Long-term outcomes of SARS-CoV-2 variants and other respiratory infections: evidence from the Virus Watch prospective cohort in England.

This study compared the likelihood of long-term sequelae following infection with SARS-CoV-2 variants, other acute respiratory infections (ARIs) and non-infected individuals. Participants (n=5,630) were drawn from Virus Watch, a prospective community cohort investigating SARS-CoV-2 epidemiology in England. Using logistic regression, we compared predicted probabilities of developing long-term symptoms (>2 months) during different variant dominance periods according to infection status (SARS-CoV-2, other ARI, or no infection), adjusting for confounding by demographic and clinical factors and vaccination status. SARS-CoV-2 infection during early variant periods up to Omicron BA.1 was associated with greater probability of long-term sequalae (adjusted predicted probability (PP) range 0.27, 95% CI = 0.22-0.33 to 0.34, 95% CI = 0.25-0.43) compared with later Omicron sub-variants (PP range 0.11, 95% CI 0.08-0.15 to 0.14, 95% CI 0.10-0.18). While differences between SARS-CoV-2 and other ARIs (PP range 0.08, 95% CI 0.04-0.11 to 0.23, 95% CI 0.18-0.28) varied by period, all post-infection estimates substantially exceeded those for non-infected participants (PP range 0.01, 95% CI 0.00, 0.02 to 0.03, 95% CI 0.01-0.06). Variant was an important predictor of SARS-CoV-2 post-infection sequalae, with recent Omicron sub-variants demonstrating similar probabilities to other contemporaneous ARIs. Further aetiological investigation including between-pathogen comparison is recommended.

The incidence of COVID-19-related hospitalisation in migrants in the UK: Findings from the Virus Watch prospective community cohort study.

Background: Migrants in the United Kingdom (UK) may be at higher risk of SARS-CoV-2 exposure; however, little is known about their risk of COVID-19-related hospitalisation during waves 1-3 of the pandemic. Methods: We analysed secondary care data linked to Virus Watch study data for adults and estimated COVID-19-related hospitalisation incidence rates by migration status. To estimate the total effect of migration status on COVID-19 hospitalisation rates, we ran mixed-effect Poisson regression for wave 1 (01/03/2020-31/08/2020; wildtype), and mixed-effect negative binomial regressions for waves 2 (01/09/2020-31/05/2021; Alpha) and 3 (01/06/2020-31/11/2021; Delta). Results of all models were then meta-analysed. Results: Of 30,276 adults in the analyses, 26,492 (87.5 %) were UK-born and 3,784 (12.5 %) were migrants. COVID-19-related hospitalisation incidence rates for UK-born and migrant individuals across waves 1-3 were 2.7 [95 % CI 2.2-3.2], and 4.6 [3.1-6.7] per 1,000 person-years, respectively. Pooled incidence rate ratios across waves suggested increased rate of COVID-19-related hospitalisation in migrants compared to UK-born individuals in unadjusted 1.68 [1.08-2.60] and adjusted analyses 1.35 [0.71-2.60]. Conclusion: Our findings suggest migration populations in the UK have excess risk of COVID-19-related hospitalisations and underscore the need for more equitable interventions particularly aimed at COVID-19 vaccination uptake among migrants.

Early special educational needs provision and its impact on unplanned hospital utilisation and school absences in children with isolated cleft lip and/or palate: a demonstration target trial emulation study protocol using ECHILD.

Background: Special educational needs (SEN) provision is designed to help pupils with additional educational, behavioural or health needs; for example, pupils with cleft lip and/or palate may be offered SEN provision to improve their speech and language skills. Our aim is to contribute to the literature and assess the impact of SEN provision on health and educational outcomes for a well-defined population. Methods: We will use the ECHILD database, which links educational and health records across England. Our target population consists of children identified within ECHILD to have a specific congenital anomaly: isolated cleft lip and/or palate. We will apply a trial emulation framework to reduce biases in design and analysis of observational data to investigate the causal impact of SEN provision (including none) by the start of compulsory education (Year One - age five year on entry) on the number of unplanned hospital utilisation and school absences by the end of primary education (Year Six - age ten/eleven). We will use propensity score-based estimators (inverse probability weighting (IPW) and IPW regression adjustment IPW) to compare categories of SEN provision in terms of these outcomes and to triangulate results obtained using complementary estimation methods (Naïve estimator, multivariable regression, parametric g-formula, and if possible, instrumental variables), targeting a variety of causal contrasts (average treatment effect/in the treated/in the not treated) of SEN provision. Conclusions: This study will evaluate the impact of reasonable adjustments at the start of compulsory education on health and educational outcomes in the isolated cleft lip and palate population by triangulating complementary methods under a target-trial framework.

Children born with cleft lip and/or palate have been shown to have lower academic performance compared to the general population and have also been shown to have higher attendances to hospitals. To support children with such health and education needs, special educational needs provisions such as teaching assistants can be provided. The aim of this study is to understand whether children with cleft lip and/or palate were better off on average in receiving special education needs at the start of primary school in terms of hospital usage and school absences.

Impact of special educational needs provision on hospital utilisation, school attainment and absences for children in English primary schools stratified by gestational age at birth: A target trial emulation study protocol.

Introduction: One third of children in English primary schools have additional learning support called special educational needs (SEN) provision, but children born preterm are more likely to have SEN than those born at term. We aim to assess the impact of SEN provision on health and education outcomes in children grouped by gestational age at birth. Methods: We will analyse linked administrative data for England using the Education and Child Health Insights from Linked Data (ECHILD) database. A target trial emulation approach will be used to specify data extraction from ECHILD, comparisons of interest and our analysis plan. Our target population is all children enrolled in year one of state-funded primary school in England who were born in an NHS hospital in England between 2003 and 2008, grouped by gestational age at birth (extremely preterm (24-<28 weeks), very preterm (28-<32 weeks), moderately preterm (32-<34 weeks), late preterm (34-<37 weeks) and full term (37-<42 weeks). The intervention of interest will comprise categories of SEN provision (including none) during year one (age five/six). The outcomes of interest are rates of unplanned hospital utilisation, educational attainment, and absences by the end of primary school education (year six, age 11). We will triangulate results from complementary estimation methods including the naïve estimator, multivariable regression, g-formula, inverse probability weighting, inverse probability weighting with regression adjustment and instrumental variables, along with a variety for a variety of causal contrasts (average treatment effect, overall, and on the treated/not treated). Ethics and dissemination: We have existing research ethics approval for analyses of the ECHILD database described in this protocol. We will disseminate our findings to diverse audiences (academics, relevant government departments, service users and providers) through seminars, peer-reviewed publications, short briefing reports and infographics for non-academics (published on the study website).

One third of all children need extra help with learning in school, such as support from a teaching assistant. Children born preterm are more likely to need extra help compared to those born at term. In England, this help is called special educational needs (SEN) provision. The aim of this study is to find out whether special educational need provision affects education and health outcomes. We will use information collected by hospitals and schools for all children who were born in England between 2003 and 2008. We will compare those with who received and did not receive extra help in school who have a similar gestational age at birth.

The changing contributory role to infections of work, public transport, shopping, hospitality and leisure activities throughout the SARS-CoV-2 pandemic in England and Wales.

Background: Understanding how non-household activities contributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections under different levels of national health restrictions is vital. Methods: Among adult Virus Watch participants in England and Wales, we used multivariable logistic regressions and adjusted-weighted population attributable fractions (aPAF) assessing the contribution of work, public transport, shopping, and hospitality and leisure activities to infections. Results: Under restrictions, among 17,256 participants (502 infections), work [adjusted odds ratio (aOR) 2.01 (1.65-2.44), (aPAF) 30% (22-38%)] and transport [(aOR 1.15 (0.94-1.40), aPAF 5% (-3-12%)], were risk factors for SARS-CoV-2 but shopping, hospitality and leisure were not. Following the lifting of restrictions, among 11,413 participants (493 infections), work [(aOR 1.35 (1.11-1.64), aPAF 17% (6-26%)] and transport [(aOR 1.27 (1.04-1.57), aPAF 12% (2-22%)] contributed most, with indoor hospitality [(aOR 1.21 (0.98-1.48), aPAF 7% (-1-15%)] and leisure [(aOR 1.24 (1.02-1.51), aPAF 10% (1-18%)] increasing. During the Omicron variant, with individuals more socially engaged, among 11,964 participants (2335 infections), work [(aOR 1.28 (1.16-1.41), aPAF (11% (7-15%)] and transport [(aOR 1.16 (1.04-1.28), aPAF 6% (2-9%)] remained important but indoor hospitality [(aOR 1.43 (1.26-1.62), aPAF 20% (13-26%)] and leisure [(aOR 1.35 (1.22-1.48), aPAF 10% (7-14%)] dominated. Conclusions: Work and public transport were important to transmissions throughout the pandemic with hospitality and leisure's contribution increasing as restrictions were lifted, highlighting the importance of restricting leisure and hospitality alongside advising working from home, when facing a highly infectious and virulent respiratory infection.

Establishing which activities and venues that were restricted in England and Wales during lockdowns were the most likely to lead to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections will help us understand how useful the restrictions were and will help us to develop proportional responses to future public health threats. We found that during periods of intense restrictions (October 2020­May 2021) many people became infected with SARS-CoV-2 if they left home to go to work or used public transport. During the period after most public health restrictions were lifted (September­mid-December 2021), while many people continued to become infected at work or if they used public transport, indoor hospitality and indoor leisure venues became increasingly important as places where people became infected. During the Omicron wave of the pandemic (December 2021­April 2022), by which point there were very few restrictions on people's activities and many people were visiting hospitality and leisure venues with increasing frequency, people continued to become infected at work and on public transport, but hospitality and leisure venues were nearly as important places where people became infected. As essential activities led to most cases during periods of tight restrictions and leisure and hospitality activities became increasingly important under periods when rules were more relaxed, it is important to recognise how vital it was to encourage people to work from home, reduce public transport use and restrict visits to leisure and hospitality settings when the country was faced with a fast-spreading virus which killed many people. Outdoor use of leisure and hospitality venues appeared to be safer than indoor use.

Chronic hepatitis B treatment eligibility and actual treatment rates in patients in community gastroenterology and primary care settings.

GOALS: This study aims to compare the eligibility and treatment rates of patients evaluated by gastroenterology [gastrointestinal (GI)] specialists for chronic hepatitis B (CHB) and patients followed by their primary care physicians (PCPs) only. BACKGROUND: Guidelines have been devised to direct the care of patients with CHB but data on the application of these guidelines, especially in primary care settings, has been limited to date. STUDY: Consecutive CHB patients were enrolled retrospectively from several community clinics in the San Francisco Bay Area: 2 GI referral clinics, 3 primary care clinics, and a multispecialty medical center. Patients were classified as group 1 if they saw a gastroenterologist for CHB within 6 months of presentation or as group 2 if they only saw PCPs. Eligibility according to AASLD 2009 and US Panel 2008 guidelines was determined using clinical and laboratory data available within 6 months of presentation. RESULTS: Patients in group 2 had lower eligibility rates according to both US Panel 2008 (32% vs. 51%, P < 0.001) and AASLD 2009 (8% vs. 24%, P < 0.001) guidelines. GI specialists treated US Panel-eligible patients more readily than PCPs (45% vs. 25%, P < 0.001), and treatment rates in AASLD-eligible patients suggested a similar trend (68% vs. 50%, P = 0.080). CONCLUSIONS: GI specialists were more likely than PCPs to see patients who were treatment eligible, and also more likely to initiate antiviral therapy. However, there are still a considerable number of patients from both settings who did not receive treatment despite being eligible.

Low treatment rates in patients meeting guideline criteria in diverse practice settings.

BACKGROUND AND AIMS: Data on usage of antiviral therapy and application of chronic hepatitis B (CHB) management guidelines in different settings are limited. Our goal is to evaluate the proportion of treatment-eligible patients by 6-month follow-up and treatment rate among eligible patients by 12-month follow-up in diverse settings. METHODS: In this retrospective cohort study, 1,976 treatment-naïve CHB patients were categorized as primary care physician (PCP) group if seen by community PCP (n = 329), gastroenterology (GI) group if seen by community gastroenterologists (n = 1,268), and hepatology group if seen by university hepatologists (n = 379). Treatment eligibility was based on the US Panel 2008 and American Association for the Study of Liver Diseases (AASLD) 2009 guidelines. RESULTS: All groups had similar age, gender, and ethnic distribution. GI and hepatology groups had similar treatment eligibility rates by US Panel (53-54 %) and AASLD guidelines (24-25 %). However, treatment rate was significantly higher in hepatology compared to GI group by the US Panel guideline (59 vs. 45 %, P = 0.001). PCP group had the lowest eligibility and treatment rates by both guidelines. Common reasons for non-treatment were perceived "normal" alanine aminotransferase, desire for further observation, and patient refusal. Male gender, age >50, and subspecialty care predicted treatment initiation in treatment-eligible patients. CONCLUSIONS: Less than half of treatment-eligible patients at primary care clinics received treatment. Community gastroenterology and university liver clinics treated about one-half to two-thirds of eligible patients. Patient and provider education should highlight treatment benefits and the new alanine aminotransferase upper limit of normal.

Hepatocellular carcinoma incidence in noncirrhotic patients with chronic hepatitis B and patients with cirrhosis of all etiologies.

BACKGROUND: Hepatocellular carcinoma (HCC) causes approximately a half million deaths annually with the majority related to chronic hepatitis B (CHB) and cirrhosis. Results on HCC incidence in CHB patients without cirrhosis are conflicting. GOALS: This study aimed to examine HCC incidence in 2 high-risk groups: (1) patients with noncirrhotic CHB and 45 years of age or older; and (2) patients with cirrhosis of all etiologies and any age. RESULTS: Through electronic query using ICD-9 diagnosis codes for CHB and cirrhosis (070.32 and 571.5, respectively) between January 2001 and January 2008, a total of 949 patients with 12 months of follow-up or longer were identified and reviewed. Over 4231.5 person-years of observation, HCC developed in 15 of the 741 noncirrhotic CHB patients and 30 of the 208 cirrhotic patients. Male and female noncirrhotic CHB patients had significantly lower annual HCC incidences than those found in male and female patients with cirrhosis regardless of etiologies (0.7% vs. 4.1%, P<0.0001 and 0.1% vs. 2.7%, P<0.0001). Annual HCC incidence increased significantly with age in both sexes of noncirrhotic CHB patients. In noncirrhotic CHB patients, annual HCC incidence was very low in young females, but increased to 0.3% to 0.4% in females 55 years of age or older. An HCC incidence rate of 1.1% per year was seen in noncirrhotic CHB men aged 55 or older. CONCLUSIONS: Although annual HCC incidence in cirrhotic patients did not differ significantly among different age groups, rates among noncirrhotic patients were significantly higher in older patients and up to 1.1% in males above 55 years.

Chronic hepatitis B management based on standard guidelines in community primary care and specialty clinics.

BACKGROUND AND AIMS: Prior studies have underlined the need for increased screening and awareness of chronic hepatitis B (CHB), especially in certain high-risk populations. However, few studies have examined the patterns of evaluation and management of CHB between primary care physicians (PCP) and specialists according to commonly-used professional guidelines. Our goal was to examine whether necessary laboratory parameters used to determine disease status and eligibility for antiviral therapy were performed by PCPs and specialists. METHODS: We conducted a retrospective study of 253 treatment-naïve CHB patients who were evaluated by PCP only (n=63) or by specialists (n=190) for CHB at a community multispecialty medical center between March 2007 and June 2009. Criteria for CHB management and treatment eligibility were based on the American Association for the Study of Liver Diseases 2007 guideline and the US Panel 2006 algorithm. Required parameters for optimal evaluation for CHB included hepatitis B e antigen (HBeAg), HBV DNA, and alanine aminotransferase (ALT). Preferred antiviral agents for CHB included pegylated interferon, adefovir, and entecavir. RESULTS: The majority of patients were Asians (90%) and (54%) with a mean age of 43±11.6 years. Compared to PCPs, specialists were more likely to order laboratory testing for ALT (94 vs. 86%, P=0.05), HBeAg (67 vs. 41%, P<0.0001) and HBV DNA (83 vs. 52%, P<0.0001). The proportion of patients having all three laboratory parameters was significantly higher among those evaluated by specialists compared to PCP (62 vs. 33%, P<0.0001). A total of 55 patients were initiated on antiviral treatment (n=47 by specialists and n=6 by PCPs). Lamivudine was prescribed more often by PCPs than specialists (33 vs. 2%, P=0.05). Preferred agents were used 96% of the time by specialists compared to 67% of those treated by PCPs (P=0.05). CONCLUSION: Patients evaluated by specialists for CHB are more likely to undergo more complete laboratory evaluation and, if eligible, are also more likely to be treated with preferred longer-term agents for CHB compared to those evaluated by PCPs only. A collaborative model of care involving both PCP and specialists may further optimize management of patients with CHB.