Tenofovir: What We Have Learnt After 7.5 Million Person-Years of Use.
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ABSTRACT:
SUBMITTER: Ustianowski A
PROVIDER: S-EPMC4471058 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Low socioeconomic status and poor medication adherence are known to be associated with increased morbidity and mortality among patients with hypertension, but their combined effects have not been studied. We therefore evaluated the joint association of household income and medication adherence with death and cardiovascular disease in patients newly treated for hypertension. Methods and Results This was a nationwide cohort study using the Korean National Health Insurance database. We included 1 651 564 individuals, aged 30 to 80 years, with newly treated hypertension and no prior cardiovascular disease and followed them for 10 years. Main exposures were household income in quintiles and adherence to antihypertensive medication, estimated by medication possession ratio: good (≥0.8), moderate (0.5 to <0.8), or poor (<0.5). The primary outcomes were all-cause and cardiovascular deaths. Higher mortality risk was observed in patients with low income (adjusted hazard ratio=1.50, 99% CI=1.46-1.53; lowest versus highest quintile) and poor medication adherence (adjusted hazard ratio=1.66, 99% CI=1.63-1.68; poor versus good adherence). When compared with the highest-income and good-adherence group, adjusted hazard ratio (99% CI) of death was 1.56 (1.52-1.61) for highest-income poor-adherers, 1.46 (1.41-1.51) for lowest-income good-adherers, and 2.46 (2.38-2.54) for lowest-income poor-adherers (P for interaction <0.001). Conclusions Low socioeconomic status and poor adherence to antihypertensive medication are associated with increased mortality and cardiovascular disease risks, but patients with low income are subject to larger excess risks by nonadherence. This highlights the potential importance of promoting medication adherence for risk reduction, especially in low-income patients with hypertension.
| S-EPMC6759906 | biostudies-other
Project description:Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease affecting both adults and children. Belimumab is the only biologic approved for SLE, and the first in a class of drugs known as B-lymphocyte stimulator-specific inhibitors. The introduction of intravenous belimumab in 2011 was a major advance, being the first new therapy approved for SLE in over 50 years. As of April 2021, more than 7200 people with SLE have received belimumab in clinical studies, and it is approved in over 75 countries for the treatment of adults with SLE. A subcutaneous, self-injectable belimumab formulation was licensed in 2017 by both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Belimumab was then approved for use in children in Europe, the USA and Japan in 2019, and China and Brazil in 2020. Recently, belimumab became the first FDA-approved drug for the treatment of adults with active lupus nephritis (LN), the most-common severe manifestation of SLE.Over the past 10 years, belimumab has established its position as a disease modifier in the SLE treatment paradigms. Robust evidence from randomised clinical studies and observational, real-world studies has demonstrated the tolerability and efficacy of belimumab for reducing disease activity and the risk of new, severe SLE flares. This enables patients to taper their glucocorticoid use, which limits damage accumulation. Significantly more patients with active LN met the criteria for renal responses and were at less risk of a renal-related event or death after receiving belimumab plus standard therapy, compared with standard therapy on top of mandatory steroid reduction. Ongoing clinical studies are evaluating belimumab's effectiveness in various indications beyond SLE. Post-marketing and registry studies are gathering additional data on key areas such as pregnancy outcomes after belimumab exposure and belimumab co-administration with other biologics.
| S-EPMC8564244 | biostudies-literature
Project description:Human behaviour is thought to spread through face-to-face social networks, but it is difficult to identify social influence effects in observational studies, and it is unknown whether online social networks operate in the same way. Here we report results from a randomized controlled trial of political mobilization messages delivered to 61 million Facebook users during the 2010 US congressional elections. The results show that the messages directly influenced political self-expression, information seeking and real-world voting behaviour of millions of people. Furthermore, the messages not only influenced the users who received them but also the users' friends, and friends of friends. The effect of social transmission on real-world voting was greater than the direct effect of the messages themselves, and nearly all the transmission occurred between 'close friends' who were more likely to have a face-to-face relationship. These results suggest that strong ties are instrumental for spreading both online and real-world behaviour in human social networks.
| S-EPMC3834737 | biostudies-literature
Project description:Four heteropod lizard trackways discovered in the Hasandong Formation (Aptian-early Albian), South Korea assigned to Sauripes hadongensis, n. ichnogen., n. ichnosp., which represents the oldest lizard tracks in the world. Most tracks are pes tracks (N?=?25) that are very small, average 22.29?mm long and 12.46?mm wide. The pes tracks show "typical" lizard morphology as having curved digit imprints that progressively increase in length from digits I to IV, a smaller digit V that is separated from the other digits by a large interdigital angle. The manus track is 19.18?mm long and 19.23?mm wide, and shows a different morphology from the pes. The predominant pes tracks, the long stride length of pes, narrow trackway width, digitigrade manus and pes prints, and anteriorly oriented long axis of the fourth pedal digit indicate that these trackways were made by lizards running bipedally, suggesting that bipedality was possible early in lizard evolution.
| S-EPMC5814403 | biostudies-literature
Project description:We compared the ability of molecular biomarkers for Alzheimer disease (AD), including amyloid imaging and CSF biomarkers (A?42, tau, ptau181, tau/A?42, ptau181/A?42), to predict time to incident cognitive impairment among cognitively normal adults aged 45 to 88 years and followed for up to 7.5 years.Longitudinal data from Knight Alzheimer's Disease Research Center participants (N = 201) followed for a mean of 3.70 years (SD = 1.46 years) were used. Participants with amyloid imaging and CSF collection within 1 year of a clinical assessment indicating normal cognition were eligible. Cox proportional hazards models tested whether the individual biomarkers were related to time to incident cognitive impairment. "Expanded" models were developed using the biomarkers and participant demographic variables. The predictive values of the models were compared.Abnormal levels of all biomarkers were associated with faster time to cognitive impairment, and some participants with abnormal biomarker levels remained cognitively normal for up to 6.6 years. No differences in predictive value were found between the individual biomarkers (p > 0.074), nor did we find differences between the expanded biomarker models (p > 0.312). Each expanded model better predicted incident cognitive impairment than the model containing the biomarker alone (p < 0.005).Our results indicate that all AD biomarkers studied here predicted incident cognitive impairment, and support the hypothesis that biomarkers signal underlying AD pathology at least several years before the appearance of dementia symptoms.
| S-EPMC3719431 | biostudies-other
Project description:The Mesoproterozoic Eon [1,600-1,000 million years ago (Ma)] is emerging as a key interval in Earth history, with a unique geochemical history that might have influenced the course of biological evolution on Earth. Indeed, although this time interval is rather poorly understood, recent chromium isotope results suggest that atmospheric oxygen levels were <0.1% of present levels, sufficiently low to have inhibited the evolution of animal life. In contrast, using a different approach, we explore the distribution and enrichments of redox-sensitive trace metals in the 1,400 Ma sediments of Unit 3 of the Xiamaling Formation, North China Block. Patterns of trace metal enrichments reveal oxygenated bottom waters during deposition of the sediments, and biomarker results demonstrate the presence of green sulfur bacteria in the water column. Thus, we document an ancient oxygen minimum zone. We develop a simple, yet comprehensive, model of marine carbon-oxygen cycle dynamics to show that our geochemical results are consistent with atmospheric oxygen levels >4% of present-day levels. Therefore, in contrast to previous suggestions, we show that there was sufficient oxygen to fuel animal respiration long before the evolution of animals themselves.
| S-EPMC4763753 | biostudies-other
Project description:Background/objectiveThe most widely used adiposity index, body mass index (BMI), is not optimal to evaluate cardiovascular (CV) risk associated with overweight and obesity. We aimed to explore the association between traditional and non-traditional adiposity indices and CV mortality, and compare their discriminative ability for CV death.MethodsWe studied participants (age 19-79 years, BMI ?18.5?kg/m2) from the population-based Norwegian Nord-Trøndelag Health Study 2 (HUNT 2). Traditional indices explored were BMI, waist circumference (WC) and waist- to-hip ratio, whereas non-traditional were estimated total body fat (eTBF), which is a sex-specific fat%-index, index of central obesity (WC/height) and a body shape index (ABSI) [WC/(BMI2/3?×??height)]. Associations between the traditional and non-traditional indices and CV death, obtained from the Norwegian Cause of Death Registry, were explored by Cox proportional hazard regression, and the indices' discriminative ability by Harrell's C statistics.ResultsBaseline assessments were done from 1995 to 1997 and the population (n?=?61,016, 52% women) was observed for 17.7?±?4.2 years (until 2016), yielding 1,080,473.6 person-years of follow-up. Thirteen thousand one hundred and ninety five (21.6%) subjects died, of whom 4908 (37.2%) died from CV causes. Across genders, eTBF had the strongest association to CV death (unadjusted hazard ratios [HRs] 4th vs. 1st quartile in women and men 13.38 [95% confidence interval (CI): 11.05-16.22] and 9.32 [8.03-10.81], respectively), together with index of central obesity in women and ABSI in men. The other indices showed weaker associations, in particular BMI in men: 1.73 [1.56-1.93]. Age adjustment attenuated the associations, but the pattern remained. In concordance with this, C-statistics was C?=?0.725 [0.713-0.737] in women and 0.711 [0.701-0.721] in men for eTBF, and C?=?0.622 [0.610-0.634] in women and 0.551 [0.541-0.562] in men for BMI.ConclusioneTBF, a sex-specific total body fat index, was more strongly associated with CV death than other adiposity indices and may be a suitable clinical tool for assessment of obesity-associated CV risk.
| S-EPMC6760583 | biostudies-literature
Project description:BackgroundThe UK's National Health Service (NHS) is currently subject to unprecedented financial strain. The identification of unnecessary healthcare resource use has been suggested to reduce spending. However, there is little very research quantifying wasteful test use, despite the £3 billion annual expenditure. Geographical variation has been suggested as one metric in which to quantify inappropriate use. We set out to identify tests ordered from UK primary care that are subject to the greatest between-practice variation in their use.MethodsWe used data from 444 general practices within the Clinical Practice Research Datalink to calculate a coefficient of variation (CoV) for the ordering of 44 specific tests from UK general practices. The coefficient of variation was calculated after adjusting for differences between practice populations. We also determined the tests that had both a higher-than-average CoV and a higher-than-average rate of use.ResultsIn total, 16,496,218 tests were ordered for 4,078,091 patients over 3,311,050 person-years from April 1, 2015, to March 31, 2016. The tests subject to the greatest variation were drug monitoring 158% (95%CI 153 to 163%), urine microalbumin (52% (95%CI 49.9 to 53.2%)), pelvic CT (51% (95%CI 50 to 53%)) and Pap smear (49% (95%CI 48 to 51%). Seven tests were classified as high variability and high rate (clotting, vitamin D, urine albumin, prostate-specific antigen (PSA), bone profile, urine MCS and C-reactive protein (CRP)).ConclusionsThere are wide variations in the use of common tests, which is unlikely to be explained by clinical indications. Since £3 billion annually are spent on tests, this represents considerable variation in the use of resources and inefficient management in the NHS. Our results can be of value to policy makers, researchers, patients and clinicians as the NHS strives towards identifying overuse and underuse of tests.
| S-EPMC6300913 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-12-12 | GSE134707 | GEO
Project description:Paleontologists typically treat major episodes of extinction as single and distinct events in which a major environmental perturbation results in a synchronous evolutionary response. Alternatively, the causes of biotic change may be multifaceted and extinction may lag behind the changes ultimately responsible because of nonlinear ecological dynamics. We examined these alternatives for the major episode of Caribbean extinction 2 million years ago (Ma). Isolation of the Caribbean from the Eastern Pacific by uplift of the Panamanian Isthmus was associated with synchronous changes in Caribbean near shore environments and community composition between 4.25 and 3.45 Ma. Seasonal fluctuations in Caribbean seawater temperature decreased 3-fold, carbonate deposition increased, and there was a striking, albeit patchy, shift in dominance of benthic ecosystems from heterotrophic mollusks to mixotrophic reef corals and calcareous algae. All of these changes correspond well with a simple model of decreased upwelling and collapse in planktonic productivity associated with the final stages of the closure of the isthmian barrier. However, extinction rates of mollusks and corals did not increase until 3-2 Ma and sharply peaked between 2 and 1 Ma, even though extinction overwhelmingly affected taxa commonly associated with high productivity. This time lag suggests that something other than environmental change per se was involved in extinction that does not occur as a single event. Understanding cause and effect will require more taxonomically refined analysis of the changing abundance and distribution patterns of different ecological guilds in the 2 million years leading up to the relatively sudden peak in extinction.
| S-EPMC1838446 | biostudies-literature