Staphylococcus aureus isolates from children with clinically differentiated osteomyelitis exhibit distinct transcriptomic signatures.

There is substantial genomic heterogeneity among Staphylococcus aureus isolates of children with acute hematogenous osteomyelitis (AHO) but transcriptional behavior of clinically differentiated strains has not been previously described. This study evaluates transcriptional activity of S. aureus isolates of children with AHO that may regulate metabolism, biosynthesis, or virulence during bacterial growth and pathogenesis. In vitro growth kinetics were compared between three S. aureus clinical isolates from children with AHO who had mild, moderate, and severe illness. Total RNA sequencing was performed for each isolate at six separate time points throughout the logarithmic phase of growth. The NASA RNA-Sequencing Consensus Pipeline was used to identify differentially expressed genes allowing for 54 comparisons between the three isolates during growth. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways were used to evaluate transcriptional variation in metabolism, biosynthesis pathways and virulence potential of the isolates. The S. aureus isolates demonstrated differing growth kinetics under standardized conditions with the mild isolate having higher optical densities with earlier and higher peak rates of growth than that of the other isolates (p<0.001). Enrichment pathway analysis established distinct transcriptional signatures according to both sampling time and clinical severity. Moderate and severe isolates demonstrated pathways of bacterial invasion, S. aureus infection, quorum sensing and two component systems. In comparison, the mild strain favored biosynthesis and metabolism. These findings suggest that transcriptional regulation during the growth of S. aureus may impact the pathogenetic mechanisms involved in the progression of severity of illness in childhood osteomyelitis. The clinical isolates studied demonstrated a tradeoff between growth and virulence. Further investigation is needed to evaluate these transcriptional pathways in an animal model or during active clinical infections of children with AHO.

Early Transition to Oral Antimicrobial Therapy Among Children With Staphylococcus aureus Bacteremia and Acute Hematogenous Osteomyelitis.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is a frequent complication of acute hematogenous osteomyelitis (AHO) in children, but data on the optimal duration of parenteral antibiotics prior to transition to oral antibiotics remains sparse. We examined clinical outcomes associated with early transition to oral antimicrobial therapy among children admitted to our institution with AHO and SAB, and evaluated the utility of a severity of illness score (SIS) to guide treatment decisions in this setting. METHODS: Children with AHO and SAB admitted to our institution between January 1, 2009, and December 31, 2018, were retrospectively reviewed and stratified according to a previously validated SIS into mild (0-3), moderate (4-7) and severe (8-10) cohorts. Groups were assessed for differences in treatment (eg, parenteral and oral antibiotic durations, surgeries) and clinical response (eg, bacteremia duration, acute kidney injury, length of stay and treatment failure). RESULTS: Among 246 children identified with AHO and SAB, median parenteral antibiotic duration differed significantly between mild (n = 80), moderate (n = 98) and severe (n = 68) cohorts (3.6 vs. 6.5 vs. 14.3 days; P ≤ 0.001). SIS cohorts also differed with regard to number of surgeries (0.4 vs. 1.0 vs. 2.1; P ≤ 0.001), duration of bacteremia (1.0 vs. 2.0 vs. 4.0 days; P ≤ 0.001), acute kidney injury (0.0% vs. 3.0% vs. 20.5%; P ≤ 0.001), hospital length of stay (4.8 vs. 7.4 vs. 16.4 days; P ≤ 0.001) and total duration of antibiotics (34.5 vs. 44.7 vs. 60.7 days; P ≤ 0.001). Early transition to oral antimicrobial therapy among mild or moderate SIS cohorts was not associated with treatment failure despite SAB. CONCLUSIONS: SAB is associated with a wide range of illness among children with AHO, and classification of severity may be useful for guiding treatment decisions. Early transition to oral antimicrobial therapy appears safe in children with mild or moderate AHO despite the presence of SAB.

Quality Improvement of Magnetic Resonance Imaging for Musculoskeletal Infection in Children Results in Decreased Scan Duration and Decreased Contrast Use.

BACKGROUND: Magnetic resonance imaging (MRI) is a heavily utilized resource to evaluate children suspected to have a musculoskeletal infection. Complex interdisciplinary workflows are involved with decision-making with regard to indications, anesthesia, contrast use, and procedural timing relative to the scan. This study assesses the impact of a quality improvement endeavor on MRI workflows at a tertiary pediatric medical center. METHODS: A registry of consecutively enrolled children for a multidisciplinary musculoskeletal infection program identified those evaluated with MRI from 2012 to 2018. Annual MRI process improvement feedback was provided to the key stakeholders. Demographic characteristics, laboratory parameters, MRI indications, anesthesia use, MRI findings, final diagnoses, scan duration, imaging protocol, surgical intervention following MRI, and length of stay were retrospectively compared between the 3 cohorts (initial, middle, and final) representing 2-year increments to assess the impact of the initiative. RESULTS: There were 526 original MRI scans performed to evaluate 1,845 children with suspected musculoskeletal infection. Anesthesia was used in 401 children (76.2%). When comparing the initial, middle, and final study period cohorts, significant improvement was demonstrated for the number of sequences per scan (7.5 sequences for the initial cohort, 5.8 sequences for the middle cohort, and 4.6 sequences for the final cohort; p < 0.00001), scan duration (73.6 minutes for the initial cohort, 52.1 minutes for the middle cohort, and 34.9 minutes for the final cohort; p < 0.00001), anesthesia duration (94.1 minutes for the initial cohort, 68.9 minutes for the middle cohort, and 53.2 minutes for the final cohort; p < 0.00001), and the rate of contrast use (87.6% for the initial cohort, 67.7% for the middle cohort, and 26.3% for the final cohort; p < 0.00001). There was also a trend toward a higher rate of procedures under continued anesthesia immediately following the MRI (70.2% in the initial cohort, 77.8% in the middle cohort, and 84.6% in the final cohort). During the final 6-month period, the mean scan duration was 24.4 minutes, anesthesia duration was 40.9 minutes, and the rate of contrast administration was 8.5%. CONCLUSIONS: Progressive quality improvement through collaborative interdisciplinary communication and workflow redesign led to improved utilization of MRI and minimized contrast use for suspected musculoskeletal infection. There was a high rate of procedural intervention under continued anesthesia for children with confirmed musculoskeletal infection. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Severity Adjusted Risk of Long-term Adverse Sequelae Among Children With Osteomyelitis.

BACKGROUND: The purpose of this investigation was to evaluate the risk for long-term, adverse outcomes among children with osteomyelitis. METHODS: Children with osteomyelitis were prospectively enrolled from 2012 to 2014. Care was accomplished by a multidisciplinary team according to an institutional algorithm. Data were collected to define the severity of illness during the initial hospitalization and assess short, intermediate and long-term outcomes. Clinical examination, radiographic assessment and functional outcome survey administration were performed at a minimum of 2 year follow-up. A comparison cohort analysis was performed according to initial severity of illness score of mild (0-2), moderate (3-6) and severe (7-10). RESULTS: Of 195 children enrolled, 139 (71.3%) returned for follow-up at an average of 2.4 years (range, 2.0-5.0 years). Children with severe illness were less likely to have normal radiographs (severe, 4.0%; moderate, 38.2%; mild, 53.2%, P < 0.0001), and more likely to have osteonecrosis, chondrolysis, or deformity (severe, 32.0%; moderate, 5.9%; mild, 1.3%, P < 0.0001). Functional outcome measures did not significantly differ between severity categories. By regression analysis severity of illness score, plus age less than 3 years and Methicillin-resistant Staphylococcus aureus predicted severe sequelae with an area under the curve of 0.8617 and an increasing odds ratio of 1.34 per point of increase in severity score. CONCLUSION: Long-term severe adverse outcomes among children with osteomyelitis occurred in 11 of 139 (7.9%) children and were predicted by initial severity of illness. Other risks that diminished the likelihood of complete resolution or increased the risk of severe sequelae included Methicillin-resistant Staphylcoccus aureus etiology and young age. The majority of children with osteomyelitis do not require long-term follow-up beyond the initial treatment period.

Differentiation of Deep Venous Thrombosis Among Children With or Without Osteomyelitis.

BACKGROUND: Children with osteomyelitis are at risk for deep venous thrombosis (DVT). This study evaluates the characteristics of DVT among children to differentiate between those with and without osteomyelitis. METHODS: Children with DVT of any cause were studied between 2008 and 2016. Children with DVT and osteomyelitis were compared with those with DVT without osteomyelitis. Another comparison cohort included children with osteomyelitis but without DVT. Comorbidities, severity of illness (SOI), and clinical course were compared between cohorts. RESULTS: DVT was identified in 224 children, a prevalence of 2.5 per 10,000 children. Among those with DVT, 28 (12.1%) had osteomyelitis. The DVT rate among 466 children with osteomyelitis was 6.0%. Children with osteomyelitis and DVT had greater SOI (9.1 vs. 2.7), bacteremia rate (82.1% vs. 38.4%), methicillin-resistant Staphylococcus aureus rate (89.3% vs. 21.2%), surgeries per child (2.1 vs. 0.7), and intensive care unit admission rate (67.9% vs. 5.9%) than that of children without DVT (P<0.00001). Of 196 children who had DVT without osteomyelitis, 166 (84.7%) had comorbidities including defined hypercoagulability (27 or 13.8%). Children with DVT due to osteomyelitis were without comorbidities or hypercoagulability (P<0.00001). The rate of pulmonary embolism was similar for children with DVT with or without osteomyelitis (3/28, or 10.7% vs. 18/196, or 9.2%). CONCLUSIONS: Children with DVT and osteomyelitis differ substantially from other children with DVT by the absence of comorbidities or post-thrombotic syndrome. They also differ from children with osteomyelitis without DVT by higher SOI, methicillin-resistant S. aureus rate, and occurrence of intensive care. Awareness of for the characteristics of DVT among children with osteomyelitis will reduce delay to diagnostic ultrasound and improve anticoagulation management which must be carefully coordinated given the high rate of surgery of these children. LEVEL OF EVIDENCE: Level II-prognostic, retrospective cohort comparison.

The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis.

BACKGROUND: Children with acute hematogenous osteomyelitis (AHO) have a broad spectrum of illness ranging from mild to severe. The purpose of this study is to evaluate the impact of genomic variation of Staphylococcus aureus on clinical phenotype of affected children and determine which virulence genes correlate with severity of illness. METHODS: De novo whole genome sequencing was conducted for a strain of Community Acquired Methicillin Resistant Staphylococcus aureus (CA-MRSA), using PacBio Hierarchical Genome Assembly Process (HGAP) from 6 Single Molecule Real Time (SMRT) Cells, as a reference for DNA library assembly of 71 Staphylococcus aureus isolates from children with AHO. Virulence gene annotation was based on exhaustive literature review and genomic data in NCBI for Staphylococcus aureus. Clinical phenotype was assessed using a validated severity score. Kruskal-Wallis rank sum test determined association between clinical severity and virulence gene presence using False Discovery Rate (FDR), significance <0.01. RESULTS: PacBio produced an assembled genome of 2,898,306 bp and 2054 Open Reading Frames (ORFs). Annotation confirmed 201 virulence genes. Statistical analysis of gene presence by clinical severity found 40 genes significantly associated with severity of illness (FDR ≤0.009). MRSA isolates encoded a significantly greater number of virulence genes than did MSSA (p < 0.0001). Phylogenetic analysis by maximum likelihood (PAML) demonstrated the relatedness of genomic distance to clinical phenotype. CONCLUSIONS: The Staphylococcus aureus genome contains virulence genes which are significantly associated with severity of illness in children with osteomyelitis. This study introduces a novel reference strain and detailed annotation of Staphylococcus aureus virulence genes. While this study does not address bacterial gene expression, a platform is created for future transcriptome investigations to elucidate the complex mechanisms involved in childhood osteomyelitis.

Seasonal Variation and Weather Changes Related to the Occurrence and Severity of Acute Hematogenous Osteomyelitis in Children.

BACKGROUND: Acute hematogenous osteomyelitis (AHO) demonstrates regional variability in incidence and severity. In this study, we evaluated seasonal variations of AHO and assessed the effects of weather trends on the occurrence and severity of illness in affected children. METHODS: National Weather Service data from the dates of symptom onset and of admission of children with AHO were gathered. Seasonal occurrence rates and the weather patterns were studied according to severity-of-illness category. Statistical analysis was performed with Pearson and Spearman correlations and analysis of variance. RESULTS: A total of 209 children with AHO were admitted within 21 days of symptom onset (average, 5.0 ± 3.8 days). Severity-of-illness scores ranged from 0 to 10 (average, 3.2 ± 3.2). Symptom onset occurred most commonly in summer (73 [34.9%]) or spring (54 [25.8%]). We found a significant correlation between severity of illness and minimum temperature at symptom onset during the summer season (P = .020). A significant change in average humidity (21.6%) occurred during the winter between the date of symptom onset and the date of admission for children with severe illness (P = .020). DISCUSSION: This study identified seasonal variation in the occurrence of AHO in children; summer was the most common season for occurrence. To our knowledge, this is the first detailed evaluation of weather parameters and trends in weather changes from symptom onset to admission with consideration of the effects of weather on the occurrence of infection and severity of illness.

Intramedullary Nailing Compared with Spica Casts for Isolated Femoral Fractures in Four and Five-Year-Old Children.

BACKGROUND: Flexible intramedullary nailing (IMN) is a valuable tool in the treatment of femoral fractures in school-age children, whereas spica cast immobilization has been the standard of care for younger children. We compared these treatment modalities in a group of preschool-age children (four to five years of age). METHODS: A retrospective cohort of consecutive patients, four to five years of age, with an isolated, complete femoral shaft or subtrochanteric fracture treated with intramedullary nailing or early spica cast immobilization and followed until fracture-healing were identified from two centers. Radiographic and clinical outcomes were compared between the groups. Statistical methods included chi-square and Fisher exact tests for categorical variables and the Mann-Whitney test for continuous variables. RESULTS: Two hundred and sixty-two patients followed for a mean of thirty-two weeks were identified. One hundred and four patients underwent IMN and 158 patients were treated with immediate spica cast immobilization at the surgeon's discretion. The patients who underwent IMN were older than those who underwent spica cast immobilization (mean, 5.2 versus 4.7 years; p < 0.001), were heavier (mean, 21.5 versus 18.0 kg; p < 0.001), and were more likely to have a higher-energy mechanism of injury (p = 0.025). At the time of final follow-up, there was no difference between groups with regard to the percentages of patients who had acceptable coronal angulation (≤15°), sagittal angulation (≤20°), and early fracture shortening (≤20 mm) (96.2% in the spica group versus 99.0% in the IMN group; p = 0.09). While there was no significant difference in the percentages who had an unplanned return to the operating room (3.8% in the IMN group versus 4.4% in the spica group; p > 0.99), the patients in the IMN group had more clinic visits (mean, 5.8 versus 4.0; p < 0.001) and longer follow-up (mean, forty-four versus twenty-five weeks; p < 0.001) than the patients in the spica group and a higher percentage of them underwent repeat procedures (89.4% versus 5.1%; p < 0.001), primarily for elective implant removal. CONCLUSIONS: Preschool-age children (four to five years old) with an isolated femoral fracture have similar clinical and radiographic outcomes regardless of whether they are treated with immediate spica cast immobilization or IMN.

Genomic Heterogeneity of Methicillin Resistant Staphylococcus aureus Associated with Variation in Severity of Illness among Children with Acute Hematogenous Osteomyelitis.

INTRODUCTION: The association between severity of illness of children with osteomyelitis caused by Methicillin-resistant Staphylococcus aureus (MRSA) and genomic variation of the causative organism has not been previously investigated. The purpose of this study is to assess genomic heterogeneity among MRSA isolates from children with osteomyelitis who have diverse severity of illness. MATERIALS AND METHODS: Children with osteomyelitis were prospectively studied between 2010 and 2011. Severity of illness of the affected children was determined from clinical and laboratory parameters. MRSA isolates were analyzed with next generation sequencing (NGS) and optical mapping. Sequence data was used for multi-locus sequence typing (MLST), phylogenetic analysis by maximum likelihood (PAML), and identification of virulence genes and single nucleotide polymorphisms (SNP) relative to reference strains. RESULTS: The twelve children studied demonstrated severity of illness scores ranging from 0 (mild) to 9 (severe). All isolates were USA300, ST 8, SCC mec IVa MRSA by MLST. The isolates differed from reference strains by 2 insertions (40 Kb each) and 2 deletions (10 and 25 Kb) but had no rearrangements or copy number variations. There was a higher occurrence of virulence genes among study isolates when compared to the reference strains (p = 0.0124). There were an average of 11 nonsynonymous SNPs per strain. PAML demonstrated heterogeneity of study isolates from each other and from the reference strains. DISCUSSION: Genomic heterogeneity exists among MRSA isolates causing osteomyelitis among children in a single community. These variations may play a role in the pathogenesis of variation in clinical severity among these children.

The Effect of Short Term Vitamin D Supplementation on the Inflammatory and Oxidative Mediators of Arterial Stiffness.

BACKGROUND: Vitamin D deficiency has been implicated as a potential risk factor for cardiovascular disease. The high rate of vitamin D deficiency (<30 ng/ml) exhibited by African Americans may account for some of the excess prevalence of cardiovascular morbidity and mortality in this vulnerable US population. Vitamin D supplementation may reduce the risk of cardiovascular disease by ameliorating the onset and progression of arterial stiffness, a strong predictor of cardiovascular mortality, usually assessed by pulse wave velocity and augmentation index. Very few prospective studies have evaluated the effect of vitamin D supplementation on the inflammatory and oxidative stress mediators of arterial stiffness. METHOD: In a double blind randomized placebo controlled study we evaluated the effect of a monthly dose of 100,000IU of vitamin D3 for three months on the level of serum 25(OH)D, intact parathyroid hormone (PTH), urinary isoprostane, adipocyte cytokine expression and arterial stiffness among 130 overweight and obese (BMI > 25) African Americans with elevated blood pressure (130 - 150/85 - 100 mmHg) and low serum vitamin D level (10 - 25 ng/ml). RESULTS: There was a significant increase in the serum 25(OH)D levels to a mean level of 34.5 ng/ml (SD = 7.1) with the intervention (p < 0.001). The increase in 25(OH)D levels was associated with a significant decrease in the serum level of intact PTH (p = 0.02), mean urinary isoprostane (p = 0.02) and adipocyte cytokine expression. Although the increase in the 25(OH)D levels was not associated with any significant change in the Pulse Wave Velocity (PWV) in the overall study sample, it was associated with a significant decrease in the augmentation index among the participants with the highest tertile of urinary isoprostane (p = 0.007). CONCLUSION: We concluded that vitamin D supplementation increased serum 25(OH)D levels, decreased intact PTH level and the levels of select inflammatory and oxidative stress mediators of arterial stiffness. Longer term prospective studies are warranted to evaluate the effect of high dose vitamin D supplementation on arterial stiffness.

Gene expression analysis of children with acute hematogenous osteomyelitis caused by Methicillin-resistant Staphylococcus aureus: correlation with clinical severity of illness.

Children with acute hematogenous osteomyelitis (AHO) demonstrate a broad spectrum of clinical manifestations, ranging from mild to severe. Several advances have been achieved in the study of host immune response to acute invasive Staphylococcus aureus infections through gene expression analysis. However, previous research has neither attempted to evaluate the response of children with AHO specific to Methicillin-resistant Staphylococcus aureus (MRSA) nor to correlate gene expression with clinical phenotype. Study objective was to correlate gene expression of children with AHO due to MRSA with clinical severity of illness. Whole blood samples were obtained in Tempus tubes from 12 children with osteomyelitis once cultures obtained directly from the site of infection confirmed to be positive for MRSA. Using an Illumina platform and a systems-wide modular analysis, microarray findings from ten of these children were compared to that of nine healthy (age, ethnicity and gender) matched controls and correlated with clinical severity of illness. Children with AHO from MRSA demonstrated over-expression of innate immunity with respect to neutrophil activity, coagulation, inflammatory response, and erythrocyte development. Concurrently, these children demonstrated under-expression of adaptive immunity with respect to lymphocyte activation and activity of T-cell, cytotoxic or NK cell, and B-cell lines. Three over-expressed genes, P2RX1, SORT1, and RETN, and two under-expressed genes, LOC641788 and STAT 4, were significantly correlated with severity of illness. STAT 4 showed the strongest correlation (R2 = -0.83). STAT4 downregulation could potentially explain under-expression of genes related to adaptive immunity in this cohort of patients with AHO. This study identified specific genes which correspond to disease severity during the early hospitalization of children with AHO from MRSA. Pattern recognition of this combination of genes could help to identify in the future severe clinical phenotypes before the disease is fully manifest and direct appropriate attention and resources to those children.

Implications of ethnicity for the treatment of hypertensive kidney disease, with an emphasis on African Americans.

The recognition of chronic kidney disease (CKD) as an important public health issue has fostered an increasing number of strategies to increase CKD awareness and to reduce both the prevalence and the complications of CKD. Despite these advances, end-stage renal disease (ESRD) and cardiovascular events remain the major complications of CKD. Although the ESRD epidemic is attributed in greater part to the increasing rate of diabetes, hypertension remains the second most common reported cause of ESRD and is present in approximately 90% of cases of diabetes-related ESRD. The disproportionately high prevalence of hypertension in ethnic minorities, as well as the difficulty of achieving adequate blood-pressure control in these populations, contributes substantially to the high rate of CKD progression and complications in these groups. Although the role of hypertension as a primary cause of CKD is debated, hypertension is commonly recognized as the most important CKD progression factor. Important differences have been reported in the degree and likelihood of blood-pressure response to antihypertensive medications between ethnic groups, but ethnicity seems to be less important as a determinant of clinical outcomes. In this Review we examine key ethnic variations in hypertensive CKD in terms of pathophysiology, response to antihypertensive therapy, clinical outcomes, and evidence-based recommendations for blood-pressure control, with an emphasis on African Americans.

The relative risk of cardiovascular death among racial and ethnic minorities with metabolic syndrome: data from the NHANES-II mortality follow-up.

The tendency for selected cardiovascular disease (CVD) risk factors to occur in clusters has led to the description of metabolic syndrome (MetS). The relative impact of the individual risk factor on the overall relative risk (RR) for cardiovascular death from metabolic syndrome is not well established and may differ across the different racial/ethnic groups. Using data from the National Health and Nutrition Examination Survey (NHANES II) mortality follow-up (NH2MS), we determined the prevalence and RR of cardiovascular death for individual components in the overall population and across racial and ethnic groups. The prevalence of MetS components varied significantly across gender and racial/ethnic groupings. The RR for CVD also varies for the number and different components of MetS. The adjusted RR for cardiovascular death was highest with diabetes (3.23; 95% CI: 2.70-3.88), elevated blood pressure (2.28; 95% CI: 1.94-2.67) and high triglycerides (1.63; 95% CI: 1.34-2.00). Although the RR for cardiovascular death differs significantly for some of the different components, the overall findings were similar across racial/ethnic groups. The two components that confer the highest risks for death are more prevalent in African Americans. We concluded that the RR of cardiovascular death associated with the diagnosis of MetS varies depending on the number and components used to establish the diagnosis of MetS and the racial/ethnic characteristic of the participants.

Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Results of several epidemiologic and clinical studies have suggested that there is an excess risk of hypertension and diabetes mellitus in persons with suboptimal intake of vitamin D. METHODS: We examined the association between serum levels of 25-hydroxyvitamin D (25[OH]D) and select cardiovascular disease risk factors in US adults. A secondary analysis was performed with data from the Third National Health and Nutrition Examination Survey, a national probability survey conducted by the National Center for Health Statistics between January 1, 1988, and December 31, 1994, with oversampling of persons 60 years and older, non-Hispanic black individuals, and Mexican American individuals. RESULTS: There were 7186 male and 7902 female adults 20 years and older with available data in the Third National Health and Nutrition Examination Survey. The mean 25(OH)D level in the overall sample was 30 ng/mL (75 nmol/L). The 25(OH)D levels were lower in women, elderly persons (>or=60 years), racial/ethnic minorities, and participants with obesity, hypertension, and diabetes mellitus. The adjusted prevalence of hypertension (odds ratio [OR], 1.30), diabetes mellitus (OR, 1.98), obesity (OR, 2.29), and high serum triglyceride levels (OR, 1.47) was significantly higher in the first than in the fourth quartile of serum 25(OH)D levels (P<.001 for all). CONCLUSIONS: Serum 25(OH)D levels are associated with important cardiovascular disease risk factors in US adults. Prospective studies to assess a direct benefit of cholecalciferol (vitamin D) supplementation on cardiovascular disease risk factors are warranted.

The association of poverty with the prevalence of albuminuria: data from the Third National Health and Nutrition Examination Survey (NHANES III).

BACKGROUND: Albuminuria is a major risk factor for the development and progression of chronic kidney disease (CKD) and cardiovascular disease. Socioeconomic factors also have been reported to modify CKD and cardiovascular risk factors and clinical outcomes. The extent to which poverty influences the prevalence of albuminuria, particularly among racial/ethnic minority populations, is not well established. The influence of poverty on the prevalence of albuminuria and the implication of this relationship for the racial and/or ethnic differences in the prevalence of albuminuria were examined. METHODS: We examined data from 6,850 male and 7,634 female adults from a national probability survey conducted between 1988 and 1994. RESULTS: In univariate analysis, poverty, defined as less than 200% federal poverty level (FPL), was associated with the presence of both microalbuminuria (odds ratio [OR], 1.35; 95% confidence interval, 1.22 to 1.49) and macroalbuminuria (OR, 1.78; 95% confidence interval, 1.40 to 2.26). The association of less than 200% FPL with microalbuminuria persisted in a multivariate model controlling for age, sex, race, education, obesity, hypertension, diabetes, reduced glomerular filtration rate, and medication use (OR, 1.18; 95% confidence interval, 1.05 to 1.33). FPL less than 200% was not associated with macroalbuminuria in the multivariate model. When multivariate analysis is stratified by FPL (<200% and > or =200%), differences in ORs for microalbuminuria and macroalbuminuria among racial/ethnic minority participants compared with whites were more apparent among the less affluent participants in the FPL-less-than-200% stratum. CONCLUSION: FPL less than 200% is associated with microalbuminuria, and differences in FPL levels may account for some of the observed differences in prevalence of albuminuria between racial/ethnic minority participants and their white counterparts.

The prevalence of hypovitaminosis D among US adults: data from the NHANES III.

OBJECTIVE: Several epidemiologic and mechanistic studies suggest that 25(OH) D3 levels should be maintained above 70 nmol/L for a positive effect on the health of adults. Prior studies have noted low 25(OH) D3 levels in subsets of minority populations. The objective of this study is to examine the prevalence of adequate 25(OH) D3 levels among US adults. METHOD: Using data from the third National Health and Nutrition Examination Survey (NHANES III), we evaluated serum levels of 25(OH) D3 (nmol/L) among 15,390 adult participants > or = 18 years of age. Racial/ethnic grouping was by self-identification as White, Black or African American, and Hispanic. RESULTS: The mean levels of 25(OH) D3 were lower among the female than male participants (71.1 vs 78.7; P=.003) and among the elderly (> or = 65 years of age vs 40-59 and 18-39) than young participants. White men and women (83.0 and 76.0) had higher mean levels of vitamin D than Hispanic men and women (68.3 and 56.7; P<.0001) and than Black men and women (52.2 and 45.3; P<.0001), respectively. The prevalence of both mild-moderate and severe deficiency of vitamin D is higher among women (P<.0001) and minority populations (P<.0001). However, even among White men, 34% had low vitamin D levels. CONCLUSION: Serum levels of 25(OH) D3 are below the recommended levels for a large portion of the general adult population and in most minorities. Need exists for a critical review and probable revision of current recommendations for adult vitamin D intake to maintain adequate 25(OH) D3 levels.

The impact of routine vitamin supplementation on serum levels of 25 (OH) D3 among the general adult population and patients with chronic kidney disease.

BACKGROUND: Vitamin D supplementation is recommended to maintain bone health in the general population and in particular in patients with chronic kidney disease (CKD). While the nutritional status of vitamin D is assessed by circulating levels of 25 (OH) D3, it is not routinely measured to ensure the adequacy of vitamin D supplementation. Current recommendations require the maintenance of serum levels of 25 (OH) D3 > or = 70 nmol/L. The objective of this study is to assess the effect of routine vitamin supplements on the serum levels of 25 (OH) D3 in the general population and among persons with CKD. METHOD: Using data from the third National Health and Nutrition Examination Survey (NHANES III) we assessed the adequacy of routine vitamin supplementation by assessing serum levels of 25 (OH) D3 among 15,390 adult participants, both with and without CKD. RESULTS: In the general population the participants with vitamin supplements had higher serum level of 25 (OH) D3 (79.47 vs 74.38 nmol/L) and a lower prevalence of vitamin D deficiency (39% vs 48%) than participants not taking any supplements. In the CKD subgroup, the prevalence of vitamin D deficiency was lower with supplements (49%), while greater without supplements (59%). Vitamin D deficiency was higher among women, elderly, and minorities as previously reported. In an adjusted regression model the odds of severe vitamin D deficiency (<25 nmol/L) was 1.43 (P=.0032) among CKD patients, with a trend toward higher rates among patients not taking vitamin supplements (odds ratio 1.47, P=.0557). CONCLUSION: Vitamin supplementation is associated with a lower prevalence of vitamin D deficiency and higher serum levels of 25 (OH) D3. However, the current dose of vitamin D in routine vitamin supplements is still insufficient to maintain adequate serum 25 (OH) D3 levels in a substantial portion of both the general and CKD populations. We must re-asses the dose of vitamin D in routine vitamin supplements in the United States.

Chronic kidney disease in African American and Mexican American populations.

African Americans and Mexican Americans suffer from disproportionately high rates of end-stage renal disease in comparison with whites from the United States. An improved understanding of both classic and novel chronic kidney disease risk factors among racial/ethnic minorities may help to facilitate improved prevention, screening, and early intervention strategies for all patients at risk for chronic kidney disease-not only in the United States, but on a global level. The economic implications are equally important to inform health policy recommendations and ensure cost-effective allocation of limited resources.

Management of early chronic kidney disease in indigenous populations and ethnic minorities.

The rate of treated end-stage renal disease (ESRD) continues to increase globally. The disproportionately high rate of ESRD among the many growing indigenous populations and racial/ethnic minorities in the United States highlights the need to reassess present treatment strategies to more appropriately identify and manage chronic kidney disease in diverse communities. Similar projections have been noted worldwide. This discrepancy between ESRD rates among racial and ethnic minority groups, and treatment strategies is due to several factors, many of which are modifiable. These include the individual, the health care provider/system, and limited participation in controlled clinical trials. Although it is unfortunate that this disparity continues to exist, a thoughtful and compassionate approach to addressing the role of diverse biobehavioral and sociocultural factors might be the key to effective translation of emerging scientific advances into improved clinical outcomes for all patients with chronic kidney disease.

Sodium disorders in the elderly.

Disorders of sodium imbalance are commonly encountered in clinical practice and can have a substantial impact on the prognosis of the patient. These disorders are more common in the elderly. Sodium disorders can cause serious neurologic symptoms and even death, particularly among hospitalized patients. The identification of sodium abnormalities and appropriate clinical intervention are critical for improving patient outcomes. Early recognition of hyponatremia and hypernatremia can provide a clue to an underlying disorder. In this update, we have summarized age-related homeostatic changes that impair sodium balance, medications that alter salt and water handling, and the recognition and management of sodium disorders in elderly patients.