Cerebrovascular risk factors and subsequent depression in older general practice patients

Background: This general practice-based case-control study tested the association between cerebrovascular risk factors (CVRFs) and the development of later-life depression by focusing on the impact of exposure duration to CVRFs and the modifying influence of age at depression onset. Methods: Cases were 286 patients aged >/=50 years with a first diagnosis of depression at age >/=50 years. Nondepressed controls (N=832) were individually matched for age, gender and practice. CVRF diagnoses (hypertension, diabetes mellitus, cardiovascular conditions) prior to depression were determined. Analyses controlled for education, somatic and nondepressive psychiatric disease. Results: No CVRF variable examined was significantly associated with subsequent depression in the total sample. An unexpected impact of age at onset of depression was observed: the odds ratio associated with having any CVRF was smaller for patients with age at onset >/=70 years than for patients with onset between ages 50-59 years (p=.002) and 60-69 years (p=.067). Subsequent analyses excluding patients with onset at age >/=70 years revealed that CVRF variables, including long-term exposure to CVRFs, significantly increased the odds of subsequent depression with onset between ages 50 and 69 years. Limitations: Reliance on GPs' records of morbidity may have resulted in bias towards underestimation in patients with depression onset at age >/=70 years. Conclusions: Our findings suggest that CVRFs play a relevant role in the development of depression with onset between ages 50 and 69 years, but no evidence was found that they contribute to the occurrence of depression with onset at age >/=70 years. Replication is warranted to exclude the possibility of bias. (aut. ref.

Cost-effectiveness of tipranavir versus comparator protease inhibitor regimens in HIV infected patients previously exposed to antiretroviral therapy in the Netherlands

<p>Abstract</p> <p>Background</p> <p>This study compares the costs and effects of a regimen with ritonavir-boosted tipranavir (TPV/r) to a physician-selected genotypically-defined standard-of-care comparator protease inhibitor regimen boosted with ritonavir (CPI/r) in HIV infected patients that were previously exposed to antiretroviral therapy in the Netherlands.</p> <p>Methods</p> <p>We compared the projected lifetime costs and effects of two theoretical groups of 1000 patients, one receiving a standard of care regimen with TPV/r as a component and the other receiving a standard of care regimen with CPI/r. A 3-stage Markov model was formulated to represent three different consecutive HAART regimens. The model uses 12 health states based on viral load and CD4+ count to simulate disease progression. The transition probabilities for the Markov model were derived from a United States cohort of treatment experienced HIV patients. Furthermore, the study design was based on 48-week data from the RESIST-2 clinical trial and local Dutch costing data. Cost and health effects were discounted at 4% and 1.5% respectively according to the Dutch guideline. The analysis was conducted from the Dutch healthcare perspective using 2006 unit cost prices.</p> <p>Results</p> <p>Our model projects an accumulated discounted cost to the Dutch healthcare system per patient receiving the TPV/r regimen of €167,200 compared to €145,400 for the CPI/r regimen. This results in an incremental cost of €21,800 per patient. The accumulated discounted effect is 7.43 life years or 6.31 quality adjusted life years (QALYs) per patient receiving TPV/r, compared to 6.91 life years or 5.80 QALYs per patient receiving CPI/r. This translates into an incremental effect of TPV/r over CPI/r of 0.52 life years gained (LYG) or 0.51 QALYs gained. The corresponding incremental cost effectiveness ratios (iCERs) are €41,600 per LYG and €42,500 per QALY.</p> <p>Conclusion</p> <p>We estimated the iCER for TPV/r compared to CPI/r at approximately €40,000 in treatment experienced HIV-1 infected patients in the Netherlands. This ratio may well be in range of what is acceptable and warrants reimbursement for new drug treatments in the Netherlands, in particular in therapeutic areas as end-stage oncology and HIV and other last-resort health-care interventions.</p

Quantitative in vivo CT arthrography of the human osteoarthritic knee to estimate cartilage sulphated glycosaminoglycan content: Correlation with ex-vivo reference standards

Objective: Recently, computed tomography arthrography (CTa) was introduced as quantitative imaging biomarker to estimate cartilage sulphated glycosaminoglycan (sGAG) content in human cadaveric knees. Our aim was to assess the correlation between in vivo CTa in human osteoarthritis (OA) knees and ex vivo reference standards for sGAG and collagen content. Design: In this prospective observational study 11 knee OA patients underwent CTa before total knee replacement (TKR). Cartilage X-ray attenuation was determined in six cartilage regions. Femoral and tibial cartilage specimens harvested during TKR were re-scanned using equilibrium partitioning of an ionic contrast agent with micro-CT (EPIC-μCT), which served as reference standard for sGAG. Next, cartilage sGAG and collagen content were determined using dimethylmethylene blue (DMMB) and hydroxyproline assays. The correlation between CTa X-ray attenuation, EPIC-μCT X-ray attenuation, sGAG content and collagen content was assessed. Results: CTa X-ray attenuation correlated well with EPIC-μCT (r = 0.76, 95% credibility interval (95%CI) 0.64 to 0.85). CTa correlated moderately with the DMMB assay (sGAG content) (r = -0.66, 95%CI -0.87 to -0.49) and to lesser extent with the hydroxyproline assay (collagen content) (r = -0.56, 95%CI -0.70 to -0.36). Conclusions: Outcomes of in vivo CTa in human OA knees correlate well with sGAG content. Outcomes of CTa also slightly correlate with cartilage collagen content. Since outcomes of CTa are mainly sGAG dependent and despite the fact that further validation using hyaline cartilage of other joints with different biochemical composition should be conducted, CTa may be suitable as quantitative imaging biomarker to estimate cartilage sGAG content in future clinical OA research

Single crystals of LnFeAsO1-xFx (Ln=La, Pr, Nd, Sm, Gd) and Ba1-xRbxFe2As2: growth, structure and superconducting properties

A review of our investigations on single crystals of LnFeAsO1-xFx (Ln=La, Pr, Nd, Sm, Gd) and Ba1-xRbxFe2As2 is presented. A high pressure technique has been applied for the growth of LnFeAsO1-xFx crystals, while Ba1-xRbxFe2As2 crystals were grown using quartz ampoule method. Single crystals were used for electrical transport, structure, magnetic torque and spectroscopic studies. Investigations of the crystal structure confirmed high structural perfection and show less than full occupation of the (O, F) position in superconducting LnFeAsO1-xFx crystals. Resistivity measurements on LnFeAsO1-xFx crystals show a significant broadening of the transition in high magnetic fields, whereas the resistive transition in Ba1 xRbxFe2As2 simply shifts to lower temperature. Critical current density for both compounds is relatively high and exceeds 2x109 A/m2 at 15 K in 7 T. The anisotropy of magnetic penetration depth, measured on LnFeAsO1-xFx crystals by torque magnetometry is temperature dependent and apparently larger than the anisotropy of the upper critical field. Ba1-xRbxFe2As2 crystals are electronically significantly less anisotropic. Point-Contact Andreev-Reflection spectroscopy indicates the existence of two energy gaps in LnFeAsO1-xFx. Scanning Tunneling Spectroscopy reveals in addition to a superconducting gap, also some feature at high energy (~20 meV).Comment: 27 pages, 19 figures, 2 tables, accepted to the special issue of the Physica C on superconducting pnictide

Heritability in genetic heart disease : the role of genetic background

Background Mutations in genes encoding ion channels or sarcomeric proteins are an important cause of hereditary cardiac disease. However, the severity of the resultant disease varies considerably even among those with an identical mutation. Such clinical variation is often thought to be explained largely by differences in genetic background or ` modifier genes'. We aimed to test the prediction that identical genetic backgrounds result in largely similar clinical expression of a cardiac disease causing mutation, by studying the clinical expression of mutations causing cardiac disease in monozygotic twins. Methods We compared first available clinical information on 46 monozygotic twin pairs and 59 control pairs that had either a hereditary cardiomyopathy or channelopathy. Results Despite limited power of this study, we found significant heritability for corrected QT interval (QTc) in long QT syndrome (LQTS). We could not detect significant heritability for structural traits, but found a significant environmental effect on thickness of the interventricular septum in hypertrophic cardiomyopathy. Conclusions Our study confirms previously found robust heritability for electrical traits like QTc in LQTS, and adds information on low or lacking heritability for structural traits in heritable cardiomyopathies. This may steer the search for genetic modifiers in heritable cardiac disease.Peer reviewe

Possible physical and thermodynamical evidence for liquid water at the Phoenix landing site

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95444/1/jgre2665.pd

Magnetization transfer imaging in ‘premanifest’ Huntington’s disease

To investigate whether magnetization transfer imaging (MTI) is a useful detector of diffuse brain abnormalities in ‘premanifest’ carriers of the Huntington’s disease (HD) gene mutation. Furthermore we examined the relations between MTI, clinical measures and CAG repeat length. Sixteen premanifest carriers of the HD gene without motor manifestation and 14 non-carriers underwent a clinical evaluation and a MRI scan. MTI analysis of whole brain, grey matter and white matter was performed producing magnetization transfer ratio (MTR) histograms. A lower peak height of the grey matter MTR histogram in carriers was significantly associated with more UHDRS motor abnormalities. Furthermore, a lower peak height of the whole brain, grey and white matter was strongly associated with a longer CAG repeat length. MTI measures themselves did not differ significantly between carriers and non-carriers. In premanifest HD mutation carriers, a lower MTR peak height, reflecting worse histological brain composition, was related to subtle motor abnormalities and higher CAG repeat length. Although we could not detect altered MTI characteristics in carriers of the HD gene mutation without clinical manifestations, we did provide evidence that the MTR peak height might reflect genetic and subclinical disease burden and may be of value in monitoring further disease progression and provide insight in clinical heterogeneity

Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG

Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity. Methodology and Principal Findings: We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16. F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation. Conclusions: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B-and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clini