Last data update: Jul 01, 2024. (Total: 47134 publications since 2009)
Records 1-30 (of 43 Records) |
Query Trace: Yeung L [original query] |
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Multivitamin use among Hispanic women of reproductive age in the United States, 2013-2022
Long K , Mai CT , Yue X , Yeung LF . J Womens Health (Larchmt) 2024 Background: The U.S. Public Health Service and the Institute of Medicine recommend that all women capable of becoming pregnant consume 400 μg of folic acid daily to help prevent neural tube defects (NTDs). Hispanic women are at higher risk of having babies with NTDs than non-Hispanic White women. This study assessed multivitamin (MV) use, a main source of folic acid, among Hispanic women of reproductive age using a survey of solely U.S. Hispanic adults. Materials and Methods: MV use was assessed as part of Porter Novelli's Estilos survey, fielded annually through the largest online U.S. Hispanic panel, Offerwise's QueOpinas. During the study period of 2013-2022, 9,999 surveys were completed; selection was weighted to match the U.S. Census American Community Survey proportions. Log-binomial regression models were applied to estimate MV use trends by age groups, acculturation levels, and pregnancy intention. Results: Among 3,700 Hispanic women of reproductive age, overall no MV use increased from 39.3% in 2013 to 54.7% in 2022 (p for trend <0.0001), especially among Hispanic women aged 18-34 years and those classified as acculturated. Among women planning to get pregnant, daily MV use was 31.1% in 2013 compared with 18.7% in 2020-2022 (p = 0.04). Conclusions: Given the increase in no MV use among Hispanic women of reproductive age, targeted interventions may help reach at-risk groups for NTDs prevention. |
Expanding the Massachusetts Birth Defects Monitoring Program to include additional pregnancy outcomes: Programmatic efforts and impacts on case ascertainment, 2012-2020
Fothergill A , Liberman RF , Nestoridi E , Mai CT , Yeung LF , Higgins C , Yazdy MM . Birth Defects Res 2024 116 (3) e2323 BACKGROUND: Birth defects affect 1 in 33 infants in the United States and are a leading cause of infant mortality. Birth defects surveillance is crucial for informing public health action. The Massachusetts Birth Defects Monitoring Program (MBDMP) began collecting other pregnancy losses (OPLs) in 2011, including miscarriages (<20 weeks gestation) or elective terminations (any gestational age), in addition to live births and stillbirths (≥20 weeks gestation). We describe programmatic changes for adding OPLs and their impact on prevalence estimates. METHODS: Using population-based, statewide, data from the MBDMP (2012-2020), we assessed prevalence per 10,000 live births and 95% confidence intervals (CIs) with and without OPLs overall and for specific birth defects by time period, maternal age, and race/ethnicity. RESULTS: Including OPLs required amending a state statute and promulgating regulations, new data sources, and additional data processing, cleaning, and verification. Overall prevalence with OPLs increased from 257.4 (95% CI: 253.5-261.4) to 333.9 (95% CI: 329.4-338.4) per 10,000; increases were observed in all time periods, age, and race/ethnicity groups. After including OPLs, the prevalence increased for neural tube defects [3.2 (2.7-3.6) to 8.3 (7.6-9.0)], and trisomies 13 [0.5 (0.3-0.7) to 4.1 (3.6-4.6)], 18 [1.5 (1.2-1.9) to 8.2 (7.5-8.9)], and 21 [12.3 (11.4-13.2) to 28.9 (27.6-30.2)]. Cardiovascular defects increased slightly, while prevalence of eye/ear, respiratory, and gastrointestinal defects remained similar. CONCLUSIONS: Adding OPLs required substantial programmatic efforts and resulted in more complete case ascertainment, particularly for certain birth defects. More complete case ascertainment will allow for improved research, screening, and resource allocation. |
Update on the impact of voluntary folic acid fortification of corn masa flour on red blood cell folate concentrations-National Health and Nutrition Examination Survey, 2011-March 2020
Wang A , Fothergill A , Yeung LF , Crider KS , Williams JL . Birth Defects Res 2024 116 (3) e2321 BACKGROUND: Folic acid is a micronutrient that is effective at preventing neural tube defects (NTDs). In 2016, the FDA authorized the voluntary fortification of corn masa flour (CMF) with folic acid to reduce disparities in NTDs among infants of women who do not regularly consume other fortified cereal grains, in particular Hispanic women of reproductive age (WRA). METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to March 2020 assessing the impact of voluntary fortification of CMF on the folate status of Hispanic WRA. We analyzed folic acid usual intake and red blood cell (RBC) folate concentrations among non-pregnant, non-lactating Hispanic WRA, comparing pre-fortification (2011-2016) to post-fortification (2017-March 2020) data. RBC folate concentrations were used to create model-based estimation of NTD rates. RESULTS: The proportion of Hispanic WRA with folic acid usual intakes <400 μg/d did not change (2011-2016: 86.1% [95% Confidence Interval, CI: 83.7-88.5]; 2017-March 2020: 87.8% [95% CI: 84.8-90.7]; p = .38) nor did the proportion of Hispanic WRA with RBC folate below optimal concentrations (<748 nmol/L, 2011-2016: 16.0% [95% CI: 13.7-18.2]; 2017-March 2020: 18.1% [95% CI: 12.1-24.0]; p = 0.49). Model-based estimates of NTD rates suggest further improvements in the folate status of Hispanic WRA might prevent an additional 157 (95% Uncertainty Interval: 0, 288) NTDs/year. CONCLUSIONS: Voluntary fortification of CMF with folic acid has yet to have a significant impact on the folate status of WRA. Continued monitoring and further research into factors such as fortified product availability, community knowledge, and awareness of folic acid benefits would inform and improve future public health interventions. |
Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome (preprint)
Sulaiman I , Chung M , Angel L , Koralov S , Wu B , Yeung S , Krolikowski K , Li Y , Duerr R , Schluger R , Thannickal S , Koide A , Rafeq S , Barnett C , Postelnicu R , Wang C , Banakis S , Perez-Perez L , Jour G , Shen G , Meyn P , Carpenito J , Liu X , Ji K , Collazo D , Labarbiera A , Amoroso N , Brosnahan S , Mukherjee V , Kaufman D , Bakker J , Lubinsky A , Pradhan D , Sterman D , Heguy A , Uyeki T , Clemente J , de Wit E , Schmidt AM , Shopsin B , Desvignes L , Wang C , Li H , Zhang B , Forst C , Koide S , Stapleford K , Khanna K , Ghedin E , Weiden M , Segal L . Res Sq 2021 Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized. |
Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome (preprint)
Sulaiman I , Chung M , Angel L , Tsay JJ , Wu BG , Yeung ST , Krolikowski K , Li Y , Duerr R , Schluger R , Thannickal SA , Koide A , Rafeq S , Barnett C , Postelnicu R , Wang C , Banakis S , Perez-Perez L , Jour G , Shen G , Meyn P , Carpenito J , Liu X , Ji K , Collazo D , Labarbiera A , Amoroso N , Brosnahan S , Mukherjee V , Kaufman D , Bakker J , Lubinsky A , Pradhan D , Sterman DH , Weiden M , Hegu A , Evans L , Uyeki TM , Clemente JC , De Wit E , Schmidt AM , Shopsin B , Desvignes L , Wang C , Li H , Zhang B , Forst CV , Koide S , Stapleford KA , Khanna KM , Ghedin E , Segal LN . medRxiv 2021 Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized. |
Folate and vitamin B12 usual intake and biomarker status by intake source in U.S. adults (19 y): National Health and Nutrition Examination Survey (NHANES) 2007-2018
Zhou Y , Wang A , Yeung LF , Qi YP , Pfeiffer CM , Crider KS . Am J Clin Nutr 2023 118 (1) 241-254 OBJECTIVES: Folate and vitamin B12 are important biomarkers of nutritional status of populations. This study aims to estimate folate and vitamin B12 usual intakes among US adults and examine folate and vitamin B12 biomarker status by intake source. METHODS: We analyzed data for U.S. adults (≥19 y) from National Health and Nutrition Examination Survey (NHANES) 2007-2018 (n=31,128), during which time voluntary corn masa flour fortification was started. Usual intake was estimated using National Cancer Institute (NCI) method. Folate intake included folate from natural foods and folic acid from four sources-enriched cereal grain products (ECGP), corn masa flour (CMF), ready-to-eat cereals (RTE), and folic acid containing supplements (SUP). Vitamin B12 is found in food and supplements. RESULTS: Median natural food folate intake (222 μg dietary folate equivalents (DFE)/d) was below the estimated average requirement (EAR) of 320 μg DFE/d. Proportions of those who consumed folic acid from ECGP/CMF only, ECGP/CMF+RTE, ECGP/CMF+SUP, and ECGP/CMF+RTE+SUP were 50%, 18%, 22%, and 10%, respectively. Median usual folic acid intakes (μg/d) were 236 (interquartile range: 152, 439) overall, and 134, 313, 496, 695 in the ECGP/CMF only, ECGP/CMF+RTE, ECGP/CMF+SUP, ECGP/CMF+RTE+SUP folic acid consumption groups, respectively. Overall, 2.0% (95% CI: 1.7%, 2.3%) of adults, all of whom used folic acid supplements, consumed greater than tolerable upper intake level (UL) of 1000 μg/d folic acid. Median usual vitamin B12 intake (μg/d) was 5.2 for vitamin B12 supplement non-users and 21.8 for users. Consumption of RTE and/or supplements with folic acid was associated with higher serum and RBC folate concentrations. Vitamin B12 supplement users had significantly higher serum vitamin B12 concentrations. CONCLUSIONS: Folic acid fortification plays a critical role in helping U.S. adults meet folate EAR. At current fortification levels, U.S. adults who do not consume supplements do not have usual folic acid intake exceeding the UL. |
A randomized trial of quadruple-fortified salt for anemia and birth defects prevention in southern India: Protocol design and methods
Finkelstein JL , Guetterman HM , Fothergill A , Johnson CB , Qi YP , Jabbar S , Zhang M , Pfeiffer CM , Rose CE , Yeung LF , Williams JL , Krisher JT , Ruth C , Roy Choudhury D , Venkatramanan S , Haas JD , Kuriyan R , Mehta S , Bonam W , Crider KS . Curr Dev Nutr 2023 7 (3) 100052 Background: Women of reproductive age are at an increased risk of anemia and micronutrient deficiencies. Evidence supports the role of periconceptional nutrition in the development of neural tube defects (NTDs) and other pregnancy complications. Vitamin B12 deficiency is a risk factor for NTDs and may modify folate biomarkers that predict NTD risk at the population level. There is an interest in mandatory fortification with vitamin B12 and folic acid for anemia and birth defect prevention. However, there are limited population-representative data needed to inform policy and guidelines. Objectives: This randomized trial will be conducted to evaluate the efficacy of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B12) in 1,000 households in Southern India. Methods: Women 18 to 49 y who are not pregnant or lactating and reside within the catchment area of our community-based research site in Southern India will be screened and invited to participate in the trial. After informed consent, women and their households will be randomized to receive one of the following 4 interventions: 1) double-fortified salt (DFS; iron, iodine), 2) DFS + folic acid (iron, iodine, folic acid), 3) DFS + vitamin B12 (iron, iodine, vitamin B12), or 4) DFS + folic acid and vitamin B12 (QFS; iron, iodine, folic acid, vitamin B12) for 12 mo. Structured interviews will be conducted by trained nurse enumerators to collect sociodemographic, anthropometric, dietary, health, and reproductive history data. Biological samples will be collected at baseline, midpoint, and endpoint. Whole blood will be analyzed for hemoglobin using Coulter Counter. Total vitamin B12 will be measured by chemiluminescence; red blood cell folate and serum folate will be evaluated using the World Health Organization-recommended microbiologic assay. Conclusions: The results of this randomized trial will help to evaluate the efficacy of QFS to prevent anemia and micronutrient deficiencies. Clinical trial registration numbers: NCT03853304 and Clinical Trial Registry of India REF/2019/03/024479. Registration number: NCT03853304 and REF/2019/03/024479. © 2023 The Author(s) |
Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages.
Xia H , Yeung J , Kalveram B , Bills CJ , Chen JY , Kurhade C , Zou J , Widen SG , Mann BR , Kondor R , Todd Davis C , Zhou B , Wentworth DE , Xie X , Shi PY . Emerg Microbes Infect 2023 12 (1) 1-19 ![]() The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e., USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titers did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach. |
Folic acid and the prevention of birth defects: 30 years of opportunity and controversies
Crider KS , Qi YP , Yeung LF , Mai CT , Head Zauche L , Wang A , Daniels K , Williams JL . Annu Rev Nutr 2022 42 423-452 For three decades, the US Public Health Service has recommended that all persons capable of becoming pregnant consume 400 μg/day of folic acid (FA) to prevent neural tube defects (NTDs). The neural tube forms by 28 days after conception. Fortification can be an effective NTD prevention strategy in populations with limited access to folic acid foods and/or supplements. This review describes the status of mandatory FA fortification among countries that fortify (n = 71) and the research describing the impact of those programs on NTD rates (up to 78% reduction), blood folate concentrations [red blood cell folate concentrations increased ∼1.47-fold (95% CI, 1.27, 1.70) following fortification], and other health outcomes. Across settings, high-quality studies such as those with randomized exposures (e.g., randomized controlled trials, Mendelian randomization studies) are needed to elucidate interactions of FA with vitamin B(12) as well as expanded biomarker testing. |
Vitamin B-12 malabsorption and renal function are critical considerations in studies of folate and vitamin B-12 interactions in cognitive performance: NHANES 2011-2014
Samson ME , Yeung LF , Rose CE , Qi YP , Taylor CA , Crider KS . Am J Clin Nutr 2022 116 (1) 74-85 BACKGROUND: Cognitive health is a public health concern among older adults. Dietary supplement (SUP) use is common and concerns have been raised about high folic acid intake among those with vitamin B-12 deficiency and exacerbation of poor cognitive performance (PCP). OBJECTIVES: We evaluated SUP use, usual folic acid intake, and blood folate and vitamin B-12 concentrations in relation to cognitive performance. METHODS: We used NHANES 2011-2014 data on adults aged ≥60 y (n = 2867) and estimated total usual folic acid intake from diet and supplements, vitamin B-12 intake from SUPs, blood folates, vitamin B-12 concentrations, vitamin B-12 insufficiency (≤258 pmol/L), high folate (serum folate ≥59 nmol/L or RBC folate ≥1609 nmol/L), and PCP (<34 on the Digit Symbol Substitution Test). We assessed folate distributions adjusted for multiple variables, including renal function. RESULTS: Compared with persons without PCP, adults with PCP were less likely to use supplements containing folic acid (mean ± SEE: 34.4% ± 2.4%) or vitamin B-12 (mean ± SEE: 47.5% ± 1.6%). Among vitamin B-12-insufficient adults, 18.0% ± 1.6% (mean ± SEE) reported taking a vitamin B-12 supplement. Among participants with high folate and insufficient vitamin B-12 concentrations, 34.3% ± 11.5% (mean ± SEE) reported taking vitamin B-12-containing supplements. Persons with high folate and normal vitamin B-12 concentrations had lower odds of PCP [aOR (adjusted odds ratio): 0.61; 95% CI: 0.45, 0.83] than persons with normal folate and vitamin B-12. Persons with high folate and normal methylmalonic acid (MMA) had lower odds of PCP (OR: 0.56; 95% CI: 0.40, 0.78) than those with normal folate and MMA concentrations. After adjustment for renal function, elevated risk of PCP was attenuated among persons with high folate and MMA. Concurrent high folate and insufficient vitamin B-12 concentrations were not associated with PCP. CONCLUSIONS: Differential associations between vitamin B-12 and MMA highlight the need to consider renal function in studies of high folate and low vitamin B-12 status. Consumption of vitamin B-12 supplements concurrent with low vitamin B-12 status may indicate vitamin B-12 malabsorption. |
Reduced kidney function is associated with increasing red blood cell folate concentration and changes in folate form distributions (NHANES 2011-2018)
Wang A , Yeung LF , Ríos Burrows N , Rose CE , Fazili Z , Pfeiffer CM , Crider KS . Nutrients 2022 14 (5) BACKGROUND: Current studies examining the effects of high concentrations of red blood cell (RBC) or serum folates assume that high folate concentrations are an indicator of high folic acid intakes, often ignoring the contributions of other homeostatic and biological processes, such as kidney function. OBJECTIVE: The current study examined the relative contributions of declining kidney function, as measured by the risk of chronic kidney disease (CKD), and usual total folic acid intake on the concentrations of RBC folate and serum folate (total as well as individual folate forms). DESIGN: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) collected in 2-year cycles were combined from 2011 to 2018. A total of 18,127 participants aged ≥16 years with available folate measures, kidney biomarker data (operationalized as a categorical CKD risk variable describing the risk of progression), and reliable dietary recall data were analyzed. RESULTS: RBC folate concentrations increased as CKD risk increased: low risk, 1089 (95% CI: 1069, 1110) nmol/L; moderate risk, 1189 (95% CI: 1158, 1220) nmol/L; high risk, 1488 (95% CI: 1419, 1561) nmol/L; and highest risk, 1443 (95% CI: 1302, 1598) nmol/L (p < 0.0001). Similarly, serum total folate concentrations increased as CKD risk increased: low risk: 37.1 (95% CI: 26.3, 38.0) nmol/L; moderate risk: 40.2 (95% CI: 38.8, 41.7) nmol/L; high risk: 48.0 (95% CI: 44.3, 52.1) nmol/L; the highest Risk: 42.8 (95% CI: 37.8, 48.4) nmol/L (p < 0.0001). The modeled usual intake of folic acid showed no difference among CKD risk groups, with a population median of 225 (interquartile range: 108-390) µg/day. CONCLUSION: Both RBC and serum folate concentrations increased with declining kidney function without increased folic acid intake. When analyzing associations between folate concentrations and disease outcomes, researchers may want to consider the confounding role of kidney function. |
WHO-led consensus statement on vaccine delivery costing: process, methods, and findings
Levin A , Boonstoppel L , Brenzel L , Griffiths U , Hutubessy R , Jit M , Mogasale V , Pallas S , Resch S , Suharlim C , Yeung KHT . BMC Med 2022 20 (1) 88 BACKGROUND: Differences in definitions and methodological approaches have hindered comparison and synthesis of economic evaluation results across multiple health domains, including immunization. At the request of the World Health Organization's (WHO) Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC), WHO convened an ad hoc Vaccine Delivery Costing Working Group, comprising experts from eight organizations working in immunization costing, to address a lack of standardization and gaps in definitions and methodological guidance. The aim of the Working Group was to develop a consensus statement harmonizing terminology and principles and to formulate recommendations for vaccine delivery costing for decision making. This paper discusses the process, findings of the review, and recommendations in the Consensus Statement. METHODS: The Working Group conducted several interviews, teleconferences, and one in-person meeting to identify groups working in vaccine delivery costing as well as existing guidance documents and costing tools, focusing on those for low- and middle-income country settings. They then reviewed the costing aims, perspectives, terms, methods, and principles in these documents. Consensus statement principles were drafted to align with the Global Health Cost Consortium costing guide as an agreed normative reference, and consensus definitions were drafted to reflect the predominant view across the documents reviewed. RESULTS: The Working Group identified four major workstreams on vaccine delivery costing as well as nine guidance documents and eleven costing tools for immunization costing. They found that some terms and principles were commonly defined while others were specific to individual workstreams. Based on these findings and extensive consultation, recommendations to harmonize differences in terminology and principles were made. CONCLUSIONS: Use of standardized principles and definitions outlined in the Consensus Statement within the immunization delivery costing community of practice can facilitate interpretation of economic evidence by global, regional, and national decision makers. Improving methodological alignment and clarity in program costing of health services such as immunization is important to support evidence-based policies and optimal resource allocation. On the other hand, this review and Consensus Statement development process revealed the limitations of our ability to harmonize given that study designs will vary depending upon the policy question that is being addressed and the country context. |
Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas
Crider KS , Williams JL , Qi YP , Gutman J , Yeung LF , Mai CT , Finkelstein JL , Mehta S , Pons-Duran C , Menéndez C , Moraleda C , Rogers LM , Daniels K , Green P . Cochrane Database Syst Rev 2022 2022 (2) Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?. Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. |
Periconceptional folic acid use prevents both rare and common neural tube defects in China
Zhou Y , Crider KS , Yeung LF , Rose CE , Li Z , Berry RJ , Li S , Moore CA . Birth Defects Res 2022 114 184-196 BACKGROUND: Neural tube defects (NTDs) encompass a variety of distinct types. We assessed if the preventive effect of folic acid (FA) varied by NTD type and infant sex. METHODS: We examined all pregnancies with NTD status confirmation from a pregnancy-monitoring system in selected locations in northern and southern regions of China between 1993 and 1996. Women who took 400 μg of FA daily during 42 days after last menstrual period were considered FA users. We analyzed NTD prevalence by FA use status, NTD type, geographic region, and infant sex. RESULTS: Among 626,042 pregnancies, 700 were affected by an NTD. Among FA nonusers, 65 pregnancies (8.8 per 10,000) in the north and 51 pregnancies (1.2 per 10,000) in the south were affected by one of the two rare NTDs, that is, craniorachischisis, iniencephaly. FA use prevented occurrence of these two rare NTDs and reduced the prevalence of spina bifida (SB) by 78% (from 17.9 to 3.9 per 10,000) in the north and 51% (from 2.4 to 1.2 per 10,000) in the south. Among FA users, SB prevalence, including SB with high lesion level, was significantly reduced in both geographic regions. FA use reduced prevalence of anencephaly and encephalocele by 85% and 50%, respectively in the north, while it did not reduce the prevalence of these two NTDs in the south. There was a greater reduction in NTD prevalence in female than in male infants and fetuses. CONCLUSIONS: This is the first study to show that FA prevents the entire spectrum of NTD types. |
Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome.
Sulaiman I , Chung M , Angel L , Tsay JJ , Wu BG , Yeung ST , Krolikowski K , Li Y , Duerr R , Schluger R , Thannickal SA , Koide A , Rafeq S , Barnett C , Postelnicu R , Wang C , Banakis S , Pérez-Pérez L , Shen G , Jour G , Meyn P , Carpenito J , Liu X , Ji K , Collazo D , Labarbiera A , Amoroso N , Brosnahan S , Mukherjee V , Kaufman D , Bakker J , Lubinsky A , Pradhan D , Sterman DH , Weiden M , Heguy A , Evans L , Uyeki TM , Clemente JC , de Wit E , Schmidt AM , Shopsin B , Desvignes L , Wang C , Li H , Zhang B , Forst CV , Koide S , Stapleford KA , Khanna KM , Ghedin E , Segal LN . Nat Microbiol 2021 6 (10) 1245-1258 ![]() Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2. |
Systematic Process Framework for Conducting Implementation Science Research in Food Fortification Programs
Teachout E , Rowe LA , Pachon H , Tsang BL , Yeung LF , Rosenthal J , Razzaghi H , Moore M , Panagides D , Milani P , Cannon MJ . Glob Health Sci Pract 2021 9 (2) 412-421 Food fortification has proven to be an effective approach for preventing micronutrient deficiencies in many settings. Factors that lead to successful fortification programs are well established. However, due to the multisectoral nature of fortification and the added complexities present in many settings, the barriers to success are not always evident and the strategies to address them are not always obvious. We developed a systematic process for identifying and addressing gaps in the implementation of a food fortification program. The framework is composed of 4 phases: (1) connect program theory of change to program implementation; (2) develop an implementation research agenda; (3) conduct implementation research; and (4) analyze findings and develop/disseminate recommendations for next steps. We detail steps in each phase to help guide teams through the process. To our knowledge, this is the first attempt to outline a systematic process for applying implementation science research to food fortification. The development of this framework is intended to promote implementation research in the field of food fortification, thus improving access to and effectiveness of this key public health intervention. |
Evaluation of an active population-based surveillance system for major birth defects in South Carolina
Samson ME , Leedom V , Mai CT , Humphries B , Yeung LF . Birth Defects Res 2020 113 (2) 128-133 INTRODUCTION: Birth defects are common, costly, and contribute substantially to infant mortality. The South Carolina Birth Defects Program (SCBDP) employs active population-based surveillance to monitor major birth defects statewide. We evaluated SCBDP's system attributes using published CDC guidelines. METHODS: To determine timeliness, completeness, and accuracy of birth defects information, we examined SCBDP's reports, program and education materials, advisory group meeting minutes, and strategic plan. We also met with program staff and stakeholders (n = 10) to discuss program goals and data utilization. We calculated the percentage of birth defects cases found 6 months after a birth cohort year for 2016-2018. RESULTS: SCBDP identifies 900-1,200 birth defects cases for a birth population of approximately 55,000 live births annually through active case reviews. SCBDP uses trained medical staff to abstract detailed information from maternal and infant medical records; SCBDP also has established auto-linkage with state vital statistics to capture demographic and birth data. SCBDP is timely and captures 97.1% (range 96.7-97.6%) of birth defects cases within 6 months after the birth cohort year closes. Active case identification using medical records as the primary data source improves quality assurance and completeness, while prepopulating demographic information improves timeliness. CONCLUSIONS: Given that birth defects significantly contribute to infant morbidity and mortality, monitoring these conditions is important to understand their impact on communities and to drive public health actions. SCBDP active surveillance and rigorous data quality practices provide the program with timely, complete, and accurate birth defects data. |
Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data
Stresman G , Sepulveda N , Fornace K , Grignard L , Mwesigwa J , Achan J , Miller J , Bridges DJ , Eisele TP , Mosha J , Lorenzo PJ , Macalinao ML , Espino FE , Tadesse F , Stevenson JC , Quispe AM , Siqueira A , Lacerda M , Yeung S , Sovannaroth S , Pothin E , Gallay J , Hamre KE , Young A , Lemoine JF , Chang MA , Phommasone K , Mayxay M , Landier J , Parker DM , Von Seidlein L , Nosten F , Delmas G , Dondorp A , Cameron E , Battle K , Bousema T , Gething P , D'Alessandro U , Drakeley C . Lancet Infect Dis 2020 20 (8) 953-963 ![]() BACKGROUND: Passively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings. METHODS: The proportion of infections detected in routine malaria data, P(Detect), was derived from paired household cross-sectional survey and routinely collected malaria data within health facilities. P(Detect) was estimated using a Bayesian model in 431 clusters spanning the Americas, Africa, and Asia. The association between P(Detect) and malaria prevalence was assessed using log-linear regression models. Changes in P(Detect) over time were evaluated using data from 13 timepoints over 2 years from The Gambia. FINDINGS: The median estimated P(Detect) across all clusters was 12.5% (IQR 5.3-25.0) for P falciparum and 10.1% (5.0-18.3) for P vivax and decreased as the estimated log-PCR community prevalence increased (adjusted odds ratio [OR] for P falciparum 0.63, 95% CI 0.57-0.69; adjusted OR for P vivax 0.52, 0.47-0.57). Factors associated with increasing P(Detect) included smaller catchment population size, high transmission season, improved care-seeking behaviour by infected individuals, and recent increases (within the previous year) in transmission intensity. INTERPRETATION: The proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that infected individuals will become symptomatic and seek care. These factors might also be true for P vivax but a better understanding of the transmission biology is needed to attribute likely reasons for the observed trend. In low transmission and pre-elimination settings, enhancing access to care and improvements in care-seeking behaviour of infected individuals will lead to an increased proportion of infections detected in the community and might contribute to accelerating the interruption of transmission. FUNDING: Wellcome Trust. |
Demographic, physiologic, and lifestyle characteristics observed with serum total folate differ among folate forms: Cross-sectional data from fasting samples in the NHANES 2011-2016
Fazili Z , Sternberg MR , Potischman N , Wang CY , Storandt RJ , Yeung L , Yamini S , Gahche JJ , Juan W , Qi YP , Paladugula N , Gabey G , Pfeiffer CM . J Nutr 2019 150 (4) 851-860 BACKGROUND: Serum folate forms were measured in the US population during recent NHANES to assess folate status. OBJECTIVE: We describe post-folic acid-fortification concentrations of serum folate forms in the fasting US population >/=1 y from the NHANES 2011-2016. METHODS: We measured 5 biologically active folates and 1 oxidation product (MeFox) of 5-methyltetrahydrofolate (5-methyl-THF). We calculated geometric means of 5-methyl-THF, unmetabolized folic acid (UMFA), nonmethyl folate (sum of tetrahydrofolate, 5-formyltetrahydrofolate, and 5,10-methenyltetrahydrofolate), total folate (sum of above biomarkers), and MeFox by demographic, physiologic, and lifestyle variables; estimated the magnitude of variables on biomarker concentrations after covariate adjustment; and determined the prevalence of UMFA >2 nmol/L. RESULTS: After demographic adjustment, age, sex, and race-Hispanic origin were significantly associated with most folate forms. MeFox increased with age, while 5-methyl-THF, UMFA, and nonmethyl folate displayed U-shaped age patterns. Compared with non-Hispanic whites, non-Hispanic blacks had 23% lower predicted 5-methyl-THF but comparable UMFA; non-Hispanic Asians had comparable 5-methyl-THF but 28% lower UMFA; Hispanics, non-Hispanic Asians, and non-Hispanic blacks had approximately 20% lower MeFox. After additional physiologic and lifestyle adjustment, predicted UMFA and MeFox concentrations were 43% and 112% higher, respectively, in adults with chronic kidney disease and 17% and 15% lower, respectively, in adults consuming daily 1-<2 alcoholic beverages; 5-methyl-THF concentrations were 20% lower in adult smokers. The prevalence of UMFA >2 nmol/L was highest in persons aged >/=70 y (9.01%) and lowest in those aged 12-19 y (1.14%). During 2011-2014, the prevalence was 10.6% in users and 2.22% in nonusers of folic acid-containing supplements. CONCLUSIONS: In fasting persons >/=1 y, the demographic, physiologic, and lifestyle characteristics observed with serum total folate differed among folate forms, suggesting biological and/or genetic influences on folate metabolism. High UMFA was mostly observed in supplement users and older persons. |
Population RBC folate concentrations can be accurately estimated from measured whole blood folate, measured hemoglobin, and predicted serum folate-cross-sectional data from the NHANES 1988-2010
Zhang M , Sternberg MR , Yeung LF , Pfeiffer CM . Am J Clin Nutr 2019 111 (3) 601-612 BACKGROUND: RBC folate (RBF) is an indicator of folate status and risk of neural-tube defects. It is calculated from whole blood folate (WBF), serum folate (SFOL), and hematocrit (Hct). SFOL and/or Hct are sometimes unavailable; hemoglobin (Hb) is generally available in surveys. OBJECTIVES: We assessed the ability of different RBF approximations to generate population data in women aged 12-49 y. METHODS: Using SFOL, RBF, Hct, Hb, and mean corpuscular Hb content (MCHC) from prefortification (1988-1994) and postfortification (1999-2006, 2007-2010) NHANES we applied 6 approaches: #1) assume SFOL = 0; #2) impute SFOL (population median); #3) impute Hct (population median); #4) estimate Hct (Hb/MCHC); #5) assume SFOL = 0 and estimate Hct; and #6) predict SFOL (from WBF) and estimate Hct. For each approach, we calculated the paired percentage difference to the "true" RBF and estimated various statistics. RESULTS: For 2007-2010 (unweighted data), the median relative difference from "true" RBF was lowest for approaches #2 (-0.74%), #4 (-0.96%), and #6 (-1.15%), intermediate for #3 (-3.36%), and highest for #5 (4.96%) and #1 (5.78%). The 95% agreement limits were smallest for approach #1 (2.33%, 13.0%) and largest for #3 (-20.8%, 11.3%). Approach #2 showed concentration-dependence (negative compared with positive differences at low compared with high RBF). Using weighted data, we found similar patterns across approaches for mean relative differences by demographic subgroup for all 3 time periods. CONCLUSIONS: We obtained the best agreement between estimated and "true" RBF when we predicted SFOL using a regression equation obtained from a subset of samples (approach #6). Alternatively, the consistent overestimation of RBF when assuming SFOL = 0 ( approximately 6%) could be addressed by adjusting the data (approach #5). Similar observations for pre- and postfortification periods suggest applicability to low and high folate status situations, but should be confirmed elsewhere. To estimate RBF, at least WBF and Hb are needed. |
Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation
Chen MY , Rose CE , Qi YP , Williams JL , Yeung LF , Berry RJ , Hao L , Cannon MJ , Crider KS . Am J Clin Nutr 2019 109 (5) 1452-1461 ![]() BACKGROUND: For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. OBJECTIVE: The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. METHODS: We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. RESULTS: Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (+/-3-4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). CONCLUSIONS: The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558. |
Systematic review and Bayesian meta-analysis of the dose-response relationship between folic acid intake and changes in blood folate concentrations
Crider KS , Devine O , Qi YP , Yeung LF , Sekkarie A , Zaganjor I , Wong E , Rose CE , Berry RJ . Nutrients 2019 11 (1) ![]() The threshold for population-level optimal red blood cell (RBC) folate concentration among women of reproductive age for the prevention of neural tube defects has been estimated at 906 nmol/L; however, the dose-response relationship between folic acid intake and blood folate concentrations is uncharacterized. To estimate the magnitude of blood folate concentration increase in response to specific dosages of folic acid under steady-state conditions (as could be achieved with food fortification), a systematic review of the literature and meta-analysis was conducted. Of the 14,002 records we identified, 533 were selected for full-text review, and data were extracted from 108 articles. The steady-state concentrations (homeostasis) of both serum/plasma and RBC folate concentrations were estimated using a Bayesian meta-analytic approach and one-compartment physiologically-based pharmacokinetic models. RBC folate concentrations increased 1.78 fold (95% credible interval (CI): 1.66, 1.93) from baseline to steady-state at 375(-)570 microg folic acid/day, and it took a median of 36 weeks of folic acid intake (95% CI: 27, 52) to achieve steady-state RBC folate concentrations. Based on regression analysis, we estimate that serum/plasma folate concentrations increased 11.6% (95% CI: 8.4, 14.9) for every 100 microg/day folic acid intake. These results will help programs plan and monitor folic acid fortification programs. |
Outcomes of infants born to women with influenza A(H1N1)pdm09
Newsome K , Alverson CJ , Williams J , McIntyre AF , Fine AD , Wasserman C , Lofy KH , Acosta M , Louie JK , Jones-Vessey K , Stanfield V , Yeung A , Rasmussen SA . Birth Defects Res 2019 111 (2) 88-95 BACKGROUND: Pregnant women with influenza are more likely to have complications, but information on infant outcomes is limited. METHODS: Five state/local health departments collected data on outcomes of infants born to pregnant women with 2009 H1N1 influenza reported to the Centers for Disease Control and Prevention from April to December 2009. Collaborating sites linked information on pregnant women with confirmed 2009 H1N1 influenza, many who were severely ill, to their infants' birth certificates. Collaborators also collected birth certificate data from two comparison groups that were matched with H1N1-affected pregnancies on month of conception, sex, and county of residence. RESULTS: 490 pregnant women with influenza, 1,451 women without reported influenza with pregnancies in the same year, and 1,446 pregnant women without reported influenza with prior year pregnancies were included. Women with 2009 H1N1 influenza admitted to an intensive care unit (ICU; n = 64) were more likely to deliver preterm infants (<37 weeks), low birth weight infants, and infants with Apgar scores <=6 at 5 min than women in comparison groups (adjusted relative risk, aRR = 3.9 [2.7, 5.6], aRR = 4.6 [2.9, 7.5], and aRR = 8.7 [3.6, 21.2], for same year comparisons, respectively). Women with influenza who were not hospitalized and hospitalized women not admitted to the ICU did not have significantly elevated risks for adverse infant outcomes. CONCLUSIONS: Severely ill women with 2009 H1N1 influenza during pregnancy were more likely to have adverse birth outcomes than women without influenza, providing more support for influenza vaccination during pregnancy. |
Trends in multivitamin use among women of reproductive age: United States, 2006-2016
Wong EC , Rose CE , Flores AL , Yeung LF . J Womens Health (Larchmt) 2019 28 (1) 37-45 BACKGROUND: Women of reproductive age can consume 0.4 milligrams of folic acid daily to reduce the risk of a neural tube defect (NTD)-affected pregnancy. Multivitamins (MVs) are one source of folic acid. MATERIALS AND METHODS: Using HealthStyles survey data (n = 9268), we assessed change in prevalence of MV use during 2006-2016 among women by age (18-24, 25-34, and 35-44 years), race/ethnicity (non-Hispanic [NH] white, NH black, Hispanic), and pregnancy status (trying to get pregnant, not pregnant nor trying to get pregnant, and pregnant) using log-binomial regression. RESULTS: Daily MV consumption decreased overall from 32.7% to 23.6% during 2006-2016 for women aged 18-44 years (p for trend <0.001). Age-specific decreases were seen in women aged 25-34 years (2006: 34.1%; 2016: 23.7%; p < 0.001) and 35-44 years (2006: 37.3%; 2016: 27.1%; p < 0.001). Decreases in daily MV intake were found among NH whites (2006: 35.4%; 2016: 24.9%; p < 0.001) and Hispanics (2006: 30.6%; 2016: 22.1%; p < 0.001), but remained unchanged among NH blacks (2006: 23.7%; 2016: 21.8%; p = 0.87). Daily MV intake remained unchanged for women trying to get pregnant (2006: 40.2%; 2012: 38.3%; p = 0.19), decreased for women not pregnant nor trying to get pregnant (2006: 31.3%; 2012: 21.3%; p < 0.001), and fluctuated for pregnant women (2006: 53.8%; 2012: 71.0%; p = 0.21). Prevalence of no MV consumption increased significantly across all age and race/ethnicity groups. CONCLUSIONS: Overall MV intake decreased for the past decade and varied by age, race/ethnicity, and pregnancy status. Innovative messaging and targeted interventions for increasing folic acid intake are needed to reduce NTDs. |
Children with heart conditions and their special health care needs - United States, 2016
Chen MY , Riehle-Colarusso T , Yeung LF , Smith C , Farr SL . MMWR Morb Mortal Wkly Rep 2018 67 (38) 1045-1049 Children with heart conditions often use more health care services and specialized care than children without a heart condition (1); however, little is known about the number of U.S. children with heart conditions and their special health care needs. CDC used data from the 2016 National Survey of Children's Health (NSCH) to estimate the prevalence of heart conditions among U.S. children aged 0-17 years, which indicated that 1.3% had a current heart condition and 1.1% had a past heart condition (representing approximately 900,000 and 755,000 children, respectively). Sixty percent and 40% of children with current and past heart conditions, respectively, had one or more special health care needs, compared with 18.7% of children without a heart condition (adjusted prevalence ratios [aPRs] = 3.1 and 2.1, respectively). Functional limitations were 6.3 times more common in children with current heart conditions (30.7%) than in those without heart conditions (4.6%). Among children with current heart conditions, males, children with lower family income, and children living in other than a two-parent household had an increased prevalence of special health care needs. These findings highlight the importance of developmental surveillance and screening for children with heart conditions and might inform public health resource planning. |
The impact of introducing malaria rapid diagnostic tests on fever case management: A synthesis of ten studies from the ACT Consortium
Bruxvoort KJ , Leurent B , Chandler CIR , Ansah EK , Baiden F , Bjorkman A , Burchett HED , Clarke SE , Cundill B , DiLiberto DD , Elfving K , Goodman C , Hansen KS , Kachur SP , Lal S , Lalloo DG , Leslie T , Magnussen P , Mangham-Jefferies L , Martensson A , Mayan I , Mbonye AK , Msellem MI , Onwujekwe OE , Owusu-Agyei S , Rowland MW , Shakely D , Staedke SG , Vestergaard LS , Webster J , Whitty CJM , Wiseman VL , Yeung S , Schellenberg D , Hopkins H . Am J Trop Med Hyg 2017 97 (4) 1170-1179 Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400-432,513). mRDTs were associated with significantly lower ACT prescription (range 8-69% versus 20-100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs. |
Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings
Hopkins H , Bruxvoort KJ , Cairns ME , Chandler CI , Leurent B , Ansah EK , Baiden F , Baltzell KA , Bjorkman A , Burchett HE , Clarke SE , DiLiberto DD , Elfving K , Goodman C , Hansen KS , Kachur SP , Lal S , Lalloo DG , Leslie T , Magnussen P , Jefferies LM , Mårtensson A , Mayan I , Mbonye AK , Msellem MI , Onwujekwe OE , Owusu-Agyei S , Reyburn H , Rowland MW , Shakely D , Vestergaard LS , Webster J , Wiseman VL , Yeung S , Schellenberg D , Staedke SG , Whitty CJ . BMJ 2017 356 j1054 Objectives To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia.Design Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study).Setting Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda.Participants 522 480 children and adults with acute febrile illness.Interventions Rapid diagnostic tests for malaria.Main outcome measures Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings.Results Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole.Conclusions Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription.This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined. |
Rotavirus vaccine effectiveness in Hong Kong children
Yeung KH , Tate JE , Chan CC , Chan MC , Chan PK , Poon KH , Siu SL , Fung GP , Ng KL , Chan IM , Yu PT , Ng CH , Lau YL , Nelson EA . Vaccine 2016 34 (41) 4935-4942 BACKGROUND: Rotavirus is a common infectious cause of childhood hospitalisation in Hong Kong. Rotavirus vaccines have been used in the private sector since licensure in 2006 but have not been incorporated in the government's universal Childhood Immunisation Programme. This study aimed to evaluate rotavirus vaccine effectiveness against hospitalisation. METHODS: This case-control study was conducted in the 2014/2015 rotavirus season in six public hospitals. Hospitalised acute gastroenteritis patients meeting inclusion criteria were recruited and copies of their immunisation records were collected. Case-patients were defined as enrolled subjects with stool specimens obtained in the first 48h of hospitalisation that tested positive for rotavirus, whereas control-patients were those with stool specimens obtained in the first 48h of hospitalisation testing negative for rotavirus. Vaccine effectiveness for administration of at least one dose of either Rotarix(R) (GlaxoSmithKline Biologicals) or RotaTeq(R) (Merck Research Laboratories) was calculated as 1 minus the odds ratio for rotavirus vaccination history for case-patients versus control-patients. RESULTS: Among the 525 eligible subjects recruited, immunisation records were seen in 404 (77%) subjects. 31% (162/525 and 126/404) tested positive for rotavirus. In the 404 subjects assessed for vaccine effectiveness, 2.4% and 24% received at least 1 dose of either rotavirus vaccine in case- and control-patients respectively. The unmatched vaccine effectiveness against hospitalisation for administration of at least one dose of either rotavirus vaccines was 92% (95% confidence interval [CI]: 75%, 98%). The matched analyses by age only and both age and admission date showed 96% (95% CI: 72%, 100%) and 89% (95% CI: 51%, 97%) protection against rotavirus hospitalisation respectively. CONCLUSIONS: Rotavirus vaccine is highly effective in preventing hospitalisation from rotavirus disease in young Hong Kong children. |
NHF-McMaster guideline on care models for haemophilia management
Pai M , Key NS , Skinner M , Curtis R , Feinstein M , Kessler C , Lane SJ , Makris M , Riker E , Santesso N , Soucie JM , Yeung CH , Iorio A , Schunemann HJ . Haemophilia 2016 22 Suppl 3 6-16 This guideline was developed to identify evidence-based best practices in haemophilia care delivery, and discuss the range of care providers and services that are most important to optimize outcomes for persons with haemophilia (PWH) across the United States. The guideline was developed following specific methods described in detail in this supplement and based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation approach). Direct evidence from published literature and the haemophilia community, as well as indirect evidence from other chronic diseases, were reviewed, synthesized and applied to create evidence-based recommendations. The Guideline panel suggests that the integrated care model be used over non-integrated care models for PWH (conditional recommendation, moderate certainty in the evidence). For PWH with inhibitors and those at high risk for inhibitor development, the same recommendation was graded as strong, with moderate certainty in the evidence. The panel suggests that a haematologist, a specialized haemophilia nurse, a physical therapist, a social worker and round-the-clock access to a specialized coagulation laboratory be part of the integrated care team, over an integrated care team that does not include all of these components (conditional recommendation, very low certainty in the evidence). Based on available evidence, the integrated model of care in its current structure, is suggested for optimal care of PWH. There is a need for further appropriately designed studies that address unanswered questions about specific outcomes and the optimal structure of the integrated care delivery model in haemophilia. |
Care models in the management of haemophilia: A systematic review
Yeung CH , Santesso N , Pai M , Kessler C , Key NS , Makris M , Navarro-Ruan T , Soucie JM , Schunemann HJ , Iorio A . Haemophilia 2016 22 Suppl 3 31-40 BACKGROUND: Haemophilia care is commonly provided via multidisciplinary specialized management. To date, there has been no systematic assessment of the impact of haemophilia care delivery models on patient-important outcomes. OBJECTIVE: To conduct a systematic review of published studies assessing the effects of the integrated care model for persons with haemophilia (PWH). SEARCH METHODS: We searched MEDLINE, EMBASE and CINAHL up to April 22, 2015, contacted experts in the field, and reviewed reference lists. SELECTION CRITERIA: Randomized and non-randomized studies of PWH or carriers, focusing mainly on the assessment of care models on delivery. DATA COLLECTION AND ANALYSIS: Two investigators independently screened title, abstract, and full text of retrieved articles for inclusion. Risk of bias and overall quality of evidence was assessed using Cochrane's ACROBAT-NRSI tool and GRADE respectively. Relative risks, mean differences, proportions, and means and their variability were calculated as appropriate. RESULTS: 27 non-randomized studies were included: eight comparative and 19 non-comparative studies. We found low- to very low-quality evidence that in comparison to other models of care, integrated care may reduce mortality, hospitalizations and emergency room visits, may lead to fewer missed days of school and work, and may increase knowledge seeking. CONCLUSION: Our comprehensive review found low- to very low-quality evidence from a limited number of non-randomized studies assessing the impact of haemophilia care models on some patient-important outcomes. While the available evidence suggests that adoption of the integrated care model may provide benefit to PWH, further high-quality research in the field is needed. |
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