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:The number of new cases of cancer is increasing each year, and rates of diabetes mellitus are also increasing dramatically over time. It is not an unusual occurrence for an individual to have both cancer and diabetes at the same time, given they are both individually common, and that one condition can increase the risk of the other. In this manuscript, we use national-level diabetes (Virtual Diabetes Register) and cancer (New Zealand Cancer Registry) data on nearly five million individuals over 44 million person-years of follow-up to examine the occurrence of cancer amongst a national prevalent cohort of patients with diabetes. We completed this analysis separately by cancer for the 24 most commonly diagnosed cancers in Aotearoa New Zealand, and then compared the occurrence of cancer among those with diabetes to those without diabetes. We found that the rate of cancer was highest amongst those with diabetes for 21 of the 24 most common cancers diagnosed over our study period, with excess risk among those with diabetes ranging between 11% (non-Hodgkin’s lymphoma) and 236% (liver cancer). The cancers with the greatest difference in incidence between those with diabetes and those without diabetes tended to be within the endocrine or gastrointestinal system, and/or had a strong relationship with obesity. However, in an absolute sense, due to the volume of breast, colorectal and lung cancers, prevention of the more modest excess cancer risk among those with diabetes (16%, 22% and 48%, respectively) would lead to a substantial overall reduction in the total burden of cancer in the population. Our findings reinforce the fact that diabetes prevention activities are also cancer prevention activities, and must therefore be prioritised and resourced in tandem.
| S-EPMC9704677 | biostudies-literature
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:BackgroundThe prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy.MethodsFor this observational study, we conducted a combined analysis of individual-participant data from 19 high-income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961-2007, median latest follow-up years 1980-2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23·1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU.FindingsFor participants with diabetes, we observed a linear dose-response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2·69 (95% CI 2·43-2·97) when diagnosed at 30-39 years, 2·26 (2·08-2·45) at 40-49 years, 1·84 (1·72-1·97) at 50-59 years, 1·57 (1·47-1·67) at 60-69 years, and 1·39 (1·29-1·51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier when diagnosed aged 50 years than an individual without diabetes. Using EU death rates, the corresponding estimates were 13, 9, or 5 years earlier.InterpretationEvery decade of earlier diagnosis of diabetes was associated with about 3-4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes.FundingBritish Heart Foundation, Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.
| S-EPMC7615299 | 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: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: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:Preeclampsia is associated with a substantially increased long-term risk for cardiovascular, cerebrovascular and renal disease. It remains unclear whether and to which extent specialized medical postpartum care is sought. We aimed to assess current utilization of postpartum primary and specialized care and medication prescription behavior in women who experienced preeclampsia. This retrospective observational study based on statutory claims data included 193,205 women with 258,344 singleton live births between 2010 and 2017 in Southern Germany. Postpartum care was evaluated by analyzing and comparing the frequency of medical consultations in primary and specialized care and prescriptions for antihypertensive medication among women with and without preeclampsia up to 7.5 years after delivery. Gynecologists and general practitioners were the main health care providers for all women. Although specialized postpartum care was sought by more women after preeclampsia, the effect size indices revealed no considerable association between a history of preeclampsia and the utilization of specialized outpatient aftercare (e.g. 2% vs. 0.6% of patients with and without preeclampsia who consulted a nephrologist during the first year postpartum, r = 0.042). Preeclampsia was associated with an increased risk to take any antihypertensive medication after delivery (HR 2.7 [2.6; 2.8]). Postpartum referral to specialized outpatient care and quarterly prescriptions of antihypertensives following preeclampsia failed to match the early and rapidly increased incidence and risk of hypertension. These data highlight the missed opportunity to implement a reasonable follow-up strategy and prevention management in order to achieve long-term clinical benefits.
| S-EPMC9732277 | biostudies-literature
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