Risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) infection: a systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is a leading cause of death in individuals with chronic hepatitis B virus (HBV) infection. It is uncertain how the presence of other metabolic factors and comorbidities influences HCC risk in HBV. Therefore, we performed a systematic literature review and meta-analysis to seek evidence for significant associations. MEDLINE, EMBASE and Web of Science databases were searched from 1 January 2000 to 24 June 2020 for studies investigating associations of metabolic factors and comorbidities with HCC risk in individuals with chronic HBV infection, written in English. We extracted data for meta-analysis and generated pooled effect estimates from a fixed-effects model. Pooled estimates from a random-effects model were also generated if significant heterogeneity was present. We identified 40 observational studies reporting on associations of diabetes mellitus (DM), hypertension, dyslipidaemia and obesity with HCC risk. Only DM had a sufficient number of studies for meta-analysis. DM was associated with >25% increase in hazards of HCC (fixed-effects hazards ratio [HR] 1.26, 95% confidence interval (CI) 1.20-1.32, random-effects HR 1.36, 95% CI 1.23-1.49). This association was attenuated towards the null in a sensitivity analysis restricted to studies adjusted for metformin use. In conclusion, in adults with chronic HBV infection, DM is a significant risk factor for HCC, but further investigation of the influence of antidiabetic drug use and glycaemic control on this association is needed. Enhanced screening of individuals with HBV and diabetes may be warranted.

Vertebral Fractures in Ireland: A Sub-analysis of the DXA HIP Project.

Osteoporosis is an important global health problem resulting in fragility fractures. The vertebrae are the commonest site of fracture resulting in extreme illness burden, and having the highest associated mortality. International studies show that vertebral fractures (VF) increase in prevalence with age, similarly in men and women, but differ across different regions of the world. Ireland has one of the highest rates of hip fracture in the world but data on vertebral fractures are limited. In this study we examined the prevalence of VF and associated major risk factors, using a sample of subjects who underwent vertebral fracture assessment (VFA) performed on 2 dual-energy X-ray absorptiometry (DXA) machines. A total of 1296 subjects aged 40 years and older had a valid VFA report and DXA information available, including 254 men and 1042 women. Subjects had a mean age of 70 years, 805 (62%) had prior fractures, mean spine T-score was - 1.4 and mean total hip T-scores was - 1.2, while mean FRAX scores were 15.4% and 4.8% for major osteoporotic fracture and hip fracture, respectively. Although 95 (7%) had a known VF prior to scanning, 283 (22%) patients had at least 1 VF on their scan: 161 had 1, 61 had 2, and 61 had 3 or more. The prevalence of VF increased with age from 11.5% in those aged 40-49 years to > 33% among those aged ≥ 80 years. Both men and women with VF had significantly lower BMD at each measured site, and significantly higher FRAX scores, P < 0.01. These data suggest VF are common in high risk populations, particularly older men and women with low BMD, previous fractures, and at high risk of fracture. Urgent attention is needed to examine effective ways to identify those at risk and to reduce the burden of VF.

Hepatitis B virus (HBV) viral load, liver and renal function in adults treated with tenofovir disoproxil fumarate (TDF) vs. untreated: a retrospective longitudinal UK cohort study.

BACKGROUND: Current clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients. METHODS: We studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively. RESULTS: We included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years, p = 0.004) and more likely to be male (63% vs. 47%, p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group. CONCLUSIONS: Risk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population.

Machine Learning Can Improve Clinical Detection of Low BMD: The DXA-HIP Study.

BACKGROUND: Identification of those at high risk before a fracture occurs is an essential part of osteoporosis management. This topic remains a significant challenge for researchers in the field, and clinicians worldwide. Although many algorithms have been developed to either identify those with a diagnosis of osteoporosis or predict their risk of fracture, concern remains regarding their accuracy and application. Scientific advances including machine learning methods are rapidly gaining appreciation as alternative techniques to develop or enhance risk assessment and current practice. Recent evidence suggests that these methods could play an important role in the assessment of osteoporosis and fracture risk. METHODS: Data used for this study included Dual-energy X-ray Absorptiometry (DXA) bone mineral density and T-scores, and multiple clinical variables drawn from a convenience cohort of adult patients scanned on one of 4 DXA machines across three hospitals in the West of Ireland between January 2000 and November 2018 (the DXA-Heath Informatics Prediction Cohort). The dataset was cleaned, validated and anonymized, and then split into an exploratory group (80%) and a development group (20%) using the stratified sampling method. We first established the validity of a simple tool, the Osteoporosis Self-assessment Tool Index (OSTi) to identify those classified as osteoporotic by the modified International Society for Clinical Densitometry DXA criteria. We then compared these results to seven machine learning techniques (MLTs): CatBoost, eXtreme Gradient Boosting, Neural network, Bagged flexible discriminant analysis, Random forest, Logistic regression and Support vector machine to enhance the discrimination of those classified as osteoporotic or not. The performance of each prediction model was measured by calculating the area under the curve (AUC) with 95% confidence interval (CI), and was compared against the OSTi. RESULTS: A cohort of 13,577 adults aged ≥40 yr at the age of their first scan was identified including 11,594 women and 1983 men. 2102 (18.13%) females and 356 (17.95%) males were identified with osteoporosis based on their lowest T-score. The OSTi performed well in our cohort in both men (AUC 0.723, 95% CI 0.659-0.788) and women (AUC 0.810, 95% CI 0.787-0.833). Four MLTs improved discrimination in both men and women, though the incremental benefit was small. eXtreme Gradient Boosting showed the most promising results: +4.5% (AUC 0.768, 95% CI 0.706-0.829) for men and +2.3% (AUC 0.833, 95% CI 0.812-0.853) for women. Similarly MLTs outperformed OSTi in sensitivity analyses-which excluded those subjects taking osteoporosis medications-though the absolute improvements differed. CONCLUSION: The OSTi retains an important role in identifying older men and women most likely to have osteoporosis by bone mineral density classification. MLTs could improve DXA detection of osteoporosis classification in older men and women. Further exploration of MLTs is warranted in other populations, and with additional data.

Utility of Osteoporosis Self-Assessment Tool as a Screening Tool for Osteoporosis in Irish Men and Women: Results of the DXA-HIP Project.

Many algorithms have been developed and publicised over the past 2 decades for identifying those most likely to have osteoporosis or low BMD, or at increased risk of fragility fracture. The Osteoporosis Self-assessment Tool index (OSTi) is one of the oldest, simplest, and widely used for identifying men and women with low BMD or osteoporosis. OSTi has been validated in many cohorts worldwide but large studies with robust analyses evaluating this or other algorithms in adult populations residing in the Republic of Ireland are lacking, where waiting times for public DXA facilities are long. In this study we evaluated the validity of OSTi in men and women drawn from a sampling frame of more than 36,000 patients scanned at one of 3 centres in the West of Ireland. 18,670 men and women aged 40 years and older had a baseline scan of the lumbar spine femoral neck and total hip available for analysis. 15,964 (86%) were female, 5,343 (29%) had no major clinical risk factors other than age, while 5,093 (27%) had a prior fracture. Approximately 2/3 had a T-score ≤-1.0 at one or more skeletal sites and 1/3 had a T-score ≤-1.0 at all 3 skeletal sites, while 1 in 5 had a DXA T-score ≤-2.5 at one or more skeletal sites and 5% had a T-score ≤-2.5 at all 3 sites. OSTi generally performed well in our population with area under the curve (AUC) values ranging from 0.581 to 0.881 in men and 0.701 to 0.911 in women. The performance of OSTi appeared robust across multiple sub-group analyses. AUC values were greater for women, proximal femur sites, those without prior fractures and those not taking osteoporosis medication. Optimal OSTi cut-points were '2' for men and '0' for women in our study population. OSTi is a simple and effective tool to aid identification of Irish men and women with low BMD or osteoporosis. Use of OSTi could improve the effectiveness of DXA screening programmes for older adults in Ireland.

Longitudinal changes of liver function and hepatitis B reactivation in COVID-19 patients with pre-existing chronic hepatitis B virus infection.

AIM: With the current coronavirus disease (COVID-19) pandemic and high endemic levels of chronic hepatitis B virus (HBV) infection worldwide, it is urgent to investigate liver function changes of COVID-19 patients with chronic HBV infection, and how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in turn affects the course of chronic HBV infection. METHOD: We undertook a retrospective study based on 347 COVID-19 patients (21 vs. 326 with vs. without chronic HBV infection). With the propensity score matching (PSM) method, we yielded 20 and 51 matched patients for the HBV group and the non-HBV group, respectively. RESULTS: At the end of follow-up, all of these 71 patients achieved SARS-CoV-2 clearance (P = 0.1). During the follow-up, 30% versus 31.4% in the HBV group versus non-HBV group progressed to severe COVID-19 (P = 0.97). After PSM, the longitudinal changes of median values for liver biochemistries were not significantly different between the two groups. In the HBV group versus non-HBV group, 35% (7/20) versus 37.25% (19/51) (P = 0.86) had abnormal alanine aminotransferase at least once during hospitalization, 30% (6/20) versus 31.37% (16/51) had abnormal aspartate aminotransferase (P = 0.91), 40% (8/20) versus 37.25% (19/51) had abnormal γ-glutamyltransferase (P = 0.83), and 45% (9/20) versus 39.22% (20/51) had abnormal total bilirubin levels (P = 0.91). Moreover, three patients in the HBV group had hepatitis B reactivation. CONCLUSIONS: Liver dysfunction presented in COVID-19 patients with/without chronic HBV. Moreover, those COVID-19 patients co-infected with chronic HBV could have a risk of hepatitis B reactivation. It is necessary to monitor liver function of COVID-19 patients, as well as HBV-DNA levels for those co-infected with HBV during the whole disease course.

Personal values and people's attitudes toward older adults.

BACKGROUND: We examine the relationship between people's personal values and their attitudes toward older adults. In addition to the two conventionally-used measures of personal values (agency subdimension and communion subdimension), we distinguish across 10 different value types and explore how each impacts attitude. METHODS: We use data from the World Values Survey for three aging Asian societies, namely Japan (N = 2448), Singapore (N = 1972), and Hong Kong PRC (N = 1000). For each sample, we perform regression-based analyses to assess the relative importance of the 10 value types in explaining people's attitudes towards older adults. Results are then compared against regressions based on the two aggregate value measures. RESULTS: In all three economies, the agency subdimension was a more consistent predictor of unfavorable attitudes toward older adults, as compared to the communion subdimension. Our disaggregated analysis reveals two additional insights. First, the positive association between agentic values and attitudes was driven predominantly by the power (wealth) and stimulation (excitement) value types. Second, the lack of association between the communion subdimension and attitudes must be interpreted with caution since certain value types within this subdimension may act in opposite directions causing effects to cancel each other out at the aggregate level. CONCLUSIONS: Disaggregating personal value types provides greater prognostic power than the two aggregate measures, as well as insights on ways to improve people's attitudes toward older adults. Interventions aimed at reducing ageist attitudes in aging societies can target individuals with agentic traits by emphasizing notions of power (e.g., older adults' economic success) and stimulation (e.g., positive images of older adults learning new things).

Ireland DXA-FRAX may differ significantly and substantially to Web-FRAX.

Appropriate use of FRAX reduces the number of people requiring DXA scans, while contemporaneously determining those most at risk. We compared the results of FRAX with and without inclusion of BMD. It suggests clinicians to carefully consider the importance of BMD inclusion in fracture risk estimation or interpretation in individual patients. PURPOSE: FRAX is a widely accepted tool to estimate the 10-year risk of hip and major osteoporotic fracture in adults. Prior calibration studies suggest this works similarly with or without the inclusion of bone mineral density (BMD). The purpose of the study is to compare within-subject differences between FRAX estimations derived using DXA and Web software with and without the inclusion of BMD. METHOD: A convenience cohort was used for this cross-sectional study, consisting of 1254 men and women aged between 40 and 90 years who had a DXA scan and complete validated data available for analysis. FRAX 10-year estimations for hip and major osteoporotic fracture were calculated using DXA software (DXA-FRAX) and the Web tool (Web-FRAX), with and without BMD. Agreements between estimates within each individual subject were examined using Bland-Altman plots. We performed exploratory analyses of the characteristics of those with very discordant results. RESULTS: Overall median DXA-FRAX and Web-FRAX 10-year hip and major osteoporotic fracture risk estimations which include BMD are very similar: 2.9% vs. 2.8% and 11.0% vs. 11% respectively. However, both are significantly lower than those obtained without BMD: 4.9% and 14% respectively, P < 0.001. Within-subject differences between hip fracture estimates with and without BMD were < 3% in 57% of cases, between 3 and 6% in 19% of cases, and > 6% in 24% of cases, while for major osteoporotic fractures such differences are < 10% in 82% of cases, between 10 and 20% in 15% of cases, and > 20% in 3% of cases. CONCLUSIONS: Although there is excellent agreement between the Web-FRAX and DXA-FRAX tools when BMD is incorporated, sometimes there are very large differences for individuals between results obtained with and without BMD. Clinicians should carefully consider the importance of BMD inclusion in FRAX estimations when assessing individual patients.

Prevalence of Low Bone Mass and Osteoporosis in Ireland: the Dual-Energy X-Ray Absorptiometry (DXA) Health Informatics Prediction (HIP) Project.

Osteoporosis is a common disease that has a significant impact on patients, healthcare systems, and society. World Health Organization (WHO) diagnostic criteria for postmenopausal women were established in 1994 to diagnose low bone mass (osteopenia) and osteoporosis using dual-energy X-ray absorptiometry (DXA)-measured bone mineral density (BMD) to help understand the epidemiology of osteoporosis, and identify those at risk for fracture. These criteria may also apply to men ≥50 years, perimenopausal women, and people of different ethnicity. The DXA Health Informatics Prediction (HIP) project is an established convenience cohort of more than 36,000 patients who had a DXA scan to explore the epidemiology of osteoporosis and its management in the Republic of Ireland where the prevalence of osteoporosis remains unknown. In this article we compare the prevalence of a DXA classification low bone mass (T-score < -1.0) and of osteoporosis (T-score ≤ -2.5) among adults aged ≥40 years without major risk factors or fractures, with one or more major risk factors, and with one or more major osteoporotic fractures. A total of 33,344 subjects met our study inclusion criteria, including 28,933 (86.8%) women; 9362 had no fractures or major risk factors, 14,932 had one or more major clinical risk factors, and 9050 had one or more major osteoporotic fractures. The prevalence of low bone mass and osteoporosis increased significantly with age overall. The prevalence of low bone mass and osteoporosis was significantly greater among men and women with major osteoporotic fractures than healthy controls or those with clinical risk factors. Applying our results to the national population census figure of 5,123,536 in 2022 we estimate between 1,039,348 and 1,240,807 men and women aged ≥50 years have low bone mass, whereas between 308,474 and 498,104 have osteoporosis. These data are important for the diagnosis of osteoporosis in clinical practice, and national policy to reduce the illness burden of osteoporosis. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bone mineral density and fractures in patients with rheumatoid arthritis: the DXA-HIP project.

Objectives: RA is a chronic disabling disease affecting 0.5-1% of adults worldwide. People with RA have a greater prevalence of multimorbidity, particularly osteoporosis and associated fractures. Recent studies suggest that fracture risk is related to both non-RA and RA factors, whose importance is heterogeneous across studies. This study seeks to compare baseline demographic and DXA data across three cohorts: healthy controls, RA patients and a non-RA cohort with major risk factors and/or prior major osteoporotic fracture (MOF). Methods: This is a cross-sectional study using data collected from three DXA centres in the west of Ireland from January 2000 to November 2018. Results: Data were available for 30 503 subjects who met our inclusion criteria: 9539 (31.3%) healthy controls, 1797 (5.9%) with RA and 19 167 (62.8%) others. Although age, BMI and BMD were similar between healthy controls, the RA cohort and the other cohort, 289 (16.1%) RA patients and 5419 (28.3%) of the non-RA cohort had prior MOF. In the RA and non-RA cohorts, patients with previous MOF were significantly older and had significantly lower BMD at the femoral neck, total hip and spine. Conclusion: Although age, BMI and BMD were similar between a healthy control cohort and RA patients and others with major fracture risk factors, those with a previous MOF were older and had significantly lower BMD at all three measured skeletal sites. Further studies are needed to address the importance of these and other factors for identifying those RA patients most likely to experience fractures.

Patient Biochemistry and Treatment Need in Chronic Hepatitis B Virus Infection Across Three Continents: Retrospective Cross-Sectional Cohort Studies.

INTRODUCTION: Chronic hepatitis B virus (HBV) infection is associated with significant global morbidity and mortality. Low treatment rates are observed in patients living with HBV; the reasons for this are unclear. This study sought to describe patients' demographic, clinical and biochemical characteristics across three continents and their associated treatment need. METHODS: This retrospective cross-sectional post hoc analysis of real-world data used four large electronic databases from the United States, United Kingdom and China (specifically Hong Kong and Fuzhou). Patients were identified by first evidence of chronic HBV infection in a given year (their index date) and characterized. An algorithm was designed and applied, wherein patients were categorized as treated, untreated but indicated for treatment and untreated and not indicated for treatment based on treatment status and demographic, clinical, biochemical and virological characteristics (age; evidence of fibrosis/cirrhosis; alanine aminotransferase [ALT] levels, HCV/HIV coinfection and HBV virology markers). RESULTS: In total, 12,614 US patients, 503 UK patients, 34,135 patients from Hong Kong and 21,614 from Fuzhou were included. Adults (99.4%) and males (59.0%) predominated. Overall, 34.5% of patients were treated at index (range 15.9-49.6%), with nucleos(t)ide analogue monotherapy most commonly prescribed. The proportion of untreated-but-indicated patients ranged from 12.9% in Hong Kong to 18.2% in the UK; almost two-thirds of these patients (range 61.3-66.7%) had evidence of fibrosis/cirrhosis. A quarter (25.3%) of untreated-but-indicated patients were aged ≥ 65 years. CONCLUSION: This large real-world dataset demonstrates that chronic hepatitis B infection remains a global health concern; despite the availability of effective suppressive therapy, a considerable proportion of predominantly adult patients apparently indicated for treatment are currently untreated, including many patients with fibrosis/cirrhosis. Causes of disparity in treatment status warrant further investigation.

Estimating the epidemiology of chronic Hepatitis B Virus (HBV) infection in the UK: what do we know and what are we missing?

Background: HBV is the leading global cause of cirrhosis and primary liver cancer. However, the UK HBV population has not been well characterised, and estimates of UK HBV prevalence and/or incidence vary widely between sources. We aimed to i) extract and summarise existing national HBV prevalence estimates, ii) add a new estimate based on primary care data, and; iii) critique data sources from which estimates were derived. Methods: We undertook a narrative review, searching for national estimates of CHB case numbers in the UK (incorporating incidence, prevalence and/or test positivity data) across a range of overlapping sources, including governmental body reports, publications from independent bodies (including medical charities and non-governmental organisations) and articles in peer-reviewed scientific journals.  An alternative proxy for population prevalence was obtained via the UK antenatal screening programme which achieves over 95% coverage of pregnant women. We also searched for diagnoses of HBV in the QResearch primary care database based on laboratory tests and standardised coding. Results: We identified six CHB case number estimates, of which three reported information concerning population subgroups, including number of infected individuals across age, sex and ethnicity categories. Estimates among sources reporting prevalence varied from 0.27% to 0.73%, congruent with an estimated antenatal CHB prevalence of <0.5%. Our estimate, based on QResearch data, suggests a population prevalence of ~0.05%, reflecting a substantial underestimation based on primary care records. Discussion: Estimates varied by sources of error, bias and missingness, data linkage, and "blind spots" in HBV diagnoses testing/registration. The UK HBV burden is likely to be concentrated in vulnerable populations who may not be well represented in existing datasets including those experiencing socioeconomic deprivation and/or homelessness, ethnic minorities and people born in high-prevalence countries. This could lead to under- or over-estimation of population prevalence estimation. Multi-agency collaboration is required to fill evidence gaps.

Distribution of multiple chalazia in eyelids of pediatrics requiring surgery in southeast China: a hospital-based cross-sectional study.

Background: Multiple chalazia are common in children, and many are treated by surgery. However, the distribution of different types of multiple chalazia has not been studied. This research aimed to investigate the location and number of multiple chalazia in pediatrics who need surgical treatments. Methods: Patients with multiple chalazia treated by incision and curettage surgery (I&C) in a tertiary children's hospital between June and December 2016 were reviewed. Demographic data, locations, and numbers of chalazia were recorded. Data were analyzed using generalized linear models of the counts and the occurrences of chalazia. Hypotheses were tested using likelihood ratio tests appropriate for each type of data. Results: The study included 128 subjects, most of which were 1-3 years old. The majority of patients had bilateral chalazia (95.3%), and the proportions of patients with internal, external, and marginal chalazion differed dramatically (99.2%, 61.7%, and 2.3%, respectively). The number of internal and external chalazia did not vary significantly with gender, age, or residence of the patients. Internal chalazia were located more frequently in the upper lids (p<0.001). External chalazia showed no preference of localization. The average number of internal chalazia in each eyelid did not relate to the presence of external chalazia. Conclusions: Multiple chalazia are common among younger children in southeast China. The anatomical distribution varies depending on the type of chalazion. Multiple chalazia often occur bilaterally and internally. If doctors are more aware of the anatomical distribution of chalazia, this might result in a higher success rate of I&C.

Conceptual design of the dual X-ray absorptiometry health informatics prediction system for osteoporosis care.

Osteoporotic fractures are a major and growing public health problem, which is strongly associated with other illnesses and multi-morbidity. Big data analytics has the potential to improve care for osteoporotic fractures and other non-communicable diseases (NCDs), reduces healthcare costs and improves healthcare decision-making for patients with multi-disorders. However, robust and comprehensive utilization of healthcare big data in osteoporosis care practice remains unsatisfactory. In this paper, we present a conceptual design of an intelligent analytics system, namely, the dual X-ray absorptiometry (DXA) health informatics prediction (HIP) system, for healthcare big data research and development. Comprising data source, extraction, transformation, loading, modelling and application, the DXA HIP system was applied in an osteoporosis healthcare context for fracture risk prediction and the investigation of multi-morbidity risk. Data was sourced from four DXA machines located in three healthcare centres in Ireland. The DXA HIP system is novel within the Irish context as it enables the study of fracture-related issues in a larger and more representative Irish population than previous studies. We propose this system is applicable to investigate other NCDs which have the potential to improve the overall quality of patient care and substantially reduce the burden and cost of all NCDs.

Impact of the COVID-19 pandemic on routine surveillance for adults with chronic hepatitis B virus (HBV) infection in the UK.

Background: To determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (alanine transferase [ALT] and HBV viral load). Methods: We used anonymized electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK National Health Service (NHS) Trusts. Results: We report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID-19 years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient. Conclusions: These results demonstrate the real-time utility of HIC data in monitoring health-care provision, and support interventions to provide catch-up services to minimise the impact of the pandemic. Further investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes.

Acute Kidney Injury and Early Predictive Factors in COVID-19 Patients.

Objectives: Our objective was to explore the incidence and early predictive factors of acute kidney injury in coronavirus disease 2019 (COVID-19) patients. Method: We established a retrospective cohort of 408 patients who were admitted to Shenzhen Third People's Hospital in Shenzhen, China, between January 1 and March 31, 2020. Clinical outcomes and renal function were monitored until April 12, 2020, with a median follow-up duration of 21 days [interquartile range (IQR) = 14-33]. Results: When first admitted to hospital (baseline), 19.36% (79/408) presented renal dysfunction [estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2]. During follow-up, 3.9% (16/408) developed acute kidney injury (AKI). Age ≥60 years [hazard ratio (HR) = 4.78, 95% CI = 1.10-20.69], PaO2/FiO2 ratio <300 (HR = 3.48, 95% CI = 1.04-11.62), and higher creatinine (HR = 1.04, 95% CI = 1.01-1.07) at baseline independently predicted the risk of AKI. Respectively, 25.0% (102/408), 3.9% (16/408), 0.5% (2/408), 1.0% (4/408), and 0.2% (1/408) experienced G2, G3a, G3b, G4, and G5 as their most severe category during hospitalization, while 69.4% (283/408) had normal eGFRs throughout the follow-up period. When finally discharged from hospital, there were 12.5% (51/408) of patients with abnormal eGFRs. Conclusions: COVID-19 patients can be at risk of AKI and continuous eGFR decline during hospitalization, which can be early predicted by baseline factors. Some individuals still had renal dysfunction when finally discharged from hospital.

How does proximal femur BMD of healthy Irish adults compare to NHANES III? Results of the DXA-HIP Project.

This study examines the distribution of proximal femur bone mineral density in a cohort of healthy Irish adults. These values are similar to those of the NHANES III Caucasian cohorts, supporting international recommendations to use this reference group for calculating DXA T-scores and Z-scores in Irish adults. INTRODUCTION: Bone mineral density (BMD) is widely used in the assessment and monitoring of osteoporosis. International guidelines recommend referencing proximal femur BMD measurements to NHANES III values to calculate T-scores and Z-scores, but their validity for the Irish population has not been established. In this study, we compare BMD values of healthy Irish Caucasian adults to those of Caucasian men and women in the NHANES III cohort study. METHODS: Men and women without bone disease and/or major risk factors for fracture, and/or not taking osteoporosis medication who had a screening DXA scan (GE Lunar, Madison, USA) at one of 3 centres in the West of Ireland were selected for this study. We calculated the mean and standard deviation (SD) used by GE for calculating white female NHANES III T-scores at the femoral neck and total hip sites, and used these values to calculate white female T-scores for men and women across each decade in our study sample. We calculated mean white female T-scores for each decade for both Caucasian men and women in the NHANES III cohort using the published data. Finally, we plotted these results against those of our study population. RESULTS: In total, 6729 (18.5%) of 36,321 adults were included in our analyses, including 5923 (88%) women. The majority of the study population were aged between 40 and 89 years. Our results show that the proximal femur BMD of healthy Irish men and women is broadly similar to that of the NHANES III reference population, especially middle-aged adults. Results differ for very young and very old adults, likely reflecting the small sample size and a referral bias. Further studies of these populations and other manufacturers could help clarify these uncertainties. CONCLUSIONS: Our results support using the NHANES III reference population to calculate proximal femur adult T-scores and Z-scores to establish the presence or prevalence of osteoporosis in Ireland.

Longitudinal Analysis of the Utility of Liver Biochemistry as Prognostic Markers in Hospitalized Patients With Corona Virus Disease 2019.

The association of liver biochemistry with clinical outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently unclear, and the utility of longitudinally measured liver biochemistry as prognostic markers for mortality is unknown. We aimed to determine whether abnormal liver biochemistry, assessed at baseline and at repeat measures over time, was associated with death in hospitalized patients with COVID-19 compared to those without COVID-19, in a United Kingdom population. We extracted routinely collected clinical data from a large teaching hospital in the United Kingdom, matching 585 hospitalized patients who were SARS-CoV-2 real-time reverse transcription-polymerase chain reaction (RT-PCR) positive to 1,165 hospitalized patients who were RT-PCR negative for age, sex, ethnicity, and preexisting comorbidities. A total of 26.8% (157/585) of patients with COVID-19 died compared to 11.9% (139/1,165) in the group without COVID-19 (P < 0.001). At presentation, a significantly higher proportion of the group with COVID-19 had elevated alanine aminotransferase (20.7% vs. 14.6%, P = 0.004) and hypoalbuminemia (58.7% vs. 35.0%, P < 0.001) compared to the group without COVID-19. Within the group with COVID-19, those with hypoalbuminemia at presentation had 1.83-fold increased hazards of death compared to those with normal albumin (adjusted hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.25-2.67), while the hazard of death was ~4-fold higher in those aged ≥75 years (adjusted HR, 3.96; 95% CI, 2.59-6.04) and ~3-fold higher in those with preexisting liver disease (adjusted HR, 3.37; 95% CI, 1.58-7.16). In the group with COVID-19, alkaline phosphatase (ALP) increased (R = 0.192, P < 0.0001) and albumin declined (R = -0.123, P = 0.0004) over time in patients who died. Conclusion: In this United Kingdom population, liver biochemistry is commonly deranged in patients with COVID-19. Baseline hypoalbuminemia and rising ALP over time could be prognostic markers for death, but investigation of larger cohorts is required to develop a better understanding of the relationship between liver biochemistry and disease outcome.

Long Short-Term Memory Recurrent Neural Networks for Multiple Diseases Risk Prediction by Leveraging Longitudinal Medical Records.

Individuals suffer from chronic diseases without being identified in time, which brings lots of burden of disease to the society. This paper presents a multiple disease risk prediction method to systematically assess future disease risks for patients based on their longitudinal medical records. In this study, medical diagnoses based on International Classification of Diseases (ICD) are aggregated into different levels for prediction to meet the needs of different stakeholders. The proposed approach gets validated using two independent hospital medical datasets, which includes 7105 patients with 18, 893 patients and 4170 patients with 13, 124 visits, respectively. The initial analysis reveals a high variation in patients' characteristics. The study demonstrates that recurrent neural network with long-short time memory units performs well in different levels of diagnosis aggregation. Especially, the results show that the developed model can be well applied to predicting future disease risks for patients, with the exact-match score of 98.90% and 95.12% using 3-digit ICD code aggregation, while 96.60% and 96.83% using 4-digit ICD code aggregation for these two datasets, respectively. Moreover, the approach can be developed as a reference tool for hospital information systems, enhancing patients' healthcare management over time.

Effect of combination treatment based on interferon and nucleos(t)ide analogues on functional cure of chronic hepatitis B: a systematic review and meta-analysis.

BACKGROUND: Priority of antiviral treatment for patients with chronic hepatitis B (CHB) is to increase the probability of functional cure. We aimed to synthesize evidence regarding the efficacy of different combination strategies of antiviral treatment based on interferon (IFN) and nucleos(t)ide analogues (NAs) in adults with CHB. METHODS: PubMed, Web of Science and Embase databases were searched from inception to May 26, 2019. Three types of combination strategies were studied: initial combination (IFN or NAs monotherapy as control), add-on (I: IFN add-on NAs vs. NAs; II: NAs add-on IFN vs. IFN), switch-to (I: IFN switch-to NAs vs. IFN; II: NAs switch-to IFN vs. NAs). RESULTS: Compared to NAs monotherapy, initial combination strategy improved the probability of HBeAg loss (RR: 1.62, 95% CI 1.33-1.97) and HBsAg loss (RR: 15.59, 95% CI 3.22-75.49), while compared to IFN monotherapy, no higher rates in the loss of HBsAg or HBeAg for initial combination. Compared to NAs monotherapy, IFN add-on NAs strategy had a higher rate of HBsAg loss (RR: 4.52, 95% CI 1.95-10.47), while compared to IFN monotherapy, NAs add-on IFN had a similar outcome. Compared to NAs monotherapy, NAs switch-to IFN strategy improved HBsAg loss (RR: 12.15, 95% CI 3.99-37.01); while compared to IFN monotherapy, IFN switch-to NAs had no improved rate of HBsAg clearance but higher rates in undetectable HBV DNA, and HBeAg loss. CONCLUSION: IFN add-on NAs, or NAs switched to IFN could significantly improve the probability of HBsAg loss compared to NAs monotherapy.