Evolution of immune genes is associated with the Black Death.

Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial.

BACKGROUND: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. METHODS: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404. FINDINGS: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90-1·11; p=0·96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention. INTERPRETATION: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths. FUNDING: British Heart Foundation.

Determinants of lipid clinic referral and attendance in a multi-ethnic adult population in south London: a cross-sectional study.

BACKGROUND: Primary dyslipidaemias, including familial hypercholesterolaemia, are underdiagnosed genetic disorders that substantially increase risk for premature coronary artery disease in adults. Early identification of primary dyslipidaemias via lipid clinic referral optimises patient management and enables cascade screening of relatives. Improving the identification of primary dyslipidaemias, and understanding disparities in ascertainment and management, is an NHS priority. We aimed to assess determinants of lipid clinic referral or attendance (LCR) in ethnically diverse adults. METHODS: We did a retrospective cross-sectional study using the Lambeth DataNet containing anonymised data from 41 general practitioner (GP) practices in south London. We looked at referral data for adult patients aged 18 years and older from Jan 1, 1995, until May 14, 2018. LCR was the main outcome. We used sequential multilevel logistic regression models adjusted for practice effects to estimate the odds of LCR assessed across six ethnic groups (reference group White) and patient-level factors (demographic, socioeconomic, lifestyle, comorbidities, total cholesterol [TC] >7·5mmol/L, statin prescription, and practice factors). The study was approved by NHS South East London Clinical Commissioning Group (CCG) and NHS Lambeth CCG. FINDINGS: 780 (0·23%) of 332 357 adult patients were coded as referred (n=538) or seen (n=252) in a lipid clinic. 164 487 (46·49%) were women (appendix). The fully adjusted model for odds of LCR showed the following significant associations for age (odds ratio [OR] 0·96, 95% CI 0·96-0·97, p<0·001); Black, African, Caribbean, or Black-British ethnicity (0·67, 0·53-0·84, p=0·001); ex-smoker status (1·29, 1·05-1·57, p=0·014); TC higher than 7·5 mmol/L (12·18, 9·60-15·45, p<0·001); statin prescription (14·01, 10·85-18·10, p<0·001); diabetes (0·72, 0·58-0·91, p=0·005); high-frequency GP attendance at seven or more GP consultations in the past year (1·49, 1·21-1·84, p<0·001); high GP-density (0·5-0·99 full-time equivalent GPs per 1000 patients; 2·70, 1·23-5·92, p=0·013). Sensitivity analyses for LCR restricted to familial hypercholesterolaemia-coded patients (n=581) found associations with TC higher than 7·5 mmol/L (4·26, 1·89-9·62, p<0·001), statin prescription (16·96, 2·19-131·36, p=0·007), and high GP-density (5·73, 1·27-25·93, p=0·023), with no significant associations with ethnicity. The relative contribution of GP practices to LCR was 6·32% of the total variance. There were no significant interactions between ethnicity and deprivation, age, or obesity. INTERPRETATION: While interpretation is limited by the accuracy and completeness of coded records, the study showed factors associated with a higher likelihood of LCR included individuals recorded as having TC higher than 7·5 mmol/L, statin prescription, ex-smoker status, high-frequency GP attendance, and registration at a GP practice with 0·5-0·99 GP density. Patients with increasing age; Black, African, Caribbean, or Black-British ethnicity patients; and patients with diabetes had lower odds of LCR. Finally, the difference in odds of LCR between Black and White patients highlights potential health inequalities. FUNDING: NHS Race & Health Observatory.

Investigating the cause of increased tetracycline-resistant Neisseria gonorrhoeae in England, 2016-20.

BACKGROUND: Antimicrobial resistance in Neisseria gonorrhoeae is a global public health concern. Tetracycline resistance (TetR) increased from 39.4% to 75.2% between 2016 and 2021 in N. gonorrhoeae isolates collected through national surveillance in England, despite the absence of use of tetracyclines for the treatment of gonorrhoea. OBJECTIVES: We investigated whether there was correlation between bacterial sexually transmitted infection (STI) tests performed and treatment with antimicrobials, with increased TetR in N. gonorrhoeae. METHODS: We examined correlations between bacterial STI tests, antimicrobial treatment and TetR in N. gonorrhoeae, using national surveillance data from three large sexual health services (SHS) in London during 2016-20. Doxycycline prescribing data and antibiograms of a non-STI pathogen from distinct patient groups (sexual health, obstetric and paediatric), at a large London hospital, were analysed to identify if doxycycline use in SHS was associated with resistance in a non-STI organism. RESULTS: A substantial increase in TetR was observed, particularly in isolates from gay, bisexual and other MSM (GBMSM). Strong positive correlations were observed exclusively in GBMSM between N. gonorrhoeae TetR and both bacterial STI tests (r = 0.97, P = 0.01) and antimicrobial treatment (r = 0.87, P = 0.05). Doxycycline prescribing increased dramatically during the study period in SHS. Prevalence of TetR in Staphylococcus aureus was higher in isolates sourced from SHS attendees than those from other settings. CONCLUSIONS: Frequent screening of GBMSM at higher risk of STIs, such as those on pre-exposure prophylaxis (PrEP) leading to/and increased use of doxycycline for the treatment of diagnosed infections, may account for the increase in TetR in N. gonorrhoeae.

Contribution of Cold Versus Climate Change to Mortality in London, UK, 1976-2019.

Objectives. To quantify past reductions in cold-related mortality attributable to anthropogenic climate change. Methods. We performed a daily time-series regression analysis employing distributed lag nonlinear models of 1 203 981 deaths in Greater London, United Kingdom, in winter months (November-March) during 1976 to 2019. We made attribution assessment by comparing differential cold-related mortality impacts associated with observed temperatures to those using counterfactual temperatures representing no climate change. Results. Over the past decade, the average number of cold days (below 8 °C) per year was 120 in the observed series and 158 in the counterfactual series. Since 1976, we estimate 447 (95% confidence interval = 330, 559) annual cold-related all-cause deaths have been avoided because of milder temperatures associated with climate change. Annually, 241 cardiovascular and 73 respiratory disease deaths have been avoided. Conclusions. Anthropogenic climate change made some contribution to reducing previous cold-related deaths in London; however, cold remains an important public health risk factor. Public Health Implications. Better adaptation to both heat and cold should be promoted in public health measures to protect against climate change. In England, this has been addressed by the development of a new year-round Adverse Weather and Health Plan. (Am J Public Health. 2024;114(4):398-402. https://doi.org/10.2105/AJPH.2023.307552).

Application of information from external data to correct for collider bias in a Covid-19 hospitalised cohort.

BACKGROUND: Throughout the Covid-19 pandemic, researchers have made use of electronic health records to research this disease in a rapidly evolving environment of questions and discoveries. These studies are prone to collider bias as they restrict the population of Covid-19 patients to only those with severe disease. Inverse probability weighting is typically used to correct for this bias but requires information from the unrestricted population. Using electronic health records from a South London NHS trust, this work demonstrates a method to correct for collider bias using externally sourced data while examining the relationship between minority ethnicities and poor Covid-19 outcomes. METHODS: The probability of inclusion within the observed hospitalised cohort was modelled based on estimates from published national data. The model described the relationship between patient ethnicity, hospitalisation, and death due to Covid-19 - a relationship suggested to be susceptible to collider bias. The obtained probabilities (as applied to the observed patient cohort) were used as inverse probability weights in survival analysis examining ethnicity (and covariates) as a risk factor for death due to Covid-19. RESULTS: Within the observed cohort, unweighted analysis of survival suggested a reduced risk of death in those of Black ethnicity - differing from the published literature. Applying inverse probability weights to this analysis amended this aberrant result to one more compatible with the literature. This effect was consistent when the analysis was applied to patients within only the first wave of Covid-19 and across two waves of Covid-19 and was robust against adjustments to the modelled relationship between hospitalisation, patient ethnicity, and death due to Covid-19 made as part of a sensitivity analysis. CONCLUSIONS: In conclusion, this analysis demonstrates the feasibility of using external publications to correct for collider bias (or other forms of selection bias) induced by the restriction of a population to a hospitalised cohort using an example from the recent Covid-19 pandemic.

Diagnosis and management of tuberculosis infection in inclusion health populations in London.

BACKGROUND: Tuberculosis in the UK is more prevalent in people with social risk factors- e.g. previous incarceration, homelessness - and in migrants from TB endemic countries. The management of TB infection is part of TB elimination strategies, but is challenging to provide to socially excluded groups and the evidence base for effective interventions is small. METHODS: We evaluated a TB infection screening and treatment programme provided by a peer-led service (Find&Treat) working in inclusion health settings (e.g. homeless hostels) in London. IGRA (interferon-gamma release assay) testing and TB infection treatment were offered to eligible adults using a community-based model. The primary outcome was successful progression through the cascade of care. We also evaluated socio-demographic characteristics associated with a positive IGRA. RESULTS: 42/312 (13.5%) participants had a positive IGRA and no one had evidence of active TB. 35/42 completed a medical evaluation; 22 started treatment, and 17 completed treatment. Having a positive IGRA was associated with previous incarceration and being born outside of the UK. DISCUSSION: Provision of TB infection diagnosis and management to this socially excluded population has several challenges including maintaining people in care and drug-drug interactions. Peer-support workers provided this service safely and effectively with appropriate support. Further work to generate data to inform risks and benefits of treatment for TB infection in this group is needed to facilitate joint decision making.

An investigation of neuropsychiatric symptoms, contextual factors, and antidepressant treatment as risk factors for dementia development in people with mild cognitive impairment.

BACKGROUND: While some people with mild cognitive impairment (MCI) progress to dementia, many others show no progression. The aim of this study was to identify factors associated with risk of dementia development in this population. METHOD: A large naturalistic retrospective cohort study was assembled from mental healthcare records in a south London catchment. Patients were selected at first recorded diagnosis of MCI and subsequent dementia diagnosis was ascertained from case notes or death certificate, excluding those with dementia diagnoses and deaths within 6 months of MCI diagnosis. A range of demographic and clinical characteristics were ascertained around MCI diagnosis and Cox proportional hazards models were used to investigate independent predictors of dementia, focussing on neuropsychiatric symptoms, contextual factors, and antidepressant treatment. RESULTS: Of 2250 patients with MCI, 236 (10.5%) developed dementia at least 6 months after MCI diagnosis. Aside from older age, lower cognitive function, and activities of daily living impairment, impaired social relationships and recorded loneliness were associated with a higher risk of developing dementia. Patients of Black (compared to White) ethnicity were at a lower risk. For depression and antidepressant receipt, only tricyclic use compared to no antidepressant use was associated with an increased dementia risk. CONCLUSIONS: No evidence was found for co-morbid affective disorders or different antidepressant classes as risk factors for dementia development following MCI diagnosis, but loneliness and social impairment were independent predictors and would be worth evaluating as targets for interventions to delay progression.

Reduced risk for Omicron SARS-CoV-2 infection observed in older adults with hybrid immunity.

BACKGROUND: Hybrid SARS-CoV-2 immunity may provide longer duration protection against severe SARS-CoV-2 infection and hospitalisation than purely vaccine-derived immunity. Older adults represent a high-risk group for severe disease, yet available data is skewed towards younger adults. METHODS: A prospective longitudinal study at a large London long-term care facility (LTCF) was conducted from March 2020 to April 2022 to assess the effect of hybrid versus vaccine-only immunity on SARS-CoV-2 infection in older adults during Omicron variant dominance. Hybrid immunity was assessed by a combination of SARS-CoV-2 polymerase chain reaction testing weekly (asymptomatic screening) and as required (symptomatic testing), as well as serial SARS-CoV-2 serology. RESULTS: 280 participants (median age 82 yrs, IQR 76-88 yrs; 95.4% male) were followed up. 168/280 (60%) had evidence of hybrid immunity prior to the Omicron variant wave. Participants with hybrid immunity had substantially lower odds of acquiring COVID-19 infection during the Omicron wave compared to those with vaccine-only immunity (unadjusted odds ratio 0.26, 95% CI 0.14-0.47, chi-squared P < .0001). Participants with hybrid immunity had an odds ratio of 0.40 (0.19-0.79) for asymptomatic infection and 0.15 (0.06-0.34) for symptomatic infection (Likelihood ratio test, P < .0001). DISCUSSION: Our data highlight potential opportunities to target ongoing booster vaccination campaigns for those most at risk of severe infection. Reporting of data in older adults will be of particular value to examine the effect of hybrid immunity as new variants continue to emerge and vaccination strategies evolve.

Changes in diet and physical activity following a community-wide pilot intervention to tackle childhood obesity in a deprived inner-London ward.

BACKGROUND: Local authorities in England have an important role in shaping healthy local environments contributing to childhood obesity. This study examined changes in diet and physical activity in primary school children following a three-year, complex, community-based intervention in Golborne ward, the second most deprived ward in London. METHODS: The Go-Golborne intervention aimed to shape the local environment across multiple settings with the engagement of a large number of local government and community stakeholders in a joint approach. Activities focused on six co-created themes to make changes to local environments and reduce sugary snacks and beverage consumption, increase fruit and vegetable intake, promote healthy snacks, increase active play and travel, and reduce screen time. We analysed changes in self-reported diet and physical activity, collected annually between 2016 and 2019, from 1,650 children aged 6-11 years through six local schools, who all received the intervention. We used multilevel, linear and logistic random-slope regression models adjusted for time on study, baseline age, gender, ethnicity, deprivation quintile, school, and baseline weight status. RESULTS: After three years of follow-up, there were reductions in sugar-sweetened beverage consumption (adjusted beta -0·43 occasions/day, 95% CI -0·55 to -0·32), fruit and vegetable consumption (adjusted beta -0.22 portions, 95% CI -0.44 to 0.001) and car travel to and from school (adjusted OR 0·19, 95% CI 0·06 to 0·66), while screen time increased (high versus moderate/low: OR 2·30, 95% CI 1·36 to 3·90). For other behavioural outcomes, there was no statistically significant evidence of changes. CONCLUSION: Local authorities have substantial powers to make positive changes to the obesogenic environment but programmes remain under-evaluated. Results from the ambitious Go-Golborne intervention demonstrated mixed results in health behaviours following programme implementation. These results underline the importance of a coordinated and comprehensive policy response to support changes in wider environmental and social conditions as well as appropriate and holistic evaluations of initiatives to inform local actions on obesogenic environments.

Using online search activity for earlier detection of gynaecological malignancy.

BACKGROUND: Ovarian cancer is the most lethal and endometrial cancer the most common gynaecological cancer in the UK, yet neither have a screening program in place to facilitate early disease detection. The aim is to evaluate whether online search data can be used to differentiate between individuals with malignant and benign gynaecological diagnoses. METHODS: This is a prospective cohort study evaluating online search data in symptomatic individuals (Google user) referred from primary care (GP) with a suspected cancer to a London Hospital (UK) between December 2020 and June 2022. Informed written consent was obtained and online search data was extracted via Google takeout and anonymised. A health filter was applied to extract health-related terms for 24 months prior to GP referral. A predictive model (outcome: malignancy) was developed using (1) search queries (terms model) and (2) categorised search queries (categories model). Area under the ROC curve (AUC) was used to evaluate model performance. 844 women were approached, 652 were eligible to participate and 392 were recruited. Of those recruited, 108 did not complete enrollment, 12 withdrew and 37 were excluded as they did not track Google searches or had an empty search history, leaving a cohort of 235. RESULTS: The cohort had a median age of 53 years old (range 20-81) and a malignancy rate of 26.0%. There was a difference in online search data between those with a benign and malignant diagnosis, noted as early as 360 days in advance of GP referral, when search queries were used directly, but only 60 days in advance, when queries were divided into health categories. A model using online search data from patients (n = 153) who performed health-related search and corrected for sample size, achieved its highest sample-corrected AUC of 0.82, 60 days prior to GP referral. CONCLUSIONS: Online search data appears to be different between individuals with malignant and benign gynaecological conditions, with a signal observed in advance of GP referral date. Online search data needs to be evaluated in a larger dataset to determine its value as an early disease detection tool and whether its use leads to improved clinical outcomes.

A recent surge of nitrous oxide misuse around London which merits a public health warning.

BACKGROUND: Use of nitrous oxide (N2O) gas for recreational purposes by young people is increasingly recognized as a public health hazard in the UK. METHODS: We looked at the hospital records of patients admitted over the last 4 years to a single neurological centre in Essex to determine the demographics, presentation, and management of patients presenting with symptoms of N2O toxicity from its recreational use. RESULTS: Of the 17 patients (mean age = 22.9 ± 3 years) admitted between September 2018 and October 2022, 70% were admitted between January and October 2022. All patients reported limb paraesthesiae and 16/17 reported (95%) imbalance; 11/17 (65%) showed objective limb weakness. Serum B12 concentration was low in 9/17 (53%). Plasma methylmalonic acid (n = 7) and homocysteine (n = 8) levels were elevated in all patients tested. Spinal cord Magnetic Resonance Imaging (MRI) imaging was abnormal in 10/17 (59%) patients. Nerve conduction studies were abnormal in 10/13 (77%) patients, with evidence of a symmetric, length-dependent, large fibre neuropathy. CONCLUSIONS: There has been a recent surge of cases with neurological complications of recreational N2O abuse in the UK, with a relatively greater rate in 2022. Greater awareness of this condition amongst clinicians and health regulators is urgently required to prevent harm from N2O misuse in young people.

Lifetime and 10-year risks of cardiovascular mortality in relation to risk factors in middle and old age: 50-year follow-up of the Whitehall study of London Civil Servants.

BACKGROUND: Cardiovascular disease (CVD)-related mortality has declined substantially in the United Kingdom (UK) in recent decades, but the continued relevance of conventional risk factors for prediction of CVD mortality throughout the life-course is uncertain. We compared the 10-year risks and lifetime risks of CVD mortality associated with conventional risk factors recorded in middle and old age. METHODS: The Whitehall study was a prospective study of 19,019 male London civil servants (mean age 52 years) when enrolled in 1967-1970 and followed-up for 50 years for cause-specific mortality. In 1997, 7044 (83%) survivors (mean age 77 years) were re-surveyed. The 10-year and lifetime risks of CVD mortality were estimated by levels of CVD risk factors recorded in middle-age and old-age, respectively. RESULTS: By July 2020, 97% had died (22%, 51% and 80% before age 70, 80 and 90 years, respectively) and 7944 of 17,673 deaths (45%) were from CVD. The 10-year and lifetime risks of CVD death increased linearly with higher levels of CVD risk factors recorded in middle-age and in old-age. Individuals in the top versus bottom 5% of CVD risk scores in middle age had a 10.3% (95% CI:7.2-13.4) vs 0.6% (0.1-1.2) 10-year risk of CVD mortality, a 61.4% (59.4-65.3) vs 31.3% (24.1-34.5) lifetime risk of CVD mortality and a 12-year difference in life expectancy from age 50 years. The corresponding differences using a CVD risk score in old-age were 11.0% (4.4-17.5) vs 0.8% (0.0-2.2) for 10-year risk and 42.1% (28.2-50.0) vs 30.3% (6.0-38.0) for lifetime risk of CVD mortality and a 6-year difference in life expectancy from age 70 years. CONCLUSIONS: Conventional risk factors remained highly predictive of CVD mortality and life expectancy through the life-course. The findings highlight the relevance of estimation of both lifetime risks of CVD and 10-year risks of CVD for primary prevention of CVD.

Sustained detection of type 2 poliovirus in London sewage between February and July, 2022, by enhanced environmental surveillance.

BACKGROUND: The international spread of poliovirus exposes all countries to the risk of outbreaks and is designated a Public Health Emergency of International Concern by WHO. This risk can be exacerbated in countries using inactivated polio vaccine, which offers excellent protection against paralysis but is less effective than oral vaccine against poliovirus shedding, potentially allowing circulation without detection of paralytic cases for long periods of time. Our study investigated the molecular properties of type 2 poliovirus isolates found in sewage with an aim to detect virus transmission in the community. METHODS: We performed environmental surveillance in London, UK, testing sewage samples using WHO recommended methods that include concentration, virus isolation in cell culture, and molecular characterisation. We additionally implemented direct molecular detection and determined whole-genome sequences of every isolate using novel nanopore protocols. FINDINGS: 118 genetically linked poliovirus isolates related to the serotype 2 Sabin vaccine strain were detected in 21 of 52 sequential sewage samples collected in London between Feb 8 and July 4, 2022. Expansion of environmental surveillance sites in London helped localise transmission to several boroughs in north and east London. All isolates have lost two key attenuating mutations, are recombinants with a species C enterovirus, and an increasing proportion (20 of 118) meet the criterion for a vaccine-derived poliovirus, having six to ten nucleotide changes in the gene coding for VP1 capsid protein. INTERPRETATION: Environmental surveillance allowed early detection of poliovirus importation and circulation in London, permitting a rapid public health response, including enhanced surveillance and an inactivated polio vaccine campaign among children aged 1-9 years. Whole-genome sequences generated through nanopore sequencing established linkage of isolates and confirmed transmission of a unique recombinant poliovirus lineage that has now been detected in Israel and the USA. FUNDING: Medicines and Healthcare products Regulatory Agency, UK Health Security Agency, Bill & Melinda Gates Foundation, and National Institute for Health Research Medical Research Council.

The impact of the COVID-19 pandemic on people experiencing homelessness: a qualitative interview study in the UK.

BACKGROUND: People experiencing homelessness faced unique challenges during the COVID-19 pandemic, including changes to accommodation availability, societal restrictions impacting access to essentials like food, and services moving to remote access. There is a paucity of in-depth qualitative research exploring how the pandemic affected this population, which this research aims to address. METHODS: 33 semi-structured qualitative interviews (22 with people who experienced homelessness during the pandemic and 11 with homelessness sector service providers) were done in the UK between April 26, 2021, and Jan, 25, 2022. Ethical approval was granted by the University College London research ethics committee (Project ID: 14895/005) and all participants provided informed consent. Interviews were audio-recorded, transcribed, and analysed using reflexive thematic analysis utilising NVivo software. Four interviews were coded by two researchers for consistency of codes. FINDINGS: In our sample of people experiencing homelessness, 11 (50%) were female, 13 (59%) White British, all were aged between 24 and 59 years, and all had lived in hostels or hotels, with friends or family, or on the streets during the pandemic. Providers interviewed worked for varied services, including support charities, housing, and addiction services. Four key themes were identified: understanding of and adherence to COVID guidelines; changes to accommodation and experiences of "Everyone In" (a government initiative in which people sleeping on the street or in accommodation where it was difficult to self-isolate were provided emergency accommodation); living through a pandemic while navigating homelessness; and, adaptations to service provision for people experiencing homelessness. INTERPRETATION: Policy makers and public health communicators must learn from people experiencing homelessness to maximise effectiveness of future public health strategies. Housing providers and support services should recognise the implications of imposing a scarcity of choice on people who need accommodation during a public health emergency. The loss of usual support was destabilising for people experiencing homelessness, triggering a need to adopt survival tactics which negatively influence their health. Although this research was limited by the possibility that views expressed might differ from those unwilling or unable to participate, it does highlight successes and difficulties in supporting people experiencing homelessness during the COVID-19 pandemic and informs planning for similar public health events. FUNDING: Nuffield Foundation, Wellcome Trust.

How did living in temporary accommodation during the COVID-19 pandemic affect children younger than 5 years' access to health care and health outcomes? A qualitative study of key professionals in a socially and ethnically diverse and deprived area of London.

BACKGROUND: Children younger than 5 years living in temporary accommodation due to homelessness (U5TA) are extremely vulnerable to the effects of the COVID-19 pandemic. Few qualitative studies have examined provider perspectives in family homelessness, but none focused on U5TA specifically. We aimed to qualitatively explore professionals' perspectives of pandemic-related challenges and barriers experienced by U5TA in accessing health care and optimising health outcomes, and their experiences of delivering U5TA services. METHODS: 16 semi-structured interviews were done online. Professionals working in the London Borough of Newham with U5TA families were purposively sampled and recruited from non-profit organisations, the health sector, and local authority. A thematic codebook approach was used to analyse the data combining inductive and deductive codes using an adapted socioecological model as a guiding theoretical framework. FINDINGS: Two non-profit organisation professionals, seven health visitors, one GP, therapist, dietician, nurse, public health consultant, and two social workers from the local authority's No Recourse to Public Funds team described adverse pandemic effects on U5TA health: delay and regression in developmental milestones and behaviours-eg, toileting, feeding skills, emotional regulation, and social-communication skills. Pre-existing systemic barriers were exacerbated during the pandemic when the reduction of in-person services with professionals necessitated remote delivery of health and social care services. Differential effects of digital poverty, language discordance, and inability to register and track U5TA rendered this population invisible to services. Professionals highly agreed that barriers to optimal health outcomes and service access included poor mental health, unsuitable housing, no social support, mistrust of mainstream services, immigration administration, financial insecurity, and loss of informal jobs among U5TA families. Professionals sometimes mitigated these barriers with good communication skills, developing trusting relations, and through community facilitators. INTERPRETATION: COVID-19 widened health inequalities and inequities, substantially affecting the lives of U5TA and ability of professionals to deliver quality care to U5TA. Innovative and tailored cross-sector strategies, including co-production of public health services, are required. Policies and services urgently need to focus on early development, mental health support, employment training, and opportunities for parents and carers, plus unambiguous definitions of what is deemed suitable accommodation and actionable planned steps to ensure enforcement. FUNDING: None.

Experience of homelessness during the COVID-19 pandemic in Tower Hamlets, London: a health needs assessment.

BACKGROUND: The COVID-19 pandemic has affected people experiencing homelessness in multiple ways. The Everyone In initiative during 2020 was initially transformative in providing short-term accommodation for this group but was accompanied by major disruptions to treatment and support services. Understanding how these changes have affected health needs of people experiencing homelessness in the inner-city London Borough of Tower Hamlets can inform future service commissioning. METHODS: We conducted a focussed health needs assessment of people experiencing homelessness in Tower Hamlets. Quantitative data were gathered from the Combined Homelessness and Information Network (CHAIN), local authority housing services, primary care datasets, and substance dependency services. These data were combined with qualitative data from stakeholder meetings, facility visits, and lived experience insight from service users through interviews and focus groups. Analysis was targeted towards identifying gaps in existing commissioning. FINDINGS: We gathered data from 80 service users experiencing homelessness in Tower Hamlets between Sept 1 to Dec 31, 2021. Participants reported the largest impact of the pandemic being on their mental health. For people registered with specific homeless primary care services, 26·3% were experiencing depression and 12·8% other severe mental health issues. Service users with lived experience of homelessness described feeling let down by mental health support systems, describing that, despite positive experiences of individual staff, they felt the system as a whole was not well integrated. Specific issues were identified in hostel-based accommodation, where poor psychological and physical safety during lockdowns contributed to declines in mental health. INTERPRETATION: Using a health needs assessment, a necessity was identified to support the mental health of people experiencing homelessness in Tower Hamlets emerging from pandemic restrictions. People with lived experience of homelessness attributed deteriorations in mental health to extended time in inadequate accommodation, and reported that environments that take account of emotional and psychological needs were required. Provision of psychologically-informed accommodation environments and improved support service integration must be priorities for future local authority commissioning. FUNDING: None.

Implementing behavioural science informed letter interventions to increase COVID-19 vaccination uptake in uncontactable London residents: a difference-in-difference study in London, UK.

BACKGROUND: The UK COVID-19 vaccination programme began in December, 2020. By February, 2021, eight North West London Clinical Commissioning Groups (CCGs) had the lowest vaccination rates nationally. This study evaluated the impact of behavioural science-informed (BI) letters on vaccination uptake. METHODS: Unvaccinated residents of the Central London CCG who were deemed uncontactable (through text messaging and phone calls) were identified with the whole systems integrated care database. BI letters were sent to residents in the intervention CCG between May and June, 2021. Three neighbouring CCGs in London with similar non-responder data were used as control groups. A linear difference-in-difference analysis was undertaken to assess change in vaccine uptake rate across all four CCGs. Percentage point change was adjusted for selected covariates including ethnicity, age, gender, and index of multiple deprivation (IMD) quintiles. Approval was obtained from the quality improvement and audit office of Imperial College Healthcare NHS Trust (London, UK). FINDINGS: Within the intervention Central London CCG, 10 161 residents received the BI letter. The control CCGs contained 27 383 uncontactable residents. All CCGs showed an increase in vaccination rates in this population. The linear difference-in-difference analysis showed an increase in vaccination uptake in the intervention CCG (relative change 31·9% (95% CI 30·5-33·3; p<0·0001). Residents in IMD quintile 5 (least deprived) showed the largest rate of change (4·1%; p<0·0001). Residents with a mixed or multiple ethnic background were less likely to receive a COVID-19 vaccine (-4·1%, p<0·0001). INTERPRETATION: BI letters improved the rate of vaccine uptake. The percentage point increase of 31·9% equates to 436 additional previously uncontactable residents being vaccinated. Our data highlighted differences in the effect of BI-informed interventions in population subgroups. BI letters are a cost-effective and trusted communication tool, effectively engaging residents where other communication strategies did not work. FUNDING: None.

The effect of indoor soundscape on sexual wellbeing during the COVID-19 lockdown in London: a thematic analysis of remote workers' experiences.

BACKGROUND: Despite sexual wellbeing representing a potential component of the overall wellbeing of individuals, its relationship to indoor soundscape has not been investigated. The aim of this study was to identify acoustic-related variables linked to sexual wellbeing during the COVID-19 lockdown; the mechanisms through which those variables exert an influence; and the components of an ideal indoor soundscape for sexual wellbeing. METHODS: We did a thematic analysis of answers to an online survey conducted on Jan 18-19, 2021, via the Prolific participant platform. The survey was completed by 464 adult individuals working at home in London during the third national COVID-19 lockdown (Jan 6 to March 8, 2021). This study focused on two optional open-ended questions concerning (1) effects of the acoustic environment on sexual activity and (2) characteristics of an ideal soundscape for best experiencing sexual intercourse. The formation of codes and themes followed a combination of inductive and deductive approaches. FINDINGS: 345 responses were collected for question 1 (134 [39%] men, 210 [61%] women, one [<1%] other) and 310 responses for question 2 (124 [40%] men, 185 [60%] women, one [<1%] other), with a respondent age range of 18-65 years. The thematic analysis produced four themes: contextual features, characteristics of the acoustic environment, soundscape interpretation, and coping strategies. With regard to the acoustic environment, the main variables were related to the type of sound, sound dominance, and temporal patterns. Among the participants who provided relevant answers (n=239), 132 (55%) considered the acoustic environment irrelevant while being focused on the sexual activity, 72 (30%) reported negative or mixed effects, and 35 (15%) described only positive effects. Indoor soundscape resulted in privacy concerns, distraction, disruption, or support to sexual wellbeing. Soundscape interpretation triggered coping strategies (eg, adjusting windows or playing music) and behavioural changes (eg, lowering voice level), which in turn limited or increased sexual freedom, and affected or promoted sexual wellbeing. The ideal soundscape was described by three themes related to the availability of privacy and control, quietness, and pleasant sounds. INTERPRETATION: Although this study is qualitative in nature and no causal link can be established, it highlights the influence the acoustic environment at home had on sexual wellbeing during lockdown. FUNDING: Chartered Institution of Building Services Engineers.

M ycobacterium avium complex genomics and transmission in a London hospital.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are environmental microorganisms and opportunistic pathogens in individuals with pre-existing lung conditions such as cystic fibrosis (CF) and non-CF bronchiectasis. While recent studies of Mycobacterium abscessus have identified transmission within single CF centres as well as nationally and globally, transmission of other NTM species is less well studied. METHODS: To investigate the potential for transmission of the Mycobacterium avium complex (MAC) we sequenced 996 isolates from 354 CF and non-CF patients at the Royal Brompton Hospital (London, UK; collected 2013-2016) and analysed them in a global context. Epidemiological links were identified from patient records. Previously published genomes were used to characterise global population structures. RESULTS: We identified putative transmission clusters in three MAC species, although few epidemiological links could be identified. For M. avium, lineages were largely limited to single countries, while for Mycobacterium chimaera, global transmission clusters previously associated with heater-cooler units (HCUs) were found. However, the immediate ancestor of the lineage causing the major HCU-associated outbreak was a lineage already circulating in patients. CONCLUSIONS: CF and non-CF patients shared transmission chains, although the lack of epidemiological links suggested that most transmission is indirect and may involve environmental intermediates or asymptomatic carriage in the wider population.