Diabetes, hepatitis C and human immunodeficiency virus influence hypertension risk differently in cohorts of haemophilia patients, veterans and the general population.

INTRODUCTION: The reasons for the high prevalence of hypertension in persons with haemophilia (PWH) are poorly understood. AIM: To examine the roles of diabetes, Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) in the etiology of hypertension for PWH. METHODS: Retrospective cross-sectional design. Adult PWH (n = 691) were divided into two groups: (A) free of diabetes, HCV and HIV; (B) with diabetes and/or HCV positivity and/or HIV positivity. Each group was matched by race and age with random samples from the general population of the US (National Health and Nutrition Examination Surveys, NHANES) and outpatients at the Veterans Affairs Medical Center (VAMC) in San Diego. Generalized additive models (GAMs) were fitted for graphical analysis of hypertension risk over the lifespan. RESULTS: In Group A, PWH had the highest prevalence of hypertension compared to NHANES and VAMC, especially in young adults. In Group B, diabetes increased the risk of hypertension for all three cohorts (PWH, NHANES and VAMC), especially for PWH. In PWH, hypertension risk was also increased by HIV, in NHANES by HCV, and in VAMC by HCV and HIV. CONCLUSION: Diabetes conferred the greatest risk of hypertension for all three cohorts. However, curves of hypertension in relation to age revealed that diabetes, HCV and HIV modulated hypertension risk differently in PWH. PWH experienced a disproportionally high risk increase with diabetes. Therefore, haemophilia care should include screening for hypertension and diabetes at a young age.

Risk of diabetes in haemophilia patients compared to clinic and non-clinic control cohorts.

INTRODUCTION: Ageing patients with haemophilia (PWH) develop cardiovascular risk factors impacting care. Little is known about the prevalence of diabetes in PWH and its relation to other comorbidities. AIM: To examine the risk of diabetes for adult PWH compared to men from the general United States population (National Health and Nutrition Examination Surveys [NHANES]) and outpatients attending a Veterans Affairs Medical Center (VAMC) clinic. METHODS: Retrospective cross-sectional design. PWH from four haemophilia centres (n = 690) were matched with random samples from NHANES and VAMC. Diabetes (yes/no) was the outcome, while age, body mass index (BMI), race and Hepatitis C (HCV; by serology) and human immunodeficiency virus (HIV) positivity were covariates. We fitted semiparametric generalized additive models (GAMs) in order to compare diabetes risk between cohorts. RESULTS: Younger PWH were at lower risk of diabetes than NHANES or VAMC subjects irrespective of BMI. However, the risk of diabetes rose in older PWH and was closely associated with HCV. For HCV-negative subjects, the risk of diabetes was considerably lower for PWH than NHANES and VAMC subjects. The difference persisted after controlling for BMI and age, indicating that the low risk of diabetes in PWH cannot be explained by lean body mass alone. CONCLUSION: Since many ageing PWH are HCV positive and therefore at heightened risk for diabetes, it is important to incorporate diabetes screening into care algorithms in Haemophilia Treatment Centers, especially since PWH are not always followed in primary care clinics.

Physician activity during outpatient visits and subjective workload.

We describe methods for capturing and analyzing EHR use and clinical workflow of physicians during outpatient encounters and relating activity to physicians' self-reported workload. We collected temporally-resolved activity data including audio, video, EHR activity, and eye-gaze along with post-visit assessments of workload. These data are then analyzed through a combination of manual content analysis and computational techniques to temporally align streams, providing a range of process measures of EHR usage, clinical workflow, and physician-patient communication. Data was collected from primary care and specialty clinics at the Veterans Administration San Diego Healthcare System and UCSD Health, who use Electronic Health Record (EHR) platforms, CPRS and Epic, respectively. Grouping visit activity by physician, site, specialty, and patient status enables rank-ordering activity factors by their correlation to physicians' subjective work-load as captured by NASA Task Load Index survey. We developed a coding scheme that enabled us to compare timing studies between CPRS and Epic and extract patient and visit complexity profiles. We identified similar patterns of EHR use and navigation at the 2 sites despite differences in functions, user interfaces and consequent coded representations. Both sites displayed similar proportions of EHR function use and navigation, and distribution of visit length, proportion of time physicians attended to EHRs (gaze), and subjective work-load as measured by the task load survey. We found that visit activity was highly variable across individual physicians, and the observed activity metrics ranged widely as correlates to subjective workload. We discuss implications of our study for methodology, clinical workflow and EHR redesign.

A Simple Dietary Questionnaire Correlates With Formal Dietitian Evaluation and Frequently Identifies Specific Clinical Interventions in an Outpatient Gastroenterology Clinic.

BACKGROUND: The spectrum of gastroenterology-related diseases related to obesity is growing. Few clinical tools exist to aid in clinician-guided dietary counseling. GOALS: (1) Develop and validate a 1-page diet history form that would provide information on dietary factors that can contribute to gastrointestinal (GI) illness and to assess adherence to the Mediterranean diet; and (2) evaluate the form in a general GI clinic to determine its potential utility as a clinical tool. STUDY: A 1-page diet history form was developed and underwent qualitative and quantitative validation in comparison to a formal diet evaluation by a registered dietitian. The form was then evaluated in consecutive patients attending a general GI clinic, and analyzed for overall diet content, compliance with a Mediterranean diet, and presence of high-risk (red flag) dietary behaviors. RESULTS: The form was evaluated in 134 patients. In a validation cohort (n=30) the qualitative dietary components measured were highly concordant with a formal dietary interview. Total daily calorie intake correlated with formal dietary review (R=0.61), but tended to underestimate total calories due to less precision in portion size. The prospective cohort (n=104) patients had a mean body mass index of 29.8. Overall, 52.9% were obese, 50% had metabolic syndrome, and 51% had a primary GI illness directly impacted by dietary factors (gastroesophageal reflux, irritable bowel, fatty liver). Overall, 85.6% of patients documented red flag behaviors. Patients with obesity trended for more red flags than overweight or normal body mass index groups. CONCLUSION: A 1-page diet questionnaire correlated well with formal dietary assessment and identified clinically relevant dietary interventions in a high percentage of GI patients.

Methylenetetrahydrofolate reductase (MTHFR) polymorphism A1298C (Glu429Ala) predicts decline in renal function over time in the African-American Study of Kidney Disease and Hypertension (AASK) Trial and Veterans Affairs Hypertension Cohort (VAHC).

BACKGROUND: Hyperhomocysteinemia is associated with increased venous thrombosis and cardiovascular disease (CVD). Mutations in the human methylenetetrahydrofolate reductase (MTHFR) gene have been associated with increased homocysteine levels and risks of CVD in various populations including those with kidney disease. Here, we evaluated the influence of MTHFR variants on progressive loss of kidney function. METHODS: We analyzed 821 subjects with hypertensive nephrosclerosis from the longitudinal National Institute of Diabetes and Digestive and Kidney Diseases African-American Study of Kidney Disease and Hypertension (AASK) Trial to determine whether decline in glomerular filtration rate (GFR) over ∼4.2 years was predicted by common genetic variation within MTHFR at non-synonymous positions C677T (Ala222Val) and A1298C (Glu429Ala) or by MTHFR haplotypes. The effect on GFR decline was then supported by a study of 1333 subjects from the San Diego Veterans Affairs Hypertension Cohort (VAHC), followed over ∼4.5 years. Linear effect models were utilized to determine both genotype [single-nucleotide polymorphism (SNP)] and genotype (SNP)-by-time interactions. RESULTS: In AASK, the polymorphism at A1298C predicted the rate of GFR decline: A1298/A1298 major allele homozygosity resulted in a less pronounced decline of GFR, with a significant SNP-by-time interaction. An independent follow-up study in the San Diego VAHC subjects supports that A1298/A1298 homozygotes have the greatest estimated GFR throughout the study. Haplotype analysis with C677T yielded concurring results. CONCLUSION: We conclude that the MTHFR-coding polymorphism at A1298C is associated with renal decline in African-Americans with hypertensive nephrosclerosis and is supported by a veteran cohort with a primary care diagnosis of hypertension. Further investigation is needed to confirm such findings and to determine what molecular mechanism may contribute to this association.

Common charge-shift mutation Glu65Lys in K+ channel ß1-Subunit KCNMB1: pleiotropic consequences for glomerular filtration rate and progressive renal disease.

BACKGROUND: Glomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca(2+) influx, which is controlled by the regulatory ß1-subunit (KCNMB1) of large-conductance heteromeric K+ ('BK') channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline. METHODS: We explored Glu65Lys effects on GFR in three populations spanning two ethnicities and two diseases (hypertension and nephrosclerosis). GFR was either estimated (eGFR from serum creatinine) or directly measured (iothalamate clearance). RESULTS: The 65Lys variant was relatively common, occurring on ∼5-10% of chromosomes in different biogeographic ancestry groups, and 65Lys carriers exhibited higher eGFR in two primary care populations: extreme BP values in Kaiser clinics (p = 0.029, accounting for ∼0.2% of trait variance), or treated hypertensives in VA clinics (p = 0.017, accounting for ∼0.9% of trait variance). In blacks with progressive renal disease (NIDDK AASK), 65Lys carriers displayed a steeper slope in GFR chronic decline (p = 0.030, accounting for ∼0.4% of trait variance), and Glu65Lys genotype also predicted time of onset of renal failure (log rank p = 0.019). CONCLUSIONS: Common KCNMB1 gain-of-function variant Glu65Lys influences GFR, and 65Lys carriers exhibit not only elevated baseline GFR, but also more rapid GFR decline (and consequent development of renal failure) in CKD. The results suggest that profiling patients at Glu65Lys can assist in gauging renal prognosis as well as selection of rational therapy in hypertension with progressive renal disease.

Soft Tissue Tumors of Lower and Upper Limb and Various Reconstructive Options with Pedicled Flaps and Review of Literature-an Experience from Mahavir Cancer Sansthan.

This article reviews the pedicled flaps we successfully used to reconstruct the defects after resection of various tumors of upper and lower limb, as well as other commonly used flaps mentioned in literature to reconstruct the similar scenario, in terms of surgical anatomy and technique of flap harvesting.

Embolic stroke complicating Staphylococcus aureus endocarditis circumstantially linked to rectal trauma from foreign body: a first case report.

BACKGROUND: Diagnostic and therapeutic instrumentation of the lower gastrointestinal tract has been reported to result in bacteremia and endocarditis. No such case has been reported in persons with a history of rectal foreign body insertion despite its potential for greater trauma. CASE PRESENTATION: A 58-year-old male was admitted with confusion and inability to speak. His past history was notable for hospitalization to extract a retained plastic soda bottle from the rectosigmoid two years prior. On examination, he was febrile, tachycardic and hypotensive. There was an apical pansystolic murmur on cardiac examination. He had a mixed receptive and expressive aphasia, and a right hemiparesis. On rectal examination he had perianal erythema and diminished sphincter tone. Magnetic resonance imaging of the brain showed infarction of the occipital and frontal lobes. Transesophageal Echocardiography of the heart revealed vegetations on the mitral valve. All of his blood culture bottles grew methicillin sensitive Staphylococcus aureus. He was successfully treated for bacterial endocarditis with intravenous nafcillin and gentamicin. The rectum is frequently colonized by Staphylococcus aureus and trauma to its mucosa can lead to bacteremia and endocarditis with this organism. In the absence of corroborative evidence such as presented here, it is difficult to make a correlation between staphylococcal endocarditis and anorectal foreign body insertion due to patients being less than forthcoming CONCLUSION: There is a potential risk of staphylococcal bacteremia and endocarditis with rectal foreign body insertion. Further studies are needed to explore this finding. Detailed sexual history and patient counseling should be made a part of routine primary care.

Paraoxonase 1 (PON1) C/T-108 association with longitudinal mean arterial blood pressure.

BACKGROUND: Blood pressure is a complex quantitative trait with a strong genetic component. In this study, we leveraged the Veterans Affairs electronic medical record system to explore the relationship between Paraoxonase 1 (PON1)-108 C/T (rs705379) and mean arterial blood pressure (MAP). METHODS: Outpatient blood pressure data over an approximate 8-year period was collected from the Veterans Affairs Hypertensive Cohort (N = 1,302). Association between genotype and longitudinal MAP was further explored using a random effects model controlling for age, ancestry, renal function, and other determinants of blood pressure. To control for population stratification, principal component groupings based on ancestry informative markers in this dataset were included as covariates (in addition to self-identified ancestry). Data from the African American Study of Kidney Disease and Hypertension (AASK, N = 857) was used to confirm significant findings in an independent cohort. RESULTS: There was a significant interaction between PON1-108 C/T genotype and follow-up age group. At a younger age (<50 years), there was an estimated 2.53 mm Hg (95% confidence interval: 1.06, 4.00) increase in MAP with each additional C-allele. At the older age groups, there were no significant associations between PON1-108 C/T genotype and MAP. Using data from the AASK trial, the C-allele at PON1-108 C/T was significantly associated with a higher MAP (P = 0.005) but only among younger participants (<54 years). CONCLUSIONS: The PON1-108 polymorphism may be associated with MAP in an age-dependent manner.

The VA Hypertension Primary Care Longitudinal Cohort: Electronic medical records in the post-genomic era.

The Veterans Affairs Hypertension Primary Care Longitudinal Cohort (VAHC) was initiated in 2003 as a pilot study designed to link the VA electronic medical record system with individual genetic data. Between June 2003 and December 2004, 1,527 hypertensive participants were recruited. Protected health information (PHI) was extracted from the regional VA data warehouse. Differences between the clinic and mail recruits suggested that clinic recruitment resulted in an over-sampling of African Americans. A review of medical records in a random sample of study participants confirmed that the data warehouse accurately captured most selected diagnoses. Genomic DNA was acquired non-invasively from buccal cells in mouthwash; ~ 96.5 per cent of samples contained DNA suitable for genotyping, with an average DNA yield of 5.02 ± 0.12 micrograms, enough for several thousand genotypes. The coupling of detailed medical databases with genetic information has the potential to facilitate the genetic study of hypertension and other complex diseases.