Naureen Tareen

The epidemiology of end-stage renal disease among African Americans.

Although disparities in outcomes among African Americans compared with whites with respect to cardiovascular disease, cancer, diabetes, infant mortality, and other health standards have been well-described, these disparities are most dramatic with respect to kidney diseases. End-stage renal disease (ESRD) occurs almost 4 times more commonly in African Americans than in their white counterparts. These disparate rates of kidney disease may be caused by the complex interplay of genetic, environmental, cultural, and socioeconomic factors. African Americans are particularly vulnerable to the deleterious renal effects of hypertension and may require more aggressive blood pressure control than whites to accrue benefit with respect to preservation of renal function. Diabetes, the leading cause of ESRD in the United States, is another important factor in the excess renal morbidity and mortality of African Americans because of its prevalence in this population. Other renal diseases, especially those associated with HIV/AIDS, are also much more likely to affect African Americans than other American population subgroups. A more thorough understanding of the epidemiology of renal diseases in African Americans and the cultural, social, and biological differences that underlie racial disparities in prevalence of renal disease will be essential to the design of effective public health strategies for prevention and treatment of this burdensome problem.

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.

The relationship between body mass index and pulse pressure in older adults with isolated systolic hypertension

BACKGROUND Many longitudinal studies have reported excess cardiovascular mortality among lean hypertensive subjects, suggesting that obesity may mitigate the cardiovascular risk of hypertension. Available evidence also suggests that in middle-aged and older hypertensive subjects, pulse pressure may be a better predictor of cardiovascular complications. However, there are limited data on the relationship between body mass index (BMI) and pulse pressure. METHODS Using data from the Third National Health and Nutrition Examination Survey we assessed the convergence validity of pulse pressure as a predictor of cardiovascular complications and examined the relationship between BMI and pulse pressure in 1192 older adults with isolated systolic hypertension who were not receiving blood pressure medicine. RESULTS There was a good concordance between high pulse pressure and most of the selected cardiovascular risk factors examined in this study. Pulse pressure is higher in the lean (BMI < 25) than in the overweight (BMI > or = 25; 79 mm Hg vs 74 mm Hg, P < .001) and decreases significantly from 82 mm Hg in the first BMI quintile to 76 mm Hg in the fifth BMI quintile. Pulse pressure continues to decrease with increasing BMI until the index exceeds 30.1. This negative correlation persists in a multivariate model with statistical adjustment for age, sex, diabetes mellitus, and hypercholesterolemia. CONCLUSION The inverse relation between BMI and pulse pressure observed here may help to explain previous reports of increased cardiovascular risk among lean versus obese subjects with isolated systolic hypertension.

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.

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.

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.

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.

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 surgeons 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.

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.

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.