scholarly journals Bimodal distribution and set point HBV DNA viral loads in chronic infection: retrospective analysis of cohorts from the UK and South Africa

2020 ◽  
Vol 5 ◽  
pp. 113
Author(s):  
Louise O. Downs ◽  
Sabeehah Vawda ◽  
Phillip Armand Bester ◽  
Katrina A. Lythgoe ◽  
Tingyan Wang ◽  
...  

Hepatitis B virus (HBV) viral load (VL) is used as a biomarker to assess risk of disease progression, and to determine eligibility for treatment. While there is a well recognised association between VL and the expression of the viral e-antigen protein, the distributions of VL at a population level are not well described. We here present cross-sectional, observational HBV VL data from two large population cohorts in the UK and in South Africa, demonstrating a consistent bimodal distribution. The right skewed distribution and low median viral loads are different from the left-skew and higher viraemia in seen in HIV and hepatitis C virus (HCV) cohorts in the same settings. Using longitudinal data, we present evidence for a stable ‘set-point’ VL in peripheral blood during chronic HBV infection. These results are important to underpin improved understanding of HBV biology, to inform approaches to viral sequencing, and to plan public health interventions.

2020 ◽  
Vol 5 ◽  
pp. 113
Author(s):  
Louise O. Downs ◽  
Sabeehah Vawda ◽  
Phillip Armand Bester ◽  
Katrina A. Lythgoe ◽  
Tingyan Wang ◽  
...  

Hepatitis B virus (HBV) viral load (VL) is used as a biomarker to assess risk of disease progression, and to determine eligibility for treatment. While there is a well recognised association between VL and the expression of the viral e-antigen (HBeAg) protein, the precise determinants and distribution of VL at a population level are not well described. We here report the distribution of HBV VL in two large cross-sectional population cohorts in the UK and in South Africa, demonstrating a consistent bimodal distribution. The right skewed distribution and low median viral loads are significantly different from the left-skew and higher viraemia in seen in comparable HIV and hepatitis C virus (HCV) cohorts. Using longitudinal data, we present evidence for a stable ‘set-point’ VL in peripheral blood during chronic HBV infection. These results are important to underpin improved understanding of HBV biology and to plan public health interventions.


Author(s):  
Louise O Downs ◽  
Sabeehah Vawda ◽  
Phillip Armand Bester ◽  
Katrina A Lythgoe ◽  
Tingyan Wang ◽  
...  

AbstractHepatitis B virus (HBV) DNA viral loads (VL) show wide variation between individuals with chronic hepatitis B (CHB) infection, and are used to determine treatment eligibility. There are few refined descriptions of VL distribution in CHB, and limited understanding of the biology that underpins these patterns. We set out to describe the VL distribution in independent cohorts from the UK and South Africa, to identify associated host characteristics, and to compare with VL in HIV-1 and hepatitis C (HCV) infection. We show the presence of a set-point in chronic HBV infection and report significant differences in the viral load distribution of HBV when compared to HIV and HCV.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A100-A101
Author(s):  
Shawn Barr ◽  
Kwanghyun Sohn ◽  
Gary Garcia

Abstract Introduction Heart rate variability (HRV) is commonly used to assess the activity of the autonomic nervous system (ANS). ANS function changes, reflected in HRV, result from factors including lifestyle, aging, cardiorespiratory illnesses, sleep state, and physiological stress. Despite broad interest in HRV, few studies have established normative overnight HRV values for a large population. To better understand population level HRV changes, ecologically-valid, overnight sleep SDNN (standard deviation of all normal heartbeat intervals, lower HRV is reflected by lower SDNN) values have been analyzed for a large sample of Sleep Number 360 smart bed users. Methods Overnight SDNN values were obtained over the course of 18.2M sleep sessions from 379,225 sleepers (48 ± 14.7 sessions/user). 50.9 percent of sleepers were female. The age was normally distributed with mean ± SD of 52.8 ± 12.7 years (range 21 to 84). Heartbeat intervals used to compute SDNN were extracted from a ballistocardiogram (BCG). BCG-based HRV estimation during sleep has previously been validated against ECG-based HRV with an R-square of 0.5. Results Using a Generalized Linear Model, significant cross-sectional associations with SDNN were observed for three variables of interest: age, gender, and day-of-the-week. For sleepers under 50, SDNN declined at a rate of about 2.1 ms/year, then leveled off for sleepers aged 50-65, and increased slightly thereafter. Women under 50 displayed lower, more slowly declining, SDNN values than men, but this trend reversed for sleepers over 50. Throughout the week, SDNN values followed a U-shaped (women) or L-shaped (men) pattern, where values were highest during the weekend and lowest at mid-week. Conclusion Using a smart bed to unobtrusively measure overnight SDNN values for a large set of sleepers in an ecologically valid environment, reveals significant effects of age, gender, and day of the week on overnight SDNN. Support (if any):


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S902-S902
Author(s):  
Holly Q Bennett ◽  
Fiona E Matthews ◽  
Louise Robinson ◽  
Lynne Corner ◽  
A Kingston ◽  
...  

Abstract Background: Previous research using cross-sectional data shows widening inequalities in disability-free life expectancy (DFLE) by socioeconomic status (SES) in the UK. We aimed to understand the underlying transitions of DFLE and years dependency free (DepFLE) using longitudinal data from the Cognitive Function and Ageing Studies (CFAS I and CFAS II). Methods: Two large population based studies of those aged 65+ in three centres (Newcastle, Nottingham, Cambridgeshire) interviewed at baseline in 1991 (CFAS I) and 2011 (CFAS II) with follow up two years later. Disability was measured using difficulty in activities of daily living (ADL), and dependency by time between help required for ADLs. SES was based on area deprivation categorised into study specific tertiles. Transitions between disability or dependency states and death were modelled using Interpolated Markov Chain software. Results: Between 1991 and 2011, DFLE and disabled life expectancy (DLE) at age 65 increased for men in every SES group, with men being less likely to become disabled or die, and more likely to recover, in 2011 than 1991 across SES groups. For the most disadvantaged women, DFLE was similar, and DLE increased, whilst for the remaining women DFLE increased and DLE was similar. For women probability of recovery increased and probability of death from disability decreased but probability of becoming disabled decreased only for the most advantaged. DepFLE patterns across time were similar but more pronounced. Conclusion: Preventive measures should focus on reducing the disability and dependency onset in the most disadvantaged to ensure inequalities do not widen further.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Julie A. Fitzpatrick ◽  
Nicolas Basty ◽  
Madeleine Cule ◽  
Yi Liu ◽  
Jimmy D. Bell ◽  
...  

AbstractPsoas muscle measurements are frequently used as markers of sarcopenia and predictors of health. Manually measured cross-sectional areas are most commonly used, but there is a lack of consistency regarding the position of the measurement and manual annotations are not practical for large population studies. We have developed a fully automated method to measure iliopsoas muscle volume (comprised of the psoas and iliacus muscles) using a convolutional neural network. Magnetic resonance images were obtained from the UK Biobank for 5000 participants, balanced for age, gender and BMI. Ninety manual annotations were available for model training and validation. The model showed excellent performance against out-of-sample data (average dice score coefficient of 0.9046 ± 0.0058 for six-fold cross-validation). Iliopsoas muscle volumes were successfully measured in all 5000 participants. Iliopsoas volume was greater in male compared with female subjects. There was a small but significant asymmetry between left and right iliopsoas muscle volumes. We also found that iliopsoas volume was significantly related to height, BMI and age, and that there was an acceleration in muscle volume decrease in men with age. Our method provides a robust technique for measuring iliopsoas muscle volume that can be applied to large cohorts.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0258644
Author(s):  
Wendy Grant-McAuley ◽  
Ethan Klock ◽  
Oliver Laeyendecker ◽  
Estelle Piwowar-Manning ◽  
Ethan Wilson ◽  
...  

Background Assays and multi-assay algorithms (MAAs) have been developed for population-level cross-sectional HIV incidence estimation. These algorithms use a combination of serologic and/or non-serologic biomarkers to assess the duration of infection. We evaluated the performance of four MAAs for individual-level recency assessments. Methods Samples were obtained from 220 seroconverters (infected <1 year) and 4,396 non-seroconverters (infected >1 year) enrolled in an HIV prevention trial (HPTN 071 [PopART]); 28.6% of the seroconverters and 73.4% of the non-seroconverters had HIV viral loads ≤400 copies/mL. Samples were tested with two laboratory-based assays (LAg-Avidity, JHU BioRad-Avidity) and a point-of-care assay (rapid LAg). The four MAAs included different combinations of these assays and HIV viral load. Seroconverters on antiretroviral treatment (ART) were identified using a qualitative multi-drug assay. Results The MAAs identified between 54 and 100 (25% to 46%) of the seroconverters as recently-infected. The false recent rate of the MAAs for infections >2 years duration ranged from 0.2%-1.3%. The MAAs classified different overlapping groups of individuals as recent vs. non-recent. Only 32 (15%) of the 220 seroconverters were classified as recent by all four MAAs. Viral suppression impacted the performance of the two LAg-based assays. LAg-Avidity assay values were also lower for seroconverters who were virally suppressed on ART compared to those with natural viral suppression. Conclusions The four MAAs evaluated varied in sensitivity and specificity for identifying persons infected <1 year as recently infected and classified different groups of seroconverters as recently infected. Sensitivity was low for all four MAAs. These performance issues should be considered if these methods are used for individual-level recency assessments.


2020 ◽  
Author(s):  
Abdulkarim Abdulrahman ◽  
Saad Mallah ◽  
Abdulla Ismael AlAwadhi ◽  
Simone Perna ◽  
Essam Janahi ◽  
...  

Introduction: Proactive prediction of the epidemiologic dynamics of viral diseases and outbreaks of the likes of COVID-19 has remained a difficult pursuit for scientists, public health researchers, and policymakers. It is unclear whether RT-PCR Cycle Threshold (Ct) values of COVID-19 (or any other virus) as indicator of viral load, could represent a possible predictor for underlying epidemiological changes on a population level. Objectives: To investigate whether population-wide changes in SARS-CoV-2 RT-PCR Ct values over time are associated with the daily fraction of positive COVID-19 tests. In addition, this study analyses the factors that could influence the RT-PCR Ct values. Method: A retrospective cross-sectional study was conducted on 63,879 patients from May 4, 2020 to September 30, 2020, in all COVID-19 facilities in the Kingdom of Bahrain. Data collected included number of tests and newly diagnosed cases, as well as Ct values, age, gender nationality, and symptomatic status. Results: Ct values were found to be negatively and very weakly correlated with the fraction of daily positive cases in the population r = -0.06 (CI95%: -0.06; -0.05; p=0.001). The R-squared for the regression model (adjusting for age and number of daily tests) showed an accuracy of 45.3%. Ct Values showed an association with nationality (p=0.012). After the stratification, the association between Ct values and the fraction of daily positive cases was only maintained for the female gender and Bahraini-nationality. Symptomatic presentation was significantly associated with lower Ct values (higher viral loads). Ct values do not show any correlation with age (p=0.333) or gender (p=0.522). Conclusion: We report one of the first and largest studies to investigate the epidemiological associations of Ct values with COVID-19. Ct values offer a potentially simple and widely accessible tool to predict and model epidemiological dynamics on a population level. More population studies and predictive models from global cohorts are necessary.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Head ◽  
K Fleming ◽  
C Kypridemos ◽  
P Schofield ◽  
M O'Flaherty

Abstract Background An estimated 25% of GP patients within the UK have multimorbidity, a large proportion of which is attributable to non-communicable diseases, many of them preventable. The heterogeneity of existing study methodologies limits comparisons to assess temporal trends. This study aims to use a large population-representative dataset to describe changes over time in multimorbidity incidence and prevalence. Methods We used two measures of multimorbidity a) basic: two or more chronic conditions; b) complex: at least three chronic conditions affecting at least three body systems. Chronic conditions for inclusion were discussed by a multidisciplinary team. A 1m random sample of patients registered between 2004 and 2019 at GP practices in England were drawn from the UK Clinical Practice Research Datalink. We calculated crude and age-sex standardised annual multimorbidity prevalence and incidence using standard formulae. Analyses were conducted using R v3.6.3. Participants will be linked to the 2015 Index of Multiple Deprivation to describe equity trends over time. Results Preliminary results show that age-sex standardised annual prevalence increased from 32.9% (95% CI: 32.7% - 33.1%) with basic multimorbidity and 14.9% (95% CI: 14.7%-15.0%) with complex multimorbidity in 2004 to 51.0% (95% CI: 50.8% - 51.3%) and 29.9% (95% CI: 29.7% - 30.1%) in 2019. Basic multimorbidity incidence per 10,000 person-years showed little change, however there was an increase in the incidence of complex multimorbidity from 322 (95% CI: 315- 330) to 418 (95% CI: 407 - 430). Conclusions The burden of multimorbidity has increased substantially over the last 15 years. Complex multimorbidity incidence and prevalence have increased more rapidly than for basic multimorbidity. This highlights the need for improved population-level prevention strategies to postpone and prevent the onset of long-term conditions. Next, we will assess whether there are socioeconomic differences in these temporal trends. Key messages The burden of multimorbidity increased between 2004 and 2019. The increase in incidence and prevalence of complex multimorbidity was greater than for basic multimorbidity.


2018 ◽  
Author(s):  
Robin N. Thompson ◽  
Chris Wymant ◽  
Rebecca A. Spriggs ◽  
Jayna Raghwani ◽  
Christophe Fraser ◽  
...  

ABSTRACTUnderstanding which HIV-1 variants are most likely to be transmitted is important for vaccine design and predicting virus evolution. Since most infections are founded by single variants, it has been suggested that selection at transmission has a key role in governing which variants are transmitted. We show that the composition of the viral population within the donor at the time of transmission is also important. To support this argument, we developed a probabilistic model describing HIV-1 transmission in an untreated population, and parameterised the model using both within-host next generation sequencing data and population-level epidemiological data on heterosexual transmission. The most basic HIV-1 transmission models cannot explain simultaneously the low probability of transmission and the non-negligible proportion of infections founded by multiple variants. In our model, transmission can only occur when environmental conditions are appropriate (e.g. abrasions are present in the genital tract of the potential recipient), allowing these observations to be reconciled. As well as reproducing features of transmission in real populations, our model demonstrates that, contrary to expectation, there is not a simple link between the number of viral variants and the number of viral particles founding each new infection. These quantities depend on the timing of transmission, and infections can be founded with small numbers of variants yet large numbers of particles. Including selection, or a bias towards early transmission (e.g. due to treatment) acts to enhance this conclusion. In addition, we find that infections initiated by multiple variants are most likely to have derived from donors with intermediate set-point viral loads, and not from individuals with high set-point viral loads as might be expected. We therefore emphasise the importance of considering viral diversity in donors, and the timings of transmissions, when trying to discern the complex factors governing single or multiple variant transmission.


2014 ◽  
Vol 18 (4) ◽  
pp. 610-614 ◽  
Author(s):  
Vânia Silva ◽  
Patrícia Padrão ◽  
Célia Novela ◽  
Albertino Damasceno ◽  
Olívia Pinho ◽  
...  

AbstractObjectiveThe Na content of bread is one of the most common targets of initiatives to reduce Na intake worldwide. Assessing the Na content of staple foods is of major relevance in Mozambique, given the high burden of hypertension in this setting. We aimed to estimate the Na content of white bread available in different bakeries and markets in Maputo.DesignA cross-sectional study of the Na content of white bread available for sale at twenty-five bakeries and markets in Mozambique. Flame photometry was used to quantify the Na content of the bread. The percentage of samples meeting manufacturer Na targets from South Africa and six countries from other regions, selected as benchmarks, was computed.SettingMaputo, Mozambique.SubjectsThree loaves of white bread from each selected bakery/market.ResultsThe mean Na content of bread was 450·3 mg/100 g (range: 254·9–638·3 mg/100 g), with no significant differences between bakeries and traditional markets. Most samples (88 %) did not meet the regulation in South Africa (≤380 mg/100 g). When considering the targets from other countries (range: ≤360–550 mg/100 g), the prevalence of non-compliance varied between 8 % and 92 %. There were no significant differences in the price of bread with Na content below and above the targets.ConclusionsThe content of Na in bread varies widely in Mozambique, reaching high values in a high proportion of the bakeries and markets in Maputo. Measures to regulate the Na content in bread may contribute to a reduction in Na intake and improved health at the population level.


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