Viral polymorphism in human papillomavirus types 33 and 35 and persistent and transient infection in the genital tract of women

BACKGROUND: Genetic polymorphism in human papillomavirus (HPV)-33 and -35 was investigated in 1055 sexually active women (732 human immunodeficiency virus [HIV] seropositive and 323 HIV seronegative). METHODS: Consecutive genital specimens obtained at 6-month intervals were screened for HPV-33 and -35 by use of MY09-MY11. HPV-33 and -35 isolates from 95 women were analyzed by polymerase chain reaction sequencing of the long control region (LCR), E6, and E7. RESULTS: For HPV-33, 101 (20%) of 506 nucleotides in the LCR were variable, compared with 10 (2.1%) of 483 nucleotides in E6 (P<.001) and 6 (1.9%) of 324 nucleotides in E7 (P<.001). For HPV-35, the proportion of variable nucleotide sites was similar between the LCR and both E6 (P=.54) and E7 (P=.33). The presence of a 78-base pair deletion in HPV-33 (relative risk [RR], 1.8 [95% confidence interval [CI], 1.2-2.7]) and the presence of nonsynonymous E7 variations in HPV-35 (RR, 2.6 [95% CI, 1.4-4.6]) were associated with persistence. When the data for HPV-33 and -35 were combined, infection by HPV isolates with nonsynonymous E7 variations (RR, 2.3 [95% CI, 1.6-3.4]; P=.001) and ethnicity (P=.04) were associated with persistence, whereas age (P = .14) and HIV infection/CD4 cell count status (P=.12) were not significantly associated with persistence, by logistic regression analysis. CONCLUSION: HPV-33 and -35 polymorphism was different between types and was associated with persistence of HPV infection.     

The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies

The endothelial protein C receptor (EPCR) limits thrombus formation by enhancing activation of the protein C anticoagulant pathway, and therefore may play a role in the etiology of thrombotic disorders. The rs867186 single-nucleotide polymorphism in the PROCR gene (g.6936A > G, c.4600A > G), resulting in a serine-to-glycine substitution at codon 219, has been associated with reduced activation of the protein C pathway, although its association with thrombosis risk remains unclear. The present study is a highly comprehensive systematic review and meta-analysis, including unpublished genome-wide association study results, conducted to evaluate the evidence for an association between rs867186 and 2 common thrombotic outcomes, venous thromboembolism (VTE) and myocardial infarction (MI), which are hypothesized to share some etiologic pathways. MEDLINE, EMBASE, and HuGE Navigator were searched through July 2011 to identify relevant epidemiologic studies, and data were summarized using random-effects meta-analysis. Twelve candidate genes and 13 genome-wide association studies were analyzed (11 VTE and 14 MI, including 37,415 cases and 84,406 noncases). Under the additive genetic model, the odds of VTE increased by a factor of 1.22 (95% confidence interval, 1.11-1.33, P < .001) for every additional copy of the G allele. No evidence for association with MI was observed.     

Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: a national, population-based study

Objective Patients with primary aldosteronism (PA) who are suitable for surgery should undergo adrenal computerised tomography (CT) and adrenal venous sampling (AVS). A retrospective study was performed of 100 patients with PA. We determined the optimal AVS lateralisation ratio for unilateral disease and reviewed adrenalectomy outcomes evaluating which characteristics predicted hypertension cure. Methods AVS was performed in 93 patients. Lateralisation criteria were assessed using ROC curve analysis. The outcome of adrenalectomy was reviewed in 39 patients and predictive factors for cure determined using univariate and multivariate analysis. Results Of previously published criteria, ROC curve analysis found a cortisol corrected aldosterone affected to unaffected (Aldo/Cort A:U) cut‐off of 2·0 was the best predictor of adenoma identifying 80·4% of patients. A novel ratio calculated by dividing the affected to unaffected ratio by the unaffected to peripheral ratio [(Aldo/Cort A:U)/(Aldo/Cort U:IVC)] was successful in identifying 87·0% of patients. Cure rate for blood pressure after adrenalectomy was 38·5% with improvement in 59·0%. On univariate analysis, predictors of post‐operative hypertension were increased weight, raised creatinine, left ventricular hypertrophy (LVH) and male sex. On multivariate analysis, male sex and higher pre‐operative systolic blood pressure were predictive. Conclusions Patients with PA should have CT scanning and AVS. Aldo/Cort A:U >2·0 is the most accurate of previously published ratios in predicting unilateral disease. When patients were carefully selected for surgery, 97% had cure or improvement in blood pressure control. Further confirmatory work is required on a novel ratio which was even more predictive in our series.     

Child and young adult-headed households in the context of the AIDS epidemic in Zimbabwe, 1988-2006

The emergence of child-headed households (CHH) is considered an indicator of the erosion of the traditional safety nets in sub-Saharan African countries and a direct consequence of the increasing number of orphans in the region. Using four available waves of the Zimbabwe Demographic and Health Surveys (1988, 1994, 1999, 2005/2006), we find that the proportion of households with no adults remained stable in the last years, although the number of orphans increased significantly. In fact, a large number of children living in CHH are nonorphans, which suggests that this kind of living arrangement is not always a direct consequence of parental death. Moreover, our analysis shows that children living in CHH and young adult households are less likely to have unmet basic needs than children in households headed by working-age adults and in other vulnerable households.     

Impact of donor age on long‐term outcomes after delayed graft function: 10‐year follow‐up

Delayed graft function (DGF) has a negative impact on graft survival in donation after brain death (DBD) but not for donation after cardiac death (DCD) kidneys. However, older donor age is associated with graft loss in DCD transplants. We sought to examine the interaction between donor age and DGF in DBD kidneys. This is a single‐center, retrospective review of 657 consecutive DBD recipients transplanted between 1990 and 2005. We stratified the cohort by decades of donor age and studied the association between DGF and graft failure using Cox models. The risk of graft loss associated with DGF was not significantly increased for donor age below 60 years (adjusted hazard ratio [aHR] 1.12, 1.51, and 0.90, respectively, for age <40, 41–50 and 51–60 years) but significantly increased after 60 years (aHR 2.67; P = 0.019). Analysis of death‐censored graft failure yielded similar results for donor age below 60 years and showed a substantially increased risk with donors above 60 years (aHR 6.98, P = 0.002). This analysis reveals an unexpectedly high impact of older donor age on the association between DGF and renal transplant outcomes. Further research is needed to determine the best use of kidneys from donors above 60 years old, where DGF is expected.     

Preoperative pregabalin does not reduce propofol ED50: a randomized controlled trial

Background

In many studies, gabapentinoids, such as pregabalin, have been shown to reduce preoperative anxiety. This anxiolysis is often accompanied by sedation, one of the most frequent side effects of pregabalin. We hypothesized that pregabalin taken preoperatively could reduce propofol requirements for induction of general anesthesia.

Methods

A randomized double-blind placebo-controlled trial was conducted after approval by the local ethics committee. Fifty women aged 18-40 yr, American Anesthesiologists Society physical status I and II, and scheduled to undergo elective laparoscopic gynecologic procedures were enrolled after written consent. Treatment group patients were given pregabalin 150 mg po one hour before surgery while patients in the control group received a placebo. The primary outcome was the propofol dose required to achieve a targeted anesthetic depth in 50% of the population, i.e., effective dose (ED)₅₀. The ED₅₀ was estimated using Dixon’s up-and-down methodology. The targeted anesthetic depth was defined based on predetermined entropy monitoring values (State Entropy [SE] < 50 and Response Entropy [RE]-SE < 10). As a secondary outcome, we tested if pregabalin reduced pre-induction anxiety levels which were measured on a 0-100 scale.

Results

The propofol ED₅₀ was not statistically different between the pregabalin group (mean 1.33 mg·kg^?1; 95% confidence interval [CI] 1.23 to 1.43) vs the placebo group (mean 1.37 mg·kg^?1; 95% CI 1.28 to 1.46); P = 0.19. Also, pre-induction anxiety level was not different between groups (median 31; interquartile range [IQR] [10-52] vs median 42; IQR [4-71], respectively; P = 0.41).

Conclusions

Preoperative pregabalin does not reduce propofol requirements in a population of healthy young women undergoing laparoscopic gynecologic procedures. This study failed to show a pre-induction anxiolytic effect of pregabalin in such a population. This trial was registered at www.clinicaltrials.gov (NCT01158859).