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We lead multidisciplinary applied research and training to rethink the way health care is delivered in general practice and across the community.
Representativeness, Vaccination Uptake, and COVID-19 Clinical Outcomes 2020-2021 in the UK Oxford-Royal College of General Practitioners Research and Surveillance Network: Cohort Profile Summary
Background: The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) is one of Europe’s oldest sentinel systems, working with the UK Health Security Agency (UKHSA) and its predecessor bodies for 55 years. Its surveillance report now runs twice weekly, supplemented by online observatories. In addition to conducting sentinel surveillance from a nationally representative group of practices, the RSC is now also providing data for syndromic surveillance. Objective: The aim of this study was to describe the cohort profile at the start of the 2021-2022 surveillance season and recent changes to our surveillance practice. Methods: The RSC’s pseudonymized primary care data, linked to hospital and other data, are held in the Oxford-RCGP Clinical Informatics Digital Hub, a Trusted Research Environment. We describe the RSC’s cohort profile as of September 2021, divided into a Primary Care Sentinel Cohort (PCSC)—collecting virological and serological specimens—and a larger group of syndromic surveillance general practices (SSGPs). We report changes to our sampling strategy that brings the RSC into alignment with European Centre for Disease Control guidance and then compare our cohort’s sociodemographic characteristics with Office for National Statistics data. We further describe influenza and COVID-19 vaccine coverage for the 2020-2021 season (week 40 of 2020 to week 39 of 2021), with the latter differentiated by vaccine brand. Finally, we report COVID-19–related outcomes in terms of hospitalization, intensive care unit (ICU) admission, and death. Results: As a response to COVID-19, the RSC grew from just over 500 PCSC practices in 2019 to 1879 practices in 2021 (PCSC, n=938; SSGP, n=1203). This represents 28.6% of English general practices and 30.59% (17,299,780/56,550,136) of the population. In the reporting period, the PCSC collected >8000 virology and >23,000 serology samples. The RSC population was broadly representative of the national population in terms of age, gender, ethnicity, National Health Service Region, socioeconomic status, obesity, and smoking habit. The RSC captured vaccine coverage data for influenza (n=5.4 million) and COVID-19, reporting dose one (n=11.9 million), two (n=11 million), and three (n=0.4 million) for the latter as well as brand-specific uptake data (AstraZeneca vaccine, n=11.6 million; Pfizer, n=10.8 million; and Moderna, n=0.7 million). The median (IQR) number of COVID-19 hospitalizations and ICU admissions was 1181 (559-1559) and 115 (50-174) per week, respectively. Conclusions: The RSC is broadly representative of the national population; its PCSC is geographically representative and its SSGPs are newly supporting UKHSA syndromic surveillance efforts. The network captures vaccine coverage and has expanded from reporting primary care attendances to providing data on onward hospital outcomes and deaths. The challenge remains to increase virological and serological sampling to monitor the effectiveness and waning of all vaccines available in a timely manner.
The role of the enrolling clinician in emergency research conducted under an exception from informed consent
The Exception from Informed Consent (EFIC) permits patient enrolment into therapeutic emergency research where obtaining informed consent is challenging. Yet this fails to resolve a core ethical conflict in the research and has generated controversy. This is because existing justification and practice has relied on applying EFIC per study—a wholesale permission to enroll irrespective of circumstance—instead of per patient. Our novel justification for enrolment centers on applying EFIC per patient, which empowers the enrolling clinician to judge whether to enroll patients with an Exception. This contrasts with the idea that clinician judgment is surplus to the judgements already made by institutions in deciding the research may proceed. Instead, we show that enrolling clinician’s judgment is ethically significant and should not be overlooked: attending to this strengthens the research ethically and reduces controversy. There should be a bigger role for the clinician in the research enrolment space.
Rethinking ‘Recovery’: A Comparative Qualitative Analysis of Experiences of Intensive Care With COVID and Long Covid in the United Kingdom
ABSTRACTIntroductionInterpretations of ‘recovery’ from illness are complex and influenced by many factors, not least patient expectations and experiences. This paper examines meanings of ‘recovery’, and how it is strived towards, drawing on the example of COVID‐19 infection.MethodsDrawing on qualitative interviews (n = 93) conducted in the UK between February 2021 and July 2022, we compare adults' accounts of being admitted to an Intensive Care Unit (ICU) with COVID‐19 to accounts of being ill with Long COVID, defined as ongoing symptoms for at least 12 weeks postinfection. We conducted a multi‐stage comparative analysis using Nvivo to organise and code the data.ResultsWe identified similarities and differences in participants' descriptions of their ‘worlds of illness’. For both groups, perceptions of recovery were shaped by the novel, unknown nature of COVID‐19. Participants questioned the achievability of full restoration of prior states of health, highlighted the heterogeneity of ‘recovery trajectories’ and described the hard physical and emotional work of adjusting to changed selves. Themes that revealed differences in ‘worlds of illness’ described included the different baselines, waymarkers, and pathways of illness experiences. Differences in other people's responses to their illness were also evident. For ICU participants, hospitalisation, and especially ICU admission, conferred legitimate patient status and authenticity to their symptoms. Family, friends and healthcare professionals acknowledged their illness, celebrated their survival, and granted them latitude to recover. For Long Covid participants, their patient status often lacked comparable authenticity in others' eyes. They reported encountering a lack of recognition and understanding of their ongoing need to recover.ConclusionsThis study highlights how the meanings of illness ascribed by others can influence how recovery is experienced. Our findings highlight the importance of ensuring people are made to feel their illness experiences are legitimate, regardless of hospitalisation status, formal diagnosis or lack of medical knowledge and pathways. They also indicate the value of emphasising the different permutations, and lack of linearity, that recovery can take. This may help to help to guard against a lack of understanding for experiences of recovery which do not meet idealised notions.Patient or Public ContributionBoth studies were guided by an advisory panel that included patient and public involvement representatives with lived experience of Intensive Care/COVID experience and Long COVID respectively. Through regular meetings with the research teams, the advisory panel had input into all aspects of the study conduct, including recruitment methods and content of the interview topic guide and feedback on preliminary analyses. The Long COVID study also included a lived experience coinvestigator who contributed to data interpretation and analysis.
When life-saving measures lead to trauma: Subcapsular hepatic hematoma after CPR.
Cardiopulmonary resuscitation (CPR) is a critical intervention for cardiac arrest but can result in significant internal injuries due to the force of chest compressions. Among these, subcapsular hepatic hematoma is a rare and serious complication. Here we present a 55-year-old male with a history of alcohol abuse presented with a severe ischemic stroke and subsequently required CPR due to pulseless ventricular tachycardia. Following resuscitation, the patient developed a subcapsular hepatic hematoma, likely caused by the trauma of chest compressions. The patient also had a complex clinical course involving hemorrhagic conversion of the stroke and the need for anticoagulation due to bilateral pulmonary emboli, which further complicated the management of the hepatic hematoma. The identification of the hematoma was achieved through contrast-enhanced CT imaging after the patient exhibited worsening abdominal discomfort and signs of internal bleeding. The management focused on balancing the need for anticoagulation with the risks of further bleeding from the hematoma. A multidisciplinary approach was essential, involving close monitoring, potential surgical intervention, and careful adjustment of anticoagulant therapy. This case emphasizes the importance of recognizing the potential for internal injuries following CPR, especially in patients requiring anticoagulation. Early detection through imaging and a coordinated, multidisciplinary approach are crucial in managing such complications and improving patient outcomes.
Process evaluation in a randomised controlled trial of DREAMS-START (dementia related manual for sleep; strategies for relatives) for sleep disturbance in people with dementia and their carers
Introduction: DREAMS-START is a multicomponent intervention targeting sleep disturbance in people with dementia. To enhance understanding of the DREAMS-START randomised controlled trial, which showed improved sleep in the intervention compared to the control arm, we conducted a process evaluation exploring (i) DREAMS-START delivery, (ii) behaviour change mechanisms and (iii) contextual factors impacting outcomes. Methods: Mixed-methods design. We measured intervention adherence, fidelity and additional therapeutic process measures. We interviewed a sub-sample of intervention arm family carers and facilitators delivering DREAMS-START. We analysed data thematically guided by a prespecified theory of change logic model informed by the Theoretical Domains Framework. We measured movement using an actigraph worn by the person with dementia at baseline and at four- and eight-month follow-ups to explore potential mechanisms of action. Results: Attendance was good (82.8% attended ≥4/6 sessions). Mean fidelity score (95.4%; SD 0.08) and median score for all four process measures assessed (5/5; IQR 5–5) were high. We interviewed 43/188 family carers and 9/49 DREAMS-START facilitators. We identified three overarching themes aligned with our model: (i) knowledge and facilitation enable behaviour change, (ii) increasing sleep pressure and developing skills to manage sleep disturbances and (iii) Establishing a routine and sense of control. We were unable to collect sufficient data for pre-specified actigraphy analyses. Conclusion: Despite competing demands, carers attended DREAMS-START. It promoted behaviour change through supportive in-session reflection, increasing carer knowledge and skills. This was embedded between sessions and actions were positively reinforced as carers experienced changes. Results will inform future implementation in clinical services.
Sleep Health and White Matter Integrity in the UK Biobank
Many people experience impaired sleep health, yet knowledge about its neurobiological correlates is limited. As previous studies have found associations between white matter integrity and several sleep traits, white matter integrity could be causally implicated in poor sleep health. However, these studies were often limited by small sample sizes. In this study, we examine associations between multiple indices of white matter integrity and sleep health in 29,114 UK Biobank participants. Late chronotype, daytime sleepiness, insomnia symptoms and, most extensively, long sleep duration were independently associated with diffusion MRI markers of reduced white matter integrity. Previous findings showing an association between insomnia symptoms and decreased fractional anisotropy (FA) in the anterior internal capsule could not be replicated. To our knowledge, the current analysis is the first study to find an association between long sleep duration and impaired microstructural white matter integrity. Previous assumptions concerning the role of white matter integrity for insomnia are challenged.
Navigating the complexities of end-stage kidney disease (ESKD) from risk factors to outcome: insights from the UK Biobank cohort
Background: The global prevalence of end-stage kidney disease (ESKD) is increasing despite optimal management of traditional risk factors such as hyperglycaemia, hypertension, and dyslipidaemia. This study examines the influence of cardiorenal risk factors, socioeconomic status, and ethnic and cardiovascular comorbidities on ESKD outcomes in the general population. Methods: This cross-sectional study analysed data from 502,408 UK Biobank study participants recruited between 2006 and 2010. Multivariable logistic regression models were fitted to assess risk factors for ESKD, with results presented as adjusted odds ratio (aOR) and 95% confidence intervals (95% CI). Results: A total of 1191 (0.2%) of the study participants reported ESKD. Diabetes increased ESKD risk by 62% [1.62 (1.36–1.93)], with early-onset diabetes (before age 40) conferring higher odds compared to later-onset (after age 40) [2.26 (1.57–3.24)]. Similarly, early-onset hypertension (before age 40), compared to later onset (after age 40), increased ESKD odds by 73% [1.73 (1.21–2.44)]. Cardiovascular comorbidities, including stroke, hypertension, myocardial infarction and angina, were strongly associated with ESKD [5.97 (3.99–8.72), 5.35 (4.38–6.56), 4.94 (3.56–6.78), and 4.89 (3.47–6.81)], respectively. Males were at 22% higher risk of ESKD than females [1.22 (1.04–1.43)]. Each additional year of diabetes duration increased ESKD odds by 2% [1.02 (1.01–1.03)]. Non-white ethnicity, compared to white and socioeconomically most deprived, compared to the least deprived quintiles, were at 70% and 83% higher odds of ESKD. Each unit of HbA1c rise increased the odds of ESKD by 2%. Compared to microalbuminuria, macroalbuminuria increased the odds of ESKD by almost 10-fold [9.47 (7.95–11.27)] while normoalbuminuria reduced the odds by 73% [0.27 (0.22–0.32)]. Conclusions: Early onset of diabetes and hypertension, male sex, non-white ethnicity, deprivation, poor glycaemic control, and prolonged hyperglycaemia are significant risk factors for ESKD. These findings highlight the complexity of ESKD and the need for multifactorial targeted interventions in high-risk populations. Clinical trial number: Not applicable.
Impact of increasing CD4 count threshold eligibility for antiretroviral therapy initiation on advanced HIV disease and tuberculosis prevalence and incidence in South Africa: an interrupted time series analysis.
INTRODUCTION: We investigated the impact of increasing CD4 count eligibility for antiretroviral therapy (ART) initiation on advanced HIV disease (AHD) and tuberculosis (TB) prevalence and incidence among people living with HIV (PLHIV) in South Africa. METHODS: We conducted an interrupted time series analysis with de-identified data of PLHIV aged ≥15 years initiating ART between April 2012 and February 2020 at 65 primary healthcare clinics in KwaZulu-Natal, South Africa. Outcomes included monthly proportions of new ART initiators presenting with AHD (CD4 count <200 cells/µL) and TB disease. We created a cohort of monthly ART initiators without TB and evaluated the cumulative incidence of TB within 12 months follow-up. We used segmented binomial regression models to estimate relative risks (RR) of outcomes, allowing for a step and slope change after expanding the ART initiation CD4 count eligibility from <350 to <500 cells/µL in January 2015 and following Universal Test and Treat (UTT) implementation in September 2016. RESULTS: Among 209 984 participants, median age was 32 (range: 26-38), and 141 499 (67.4%) were female. After January 2015, the risk of AHD at initiation decreased in step by 25.0% (RR=0.750, 95% CI 0.688 to 0.812) and further reduced by 26.9% following UTT implementation (RR=0.731, 95% CI 0.681 to 0.781). The risk of TB at initiation also decreased in step by 27.6% after January 2015 (RR=0.724, 95% CI 0.651 to 0.797) and further decreased by 17.4% after UTT implementation (RR=0.826, 95% CI 0.711 to 0.941) but remained stable among initiators with AHD. Among the incidence cohort, we saw a step decrease in the risk of new TB by 31.4% (RR=0.686, 95% CI 0.465 to 0.907) following UTT implementation. Among the incidence cohort with AHD, there was weak evidence of a step decrease in the risk of new TB (RR=0.755, 95% CI 0.489 to 1.021), but the slope decreased by 9.7% per month (RR=0.903, 95% CI 0.872 to 0.934) following UTT implementation. CONCLUSIONS: Our data support the added benefit of decreased TB co-burden with expanded ART access. Early diagnosis and immediate linkage to care should be prioritised among PLHIV.
Differences in the risk of frailty based on care receipt, unmet care needs and socio-economic inequalities: A longitudinal analysis of the English Longitudinal Study of Ageing
Background: The older population is increasingly reliant on social care, especially those who are frail. However, an estimated 1.5 million people over 65 in England have unmet care needs. The relationship between receiving care, or receiving insufficient care, and changes in frailty status remains unclear. Objectives: To investigate the associations between care receipt (paid or unpaid), unmet care needs, frailty status, and mortality. Design: We used multistate models to estimate the risk of increasing or decreasing levels of frailty, using English Longitudinal Study of Ageing (ELSA) data. Covariates included age, gender, wealth, area deprivation, education, and marital status. Care status was assessed through received care and self-reported unmet care needs, while frailty status was determined using a frailty index. Participants: 15,003 individuals aged 50+, using data collected over 18 years (2002–2019). Results: Individuals who receive care are more susceptible to frailty and are less likely to recover from frailty to a less frail state. The hazard ratio of males receiving care transitioning from prefrailty to frailty was 2.1 [95 % CI: 1.7–2.6] and for females 1.8 [1.5–2.0]. Wealth is an equally influential predictor of changes in frailty status: individuals in the lowest wealth quintile who do not receive care are as likely to become frail as those in the highest wealth quintile who do receive care. As individuals receiving care (including unpaid care) are likely to be in poorer health than those who do not receive care, this highlights stark inequalities in the risk of frailty between the richest and poorest individuals. Unmet care needs were associated with transitioning from prefrailty to frailty for males (hazard ratio: 1.7 [1.2–2.4]) but not for females. Conclusions: Individuals starting to receive care (paid or unpaid) and people in the poorest wealth quintile are target groups for interventions aimed at delaying the onset of frailty.
Uptake of patient enrolment in primary care and associated factors: a systematic review and meta-analysis
Background: Patient enrolment in primary care refers to the formal process of registering patients with a specific primary care provider, team, or practice. This approach is often expected to enhance continuity and coordination of care. However, limited information exists on the uptake of patient enrolment and its associated characteristics. This review aimed to estimate the uptake of patient enrolment in primary care and examine factors associated with decisions around enrolment. Methods: Eight electronic databases (PubMed, Cochrane Register of Systematic Reviews, Embase, CINAHL, PsycINFO, PAIS, Web of Science, and Scopus) were searched for peer-reviewed articles published from January 2014 to July 2024. Findings from included studies were extracted and synthesised, with uptake estimated through meta-analysis and factors associated with enrolment summarised narratively. Review registration: PROSPERO CRD42024597078. Results: Ten studies across nine publications were included. Of these, eight studies with 27,919,216 participants were included in the meta-analysis. The results showed a pooled patient enrolment uptake rate of 71.4% (95% Confidence Interval [CI]: 13.6–97.5%). There was no significant difference in enrolment rates between population-wide and program-based enrolment (72.4% vs. 73.5%; p = 0.980). Several associated factors were identified in three publications. Women showed higher enrolment rates than men (adjusted odds ratio [aOR] = 1.07, 95% CI: 1.07–1.08), while recently arrived immigrants in a country had lower enrolment rates than the established population (aOR = 0.40, 95% CI: 0.40–0.41). Patients living in small urban/suburban/rural areas had higher enrolment rates than those in large urban/metropolitan regions (aORs: 1.17–2.18). Higher socioeconomic level was associated with increased rates of enrolment. Patients with some specific chronic health conditions, such as those with diagnosed mental illness or substance use disorders, had lower enrolment rates. Conclusions: The findings reveal that more than two-thirds of patients were enrolled with a primary care provider or practice; enrolment was influenced by demographic, geographic, socioeconomic, and clinical factors. Lower enrolment among men, recent immigrants, individuals living in large urban/metropolitan areas, lower socioeconomic groups, and those with certain health conditions may indicate potential barriers to health service access and opportunities for enrolment. Addressing these disparities is essential to promote equitable access and enhance opportunities for continuity and coordination of primary care.
Open science interventions to improve reproducibility and replicability of research: a scoping review.
Various open science practices have been proposed to improve the reproducibility and replicability of scientific research, but not for all practices, there may be evidence they are indeed effective. Therefore, we conducted a scoping review of the literature on interventions to improve reproducibility. We systematically searched Medline, Embase, Web of Science, PsycINFO, Scopus and Eric, on 18 August 2023. Any study empirically evaluating the effectiveness of interventions aimed at improving the reproducibility or replicability of scientific methods and findings was included. We summarized the retrieved evidence narratively and in evidence gap maps. Of the 105 distinct studies we included, 15 directly measured the effect of an intervention on reproducibility or replicability, while the remainder addressed a proxy outcome that might be expected to increase reproducibility or replicability, such as data sharing, methods transparency or pre-registration. Thirty studies were non-comparative and 27 were comparative but cross-sectional observational designs, precluding any causal inference. Despite studies investigating a range of interventions and addressing various outcomes, our findings indicate that in general the evidence base for which various interventions to improve reproducibility of research remains remarkably limited in many respects.
The impact of the COVID-19 pandemic on antimicrobial usage: An international patient-level cohort study
Background: This study aimed to evaluate the trends in antimicrobial prescription during the first 1.5 years of COVID-19 pandemic. Methods: This was an observational, retrospective cohort study using patient-level data from Bangladesh, Brazil, India, Italy, Malawi, Nigeria, South Korea, Switzerland and Turkey from patients with pneumonia and/or acute respiratory distress syndrome and/or sepsis, regardless of COVID-19 positivity, who were admitted to critical care units or COVID-19 specialized wards. The changes of antimicrobial prescription between pre-pandemic and pandemic were estimated using logistic or linear regression. Pandemic effects on month-wise antimicrobial usage were evaluated using interrupted time series analyses (ITSAs). Results: Antimicrobials for which prescriptions significantly increased during the pandemic were as follows: meropenem in Bangladesh (95% CI: 1.94-4.07) with increased prescribed daily dose (PDD) (95% CI: 1.17-1.58) and Turkey (95% CI: 1.09-1.58), moxifloxacin in Bangladesh (95% CI: 4.11-11.87) with increased days of therapy (DOT) (95% CI: 1.14-2.56), piperacillin/tazobactam in Italy (95% CI: 1.07-1.48) with increased DOT (95% CI: 1.01-1.25) and PDD (95% CI: 1.05-1.21) and azithromycin in Bangladesh (95% CI: 3.36-21.77) and Brazil (95% CI: 2.33-8.42). ITSA showed a significant drop in azithromycin usage in India (95% CI: -8.38 to -3.49â€...g/100 patients) and South Korea (95% CI: -2.83 to -1.89 g/100 patients) after WHO guidelines v1 release and increased meropenem usage (95% CI: 93.40-126.48 g/100 patients) and moxifloxacin (95% CI: 5.40-13.98 g/100 patients) in Bangladesh and sulfamethoxazole/trimethoprim in India (95% CI: 0.92-9.32 g/100 patients) following the Delta variant emergence. Conclusions: This study reinforces the importance of developing antimicrobial stewardship in the clinical settings during inter-pandemic periods.
Burden of RSV infections among young children in primary care: a prospective cohort study in five European countries (2021–23)
Background: The majority of respiratory syncytial virus (RSV) infections in young children are managed in primary care, however, the disease burden in this setting remains poorly defined. Methods: We did a prospective cohort study in primary care settings in Belgium, Italy, Spain, the Netherlands, and the UK during the RSV seasons of 2020–21 (UK only; from Jan 1, 2021), 2021–22, and 2022–23. Children aged younger than 5 years presenting to their general practitioner or primary care paediatrician with symptoms of an acute respiratory tract infection were eligible for RSV testing. Children who tested positive for RSV were consented and followed up for 30 days via a physician clinical report (initial primary care visit on day 1) and two parent-report questionnaires (days 14 and 30). We assessed the burden of RSV in terms of clinical course (symptoms, illness duration, and complications), health-care resource utilisation (primary care visits, emergency department visits, hospitalisation rate, and medication use), and societal impact (daycare or school absence and parental work absence) for the 30-day follow-up period. Findings: Among 3414 tested children, 1124 (32·9%; 95% CI 31·3–34·5) tested positive for RSV. Among children with data on age, RSV positivity rate was 38·9% (36·1–41·7; n=466 of 1198) in children younger than 1 year and 25·9% (24·0–27·9; n=513 of 1979) in those aged 1 to <5 years. Of the 1124 RSV-positive children, 878 (78·1%) were enrolled and had day 1 data collected (median age 11·1 months [IQR 6·0–22·0]; 446 [50·9%] boys and 431 [49·1%] girls [N=877]). RSV illness lasted a mean of 11·7 days (95% CI 11·2–12·2; n=794). At day 14 and day 30, any remaining symptoms were reported in 451 of 804 (56·1% [95% CI 52·6–59·6]) and 261 of 724 (36·0% [32·6–39·7]) children. The mean number of primary care visits per child ranged from 1·4 (95% CI 1·2–1·6; the Netherlands) to 3·0 (2·8–3·3; Spain), and was higher in children younger than 1 year (2·7 visits [2·4–2·9]) than in those aged 1 to <5 years (2·1 [1·9–2·2]). Prescribed medication use varied, from 25 of 96 children (26·0% [95% CI 17·6–36·0]; the UK) to 228 of 297 children (76·8% [71·5–81·5]; Italy), with bronchodilators and antibiotics being the most commonly prescribed medicines across all countries. Prescribed medication use was reported in 258 of 418 children aged 1 to <5 years (61·7% [56·9–66·4]) and 196 of 394 children younger than 1 year (49·7% [44·7–54·8]). Missed working days by parents due to their child's RSV illness were reported in 340 of 744 cases (45·7% [42·1–49·4]); the mean number of missed workdays ranged from 1·3 days (95% CI 0·5–2·2) in Spain to 4·1 days (3·3–5·0) in Belgium. Interpretation: RSV infections in children younger than 5 years in primary care are associated with substantial symptomatology, health-care utilisation, and parental work absence. Notable differences in RSV burden existed across countries, likely due to differences in primary health-care systems, clinical practice, and health-care-seeking behaviour. This study emphasises the importance of considering country-specific primary care burden estimates when considering the implementation of RSV immunisations programmes. Funding: Sanofi and AstraZeneca.
Fundamental causation and candidacy: Harnessing explanatory frames to better understand how structural determinants of health inequalities shape disengagement from primary healthcare.
This paper aims to better understand how structural determinants of health inequalities shape disengagement from healthcare for vulnerable groups across a range of social conditions. Using a sub-sample (N = 20) from a qualitative interview UK study of those missing from primary-care, it illuminates how structural drivers of health inequalities operate at organisational and practice levels to weaken engagement with primary-care. Finding ways of better analysing and demonstrating the causal chains between structural determinants and patterns of disengagement is important because previous research has shown that practitioner and policy understanding of structural determination, an important precursor for mitigatory action, is not always sufficient, and research on healthcare utilisation can itself be weak in investigating structures of inequality. We address this deductively by testing a novel combination of Link and Phelan's Fundamental Cause Theory and Dixon-Woods and colleagues' Candidacy framework. Combining elements of these frameworks compensates for identified gaps in each. We demonstrate how Candidacy can be strengthened through incorporating more systematic theorisation of structural processes and that the more abstract arguments of fundamental (structural) causes can be made concrete via Candidacy's focus on inequalities in patients' access to, and utilisation of, healthcare. We also argue that both theories are enhanced by including Metzl and Hansen's concept of 'structural competency' as a potential mitigatory mechanism operating between fundamental causes and patient engagement.