72 research outputs found

    Personal and Societal Health Quality Lost to Tuberculosis

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    BACKGROUND: In developed countries, tuberculosis is considered a disease with little loss of Quality-Adjusted Life Years (QALYs). Tuberculosis treatment is predominantly ambulatory and death from tuberculosis is rare. Research has shown that there are chronic pulmonary sequelae in a majority of patients who have completed treatment for pulmonary tuberculosis (PTB). This and other health effects of tuberculosis have not been considered in QALY calculations. Consequently both the burden of tuberculosis on the individual and the value of tuberculosis prevention to society are underestimated. We estimated QALYs lost to pulmonary TB patients from all known sources, and estimated health loss to prevalent TB disease. METHODOLOGY/PRINCIPAL FINDINGS: We calculated values for health during illness and treatment, pulmonary impairment after tuberculosis (PIAT), death rates, years-of-life-lost to death, and normal population health. We then compared the lifetime expected QALYs for a cohort of tuberculosis patients with that expected for comparison populations with latent tuberculosis infection and without tuberculosis infection. Persons with culture-confirmed tuberculosis accrued fewer lifetime QALYs than those without tuberculosis. Acute tuberculosis morbidity cost 0.046 QALYs (4% of total) per individual. Chronic morbidity accounted for an average of 0.96 QALYs (78% of total). Mortality accounted for 0.22 QALYs lost (18% of total). The net benefit to society of averting one case of PTB was about 1.4 QALYs. CONCLUSIONS/SIGNIFICANCE: Tuberculosis, a preventable disease, results in QALYs lost owing to illness, impairment, and death. The majority of QALYs lost from tuberculosis resulted from impairment after microbiologic cure. Successful TB prevention efforts yield more health quality than previously thought and should be given high priority by health policy makers. (Refer to Abstracto S1 for Spanish language abstract)

    Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density

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    The antiresorptive potency varies between different bisphosphonates. We investigated the effect of stopping oral bisphosphonate treatment for postmenopausal osteoporosis (ibandronate, alendronate, risedronate) on BTMs and BMD. After stopping treatment, all three groups showed an increase in BTMs and a decrease in hip BMD; however, none returned to pre-treatment baseline values. INTRODUCTION: Bisphosphonates (BPs) continue to suppress bone turnover markers (BTMs) after treatment has stopped, leading to the suggestion that a pause in treatment could be considered for low-risk patients. Indirect comparisons suggest that after cessation of treatment, the effects on bone may differ between drugs. We investigated the effects of stopping oral BP treatments for postmenopausal osteoporosis on BTMs and bone mineral density (BMD). METHODS: We studied postmenopausal osteoporotic women who had previously taken part in a 2-year randomised study of three oral BPs (ibandronate, alendronate, or risedronate). At the end of the study, women with hip BMD T-score > - 2.5 and considered clinically appropriate to discontinue treatment were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs, and BMD was measured by dual-energy X-ray absorptiometry. RESULTS: All BTMs increased after treatment withdrawal but remained below the pre-treatment baseline with less suppression of BTMs for the risedronate group compared to alendronate and ibandronate up to 48 weeks. There was no difference between the BP groups 96 weeks after stopping treatment. The change in BMD during the 96 weeks after stopping treatment was - 1.6% (95% CI - 1.9 to - 1.2, P < 0.001) for the total hip and - 0.6% (95% CI - 1.1 to - 0.2, P = 0.17) at the lumbar spine with no difference between the three BP groups (P = 0.85 and P = 0.48, respectively). CONCLUSION: For all treatment groups, there was an increase in BTMs and a decrease in hip BMD after stopping BPs for 2 years; however, none returned to pre-treatment baseline values

    Transient Reversal of Episome Silencing Precedes VP16-Dependent Transcription during Reactivation of Latent HSV-1 in Neurons

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    Herpes simplex virus type-1 (HSV-1) establishes latency in peripheral neurons, creating a permanent source of recurrent infections. The latent genome is assembled into chromatin and lytic cycle genes are silenced. Processes that orchestrate reentry into productive replication (reactivation) remain poorly understood. We have used latently infected cultures of primary superior cervical ganglion (SCG) sympathetic neurons to profile viral gene expression following a defined reactivation stimulus. Lytic genes are transcribed in two distinct phases, differing in their reliance on protein synthesis, viral DNA replication and the essential initiator protein VP16. The first phase does not require viral proteins and has the appearance of a transient, widespread de-repression of the previously silent lytic genes. This allows synthesis of viral regulatory proteins including VP16, which accumulate in the cytoplasm of the host neuron. During the second phase, VP16 and its cellular cofactor HCF-1, which is also predominantly cytoplasmic, concentrate in the nucleus where they assemble an activator complex on viral promoters. The transactivation function supplied by VP16 promotes increased viral lytic gene transcription leading to the onset of genome amplification and the production of infectious viral particles. Thus regulated localization of de novo synthesized VP16 is likely to be a critical determinant of HSV-1 reactivation in sympathetic neurons

    Stable Isotope Biogeochemistry of Seabird Guano Fertilization: Results from Growth Chamber Studies with Maize (Zea Mays)

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    Stable isotope analysis is being utilized with increasing regularity to examine a wide range of issues (diet, habitat use, migration) in ecology, geology, archaeology, and related disciplines. A crucial component to these studies is a thorough understanding of the range and causes of baseline isotopic variation, which is relatively poorly understood for nitrogen (δ(15)N). Animal excrement is known to impact plant δ(15)N values, but the effects of seabird guano have not been systematically studied from an agricultural or horticultural standpoint.This paper presents isotopic (δ(13)C and δ(15)N) and vital data for maize (Zea mays) fertilized with Peruvian seabird guano under controlled conditions. The level of (15)N enrichment in fertilized plants is very large, with δ(15)N values ranging between 25.5 and 44.7‰ depending on the tissue and amount of fertilizer applied; comparatively, control plant δ(15)N values ranged between -0.3 and 5.7‰. Intraplant and temporal variability in δ(15)N values were large, particularly for the guano-fertilized plants, which can be attributed to changes in the availability of guano-derived N over time, and the reliance of stored vs. absorbed N. Plant δ(13)C values were not significantly impacted by guano fertilization. High concentrations of seabird guano inhibited maize germination and maize growth. Moreover, high levels of seabird guano greatly impacted the N metabolism of the plants, resulting in significantly higher tissue N content, particularly in the stalk.The results presented in this study demonstrate the very large impact of seabird guano on maize δ(15)N values. The use of seabird guano as a fertilizer can thus be traced using stable isotope analysis in food chemistry applications (certification of organic inputs). Furthermore, the fertilization of maize with seabird guano creates an isotopic signature very similar to a high-trophic level marine resource, which must be considered when interpreting isotopic data from archaeological material

    Gravitational Wave Detection by Interferometry (Ground and Space)

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    Significant progress has been made in recent years on the development of gravitational wave detectors. Sources such as coalescing compact binary systems, neutron stars in low-mass X-ray binaries, stellar collapses and pulsars are all possible candidates for detection. The most promising design of gravitational wave detector uses test masses a long distance apart and freely suspended as pendulums on Earth or in drag-free craft in space. The main theme of this review is a discussion of the mechanical and optical principles used in the various long baseline systems in operation around the world - LIGO (USA), Virgo (Italy/France), TAMA300 and LCGT (Japan), and GEO600 (Germany/U.K.) - and in LISA, a proposed space-borne interferometer. A review of recent science runs from the current generation of ground-based detectors will be discussed, in addition to highlighting the astrophysical results gained thus far. Looking to the future, the major upgrades to LIGO (Advanced LIGO), Virgo (Advanced Virgo), LCGT and GEO600 (GEO-HF) will be completed over the coming years, which will create a network of detectors with significantly improved sensitivity required to detect gravitational waves. Beyond this, the concept and design of possible future "third generation" gravitational wave detectors, such as the Einstein Telescope (ET), will be discussed.Comment: Published in Living Reviews in Relativit

    Sofosbuvir/velpatasvir for 12 weeks results in high SVR12 rates with a favorable safety profile in asian patients: an integrated subgroup analysis of the ASTRAL-1, ASTRAL-2, and ASTRAL-3 studies

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    Plenary Presentation 01 - paper no. PL002Background: Sofosbuvir (SOF)/velpatasvir (VEL) 400/100 mg for 12 weeks resulted in an overall 98% sustained virologic response rates 12 week after treatment completion (SVR12) with a favorable safety profile in genotype (GT) 1–6 HCV-infected patients in the SOF/VEL phase 3 clinical development program conducted in North America, Western Europe, Australia, New Zealand, and Hong Kong. Here we compare the safety and efficacy of SOF/VEL in Asian versus non-Asian patients enrolled and treated in these 3 Phase 3 SOF/VEL registrational trials. Methods: An integrated analysis of ASTRAL-1 (SOF/VEL for 12 weeks versus placebo in patients with GT1, 2, and 4–6 HCV infections), ASTRAL-2 (SOF/VEL for 12 weeks versus SOF + ribavirin for 12 weeks in patients with GT2 HCV infections), and ASTRAL-3 (SOF/VEL for 12 weeks versus SOF + ribavirin for 24 weeks in patients with GT3 HCV infections) was performed. Selfreported race collected at baseline was used to categorize patients as either Asian or non-Asian, and patients who did not disclose race were excluded. Efficacy was determined by the proportion of patients achieving SVR12. Safety was assessed by ascertainment of adverse events (AEs) and monitoring of laboratory parameters. Result: In ASTRAL-1, 2, and 3, there were 86 (2% GT1a, 14% GT1b, 7% GT2, 27% GT3, 4% GT4, and 47% GT6) Asian and 944 (22% GT1a, 11% GT1b, 24% GT2, 27% GT3, 12% GT4, 4% GT5, and 1% GT6) non-Asian patients who received SOF/VEL for 12 weeks. Asians tended to be younger [mean (SD) age 47 (12.1) versus 54 (10.7) years] with lower BMIs [24.9 (4.1) versus 26.9 (5.1) kg/m2 ], relative to non-Asian patients. The proportions of patients with compensated cirrhosis were 22 and 21%, treatment experience were 16 and 29%, and IL28B CC genotype were 65 and 30% for Asian and non-Asian patients, respectively. SVR12 was achieved in 99% of Asian and 98% of non-Asian patients (Table 1). The one Asian patient failing to achieve SVR12 had GT3 infection and was lost to follow-up. Of note, 100% of the seven Asian patients with GT3 infection and cirrhosis achieved SVR12 compared to 90% (66/73) of non-Asian patients. SOF/VEL was generally safe and well tolerated among Asian patients who had no discontinuations due to AEs, and fewer overall AEs [54 (63%)] and Grade 3 or above AEs [2 (2%)] compared with non-Asian patients [764 (81%) and 30 (3%), respectively]. The four serious AEs in Asian patients were all considered unrelated to treatment. Asians had 1 or more Grade 3 or above laboratory abnormality less frequently than non-Asians [5 (6%) versus 72 (8%)]. Conclusion: SOF/VEL was highly effective in Asian patients with an overall SVR12 rate of 99% and no Asian patients experiencing virologic failure. SOF/VEL was well tolerated among Asian patients with no one prematurely discontinuing treatment due to AEs
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