Comprehensive sexuality education in Hong Kong: study protocol for process and outcome evaluation.

BACKGROUND: Hong Kong lacks comprehensive school-based sexuality education. Recent public health concerns have brought the inadequacies of sex education in Hong Kong to the forefront. The aim of the proposed study is to develop and evaluate the effectiveness of a comprehensive school-based sexuality education program in Hong Kong. METHODS: The proposed study is a prospective longitudinal study implemented in six secondary schools in Hong Kong over two academic years. The study adopts an ecological approach providing informational workshops for students, teachers and school management, social workers and guidance counsellors and parents. Study outcomes will be evaluated through pre- and post-tests. RESULTS: Key outcomes of interest among students include sexual health knowledge, awareness of values motivating healthy sexual decisions, understanding and efficacy of sexual communication and intention to use contraception. Among school employees and parents key outcomes include self-efficacy to engage in sexual health discussions with students/children, sexual health knowledge and awareness of Hong Kong community sexual health resources. CONCLUSIONS: The proposed study will result in the development of a tested school-based culturally relevant comprehensive sexual health education program. Ultimately, this program aims to not only empower adolescents and their trusted adults in building a supportive environment for sexual health promotion but also construct a learning network to generate longitudinal evidence for the effectiveness of comprehensive sexuality education in improving sexual health outcomes. The program has the potential for expansion through widespread adoption in Hong Kong schools to benefit more adolescents and reduce the medical and societal burdens related to crisis pregnancy, sexually transmitted infections and sexual abuse.

Positive relationship between consumption of specific fish type and n-3 PUFA in milk of Hong Kong lactating mothers.

Residents of Hong Kong have undergone a dietary transition from a traditional Chinese diet that is high in seafood to a more Western diet. This may have affected the nutritional composition of breast milk of Hong Kong mothers. The present study aims to investigate the relationship between the dietary pattern and the fatty acid profile of the breast milk of lactating women in Hong Kong. Seventy-three volunteering healthy Hong Kong lactating mothers participated in the study. Their dietary intakes were assessed by using a 3-d dietary record and FFQ. The mean n-3 fatty acid levels were approximately 0·4 % (EPA) and 0·9 % (DHA) of total fatty acids in the breast milk of lactating mothers who had exclusively breastfed their infants aged 2-6 months. Maternal dietary intakes of n-3 fatty acids were positively associated with their levels in the breast milk. The levels of maternal intakes of freshwater and saltwater fish, especially the consumption of salmon, croaker and mandarin, were significantly correlated with the content of DHA in breast milk. The present study is among the very few in the literature to determine the fatty acid profile of breast milk in Hong Kong populations and verify certain dietary factors that influence this profile. High levels of n-3 PUFA, especially DHA, were observed in the breast milk of Hong Kong lactating women. The findings may serve as a dietary reference for lactating mothers to optimise the fatty acid profile of their breast milk.

Chronic Methylmercury Exposure Induces Production of Prostaglandins: Evidence From A Population Study and A Rat Dosing Experiment.

Methylmercury (MeHg) is a well-known environmental neurotoxicant affecting millions worldwide who consume contaminated fishes and other food commodities. Exposure to MeHg has been shown to associate positively with some chronic diseases including cardiovascular diseases, but the mechanism is poorly characterized. MeHg had been shown to affect prostaglandin (PG) regulations in in vitro studies, but neither in vivo nor human studies investigating the effects of MeHg on PG regulations has been reported. Thus, the current study aimed to investigate the association between MeHg exposure and serum PG concentrations in a cross-sectional study among human adults followed by a validation investigation on the cause-effect relationship using a rat model. First, a total of 121 women were recruited from two cities: Wanshan and Leishan in Guizhou, China. Statistical analysis of the human data showed a positive association between blood total mercury (THg) levels and serum concentrations of PGF2α, 15-deoxy-PGJ2, and PGE2 after adjusting for site effects. In the animal study, adult female Sprague-Dawley rats were dosed with 40 µg MeHg/kg body weight/day for 12 weeks. Serum 15-deoxy-PGJ2 and 2,3 d-6-keto-PGF1α concentrations were found to increase significantly after 6 and 10 weeks of MeHg dosing, respectively, while serum PGF2α concentration increased significantly after 12 weeks of MeHg dosing. Combined results of our human and rat studies have shown that chronic MeHg exposure induced dysregulation of PG metabolism. As PGs are a set of mediators with very diverse functions, its abnormal production may serve as the missing mechanistic link between chronic MeHg exposure and various kinds of associated clinical conditions including neurodegeneration and cardiovascular diseases.

Anti-bacterial effects, and metabolites derived from bifidobacterial fermentation of an exopolysaccharide of Cs-HK1 medicinal fungus.

This study was to investigate the antibacterial effects and metabolites derived from bifidobacterial fermentation of an exopolysaccharide EPS-LM produced by a medicinal fungus Cordyceps sinensis, Cs-HK1. EPS-LM was a partially purified polysaccharide fraction which was mainly composed of Man, Glc and Gal at 7.31:12.95:1.00 mol ratio with a maximum molecular weight of 360 kDa. After fermentation of EPS-LM in two bifidobacterial cultures, B. breve and B. longum, the culture digesta showed significant antibacterial activities, inhibiting the proliferation and biofilm formation of Escherichia coli. Based on untargeted metabolomic profiling of the digesta, the levels of short chain fatty acids, carboxylic acids, benzenoids and their derivatives were all increased significantly (p < 0.01), which probably contributed to the enhanced antibacterial activity by EPS-LM. Since EPS-LM was only slightly consumed for the bifidobacterial growth, it mainly stimulated the biosynthesis of bioactive metabolites in the bifidobacterial cells. The results also suggested that EPS-LM polysaccharide may have a regulatory function on the bifidobacterial metabolism leading to production of antibacterial metabolites, which may be of significance for further exploration.

Untargeted foodomics for authenticating the organic farming of water spinach (Ipomoea aquatica).

This study aimed to conduct a comprehensive analysis of the primary and secondary metabolites of water spinach (Ipomoea aquatica) using hydrophilic interaction liquid chromatography coupled with Orbitrap high-resolution mass spectrometry (HILIC-Orbitrap-HRMS). Certified samples from two cultivars, Green stem water spinach (G) and White stem water spinach (W) cultivated using organic and conventional farming methods, were collected from the Hong Kong market. Multivariate analysis was used to differentiate water spinach of different cultivars and farming methods. We identified 12 metabolites to distinguish between G and W, 26 metabolites to identify G from organic farming and 8 metabolites to identify W from organic farming. Then, two metabolites, isorhamnetin and jasmonic acid, have been proposed to serve as biomarkers for organic farming (in both G and W). Our foodomics findings provide useful tools for improving the crop performance of water spinach under abiotic/biotic stressesand authentication of organic produce.

Bioaccumulation of pollutants in the green-lipped mussel Perna viridis: Assessing pollution abatement in Victoria Harbour and its adjacent aquaculture area, Hong Kong, and the minimal human health risks from mussel consumption.

The green-lipped mussel Perna viridis was utilised for pollution biomonitoring in Victoria Harbour and its adjacent aquaculture area in Hong Kong. P. viridis was collected from a reference site and redeployed at five study sites for five weeks during the dry and wet seasons of 2019. Our study found various polycyclic aromatic hydrocarbons (PAHs) and heavy metals in the mussel tissue, while polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were not detected. P. viridis at the reference site generally displayed lower levels of pollutants. Comparing with previous research in the 1980s and 2000s, we observed substantial reduction in the tissue levels of PAHs, PCBs, OCPs and heavy metals in P. viridis. The human health risks associated with consuming these mussels were determined to be insignificant. Our findings imply that the Harbour Area Treatment Scheme has been effective in improving the water quality in Victoria Harbour and its adjacent aquaculture area.

Development of a multiple-biomarker approach using the green-lipped mussel Perna viridis for marine pollution monitoring: a case study in Victoria Harbour, Hong Kong.

Pollutants often exist as mixtures in environmental settings, creating a challenge in selecting the most effective combination of biomarkers for routine monitoring. This study was conducted seasonally in Victoria Harbour, Hong Kong, to compare the responses of nine biomarkers in the green-lipped mussel Perna viridis with respect to its tissue levels of persistent organic pollutants and heavy metals. Multivariate statistical techniques were utilised to determine the single best predictor and optimal subset of biomarkers in P. viridis for each of the four scenarios: representing overall biomarker responses in the dry season, and wet season, as well as correlating tissue levels of mixed pollutants in the dry season, and wet season. Our findings recommend lysosomal destabilisation, and the nucleic acid ratio of RNA to DNA, as the core biomarkers in P. viridis for marine pollution monitoring. The non-specificity of these biomarkers allows effective identification of pollution hotspots and guides further detailed assessment.

Improved Raman spectroscopy-based approach to assess microplastics in seafood.

Microplastics represent an emerging environmental issue and have been found almost everywhere including seafood, raising a great concern about the ecological and human health risks they pose. This study addressed the common technical challenges in the assessment of microplastics in seafood by developing an improved protocol based on Raman spectroscopy and using the green-lipped mussel Perna viridis and the Japanese jack mackerel Trachurus japonicus as the test models. Our findings identified a type of stainless-steel filter membranes with minimal Raman interference, and a combination of chemicals that achieved 99-100% digestion efficiency for both organic and inorganic biomass. This combined chemical treatment reached 90-100% recovery rates for seven types of microplastics, on which the surface modification was considered negligible and did not affect the accuracy of polymer identification based on Raman spectra, which showed 94-99% similarity to corresponding untreated microplastics. The developed extraction method for microplastics was further combined with an automated Raman mapping approach, from which our results confirmed the presence of microplastics in P. viridis and T. japonicus collected from Hong Kong waters. Identified microplastics included polypropylene, polyethylene, polystyrene and poly(ethylene terephthalate), mainly in the form of fragments and fibres. Our protocol is applicable to other biological samples, and provides an improved alternative to streamline the workflow of microplastic analysis for routine monitoring purposes.

Mass spectrometry-based untargeted metabolomics approach for differentiation of beef of different geographic origins.

Beef is a common staple food in many countries, and there is a growing concern over misinformation of beef products, such as false claims of origin, species and production methods. In this study, we used a mass spectrometry-based metabolomics approach to study the metabolite profiles of beef samples purchased from local retailers in Hong Kong. Using multivariate analysis, beef samples from different a) geographical origins, namely the United States (US), Japan and Australia, and b) feeding regimes could be differentiated. We identified twenty-four metabolites to distinguish beef samples from different countries, ten metabolites to identify Angus beef samples from others and seven metabolites to discriminate Australian beef produced by the organic farming from that produced using other farming modes. Based on results of this study, it is concluded that metabolomics provides an efficient strategy for tracing and authenticating beef products to ensure their quality and to protect consumer rights.

Incorporating sustainability in small health-care facilities: an integrated model.

Purpose It is challenging for small health-care facilities to implement changes when human and financial resources are limited for day-to-day operations. This paper aims to propose an integrated model for small- and medium-sized health-care facilities to integrate sustainability in their day-to-day operations, which have been derived from the leadership and change theories. Design/methodology/approach Drawing on previous research on leadership and change theories, the paper first critically reviewed the approaches to implementing changes and how applicable they are in the context of small- and medium-sized health-care facilities. Next, it proposes an integrated model with an execution plan. Findings The first part of the paper discusses how either the planned approach or emergent approach for change may fail in facilitating the implementation of sustainable initiatives, as incorporating sustainability into operations require both leadership of change and open learning systems. The second part outlines the four-phase combined approach, which includes phases of "exploration", "planning", "action" and "integration", and discusses how change readiness is ensured through such approach. Practical implications The authors propose an integrated model as a framework for integrating sustainability into the operations of small health-care facilities. The clearest possible steps at various phases are proposed. Potential barriers and risks are highlighted and the coping strategies proposed to maximise the chance of successfully transforming organisations. Originality/value Applying the "how to" ideas based on the integrated model for change management will help leaders of health-care facilities gradually integrate sustainability into their day-to-day operations.

Polysaccharide-protein complex-decorated selenium nanosystem as an efficient bone-formation therapeutic.

Polysaccharide-protein complex-coated selenium nanoparticles (PTR-SeNPs) system has been rationally designed and identified as a potent bone-formation therapeutic to antagonize osteoporosis. The nanosystem presents high cellular uptake in osteoblast cells and significantly enhances bone formation in vitro and in vivo, mainly through BMP-2/Smad-mediated signalling pathways.

Expression of macrophage migration inhibitory factor in acute ischemic myocardial injury.

Macrophage migration inhibitory factor (MIF) is a key mediator in inflammatory or immune-mediated diseases, although its role in heart diseases is unknown. This study investigated the expression of MIF in the myocardium in the development of acute myocardial infarction (AMI). By use of immunohistochemistry, Western blotting, RT-PCR, and in situ hybridization, the gene and protein expression of MIF in the heart at 6 hr, 1 day, 3 days, 1 week, and 2 weeks after AMI was studied. In both normal and sham-operated rats, MIF mRNA and protein were expressed constitutively at low levels by the myocytes. By contrast, MIF mRNA was rapidly upregulated by the surviving myocytes in the infarcted region and, to a lesser extent, the non-infarcted region, accounting for a sevenfold increase at 6 hr after AMI (p<0.001). This was followed by a fourfold increase in MIF protein expression at day 1 after AMI (p<0.05). Macrophages were found accumulated in the infarcted region, being significant at day 1 (p<0.01) and progressive increased over the 2-week time course (p<0.01) in which MIF was found expressed in these cells. The results indicated that the infiltrating macrophages and myocytes were sources of MIF in the infarcted region. The latter cells became activated and involved in the amplification of inflammatory response in AMI. Therefore, upregulation of myocardial MIF may contribute to macrophage accumulation in the infarcted region and their pro-inflammatory role may participate in the myocyte damage seen in AMI.

The effects of model polysiloxane and fouling-release coatings on embryonic development of a sea urchin (Arbacia punctulata) and a fish (Oryzias latipes).

In recent decades attention has focused on the development of non-toxic fouling-release coatings based on silicone polymers as an alternative to toxic antifouling coatings. As fouling-release coatings gain market share, they will contribute to environmental contamination by silicones. We report effects of eight model polysiloxane and three commercial foul-release coatings on embryonic development of sea urchins and fish, Japanese medaka. We used model coatings because they have known composition and commercially available components and molecules leaching from these coatings have been partially characterized. The commercial fouling-release coatings are purported to be non-toxic and components are proprietary. Our goal was to expose embryos of well studied model animals to the coatings to determine if the complex mixtures leaching from the coatings impact development. Urchins were chosen because development is rapid and embryos can enter the non-slip layer over surfaces. Medaka was chosen because the female deposits the sticky eggs onto the anal fin and then scrapes them off onto surfaces. Embryos were confined in water over coatings in 24 well plates. Fresh model coatings had no effect on urchin development while commercial fouling-release coatings inhibited development. Fish embryos had delayed hatching, increased mortality of hatchlings and dramatically decreased ability of hatchlings to inflate the swim bladder and reduced hatching success on all coatings. After one-month immersion of coatings in running seawater to simulate initial application in the marine environment, sea urchin embryos died when placed over model silicones. Effects of the commercial coatings were reduced but included retarded development. Effects on fish embryos over leached coating were reduced compared to those of fresh coating and included decreased hatching success, decreased hatchling survival and inability to inflate the swim bladder for commercial coatings. These findings suggest, similar to medical conclusions, compounds leaching from silicone coatings can impact development and the topic deserves study.

Association between household composition and severe COVID-19 outcomes in older people by ethnicity: an observational cohort study using the OpenSAFELY platform

Ethnic differences in the risk of severe COVID-19 may be linked to household composition. We quantified the association between household composition and risk of severe COVID-19 by ethnicity for older individuals. With the approval of NHS England, we analysed ethnic differences in the association between household composition and severe COVID-19 in people aged 67 or over in England. We defined households by number of generations living together, and used multivariable Cox regression stratified by location and wave of the pandemic and accounted for age, sex, comorbidities, smoking, obesity, housing density and deprivation. We included 2 692 223 people over 67 years in wave 1 (01/02/2020-31/08/2020) and 2 731 427 in wave 2 (01/09/2020-31/01/2021). Multigenerational living was associated with increased risk of severe COVID-19 for White and South Asian older people in both waves (e.g. wave 2, 67+ living with 3 other generations vs 67+ year olds only: White HR 1{middle dot}61 95% CI 1{middle dot}38-1{middle dot}87, South Asian HR 1{middle dot}76 95% CI 1{middle dot}48-2{middle dot}10), with a trend for increased risks of severe COVID-19 with increasing generations in wave 2. Multigenerational living was associated with severe COVID-19 in older adults. Older South Asian people are over-represented within multigenerational households in England, especially in the most deprived settings. The number of generations in a household, number of occupants, ethnicity and deprivation status are important considerations in the continued roll-out of COVID-19 vaccination and targeting of interventions for future pandemics. FundingThis research was funded in part, by the Wellcome Trust. For the purpose of open access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

COVID-19 collateral: Indirect acute effects of the pandemic on physical and mental health in the UK

BackgroundConcerns have been raised that the response to the UK COVID-19 pandemic may have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We asked what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic? MethodsUsing electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (2017-2020), we calculated weekly primary care contacts for selected acute physical and mental health conditions (including: anxiety, depression, acute alcohol-related events, asthma and chronic obstructive pulmonary disease [COPD] exacerbations, cardiovascular and diabetic emergencies). We used interrupted time series (ITS) analysis to formally quantify changes in conditions after the introduction of population-wide restrictions ( lockdown) compared to the period prior to their introduction in March 2020. FindingsThe overall population included 9,863,903 individuals on 1st January 2017. Primary care contacts for all conditions dropped dramatically after introduction of population-wide restrictions. By July 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels. The largest reductions were for contacts for: diabetic emergencies (OR: 0.35, 95% CI: 0.25-0.50), depression (OR: 0.53, 95% CI: 0.52-0.53), and self-harm (OR: 0.56, 95% CI: 0.54-0.58). InterpretationThere were substantial reductions in primary care contacts for acute physical and mental conditions with restrictions, with limited recovery by July 2020. It is likely that much of the deficit in care represents unmet need, with implications for subsequent morbidity and premature mortality. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people experiencing the conditions and healthcare provision. Maintaining access must be a key priority in future public health planning (including further restrictions). FundingWellcome Trust Senior Fellowship (SML), Health Data Research UK. RESULTS IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSA small study in 47 GP practices in a largely deprived, urban area of the UK (Salford) reported that primary care consultations for four broad diagnostic groups (circulatory disease, common mental health problems, type 2 diabetes mellitus and malignant cancer) declined by 16-50% between March and May 2020, compared to what was expected based on data from January 2010 to March 2020. We searched Medline for other relevant evidence of the indirect effect of the COVID-19 pandemic on physical and mental health from inception to September 25th 2020, for articles published in English, with titles including the search terms ("covid*" or "coronavirus" or "sars-cov-2"), and title or abstracts including the search terms ("indirect impact" or "missed diagnos*" or "missing diagnos*" or "delayed diagnos*" or (("present*" or "consult*" or "engag*" or "access*") AND ("reduction" or "decrease" or "decline")). We found no further studies investigating the change in primary care contacts for specific physical- and mental-health conditions indirectly resulting from the COVID-19 pandemic or its control measures. There has been a reduction in hospital admissions and presentations to accident and emergency departments in the UK, particularly for myocardial infarctions and cerebrovascular accidents. However, there is no published evidence specifically investigating the changes in primary care contacts for severe acute physical and mental health conditions. Added value of this studyTo our knowledge this is the first study to explore changes in healthcare contacts for acute physical and mental health conditions in a large population representative of the UK. We used electronic primary care health records of nearly 10 million individuals across the UK to investigate the indirect impact of COVID-19 on primary care contacts for mental health, acute alcohol-related events, asthma/chronic obstructive pulmonary disease (COPD) exacerbations, and cardiovascular and diabetic emergencies up to July 2020. For all conditions studied, we found primary care contacts dropped dramatically following the introduction of population-wide restriction measures in March 2020. By July 2020, with the exception of unstable angina and acute alcohol-related events, primary care contacts for all conditions studied had not recovered to pre-lockdown levels. In the general population, estimates of the absolute reduction in the number of primary care contacts up to July 2020, compared to what we would expect from previous years varied from fewer than 10 contacts per million for some cardiovascular outcomes, to 12,800 per million for depression and 6,600 for anxiety. In people with COPD, we estimated there were 43,900 per million fewer contacts for COPD exacerbations up to July 2020 than what we would expect from previous years. Implicatins of all the available evidenceWhile our results may represent some genuine reduction in disease frequency (e.g. the restriction measures may have improved diabetic glycaemic control due to more regular daily routines at home), it is more likely the reduced primary care conatcts we saw represent a substantial burden of unmet need (particularly for mental health conditions) that may be reflected in subsequent increased mortality and morbidity. Health service providers should take steps to prepare for increased demand in the coming months and years due to the short and longterm ramifications of reduced access to care for severe acute physical and mental health conditions. Maintaining access to primary care is key to future public health planning in relation to the pandemic.

Inhaled corticosteroid use and risk COVID-19 related death among 966,461 patients with COPD or asthma: an OpenSAFELY analysis

BackgroundEarly descriptions of the coronavirus outbreak showed a lower prevalence of asthma and COPD than was expected for people diagnosed with COVID-19, leading to speculation that inhaled corticosteroids (ICS) may protect against infection with SARS-CoV-2, and development of serious sequelae. We evaluated the association between ICS and COVID-19 related death using linked electronic health records in the UK. MethodsWe conducted cohort studies on two groups of people (COPD and asthma) using the OpenSAFELY platform to analyse data from primary care practices linked to national death registrations. People receiving an ICS were compared to those receiving alternative respiratory medications. Our primary outcome was COVID-19 related death. FindingsWe identified 148,588 people with COPD and 817,973 people with asthma receiving relevant respiratory medications in the four months prior to 01 March 2020. People with COPD receiving ICS were at a greater risk of COVID-19 related death compared to those receiving a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) (adjusted HR = 1.38, 95% CI = 1.08 - 1.75). People with asthma receiving high dose ICS were at an increased risk of death compared to those receiving a short-acting beta agonist (SABA) only (adjusted HR = 1.52, 95%CI = 1.08 - 2.14); the adjusted HR for those receiving low-medium dose ICS was 1.10 (95% CI = 0.82 - 1.49). Quantitative bias analyses indicated that an unmeasured confounder of only moderate strength of association with exposure and outcome could explain the observed associations in both populations. InterpretationThese results do not support a major role of ICS in protecting against COVID-19 related deaths. Observed increased risks of COVID-19 related death among people with COPD and asthma receiving ICS can be plausibly explained by unmeasured confounding due to disease severity. FundingThis work was supported by the Medical Research Council MR/V015737/1.

Accident and emergency (AE) attendance in England following infection with SARS-CoV-2 Omicron or Delta

The SARS-CoV-2 Omicron variant is increasing in prevalence around the world. Accurate estimation of disease severity associated with Omicron is critical for pandemic planning. We found lower risk of accident and emergency (AE) attendance following SARS-CoV-2 infection with Omicron compared to Delta (HR: 0.39 (95% CI: 0.30 - 0.51; P<.0001). For AE attendances that lead to hospital admission, Omicron was associated with an 85% lower hazard compared with Delta (HR: 0.14 (95% CI: 0.09 - 0.24; P<.0001)). Conflicts of InterestsNothing to declare. Funding statementThis work was supported by the Medical Research Council MR/V015737/1. TPP provided technical expertise and infrastructure within their data centre pro bono in the context of a national emergency. Rosalind Eggo is funded by HDR UK (grant: MR/S003975/1), MRC (grant: MC_PC 19065), NIHR (grant: NIHR200908).

Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: cohort study in OpenSAFELY using linked primary care, secondary care and death registration data

BackgroundThere is concern about medium to long-term adverse outcomes following acute COVID-19, but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation. Methods and FindingsWorking on behalf of NHS-England, we used linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February-December 2020), and (i) demographically-matched controls from the 2019 general population; (ii) people discharged from influenza hospitalisation in 2017-19. We used Cox regression adjusted for personal and clinical characteristics. 24,673 post-discharge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls were followed for [≤]315 days. Overall risk of hospitalisation or death (30968 events) was higher in the COVID-19 group than general population controls (adjusted-HR 2.23, 2.14-2.31) but similar to the influenza group (adjusted-HR 0.94, 0.91-0.98). All-cause mortality (7439 events) was highest in the COVID-19 group (adjusted-HR 4.97, 4.58-5.40 vs general population controls and 1.73, 1.60-1.87 vs influenza controls). Risks for cause-specific outcomes were higher in COVID-19 survivors than general population controls, and largely comparable between COVID-19 and influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted/die due to their initial infection/other lower respiratory tract infection (adjusted-HR 1.37, 1.22-1.54), and to experience mental health or cognitive-related admission/death (adjusted-HR 1.36, 1.01-2.83); in particular, COVID-19 survivors with pre-existing dementia had higher risk of dementia death. One limitation of our study is that reasons for hospitalisation/death may have been misclassified in some cases due to inconsistent use of codes. ConclusionsPeople discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations; but COVID-19 patients had higher risks of all-cause mortality, readmissions/death due to the initial infection, and dementia death, highlighting the importance of post-discharge monitoring.

Association between oral anticoagulants and COVID-19 related outcomes: two cohort studies

ObjectivesWe investigated the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes, comparing current OAC use versus non-use in Study 1; and warfarin versus direct oral anticoagulants (DOACs) in Study 2. DesignTwo cohort studies, on behalf of NHS England. SettingPrimary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. ParticipantsStudy 1: 70,464 people with atrial fibrillation (AF) and CHA{square}DS{square}-VASc score of 2. Study 2: 372,746 people with non-valvular AF. Main outcome measuresTime to test for SARS-CoV-2, testing positive for SARS-CoV-2, COVID-19 related hospital admission, COVID-19 deaths or non-COVID-19 deaths in Cox regression. ResultsIn Study 1, we included 52,416 current OAC users and 18,048 non-users. We observed no difference in risk of being tested for SARS-CoV-2 associated with current use (adjusted HR, 1.01, 95%CI, 0.96 to 1.05) versus non-use. We observed a lower risk of testing positive for SARS-CoV-2 (adjusted HR, 0.73, 95%CI, 0.60 to 0.90), and COVID-19 deaths (adjusted HR, 0.69, 95%CI, 0.49 to 0.97) associated with current use versus non-use. In Study 2, we included 92,339 warfarin users and 280,407 DOAC users. We observed a lower risk of COVID-19 deaths (adjusted HR, 0.79, 95%CI, 0.76 to 0.83) associated with warfarin versus DOACs. Similar associations were found for all other outcomes. ConclusionsAmong people with AF and a CHA{square}DS{square}-VASc score of 2, those receiving OACs had a lower risk of receiving a positive COVID-19 test and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or more cautious behaviours leading to reduced infection risk. There was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin versus DOACs in people with non-valvular AF regardless of CHA{square}DS{square}-VASc score. Key pointsO_ST_ABSWhat is already known on this topicC_ST_ABSO_LICurrent studies suggest that prophylactic or therapeutic anticoagulant use, particularly low molecular weight heparin, lower the risk of pulmonary embolism and mortality during hospitalisation among patients with COVID-19. C_LIO_LIReduced vitamin K status has been reported to be correlated with severity of COVID-19. This could mean that warfarin, as a vitamin K antagonist, is associated with more severe COVID-19 disease than non-vitamin K anticoagulants. C_LI What this study addsO_LIIn 70,464 people with atrial fibrillation, at the threshold of being treated with an OAC based on risk of stroke, we observed a lower risk of testing positive for SARS-CoV-2 and COVID-19 related deaths associated with routinely prescribed OACs, relative to non-use. C_LIO_LIThis might be explained by OACs preventing severe COVID-19 outcomes, or more cautious behaviours and environmental factors reducing the risk of SARS-CoV-2 infection in those taking OACs. C_LIO_LIIn 372,746 people with non-valvular atrial fibrillation, there was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin compared with DOACs. C_LI

Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England

The B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (HR: 1.67 (95% CI: 1.34 - 2.09; P<.0001). Absolute risk of death by 28-days increased with age and comorbidities. VOC has potential to spread faster with higher mortality than the pandemic to date.