Search

Objective To assess the feasibility of identifying markers of health-seeking behaviour and healthcare access in UK electronic health records (EHR), for identifying populations at risk of poor health outcomes and adjusting for confounding in epidemiological studies.Design Cross-sectional observational study using the Clinical Practice Research Datalink Aurum prelinked to Hospital Episode Statistics.Setting Individual-level routine clinical data from 13 million patients across general practices (GPs) and secondary data in England.Participants Individuals aged ≥66 years on 1 September 2019.Main outcome measures We used the Theory of Planned Behaviour (TPB) model and the literature to iteratively develop criteria for markers selection. Based on this we selected 15 markers: those that represented uptake of public health interventions, markers of active healthcare access/use and markers of lack of access/underuse. We calculated the prevalence of each marker using relevant lookback periods prior to the index date (1 September 2019) and compared with national estimates. We assessed the correlation coefficients (phi) between markers with inferred hierarchical clustering.Results We included 1 991 284 individuals (mean age: 75.9 and 54.0% women). The prevalence of markers ranged from

Summary: Background: Long COVID is the patient-coined term for the persistent symptoms of COVID-19 illness for weeks, months or years following the acute infection. There is a large burden of long COVID globally from self-reported data, but the epidemiology, causes and treatments remain poorly understood. Primary care is used to help identify and treat patients with long COVID and therefore Electronic Health Records (EHRs) of past COVID-19 patients could be used to help fill these knowledge gaps. We aimed to describe the incidence and differences in demographic and clinical characteristics in recorded long COVID in primary care records in England. Methods: With the approval of NHS England we used routine clinical data from over 19 million adults in England linked to SARS-COV-2 test result, hospitalisation and vaccination data to describe trends in the recording of 16 clinical codes related to long COVID between November 2020 and January 2023. Using OpenSAFELY, we calculated rates per 100,000 person-years and plotted how these changed over time. We compared crude and adjusted (for age, sex, 9 NHS regions of England, and the dominant variant circulating) rates of recorded long COVID in patient records between different key demographic and vaccination characteristics using negative binomial models. Findings: We identified a total of 55,465 people recorded to have long COVID over the study period, which included 20,025 diagnoses codes and 35,440 codes for further assessment. The incidence of new long COVID records increased steadily over 2021, and declined over 2022. The overall rate per 100,000 person-years was 177.5 cases in women (95% CI: 175.5–179) and 100.5 in men (99.5–102). The majority of those with a long COVID record did not have a recorded positive SARS-COV-2 test 12 or more weeks before the long COVID record. Interpretation: In this descriptive study, EHR recorded long COVID was very low between 2020 and 2023, and incident records of long COVID declined over 2022. Using EHR diagnostic or referral codes unfortunately has major limitations in identifying and ascertaining true cases and timing of long COVID. Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).

Summary: Background: Long COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. We aimed to evaluate and estimate the differences in health impacts of long COVID across sociodemographic categories and quantify this in Quality-Adjusted Life-Years (QALYs), widely used measures across health systems. Methods: With the approval of NHS England, we utilised OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID. Findings: The total OpenPROMPT cohort consisted of 7575 individuals who consented to data collection, with which we used data from 6070 participants who completed a baseline research questionnaire where 24.6% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a higher likelihood or odds of reporting loss in quality-of-life (Odds Ratio (OR): 4.7, 95% CI: 3.72–5.93) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 17.7, 95% CI: 10.37–30.33) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss. Interpretation: We found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease. Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).

High-throughput total nucleic acid (TNA) purification methods based on solid-phase reversible immobilization (SPRI) beads produce TNA suitable for both genomic and transcriptomic applications. Even so, small RNA species, including miRNA, bind weakly to SPRI beads under standard TNA purification conditions, necessitating a separate workflow using column-based methods that are difficult to automate. Here, an SPRI-based high-throughput TNA purification protocol that recovers DNA, RNA and small RNA, called GSC-modified RLT+ Aline bead-based protocol (GRAB-ALL), which incorporates modifications to enhance small RNA recovery is presented. GRAB-ALL was benchmarked against existing nucleic acid purification workflows and GRAB-ALL efficiently purifies TNA, including small RNA, for next-generation sequencing applications in a plate-based format suitable for automated high-throughput sample preparation.

We present a genome assembly of Caretta caretta (the Loggerhead sea turtle; Chordata, Testudines, Cheloniidae), generated from genomic data from two unrelated females. The genome sequence is 2.13 gigabases in size. The assembly has a busco completion score of 96.1% and N50 of 130.95 Mb. The majority of the assembly is scaffolded into 28 chromosomal representations with a remaining 2% of the assembly being excluded from these.

Abstract Background While the vaccines against COVID-19 are highly effective, COVID-19 vaccine breakthrough is possible despite being fully vaccinated. With SARS-CoV-2 variants still circulating, describing the characteristics of individuals who have experienced COVID-19 vaccine breakthroughs could be hugely important in helping to determine who may be at greatest risk. Methods With the approval of NHS England, we conducted a retrospective cohort study using routine clinical data from the OpenSAFELY-TPP database of fully vaccinated individuals, linked to secondary care and death registry data and described the characteristics of those experiencing COVID-19 vaccine breakthroughs. Results As of 1st November 2021, a total of 15,501,550 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 149 days (IQR: ​107–179). From within this population, a total of 579,780 (

Objectives We quantified associations between household tenure – whether someone privately or socially rents their property, or owner occupies – and prevalence of multiple long-term conditions (MLTCs) amongst working age adults. We also assessed whether the success of data linkages conducted to enable this study introduced potential selection biases. Approach This cross-sectional study used the 2019/20 wave of an innovative dataset linking health and local government data at individual and household levels for residents of an East London borough. To assess potential biases, we calculated standardised differences in variables for matched and unmatched primary care records. Our primary outcome was basic MLTCs, defined as two or more long-term conditions from a list of 38. Two further definitions of MLTCs were operationalised. Multilevel logistic regression was used to explore associations for working age adults (16-64 years, inclusive). Interaction terms were used to evaluate potential interactions between tenure and other household factors. Results Standardised differences in selected health variables for matched and unmatched primary care records were

Objective To investigate features of Guillain-Barré syndrome (GBS) following SARS-CoV-2 vaccines and evaluate for a causal link between the two.Methods We captured cases of GBS after SARS-CoV-2 vaccination through a national, open-access, online surveillance system. For each case, the certainty of GBS was graded using the Brighton criteria, and the relationship to the vaccine was examined using modified WHO Causality Assessment criteria. We compared age distribution of cases with that of prepandemic GBS cases and clinical features with the International GBS Outcome Study (IGOS).Results Between 1 January and 30 June 2021, we received 67 reports of GBS following the ChAdOx1 vaccine (65 first doses) and three reports following the BNT162b2 vaccine (all first doses). The causal association with the vaccine was classified as probable for 56 (80%, all ChAdOx1), possible for 12 (17%, 10 ChAdOx1) and unlikely for two (3%, 1 ChAdOx1). A greater proportion of cases occurred in the 50–59 age group in comparison with prepandemic GBS. Most common clinical variants were sensorimotor GBS (n=55; 79%) and facial diplegia with paraesthesias (n=10; 14%). 10% (n=7/69) of patients reported an antecedent infection, compared with 77% (n=502/652) of the IGOS cohort (p

Abstract Background Previous studies have noted traditional physical, demographic, and obstetrical predictors of inadequate or excess gestational weight gain, but the roles of psychological and behavioral factors are not well established. Few interventions targeting traditional factors of gestational weight gain have been successful, necessitating exploration of new domains. The objective of this study was to identify novel psychological and behavioral factors, along with physical, demographic, and obstetrical factors, associated with gestational weight gain that is discordant with the 2009 Institute of Medicine guidelines (inadequate or excess gain). Methods We recruited English-speaking women with a live singleton fetus at 8 to 20 weeks of gestation who received antenatal care from 12 obstetrical, family medicine, and midwifery clinics. A questionnaire was used to collect information related to demographic, physical, obstetrical, psychological, and behavioural factors anticipated to be related to weight gain. The association between these factors and total gestational weight gain, classified as inadequate, appropriate, and excess, was examined using stepwise multinomial logistic regression. Results Our study population comprised 970 women whose baseline data were obtained at a mean of 14.8 weeks of gestation ±3.4 weeks (standard deviation). Inadequate gestational weight gain was associated with obesity, planned gestational weight gain (below the guidelines or not reported), anxiety, and eating sensibly when with others but overeating when alone, while protective factors were frequent pregnancy-related food cravings and preferring an overweight or obese body size image. Excess gestational weight gain was associated with pre-pregnancy overweight or obese body mass index, planned gestational weight gain (above guidelines), frequent eating in front of a screen, and eating sensibly when with others but overeating when alone, while a protective factor was being underweight pre-pregnancy. Conclusions In addition to commonly studied predictors, this study identified psychological and behavioral factors associated with inadequate or excess gestational weight gain. Factors common to both inadequate and excessive gestational weight gain were also identified, emphasizing the multidimensional nature of the contributors to guideline-discordant weight gain.

Background The increasing number of individuals living with multiple long-term conditions (MLTCs) is a huge public health challenge both globally and in the UK. MLTCs are more prevalent, have earlier onset, and are more likely to include mental health conditions for residents of more deprived areas. However, the influence of household-level social determinants of health have received little attention. This is despite evidence suggesting that risk factors for MLTCs cluster within households. We aimed to quantify associations between household tenure – whether someone privately rents, rents from social housing, or owns their property – and different definitions of MLTCs amongst working age adults. Methods This cross-sectional study used the 2019/2020 wave of a novel dataset linking individual and household data across health services and local government for a deprived borough in North East London. Three definitions of MLTCs were operationalised: basic MLTCs (defined as two or more long-term conditions within an individual), physical-mental MLTCs (basic MLTCs where one condition is physical and one is depression or anxiety), and complex MLTCs (three or more long-term conditions affecting three or more different bodily systems). Multilevel logistic regression modelling was used to explore associations between tenure and MLTCs prevalence for working age adults (16-64 years old, inclusive). Findings Prevalence of basic, physical-mental and complex MLTCs was 18.0%, 4.8% and 6.0%, respectively. In unadjusted analyses, prevalence of all definitions of MLTCs was greater with increasing age, for women and individuals of white ethnicity. Compared to working age owner-occupiers, odds of basic MLTCs were 36% higher for social housing tenants (OR 1.36, 95% CI 1.31-1.42) and 21% lower for private renters (OR 0.79, 95% CI 0. 75-0.83) after adjusting for a range of health behaviours, and socioeconomic and demographic factors. Results were consistent across MLTCs definitions, although stronger for social housing tenants with physical-mental MLTCs. Conclusions This study finds strong evidence that household tenure is associated with MLTCs, emphasising the importance of understanding and addressing household-level determinants of health. Our findings suggest that resources to prevent and tackle MLTCs could be differentially targeted by tenure type and that working age adults are an important population to consider in preventative strategies that address social determinants of health. Further research should employ longitudinal research methods to assess causal relationships between household social determinants such as tenure and prevalence of MLTCs.

Background: People of non-White ethnicity have a higher risk of severe outcomes following influenza infection. It is unclear whether this is driven by an increased risk of infection or complications. We therefore aimed to investigate the incidence of clinically diagnosed influenza/influenza-like illness (ILI) by ethnicity in England from 2008-2018. Methods: We used linked primary and secondary healthcare data (from the Clinical Practice Research Datalink [CPRD] GOLD and Aurum databases and Hospital Episodes Statistics Admitted Patient Care [HES APC]). We included patients with recorded ethnicity who were aged 40-64 years and did not have a chronic health condition that would render them eligible for influenza vaccination. ILI infection was identified from diagnostic codes in CPRD and HES APC. We calculated crude annual infection incidence rates by ethnic group. Multivariable Poisson regression models with random effects were used to estimate any ethnic disparities in infection risk. Our main analysis adjusted for age, sex, and influenza year. Results: A total of 3,735,308 adults aged 40-64 years were included in the study; 87.6% White, 5.2% South Asian, 4.2% Black, 1.9% Other, and 1.1% Mixed. We identified 102,316 ILI episodes recorded among 94,623 patients. The rate of ILI was highest in the South Asian (9.6 per 1,000 person-years), Black (8.4 per 1,000 person-years) and Mixed (6.9 per 1,000 person-years) ethnic groups. The ILI rate in the White ethnic group was 5.7 per 1,000 person-years. After adjustment for age sex and influenza year, higher incidence rate ratios (IRR) for ILI were seen for South Asian (1.70, 95% CI 1.66-1.75), Black (1.48, 1.44-1.53) and Mixed (1.22, 1.15-1.30) groups compared to White ethnicity. Conclusions: Our results suggest that influenza infection risk differs between White and non-White groups who are not eligible for routine influenza vaccination.

The analysis of cell-free circulating tumor DNA (ctDNA) is potentially a less invasive, more dynamic assessment of cancer progression and treatment response than characterizing solid tumor biopsies. Standard isolation methods require separation of plasma by centrifugation, a time-consuming step that complicates automation. To address these limitations, we present an automatable magnetic bead-based ctDNA isolation method that eliminates centrifugation to purify ctDNA directly from peripheral blood (PB). To develop and test our method, ctDNA from cancer patients was purified from PB and plasma. We found that allelic fractions of somatic single-nucleotide variants from target gene capture libraries were comparable, indicating that the PB ctDNA purification method may be a suitable replacement for the plasma-based protocols currently in use.

Background: People of non-White ethnicity have a higher risk of severe outcomes following influenza infection. It is unclear whether this is driven by an increased risk of infection or complications. We therefore aimed to investigate the incidence of clinically diagnosed influenza/influenza-like illness (ILI) by ethnicity in England from 2008-2018. Methods: We used linked primary and secondary healthcare data (from the Clinical Practice Research Datalink [CPRD] GOLD and Aurum databases and Hospital Episodes Statistics Admitted Patient Care [HES APC]). We included patients with recorded ethnicity who were aged 40-64 years and did not have a chronic health condition that would render them eligible for influenza vaccination. ILI infection was identified from diagnostic codes in CPRD and HES APC. We calculated crude annual infection incidence rates by ethnic group. Multivariable Poisson regression models with random effects were used to estimate any ethnic disparities in infection risk. Our main analysis adjusted for age, sex, and influenza year. Results: A total of 3,735,308 adults aged 40-64 years were included in the study; 87.6% White, 5.2% South Asian, 4.2% Black, 1.9% Other, and 1.1% Mixed. We identified 102,316 ILI episodes recorded among 94,623 patients. The rate of ILI was highest in the South Asian (9.6 per 1,000 person-years), Black (8.4 per 1,000 person-years) and Mixed (6.9 per 1,000 person-years) ethnic groups. The ILI rate in the White ethnic group was 5.7 per 1,000 person-years. After adjustment for age sex and influenza year, higher incidence rate ratios (IRR) for ILI were seen for South Asian (1.70, 95% CI 1.66-1.75), Black (1.48, 1.44-1.53) and Mixed (1.22, 1.15-1.30) groups compared to White ethnicity. Conclusions: Our results suggest that influenza infection risk differs between White and non-White groups who are not eligible for routine influenza vaccination.

OBJECTIVE:To develop and validate a prediction model for excess pregnancy weight gain using early pregnancy factors. DESIGN:Prospective cohort study. SETTING:We recruited from 12 obstetrical, family medicine, and midwifery centers in Ontario, Canada. PARTICIPANTS:We recruited English-speaking women with singleton pregnancies between 8+0-20+6 weeks. Of 1296 women approached, 1050 were recruited (81%). Of those, 970 women had complete data (970/1050, 92%) and were recruited at a mean of 14.8 weeks. PRIMARY OUTCOME MEASURE:We collected data on psychological, physical, and social factors and used stepwise logistic regression analysis to develop a multivariable model predicting our primary outcome of excess pregnancy weight gain, with random selection of 2/3 of women for training data and 1/3 for testing data. RESULTS:Nine variables were included in the final model to predict excess pregnancy weight gain. These included nulliparity, being overweight, planning excessive gain, eating in front of a screen, low self-efficacy regarding pregnancy weight gain, thinking family or friends believe pregnant women should eat twice as much as before pregnancy, being agreeable, and having emotion control difficulties. Training and testing data yielded areas under the receiver operating characteristic curve of 0.76 (95% confidence interval, 0.72 to 0.80) and 0.62 (95% confidence interval 0.56 to 0.68), respectively. CONCLUSIONS:In this first validated prediction model in early pregnancy, we found that nine psychological, physical, and social factors moderately predicted excess pregnancy weight gain in the final model. This research highlights the importance of several predictors, including relatively easily modifiable ones such as appropriate weight gain plans and mindfulness during eating, and lays an important methodological foundation for other future prediction models.

Abstract Background RNA-Sequencing (RNA-seq) is now commonly used to reveal quantitative spatiotemporal snapshots of the transcriptome, the structures of transcripts (splice variants and fusions) and landscapes of expressed mutations. However, standard approaches for library construction typically require relatively high amounts of input RNA, are labor intensive, and are time consuming. Methods Here, we report the outcome of a systematic effort to optimize and streamline steps in strand-specific RNA-seq library construction. Results This work has resulted in the identification of an optimized messenger RNA isolation protocol, a potent reverse transcriptase for cDNA synthesis, and an efficient chemistry and a simplified formulation of library construction reagents. We also present an optimization of bead-based purification and size selection designed to maximize the recovery of cDNA fragments. Conclusions These developments have allowed us to assemble a rapid high throughput pipeline that produces high quality data from amounts of total RNA as low as 25 ng. While the focus of this study is on RNA-seq sample preparation, some of these developments are also relevant to other next-generation sequencing library types.

Next generation RNA-sequencing (RNA-seq) is a flexible approach that can be applied to a range of applications including global quantification of transcript expression, the characterization of RNA structure such as splicing patterns and profiling of expressed mutations. Many RNA-seq protocols require up to microgram levels of total RNA input amounts to generate high quality data, and thus remain impractical for the limited starting material amounts typically obtained from rare cell populations, such as those from early developmental stages or from laser micro-dissected clinical samples. Here, we present an assessment of the contemporary ribosomal RNA depletion-based protocols, and identify those that are suitable for inputs as low as 1-10 ng of intact total RNA and 100-500 ng of partially degraded RNA from formalin-fixed paraffin-embedded tissues.

Curation and storage of formalin-fixed, paraffin-embedded (FFPE) samples are standard procedures in hospital pathology laboratories around the world. Many thousands of such samples exist and could be used for next generation sequencing analysis. Retrospective analyses of such samples are important for identifying molecular correlates of carcinogenesis, treatment history and disease outcomes. Two major hurdles in using FFPE material for sequencing are the damaged nature of the nucleic acids and the labor-intensive nature of nucleic acid purification. These limitations and a number of other issues that span multiple steps from nucleic acid purification to library construction are addressed here. We optimized and automated a 96-well magnetic bead-based extraction protocol that can be scaled to large cohorts and is compatible with automation. Using sets of 32 and 91 individual FFPE samples respectively, we generated libraries from 100 ng of total RNA and DNA starting amounts with 95-100% success rate. The use of the resulting RNA in micro-RNA sequencing was also demonstrated. In addition to offering the potential of scalability and rapid throughput, the yield obtained with lower input requirements makes these methods applicable to clinical samples where tissue abundance is limiting.

Background The prevalence of diabetes is increasing with growing levels of obesity and an aging population. New practical guidelines for diabetes provide an applicable classification. Inconsistent coding of diabetes hampers the use of computerised disease registers for quality improvement, and limits the monitoring of disease trends.Objective To develop a consensus set of codes that should be used when recording diabetes diagnostic data.Methods The consensus approach was hierarchical, with a preference for diagnostic/disorder codes, to define each type of diabetes and non-diabetic hyperglycaemia, which were listed as being completely, partially or not readily mapped to available codes. The practical classification divides diabetes into type 1 (T1DM), type 2 (T2DM), genetic, other, unclassified and non-diabetic fasting hyperglycaemia. We mapped the classification to Read version 2, Clinical Terms version 3 and SNOMED CT.Results T1DMand T2DM were completely mapped to appropriate codes. However, in other areas only partial mapping is possible. Genetics is a fast-moving field and there were considerable gaps in the available labels for genetic conditions; what the classification calls ‘other’ the coding system labels ‘secondary’ diabetes. The biggest gap was the lack of a code for diabetes where the type of diabetes was uncertain. Notwithstanding these limitations we were able to develop a consensus list.Conclusions It is a challenge to develop codes that readily map to contemporary clinical concepts. However, clinicians should adopt the standard recommended codes; and audit the quality of their existing records.

Sequence-based methods for transcriptome characterization have typically relied on generation of either serial analysis of gene expression tags or expressed sequence tags. Although such approaches have the potential to enumerate transcripts by counting sequence tags derived from them, they typically do not robustly survey the majority of transcripts along their entire length. Here we show that massively parallel sequencing of randomly primed cDNAs, using a next-generation sequencing-by-synthesis technology, offers the potential to generate relative measures of mRNA and individual exon abundance while simultaneously profiling the prevalence of both annotated and novel exons and exon-splicing events. This technique identifies known single nucleotide polymorphisms (SNPs) as well as novel single-base variants. Analysis of these variants, and previously unannotated splicing events in the HeLa S3 cell line, reveals an overrepresentation of gene categories including those previously implicated in cancer.

We present a genome assembly of Caretta caretta (the Loggerhead sea turtle; Chordata, Testudines, Cheloniidae), generated from genomic data from two unrelated females. The genome sequence is 2.13 gigabases in size. The assembly has a busco completion score of 96.1% and N50 of 130.95 Mb. The majority of the assembly is scaffolded into 28 chromosomal representations with a remaining 2% of the assembly being excluded from these.

Medical and rehabilitation systems care for children who sustain brain injuries. Their much needed services, however, are short in comparison with the long term needs of these children and their families. For the most part, it is schools and families who provide the long term supports to help children make the best outcomes and create a better quality of life. Professionals and families who develop collaborative models find that they can more effectively manage services for these children by carefully crafting Individual Education Plans (IEP's). Through the IEP process students' complex needs; the multiple transitions they experience; and their long term needs can be met. [ABSTRACT FROM AUTHOR]