Neutrophil lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality: Insights from the National Health and Nutrition Examination Survey-III

Background

Neutrophil lymphocyte ratio (NLR) has been shown to predict cardiovascular events in several studies. We sought to study if NLR predicts coronary heart disease (CHD) in a healthy US cohort and if it reclassifies the traditional Framingham risk score (FRS) model.

Methods

We performed post hoc analysis of National Health and Nutrition Examination Survey-III (1998–94) including subjects aged 30–79 years free from CHD or CHD equivalent at baseline. Primary endpoint was death from ischemic heart disease. NLR was divided into four categories: < 1.5, ≥ 1.5 to < 3.0, 3.0–4.5 and > 4.5. Statistical analyses involved multivariate Cox proportional hazards models as well as discrimination, calibration and reclassification.

Results

We included 7363 subjects with a mean follow up of 14.1 years. There were 231 (3.1%) CHD deaths, more in those with NLR > 4.5 (11%) compared to NLR < 1.5 (2.4%), p < 0.001. Adjusted hazard ratio of NLR > 4.5 was 2.68 (95% CI 1.07–6.72, p = 0.035). There was no significant improvement in C-index (0.8709 to 0.8713) or area under curve (0.8520 to 0.8531) with addition of NLR to FRS model. Model with NLR was well calibrated with Hosmer–Lemeshow chi-square of 8.57 (p = 0.38). Overall net reclassification index (NRI) was 6.6% (p = 0.003) with intermediate NRI of 10.1% (p < 0.001) and net upward reclassification of 5.6%. Absolute integrated discrimination index (IDI) was 0.003 (p = 0.039) with relative IDI of 4.3%.

Conclusions

NLR can independently predict CHD mortality in an asymptomatic general population cohort. It reclassifies intermediate risk category of FRS, with significant upward reclassification. NLR should be considered as an inflammatory biomarker of CHD.     

Accelerated alveolar bone loss in mice lacking interleukin-10: late onset

OBJECTIVE AND BACKGROUND: Interleukin-10 (IL-10) is an anti-inflammatory cytokine regulating immune responses. We have previously reported that IL-10(-/-) mice experience accelerated alveolar bone loss. The purpose of the present study was to examine the timing of the manifestation of accelerated alveolar bone loss in IL-10(-/-) mice. MATERIALS AND METHODS: Twenty-four IL-10(-/-) and 21 IL-10(+/+) age-matched male 129/SvEv mice were used. Sacrifice times occurred at 1, 3 and 9.5 months of age. Alveolar bone loss was determined morphometrically on defleshed jaws. Enzyme-linked immunosorbent assay (ELISA) was used for determination of serum concentration of type I collagen C-telopeptide, a systemic marker of bone resorption. RESULTS: Alveolar bone loss for the entire IL-10(-/-) group was significantly different than for the IL-10(+/+) group (p = 0.025). There was no significant difference in alveolar bone loss between IL-10(-/-) and IL-10(+/+) mice at 1 and 3 months of age. At 9.5 months of age, IL-10(-/-) mice exhibited 39% greater alveolar bone loss than IL-10(+/+) mice (p = 0.018). For IL-10(-/-) mice, alveolar bone loss significantly increased with age. Serum C-telopeptide levels significantly decreased with age in both groups. IL-10(-/-) mice had consistently higher C-telopeptide levels than IL-10(+/+) mice and the difference between the two groups reached statistical significance (p = 0.011) for the 9.5-month-old mice. CONCLUSIONS: These results suggest that the accelerated alveolar bone loss observed in IL-10(-/-) mice is a late-onset condition and that lack of IL-10 may have an effect on bone homeostasis.     

Addressing methodological issues in studying antidepressant onset efficacy using prespecified sensitivity analyses

Objectives: Assessing antidepressant onset efficacy presents substantial methodological challenges. Most assessments of onset efficacy are based on post hoc analyses. This article presents a case study of a prospectively designed trial to compare antidepressant onset efficacy. Experimental Design: The current study design was compared with previously published criteria for an ideal onset of action study. Prospectively defined sensitivity analyses were used to assess whether results of the present study were influenced by the assumptions and decisions necessary to implement this study. Principal Observations: The study achieved its primary objective of establishing noninferiority between SNRI and SSRI. Sensitivity analyses suggested that results from the primary analysis were not influenced by patient population, outcome measure, cut-off for defining clinically meaningful sustained improvement, or analytical method. Although not all limitations could be addressed, appropriate conclusions could be drawn. For example, the study tested only one fixed dose of each drug; hence, conclusions are limited to those dosages and cannot be extrapolated across the entire dose ranges, as would be possible in the ideal study. Conclusion: This article illustrates that prospectively designed studies (as opposed to retrospective comparisons) can be implemented and sensitivity analyses can be used to address concerns regarding assumptions and arbitrary decisions.     

Successful Hemodialysis Through Persistent Left Superior Vena Cava: a Case Report

Persistent left superior vena cava is an extremely rare venous anomaly affecting 0.5% to 2% of the general population. Persistent left superior vena cava with absent right superior vena cava, also termed as “isolated persistent left superior vena cava.” Persistent left superior vena cava, without associated cardiac anomalies, is usually innocuous. Its discovery, however, has important clinical implications. It can pose clinical difficulties with central venous access, hemodialysis catheter placement, and pacemaker implantation. We hereby present a case of persistent left superior vena cava that was incidentally encountered after the placement of a hemodialysis catheter through the left internal jugular vein. This case highlights the pertinent radiologic findings and emphasizes the importance of familiarity to such an anatomic anomaly.     

Viral hepatitis and HIV in Africa

With increasing access to antiretroviral therapy across sub-Saharan Africa, progress is finally being made in combating the devastating HIV epidemic. As HIV-infected individuals live longer, the effects of coinfection with chronic hepatitis B and C will likely become an increasingly relevant issue. Indeed, HIV adversely affects the natural history of HBV and HCV, both of which are endemic across the African continent, Issues ranging from appropriate diagnostic testing to prevention and treatment are affected by HIV coinfection, particularly in resource-limited settings. In addition, some of the more complex problems such as occult infection, immune reconstitution, and antiretroviral hepatotoxicity are becoming increasingly important considerations. In this review, we present the available data on coinfection in Africa with a major emphasis on prevalence, routes of transmission, prevention and treatment strategies.