Prevalence and Predictors of Pulmonary Embolism in Hospitalized Patients with Syncope.

OBJECTIVES: Approximately one in six patients hospitalized with syncope have pulmonary embolism (PE), according to the PE in Syncope Italian Trial study. Subsequent studies using administrative data have reported a PE prevalence of <3%. The aim of the study was to determine the prevalence and predictors of PE in hospitalized patients with syncope. METHODS: We retrospectively reviewed the records of patients who were hospitalized in the MedStar Washington Hospital Center between May 1, 2015 and June 30, 2017 with deep venous thrombosis, PE, and syncope. Only patients who presented to the emergency department with syncope were included in the final analysis. PE was diagnosed by either positive computed tomographic angiography or a high-probability ventilation-perfusion scan. Univariate and multivariate logistic regressions were used to assess the associations between clinical variables and the diagnosis of PE in patients with syncope. RESULTS: Of the 408 patients hospitalized with syncope (mean age, 67.5 years; 51% men [N = 208]), 25 (6%) had a diagnosis of PE. Elevated troponin levels (odds ratio 6.6, 95% confidence interval 1.9-22.9) and a dilated right ventricle on echocardiogram (odds ratio 6.9, 95% confidence interval 2.0-23.6) were independently associated with the diagnosis of PE. Age, active cancer, and history of deep venous thrombosis were not associated with the diagnosis of PE. CONCLUSIONS: The prevalence of PE in this study is approximately one-third of the reported prevalence in the PE in Syncope Italian Trial study and almost three times the value reported in administrative data-based studies. PE should be suspected in patients with syncope and elevated troponin levels or a dilated right ventricle on echocardiogram.

A Genome-Wide Association Study of Skin and Iris Pigmentation among Individuals of South Asian Ancestry.

South Asia has a complex history of migrations and is characterized by substantial pigmentary and genetic diversity. For this reason, it is an ideal region to study the genetic architecture of normal pigmentation variation. Here, we present a meta-analysis of two genome-wide association studies (GWASs) of skin pigmentation using skin reflectance (M-index) as a quantitative phenotype. The meta-analysis includes a sample of individuals of South Asian descent living in Canada (N = 348), and a sample of individuals from two caste and four tribal groups from West Maharashtra, India (N = 480). We also present the first GWAS of iris color in South Asian populations. This GWAS was based on quantitative measures of iris color obtained from high-resolution iris pictures. We identified genome-wide significant associations of variants within the well-known gene SLC24A5, including the nonsynonymous rs1426654 polymorphism, with both skin pigmentation and iris color, highlighting the pleiotropic effects of this gene on pigmentation. Variants in the HERC2 gene (e.g., rs12913832) were also associated with iris color and iris heterochromia. Our study emphasizes the usefulness of quantitative methods to study iris color variation. We also identified novel genome-wide significant associations with skin pigmentation and iris color, but we could not replicate these associations due to the lack of independent samples. It will be critical to expand the number of studies in South Asian populations in order to better understand the genetic variation driving the diversity of skin pigmentation and iris color observed in this region.

Association of genetic variants with skin pigmentation phenotype among populations of west Maharashtra, India.

OBJECTIVES: South Asians exhibit extensive variation in skin melanin index (MI) which is observed across the broader region of South Asia as well as within restricted geographic regions. However, the genetic variants associated with variation in the skin pigmentation phenotype are poorly understood in these populations. The present study examines the association between MI measures and genetic variants from 5 candidate pigmentation genes among 533 individuals representing 6 populations of West Maharashtra. METHODS: Associations between five single nucleotide polymorphisms (SNPs) known to play a role in pigmentation (rs1426654-SLC24A5, rs1042602-TYR, rs16891982-SLC45A2, rs6058017-ASIP, and rs642742-KITLG) and MI measures were tested using standard one-way analysis of variance (ANOVA) within each population. Multiple linear regression was used to test the effects of these SNPs in the full West Maharashtra sample using sex, age, and population or social group as covariates. RESULTS: rs1426654 showed significant association with MI in all six study populations (P < 0.01). Association tests using sex, age, and population as covariates showed rs1426654 and rs1042602 to be significantly (P < 0.01) associated with lighter skin pigmentation in West Maharashtra as a whole. By contrast, when social group was added as a covariate instead of population, rs1426654, rs1042602, and rs16891982 were significantly (P < 0.01) associated with lighter skin pigmentation. CONCLUSIONS: Only rs1426654 is significantly associated with MI in each individual population; however, rs1426654, rs1042602, and rs16891982 are significantly associated with pigmentation in the broader West Maharashtra region after controlling for population and social group, with rs1426654 (SLC24A5) explaining the majority of the observed variation. Am. J. Hum. Biol. 28:610-618, 2016. © 2016 Wiley Periodicals, Inc.

Skin pigmentation variation among populations of West Maharashtra, India.

OBJECTIVES: Global patterns of skin pigmentation have evolved as an adaptation to local ultraviolet radiation (UVR). Indian populations exposed to intense UVR show great variation in skin pigmentation. The UVR-based selection model cannot satisfactorily address the high prevalence of light skin among these populations. Thus, the present study examines pigmentation variation among populations of West Maharashtra and the Indian subcontinent within the context of population structure and social hierarchy. METHODS: Melanin index (MI) was measured from 555 individuals representing six endogamous populations of West Maharashtra. Skin pigmentation was assessed in terms of variation between populations and differences between and among castes and tribes. A linear regression analysis was run to assess the relationship among MI, UVR, and social hierarchy using published MI data from 13 Indian endogamous populations. RESULTS: Skin pigmentation differed significantly among populations of West Maharashtra. Significant pigmentation variation exists between castes and tribes of West Maharashtra as well as across the Indian subcontinent. We observe a significant negative relationship between social hierarchy and skin pigmentation, whereas the relationship between UVR and MI is weak. CONCLUSIONS: Our results suggest that various factors may have contributed to pigmentation diversity across the Indian subcontinent. The lack of correlation between UVR and MI suggests that natural selection may not have played a significant role in shaping pigmentation variation across the subcontinent. We discuss other possible explanations, including metabolic conservation and cultural factors such as traditional social hierarchies and strict endogamy that have led to the development of population structure.

Pharmacokinetics of single-dose primaquine in patients with chronic kidney dysfunction.

AIM: The pharmacokinetics of primaquine has not been studied in special populations. Being a basic compound, preferential binding to alpha-1 acid glycoprotein and substrate for P-glycoprotein, may predispose the drug for an altered pharmacokinetics in states of renal dysfunction. This study attempts to evaluate the pharmacokinetics of a single oral dose (15 mg) of primaquine in severely impaired renal function and end stage renal dysfunction patients compared to healthy participants. MATERIALS AND METHODS: Twelve patients each with chronic kidney disease classified as either Stage IV or V (not on dialysis) were recruited. Data from 12 healthy participants was used as concurrent controls. Serial blood collections were performed following a single dose 15 mg Primaquine orally. Primaquine concentrations were measured in the plasma using a validated HPLC method. RESULTS: The Cmax [median (range) in ng/ml] was 29.3 (14.6-104.3), 40.3 (14.8 - 78.6), and 49.8 (15 - 169.6) and the tmax [median (range) in hours] was 3.0 (1.0- 6.0), 2.0 (1.5 - 8) and 2.0 (1.0 - 4.0) for healthy and stage IV, V (not on dialysis) CKD participants, respectively. No statistically significant difference was observed in any of the pharmacokinetic parameters between healthy, stage IV and V CKD participants. CONCLUSION: Pharmacokinetics of single oral dose primaquine (15 mg) does not appear to be altered in patients with severely impaired renal function and end stage renal dysfunction. A change in dose or frequency of the drug administration perhaps may not be required in this population.

Evaluation of factors that motivate participants to consent for non-therapeutic trials in India.

BACKGROUND AND RATIONALE: Several factors that motivate individuals to participate in non-therapeutic studies have been identified. This study was conducted as limited data is available regarding these motivations from developing countries. METHODS: This was a single-centre study conducted over 4 months in which a questionnaire was administered to 102 healthy participants and 16 patient participants who had earlier taken part in non-therapeutic studies at our centre. Descriptive statistics and univariate analysis were used to analyse data. RESULTS: The most common motivation among healthy participants was financial reward (65%) followed by altruism, free medical check up, curiosity and personal health benefit. Patient participants, however, most commonly said they consented to take part in the trial as they were 'invited to participate by the treating physician' (88%). In comparison with the patient participants, healthy participants were more likely to be satisfied with the financial reward (p=0.02), and recommend participation in studies to friends or relatives (p=0.0013). CONCLUSIONS: The most common motivating factor to participate in non-therapeutic studies appears to be different for healthy participants (financial reward) and patient participants (invitation to participate by the physician). Participants also felt that adequate information and care was given to them during the trial, and that they would participate in future clinical studies, and would also recommend such studies to their friends.