Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

Maximum-likelihood scintillation detection for EM-CCD based gamma cameras

Gamma cameras based on charge-coupled devices (CCDs) coupled to continuous scintillation crystals can combine a good detection efficiency with high spatial resolutions with the aid of advanced scintillation detection algorithms. A previously developed analytical multi-scale algorithm (MSA) models the depth-dependent light distribution but does not take statistics into account. Here we present and validate a novel statistical maximum-likelihood algorithm (MLA) that combines a realistic light distribution model with an experimentally validated statistical model. The MLA was tested for an electron multiplying CCD optically coupled to CsI(Tl) scintillators of different thicknesses. For (99m)Tc imaging, the spatial resolution (for perpendicular and oblique incidence), energy resolution and signal-to-background counts ratio (SBR) obtained with the MLA were compared with those of the MSA. Compared to the MSA, the MLA improves the energy resolution by more than a factor of 1.6 and the SBR is enhanced by more than a factor of 1.3. For oblique incidence (approximately 45°), the depth-of-interaction corrected spatial resolution is improved by a factor of at least 1.1, while for perpendicular incidence the MLA resolution does not consistently differ significantly from the MSA result for all tested scintillator thicknesses. For the thickest scintillator (3 mm, interaction probability 66% at 141 keV) a spatial resolution (perpendicular incidence) of 147 μm full width at half maximum (FWHM) was obtained with an energy resolution of 35.2% FWHM. These results of the MLA were achieved without prior calibration of scintillations as is needed for many statistical scintillation detection algorithms. We conclude that the MLA significantly improves the gamma camera performance compared to the MSA.     

Quantitative multi-pinhole small-animal SPECT: uniform versus non-uniform Chang attenuation correction

Attenuation of photon flux on trajectories between the source and pinhole apertures affects the quantitative accuracy of reconstructed single-photon emission computed tomography (SPECT) images. We propose a Chang-based non-uniform attenuation correction (NUA-CT) for small-animal SPECT/CT with focusing pinhole collimation, and compare the quantitative accuracy with uniform Chang correction based on (i) body outlines extracted from x-ray CT (UA-CT) and (ii) on hand drawn body contours on the images obtained with three integrated optical cameras (UA-BC). Measurements in phantoms and rats containing known activities of isotopes were conducted for evaluation. In (125)I, (201)Tl, (99m)Tc and (111)In phantom experiments, average relative errors comparing to the gold standards measured in a dose calibrator were reduced to 5.5%, 6.8%, 4.9% and 2.8%, respectively, with NUA-CT. In animal studies, these errors were 2.1%, 3.3%, 2.0% and 2.0%, respectively. Differences in accuracy on average between results of NUA-CT, UA-CT and UA-BC were less than 2.3% in phantom studies and 3.1% in animal studies except for (125)I (3.6% and 5.1%, respectively). All methods tested provide reasonable attenuation correction and result in high quantitative accuracy. NUA-CT shows superior accuracy except for (125)I, where other factors may have more impact on the quantitative accuracy than the selected attenuation correction.     

Human longevity and 11p15.5: a study in 1321 centenarians

The 11p15.5 chromosomal region (2.8 Mb) is of particular interest as it encloses five genes (HRAS1, SIRT3, TH, INS and IGF2), the variability of which was found to be associated with life extension by association studies. Mostly important, the above genes are homologous of genes that modulate lifespan in model organisms. We scanned the area in four European sample groups for a total of 1321 centenarians and 1140 younger subjects, who shared with centenarians ethnicity and geographical origin, with a set of 239 SNPs. No significant results (P<0.05) have been found on the earlier associated loci (ie, TH, IGF2, INS and HRAS1), and this study could not confirm the earlier findings on each of those genes. A meta-analysis was carried out on the SIRT3 SNP data; a total number of 2461 samples were included, but no positive association was found except for one SNP having a significant effect (rs939915). The same meta-analysis approach has been applied to the other 229 markers, and six SNPs have been found significant for the frequent genotype (rs4073591, DEAF1-rs4073590, KRTAP5-6-rs11040489, rs4930001, TSPAN32-rs800140 and rs16928120). This experience, although unable to confirm the earlier findings of the literature, highlights all the common difficulties of such studies in human longevity. Despite the rather negative findings presented here, the results derived from unprecedented studies involving such a large number of centenarians should be disseminated, thus contributing to set up adequate strategies to disentangle complex and likely heterogeneous phenotypes.     

Associations between sex steroid hormone levels and depressive symptoms in elderly men and women: results from the Health ABC study

INTRODUCTION: Sex steroid hormone levels decline with age and in some studies this decline has been linked with depressive symptoms. This study investigates the association between total testosterone, free testosterone, and DHEAS levels with depressive symptoms in a well-functioning elderly population. METHODS: Data are from 2855 well-functioning elderly men and women, 70-79 years of age, participating in the Health, Aging, and Body Composition study. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression scale. Total testosterone, free testosterone, and DHEAS levels were assessed after an overnight fast. RESULTS: In men and women, DHEAS levels and depressive symptoms were inversely associated after adjustment for covariates (men: beta=-0.059, p=0.03, women: beta=-0.054, p=0.05). In addition, free testosterone levels in women, but not in men, were inversely associated with depressive symptoms (adjusted beta=-0.079, p=0.004). Men, but not women, in the lowest total testosterone quartile reported significantly more depressive symptoms than men in the other total testosterone quartiles (adjusted beta=-0.166, p=0.04). DISCUSSION: Our study is consistent with the idea that testosterone and DHEAS levels may play a role in mechanisms underlying depressive symptoms in old age.     

Economic costs of minor depression: a population-based study

OBJECTIVE: Although the clinical relevance of minor depression has been demonstrated in many studies, the economic costs are not well explored. In this study, we examine the economic costs of minor depression. METHOD: In a large-scale, population-based study in the Netherlands (n = 5504) the costs of minor depression were compared with the costs of major depression and dysthymia. Excess costs, i.e. the costs of a disorder over and above the costs attributable to other illnesses, were estimated with help of regression analysis. The direct medical costs, the direct non-medical costs and the indirect non-medical costs were calculated. The year 2003 was used as the reference year. RESULTS: The annual per capita excess costs of minor depression were US$ 2141 (95% CI = 753-3529) higher than the base rate costs of US$ 1023, while the costs of major depression were US$ 3313 (95% CI = 1234-5390) higher than the base rate. The costs of minor depression per 1 million inhabitants were 160 million dollars per year, which is somewhat less than the costs of major depression (192 million dollars per year). CONCLUSION: The economic costs associated with minor depression are considerable and approach those of major depression.