Assessing Accuracy and Precision of Hemoglobin Determination in Venous, Capillary Pool, and Single-Drop Capillary Blood Specimens Using three Different HemoCue® Hb Models: The Multicountry Hemoglobin Measurement (HEME) Study.

BACKGROUND: Anemia prevalence estimates reported in population surveys can vary based on the blood specimen source (capillary or venous) and analytic device (hematology autoanalyzers or portable hemoglobinometers) used for hemoglobin (Hb) determination. OBJECTIVES: This study aimed to compare accuracy and precision of Hb measurement in three blood specimen types on three models of hemoglobinometers against the results from venous blood from the same individuals measured on automated analyzers (AAs). METHODS: This multisite (Cambodia, Ethiopia, Guatemala, Lebanon, Nigeria, and Tanzania) study assessed Hb measurements in paired venous and capillary blood specimens from apparently healthy women (aged 15-49 y) and children (aged 12-59 mo) using three HemoCue® Hb models (201+, 301, and 801). Measurements were compared against reference values: venous blood in hematology AA and adjusted via regression calibration or mean difference in HemoCue® Hb. Venous, capillary pool, and single-drop capillary blood specimens were assessed for accuracy and precision. RESULTS: Venous blood measured using HemoCue® Hb 301 exhibited a positive mean error, whereas responses in HemoCue® Hb 201+ and 801 were nondirectional compared with the reference. Adjustment with the reference harmonized mean errors for all devices across study sites to <1.0 g/L using venous blood. Precision was highest for venous blood (±5-16 g/L) in all sites, lowest for single-drop capillary (±9-37 g/L), and intermediate (±9-28 g/L) for capillary pool blood specimen. Imprecision differed across sites, especially with both capillary blood specimens, suggesting different levels of personnel skills. CONCLUSIONS: Findings suggest that venous blood is needed for accurate and precise Hb determination. Single-drop capillary blood use should be discouraged owing to high measurement variability. Further research should evaluate the viability and reliability of capillary pool blood for this purpose. Accuracy of HemoCue® Hb devices can be improved via standardization against results from venous blood assessed using AA.

Firm-Level and Public-Sector Costs Make Small-Scale Maize Flour Fortification Challenging in Uganda.

BACKGROUND: Maize flour in Uganda is milled by hundreds of enterprises, mostly small- (5-20 metric tons [MT]/day) and micro-scale (<5 MT/day) mills or firms. A mandatory maize flour fortification program exists for medium-scale mills (>20 MT/day) and policymakers are considering including smaller-scale millers. OBJECTIVE: We estimated the private and public costs of maize flour fortification at different scales and explored their implications for extending the mandatory fortification to include smaller-scale mills. METHODS: We used secondary data on the structure of the maize flour market and primary data on milling and fortification costs to estimate mill and regulatory costs at 3 scales of flour production: micro, small, and medium. RESULTS: For micro-, small-, and medium-size operations, respectively, operational costs of fortification were US$13, US$9, and US$7 per metric ton (MT) of maize flour, which represented 20%, 16%, and 16% of annual operating costs, and the ratio of fortification equipment cost to mill equipment costs was higher for micro-scale mills (2.7) than for small- (0.38) and medium-scale (0.54) maize mills. Governmental regulatory costs rise if smaller-scale mills are included due to the increased number of facility inspections. CONCLUSIONS: Fortification and regulatory costs increase as production scale decreases. Up-front capital costs of fortification would be daunting for micro- and small-scale mills. Medium-scale mills, which supply social protection programs, might be able to manage fortification costs and other challenges. Decision-makers should consider all costs and cost burdens, and the realities of enforcement capabilities before expanding fortification programs to include smaller-scale operations.

Plain language titleCosts of Small-scale Maize Flour Fortification in UgandaPlain language summaryA study of the costs of adding vitamins and minerals by small-scale maize flour millers in Uganda was undertaken to understand if it would be commercially beneficial from a business and operations perspective for them to do so, and if requiring them to do so would impose additional cost burdens on government to ensure that fortification standards were met.Why was the study done?Maize flour is consumed by the majority of Uganda's population, especially the rural poor. If the flour were fortified, it would reduce vitamin and mineral deficiencies among those at risk. The most important constraint to market-wide fortification is the presence of many small-scale mills or firms that neither have the resources nor the technology to adopt and sustain the fortification process. To date, no study has been done to calculate the costs that small-scale mills would have to face to fortify flour, or what the cost implications for government would be for including smaller-scale mills in a national fortification program, including the costs of enforcing regulations.What did the researchers do?The researchers interviewed millers of several scales of operation to collect cost information on their operations and interviewed representatives of government regulatory bodies to estimate the costs of testing maize flour to ensure compliance with regulations. Researchers estimated the cost to the mills of adding fortification to their business models, and the impacts on the government costs (eg, testing additional samples, etc.) of including smaller-scale mills in the fortification program.What did the researchers find?The researchers looked at 3 different types of mills based on their capacity to mill maize flour­micro-scale firms milled less than 5 metric tons (MT) a day, small-scale firms milled 5 to 20 MT per day, and medium-scale firms milled over 20 MT a day. For micro-, small-, and medium-size firms, respectively, fortification increased operational costs by US$13, US$9, and US$7 per MT of maize flour, which represented 20%, 16%, and 16% of annual operating costs. Similarly, governmental regulatory costs rose if smaller-scale mills were included because of the increased number of facility inspections required since the current legislation requires mandatory annual inspections.What do the findings mean?Fortification and regulatory costs increase as the scale of production by the millers decreases. If fortification by small- and micro-scale mills were made mandatory, up-front costs of fortification equipment and materials would be daunting for micro- and small-scale millers. Ugandan medium-scale millers might manage fortification costs and other challenges, but only if the social protection programs they supplied were of sufficient volume and regularity.

Exploring the Anemia Ecology: A New Approach to an Old Problem.

Our ability to identify anemia and all its permutations demands an approach that integrates the key elements of a complex "ecology," which intertwines biology and mechanistic aspects of nutrients with both the health status and underlying factors-physical, economic, social, behavioral, demographic, and environmental. The complexity of anemia demands an ecologic approach that appreciates systems biology, translates sensitive and specific assessment methodologies and interventions, and ultimately improves clinical and public health outcomes. This series of technical papers on anemia by the U.S. Agency for International Development (USAID) Advancing Nutrition Anemia Task Force (ATF) is a first step in translating our ecologic approach to anemia with a view toward balancing research with its translation to effective programs, interventions, and policy. This introductory overview describes the components of our ecologic approach-linking the biology of anemia with its assessment and using the learning from that confluence to devise context-specific interventions. This introductory review briefly discusses the topics that underlie the biology and primary etiologies of anemia and presents a framework for public health assessment of anemia, leading to appropriate public health interventions. The other 3 manuscripts in the supplement provide the details of the arguments laid out in the introduction.

Improving Anemia Assessment in Clinical and Public Health Settings.

We aim to provide a practical approach to assess anemia and its primary causes, both in clinical settings and in the context of public health programs. Anemia remains a global challenge; thus, to achieve goals for anemia reduction and assess progress, standardized approaches are required for the assessment of anemia and its causes. We first provide a brief review of how to assess anemia, based on hemoglobin concentrations and cutoffs that correspond to age, sex, and physiologic status. Next, we discuss how to assess the likely causes of anemia in different settings. The causes of anemia are classified as non-nutritional (for example, because of infection, inflammation, blood loss, or genetic disorders) or nutrition-specific (for example, because of deficiencies of iron, vitamin A, riboflavin, vitamin B12, or folate). There is an important overlap between these 2 categories, such as the increased likelihood of iron deficiency in the context of inflammation. Given the multifaceted nature of anemia etiology, we introduce a framework for anemia assessment based on the "ecology of anemia," which recognizes its many overlapping causes. This conceptual framework is meant to inform what data on anemia causes may need to be collected in population surveys. The framework has a supporting table with information on the diagnostic tests, biomarkers and proposed cutoffs, characteristics, and feasibility of collecting the myriad information that can help elucidate the anemia etiology. We also provide examples of how this framework can be applied to interpret the anemia risk factor data from population-based surveys that can inform decisions about context-specific interventions. Finally, we present research gaps and priorities related to anemia assessment.

Approaches to Address the Anemia Challenge.

Anemia is a multifactorial condition; approaches to address it must recognize that the causal factors represent an ecology consisting of internal (biology, genetics, and health) and external (social/behavioral/demographic and physical) environments. In this paper, we present an approach for selecting interventions, followed by a description of key issues related to the multiple available interventions for prevention and reduction of anemia. We address interventions for anemia using the following 2 main categories: 1) those that address nutrients alone, and, 2) those that address nonnutritional causes of anemia. The emphasis will be on interventions of public health relevance, but we also consider the clinical context. We also focus on interventions at different stages of the life course, with a particular focus on women of reproductive age and preschool-age children, and present evidence on various factors to consider when selecting an intervention-inflammation, genetic mutations, nutrient delivery, bioavailability, and safety. Each section on an intervention domain concludes with a brief discussion of key research areas.

Evaluation of Global Experiences in Large-Scale Double-Fortified Salt Programs.

BACKGROUND: Double-fortified salt (DFS) is a vehicle for dual fortification with iron and iodine, to reduce their respective deficiencies. This background article is the third in a series reviewing available research, analyses, and experiences on DFS as an effective delivery vehicle for iron and iodine. OBJECTIVES: The objective of this article is to systematically evaluate current programs distributing DFS around the world and catalogue opportunities, risks, and challenges related to programs that incorporate DFS. We carried out a narrative review of DFS programs from around the world with our data sources deriving from a mix of a nonsystematic literature search and interviews with key informants. METHODS: We assessed programmatic experience with DFS from social safety net programs in India (from the states of Bihar, Madhya Pradesh, and Uttar Pradesh) and from non-social safety net country programs or projects in Argentina, Cote d'Ivoire, Kenya, Morocco, Nigeria, Philippines, and Sri Lanka. RESULTS: Findings revealed color change of the final DFS product was an issue in 9 of the 14 programs or studies reviewed and was the most significant challenge that had a direct impact on consumer acceptance and uptake regardless of type of program (open market or social safety net). Other challenges identified were related to the quality of the salt and lack of DFS formulation standards and regulatory monitoring protocols. CONCLUSIONS: DFS programs need to focus on 1) improved technology with better consumer acceptance and better performance when used with lower-quality salt; 2) elucidation and enforcement of DFS formulation quality standards, along with producer incentives; and 3) strong government backing at the policy level. DFS offers a unique opportunity to leverage an almost universally consumed product with the addition of 2 important nutrients missing in many populations. However, program "maturity" will take time with urgent attention needed for quality production.

Variability in haemoglobin concentration by measurement tool and blood source: an analysis from seven countries.

OBJECTIVE: We explore factors such as the blood sampling site (capillary vs venous), the equipment (HemoCue vs automated haematology analyser) and the model of the HemoCue device (201+ vs 301) that may impact haemoglobin measurements in capillary and venous blood. METHODS: Eleven studies were identified, and bias, concordance and measures of diagnostic performance were assessed within each study. FINDINGS: Our analysis included 11 studies from seven countries (Cambodia, India, The Gambia, Ghana, Laos, Rwanda and USA). Samples came from children, men, non-pregnant women and pregnant women. Mean bias ranged from -8.7 to 2.5 g/L in Cambodian women, 6.2 g/L in Laotian children, 2.4 g/L in Ghanaian women, 0.8 g/L in Gambian children 6-23 months and 1.4 g/L in Rwandan children 6-59 months when comparing capillary blood on a HemoCue to venous blood on a haematology analyser. Bias was 8.3 g/L in Indian non-pregnant women and 2.6 g/L in Laotian children and women and 1.5 g/L in the US population when comparing capillary to venous blood using a HemoCue. For venous blood measured on the HemoCue compared with the automated haematology analyser, bias was 5.3 g/L in Gambian pregnant women 18-45 years and 11.3 g/L in Laotian children 6-59 months. CONCLUSION: Our analysis found large variability in haemoglobin concentration measured on capillary or venous blood and using HemoCue Hb 201+ or Hb 301 or automated haematology analyser. We cannot ascertain whether the variation is due to differences in the equipment, differences in capillary and venous blood, or factors affecting blood collection techniques.

The Impact of Nutrition-Specific and Nutrition-Sensitive Interventions on Hemoglobin Concentrations and Anemia: A Meta-review of Systematic Reviews.

Anemia is a multifactorial condition arising from inadequate nutrition, infection, chronic disease, and genetic-related etiologies. Our aim was to assess the impact of nutrition-sensitive and nutrition-specific interventions on hemoglobin (Hb) concentrations and anemia to inform the prioritization and scale-up of interventions to address the multiple causes of anemia. We performed a meta-review synthesis of information by searching multiple databases for reviews published between 1990 and 2017 and used standard methods for conducting a meta-review of reviews, including double independent screening, extraction, and quality assessment. Quantitative pooling and narrative syntheses were used to summarize information. Hb concentration and anemia outcomes were pooled in specific population groups (children aged <5 y, school-age children, and pregnant women). Methodological quality of the systematic reviews was assessed using Assessing the Methodological Quality of Systematic Reviews (AMSTAR) criteria. Of the 15,444 records screened, we identified 118 systematic reviews that met inclusion criteria. Reviews focused on nutrition-specific interventions (96%). Daily and intermittent iron supplementation, micronutrient powders, malaria treatment, use of insecticide-treated nets (ITNs), and delayed cord clamping were associated with increased Hb concentration in children aged <5 y. Among children older than 5 y, daily and intermittent iron supplementation and deworming, and in pregnant women, daily iron-folic acid supplementation, use of ITNs, and delayed cord clamping, were associated with increased Hb concentration. Similar results were obtained for the reduced risk of anemia outcome. This meta-review suggests the importance of nutrition-specific interventions for anemia and highlights the lack of evidence to understand the influence of nutrition-sensitive and multifaceted interventions on the condition.

Measurement and interpretation of hemoglobin concentration in clinical and field settings: a narrative review.

Anemia affects over 800 million women and children globally. Defined as a limited or insufficient functional red blood cell supply in peripheral blood, anemia causes a reduced oxygen supply to tissues and can have serious health consequences for women and children. Hemoglobin (Hb) concentration is most commonly measured for anemia diagnosis. Methods to measure Hb are usually invasive (requiring a blood sample); however, advances in diagnostic and clinical chemistry over the past decade have led to the development of new noninvasive methods. Accurate diagnosis at the individual level is important to identify individuals who require treatment. At the population level, anemia prevalence estimates are often the impetus for national nutrition policies or programs. Thus, it is essential that methods for Hb measurement are sensitive, specific, accurate, and reproducible. The objective of our narrative review is to describe the basic principles, advantages, limitations, and quality control issues related to methods of Hb measurement in clinical and field settings. We also discuss other biomarkers and tests that can help to determine the severity and underlying causes of anemia. In conclusion, there are many established and emerging methods to measure Hb concentration, each with their own advantages, limitations, and factors to consider before use.

The Role of Dairy in Effectiveness and Cost of Treatment of Children With Moderate Acute Malnutrition: A Narrative Review.

BACKGROUND: Dairy is recommended in specially formulated supplementary foods to treat children with moderate acute malnutrition (MAM) but with limited evidence and added cost. OBJECTIVE: Review studies of ready-to-use foods (RUFs) versus fortified blended foods (FBFs) to determine whether inclusion of dairy modifies the comparative effectiveness and cost. METHODS: We reviewed literature comparing FBF and RUF in treatment of MAM among children younger than 5 years in developing countries. Outcomes of recovery from MAM, weight, and length gain were compared among treatment categories: FBF with dairy (FBF+), FBF without dairy (FBF-), RUF with dairy (RUF+), and RUF without dairy (RUF-). Supplement cost was compared per 500 kcal. RESULTS: Eight studies were included. Rations were heterogeneous in energy and type of dairy. Overall, RUF+, RUF-, and FBF+ performed similarly, with higher recovery and weight gain compared with FBF-. RUF+ had higher recovery (in 5 of 6 comparisons), weight gain (4 of 4), and length gain (1 of 4) versus FBF-. The RUF+ had higher recovery (1 of 2) versus FBF+, with no other differences. The RUF- versus FBF+ had no differences (0 of 2). The RUF- had higher recovery (1 of 2), weight gain (2 of 2) versus FBF-. Four studies reported supplement costs, which averaged US$0.15 (FBF-), US$0.18 (FBF+), US$0.18 (RUF-), and US$0.37 (RUF+) per 500 kcal. CONCLUSIONS: There is a consistent benefit of FBF that include dairy in treatment of children with MAM. Benefits of dairy in RUF require further investigation. Evidence from rigorous quantitative analysis of existing data, cost-effectiveness, and prospective trials will be essential in determining policy on treatment for children with MAM.

Dihydrofolate reductase 19-bp deletion polymorphism modifies the association of folate status with memory in a cross-sectional multi-ethnic study of adults.

BACKGROUND: Folate status has been positively associated with cognitive function in many studies; however, some studies have observed associations of poor cognitive outcomes with high folate. In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. To our knowledge, the cognitive effects of this gene have not been studied previously. OBJECTIVE: We examined the association between cognitive outcomes with the 19-bp deletion DHFR polymorphism, folate status, and their interaction with high or normal plasma folate. DESIGN: This was a pooled cross-sectional study of the following 2 Boston-based cohorts of community living adults: the Boston Puerto Rican Health Study and the Nutrition, Aging, and Memory in Elders study. Individuals were genotyped for the DHFR 19-bp deletion genotype, and plasma folate status was determined. Cognitive outcomes included the Mini-Mental State Examination, Center for Epidemiologic Studies Depression Scale, and factor scores for the domains of memory, executive function, and attention from a set of cognitive tests. RESULTS: The prevalence of the homozygous deletion (del/del) genotype was 23%. In a multivariable analysis, high folate status (>17.8 ng/mL) was associated with better memory scores than was normal-folate status (fourth-fifth quintiles compared with first-third quintiles: ß ± SE = -0.22 ± 0.06, P < 0.01). Carriers of the DHFR del/del genotype had worse memory scores (ß ± SE = -0.24 ± 0.10, P < 0.05) and worse executive scores (ß = -0.19, P < 0.05) than did those with the del/ins and ins/ins genotypes. Finally, we observed an interaction such that carriers of the del/del genotype with high folate had significantly worse memory scores than those of both noncarriers with high-folate and del/del carriers with normal-folate (ß-interaction = 0.26 ± 0.13, P < 0.05). CONCLUSIONS: This study identifies a putative gene-nutrient interaction that, if confirmed, would predict that a sizable minority carrying the del/del genotype might not benefit from high-folate status and could see a worsening of memory. An understanding of how genetic variation affects responses to high-folate exposure will help weigh risks and benefits of folate supplementation for individuals and public health.

Asymptomatic carotid artery stenosis treated with medical therapy alone: temporal trends and implications for risk assessment and the design of future studies.

BACKGROUND: The rate of adverse clinical outcomes among patients with asymptomatic carotid stenosis receiving medical therapy alone can be used to guide clinical decision-making and to inform future research. We aimed to investigate temporal changes in the incidence rate of clinical outcomes among patients with asymptomatic carotid stenosis receiving medical therapy alone and to explore the implications of these changes for the design of future comparative studies. SUMMARY: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, US Food and Drug Administration documents, and reference lists of included studies (last search: December 31, 2012). We selected prospective cohort studies of medical therapy for asymptomatic carotid artery stenosis and we extracted information on study characteristics, risk of bias, and outcomes. We performed meta-analyses to estimate summary incidence rates, meta-regressions to assess trends over time, and simulations to explore sample size requirements for the design of future studies comparing new treatments against medical therapy. The main outcomes of interest were ipsilateral stroke, any stroke, cardiovascular death, death, and myocardial infarction. We identified 41 studies of medical therapy for patients with asymptomatic carotid stenosis (last recruitment year: 1978-2009). The summary incidence rate of ipsilateral carotid territory stroke (25 studies) was 1.7 per 100 person-years. This incidence rate was significantly lower in recent studies (last recruitment year from 2000 onwards) as compared to studies that ended recruitment earlier (1.0 vs. 2.3 events per 100 person-years; p < 0.001). The incidence rates of any territory stroke (17 studies), cardiovascular death (6 studies), death (13 studies), and myocardial infarction (5 studies) were 2.7, 4.1, 4.6, and 1.8 per 100 person-years, respectively. Simulations showed that future studies would need to enroll large numbers of patients with a relatively high incidence rate under medical therapy, and evaluate interventions with large effect sizes, to have adequate power to reliably detect treatment effects. KEY MESSAGES: Improved prognosis under medical therapy alone has narrowed the potential range of risk reduction attainable with new treatments for asymptomatic carotid stenosis. Future comparative studies will need to enroll large numbers of patients to assess treatment effectiveness.

Management strategies for asymptomatic carotid stenosis: a systematic review and meta-analysis.

BACKGROUND: Adults with asymptomatic carotid artery stenosis are at increased risk for ipsilateral carotid territory ischemic stroke. PURPOSE: To examine comparative evidence on management strategies for asymptomatic carotid stenosis and the incidence of ipsilateral stroke with medical therapy alone. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, U.S. Food and Drug Administration documents, and review of references through 31 December 2012. STUDY SELECTION: Randomized, controlled trials (RCTs) and prospective or retrospective nonrandomized, comparative studies of medical therapy alone, carotid endarterectomy (CEA) plus medical therapy, or carotid artery stenting (CAS) plus medical therapy for adults with asymptomatic carotid stenosis, as well as single-group prospective cohort studies of medical therapy, were reviewed. DATA EXTRACTION: Two investigators extracted information on study and population characteristics, results, and risk of bias. DATA SYNTHESIS: Forty-seven studies in 56 publications were eligible. The RCTs comparing CAS and CEA were clinically heterogeneous; 1 RCT reported more but not statistically significant ipsilateral stroke events (including any periprocedural stroke) in CAS compared with CEA, whereas another RCT, in a population at high surgical risk for CEA, did not. Three RCTs showed that CEA reduced the risk for ipsilateral stroke (including any periprocedural stroke) compared with medical therapy alone, but these results may no longer be applicable to contemporary clinical practice. No RCT compared CAS versus medical therapy alone. The summary incidence of ipsilateral stroke across 26 cohorts receiving medical therapy alone was 1.68% per year. LIMITATIONS: Studies defined asymptomatic status heterogeneously. Participants in RCTs did not receive best-available medical therapy. CONCLUSION: Future RCTs of asymptomatic carotid artery stenosis should explore whether revascularization interventions provide benefit to patients treated by best-available medical therapy. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

High priority future research needs for obstructive sleep apnea diagnosis and treatment.

STUDY OBJECTIVES: To identify and prioritize future research needs (FRN) topics for diagnosis and treatment of obstructive sleep apnea (OSA). METHODS: Twenty-one panel members represented six stake-holder categories: patients and the public, providers; purchasers of health care, payers, policymakers, and principal investigators. Building on a recently completed comparative effectiveness review, stakeholders nominated and discussed potential FRN topics. Stakeholders then nominated their top priority FRN topics based on the Agency for Healthcare Research and Quality Effective Health Care Program Selection Criteria. From these nominations, the highest priority FRN topics were determined and were elaborated upon to include possible study designs to address the topics. RESULTS: Thirty-seven topics were discussed and prioritized. The nine highest priority FRN topics included: cost-effectiveness of management strategies, defining age- and sex-specific criteria for OSA, evaluating routine preoperative screening for OSA, evaluating involvement of a sleep medicine specialist in diagnosis of OSA, evaluating clinical prediction rules, assessing the effect of treating sleep disordered breathing and long-term clinical outcomes, comparing treatments for patients who do not tolerate positive airway pressure, evaluating strategies to improve treatment compliance, and evaluating the association between sleep apnea severity and long-term clinical outcomes. CONCLUSIONS: While there are numerous specific research questions with low or insufficient strength of evidence for OSA management, OSA patients, their healthcare providers, and society at large would benefit from refocusing research efforts into the prioritized research questions and away from simple comparisons of short-term outcomes between specific interventions.

Status of vitamins B-12 and B-6 but not of folate, homocysteine, and the methylenetetrahydrofolate reductase C677T polymorphism are associated with impaired cognition and depression in adults.

The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene differs in frequency in various ethnic groups that have differing prevalence of age-related cognitive impairments. We used a series of neuro-psychological tests to examine the association of the MTHFR C677T polymorphism with cognition and depression and also to assess whether genotype modifies the association of folate and homocysteine with these outcomes. This study analyzed pooled cross-sectional data from 2 ethnically diverse cohorts of community-living adults: the Boston Puerto Rican Health Study (n = 939) and the Nutrition, Aging, and Memory in Elders study (n = 1017). Individuals in both cohorts underwent anthropometric and laboratory measurements and dietary and health assessments using validated questionnaires between the years 2003 and 2007. Cognitive outcomes included measures of global cognition [Mini-Mental Status Exam (MMSE)], depression (Center for Epidemiological Studies Depression Scale), and 3 factor scores for the domains of attention, executive function, and memory that were derived from a detailed set of neuropsychological tests. Low plasma vitamin B-12 concentrations were associated with poorer MMSE scores and higher depression scores, and low vitamin B-6 concentrations were associated with lower MMSE and worse attention and executive function in the multivariate analysis. In contrast, MTHFR genotype, folate, and homocysteine were not associated with cognition or depression in either ethnicity-pooled or stratified analysis. The current study did not find evidence of an association between the MTHFR C677T TT genotype and impaired cognition or depression in a population with adequate folate status and a high prevalence of cognitive impairment and depression.

Concordance of randomized and nonrandomized studies was unrelated to translational patterns of two nutrient-disease associations.

OBJECTIVE: There are several examples in nutrition of discordance between the results of observational studies and randomized controlled trials (RCTs). We hypothesized that this discordance is attributable to differences in the translational paths of nutrient-disease associations. Translational paths can be assessed using citation analysis. STUDY DESIGN AND SETTING: We compared the characteristics of citation networks using examples, where RCTs and observational studies agreed (long-chain n-3 polyunsaturated fatty acids [n-3 PUFA]) or disagreed (vitamin E). We performed systematic reviews in each example, constructed citation networks, and compared them with respect to the number of articles and citation relationships between them, as well as the distribution of articles' hub and authority scores. RESULTS: For n-3 PUFA, meta-analyses of 14 RCTs and 10 observational studies both suggested that higher intake was associated with lower cardiovascular mortality. For vitamin E, the meta-analysis of 14 RCTs excluded a clinically significant effect, whereas 14 observational studies reported a significant inverse association. The respective citation networks consisted of 392 (n-3 PUFA) and 351 (vitamin E) articles. No differences between the characteristics of the two networks were identified. There was no evidence that the observational studies predated RCTs in the translational process in either example. CONCLUSION: In the two examples, citation network characteristics do not predict concordance in the results of observational studies and RCTs.

Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT).

OBJECTIVE: Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment, and depression are all common in individuals with kidney disease, including kidney transplant recipients. Accordingly, we assessed the prevalence of cognitive impairment and depressive symptoms in transplant recipients and their association with kidney function, plasma total homocysteine, and B-vitamin concentrations. SETTING: Cross-sectional analysis of baseline data from the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) Ancillary Cognitive Trial (FACT), which included 183 participants in FAVORIT who underwent detailed neuropsychological assessment before the study intervention. RESULTS: The mean age was 54.0 ± 9.5 years (range: 7 to 386 months). Men comprised 55.2% of the cohort, and the mean time between the current transplant and cognitive testing was 7.0 ± 5.8 years. Twenty-four percent of participants reported neurological or psychiatric complaints, and 30% exhibited symptoms of mild to severe depression. Testing revealed evidence of significant and selective deficits in this population: 33% performed more than 1 standard deviation (SD) below normed means on a memory test, 58% fell lower than 1 SD below the norms on a test of attention and mental processing speed, and 33% to 42% fell lower than 1 SD below the norms on several tests of executive function. Lower estimated glomerular filtration rate and lower folate were associated with poorer performance on tests of memory and executive function. CONCLUSIONS: These observations confirm previous reports of mood and cognitive impairments in adult kidney transplant recipients. Further research is needed to determine the benefit of B-vitamin supplementation and other interventions in this patient population.

Nutrition and Crohn's disease: an update of print and Web-based guidance.

This article reviews the role of nutrition in Crohn's disease, one of the inflammatory bowel diseases. In addition to presenting a comprehensive review of the state-of-the-evidence on nutritional risks and nutritional therapies in Crohn's disease, and making specific nutrient recommendations, this article includes a list of Web-based resources, including websites, blogs, newsletters, and multimedia podcasts that can be utilized by patients and healthcare providers alike to learn more about the etiology, pathophysiology, and nutritional management of Crohn's disease.