A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds.

The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection of breast cancer patient-derived tumor xenografts (PDTXs), in which the morphological and molecular characteristics of the originating tumor are preserved through passaging in the mouse. An integrated platform combining in vivo maintenance of these PDTXs along with short-term cultures of PDTX-derived tumor cells (PDTCs) was optimized. Remarkably, the intra-tumor genomic clonal architecture present in the originating breast cancers was mostly preserved upon serial passaging in xenografts and in short-term cultured PDTCs. We assessed drug responses in PDTCs on a high-throughput platform and validated several ex vivo responses in vivo. The biobank represents a powerful resource for pre-clinical breast cancer pharmacogenomic studies (http://caldaslab.cruk.cam.ac.uk/bcape), including identification of biomarkers of response or resistance.

Prospective derivation of a living organoid biobank of colorectal cancer patients.

In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely recapitulate several properties of the original tumor. The spectrum of genetic changes within the "living biobank" agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design. PAPERCLIP.

Raising ethnicity recording in NHS Lothian from 3% to 90% in 3 years: processes and analysis of data from Accidents and Emergencies.

BACKGROUND: The disproportionate burden of COVID-19 on ethnic minority populations has recently highlighted the necessity of maintaining accessible, routinely collected, ethnicity data within healthcare services. Despite 25 years of supportive legislation and policy in the UK, ethnicity data recording remains inconsistent, which has hindered needs assessment, evaluation and decision-making. We describe efforts to improve the completeness, quality and usage of ethnicity data within our regional health board, NHS Lothian. METHODS: The Ethnicity Coding Task Force was established with the aim of increasing ethnicity recording within NHS Lothian secondary care services from 3 to 90% over 3 years. We subsequently analysed these data specifically focusing on Accident and Emergency (A&E) use by ethnic group. RESULTS: We achieved 91%, 85% and 93% completeness of recording across inpatients, outpatients and A&E, respectively. Analysis of A&E data found a mixed pattern of attendance amongst ethnic minority populations and did not support the commonly perceived relationship between lower GP registration and higher A&E use within this population. CONCLUSIONS: We identified a successful approach to increase ethnicity recording within a regional health board, which could potentially be useful in other settings, and demonstrated the utility of these data in informing assessment of healthcare delivery and future planning.

Effects of dietary and physical activity interventions on the risk of type 2 diabetes in South Asians: meta-analysis of individual participant data from randomised controlled trials.

AIMS/HYPOTHESIS: Individuals of South Asian origin have a high risk of type 2 diabetes and of dying from a diabetes-attributable cause. Lifestyle modification intervention trials to prevent type 2 diabetes in high-risk South Asian adults have suggested more modest effects than in European-origin populations. The strength of the evidence of individual studies is limited, however. We performed an individual participant data meta-analysis of available RCTs to assess the effectiveness of lifestyle modification in South Asian populations worldwide. METHODS: We searched PubMed, EMBASE, Cochrane Library and Web of Science (to 24 September 2018) for RCTs on lifestyle modification interventions incorporating diet and/or physical activity in South Asian adults. Reviewers identified eligible studies and assessed the quality of the evidence. We obtained individual participant data on 1816 participants from all six eligible trials (four from Europe and two from India). We generated HR estimates for incident diabetes (primary outcome) and mean differences for fasting glucose, 2 h glucose, weight and waist circumference (secondary outcomes) using mixed-effect meta-analysis overall and by pre-specified subgroups. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence of the estimates. The study is registered with the International Prospective Register of Systematic Reviews ([PROSPERO] CRD42017078003). RESULTS: Incident diabetes was observed in 12.6% of participants in the intervention groups and in 20.0% of participants in the control groups. The pooled HR for diabetes incidence was 0.65 (95% CI 0.51, 0.81; I2 = 0%) in intervention compared with control groups. The absolute risk reduction was 7.4% (95% CI 4.0, 10.2), with no interactions for the pre-specified subgroups (sex, BMI, age, study duration and region where studies were performed). The quality of evidence was rated as moderate. Mean difference for lifestyle modification vs control groups for 2 h glucose was -0.34 mmol/l (95% CI -0.62, -0.07; I2 = 50%); for weight -0.75 kg (95% CI -1.34, -0.17; I2 = 71%) and for waist -1.16 cm (95% CI -2.16, -0.16; I2 = 75%). No effect was found for fasting glucose. Findings were similar across subgroups, except for weight for European vs Indian studies (-1.10 kg vs -0.08 kg, p = 0.02 for interaction). CONCLUSIONS/INTERPRETATION: Despite modest changes for adiposity, lifestyle modification interventions in high-risk South Asian populations resulted in a clinically important 35% relative reduction in diabetes incidence, consistent across subgroups. If implemented on a large scale, lifestyle modification interventions in high-risk South Asian populations in Europe would reduce the incidence of diabetes in these populations.

Mortality, ethnicity, and country of birth on a national scale, 2001-2013: A retrospective cohort (Scottish Health and Ethnicity Linkage Study).

BACKGROUND: Migrant and ethnic minority groups are often assumed to have poor health relative to the majority population. Few countries have the capacity to study a key indicator, mortality, by ethnicity and country of birth. We hypothesized at least 10% differences in mortality by ethnic group in Scotland that would not be wholly attenuated by adjustment for socio-economic factors or country of birth. METHODS AND FINDINGS: We linked the Scottish 2001 Census to mortality data (2001-2013) in 4.62 million people (91% of estimated population), calculating age-adjusted mortality rate ratios (RRs; multiplied by 100 as percentages) with 95% confidence intervals (CIs) for 13 ethnic groups, with the White Scottish group as reference (ethnic group classification follows the Scottish 2001 Census). The Scottish Index of Multiple Deprivation, education status, and household tenure were socio-economic status (SES) confounding variables and born in the UK or Republic of Ireland (UK/RoI) an interacting and confounding variable. Smoking and diabetes data were from a primary care sub-sample (about 53,000 people). Males and females in most minority groups had lower age-adjusted mortality RRs than the White Scottish group. The 95% CIs provided good evidence that the RR was more than 10% lower in the following ethnic groups: Other White British (72.3 [95% CI 64.2, 81.3] in males and 75.2 [68.0, 83.2] in females); Other White (80.8 [72.8, 89.8] in males and 76.2 [68.6, 84.7] in females); Indian (62.6 [51.6, 76.0] in males and 60.7 [50.4, 73.1] in females); Pakistani (66.1 [57.4, 76.2] in males and 73.8 [63.7, 85.5] in females); Bangladeshi males (50.7 [32.5, 79.1]); Caribbean females (57.5 [38.5, 85.9]); and Chinese (52.2 [43.7, 62.5] in males and 65.8 [55.3, 78.2] in females). The differences were diminished but not eliminated after adjusting for UK/RoI birth and SES variables. A mortality advantage was evident in all 12 minority groups for those born abroad, but in only 6/12 male groups and 5/12 female groups of those born in the UK/RoI. In the primary care sub-sample, after adjustment for age, UK/RoI born, SES, smoking, and diabetes, the RR was not lower in Indian males (114.7 [95% CI 78.3, 167.9]) and Pakistani females (103.9 [73.9, 145.9]) than in White Scottish males and females, respectively. The main limitations were the inability to include deaths abroad and the small number of deaths in some ethnic minority groups, especially for people born in the UK/RoI. CONCLUSIONS: There was relatively low mortality for many ethnic minority groups compared to the White Scottish majority. The mortality advantage was less clear in UK/RoI-born minority group offspring than in immigrants. These differences need explaining, and health-related behaviours seem important. Similar analyses are required internationally to fulfil agreed goals for monitoring, understanding, and improving health in ethnically diverse societies and to apply to health policy, especially on health inequalities and inequities.

Systematic identification of genomic markers of drug sensitivity in cancer cells.

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Is the linkage of census and health data justified? Views from a public panel of the Scottish Health and Ethnicity Linkage study.

Background: Using routine health data for research aimed at improving health requires the public's awareness and trust. The Scottish Health and Ethnicity Linkage study explores variations in health between ethnic groups. We aimed to establish a public panel to obtain their views on its methods, findings and dissemination, including use of routine health data without individual opt-in consent. Methods: Adult applicants were sought via a range of sources, aiming for a balance of age, gender and ethnicity. Three half-day meetings were held in 2015-16. Discussion covered the study's aims and governance; record linkage methods; data security; main findings, dissemination and publication processes. Results: Of 29 applicants, 19 joined the panel. Panellists were from 10 ethnic groups, 11 were females, ages 29-69 years. With some reservations, they enjoyed the meetings. After methods and security were explained, they unanimously accepted the study's use of linked data without individual opt-in consent. They thought explaining such complex methods to the general public was difficult. They recommended more should be done to communicate study findings to the public, practitioners and policy makers. Conclusions: The panellists' support for the study methods was reassuring. Their recommendations have led to the implementation of a wider dissemination plan.

Retrospective cohort study of breast cancer incidence, health service use and outcomes in Europe: a study of feasibility.

Background: Comparisons of outcomes of health care in different systems can be used to inform health policy. The EuroHOPE (European Healthcare Outcomes, Performance and Efficiency) project investigated the feasibility of comparing routine data on selected conditions including breast cancer across participating European countries. Methods: Routine data on incidence, treatment and mortality by age and clinical characteristics for breast cancer in women over 24 years of age were obtained (for a calendar year) from linked hospital discharge records, cancer and death registers from Finland, the Turin metropolitan area, Scotland and Sweden (all 2005), Hungary (2006) and Norway (2009). Age-adjusted breast cancer incidence and 1-year survival were estimated for each country/region. Results: In total, 24 576 invasive breast cancer cases were identified from cancer registries from over 13 million women. Age-adjusted incidence ranged from 151.1 (95%CI 147.2-155.0) in Hungary to 234.7 (95%CI 227.4-242.0)/100 000 in Scotland. One-year survival ranged from 94.1% (95%CI 93.5-94.7%) in Scotland to 97.1% (95%CI 96.2-98.1%) in Italy. Scotland had the highest proportions of poor prognostic factors in terms of tumour size, nodal status and metastases. Significant variations in data completeness for prognostic factors prevented adjustment for case mix. Conclusion: Incidence of and survival from breast cancer showed large differences between countries. Substantial improvements in the use of internationally recognised common terminology, standardised data coding and data completeness for prognostic indicators are required before international comparisons of routine data can be used to inform health policy.

Ethnic variations in asthma hospital admission, readmission and death: a retrospective, national cohort study of 4.62 million people in Scotland.

BACKGROUND: Our previous meta-analysis found that South Asians and Blacks in the UK were at a substantially increased risk of hospital admission from asthma. These estimates were, however, derived from pooling data from a limited number of now dated studies, confined to only three very broad ethnic groups (i.e. Whites, South Asians and Blacks) and failed to take account of possible sex-related differences in outcomes within these ethnic groups. We undertook the first study investigating ethnic variations in asthma outcomes across an entire population. METHODS: This retrospective 9-year cohort study linked Scotland's hospitalisation/death records on asthma to the 2001 census (providing ethnic group). We calculated age, country of birth and Scottish Index of Multiple Deprivation adjusted incident rate ratios (IRRs) for hospitalisation or death by sex for the period May 2001-2010. We calculated hazard ratios (HRs) for asthma readmission and subsequent asthma death. RESULTS: We were able to link data on 4.62 million people (91.8% of the Scottish population), yielding over 38 million patient-years of data, 1,845 asthma deaths, 113,795 first asthma admissions, and 107,710 readmissions (40,075 of which were for asthma). There were substantial ethnic variations in the rate of hospitalisation/death in both males and females. When compared to the reference Scottish White population, the highest age-adjusted rates were in Pakistani males (IRR = 1.59; 95% CI, 1.30-1.94) and females (IRR = 1.50; 95% CI, 1.06-2.11) and Indian males (IRR = 1.34; 95% CI, 1.16-1.54), and the lowest were seen in Chinese males (IRR = 0.62; 95% CI, 0.41-0.94) and females (IRR = 0.49; 95% CI, 0.39-0.61). CONCLUSION: There are very substantial ethnic variations in hospital admission/deaths from asthma in Scotland, with Pakistanis having the worst and Chinese having the best outcomes. Cultural factors, including self-management and health seeking behaviours, and variations in the quality of primary care provision are the most likely explanations for these differences and these now need to be formally investigated.

Parameter Heterogeneity In Breast Cancer Cost Regressions - Evidence From Five European Countries.

We investigate parameter heterogeneity in breast cancer 1-year cumulative hospital costs across five European countries as part of the EuroHOPE project. The paper aims to explore whether conditional mean effects provide a suitable representation of the national variation in hospital costs. A cohort of patients with a primary diagnosis of invasive breast cancer (ICD-9 codes 174 and ICD-10 C50 codes) is derived using routinely collected individual breast cancer data from Finland, the metropolitan area of Turin (Italy), Norway, Scotland and Sweden. Conditional mean effects are estimated by ordinary least squares for each country, and quantile regressions are used to explore heterogeneity across the conditional quantile distribution. Point estimates based on conditional mean effects provide a good approximation of treatment response for some key demographic and diagnostic specific variables (e.g. age and ICD-10 diagnosis) across the conditional quantile distribution. For many policy variables of interest, however, there is considerable evidence of parameter heterogeneity that is concealed if decisions are based solely on conditional mean results. The use of quantile regression methods reinforce the need to consider beyond an average effect given the greater recognition that breast cancer is a complex disease reflecting patient heterogeneity.

Risk of respiratory hospitalization and death, readmission and subsequent mortality: scottish health and ethnicity linkage study.

BACKGROUND: Limited and dated evidence shows ethnic inequalities in health status and health care in respiratory diseases. METHODS: This retrospective, cohort study linked Scotland's hospitalization/death records on respiratory disorders to 4.65 million people in the 2001 census (providing ethnic group). For all-respiratory diseases and chronic obstructive pulmonary disease (COPD) from April 2001 to 2010 we calculated age, country of birth and Scottish Index of Multiple Deprivation (SIMD) adjusted risk ratios (RRs), by sex. We calculated hazard ratios (HRs) for death following hospitalization and for readmission. We multiplied ratios and confidence intervals (CIs) by 100, so the reference Scottish White population's RR/HR = 100. RESULTS: RRs were comparatively low for all-respiratory diseases in Other White British (84.0, 95% CI 79.6, 88.6) and Chinese (67.4, 95% CI 55.2, 82.3) men and high in Pakistani men (138.1, 95% CI 125.5, 151.9) and women (132.7, 95% CI 108.8, 161.8). For COPD, White Irish men (142.5, 95% CI 125.3, 162.1) and women (141.9, CI 124.8, 161.3) and any Mixed Background men (161, CI 127.1, 203.9) and women (215.4, CI 158.2, 293.3) had high RRs, while Indian men (54.5, CI 41.9, 70.9) and Chinese women (50.5, CI 31.4, 81.1) had low RRs. In most non-White groups, mortality following hospitalization and readmission was similar or lower than the reference. CONCLUSIONS: The pattern of ethnic variations in these respiratory disorders was complex and did not merely reflect smoking patterns. Readmission and death after hospitalization data did not signal inequity in services for ethnic minority groups.

Clinical Reasoning: A Young Adult With New Seizures and Chapeau de Gendarme.

The evaluation of new seizures is a common clinical query for neurologists. It can be challenging to delineate between the numerous etiologies of new focal or generalized seizures and, if focal, to localize their onset. In this case report, we present a 26-year-old patient with a new onset of stereotyped events concerning for seizures featuring facial grimacing, dystonic left-hand posturing, and convulsions with immediate return to baseline. Throughout the case, we highlight a stepwise diagnostic approach to the evaluation of new-onset seizures, discuss clues that seizure semiology can provide for localization of ictal onset, and review a novel and atypical presentation of a disease entity frequently encountered by neurologists.

Approach to Myelopathy and Myelitis.

Myelopathy can present acutely or more insidiously and has a broad differential diagnosis. In addition to the clinical history and neurologic examination, diagnostic testing, including MRI and cerebrospinal fluid analysis, as well as thorough review of patient comorbidities, risk factors, and potential toxic exposures, can help neurohospitalists distinguish between various causes and potentially start appropriate empiric therapy while awaiting definitive testing. This article focuses on how imaging can help in determining the most likely cause of myelopathy and highlights a range of causes, including compressive, vascular, metabolic and toxic, infectious, autoimmune, neoplastic, and paraneoplastic causes of spinal cord dysfunction.

Low dose dexamethasone as treatment for women with heavy menstrual bleeding: A response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM).

BACKGROUND: The symptom of heavy menstrual bleeding (HMB) diminishes quality-of-life for many mid-age women and imposes substantial societal burden. We investigated our hypothesis that HMB reflects impaired endometrial vasoconstriction due to endometrial glucocorticoid deficiency. Does reversing this deficiency, by short-term luteal-phase treatment with exogenous glucocorticoid (dexamethasone), ameliorate HMB? METHODS: In our Bayesian response-adaptive parallel-group placebo-controlled randomised trial, five pre-planned interim analyses used primary outcome data to adjust randomisation probabilities to favour doses providing most dose-response information. Participants with HMB, recruited from Lothian (Scotland) NHS clinics and via community invitations/advertisements, were aged over 18 years; reported regular 21-42 day menstrual cycles; and had measured menstrual blood loss (MBL) averaging ≥ 50 mL over two screening periods. Identically encapsulated placebo, or one of six Dexamethasone doses (0·2 mg, 0·4 mg, 0·5 mg, 0·6 mg, 0·75 mg, 0·9 mg), were taken orally twice-daily over five days in the mid-luteal phase of three menstrual cycles. Participants, investigators, and those measuring outcomes were masked to group assignment. Primary outcome, change in average MBL from screening to 'treatment', was analysed by allocated treatment, for all with data. TRIAL REGISTRATION: ClinicalTrials.gov NCT01769820; EudractCT 2012-003,405-98 FINDINGS: Recruitment lasted 29/01/2014 to 25/09/2017; 176 were screened, 107 randomised and 97 provided primary outcome data (n = 24,5,9,21,8,14,16 in the seven arms, placebo to 1·8 mg total daily active dose). In Bayesian normal dynamic linear modelling, 1·8 mg dexamethasone daily showed a 25 mL greater reduction in MBL from screening, than placebo (95% credible interval 1 to 49 mL), and probability 0·98 of benefit over placebo. Adverse events were reported by 75% (58/77) receiving dexamethasone, 58% (15/26) taking placebo. Three serious adverse events occurred, two during screening, one in a placebo participant. No woman withdrew due to adverse effects. INTERPRETATION: Our adaptive trial in HMB showed that dexamethasone 1·8 mg daily reduced menstrual blood loss. The role of dexamethasone in HMB management deserves further investigation. FUNDING: UK MRC DCS/DPFS grant MR/J003611/1.

Are there ethnic and religious variations in uptake of bowel cancer screening? A retrospective cohort study among 1.7 million people in Scotland.

OBJECTIVE: Cancer screening should be equitably accessed by all populations. Uptake of colorectal cancer screening was examined using the Scottish Health and Ethnicity Linkage Study that links the Scottish Census 2001 to health data by individual-level self-reported ethnicity and religion. SETTING: Data on 1.7 million individuals in two rounds of the Scottish Bowel Cancer Screening Programme (2007-2013) were linked to the 2001 Census using the Scottish Community Health Index number. MAIN OUTCOME MEASURE: Uptake of colorectal cancer screening, reported as age-adjusted risk ratios (RRs) by ethnic group and religion were calculated for men and women with 95% CI. RESULTS: In the first, incidence screening round, compared with white Scottish men, Other White British (RR 109.6, 95% CI 108.8 to 110.3) and Chinese (107.2, 95% CI 102.8 to 111.8) men had higher uptake. In contrast, men of all South Asian groups had lower uptake (Indian RR 80.5, 95% CI 76.1 to 85.1; Pakistani RR 65.9, 95% CI 62.7 to 69.3; Bangladeshi RR 76.6, 95% CI 63.9 to 91.9; Other South Asian RR 88.6, 95% CI 81.8 to 96.1). Comparable patterns were seen among women in all ethnic groups, for example, Pakistani (RR 55.5, 95% CI 52.5 to 58.8). Variation in uptake was also observed by religion, with lower rates among Hindu (RR (95%CI): 78.4 (71.8 to 85.6)), Muslim (69.5 (66.7 to 72.3)) and Sikh (73.4 (67.1 to 80.3)) men compared with the reference population (Church of Scotland), with similar variation among women: lower rates were also seen among those who reported being Jewish, Roman Catholic or with no religion. CONCLUSIONS: There are important variations in uptake of bowel cancer screening by ethnic group and religion in Scotland, for both sexes, that require further research and targeted interventions.

Drug Sensitivity Assays of Human Cancer Organoid Cultures.

Drug sensitivity testing utilizing preclinical disease models such as cancer cell lines is an important and widely used tool for drug development. Importantly, when combined with molecular data such as gene copy number variation or somatic coding mutations, associations between drug sensitivity and molecular data can be used to develop markers to guide patient therapies. The use of organoids as a preclinical cancer model has become possible following recent work demonstrating that organoid cultures can be derived from patient tumors with a high rate of success. A genetic analysis of colon cancer organoids found that these models encompassed the majority of the somatic variants present within the tumor from which it was derived, and capture much of the genetic diversity of colon cancer observed in patients. Importantly, the systematic sensitivity testing of organoid cultures to anticancer drugs identified clinical gene-drug interactions, suggestive of their potential as preclinical models for testing anticancer drug sensitivity. In this chapter, we describe how to perform medium/high-throughput drug sensitivity screens using 3D organoid cell cultures.

Erratum to: Drug Sensitivity Assays of Human Cancer Organoid Cultures.

The protocol Drug Sensitivity Assays of Human Cancer Organoid Cultures has now been made available open access under a CC BY 4.0 license.

Assessment of health care, hospital admissions, and mortality by ethnicity: population-based cohort study of health-system performance in Scotland.

BACKGROUND: Ethnic minorities often experience barriers to health care. We studied six established quality indicators of health-system performance across ethnic groups in Scotland. METHODS: In this population-based cohort study, we linked ethnicity from Scotland's Census 2001 (April 29, 2001) to hospital admissions and mortality records, with follow-up until April 30, 2013. Indicators of health-system performance included amenable deaths (ie, deaths avertable by effective treatment), preventable deaths (ie, deaths avertable by public health policy), avoidable deaths (combined amenable and preventable deaths), avoidable hospital admissions, unplanned readmissions, and length of stay. We calculated rate ratios and odds ratios (with 95% CIs) using Poisson and logistic regression, which we multiplied by 100, adjusting first for age-related covariates and then for socioeconomic-related and birthplace-related covariates. The white Scottish population was the reference (rate ratio [RR] 100). FINDINGS: The results are based on 4·61 million people. During the 50·5 million person-years of study, 1·17 million avoidable hospital admissions, 587 740 unplanned readmissions, and 166 245 avoidable deaths occurred. South Asian groups had higher avoidable hospital admissions than the white Scottish group, with the highest reported RRs in Pakistani groups (RR 140·6 [95% CI 131·9-150·0] in men; RR 141·0 [129·0-154·1] in women). There was little variation between ethnic groups in length of stay or unplanned readmission. Preventable and amenable mortality were higher in the white Scottish group than several ethnic minorities including other white British, other white, Indian, and Chinese groups. Such differences were partly diminished by adjustment for socioeconomic status, whereas adjustment for country of birth had little additional effect. INTERPRETATION: These data suggest concerns about the access to and quality of primary care to prevent avoidable hospital admissions, especially for south Asians. Relatively high preventable and amenable deaths in white Scottish people, compared with several ethnic minority populations, were unexpected. Future studies should both corroborate and examine explanations for these patterns. Studies using several indicators simultaneously are also required internationally. FUNDING: Chief Scientist's Office, Medical Research Council, NHS Research Scotland, Farr Institute.

Life expectancy of different ethnic groups using death records linked to population census data for 4.62 million people in Scotland.

BACKGROUND: Few countries record the data needed to estimate life expectancy by ethnic group. Such information is helpful in assessing the extent of health inequality. METHOD: Life tables were created using 3 years of deaths (May 2001-April 2004) linked to Scottish 2001 Census data for 4.62 million individuals with self-reported ethnicity. We created 8 ethnic groups based on the census definitions, each with at least 5000 individuals and 40 deaths. Life expectancy at birth was calculated using the revised Chiang method. RESULTS: The life expectancy of White Scottish males at birth was 74.7 years (95% CI 74.6 to 74.8), similar to Mixed Background (73.0; 70.2 to 75.8) and White Irish (75.0; 74.0 to 75.9), but shorter than Indian (80.9; 78.4 to 83.4), Pakistani (79.3; 76.9 to 81.6), Chinese (79.0; 76.5 to 81.5), Other White British (78.9; 78.6 to 79.2) and Other White (77.2; 76.4 to 78.1). The life expectancy of White Scottish females was 79.4 years (79.3 to 79.5), similar to mixed background (79.3; 76.6 to 82.0), but shorter than Pakistani (84.6; 82.0 to 87.3), Chinese (83.4; 81.1 to 85.7), Indian (83.3; 80.7 to 85.9), Other White British (82.6; 82.3 to 82.9), other White (82.0; 81.3 to 82.8) and White Irish (81; 80.2 to 81.8). CONCLUSIONS: Males and females in most of the larger ethnic minority groups in Scotland have longer life expectancies than the majority White Scottish population.