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Detecting and quantifying changes in the growth rates of infectious diseases is vital to informing public health strategy and can inform policymakers' rationale for implementing or continuing interventions aimed at reducing their impact. Substantial changes in SARS-CoV-2 prevalence with the emergence of variants have provided an opportunity to investigate different methods for doing this. We collected polymerase chain reaction (PCR) results from all participants in the United Kingdom's COVID-19 Infection Survey between August 1, 2020, and June 30, 2022. Change points for growth rates were identified using iterative sequential regression (ISR) and second derivatives of generalized additive models (GAMs). Consistency between methods and timeliness of detection were compared. Of 8 799 079 study visits, 147 278 (1.7%) were PCR-positive. Change points associated with the emergence of major variants were estimated to occur a median of 4 days earlier (IQR, 0-8) when using GAMs versus ISR. When estimating recent change points using successive data periods, 4 change points (4/96) identified by GAMs were not found when adding later data or by ISR. Change points were detected 3-5 weeks after they occurred under both methods but could be detected earlier within specific subgroups. Change points in growth rates of SARS-CoV-2 can be detected in near real time using ISR and second derivatives of GAMs. To increase certainty about changes in epidemic trajectories, both methods could be used in parallel. [ABSTRACT FROM AUTHOR]

The associations of certain factors, such as age and menopausal hormone therapy, with breast cancer risk are known to differ for interval and screen‐detected cancers. However, the extent to which associations of other established breast cancer risk factors differ by mode of detection is unclear. We investigated associations of a wide range of risk factors using data from a large UK cohort with linkage to the National Health Service Breast Screening Programme, cancer registration, and other health records. We used Cox regression to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for associations between risk factors and breast cancer risk. A total of 9421 screen‐detected and 5166 interval cancers were diagnosed in 517,555 women who were followed for an average of 9.72 years. We observed the following differences in risk factor associations by mode of detection: greater body mass index (BMI) was associated with a smaller increased risk of interval (RR per 5 unit increase 1.07, 95% CI 1.03–1.11) than screen‐detected cancer (RR 1.27, 1.23–1.30); having a first‐degree family history was associated with a greater increased risk of interval (RR 1.81, 1.68–1.95) than screen‐detected cancer (RR 1.52, 1.43–1.61); and having had previous breast surgery was associated with a greater increased risk of interval (RR 1.85, 1.72–1.99) than screen‐detected cancer (RR 1.34, 1.26–1.42). As these differences in associations were relatively unchanged after adjustment for tumour grade, and are in line with the effects of these factors on mammographic density, they are likely to reflect the effects of these risk factors on screening sensitivity. [ABSTRACT FROM AUTHOR]

Purpose: In April 2020, the UK Government implemented NHS Test and Trace to provide SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (qRT-PCR) testing for the public, with nose-and-throat swabbing for samples performed by trained staff. Self-swabbing (SS) would allow rapid scale-up of testing capacity and access. Six studies were undertaken to determine whether SS was as effective for detecting SARS-CoV-2 as swabbing performed by trained staff. Methods: Six prospective studies were conducted between April–October 2020, using six swab/media combinations. Differences between assisted swabbing (AS) and SS were evaluated for concordance, positivity, sensitivity, cycle threshold (Ct) values and void rates. Statistical analysis was performed using 95% confidence intervals (CIs), paired t-tests and model-based methods. Results: Overall, 3,253 individuals were recruited (median age 37 years, 49% female), with 2,933 having valid paired qRT-PCR results. Pooled concordance rate was 98% (95% CI: 96%, 99%). Positivity rate differences for SS (8.1%) and AS (8.4%) and differences in pooled sensitivities between SS (86%; 95% CI: 78%, 92%) and AS (91%; 95% CI: 78%, 96%) were nonsignificant. Both types of swabbing led to pooled void rates below 2% and strongly correlated Ct values. Age, sex and previous swabbing experience did not have a significant impact on concordance or sensitivity. Conclusion: The UK adopted a policy to promote self-testing for SARS-CoV-2 based on data demonstrating equivalence of SS versus AS. Positive outcomes with SS are likely generalisable to testing for other respiratory pathogens, and we consider self-sampling and self-testing essential for future pandemic preparedness. [ABSTRACT FROM AUTHOR]

Population-representative estimates of SARS-CoV-2 infection prevalence and antibody levels in specific geographic areas at different time points are needed to optimise policy responses. However, even population-wide surveys are potentially impacted by biases arising from differences in participation rates across key groups. Here, we used spatio-temporal regression and post-stratification models to UK's national COVID-19 Infection Survey (CIS) to obtain representative estimates of PCR positivity (6,496,052 tests) and antibody prevalence (1,941,333 tests) for different regions, ages and ethnicities (7-December-2020 to 4-May-2022). Not accounting for vaccination status through post-stratification led to small underestimation of PCR positivity, but more substantial overestimations of antibody levels in the population (up to 21 percentage points), particularly in groups with low vaccine uptake in the general population. There was marked variation in the relative contribution of different areas and age-groups to each wave. Future analyses of infectious disease surveys should take into account major drivers of outcomes of interest that may also influence participation, with vaccination being an important factor to consider. Estimates of infection rates from the UK COVID-19 Infection Survey may have been biased by the characteristics of people who chose to take part. Here, the authors show that the survey population had unusually high vaccination rates and adjust infection estimates taking this into account. [ABSTRACT FROM AUTHOR]

Background: Syndromic surveillance often relies on patients presenting to healthcare. Community cohorts, although more challenging to recruit, could provide additional population-wide insights, particularly with SARS-CoV-2 co-circulating with other respiratory viruses. Methods: We estimated the positivity and incidence of SARS-CoV-2, influenza A/B, and RSV, and trends in self-reported symptoms including influenza-like illness (ILI), over the 2022/23 winter season in a broadly representative UK community cohort (COVID-19 Infection Survey), using negative-binomial generalised additive models. We estimated associations between test positivity and each of the symptoms and influenza vaccination, using adjusted logistic and multinomial models. Results: Swabs taken at 32,937/1,352,979 (2.4%) assessments tested positive for SARS-CoV-2, 181/14,939 (1.2%) for RSV and 130/14,939 (0.9%) for influenza A/B, varying by age over time. Positivity and incidence peaks were earliest for RSV, then influenza A/B, then SARS-CoV-2, and were highest for RSV in the youngest and for SARS-CoV-2 in the oldest age groups. Many test positives did not report key symptoms: middle-aged participants were generally more symptomatic than older or younger participants, but still, only ~ 25% reported ILI-WHO and ~ 60% ILI-ECDC. Most symptomatic participants did not test positive for any of the three viruses. Influenza A/B-positivity was lower in participants reporting influenza vaccination in the current and previous seasons (odds ratio = 0.55 (95% CI 0.32, 0.95)) versus neither season. Conclusions: Symptom profiles varied little by aetiology, making distinguishing SARS-CoV-2, influenza and RSV using symptoms challenging. Most symptoms were not explained by these viruses, indicating the importance of other pathogens in syndromic surveillance. Influenza vaccination was associated with lower rates of community influenza test positivity. [ABSTRACT FROM AUTHOR]

The article focuses on the importance of community involvement in addressing the mpox outbreak. Topics include the potential negative impact of classifying mpox as an STI on stigma, the need for community input in discussions about mpox, and the value of including affected communities in response efforts, as exemplified by a UK clinical treatment trial.

Antimicrobial resistance (AMR) is a threat to global public health. However, unsatisfactory approaches to directly measuring the AMR burden carried by individuals has hampered efforts to assess interventions aimed at reducing selection for AMR. Metagenomics can provide accurate detection and quantification of AMR genes within an individual person's faecal flora (their gut "resistome"). Using this approach, we aimed to test the hypothesis that differences in antimicrobial use across different hospitals in the United Kingdom will result in observable differences in the resistome of individual patients. Three National Health Service acute Hospital Trusts with markedly different antibiotic use and Clostridioides difficile infection rates collected faecal samples from anonymous patients which were discarded after C. difficile testing over a period of 9 to 15 months. Metagenomic DNA was extracted from these samples and sequenced using an Illumina NovaSeq 6000 platform. The resulting sequencing reads were analysed for taxonomic composition and for the presence of AMR genes. Among 683 faecal metagenomes we found huge variation between individuals in terms of taxonomic diversity (Shannon Index range 0.10–3.99) and carriage of AMR genes (Median 1.50 genes/cell/sample overall). We found no statistically significant differences in diversity (median Shannon index 2.16 (IQR 1.71–2.56), 2.15 (IQR 1.62–2.50) and 2.26 (IQR 1.55–2.51)) or carriage of AMR genes (median 1.37 genes/cell/sample (IQR 0.70–3.24), 1.70 (IQR 0.70–4.52) and 1.43 (IQR 0.55–3.71)) at the three trusts respectively. This was also the case across the sample collection period within the trusts. While we have not demonstrated differences over place or time using metagenomic sequencing of faecal discards, other sampling frameworks may be more suitable to determine whether organisational level differences in antibiotic use are associated with individual-level differences in burden of AMR carriage. [ABSTRACT FROM AUTHOR]

We aimed to assess the frequency of value preferences in recording of vital signs in electronic healthcare records (EHRs) and associated patient and hospital factors. We used EHR data from Oxford University Hospitals, UK, between 01-January-2016 and 30-June-2019 and a maximum likelihood estimator to determine the prevalence of value preferences in measurements of systolic and diastolic blood pressure (SBP/DBP), heart rate (HR) (readings ending in zero), respiratory rate (multiples of 2 or 4), and temperature (readings of 36.0 °C). We used multivariable logistic regression to investigate associations between value preferences and patient age, sex, ethnicity, deprivation, comorbidities, calendar time, hour of day, days into admission, hospital, day of week and speciality. In 4,375,654 records from 135,173 patients, there was an excess of temperature readings of 36.0 °C above that expected from the underlying distribution that affected 11.3% (95% CI 10.6–12.1%) of measurements, i.e. these observations were likely inappropriately recorded as 36.0 °C instead of the true value. SBP, DBP and HR were rounded to the nearest 10 in 2.2% (1.4–2.8%) and 2.0% (1.3–5.1%) and 2.4% (1.7–3.1%) of measurements. RR was also more commonly recorded as multiples of 2. BP digit preference and an excess of temperature recordings of 36.0 °C were more common in older and male patients, as length of stay increased, following a previous normal set of vital signs and typically more common in medical vs. surgical specialities. Differences were seen between hospitals, however, digit preference reduced over calendar time. Vital signs may not always be accurately documented, and this may vary by patient groups and hospital settings. Allowances and adjustments may be needed in delivering care to patients and in observational analyses and predictive tools using these factors as outcomes or exposures. [ABSTRACT FROM AUTHOR]

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant has been replaced by the highly transmissible Omicron BA.1 variant, and subsequently by Omicron BA.2. It is important to understand how these changes in dominant variants affect reported symptoms, while also accounting for symptoms arising from other cocirculating respiratory viruses. Methods In a nationally representative UK community study, the COVID-19 Infection Survey, we investigated symptoms in polymerase chain reaction (PCR)–positive infection episodes versus PCR-negative study visits over calendar time, by age and vaccination status, comparing periods when the Delta, Omicron BA.1, and BA.2 variants were dominant. Results Between October 2020 and April 2022, a total of 120 995 SARS-CoV-2 PCR-positive episodes occurred in 115 886 participants, with 70 683 (58%) reporting symptoms. The comparator comprised 4 766 366 PCR-negative study visits (483 894 participants), with symptoms reported at 203 422 visits (4%). Symptom reporting in PCR-positive infections varied over time, with a marked reduction in loss of taste/smell as Omicron BA.1 dominated, which was maintained with BA.2 (44% symptomatic infections reporting loss of taste/45% symptomatic infections reporting loss of smell on 17 October 2021, 16%/13% 2 January 2022, 15%/12% 27 March 2022). Cough, fever, shortness of breath, myalgia, fatigue/weakness, and headache also decreased after Omicron BA.1 dominated, but sore throat increased, the latter to a greater degree than concurrent increases in PCR-negative visits. Fatigue/weakness increased again after BA.2 dominated, although to a similar degree to concurrent increases in PCR-negative visits. Symptoms were consistently more common in adults aged 18–65 years than in children or older adults. Conclusions Increases in sore throat (also common in the general community), along with a marked reduction in loss of taste/smell, make Omicron harder to detect with symptom-based testing algorithms, with implications for institutional and national testing policies. [ABSTRACT FROM AUTHOR]

Background "Classic" symptoms (cough, fever, loss of taste/smell) prompt severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing in the United Kingdom. Studies have assessed the ability of different symptoms to identify infection, but few have compared symptoms over time (reflecting variants) and by vaccination status. Methods Using the COVID-19 Infection Survey, sampling households across the United Kingdom, we compared symptoms in PCR-positives vs PCR-negatives, evaluating sensitivity of combinations of 12 symptoms (percentage symptomatic PCR-positives reporting specific symptoms) and tests per case (TPC) (PCR-positives or PCR-negatives reporting specific symptoms/ PCR-positives reporting specific symptoms). Results Between April 2020 and August 2021, 27 869 SARS-CoV-2 PCR-positive episodes occurred in 27 692 participants (median 42 years), of whom 13 427 (48%) self-reported symptoms ("symptomatic PCR-positives"). The comparator comprised 3 806 692 test-negative visits (457 215 participants); 130 612 (3%) self-reported symptoms ("symptomatic PCR-negatives"). Symptom reporting in PCR-positives varied by age, sex, and ethnicity, and over time, reflecting changes in prevalence of viral variants, incidental changes (eg, seasonal pathogens (with sore throat increasing in PCR-positives and PCR-negatives from April 2021), schools reopening) and vaccination rollout. After May 2021 when Delta emerged, headache and fever substantially increased in PCR-positives, but not PCR-negatives. Sensitivity of symptom-based detection increased from 74% using "classic" symptoms, to 81% adding fatigue/weakness, and 90% including all 8 additional symptoms. However, this increased TPC from 4.6 to 5.3 to 8.7. Conclusions Expanded symptom combinations may provide modest benefits for sensitivity of PCR-based case detection, but this will vary between settings and over time, and increases tests/case. Large-scale changes to targeted PCR-testing approaches require careful evaluation given substantial resource and infrastructure implications. [ABSTRACT FROM AUTHOR]

Given high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out in many settings, there is a need for evidence to underpin optimum vaccine deployment, aiming to maximise global population immunity. We evaluate whether a single vaccination in individuals who have already been infected with SARS-CoV-2 generates similar initial and subsequent antibody responses to two vaccinations in those without prior infection. We compared anti-spike IgG antibody responses after a single vaccination with ChAdOx1, BNT162b2, or mRNA-1273 SARS-CoV-2 vaccines in the COVID-19 Infection Survey in the UK general population. In 100,849 adults median (50 (IQR: 37–63) years) receiving at least one vaccination, 13,404 (13.3%) had serological/PCR evidence of prior infection. Prior infection significantly boosted antibody responses, producing higher peak levels and/or longer half-lives after one dose of all three vaccines than those without prior infection receiving one or two vaccinations. In those with prior infection, the median time above the positivity threshold was >1 year after the first vaccination. Single-dose vaccination targeted to those previously infected may provide at least as good protection to two-dose vaccination among those without previous infection. The impact of prior infection on the immune response to COVID-19 vaccination has not been fully characterised. Here, the authors use data from ~100,000 adults in the UK and find that a single vaccine dose in those with prior infection produces a comparable or stronger response to two doses in those without infection. [ABSTRACT FROM AUTHOR]

Introduction: Anti‐vascular endothelial growth factors (anti‐VEGFs) are considered standard of care therapy for diabetic macular oedema (DME). This study examined treatment patterns and outcomes in patients with DME treated with anti‐VEGF therapy. Methods: Using anonymized electronic medical record data collected from three UK sites, this retrospective cohort study assessed rates of anti‐VEGF intravitreal injections in adults with treatment‐naïve DME who received their first treatment between 1 September 2010 and 31 July 2018. The proportion of patients with at least one interval of at least 12 weeks between injections; the distribution of injection intervals; the discontinuation rates; and the number of anti‐VEGF injection‐, injection‐free‐ and total visits were assessed during the first and second years of treatment. Results: Overall, 1606 patient eyes with DME were included, with no minimum follow‐up. During the first and second year of treatment, 63.2% and 73.1% of eyes had at least one anti‐VEGF injection interval of at least 12 weeks, respectively. In the first and second years of treatment, the mean (standard deviation) numbers of injections were 7.7 (1.9) and 5.6 (2.2), with 14.2 (5.7) and 13.4 (6.4) total clinic visits, and 6.6 (5.0) and 7.8 (5.8) injection‐free visits, respectively. In total, 27.8% of patient eyes discontinued treatment during the first 2 years. Conclusions: The high number of clinic visits and high discontinuation rates demonstrate a significant unmet need for a treatment to enable sustainable extended injection intervals, while maintaining visual acuity. This could improve patient adherence and health‐related quality of life for patients with DME. [ABSTRACT FROM AUTHOR]

Background The incidence of bloodstream infections (BSIs) caused by Escherichia coli and Klebsiella pneumoniae is increasing, with substantial associated morbidity, mortality, and antimicrobial resistance. Unbiased serotyping studies to guide vaccine target selection are limited. Methods We conducted unselected, population-level genomic surveillance of bloodstream E. coli and Klebsiella pneumoniae isolates from 2008 to 2018 in Oxfordshire, United Kingdom. We supplemented this with an analysis of publicly available global sequencing data (n = 3678). Results We sequenced 3478 E. coli isolates (3278 passed quality control) and 556 K. pneumoniae isolates (535 [K-antigen] and 549 [O-antigen] passed quality control). The 4 most common E. coli O-antigens (O1/O2/O6/O25) were identified in 1499/3278 isolates; the incidence of these O-types increased over time (incidence rate ratio per year [IRRy] = 1.14, 95% confidence interval [CI]: 1.11–1.16). These O-types accounted for 616/1434 multidrug-resistant (MDR) and 173/256 extended-spectrum beta-lactamase (ESBL)-resistant isolates in Oxfordshire but only 19/90 carbapenem-resistant isolates across all studies. For Klebsiella pneumoniae , the most common O-antigens (O2v2/O1v1/O3b/O1v2) accounted for 410/549 isolates; the incidence of BSIs caused by these also increased annually (IRRy = 1.09; 95% CI: 1.05–1.12). These O-types accounted for 122/148 MDR and 106/123 ESBL isolates in Oxfordshire and 557/734 carbapenem-resistant isolates across all studies. Conversely we observed substantial capsular antigen diversity. Analysis of 3678 isolates from global studies demonstrated the generalizability of these findings. For E. coli , based on serotyping, the ExPEC4V and ExPEC10V vaccines under investigation would cover 46% and 72% of Oxfordshire isolates respectively, and 47% and 71% of MDR isolates. Conclusions O-antigen targeted vaccines may be useful in reducing the morbidity, mortality, and antimicrobial resistance associated with E. coli and K. pneumoniae BSIs. [ABSTRACT FROM AUTHOR]

Understanding the trajectory, duration, and determinants of antibody responses after SARS-CoV-2 infection can inform subsequent protection and risk of reinfection, however large-scale representative studies are limited. Here we estimated antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 United Kingdom COVID-19 infection survey participants who had positive swab SARS-CoV-2 PCR tests from 26-April-2020 to 14-June-2021. A latent class model classified 24% of participants as 'non-responders' not developing anti-spike antibodies, who were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. Among those who seroconverted, using Bayesian linear mixed models, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels associated with protection against reinfection likely last 1.5-2 years on average, with levels associated with protection from severe infection present for several years. These estimates could inform planning for vaccination booster strategies. Most people who are infected with SARS-CoV-2 seroconvert within a few weeks, but the determinants and duration of the antibody response are not known. Here, the authors characterise these features of the immune response using data from a large representative community sample of the UK population. [ABSTRACT FROM AUTHOR]

Background: Both genetic and cardiovascular factors contribute to the risk of developing heart failure (HF), but whether idea cardiovascular health metrics (ICVHMs) offset the genetic association with incident HF remains unclear.Objectives: To investigate the genetic association with incident HF as well as the modification effect of ICVHMs on such genetic association in Chinese and British populations.Methods: An ICVHMs based on smoking, drinking, physical activity, diets, body mass index, waist circumference, blood pressure, blood glucose, and blood lipids, and a polygenic risk score (PRS) for HF were constructed in the China Kadoorie Biobank (CKB) of 96,014 participants and UK Biobank (UKB) of 335,782 participants which were free from HF and severe chronic diseases at baseline.Results: During the median follow-up of 11.38 and 8.73 years, 1451 and 3169 incident HF events were documented in CKB and UKB, respectively. HF risk increased monotonically with the increase of PRS per standard deviation (CKB: hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07, 1.32; UKB: 1.07; 1.03, 1.11; P for trend < 0.001). Each point increase in ICVHMs was associated with 15% and 20% lower risk of incident HF in CKB (0.85; 0.81, 0.90) and UKB (0.80; 0.77, 0.82), respectively. Compared with unfavorable ICVHMs, favorable ICVHMs was associated with a lower HF risk, with 0.71 (0.44, 1.15), 0.41 (0.22, 0.77), and 0.48 (0.30, 0.77) in the low, intermediate, and high genetic risk in CKB and 0.34 (0.26, 0.44), 0.32 (0.25, 0.41), and 0.37 (0.28, 0.47) in UKB (P for multiplicative interaction > 0.05). Participants with low genetic risk and favorable ICVHMs, as compared with high genetic risk and unfavorable ICVHMs, had 56~72% lower risk of HF (CKB 0.44; 0.28, 0.70; UKB 0.28; 0.22, 0.37). No additive interaction between PRS and ICVHMs was observed (relative excess risk due to interaction was 0.05 [-0.22, 0.33] in CKB and 0.04 [-0.14, 0.22] in UKB).Conclusions: In CKB and UKB, genetic risk and ICVHMs were independently associated with the risk of incident HF, which suggested that adherence to favorable cardiovascular health status was associated with a lower HF risk among participants with all gradients of genetic risk. [ABSTRACT FROM AUTHOR]

Background: To reduce inappropriate antibiotic use, public health campaigns often provide fear-based information about antimicrobial resistance (AMR). Meta-analyses have found that fear-based campaigns in other contexts are likely to be ineffective unless respondents feel confident they can carry out the recommended behaviour ('self-efficacy'). This study aimed to test the likely impact of fear-based messages, with and without empowering self-efficacy elements, on patient consultations/antibiotic requests for influenza-like illnesses, using a randomised design.Methods: We hypothesised that fear-based messages containing empowering information about self-management without antibiotics would be more effective than fear alone, particularly in a pre-specified subgroup with low AMR awareness. Four thousand respondents from an online panel, representative of UK adults, were randomised to receive three different messages about antibiotic use and AMR, designed to induce fear about AMR to varying degrees. Two messages (one 'strong-fear', one 'mild-fear') also contained empowering information regarding influenza-like symptoms being easily self-managed without antibiotics. The main outcome measures were self-reported effect of information on likelihood of visiting a doctor and requesting antibiotics, for influenza-like illness, analysed separately according to whether or not the AMR information was 'very/somewhat new' to respondents, pre-specified based on a previous (non-randomised) survey.Results: The 'fear-only' message was 'very/somewhat new' to 285/1000 (28.5%) respondents, 'mild-fear-plus-empowerment' to 336/1500 (22.4%), and 'strong-fear-plus-empowerment' to 388/1500 (25.9%) (p = 0.002). Of those for whom the respective information was 'very/somewhat new', only those given the 'strong-fear-plus-empowerment' message said they would be less likely to request antibiotics if they visited a doctor for an influenza-like illness (p < 0.0001; 182/388 (46.9%) 'much less likely'/'less likely', versus 116/336 (34.5%) with 'mild-fear-plus-empowerment' versus 85/285 (29.8%) with 'fear-alone'). Those for whom the respective information was not 'very/somewhat new' said they would be less likely to request antibiotics for influenza-like illness (p < 0.0001) across all messages (interaction p < 0.0001 versus 'very/somewhat new' subgroup). The three messages had analogous self-reported effects on likelihood of visiting a doctor and in subgroups defined by believing antibiotics would 'definitely/probably' help an influenza-like illness. Results were reproduced in an independent randomised survey (additional 4000 adults).Conclusions: Fear could be effective in public campaigns to reduce inappropriate antibiotic use, but should be combined with messages empowering patients to self-manage symptoms effectively without antibiotics. [ABSTRACT FROM AUTHOR]

Background: Hospital antimicrobial stewardship strategies, such as 'Start Smart, Then Focus' in the UK, balance the need for prompt, effective antibiotic treatment with the need to limit antibiotic overuse using 'review and revise'. However, only a minority of review decisions are to stop antibiotics. Research suggests that this is due to both behavioural and organizational factors.Objectives: To develop and optimize the Antibiotic Review Kit (ARK) intervention. ARK is a complex digital, organizational and behavioural intervention that supports implementation of 'review and revise' to help healthcare professionals safely stop unnecessary antibiotics.Methods: A theory-, evidence- and person-based approach was used to develop and optimize ARK and its implementation. This was done through iterative stakeholder consultation and in-depth qualitative research with doctors, nurses and pharmacists in UK hospitals. Barriers to and facilitators of the intervention and its implementation, and ways to address them, were identified and then used to inform the intervention's development.Results: A key barrier to stopping antibiotics was reportedly a lack of information about the original prescriber's rationale for and their degree of certainty about the need for antibiotics. An integral component of ARK was the development and optimization of a Decision Aid and its implementation to increase transparency around initial prescribing decisions.Conclusions: The key output of this research is a digital and behavioural intervention targeting important barriers to stopping antibiotics at review (see http://bsac-vle.com/ark-the-antibiotic-review-kit/ and http://antibioticreviewkit.org.uk/). ARK will be evaluated in a feasibility study and, if successful, a stepped-wedge cluster-randomized controlled trial at acute hospitals across the NHS. [ABSTRACT FROM AUTHOR]

We describe our experience in several settings, following a suggestion in 1983 to add questions on the smoking status of the deceased on the UK death certificate as an effective way to monitor the evolution of the smoking epidemic. In South Africa in 1997 and in Tianjin Municipality, China, in 2010, questions about the smoking habits of the deceased were inserted on the official death certificates. In both places a system now exists to routinely collect information on smoking status in relation to causes of death. Results from two million South African and 300 000 Chinese deceased individuals have been reported, and the sample size in both places continues to grow. An unsuccessful attempt was made in 2008 to insert smoking questions on the Australian death notification forms but comments and concerns from the registrars of births, marriages and deaths have international applicability. In both China and South Africa, inserting questions on smoking on the death notification forms was not a trivial task-in each it required, as a minimum, significant commitment from several government agencies. Benefits, however, include a better local understanding of the smoking epidemic and allowing for planning and monitoring of tobacco control programmes. Documenting the varied experiences of collecting information on smoking on death notification forms is useful to those wishing to introduce such questions in their own settings. This is pertinent especially at a time when vital registration systems are being improved, with an aim to monitoring sustainable development goals. [ABSTRACT FROM AUTHOR]

Background: Digital retinal imaging is the gold standard technique for diabetic retinopathy (DR) and diabetic macular oedema (DME) assessment during DR screening. Objectives: To evaluate the diagnostic accuracy of digital retinal fundus image (DRFI) analysis in detecting DME using three manual grading systems (MGS) and comparing it with optical coherence tomography (OCT) findings. Method: A total of 287 DRFI of 287 eyes were analysed. Non-stereoscopic 45° images were acquired using a Kowa VX-20 camera and were graded according to three MGS: Early Treatment Diabetic Retinopathy Study (ETDRS), International Clinical Diabetic Retinopathy (ICDR), and United Kingdom National Screening Committee (UKNSC). The two graders were masked to the patient's clinical DR status. DME characteristics were analysed using OCTs. Results: A very good agreement in detecting DME was found with Cohen's κ = 0.83 (ICDR vs. ETDRS), κ = 0.83 (ICDR vs. UKNSC), and κ = 0.82 (ETDRS vs. UKNSC). Sensitivity and specificity of DRFI analysis in DME assessment were 70.0 and 69.6% for UKNSC, 71.9 and 67.4% for ETDRS, and 70.9 and 65.2% for ICDR, respectively. Positive and negative predictive values were 91.7 and 32.7% for UKNSC, 91.4 and 33.3% for ETDRS, and 90.7 and 31.9% for ICDR, respectively. On OCT scans, micro-architectural damages of both inner and outer retinal layers and mean ganglion cell layer thickness showed a significant association with the presence of DME detected with DRFI analysis. Conclusions: Despite the low negative predictive value, the good specificity and sensitivity of DRFI in detecting DME make it a useful tool in a routine clinical setting, and its potential in diabetic eye screening is yet to be realized. [ABSTRACT FROM AUTHOR]

The clinical phenotype of zoonotic tuberculosis and its contribution to the global burden of disease are poorly understood and probably underestimated. This shortcoming is partly because of the inability of currently available laboratory and in silico tools to accurately identify all subspecies of the Mycobacterium tuberculosis complex (MTBC). We present SNPs to Identify TB (SNP-IT), a single-nucleotide polymorphism-based tool to identify all members of MTBC, including animal clades. By applying SNP-IT to a collection of clinical genomes from a UK reference laboratory, we detected an unexpectedly high number of M. orygis isolates. M. orygis is seen at a similar rate to M. bovis, yet M. orygis cases have not been previously described in the United Kingdom. From an international perspective, it is possible that M. orygis is an underestimated zoonosis. Accurate identification will enable study of the clinical phenotype, host range, and transmission mechanisms of all subspecies of MTBC in greater detail. [ABSTRACT FROM AUTHOR]

This article examines whether the voting age should be lowered to 16. The dominant view in the literature is that 16-year-olds in the United Kingdom are not politically mature enough to vote since they lack political knowledge, political interest and stable political preferences (Chan and Clayton, 2006). I reject this conclusion and instead argue that the voting age should be lowered to 16. First, I look at Chan and Clayton’s empirical claims and show that these features of 16- and 17-year-olds are in fact created by exclusionary social practices and therefore that these features cannot be used to justify their exclusion from the vote. Second, I evaluate preliminary evidence from Austria which suggests that 16- and 17-year-olds, when actually given the vote, are politically mature. Third, I show that, on a balance of harms, considering that some 16- and 17-year-olds are mature, we still should lower the voting age even if some 16- and 17-year-olds are not politically mature. I conclude that the voting age should be lowered to (at least) 16. [ABSTRACT FROM AUTHOR]

Purpose: To describe an approach to the use of optical coherence tomography (OCT) imaging in large, population-based studies, including methods for OCT image acquisition, storage, and the remote, rapid, automated analysis of retinal thickness. Methods: In UK Biobank, OCT images were acquired between 2009 and 2010 using a commercially available “spectral domain” OCT device (3D OCT-1000, Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area, and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers in a central repository, adjacent to high performance computers. Rapid, automated analysis of retinal thickness was performed using custom image segmentation software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL). This software employs dual-scale gradient information to allow for automated segmentation of nine intraretinal boundaries in a rapid fashion. Results: 67,321 participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as part of the ocular module. 134,611 images were successfully processed with 31 images failing segmentation analysis due to corrupted OCT files or withdrawal of subject consent for UKBB study participation. Average time taken to call up an image from the database and complete segmentation analysis was approximately 120 seconds per data set per login, and analysis of the entire dataset was completed in approximately 28 days. Conclusions: We report an approach to the rapid, automated measurement of retinal thickness from nearly 140,000 OCT image sets from the UK Biobank. In the near future, these measurements will be publically available for utilization by researchers around the world, and thus for correlation with the wealth of other data collected in UK Biobank. The automated analysis approaches we describe may be of utility for future large population-based epidemiological studies, clinical trials, and screening programs that employ OCT imaging. [ABSTRACT FROM AUTHOR]

The Randomised Evaluation of COVID-19 Therapy (RECOVERY) Trial was set up in March 2020 to evaluate treatments for people hospitalised with COVID-19. To maximise recruitment it was designed to fit into routine clinical care throughout the UK, and as a result it has enrolled more patients than any other COVID-19 treatment trial. RECOVERY has shown four drugs to be life-saving – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab – and a further six have been shown to be of little or no benefit. In each case, results from RECOVERY were clear enough to rapidly influence global practice. Some of the reasons for this success relate to its particular setting in the UK during the SARS-CoV-2 pandemic, but many are generalisable to other contexts. In particular, its focus on recruiting large numbers of patients to identify or rule out moderate but worthwhile benefits of treatment, and the design decisions that followed from this. Similar large streamlined trials could produce similarly clear answers about the treatment of many other common diseases. [ABSTRACT FROM AUTHOR]

Aim: We sought to ascertain the current nature of specialist community mental health provision for young people presenting with risk of harm to others or involvement with the youth justice system in England, Wales and Scotland.Methods: Questionnaire-based survey.Results: Fifty-five services were contacted, 48 responded and 35 of these were found to be providing some form of community mental health provision to high-risk young people. Thirteen services provided comprehensive community forensic child and adolescent mental health (FCAMH) services, whilst the remainder offered more ad hoc clinical input. Amongst the comprehensive FCAMH services, staffing, function, commissioning arrangements and population served varied widely.Conclusions: There is patchy geographical provision of comprehensive community FCAMH services across England, Scotland and Wales with heterogeneous commissioning arrangements, staffing and function. Development of a national commissioning strategy for community FCAMH services is required to ensure that the complex needs of high-risk young people are adequately addressed. [ABSTRACT FROM AUTHOR]

Background: Mutations in the BRCA1 and BRCA2 genes are found in most families with cases of both breast and ovarian cancer or with many cases of early-onset breast cancer. However, in an outbred population, the prevalence of BRCA1 and BRCA2 mutations in patients with breast cancer who were unselected for a family history of this disease has not been determined.Methods: Mutations in the BRCA1 and BRCA2 genes were detected in blood samples from two population-based series of young patients with breast cancer from Britain.Results: Mutations were detected in 15 (5.9%) of 254 women diagnosed with breast cancer before age 36 years (nine [3.5%] in BRCA1 and six [2.4%] in BRCA2) and in 15 (4.1%) of 363 women diagnosed from ages 36 through 45 years (seven [1.9%] in BRCA1 and eight [2.2%] in BRCA2). Eleven percent (six of 55) of patients with a first-degree relative who developed ovarian cancer or breast cancer by age 60 years were mutation carriers, compared with 45% (five of 11) of patients with two or more affected first- or second-degree relatives. The standardized incidence ratio for breast cancer in mothers and sisters was 365 (five observed and 1.37 expected) for 30 mutation carriers and 199 (64 observed and 32.13 expected) for 587 noncarriers. If we assume recent penetrance estimates, the respective proportions of BRCA1 and BRCA2 mutation carriers are 3.1% and 3.0%, respectively, of patients with breast cancer who are younger than age 50 years, 0.49% and 0.84% of patients with breast cancer who are age 50 years or older, and 0.11% and 0.12% of women in the general population.Conclusions: Mutations in the BRCA1 and BRCA2 genes make approximately equal contributions to early-onset breast cancer in Britain and account for a small proportion of the familial risk of breast cancer. [ABSTRACT FROM AUTHOR]

The article presents the study which examined the hazards of smoking, as well as the benefits of smoking cessation in Great Britain. In the Million Women Study, 1.3 million British women were recruited in 1996-2001 through the National Health Service Breast Screening Programme (NHSBSP). The study was financed by the Cancer Research UK and the Medical Research Council.

Background: Integration of information on individuals (record linkage) is a key problem in healthcare delivery, epidemiology, and "business intelligence" applications. It is now common to be required to link very large numbers of records, often containing various combinations of theoretically unique identifiers, such as NHS numbers, which are both incomplete and error-prone. Methods: We describe a two-step record linkage algorithm in which identifiers with high cardinality are identified or generated, and used to perform an initial exact match based linkage. Subsequently, the resulting clusters are studied and, if appropriate, partitioned using a graph based algorithm detecting erroneous identifiers. Results: The system was used to cluster over 250 million health records from five data sources within a large UK hospital group. Linkage, which was completed in about 30 minutes, yielded 3.6 million clusters of which about 99.8% contain, with high likelihood, records from one patient. Although computationally efficient, the algorithm's requirement for exact matching of at least one identifier of each record to another for cluster formation may be a limitation in some databases containing records of low identifier quality. Conclusions: The technique described offers a simple, fast and highly efficient two-step method for large scale initial linkage for records commonly found in the UK's National Health Service. [ABSTRACT FROM AUTHOR]

The article discusses medical research on the risks of breast cancer and its subtypes in relation to individual and multiple low-penetrance genetic susceptibility loci in Great Britain. It investigates 14 individual single-nucleotide polymorphisms (SNPs) previously linked to breast cancer. It mentions that participants in the study include 10,306 women with breast cancer and 10,393 women without breast cancer who provided blood samples for genotyping in a large prospective study in the country in 2005 to 2008. It concludes that breast cancer was substantially more predictive of estrogen receptor (ER)-positive than of ER-negative.

We obtained lifetime occupational and residential histories by telephone interview with 622 mesothelioma patients (512 men, 110 women) and 1420 population controls. Odds ratios (ORs) were converted to lifetime risk (LR) estimates for Britons born in the 1940s. Male ORs (95% confidence interval (CI)) relative to low-risk occupations for >10 years of exposure before the age of 30 years were 50.0 (25.8-96.8) for carpenters (LR 1 in 17), 17.1 (10.3-28.3) for plumbers, electricians and painters, 7.0 (3.2-15.2) for other construction workers, 15.3 (9.0-26.2) for other recognised high-risk occupations and 5.2 (3.1-8.5) in other industries where asbestos may be encountered. The LR was similar in apparently unexposed men and women (approximately 1 in 1000), and this was approximately doubled in exposed workers' relatives (OR 2.0, 95% CI 1.3-3.2). No other environmental hazards were identified. In all, 14% of male and 62% of female cases were not attributable to occupational or domestic asbestos exposure. Approximately half of the male cases were construction workers, and only four had worked for more than 5 years in asbestos product manufacture. [ABSTRACT FROM AUTHOR]

Background: Active smoking has little or no effect on women's risk of developing breast cancer, but it has been suggested that passive exposure to tobacco smoke may increase this risk among women who have never smoked.Objective: To evaluate the possible relationship between passive smoking and breast cancer risk within the Million Women Study, a large UK prospective study, and to report a meta-analysis of published results.Methods: In the large prospective study, 224 917 never smokers who completed a questionnaire that asked women whether their parents had smoked and if their current partner smoked were followed up for an average of 3.5 years for incident breast cancer. In the meta-analysis, studies that had recorded exposure information prospectively and retrospectively were considered separately. Main outcome measures Adjusted relative risk of breast cancer in never smokers who were passively exposed to tobacco smoke at various ages compared with never smokers with no such exposure.Results: In the prospective study, 2518 incident invasive breast cancers occurred during follow-up and the adjusted relative risk of breast cancer for passive exposure either as a child or as an adult vs neither exposure was 0.98 (95% CI 0.88-1.09); results were similarly null for childhood exposure (0.98, 0.88-1.08) and adult exposure (1.02, 0.89-1.16) separately. We identified seven other studies with prospectively recorded exposure data; when results of all eight studies were combined (including 5743 never smokers with breast cancer), the aggregate relative risk was 0.99 (0.93-1.05) for any passive exposure. The aggregate findings differed substantially (P = 0.0002) between these 8 studies and 17 other studies with retrospectively recorded information (including 5696 never smokers with breast cancer).Conclusions: Aggregate results from studies with prospectively reported information show that the incidence of breast cancer is similar in women who did and did not report passive exposure to tobacco smoke either as a child or as an adult. The aggregate findings from the retrospective studies may have been distorted by some women becoming more likely to report past exposures because they knew that they had breast cancer. [ABSTRACT FROM AUTHOR]

The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. Polymorphisms in the gene encoding subunit α type 6 (PSMA6) – in particular the rs1048990 exon 1–8C/G SNP – have been implicated with susceptibility to myocardial infarction (MI) in a Japanese study. We examined whether several polymorphisms in the PSMA6 gene were related to MI risk in 6946 nonfatal MI cases and 2720 unrelated controls in a UK population. The homozygous GG genotype for rs1048990 was much less frequent in this UK population than in the Japanese population (2.1 vs 8.9%), and was associated with an odds ratio (OR) for MI of 1.09 (95% confidence interval (CI): 0.98–1.21) per G allele in a co-dominant genetic model and 1.32 (95% CI: 0.90–1.93) in a recessive genetic model. Although not statistically significant, these results for this variant are still consistent with the Japanese hypothesis-generating study. Our findings, when taken together with four other studies (including the hypothesis-generating one), yielded a combined OR for MI of 1.15 (95% CI: 1.08–1.21) per G allele in a co-dominant model and 1.38 (95% CI: 1.22–1.57) for the GG genotype in a recessive model. Larger studies involving more than 10 000 disease cases would be required to further elucidate the role of this variant for susceptibility to MI. However, given the rarity of this variant in Caucasians, the attributable risk of rs1048990 for MI is unlikely to be great in western populations.European Journal of Human Genetics (2008) 16, 480–486; doi:10.1038/sj.ejhg.5201948; published online 30 January 2008 [ABSTRACT FROM AUTHOR]

Approximately, a third of all colorectal cancer (CRC) is due to inherited susceptibility. However, high-risk mutations in APC, the mismatch repair (MMR) genes, MUTYH/MYH, SMAD4, ALK3 and STK11/LKB1 are rare and account for <5% of cases. Much of the remaining variation in genetic risk is likely to be explained by combinations of more common gene variants that modestly increase risk. Reliable identification of such 'low penetrance' alleles would provide insight into the aetiology of CRC and might highlight potential therapeutic and preventative interventions. In 2003, the National Study of Colorectal Cancer Genetics (NSCCG) was established with the aim of collecting DNA and clinicopathological data from 20,000 CRC cases and a series of spouse/partner controls, thereby creating a unique resource for identifying low-penetrance CRC susceptibility alleles. The National Cancer Research Network (NCRN) adopted NSCCG onto its portfolio of trials and 148 centres in the United Kingdom (UK) are now actively participating. Over 8,700 cases and 2,185 controls have so far been entered into NSCCG. Our experience in developing NSCCG serves to illustrate how world-class DNA databases for genetic analyses can be rapidly developed in the United Kingdom. [ABSTRACT FROM AUTHOR]

The British public have been offered alternating periods of lockdown and relaxation of restrictions as part of the coronavirus disease 2019 (COVID-19) lockdown exit strategy.[1] Extended periods of lockdown will increase economic and social damage, and each relaxation will almost certainly trigger a further epidemic wave of deaths. If the epidemic is controlled, hundreds of thousands of lives could be saved, intensive care units will no longer be overloaded, and the adverse effects of lockdown on mental ill health and unemployment will end. [Extracted from the article]

Tests the hypothesis that a lower exposure to common infections in the first year of life can increase the risk of developing acute lymphoblastic leukemia (ALL). Use of data from the United Kingdom childhood cancer study (UKCCS); Comparison of social activity of cases and controls for ALL and subgroups of ALL; Design, setting, participants, main outcome measures, and results; Finding that reduced exposure to infection during the early months of life increases the risk of developing acute lymphoblastic leukemia.

The United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of Great Britain, incorporated a pilot study measuring electric fields. Measurements were made in the homes of 473 children who were diagnosed with a malignant neoplasm between 1992 and 1996 and who were aged 0-14 at diagnosis, together with 453 controls matched on age, sex and geographical location. Exposure assessments comprised resultant spot measurements in the child's bedroom and the family living-room. Temporal stability of bedroom fields was investigated through continuous logging of the 48-h vertical component at the child's bedside supported by repeat spot measurements. The principal exposure metric used was the mean of the pillow and bed centre measurements. For the 273 cases and 276 controls with fully validated measures, comparing those with a measured electric field exposure >/=20 V m(-1) to those in a reference category of exposure <10 V m(-1), odds ratios of 1.31 (95% confidence interval 0.68-2.54) for acute lymphoblastic leukaemia, 1.32 (95% confidence interval 0.73-2.39) for total leukaemia, 2.12 (95% confidence interval 0.78-5.78) for central nervous system cancers and 1.26 (95% confidence interval 0.77-2.07) for all malignancies were obtained. When considering the 426 cases and 419 controls with no invalid measures, the corresponding odds ratios were 0.86 (95% confidence interval 0.49-1.51) for acute lymphoblastic leukaemia, 0.93 (95% confidence interval 0.56-1.54) for total leukaemia, 1.43 (95% confidence interval 0.68-3.02) for central nervous system cancers and 0.90 (95% confidence interval 0.59-1.35) for all malignancies. With exposure modelled as a continuous variable, odds ratios for an increase in the principal metric of 10 V m(-1) were close to unity for all disease categories, never differing significantly from one. [ABSTRACT FROM AUTHOR]

AbstractObjective and design: To relate UK national trends since 1950 in smoking, in smoking cessation, and in lung cancer to the contrasting results from two large case-control studies centred around 1950 and 1990.Setting: United Kingdom.Participants: Hospital patients under 75 years of age with and without lung cancer in 1950 and 1990, plus, in 1990, a matched sample of the local population: 1465 case-control pairs in the 1950 study, and 982 cases plus 3185 controls in the 1990 study.Main outcome measures: Smoking prevalence and lung cancer.Results: For men in early middle age in the United Kingdom the prevalence of smoking halved between 1950 and 1990 but the death rate from lung cancer at ages 35-54 fell even more rapidly, indicating some reduction in the risk among continuing smokers. In contrast, women and older men who were still current smokers in 1990 were more likely than those in 1950 to have been persistent cigarette smokers throughout adult life and so had higher lung cancer rates than current smokers in 1950. The cumulative risk of death from lung cancer by age 75 (in the absence of other causes of death) rose from 6% at 1950 rates to 16% at 1990 rates in male cigarette smokers, and from 1% to 10% in female cigarette smokers. Among both men and women in 1990, however, the former smokers had only a fraction of the lung cancer rate of continuing smokers, and this fraction fell steeply with time since stopping. By 1990 cessation had almost halved the number of lung cancers that would have been expected if the former smokers had continued. For men who stopped at ages 60, 50, 40, and 30 the cumulative risks of lung cancer by age 75 were 10%, 6%, 3%, and 2%.Conclusions: People who stop smoking, even well into middle age, avoid most of their subsequent risk of lung cancer, and stopping before middle age avoids more than 90% of the risk attributable to tobacco. Mortality in the near future and throughout the first half of the 21st century could be substanti... [ABSTRACT FROM AUTHOR]

Purpose: To determine the number of patients with diabetes mellitus (PwDM) who were certified as visually impaired (CVI) over the past 5 years in Northern Ireland, UK. Methods: CVI data were collected from 11 sites and 50 eye‐specialists using pre‐defined CVI forms. Eye‐specialists must provide patient demographics and vision information such as visual acuity and diagnosis for certification purposes. Data were transcribed into Microsoft Excel before analysis was undertaken to produce an annual CVI report for eye and healthcare professionals. Our analysis determined the contribution of diabetes and diabetic eye disease (DED) to the sight‐impairment burden between 2014 and 2018. Results: In 2014, 332 CVIs were registered: 184 as severely sight impaired (SSI) and 142 sight impaired (SI). Of the 24 who had diabetes, 19 were certified due to diabetic retinopathy (DR) and 2 to diabetic macular oedema (DMO). Between 2015 and 2017 the number of CVIs increased to 412, 428 and 453 respectively with PwDM having grown to 48, 43 and 41, respectively. PwDM were also certified due to AMD and glaucoma (range of 2%–31% and 2–4% respectively) from 2015 to 2017. After an intense education campaign, in 2018, the total CVI submissions increased to 575; of these 368 were SSI and 196 were SI. The number of people who were certified as having diabetes more than doubled in 2018 to 107 of these, 51 (48%) were certified due to DED. AMD was found to be the second largest cause of visual impairment in PwDM at 40%, the remaining people had other ophthalmic issues such as keratoconus and optic atrophy. Conclusions: PwDM were previously underrepresented in the sight impaired registers in Northern Ireland. Since the awareness campaign and introduction of improved pre‐defined forms in 2018, Northern Ireland is now on par with certification rates in the rest of the UK. This information provides insight into the epidemiology of sight impairment in Northern Ireland while providing appropriate data for policymaking and service planning purposes. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic test accuracy (DTA) of trained nurses, mid‐level and senior ophthalmologists in Vietnam against a reference standard from the UK, and assess the impact of further training on graders. Methods: Fundus photographs were taken and graded at two different time points by trained nurses, mid‐level ophthalmologists and senior ophthalmologists in Vietnam using the UK National Screening Committee classification system. A reference standard from the UK regraded all images in masked fashion and DTA was calculated using sensitivity and specificity (with 95% CIs), and positive and negative predictive values. Results: Between September and November 2018, 431 people with diabetes attended diabetic retinopathy (DR) screening in Southern Vietnam. The sensitivity for detecting any DR for all grader groups in Vietnam was low (<43%) against the reference standard in the UK. The sensitivity for detecting referable DR and referrable diabetic macular oedema was particularly low (<20%) for all grader groups. Subsequently, an additional subset of images from 138 consecutive patients screened from March to April 2021 was regraded in the UK to evaluate graders' performance after additional training was delivered. A significant improvement in DTA among all grader groups in Vietnam was identified, with sensitivity for detecting any DR exceeding 85%. Nurses achieved the highest sensitivity for grading referable DR (76.9%, 60.3–88.3%) and mid‐level ophthalmologists attained the highest sensitivity for detecting referable maculopathy (77.5%, 61.2–88.6). Conclusions: Grading accuracy was low in Vietnam in the first six months of implementing a training programme. Many factors may have contributed to poor grader performance, including inadequate training and feedback, insufficient time to participate in quality assurance testing and competing work responsibilities. After further training was delivered, DTA among all graders in Vietnam increased. Findings from this study are particularly important for DR programme planners in low‐ and middle‐income countries. [ABSTRACT FROM AUTHOR]

Assesses the risk of death associated to consumption of alcohol in Great Britain. Examination of British male doctors; Relation between all cause of mortality and the average amount of alcohol; Conclusion that consumption of alcohol reduces the risk of ischemic heart disease. INSET: Public health implications.

Examines the number of mortality associated to smoking in Great Britain. Assessment of British male doctors; Association of respiratory diseases to smoking; Conclusion on the hazards of long term use of tobacco. INSET: Clinical implications.

Presents several letters received by the staff of a medical journal publication in Great Britain as od July 1977. Comments on the work of Hugh Dudley; Reaction on the article written by W.M. Ross; Question on the prohibition regarding data collections for medical studies.

Focuses on the mortality of doctors due to smoking in Great Britain. Ration of the death rate among cigarette smokers and lifelong non-smokers; Relationship between the causes of death to age and tobacco consumption; Causal nature of the association between smoking and lung cancer.

Examines the development of mechanisms for the acquisition, transport and storage of iron in Great Britain. Significance of the siderophores; Importance of hypoferraemia as host defense mechanism; Studies on the relation between infection and iron availability; Formulation for the plans of adding iron to diets in the developing countries.

Presents the results of a randomized trial on the prophylactic daily aspirin among males in Great Britain. Analysis on the efficacy of aspirin in reducing stroke, myocardial infarction and other vascular conditions; Significance of migraine and musculoskeletal pain in the control and treated group; Correlation between the disabling stroke and the established value of antiplatelet treatment.

Analyzes mesothelioma mortality since 1968 in Great Britain. Assessment of current state of the mesothelioma epidemic; Age and birth cohort; Diagnostic trend; Occupations at risk; Forecasts on the epidemic; Mesothelioma mortality as an index of past exposure to asbestos in the population.

Comments on various topics published in the volume 295 of the 'British Medical Journal'. Debate on hospices for children with diseases; Appearance of lichen sclerosus in sexually-abused children; Confusion between infantile copper deficiency and child abuse.

The article presents a study that investigates the efforts of asbestos exposure and mesothelioma mortality on occupational groups in Great Britain. It presents the recorded data of mesothelioma cases from illness, health and safety non-departmental watchdog Health & Safety Executive (HSE). Moreover, results of the cohort analysis on mesothelioma death rates in the country.

Focuses on medical-related issues in Great Britain. Improvement of intelligence levels by vitamin supplements; Etiology of pulmonary aspergillosis in ill patients; Provision of cost effective service to patients with problems in early pregnancy.

Reports global developments related to medicine. Relation between iron deficiency and the incidence of sudden infant death syndrome; Identification of high density lipoprotein cholesterol as a risk factor for ischemic heart disease; Effectiveness of omeprazole and cimetidine in healing gastric body ulcers.

Examines the relation between mortality and the smoking habits of women doctors in Great Britain. Effects of cigarette smoking; Female death rates caused by smoking habits; Features of the smoking habits of men and women.