Developing better information about the health and health care of people with developmental disabilities in Scotland

Introduction: Neurodevelopmental disorders are a group of disorders that manifest early in development, and include intellectual disabilities and autism, among others. Intellectual disabilities refer to impairments in intellectual functioning (an intelligence quotient <70), together with deficits in adaptive functioning (need for support for daily personal independence and social functioning), with onset during the developmental period. Autism is characterised by persistent deficits in social communication and social interactions across multiple contexts, and restricted, repetitive patterns of behaviour, interests or activities, with onset of these symptoms in the early developmental period. People with intellectual disabilities and people with autism are thought to experience high levels of physical and mental health problems and earlier mortality than other people on average. Yet, there is a dearth of empirical evidence about the health of people with intellectual disabilities and people with autism which presents a barrier to understanding the complex factors that produce differential health outcomes. Ensuring adults with intellectual disabilities or autism live not only longer but healthier lives is a priority for the World Health Organisation and the Scottish Government. Methods: The portfolio of publications (n=15) presented in this mixed methods PhD thesis, represents a selection of my peer reviewed publications in international scientific journals since 2015. I [Laura Hughes-McCormack] am the lead author on 4 of these publications and co-author on 11 publications (including being second author on 8 of these) which were prepared from research I undertook within the Scottish Learning Disabilities Observatory (SLDO) at the Institute of Health and Wellbeing, University of Glasgow. This research programme was funded by the Scottish Government in 2014 to provide evidence on the health of people with intellectual disabilities and autism in Scotland, and thus to inform the development of public policy. The research presented includes systematic reviews, quantitative research, data linkage research, and is presented in three themes throughout this thesis, as follows. Theme I. Health of people with intellectual disabilities and autism; seven of the nine quantitative studies presented under this theme/section analysed data from the Scottish Census, relating to people with intellectual disabilities or autism from 94% of the Scottish population (n=5,269,054) who responded to the Census in 2011. Two further studies (a quantitative study and a systematic review study) are reported, which investigated sedentary behaviour and oral health. Theme II. Health care of people with intellectual disabilities and Down syndrome; to quantify the management of long-term conditions, data for a population-based cohort of people with intellectual disabilities (n=721) was compared using an established evidence-based approach to measuring the quality of primary health care for all people without intellectual disabilities (n=764,672) in the largest health board in Scotland, throughout 2007-2010. A further systematic review study investigated hospital admissions for physical health conditions in adults with intellectual disabilities. Theme III. Survival/ death of people with intellectual disabilities and Down syndrome; two systematic reviews are reported, investigating deaths in people with intellectual disabilities and people with Down syndrome, and a further data linkage study which investigated birth and death rates and hospitalisations (throughout a 25-year period) among children/young people with Down syndrome in Scotland. Each theme includes a clear overview of the background/ rationale, methodology, results and impact of this body of work in relation to the development of better information on health and health care of people with intellectual disabilities and autism in Scotland. Results: Theme I: Health of people with intellectual disabilities and autism: Findings of the Scottish Census 2011 studies (I-VII), show that poor health was more common for people with intellectual disabilities (odds of 43 in statistically predicting poor general health) and they were seven times more likely to report a current mental health condition than people without intellectual disabilities. Autism had odds of 11.3 in predicting poor general health in children and young people, and odds of 7.5 in adults. Comorbidities were found to be common among people with autism. Other studies presented under this theme (VIII, IX) show adults with intellectual disabilities have higher levels, and different correlates, of sedentary behaviour and poorer oral health. Theme II: Health care of people with intellectual disabilities and Down syndrome: Findings from two studies (X, XI) show, people with intellectual disabilities were receiving lower quality health care compared to other people across all long‐term conditions investigated on 38/57 (66.7%) quality indicators. A follow up study, comparing baseline data to data in 2014 found adults with intellectual disabilities still had a lower proportion of indicators met than the general population; but by 2014, the healthcare inequality gap had reduced compared with 2007-10. A systematic review (XII), further investigating the quality of health care of people with intellectual disabilities, found people with intellectual disabilities were admitted to hospital more frequently than the general population for physical conditions which if managed effectively at the primary care level, should not lead to hospital admission, although evidence is limited. Theme III: Survival/ death of people with intellectual disabilities and Down syndrome: Findings from the two systematic reviews (XIII, XIV) found mortality rates are higher in (1) the intellectual disabilities population and (2) the Down syndrome population, compared with the general population. For the intellectual disabilities’ population, an average age of death of 20 years lower was found compared to the general population. For the Down syndrome population, compared with the general population, an average age of death of 28 years lower was found although survival rates have improved over time. Patterns of cause of death were different for people with intellectual disabilities and people with Down syndrome compared to the general population. The data linkage study (XV) found the incidence of Down syndrome live-births was 1.0/1,000 births over the last 25 years. More children and young people with Down syndrome died (n=92; 7.4%) over the 25-year period compared to controls (n=23; 0.4%); that is 18.5 times more. There was increased risk of hospitalisation as more of the Down syndrome group had at least one admission (1,105 [89.5%] versus 3,305 [53.5%]; adjusted HR=1.84 [1.68, 2.01]). Re-admissions, emergency admissions and length of stay were also higher for the Down syndrome group. Conclusions: This thesis has presented for each of the three inter-related themes, a range of my peer reviewed publications from international journals. A previous dearth of empirical evidence about the health and health care of people with intellectual disabilities and people with autism has presented barriers to understanding the complex factors that produce differential health outcomes. The research presented in this thesis has provided robust evidence on the extent of poor health, health care, and premature mortality among people with intellectual disabilities, and people with autism which has not previously been quantified in research. This evidence has led to shaping Scottish policy and practice to support the needs of people with intellectual disabilities, for example, the most recent learning disabilities strategy in Scotland, The Keys to Life, updated in 2019, includes input from my research

The relative influence of intellectual disabilities and autism on mental and general health in Scotland: a cross-sectional study of a whole country of 5.3 million children and adults

Objectives: To determine the relative extent that autism and intellectual disabilities are independently associated with poor mental and general health, in children and adults. Design: Cross-sectional study. For Scotland’s population, logistic regressions investigated odds of intellectual disabilities and autism predicting mental health conditions, and poor general health, adjusted for age and gender. Participants: 1 548 819 children/youth aged 0-24 years, and 3 746 584 adults aged more than 25 years, of whom 9396/1 548 819 children/youth had intellectual disabilities (0.6%), 25 063/1 548 819 children/youth had autism (1.6%); and 16 953/3 746 584 adults had intellectual disabilities (0.5%), 6649/3 746 584 adults had autism (0.2%). These figures are based on self-report. Main outcome measures: Self-reported general health status and mental health. Results: In children/youth, intellectual disabilities (OR 7.04, 95% CI 6.30 to 7.87) and autism (OR 25.08, 95% CI 23.08 to 27.32) both independently predicted mental health conditions. In adults, intellectual disabilities (OR 3.50, 95% CI 3.20 to 3.84) and autism (OR 5.30, 95% CI 4.80 to 5.85) both independently predicted mental health conditions. In children/youth, intellectual disabilities (OR 18.34, 95% CI 17.17 to 19.58) and autism (OR 8.40, 95% CI 8.02 to 8.80) both independently predicted poor general health. In adults, intellectual disabilities (OR 7.54, 95% CI 7.02 to 8.10) and autism (OR 4.46, 95% CI 4.06 to 4.89) both independently predicted poor general health. Conclusions: Both intellectual disabilities and autism independently predict poor health, intellectual disabilities more so for general health and autism more so for mental health. Intellectual disabilities and autism are not uncommon, and due to their associated poor health, sufficient services/supports are needed. This is not just due to coexistence of these conditions or just to having intellectual disabilities, as the population with autism is independently associated with substantial health inequalities compared with the general population, across the entire life course

Prevalence of long-term health conditions in adults with autism:Observational study of a whole country population

Objectives: To investigate the prevalence of comorbid mental health conditions and physical disabilities in a whole country population of adults aged 25+ with and without reported autism. Design: Secondary analysis of Scotland’s Census, 2011 data. Cross-sectional study. Setting: General population. Participants: 94% of Scotland’s population, including 6649/3 746 584 adults aged 25+ reported to have autism. Main outcome measures: Prevalence of six comorbidities: deafness or partial hearing loss, blindness or partial sight loss, intellectual disabilities, mental health conditions, physical disability and other condition; ORs (95% CI) of autism predicting these comorbidities, adjusted for age and gender; and OR for age and gender in predicting comorbidities within the population with reported autism. Results: Comorbidities were common: deafness/hearing loss—17.5%; blindness/sight loss—12.1%; intellectual disabilities—29.4%; mental health conditions—33.0%; physical disability—30.7%; other condition—34.1%. Autism statistically predicted all of the conditions: OR 3.3 (95% CI 3.1 to 3.6) for deafness or partial hearing loss, OR 8.5 (95% CI 7.9 to 9.2) for blindness or partial sight loss, OR 94.6 (95% CI 89.4 to 100.0) for intellectual disabilities, OR 8.6 (95% CI 8.2 to 9.0) for mental health conditions, OR 6.2 (95% CI 5.8 to 6.6) for physical disability and OR 2.6 (95% CI 2.5 to 2.8) for other condition. Contrary to findings within the general population, female gender predicted all conditions within the population with reported autism, including intellectual disabilities (OR=1.4). Conclusions: Clinicians need heightened awareness of comorbidities in adults with autism to improve detection and suitable care, especially given the added complexity of assessment in this population and the fact that hearing and visual impairments may cause additional difficulties with reciprocal communication which are also a feature of autism; hence posing further challenges in assessment

Birth incidence, deaths and hospitalisations of children and young people with Down syndrome, 1990–2015: birth cohort study

Objective: To investigate current Down syndrome live birth and death rates, and childhood hospitalisations, compared with peers.Setting: General community.Participants: All live births with Down syndrome, 1990–2015, identified via Scottish regional cytogenetic laboratories, each age–sex–neighbourhood deprivation matched with five non-Down syndrome controls. Record linkage to Scotland’s hospital admissions and death data.Primary outcome: HRs comparing risk of first hospitalisation (any and emergency), readmission for children with Down syndrome and matched controls were calculated using stratified Cox proportional hazards (PH) model, and length of hospital stay was calculated using a conditional log-linear regression model.Results: 689/1479 (46.6%) female and 769/1479 (51.9%) male children/young people with Down syndrome were identified (1.0/1000 births, with no reduction over time); 1235 were matched. 92/1235 (7.4%) died during the period, 18.5 times more than controls. More of the Down syndrome group had at least one admission (incidence rate ratio(IRR) 72.89 (68.72–77.32) vs 40.51 (39.15–41.92); adjusted HR=1.84 (1.68, 2.01)) and readmissions (IRR 54.85 (51.46–58.46) vs 15.06 (14.36–15.80); adjusted HR=2.56 (2.08, 3.14)). More of their admissions were emergencies (IRR 56.78 (53.13–60.72) vs 28.88 (27.73–30.07); first emergency admission adjusted HR=2.87 (2.61, 3.15)). Children with Down syndrome had 28% longer first admission after birth. Admission rate increased from 1990–2003 to 2004–2014 for the Down syndrome group (from 90.7% to 92.2%) and decreased for controls (from 63.3% to 44.8%).Conclusions: We provide contemporaneous statistics on the live birth rate of babies with Down syndrome, and their childhood death rate. They require more hospital admissions, readmissions emergency admissions and longer lengths of stays than their peers, which has received scant research attention in the past. This demonstrates the importance of statutory planning as well as informal support to families to avoid added problems in child development and family bonding over and above that brought by the intellectual disabilities associated with Down syndrome

Cohort profile:Scotland’s record-linkage e-cohorts of people with intellectual disabilities, and autistic people (SCIDA)

Purpose: To investigate health, mortality and healthcare inequalities experienced by people with intellectual disabilities, and autistic people, and their determinants; an important step towards identifying and implementing solutions to reduce inequalities. This paper describes the cohorts, record-linkages and variables that will be used. Participants: Scotland’s Census, 2011 was used to identify Scotland’s citizens with intellectual disabilities, and autistic citizens, and representative general population samples with neither. Using Scotland’s community health index, the Census data (demography, household, employment, long-term conditions) were linked with routinely collected health, death and healthcare data: Scotland’s register of deaths, Scottish morbidity data 06 (SMR06: cancer incidence, mortality, treatments), Prescribing Information System (identifying asthma/chronic obstructive pulmonary disease; angina/congestive heart failure/hypertension; peptic ulcer/reflux; constipation; diabetes; thyroid disorder; depression; bipolar disorders; anxiety/sleep; psychosis; attention deficit hyperactivity disorder; epilepsy; glaucoma), SMR01 (general/acute hospital admissions and causes, ambulatory care sensitive admissions), SMR04 (mental health admissions and causes), Scottish Care Information–Diabetes Collaboration (diabetic care quality, diabetic outcomes), national bowel screening programme and cervical screening. Findings to date: Of the whole population, 0.5% had intellectual disabilities, and 0.6% were autistic. Linkage was successful for &gt;92%. The resultant e-cohorts include: (1) 22 538 people with intellectual disabilities (12 837 men and 9701 women), 4509 of whom are children &lt;16 years, (2) 27 741 autistic people (21 390 men and 6351 women), 15 387 of whom are children &lt;16 years and (3) representative general population samples with neither condition. Very good general health was reported for only 3389 (15.0%) people with intellectual disabilities, 10 510 (38.0%) autistic people, compared with 52.4% general population. Mental health conditions were reported for 4755 (21.1%) people with intellectual disabilities, 3998 (14.4%) autistic people, compared with 4.2% general population. Future plans: Analyses will determine the extent of premature mortality, causes of death, and avoidable deaths, profile of health conditions and cancers, healthcare quality and screening and determinants of mortality and healthcare

Rates, causes and predictors of all-cause and avoidable mortality in 163 686 children and young people with and without intellectual disabilities:A record linkage national cohort study

Objectives: To investigate mortality rates and associated factors, and avoidable mortality in children/young people with intellectual disabilities. Design: Retrospective cohort; individual record-linked data between Scotland’s 2011 Census and 9.5 years of National Records for Scotland death certification data. Setting: General community. Participants: Children and young people with intellectual disabilities living in Scotland aged 5–24 years, and an age-matched comparison group. Main outcome measures: Deaths up to 2020: age of death, age-standardised mortality ratios (age-SMRs); causes of death including cause-specific age-SMRs/sex-SMRs; and avoidable deaths. Results: Death occurred in 260/7247 (3.6%) children/young people with intellectual disabilities (crude mortality rate=388/100 000 person-years) and 528/156 439 (0.3%) children/young people without intellectual disabilities (crude mortality rate=36/100 000 person-years). SMRs for children/young people with versus those without intellectual disabilities were 10.7 for all causes (95% CI 9.47 to 12.1), 5.17 for avoidable death (95% CI 4.19 to 6.37), 2.3 for preventable death (95% CI 1.6 to 3.2) and 16.1 for treatable death (95% CI 12.5 to 20.8). SMRs were highest for children (27.4, 95% CI 20.6 to 36.3) aged 5–9 years, and lowest for young people (6.6, 95% CI 5.1 to 8.6) aged 20–24 years. SMRs were higher in more affluent neighbourhoods. Crude mortality incidences were higher for the children/young people with intellectual disabilities for most International Statistical Classification of Diseases and Related Health Problems, 10th Revision chapters. The most common underlying avoidable causes of mortality for children/young people with intellectual disabilities were epilepsy, aspiration/reflux/choking and respiratory infection, and for children/young people without intellectual disabilities were suicide, accidental drug-related deaths and car accidents. Conclusion: Children with intellectual disabilities had significantly higher rates of all-cause, avoidable, treatable and preventable mortality than their peers. The largest differences were for treatable mortality, particularly at ages 5–9 years. Interventions to improve healthcare to reduce treatable mortality should be a priority for children/young people with intellectual disabilities. Examples include improved epilepsy management and risk assessments, and coordinated multidisciplinary actions to reduce aspiration/reflux/choking and respiratory infection. This is necessary across all neighbourhoods

Prevalence and general health status of people with intellectual disabilities in Scotland: a total population study

Background: Prevalence of intellectual disabilities varies considerably between studies. People with intellectual disabilities experience health inequalities, but most studies comprise small or incomplete populations. We investigated in a whole country population the (1) prevalence of intellectual disabilities and (2) general health status compared with the general population. Method: Data were from Scotland’s Census, 2011. We calculated the prevalence of intellectual disabilities, reported general health status of people with and without intellectual disabilities and the extent of health-related limitations to daily activities. We conducted logistic regressions to determine the ORs of intellectual disabilities predicting poor health and associations with age and gender. Results: Of Scotland’s 5 295 403 population, 26 349 (0.5%) had intellectual disabilities; 15 149 (57.5%) were males and 11 200 (42.5%) were females; 5234 (0.6%) were children/youth (0–15) and 21 115 (0.5%) were adults (16–75+ years). Identification of intellectual disabilities rises until age 5 years, with a further small rise by age 9 years. Children and adults with intellectual disabilities reported more poor health (47.9% and 40.3%) than the general population (2.1% and 13.8%) and were more limited in activities by their health. Intellectual disabilities had an OR of 43.2 (95% CI 40.8 to 45.7) in predicting poor health; the influence of increasing age on poor health was markedly interacted by presence of intellectual disabilities, likely to be due to a ‘healthy survivor’ effect within the intellectual disabilities population. Conclusion: People with intellectual disabilities have poorer general health than other people, especially children and young people. Accurate information on population prevalence and health status is essential to plan appropriate resources

Respiratory-associated deaths in people with intellectual disabilities: a systematic review and meta-analysis

Objective To review and synthesise evidence on rates of respiratory-associated deaths and associated risk factors in the intellectual disability population.Design Systematic review and meta-analysis.Data sources Embase, CINAHL, ISI Web of Science (all databases including Medline) and PsychINFO were searched for studies published between 1st January 1985 and 27th April 2020 and examined study and outcome quality. Reference lists and Google Scholar were also hand searched.Results We identified 2295 studies, 17 were included in the narrative synthesis and 10 studies (11 cohorts) in the meta-analysis. Data from 90 302 people with intellectual disabilities and 13 808 deaths from all causes in people with intellectual disabilities were extracted. Significantly higher rates of respiratory-associated deaths were found among people with intellectual disabilities (standardised mortality ratio(SMR): 10.86 (95% CI: 5.32 to 22.18, p&lt;0.001) compared with those in the general population, lesser rates for adults with ID (SMR: 6.53 (95% CI: 4.29 to 9.96, p&lt;0.001); and relatively high rates from pneumonia 26.65 (95% CI: 5.63 to 126.24, p&lt;0.001). The overall statistical heterogeneity was I2=99.0%.Conclusion Premature deaths due to respiratory disorders are potentially avoidable with improved public health initiatives and equitable access to quality healthcare. Further research should focus on developing prognostic guidance and validated tools for clinical practice to mitigate risks of respiratory-associated deaths.PROSPERO registration number CRD42020180479

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease