Search

Background and purpose: Factors influencing the outcome after the critical care unit (CCU) for patients with status epilepticus (SE) are poorly understood. Survival for these patients was examined to establish (i) whether the risk of mortality has changed over time and (ii) whether admission to different unit types affects mortality risk over and above other risk factors. Methods: The Intensive Care National Audit and Research Centre database and the Case Mix Programme database (January 2001 to December 2016) were analysed. Units were defined as neuro‐CCU (NCCU), general CCU with 24‐h neurological support (GCCU‐N) or general CCU with limited neurological support (GCCU‐L). Results: There were 35 595 CCU cases of SE with a 3‐fold increase over time (4739 in 2001–2004 to 14 166 in 2013–2016). More recent admissions were older and were more often unsedated on admission. Mortality declined for all units although this was more marked for NCCUs (8.1% in 2001–2004 to 4.4% in 2013–2016 compared to 5.1% and 4.1% for GCCU‐L). Acute hospital mortality was two to three times higher than CCU mortality although this has also declined with time. GCCU‐L appeared to have lower mortality than NCCUs (odds ratio 0.84, 95% confidence interval 0.72, 0.98) but after post hoc adjustment for case mix there were no differences. Older age and markers of seriousness of morbidity were all associated with increased mortality risk. Conclusions: The number of patients admitted to a CCU for SE is rising but critical care and acute hospital mortality is decreasing. Patients treated in an NCCU have higher mortality but this is explicable by more severe underlying disease. [ABSTRACT FROM AUTHOR]

Background:Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing.Methods:Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up.Results:Among randomised practices, 271 (68%) in the intervention arm (198 114 men) and 302 (78%) in the control arm (221 929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices).Conclusions:The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening. [ABSTRACT FROM AUTHOR]

Introduction People with parkinsonism (PwP) are a highly heterogeneous group and the condition encompasses a spectrum of motor and nonmotor symptoms which variably emerge and manifest across the disease course, fluctuate over time and negatively impact quality of life. Whilst parkinsonism is not directly the result of ageing, it is a condition that mostly affects older people, who may also be living with frailty and multimorbidity. This study aims to describe a broad range of PwP in relation to their symptomatology, disability, health needs, disease stage, comorbidities and sociodemographics. Methods In this cross-sectional study, performed at one site, PwP (excluding those with drug-induced parkinsonism) will be sent a study information pack for themselves and their primary informal caregiver, if relevant. Data are collected via questionnaire, with additional support if required to maximise participation. A specific strategy has been developed to target and proactively recruit patients lacking capacity to consent, including those in residential care settings, with input from a personal consultee prior to completion of a bespoke questionnaire by a representative. Caregivers are also recruited to look at various health outcomes. Results Our primary outcome is the frequency of various health outcomes (e.g. depression) and how they cluster together. Linear and logistic regression models will be used to test simple associations and interactions with gender, age group and socio-economic status. Conclusion It is necessary to consider the multifaceted problems that PwP experience, together with frailty and comorbidities, in order to fully appreciate the clinical complexity as well as the impact on caregiver well-being. This information is necessary to inform the development of a person-centered, individualised multicomponent intervention to target patients and caregivers most at risk of adverse outcomes. We hope that these findings will inform future intervention trials and improve accessibility to research participation. [ABSTRACT FROM AUTHOR]

BackgroundSymptoms of anxiety and depression are common in older people, but the relative importance of factors operating in early and later life in influencing risk is unclear, particularly in the case of anxiety.MethodWe used data from five cohorts in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme: the Aberdeen Birth Cohort 1936, the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study and the Lothian Birth Cohort 1921. We used logistic regression to examine the relationship between factors from early and later life and risk of anxiety or depression, defined as scores of 8 or more on the subscales of the Hospital Anxiety and Depression Scale, and meta-analysis to obtain an overall estimate of the effect of each.ResultsGreater neuroticism, poorer cognitive or physical function, greater disability and taking more medications were associated in cross-sectional analyses with an increased overall likelihood of anxiety or depression. Associations between lower social class, either in childhood or currently, history of heart disease, stroke or diabetes and increased risk of anxiety or depression were attenuated and no longer statistically significant after adjustment for potential confounding or mediating variables. There was no association between birth weight and anxiety or depression in later life.ConclusionsAnxiety and depression in later life are both strongly linked to personality, cognitive and physical function, disability and state of health, measured concurrently. Possible mechanisms that might underlie these associations are discussed. [ABSTRACT FROM PUBLISHER]

We investigated whether angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACE-Is) are more strongly associated with Alzheimer's disease (AD), vascular dementia (VaD), and other dementias, than other anti-hypertensive drugs. We conducted a nested case-control analysis within the UK general practice research database, with prospectively recorded anti-hypertensive prescribing data. We sampled cases aged ≥60 years and diagnosed between 1997-2008 (5,797 with AD, 2,186 with VaD, 1,214 with unspecified/other dementia) which were matched to up to four controls by age, general practice and gender. We computed odds-ratios and dose response effects for AD, vascular and unspecified/other dementia, comparing those prescribed ARBs or ACE-Is for at least six months with patients prescribed other anti-hypertensives. We controlled for matching factors, co-morbidities, smoking status, an area measure of socioeconomic status, consultation rate and blood pressure and accounted for reverse causality by introducing time-lags of up to eight years prior to diagnosis/index date. Patients diagnosed with AD, vascular and unspecified/other dementia had fewer prescriptions for ARBs and ACE-Is. Inverse associations with AD were strongest for ARBs (odds-ratio; 0.47, 95%CI, 0.37-0.58) compared with ACE-Is (odds-ratio; 0.76, 95%CI, 0.69-0.84) (p(difference) < 0.001). Associations of ARBs with AD were stronger than for vascular dementia (p(difference) = 0.01) and unspecified/other dementia (p(difference) = 0.23). There were inverse dose-response relationships between ARBs and ACE-Is with AD (both p(trend) < 0.01). The inverse association of ACE-Is with AD diminished when using longer time lags but the ARB-AD association persisted. Patients with AD were around half as likely to be prescribed ARBs. Further randomized controlled trial evidence is required to rigorously test these findings. [ABSTRACT FROM AUTHOR]

Background: In the United States, Black men have a higher risk of prostate cancer and worse survival than do White men, but it is unclear whether this is because of differences in diagnosis and management. We re-examined these differences in the United Kingdom, where health care is free and unlikely to vary by socioeconomic status.Methods: This study is a population-based retrospective cohort study of men diagnosed with prostate cancer with data on ethnicity, prognostic factors, and clinical care. A Delphi panel considered the appropriateness of investigations and treatments received.Results: At diagnosis, Black men had similar clinical stage and Gleason scores but higher age-adjusted prostate-specific antigen levels (geometric mean ratio 1.41, 95% confidence interval (95% CI): 1.15-1.73). Black men underwent more investigations and were more likely to undergo radical treatment, although this was largely explained by their younger age. Even after age adjustment, Black men were more likely to undergo a bone scan (odds ratio 1.37, 95% CI: 1.05-1.80). The Delphi analysis did not suggest differential management by ethnicity.Conclusions: This UK-based study comparing Black men with White men found no evidence of differences in disease characteristics at the time of prostate cancer diagnosis, nor of under-investigation or under-treatment in Black men. [ABSTRACT FROM AUTHOR]

Black men in England have three times the age-adjusted incidence of diagnosed prostate cancer as compared with their White counterparts. This population-based retrospective cohort study is the first UK-based investigation of whether access to diagnostic services underlies the association between race and prostate cancer. Prostate cancer was ascertained using multiple sources including hospital records. Race and factors that may influence prostate cancer diagnosis were assessed by questionnaire and hospital records review. We found that Black men were diagnosed an average of 5.1 years younger as compared with White men (P<0.001). Men of both races were comparable in their knowledge of prostate cancer, in the delays reported before presentation, and in their experience of co-morbidity and symptoms. Black men were more likely to be referred for diagnostic investigation by a hospital department (P=0.013), although general practitioners referred the large majority of men. Prostate-specific antigen levels were comparable at diagnosis, although Black men had higher levels when compared with same-age White men (P<0.001). In conclusion, we found no evidence of Black men having poorer access to diagnostic services. Differences in the run-up to diagnosis are modest and seem insufficient to explain the higher rate of prostate cancer diagnosis in Black men. [ABSTRACT FROM AUTHOR]

Purpose Age‐related macular degeneration (AMD) is a progressive eye disease, with a pre‐clinical stage of age‐related maculopathy (ARM), and is the leading cause of blindness in the Western world. This study aimed to determine the population prevalence in a representative group of men (65‐83 years) and identify prospective risk factors for ARM/AMD. Methods 2348 men (45‐63 years from Speedwell, Bristol) were enlisted into a cohort study in 1979. At phase V (mean of 17.9 years follow‐up) they had retinal photographs taken which were assessed using the Wisconsin Age‐related Maculopathy Grading System. Results Data were obtained on 934 men from a potentially eligible sample of 1394 (67%). Early ARM was found in 9.2% of all men and late ARM in 0.5%; the rates increased with age. Baseline risk factors collected in 1979 that were associated with increased risk of AMD (ARM stage 2‐4) seen in 1997 were: diastolic blood pressure, C‐reactive protein, and increased consumption of lard, oils and fats whilst triglycerides were associated with a reduced risk. In multivariable analyses, elevated mean arterial pressure (OR per z‐score 1.37, 95% CI 1.04, 1.79) and fat consumption were significant predictors of increased risk, whilst triglycerides had reduced risk (OR 0.68, 95% CI 0.47, 0.99). Conclusion Whilst the prevalence of AMD was only 0.5%, almost 10% of elderly men in this UK sample were at high risk of developing AMD over the next 5 years. Our observation that elevated triglycerides is associated with reduced risk, if replicated, may provide insights into pathophysiological pathways. Early detection and possible risk factor modification should be explored to prevent ARM progression and blindness. [ABSTRACT FROM AUTHOR]

Background and Objectives: People with parkinsonism who are older, living in a care home, with frailty, multimorbidity or impaired capacity to consent are under-represented in research, limiting its generalisability. We aimed to evaluate more inclusive recruitment strategies., Methods: From one UK centre, we invited people with parkinsonism to participate in a cross-sectional study. Postal invitations were followed by telephone reminders and additional support to facilitate participation. Personal consultees provided information on the views regarding research participation of adults with impaired capacity. These approaches were evaluated: (i) using external data from the Parkinson's Real World Impact assesSMent (PRISM) study and Clinical Practice Research Datalink (CPRD), a sample of all cases in UK primary care, and (ii) comparing those recruited with or without intensive engagement., Results: We approached 1,032 eligible patients, of whom 542 (53%) consented and 477 (46%) returned questionnaires. The gender ratio in PRIME-UK (65% male) closely matched CPRD (61% male), unlike in the PRISM sample (46%). Mean age of PRIME participants was 75.9 (SD 8.5) years, compared to 75.3 (9.5) and 65.4 (8.9) years for CPRD and PRISM, respectively. More intensive engagement enhanced recruitment of women (13.3%; 95% CI 3.8, 22.9%; P = 0.005), care home residents (6.2%; 1.1, 11.2%; P = 0.004), patients diagnosed with atypical parkinsonism (13.7%; 5.4, 19.9%; P < 0.001), and those with a higher frailty score (mean score 0.2, 0.1, 0.2; P < 0.001)., Conclusions: These recruitment strategies resulted in a less biased and more representative sample, with greater inclusion of older people with more complex parkinsonism., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Objectives: Previous studies have suggested that fibrates and glitazones may have a role in brain tumour prevention. We examined if there is support for these observations using primary care records from the UK Clinical Practice Research Datalink (CPRD)., Design: We conducted two nested case-control studies using primary and secondary brain tumours identified within CPRD between 2000 and 2016. We selected cases and controls among the population of individuals who had been treated with any anti-diabetic or anti-hyperlipidaemic medication to reduce confounding by indication., Setting: Adults older than 18 years registered with a general practitioner in the UK contributing data to CPRD., Results: We identified 7496 individuals with any brain tumour (4471 primary; 3025 secondary) in total. After restricting cases and controls to those prescribed any anti-diabetic or anti-hyperlipidaemic medication, there were 1950 cases and 7791 controls in the fibrate and 480 cases with 1920 controls in the glitazone analyses. Longer use of glitazones compared with all other anti-diabetic medications was associated with a reduced risk of primary (adjusted OR (aOR) 0.89 per year, 95% CI 0.80 to 0.98), secondary (aOR 0.87 per year, 95% CI 0.77 to 0.99) or combined brain tumours (aOR 0.88 per year, 95% CI 0.81 to 0.95). There was little evidence that fibrate exposure was associated with risk of either primary or secondary brain tumours., Conclusions: Longer exposure to glitazones was associated with reduced primary and secondary brain tumour risk. Further basic science and population-based research should explore this finding in greater detail, in terms of replication and mechanistic studies., Competing Interests: Competing interests: JWR receives funding from Biogen for unrelated research. All other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: People living with Parkinson's disease experience progressive motor and non-motor symptoms, which negatively impact on health-related quality of life and can lead to an increased risk of hospitalisation. It is increasingly recognised that the current care models are not suitable for the needs of people with parkinsonism whose care needs evolve and change as the disease progresses. This trial aims to evaluate whether a complex and innovative model of integrated care will increase an individual's ability to achieve their personal goals, have a positive impact on health and symptom burden and be more cost-effective when compared with usual care., Methods: This is a single-centre, randomised controlled trial where people with parkinsonism and their informal caregivers are randomised into one of two groups: either PRIME Parkinson multi-component model of care or usual care. Adults ≥18 years with a diagnosis of parkinsonism, able to provide informed consent or the availability of a close friend or relative to act as a personal consultee if capacity to do so is absent and living in the trial geographical area are eligible. Up to three caregivers per patient can also take part, must be ≥18 years, provide informal, unpaid care and able to give informed consent. The primary outcome measure is goal attainment, as measured using the Bangor Goal Setting Interview. The duration of enrolment is 24 months. The total recruitment target is n=214, and the main analyses will be intention to treat., Discussion: This trial tests whether a novel model of care improves health and disease-related metrics including goal attainment and decreases hospitalisations whilst being more cost-effective than the current usual care. Subject to successful implementation of this intervention within one centre, the PRIME Parkinson model of care could then be evaluated within a cluster-randomised trial at multiple centres., (© 2023. The Author(s).)

Hypertension appears to be one of the commonest comorbidities in COVID-19 patients, although whether hypertensive individuals have a higher risk of severe COVID-19 compared with non-hypertensives is unclear. It is also unclear whether the absolute level of systolic blood pressure, or the type of anti-hypertensive medication is related to this risk. Analyses were conducted using data from the UK Biobank and linked health records. Logistic regression models were fitted to assess the impact of hypertension, systolic blood pressure (SBP) and medications on the risk of severe COVID-19. 16,134 individuals tested positive for severe acute respiratory syndrome-coronavirus, 22% (n = 3,584) developed severe COVID-19 and 40% (n = 6,517) were hypertensive. Hypertension was associated with 22% higher odds of severe COVID-19 (Odds ratio (OR) 1.22; 95% confidence interval (CI) 1.12, 1.33), compared with normotension after adjusting for confounding variables. In those taking anti-hypertensive medications, elevated SBP showed a dose-response relationship with severe COVID-19 (150-159mmHg versus 120-129mmHg (OR 1.91; 95% CI 1.44, 2.53), &gt;180+mmHg versus 120-129mmHg (OR 1.93; 95% CI 1.06, 3.51)). SBP &lt;120mmHg was associated with greater odds of severe COVID-19 (OR 1.40; 95% CI 1.11, 1.78). Angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers were not associated with altered risk of severe COVID-19. Hypertension is an important risk factor for COVID-19. A better understanding of the underlying mechanisms is warranted in case of more severe strains or other viruses in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Pavey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: People with parkinsonism are a highly heterogeneous group and the disease encompasses a spectrum of motor and non-motor symptoms which variably emerge and manifest across the disease course, fluctuate over time and negatively impact quality of life. While parkinsonism is not directly the result of ageing, it is a condition that mostly affects older people, who may also be living with frailty and multimorbidity. This study aims to describe the broad range of health needs for people with parkinsonism and their carers in relation to their symptomatology, disability, disease stage, comorbidities and sociodemographic characteristics., Methods and Analysis: In this single site cross-sectional study, people with parkinsonism will be sent a study information pack for themselves and their primary informal caregiver, if relevant. Data are collected via questionnaire, with additional support, if required, to maximise participation. A specific strategy has been developed to target and proactively recruit patients lacking capacity to consent, including those in residential care settings, with input from a personal consultee prior to completion of a bespoke questionnaire by a representative. Caregivers are also recruited to look at various health outcomes. Results will be displayed as descriptive statistics and regression models will be used to test simple associations and interactions., Ethics and Dissemination: This protocol was approved by the London-Brighton & Sussex Research Ethics Committee (REC reference 20/LO/0890). The results of this protocol will be disseminated through publication in an international peer-reviewed journal; presentation at academic meetings and conferences; and a lay summary uploaded to the PRIME-Parkinson website., Trial Registration Number: ISRCTN11452969; Pre-results., Competing Interests: Competing interests: EJH received funding from the National Institute of Health Technology (NIHR), the Gatsby Foundation and Parkinson’s UK; received fees for speaking and consultancy from Profile pharma Medicys and Luye; and received travel support from Bial Abbvie and Ever pharma. YB-S is a recipient of a Radboud Excellence award. He has received research support from the UK Medical Research Council, Wellcome Trust, NIHR, Parkinson’s UK, vs Arthritis, Gatsby Foundation, Dunhill Trust, and received a Radboud Excellence Award., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database., Methods: Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 374,359 primary THAs with up to 14.5 years' follow-up. We excluded any patients with bilateral THAs, knee arthroplasties, indications other than osteoarthritis, aged under 55 years, and diagnosis of one or more outcome of interest before THA. Implants were grouped as either containing CoCr or not containing CoCr. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined., Results: There were 158,677 individuals (42.4%) with an implant containing CoCr. There were 47,963 deaths, 27,332 heart outcomes, 35,720 cancers, and 22,025 neurodegenerative disorders. There was no evidence of an association between patients with CoCr implants and higher rates of any of the outcomes., Conclusion: CoCr-containing THAs did not have an increased risk of all-cause mortality, or clinically meaningful heart outcomes, cancer, or neurodegenerative disorders into the second decade post-implantation. Our findings will help reassure clinicians and the increasing number of patients receiving primary THA worldwide that the use of CoCr-containing implants is not associated with significant adverse systemic effects. Cite this article: Bone Joint J  2022;104-B(3):359-367.

Background: Little is known about the clinical demographics of and access to transplantation for Chinese diaspora populations with kidney disease., Methods: The UK Renal Registry provided data on adults with ethnicity recorded as 'Chinese' or 'White' starting Kidney Replacement Therapy (KRT) 1/1/97-31/12/17. Baseline characteristics were compared between Chinese and White patients. Multivariable logistic regression models were used to investigate the relationships between Chinese ethnicity and i) being listed for deceased-donor transplantation at start of KRT, ii) being listed 2 years after start of KRT, iii) pre-emptive kidney transplantation, iv) kidney transplantation 3 years after start of KRT, and v) living-donor kidney transplantation (LDKT)., Results: UK Chinese patients were younger at start of KRT (61.6 vs 65.6 years, p <0.001) and had more diabetic kidney disease (29% vs 20%, p<0.001) and glomerulonephritis (21% vs 13%, p<0.001) than White patients. We found evidence of interaction between ethnicity and sex. Compared to UK White men, UK Chinese men had lower odds of pre-emptive transplant (aOR 0.28, 95% CI [0.10-0.76]) and transplant within 3 years of KRT start (aOR 0.65, [95% CI 0.49-0.87], P = 0.004). UK White women and Chinese women had the same likelihood of pre-emptive transplant (aOR 0.78, 95% CI [0.38-1.61]), or transplant within 3 years of KRT start (aOR 0.94, 95% CI [0.60-1.46]). Both UK Chinese men and women had markedly lower odds of LDKT compared to Whites aOR 0.34 [95% CI 0.21-0.53]., Conclusions: UK Chinese are less likely to receive a LDKT. UK Chinese men have lower odds of accessing pre-emptive wait-listing and transplantation. Understanding whether these disparities reflect modifiable barriers will help ensure equitable access to transplantation., Competing Interests: The authors have declared that no competing interests exist.

A living-donor kidney transplant (LDKT) is one of the best treatments for kidney failure. The UK's LDKT activity falls behind that of many other countries, and there is evidence of socioeconomic inequity in access. We aimed to develop a UK-specific multicomponent intervention to support eligible individuals to access a LDKT. The intervention was designed to support those who are socioeconomically-deprived and currently disadvantaged, by targeting mediators of inequity identified in earlier work. We identified three existing interventions in the literature which target these mediators: a) the Norway model (healthcare practitioners contact patients' family with information about kidney donation), b) a home education model, and c) a Transplant candidate advocate model. We undertook intervention development using the Person-Based Approach (PBA). We performed in-depth qualitative interviews with people with advanced kidney disease (n = 13), their family members (n = 4), and renal and transplant healthcare practitioners (n = 15), analysed using thematic analysis. We investigated participant views on each proposed intervention component. We drafted intervention resources and revised these in light of comments from qualitative 'think-aloud' interviews. Four general themes were identified: i) Perceived cultural and societal norms; ii) Influence of family on decision-making; iii) Resource limitation, and iv) Evidence of effectiveness. For each intervention discussed, we identified three themes: for the Norway model: i) Overcoming communication barriers and assumptions; ii) Request from an official third party, and iii) Risk of coercion; for the home education model: i) Intragroup dynamics; ii) Avoidance of hospital, and iii) Burdens on participants; and for the transplant candidate advocates model: i) Vested interest of advocates; ii) Time commitment, and iii) Risk of misinformation. We used these results to develop a multicomponent intervention which comprises components from existing interventions that have been adapted to increase acceptability and engagement in a UK population. This will be evaluated in a future randomised controlled trial., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: Pre-emptive kidney transplantation is advocated as best practice for children with kidney failure who are transplant eligible; however, it is limited by late presentation. We aimed to determine whether socioeconomic deprivation and/or geographic location (distance to the center and rural/urban residence) are associated with late presentation, and to what degree these factors could explain differences in accessing pre-emptive transplantation., Design, Setting, Participants, & Measurements: A cohort study using prospectively collected United Kingdom Renal Registry and National Health Service Blood and Transplant data from January 1, 1996 to December 31, 2016 was performed. We included children aged >3 months to ≤16 years at the start of KRT. Multivariable logistic regression models were used to determine associations between the above exposures and our outcomes: late presentation (defined as starting KRT within 90 days of first nephrology review) and pre-emptive transplantation, with a priori specified covariates., Results: Analysis was performed on 2160 children (41% females), with a median age of 3.8 years (interquartile range, 0.2-9.9 years) at first nephrology review. Excluding missing data, 478 were late presenters (24%); 565 (26%) underwent pre-emptive transplantation, none of whom were late presenting. No association was seen between distance or socioeconomic deprivation with late presentation, in crude or adjusted analyses. Excluding late presenters, greater area affluence was associated with higher odds of pre-emptive transplantation, (odds ratio, 1.20 per quintile greater affluence; 95% confidence interval, 1.10 to 1.31), with children of South Asian (odds ratio, 0.52; 95% confidence interval, 0.36 to 0.76) or Black ethnicity (odds ratio, 0.31; 95% confidence interval, 0.12 to 0.80) less likely to receive one. A longer distance to the center was associated with pre-emptive transplantation on crude analyses; however, this relationship was attenuated (odds ratio, 1.02 per 10 km; 95% confidence interval, 0.99 to 1.05) in the multivariable model., Conclusions: Socioeconomic deprivation or geographic location are not associated with late presentation in children in the United Kingdom. Geographic location was not independently associated with pre-emptive transplantation; however, children from more affluent areas were more likely to receive a pre-emptive transplant., (Copyright © 2021 by the American Society of Nephrology.)

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.

Background We aimed at investigating the association of circulating fatty acids with coronary heart disease (CHD) and stroke risk. Methods and Results We conducted an individual-participant data meta-analysis of 5 UK-based cohorts and 1 matched case-control study. Fatty acids (ie, omega-3 docosahexaenoic acid, omega-6 linoleic acid, monounsaturated and saturated fatty acids) were measured at baseline using an automated high-throughput serum nuclear magnetic resonance metabolomics platform. Data from 3022 incident CHD cases (13 104 controls) and 1606 incident stroke cases (13 369 controls) were included. Logistic regression was used to model the relation between fatty acids and odds of CHD and stroke, adjusting for demographic and lifestyle variables only (ie, minimally adjusted model) or with further adjustment for other fatty acids (ie, fully adjusted model). Although circulating docosahexaenoic acid, but not linoleic acid, was related to lower CHD risk in the fully adjusted model (odds ratio, 0.85; 95% CI, 0.76-0.95 per standard unit of docosahexaenoic acid), there was evidence of high between-study heterogeneity and effect modification by study design. Stroke risk was consistently lower with increasing circulating linoleic acid (odds ratio for fully adjusted model, 0.82; 95% CI, 0.75-0.90). Circulating monounsaturated fatty acids were associated with higher CHD risk across all models and with stroke risk in the fully adjusted model (odds ratio, 1.22; 95% CI, 1.03-1.44). Saturated fatty acids were not related to increased CHD risk in the fully adjusted model (odds ratio, 0.94; 95% CI, 0.82-1.09), or stroke risk. Conclusions We found consistent evidence that linoleic acid was associated with decreased risk of stroke and that monounsaturated fatty acids were associated with increased risk of CHD. The different pattern between CHD and stroke in terms of fatty acids risk profile suggests future studies should be cautious about using composite events. Different study designs are needed to assess which, if any, of the associations observed is causal.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Our objective was to define the prevalence and clinical features of genetic Parkinson's disease in a large UK population-based cohort, the largest multicentre prospective clinico-genetic incident study in the world. We collected demographic data, Movement Disorder Society Unified Parkinson's Disease Rating Scale scores, and Montreal Cognitive Assessment scores. We analysed mutations in PRKN (parkin), PINK1, LRRK2 and SNCA in relation to age at symptom onset, family history and clinical features. Of the 2262 participants recruited to the Tracking Parkinson's study, 424 had young-onset Parkinson's disease (age at onset ≤ 50) and 1799 had late onset Parkinson's disease. A range of methods were used to genotype 2005 patients: 302 young-onset patients were fully genotyped with multiplex ligation-dependent probe amplification and either Sanger and/or exome sequencing; and 1701 late-onset patients were genotyped with the LRRK2 'Kompetitive' allele-specific polymerase chain reaction assay and/or exome sequencing (two patients had missing age at onset). We identified 29 (1.4%) patients carrying pathogenic mutations. Eighteen patients carried the G2019S or R1441C mutations in LRRK2, and one patient carried a heterozygous duplication in SNCA. In PRKN, we identified patients carrying deletions of exons 1, 4 and 5, and P113Xfs, R275W, G430D and R33X. In PINK1, two patients carried deletions in exon 1 and 5, and the W90Xfs point mutation. Eighteen per cent of patients with age at onset ≤30 and 7.4% of patients from large dominant families carried pathogenic Mendelian gene mutations. Of all young-onset patients, 10 (3.3%) carried biallelic mutations in PRKN or PINK1. Across the whole cohort, 18 patients (0.9%) carried pathogenic LRRK2 mutations and one (0.05%) carried an SNCA duplication. There is a significant burden of LRRK2 G2019S in patients with both apparently sporadic and familial disease. In young-onset patients, dominant and recessive mutations were equally common. There were no differences in clinical features between LRRK2 carriers and non-carriers. However, we did find that PRKN and PINK1 mutation carriers have distinctive clinical features compared to young-onset non-carriers, with more postural symptoms at diagnosis and less cognitive impairment, after adjusting for age and disease duration. This supports the idea that there is a distinct clinical profile of PRKN and PINK1-related Parkinson's disease. We estimate that there are approaching 1000 patients with a known genetic aetiology in the UK Parkinson's disease population. A small but significant number of patients carry causal variants in LRRK2, SNCA, PRKN and PINK1 that could potentially be targeted by new therapies, such as LRRK2 inhibitors., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objectives: To evaluate the utility of different symptoms, alone or combined, presented to primary care for an adult brain tumour diagnosis., Design and Setting: Matched case-control study, using the data from Clinical Practice Research Datalink (2000-2014) from primary care consultations in the UK., Method: All presentations within 6 months of the index diagnosis date (cases) or equivalent (controls) were coded into 32 symptom groups. Sensitivity, specificity, positive predictive values (PPVs) and positive likelihood ratios were calculated for symptoms and combinations of symptoms with headache and cognitive features. Diagnostic odds ratios were calculated using conditional logistic regression, adjusted for age group, sex and Charlson comorbidity. Stratified analyses were performed for age group, sex and whether the tumour was of primary or secondary origin., Results: We included 8,184 cases and 28,110 controls. Seizure had the highest PPV of 1.6% (95% CI 1.4% to 1.7%) followed by weakness 1.5% (1.3 to 1.7) and confusion 1.4% (1.3 to 1.5). Combining headache with other symptoms increased the PPV. For example, headache plus combined cognitive symptoms PPV 7.2% (6.0 to 8.6); plus weakness 4.4% (3.2 to 6.2), compared with headache alone PPV 0.1%. The diagnostic ORs were generally larger for patients <70 years; this was most marked for confusion, seizure and visual symptoms., Conclusion: We found seizure, weakness and confusion had relatively higher predictive values than many other symptoms. Headache on its own was a weak predictor but this was enhanced when combined with other symptoms especially in younger patients. Clinicians need to actively search for other neurological symptoms such as cognitive problems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Physical capability, a key component of healthy aging, is associated with cardiovascular and other risk factors across life. We investigated whether midlife biomarkers of heart and kidney damage capturing the cumulative impact of long-term adverse exposures were associated with the level and decline in physical capability over 9 years of follow-up, taking account of systemic inflammatory biomarkers and conventional cardiovascular risk factors., Methods: We used data on 1736 men and women from the oldest British birth cohort study with walking speed, chair rise speed, balance time, and grip strength assessed at ages 60 to 64 and 69 years. We tested associations between logged and standardized measures of cystatin C, NT-proBNP (N-terminal pro-B-type natriuretic peptide), interleukin (IL)-6, and E-selectin at age 60 to 64 years with performance at age 69 years, adjusting for sex, height, and body mass index; then for performance at age 60 to 64 years. These biomarkers were mutually adjusted, and additionally adjusted for cardiovascular risk factors (pulse pressure, total/high density lipoprotein cholesterol, glycosylated hemoglobin), diabetes mellitus, cardiovascular and kidney disease, smoking status, and lifetime socioeconomic position., Results: Cystatin C, NT-proBNP, and IL-6 (but not E-selectin) were inversely associated with all outcomes, adjusted for sex, height, and body mass index. For example, a 1-SD increase in logged NT-proBNP was associated with weaker grip (-0.63 kg, 95% CI, -0.99 to -0.28); the equivalent association for cystatin C was -0.60 kg (95% CI, -0.94 to -0.25) and for IL-6 was -0.76 kg (95% CI, -1.11 to -0.41). Most associations remained, albeit attenuated, after adjustment for previous performance and mutual adjustment of the biomarkers. NT-proBNP and IL-6 (but not cystatin C) were more strongly associated with the outcomes than many of the conventional risk factors after mutual adjustment., Conclusions: Higher levels of NT-proBNP may identify those in midlife at risk of accelerated physical decline. Before considering the use of NT-proBNP for risk stratification, further research should untangle whether these associations exist because the biomarker is an integrated measure of cumulative exposures to relevant stressors across life, or whether it is marking additional risk pathways. Randomized trials to reduce the rate of decline in physical capability or delay incident disability could benefit from including middle-aged adults and adding NT-proBNP and IL-6 as intermediate outcomes.

Background: Because multiple sclerosis (MS) is a chronic disease causing disability over decades, it is crucial to know if the short-term effects of disease-modifying therapies reported in randomised controlled trials reduce long-term disability. This 10-year prospective observational study of disability outcomes (Expanded Disability Status Scale (EDSS) and utility) was set up, in conjunction with a risk-sharing agreement between payers and producers, to investigate this issue., Methods: The outcomes of the UK treated patients were compared with a modelled untreated control based on the British Columbia MS data set to assess the long-term effectiveness of these treatments. Two complementary analysis models were used: a multilevel model (MLM) and a continuous Markov model., Results: 4862 patients with MS were eligible for the primary analysis (mean and median follow-up times 8.7 and 10 years). EDSS worsening was reduced by 28% (MLM), 7% (Markov) and 24% time-adjusted Markov in the total cohort, and by 31% (MLM) and 14% (Markov) for relapsing remitting patients. The utility worsening was reduced by 23%-24% in the total cohort and by 24%-31% in the RR patients depending on the model used. All sensitivity analyses showed a treatment effect. There was a 4-year (CI 2.7 to 5.3) delay to EDSS 6.0. An apparent waning of treatment effect with time was seen. Subgroup analyses suggested better treatment effects in those treated earlier and with lower EDSS scores., Conclusions: This study supports a beneficial effect on long-term disability with first-line MS disease-modifying treatments, which is clinically meaningful. However the waning effect noted requires further study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE)., Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism., Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018., Exposures: A panel of several established cardiovascular risk factors., Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI)., Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers., Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

Objectives: To examine the influence of the glucocerebrosidase ( GBA ) mutation carrier state on age at onset of Parkinson's disease (PD), the motor phenotype and cognitive function at baseline assessment in a large cohort of UK patients. We also analysed the prevalence of mood and behavioural problems that may confound the assessment of cognitive function., Methods: We prospectively recruited patients with PD in the Tracking Parkinson's study. We fully sequenced the GBA gene in all recently diagnosed patients (≤3.5 years). We examined cognitive (Montreal Cognitive Assessment) and motor (Movement Disorder Society Unified Parkinson's Disease Rating Scale part 3) function at a baseline assessment, at an average of 1.3 years after diagnosis. We used logistic regression to determine predictors of PD with mild cognitive impairment and PD with dementia., Results: We studied 1893 patients with PD: 48 (2.5%) were heterozygous carriers for known Gaucher's disease (GD) causing pathogenic mutations; 117 (6.2%) had non-synonymous variants, previously associated with PD, and 28 (1.5%) patients carried variants of unknown significance in the GBA gene. L444P was the most common pathogenic GBA mutation. Patients with pathogenic GBA mutations were on average 5 years younger at disease onset compared with non-carriers (P=0.02). PD patients with GD-causing mutations did not have an increased family risk of PD. Patients with GBA mutations were more likely to present with the postural instability gait difficulty phenotype compared with non-carriers (P=0.02). Patients carrying pathogenic mutations in GBA had more advanced Hoehn and Yahr stage after adjustment for age and disease duration compared with non-carriers (P=0.005). There were no differences in cognitive function between GBA mutation carriers and non-carriers at this early disease stage., Conclusions: Our study confirms the influence of GBA mutations on the age of onset, disease severity and motor phenotype in patients with PD. Cognition did not differ between GBA mutation carriers and non-carriers at baseline, implying that cognitive impairment/dementia, reported in other studies at a later disease stage, is not present in recently diagnosed cases. This offers an important window of opportunity for potential disease-modifying therapy that may protect against the development of dementia in GBA -PD., Clinical Trial Registration: NCT02881099; Results., Competing Interests: Competing interests: YB-S has received grant funding from the MRC, NIHR, Parkinson’s UK, NIH and ESRC. RSW is supported by a UCL Excellence Fellowship and has received funding from the Academy of Medical Sciences and the NIHR, the MRC and the Wellcome Trust. NB has received payment for advisory board attendance from UCB, Teva Lundbeck, Britannia, GSK, Boehringer and honoraria from UCB Pharma, GE Healthcare, Lily Pharma, Medtronic. He has received research grant support from GE Healthcare, Wellcome Trust, Medical Research Council, Parkinson’s UK and National Institute for Health Research. RAB has received grants from Parkinson’s UK, NIHR, Cure Parkinson’s Trust, Evelyn Trust, Rosetrees Trust, MRC and EU along with payment for advisory board attendance from Oxford Biomedica LCT and FCDI and honoraria from Wiley and Springer. DJB has received grants from NIHR, Wellcome Trust, GlaxoSmithKline Ltd, Parkinson’s UK and Michael J Fox Foundation. JH has received honoraria from Eisai and grant support from MRC/Wellcome, Parkinson’s UK and the Michael J Fox Foundation. DGG has received grants from Michael’s Movers, The Neurosciences Foundation, and Parkinson’s UK, and honoraria from UCB Pharma and GE Healthcare, and consultancy fees from Acorda Therapeutics. HRM has received grants from Medical Research Council UK, Wellcome Trust, Parkinson’s UK, Ipsen Fund, Motor Neurone Disease Association, Welsh Assembly Government, PSP Association, CBD Solutions and Drake Foundation, and payment for advisory board attendance and lectures from Teva, AbbVie, Boehringer Ingelheim, and GSK. NWW is supported by the MRC and NIHR UCLH Biomedical research centre. TF has received grants from Michael J Fox Foundation, Cure Parkinson’s Trust, Brain Research trust, John Black Charitable Foundation, Rosetrees trust and honoraria for speaking at meetings from Bial, Profile Pharma and Medtronic., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A disease registry uses observational study methods to collect defined data on patients with a particular condition for a predetermined purpose. By providing comprehensive standardised data on patients with kidney disease, renal registries aim to provide a 'real world' representation of practice patterns, treatment and patient outcomes that may not be captured accurately by other methods, including randomised controlled trials. Additionally, using registries to measure variations in outcomes and audit care against standards is crucial to understanding how to improve quality of care for patients in an efficacious and cost-effective manner. Registries also have the potential to be a powerful scientific tool that can monitor and support the translational process between research and routine clinical practice, although their limitations must be borne in mind. In this review, we describe the role of the UK Renal Registry as a tool to support translational research. We describe its involvement across each stage of the translational pathway: from hypothesis generation, study design and data collection, to reporting of long-term outcomes and quality improvement initiatives. Furthermore we explore how this role may bring about improvements in care for adults and children with kidney disease.

Background: Clinical epidemiology data for young adults on renal replacement therapy (RRT) are lacking. While mostly transplanted, they have an increased risk of graft loss during young adulthood., Methods: We combined the UK Renal Registry paediatric and adult databases to describe patient characteristics, transplantation and survival for young adults. We grouped patients 11-30 years of age starting RRT from 1999 to 2008 by age band and examined their course during 5 years of follow-up., Results: The cohort (n = 3370) was 58% male, 79% white and 29% had glomerulonephritis. Half (52%) started RRT on haemodialysis (HD). Most (78%) were transplanted (18% pre-emptive, 61% as second modality); 11% were not listed for transplant. Transplant timing varied by age group. The deceased:living donor kidney transplant ratio was 2:1 for 11-<16 year olds and 1:1 otherwise. Median deceased donor transplant waiting times ranged from 6 months if <16 years of age to 17 months if ≥21 years. Overall 8% died, with being on dialysis and not transplant listed versus transplanted {hazard ratio [HR] 16.6 [95% confidence interval (CI) 10.8-25.4], P < 0.0001} and diabetes versus glomerulonephritis [HR 4.03 (95% CI 2.71-6.01), P < 0.0001] increasing mortality risk., Conclusions: This study highlights the frequent use of HD and the importance of transplant listing and diabetes for young adults. More than half the young adults in our cohort started renal replacement therapy on HD. One in 10 young adults were not listed for transplant by 5 years and were ∼20 times more likely to die than those who were transplanted. Diabetes as a primary renal disease was common among young adults and associated with increased mortality. Overall, almost 1 in 10 young adults had died by 5 years from the start of RRT., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.)

Objectives: The observed associations between smoking and functional measures at older ages are vulnerable to bias and confounding. Mendelian randomisation (MR) uses genotype as an instrumental variable to estimate unconfounded causal associations. We conducted a meta-analysis of the observational associations and implemented an MR approach using the smoking-related single nucleotide polymorphism rs16969968 to explore their causal nature., Setting: 9 British cohorts belonging to the HALCyon collaboration., Participants: Individual participant data on N=26,692 individuals of European ancestry (N from earliest phase analysed per study) of mean ages 50-79 years were available for inclusion in observational meta-analyses of the primary outcomes., Primary Outcomes: Physical capability, cognitive capability and cognitive decline. The smoking exposures were cigarettes per day, current versus ex-smoker, current versus never smoker and ever versus never smoker., Results: In observational analyses current and ever smoking were generally associated with poorer physical and cognitive capability. For example, current smokers had a general fluid cognition score which was 0.17 z-score units (95% CI -0.221 to -0.124) lower than ex-smokers in cross-sectional analyses. Current smokers had a walk speed which was 0.25 z-score units lower than never smokers (95% CI -0.338 to -0.170). An MR instrumental variable approach for current versus ex-smoker and number of cigarettes smoked per day produced CIs which neither confirmed nor refuted the observational estimates. The number of genetic associations stratified by smoking status were consistent with type I error., Conclusions: Our observational analysis supports the hypothesis that smoking is detrimental to physical and cognitive capability. Further studies are needed for a suitably powered MR approach., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Physical capability in later life is influenced by factors occurring across the life course, yet exposures to area conditions have only been examined cross-sectionally. Data from the National Survey of Health and Development, a longitudinal study of a 1946 British birth cohort, were used to estimate associations of area deprivation (defined as percentage of employed people working in partly skilled or unskilled occupations) at ages 4, 26, and 53 years (residential addresses linked to census data in 1950, 1972, and 1999) with 3 measures of physical capability at age 53 years: grip strength, standing balance, and chair-rise time. Cross-classified multilevel models with individuals nested within areas at the 3 ages showed that models assessing a single time point underestimate total area contributions to physical capability. For balance and chair-rise performance, associations with area deprivation in midlife were robust to adjustment for individual socioeconomic position and prior area deprivation (mean change for a 1-standard-deviation increase: balance, -7.4% (95% confidence interval (CI): -12.8, -2.8); chair rise, 2.1% (95% CI: -0.1, 4.3)). In addition, area deprivation in childhood was related to balance after adjustment for childhood socioeconomic position (-5.1%, 95% CI: -8.7, -1.6). Interventions aimed at reducing midlife disparities in physical capability should target the socioeconomic environment of individuals-for standing balance, as early as childhood.

Approximately 3.6% of patients with Parkinson's disease develop symptoms before age 45. Early-onset Parkinson's disease (EOPD) patients have a higher familial recurrence risk than late-onset patients, and 3 main recessive EOPD genes have been described. We aimed to establish the prevalence of mutations in these genes in a UK cohort and in previous studies. We screened 136 EOPD probands from a high-ascertainment regional and community-based prevalence study for pathogenic mutations in PARK2 (parkin), PINK1, PARK7 (DJ-1), and exon 41 of LRRK2. We also carried out a systematic review, calculating the proportion of cases with pathogenic mutations in previously reported studies. We identified 5 patients with pathogenic PARK2, 1 patient with PINK1, and 1 with LRRK2 mutations. The rate of mutations overall was 5.1%. Mutations were more common in patients with age at onset (AAO) < 40 (9.5%), an affected first-degree relative (6.9%), an affected sibling (28.6%), or parental consanguinity (50%). In our study EOPD mutation carriers were more likely to present with rigidity and dystonia, and 6 of 7 mutation carriers had lower limb symptoms at onset. Our systematic review included information from >5800 unique cases. Overall, the weighted mean proportion of cases with PARK2 (parkin), PINK1, and PARK7 (DJ-1) mutations was 8.6%, 3.7%, and 0.4%, respectively. PINK1 mutations were more common in Asian subjects. The overall frequency of mutations in known EOPD genes was lower than previously estimated. Our study shows an increased likelihood of mutations in patients with lower AAO, family history, or parental consanguinity., (Copyright © 2012 Movement Disorder Society.)

Background: Socioeconomic disparities and their contribution to the ethnic differences in living kidney donor transplantation have not been adequately studied., Methods: A total of 12,282 patients aged 18 to 69 years starting renal replacement therapy (January 1, 1997, to December 31, 2004) in the United Kingdom were included. Logistic regression models were used to examine probability of living donor transplantation within 3 years of renal replacement therapy. The effect of area deprivation (Townsend index) was studied among whites only adjusted for patient characteristics and the effect of ethnic origin (South Asians and blacks compared with whites) was then examined among all patients adjusting for area deprivation., Results: Among whites, increasing social deprivation was associated with lower odds of living donor transplantation. In the fully adjusted model, odds ratio (OR) for the most deprived quintile was 0.40 (95% confidence interval [CI] 0.33, 0.49; P trend<0.0001) compared with the least deprived. These gradients were more pronounced among centers performing more live donor transplants (P value for interaction <0.0001). South Asians and blacks had lower odds of living donor transplantation compared with whites, but there was an interaction with age (P<0.0001), so that this disparity was observed only in those younger than 50 years (blacks: OR, 0.31; 95% CI, 0.18, 0.54; South Asians: OR, 0.55; 95% CI, 0.34, 0.90; P value <0.0001)., Conclusions: Socially deprived and younger ethnic minority patients have lower probability of living kidney donor transplantation. The extent to which these inequalities reflect modifiable societal healthcare system barriers and donor/recipient factors requires further study.

Vitamin B-12 is essential for the development and maintenance of a healthy nervous system. Brain development occurs primarily in utero and early infancy, but the role of maternal vitamin B-12 status during pregnancy on offspring cognitive function is unclear. In this study we assessed the effect of vitamin B-12 status in well-nourished pregnant women on the cognitive ability of their offspring in a UK birth cohort (ALSPAC). We then examined the association of SNPs in maternal genes FUT2 (rs492602) and TCN2 (rs1801198, rs9606756) that are related to plasma vitamin B-12, with offspring IQ. Observationally, there was a positive association between maternal vitamin B-12 intake and child's IQ that was markedly attenuated after adjustment for potential confounders (mean difference in offspring IQ score per doubling of maternal B-12 intake, before adjustment: 2.0 (95% CI 1.3, 2.8); after adjustment: 0.7 (95% CI -0.04, 1.4)). Maternal FUT2 was weakly associated with offspring IQ: mean difference in IQ per allele was 0.9 (95% CI 0.1, 1.6). The expected effect of maternal vitamin B-12 on offspring IQ, given the relationships between SNPs and vitamin B-12, and SNPs and IQ was consistent with the observational result. Our findings suggest that maternal vitamin B-12 may not have an important effect on offspring cognitive ability. However, further examination of this issue is warranted.

Background and Objectives: The role of socioeconomic status (SES) and its contribution to ethnic differences in standards attainment among dialysis patients is not known., Design, Setting, Participants, & Measurements: We examined associations between area- level SES (Townsend index) and ethnicity (white, black, South Asian) and standards attainment in 14,117 incident dialysis patients (1997-2004) in the UK., Results: Deprived patients were less likely to achieve hemoglobin (Hb) > or = 10 g/dl (trend P < 0.001) but not after controlling for patient and center characteristics (trend P = 0.1). There was no association with hemodialysis dose and parathyroid hormone (PTH) standard but deprived patients had better attainment of phosphate (PO4) <5.6 mg/dl, calcium (Ca) and Calcium-phosphate (CaPO4) standard (e.g., most deprived versus least deprived adjusted odds ratio [OR] 1.25, 95% confidence intervals [CI] 1.12, 1.38). There was no association with SES using a lower limit for PO4 (3.5 - 5.5 mg/dl). Compared with Whites, Blacks had lower attainment of Hb (adjusted OR 0.57, 95% CI 0.45, 0.71) and PTH standards (adjusted OR 0.27, 95% CI 0.22, 0.33) but better attainment of PO4 and CaPO4, while South Asians experienced better or comparable outcomes for most standards except Ca and PTH., Conclusions: There was no evidence of socioeconomic inequity in standards attainment or a consistent pattern of inequity by ethnic group. The lower attainment of some standards in ethnic minorities may reflect biologic differences rather than ethnicity-related inequity of care.

Objectives: It is known that African American men have a greater risk of prostate cancer than white men. We investigated whether this was true for first-generation black Caribbean and black African men in the United Kingdom., Methods: A clinical cohort study design recruiting all cases of prostate cancer diagnosed over a 5-yr period and residing in defined areas of London and Bristol. We calculated the age-standardised incidence rates and relative risk for all black men, and black Caribbean and black African men versus white men., Results: Black men had higher age-adjusted rates of prostate cancer (166 per 100,000, 95% confidence interval [95%CI], 151-180 per 100,000) than white men (56.4 per 100,000, 95%CI, 53.3-59.5 per 100,000). The relative risks for all black, black Caribbean, and black African men were 3.09 (95%CI, 2.79-3.43; p<0.0001), 3.19 (95%CI, 2.85-3.56; p<0.0001) and 2.87 (95%CI, 2.34-3.53; p<0.0001), respectively. There was no strong evidence that the rates for black Caribbean differed from black African men. The higher risk in black men compared with white men was more apparent in younger age groups (p value for interaction<0.001)., Conclusions: Black men in the United Kingdom have substantially greater risk of developing prostate cancer compared with white men, although this risk is lower than that of black men in the United States. The similar rates in black Caribbean and black African men suggest a common genetic aetiology, although migration may be associated with an increased risk attributable to a gene-environment interaction.

While the pursuit of equity of access to health care is a central objective of many health care systems, there is evidence that patients of ethnic minority descent, in lower socio-economic position (SEP) or of female gender are less likely than Whites, more affluent groups or men, respectively, to access secondary and tertiary medical care. However, it is unclear at which point in the chain of events leading from perception of need through attendance at primary/emergency care, to referral and receipt of secondary care, this inequality occurs. This study examined the influence of ethnicity, socio-economic position and gender on an individual's perception of the need and urgency for seeking health care. A random sample was selected from two large city General Practices in the UK who were sent postal questionnaires which included two clinical vignettes describing characters experiencing chest pain and discovering a lump in the armpit. The main outcome measure was response to the 'chest pain' and 'lump' vignettes in terms of immediate health care utilisation. The questionnaire survey (n=1350, response rate 66%) indicated that Black respondents, respondents from lower socio-economic groups and women were at least as likely to report immediate health care seeking in response to the clinical vignettes than White respondents, those from higher socio-economic groups or men. This finding was consistent across all scenarios after adjustment for interpretation of the vignette, access to health services and attitudes to health and health care. For example, those in the lowest SEP group were almost 60% more likely to report immediate care seeking in response to the lump vignette (OR 1.59, 95% CI 1.08-2.33) compared to those in the highest SEP group; and Black respondents 40% more likely (OR 1.41, 95% CI 0.92-2.17). This study suggests inequalities in access to health care by ethnicity, socio-economic position and gender are not related to patients in these groups failing to self-refer to primary or accident and emergency care, barriers must therefore occur at the level of health care provision.

Background: Many patients diagnosed with Parkinson's disease are later found to have an erroneous diagnosis, often only when they come to necropsy; conversely, many patients with Parkinson's disease in the community remain undiagnosed., Objective: To assess the validity of a clinical diagnosis of parkinsonism in the general population according to strict published criteria., Methods: As part of a population based study on the prevalence of Parkinson's disease in London, all patients were identified with a diagnosis of parkinsonism, tremor with onset over age 50 years, or who had ever received antiparkinsonian drugs. All patients who agreed to participate were diagnosed according to strict clinical diagnostic criteria, after a detailed neurological interview and examination and discussion of the findings with examination of their video recordings. Follow up information was obtained over a period of at least one year, and atypical cases were reviewed at the end of the study., Results: A diagnosis of probable Parkinson's disease was confirmed in 83% of patients with this diagnosis, including three (2%) in whom atypical features were found that were insufficient to discard a diagnosis of Parkinson's disease. Two additional patients (2%) were found to have possible Parkinson's disease. However, in 15% of patients the diagnosis was unequivocally rejected. Conversely, 13 patients who had previously not been diagnosed with Parkinson's disease (19%) were found to have this disorder., Conclusions: At least 15% of patients with a diagnosis of Parkinson's disease in the population do not fulfil strict clinical criteria for the disease, and approximately 20% of patients with Parkinson's disease who have already come to medical attention have not been diagnosed as such.

Although need is often assumed to be the most important factor in determining the use of health services, there are many inequities in the provision and use of NHS services in both primary and secondary care. For example, existing data from district child health information services have been combined with census data for small areas to show wide variations in immunisation rates between affluent and deprived areas. Purchasers of health care are already responsible for assessing health needs and evaluating services, and the process of monitoring equity is a logical extension of these activities. Routine data sources used to collect activity data in both primary and secondary care can be used to assess needs for care and monitor how well these needs are met. Purchasers and providers should collaborate to improve the usefulness of these routine data and to develop a framework for monitoring and promoting equity more systematically.