse.


Subject(s)
Child Abuse/diagnosis , Medical History Taking/methods , Physical Abuse , Social Work/methods , Adolescent , Adult , Aged , Child , Child Abuse/statistics & numerical data , Child, Preschool , Female , Humans , Male , Medical History Taking/standards , Middle Aged , Reproducibility of Results , Social Work/standards , Social Workers , Young Adult
18.
Hepatol Res ; 45(13): 1292-8, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25689487

ABSTRACT

AIM: The first hepatitis C virus (HCV) recombinant, RF2k/1b, was initially described from Russia and has since then been identified from patients in Ireland, Estonia, Uzbekistan and Cyprus. Many of these patients originated from Georgia; however, there is no information on its prevalence in Georgia or its susceptibility to antiviral treatment. METHODS: We retrospectively sequenced the non-structural region 5B (NS5B) of the HCV genome in samples from 72 Georgian patients, 36 of whom had been treated with pegylated interferon and ribavirin. RESULTS: The HCV genotype was determined using the Versant HCV Genotype v2 kit. Based on this typing, 32 patients (44.4%) were infected with genotype 1, 21 (29.1%) genotype 2 and 19 (26.3%) genotype 3. Partial NS5B of these strains was sequenced and analyzed for type, with concordant genotype results for all type 1 and 3 strains. Discrepant results were observed for genotyped 2 strains, with 16 (76%) having NS5B of subtype 1b. On phylogenetic analysis, 15 NS5B sequences of these strains were found in a clade formed by recombinant RF2k/1b strains. The remaining discordant sequence was found within a clade formed by 1b strains. CONCLUSION: Our findings show that the RF2k/1b recombinant strain is common among Georgian patients previously assumed to be infected with genotype 2. Because genotyping is mainly performed to decide treatment strategies, there is a need to determine the genotype by analysis of at least two genomic regions in strains from Georgian patients considered infected with genotype 2 based on standard HCV genotyping methods.

19.
Clin Infect Dis ; 59(6): 875-82, 2014 Sep 15.
Article in English | MEDLINE | ID: mdl-24867787

ABSTRACT

In the United States, of the 1.1 million persons infected with human immunodeficiency virus (HIV) and the 2.7 million infected with hepatitis C virus (HCV), approximately 16% and 50%, respectively, are unaware of their infection. Highly effective treatments have turned both diseases into manageable conditions, and in the case of hepatitis C, a disease that can be cured. Early diagnosis is imperative so that infected persons can take measures to stay healthy, get into care, benefit from therapy, and reduce the risk of transmission. In this report, we review current recommendations provided by the Centers for Disease Control and Prevention (CDC) and the United States Preventive Services Task Force on whom to screen for HIV and HCV infections, and recommendations from the CDC, the Association of Public Health Laboratories, and the Clinical and Laboratory Standards Institute on how to test for these infections.


Subject(s)
HIV Infections/epidemiology , HIV , Hepacivirus , Hepatitis C/epidemiology , Centers for Disease Control and Prevention, U.S. , Female , HIV/physiology , HIV Infections/diagnosis , Hepacivirus/physiology , Hepatitis C/diagnosis , Humans , Male , Mass Screening/legislation & jurisprudence , Mass Screening/methods , Mass Screening/standards , United States/epidemiology , United States Food and Drug Administration
20.
J Am Geriatr Soc ; 72(7): 1995-2005, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38553838

ABSTRACT

BACKGROUND: "Super-agers" are adults aged ≥80 with cognitive performance similar to persons two to three decades younger. Characteristics such as larger hippocampal volume, APOE-ε4 allele absence, higher educational attainment, female sex, and lifelong cognitive stimulation are associated with cognitive performance compatible with super-aging. These findings are based on predominantly white research samples. Limited data are available on African-American super-agers. To fill this gap, we explored potential factors associated with super-aging in older African-American adults. METHODS: Data from African-American participants aged ≥80 in the National Alzheimer's Coordinating Center (NACC) dataset were analyzed. Using global Clinical Dementia Rating (CDR) scores, participants were first categorized as impaired (score ≥0.5) or non-impaired/normal cognition (NC) (score = 0). From the NC group, super-agers were identified using NACC-data-driven cutoffs. Participants were considered super-agers if their memory performance was similar to persons aged 50-60 with NC, and their performance on other domains was within one standard deviation of the mean for persons aged ≥80. We examined group characteristics (NC, super-ager, impaired) using chi-square and ANOVA with pairwise comparisons. Multinomial logistic regression, adjusted for sex and education, evaluated correlates of super-ager group assignment. RESULTS: Data for 1285 African-American participants aged ≥80 were analyzed. We identified 24.7% (n = 316) NC, 4.8% (n = 61) super-agers, and 70.6% (n = 905) impaired. Super-agers were mostly female and more educated, had similar vascular comorbidities as the other groups, and had less sleep disorders, depression, and alcohol use. After adjusting for sex and education, super-ager group assignment was associated with less sleep disorders, less depression, and moderate alcohol use. CONCLUSIONS: Participants with controlled vascular risk, mental health, alcohol use, and sleep disorders tended to be in the super-ager group. These factors may be important focus areas in clinical practice to support cognitive resilience with aging in older African-American adults.


Subject(s)
Alzheimer Disease , Black or African American , Humans , Female , Male , Black or African American/statistics & numerical data , Black or African American/psychology , Aged, 80 and over , Alzheimer Disease/ethnology , United States/epidemiology , Cognition , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/ethnology , Cohort Studies , Educational Status , Aging/psychology , Middle Aged
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