Identifying health inequalities in individuals with major mental illness (MMI) using routine data

Abstract and Summary of Thesis: Background: Individuals with Major Mental Illness (such as schizophrenia and bipolar disorder) experience increased rates of physical health comorbidity compared to the general population. They also experience inequalities in access to certain aspects of healthcare. This ultimately leads to premature mortality. Studies detailing patterns of physical health comorbidity are limited by their definitions of comorbidity, single disease approach to comorbidity and by the study of heterogeneous groups. To date the investigation of possible sources of healthcare inequalities experienced by individuals with Major Mental Illness (MMI) is relatively limited. Moreover studies detailing the extent of premature mortality experienced by individuals with MMI vary both in terms of the measure of premature mortality reported and age of the cohort investigated, limiting their generalisability to the wider population. Therefore local and national data can be used to describe patterns of physical health comorbidity, investigate possible reasons for health inequalities and describe mortality rates. These findings will extend existing work in this area. Aims and Objectives: To review the relevant literature regarding: patterns of physical health comorbidity, evidence for inequalities in physical healthcare and evidence for premature mortality for individuals with MMI. To examine the rates of physical health comorbidity in a large primary care database and to assess for evidence for inequalities in access to healthcare using both routine primary care prescribing data and incentivised national Quality and Outcome Framework (QOF) data. Finally to examine the rates of premature mortality in a local context with a particular focus on cause of death across the lifespan and effect of International Classification of Disease Version 10 (ICD 10) diagnosis and socioeconomic status on rates and cause of death. Methods: A narrative review of the literature surrounding patterns of physical health comorbidity, the evidence for inequalities in physical healthcare and premature mortality in MMI was undertaken. Rates of physical health comorbidity and multimorbidity in schizophrenia and bipolar disorder were examined using a large primary care dataset (Scottish Programme for Improving Clinical Effectiveness in Primary Care (SPICE)). Possible inequalities in access to healthcare were investigated by comparing patterns of prescribing in individuals with MMI and comorbid physical health conditions with prescribing rates in individuals with physical health conditions without MMI using SPICE data. Potential inequalities in access to health promotion advice (in the form of smoking cessation) and prescribing of Nicotine Replacement Therapy (NRT) were also investigated using SPICE data. Possible inequalities in access to incentivised primary healthcare were investigated using National Quality and Outcome Framework (QOF) data. Finally a pre-existing case register (Glasgow Psychosis Clinical Information System (PsyCIS)) was linked to Scottish Mortality data (available from the Scottish Government Website) to investigate rates and primary cause of death in individuals with MMI. Rate and primary cause of death were compared to the local population and impact of age, socioeconomic status and ICD 10 diagnosis (schizophrenia vs. bipolar disorder) were investigated. Results: Analysis of the SPICE data found that sixteen out of the thirty two common physical comorbidities assessed, occurred significantly more frequently in individuals with schizophrenia. In individuals with bipolar disorder fourteen occurred more frequently. The most prevalent chronic physical health conditions in individuals with schizophrenia and bipolar disorder were: viral hepatitis (Odds Ratios (OR) 3.99 95% Confidence Interval (CI) 2.82-5.64 and OR 5.90 95% CI 3.16-11.03 respectively), constipation (OR 3.24 95% CI 3.01-3.49 and OR 2.84 95% CI 2.47-3.26 respectively) and Parkinson’s disease (OR 3.07 95% CI 2.43-3.89 and OR 2.52 95% CI 1.60-3.97 respectively). Both groups had significantly increased rates of multimorbidity compared to controls: in the schizophrenia group OR for two comorbidities was 1.37 95% CI 1.29-1.45 and in the bipolar disorder group OR was 1.34 95% CI 1.20-1.49. In the studies investigating inequalities in access to healthcare there was evidence of: under-recording of cardiovascular-related conditions for example in individuals with schizophrenia: OR for Atrial Fibrillation (AF) was 0.62 95% CI 0.52 - 0.73, for hypertension 0.71 95% CI 0.67 - 0.76, for Coronary Heart Disease (CHD) 0.76 95% CI 0.69 - 0.83 and for peripheral vascular disease (PVD) 0.83 95% CI 0.72 - 0.97. Similarly in individuals with bipolar disorder OR for AF was 0.56 95% CI 0.41-0.78, for hypertension 0.69 95% CI 0.62 - 0.77 and for CHD 0.77 95% CI 0.66 - 0.91. There was also evidence of less intensive prescribing for individuals with schizophrenia and bipolar disorder who had comorbid hypertension and CHD compared to individuals with hypertension and CHD who did not have schizophrenia or bipolar disorder. Rate of prescribing of statins for individuals with schizophrenia and CHD occurred significantly less frequently than in individuals with CHD without MMI (OR 0.67 95% CI 0.56-0.80). Rates of prescribing of 2 or more anti-hypertensives were lower in individuals with CHD and schizophrenia and CHD and bipolar disorder compared to individuals with CHD without MMI (OR 0.66 95% CI 0.56-0.78 and OR 0.55 95% CI 0.46-0.67, respectively). Smoking was more common in individuals with MMI compared to individuals without MMI (OR 2.53 95% CI 2.44-2.63) and was particularly increased in men (OR 2.83 95% CI 2.68-2.98). Rates of ex-smoking and non-smoking were lower in individuals with MMI (OR 0.79 95% CI 0.75-0.83 and OR 0.50 95% CI 0.48-0.52 respectively). However recorded rates of smoking cessation advice in smokers with MMI were significantly lower than the recorded rates of smoking cessation advice in smokers with diabetes (88.7% vs. 98.0%, p<0.001), smokers with CHD (88.9% vs. 98.7%, p<0.001) and smokers with hypertension (88.3% vs. 98.5%, p<0.001) without MMI. The odds ratio of NRT prescription was also significantly lower in smokers with MMI without diabetes compared to smokers with diabetes without MMI (OR 0.75 95% CI 0.69-0.81). Similar findings were found for smokers with MMI without CHD compared to smokers with CHD without MMI (OR 0.34 95% CI 0.31-0.38) and smokers with MMI without hypertension compared to smokers with hypertension without MMI (OR 0.71 95% CI 0.66-0.76). At a national level, payment and population achievement rates for the recording of body mass index (BMI) in MMI was significantly lower than the payment and population achievement rates for BMI recording in diabetes throughout the whole of the UK combined: payment rate 92.7% (Inter Quartile Range (IQR) 89.3-95.8 vs. 95.5% IQR 93.3-97.2, p<0.001 and population achievement rate 84.0% IQR 76.3-90.0 vs. 92.5% IQR 89.7-94.9, p<0.001 and for each country individually: for example in Scotland payment rate was 94.0% IQR 91.4-97.2 vs. 96.3% IQR 94.3-97.8, p<0.001. Exception rate was significantly higher for the recording of BMI in MMI than the exception rate for BMI recording in diabetes for the UK combined: 7.4% IQR 3.3-15.9 vs. 2.3% IQR 0.9-4.7, p<0.001 and for each country individually. For example in Scotland exception rate in MMI was 11.8% IQR 5.4-19.3 compared to 3.5% IQR 1.9-6.1 in diabetes. Similar findings were found for Blood Pressure (BP) recording: across the whole of the UK payment and population achievement rates for BP recording in MMI were also significantly reduced compared to payment and population achievement rates for the recording of BP in chronic kidney disease (CKD): payment rate: 94.1% IQR 90.9-97.1 vs.97.8% IQR 96.3-98.9 and p<0.001 and population achievement rate 87.0% IQR 81.3-91.7 vs. 97.1% IQR 95.5-98.4, p<0.001. Exception rates again were significantly higher for the recording of BP in MMI compared to CKD (6.4% IQR 3.0-13.1 vs. 0.3% IQR 0.0-1.0, p<0.001). There was also evidence of differences in rates of recording of BMI and BP in MMI across the UK. BMI and BP recording in MMI were significantly lower in Scotland compared to England (BMI:-1.5% 99% CI -2.7 to -0.3%, p<0.001 and BP: -1.8% 99% CI -2.7 to -0.9%, p<0.001). While rates of BMI and BP recording in diabetes and CKD were similar in Scotland compared to England (BMI: -0.5 99% CI -1.0 to 0.05, p=0.004 and BP: 0.02 99% CI -0.2 to 0.3, p=0.797). Data from the PsyCIS cohort showed an increase in Standardised Mortality Ratios (SMR) across the lifespan for individuals with MMI compared to the local Glasgow and wider Scottish populations (Glasgow SMR 1.8 95% CI 1.6-2.0 and Scotland SMR 2.7 95% CI 2.4-3.1). Increasing socioeconomic deprivation was associated with an increased overall rate of death in MMI (350.3 deaths/10,000 population/5 years in the least deprived quintile compared to 794.6 deaths/10,000 population/5 years in the most deprived quintile). No significant difference in rate of death for individuals with schizophrenia compared with bipolar disorder was reported (6.3% vs. 4.9%, p=0.086), but primary cause of death varied: with higher rates of suicide in individuals with bipolar disorder (22.4% vs. 11.7%, p=0.04). Discussion: Local and national datasets can be used for epidemiological study to inform local practice and complement existing national and international studies. While the strengths of this thesis include the large data sets used and therefore their likely representativeness to the wider population, some limitations largely associated with using secondary data sources are acknowledged. While this thesis has confirmed evidence of increased physical health comorbidity and multimorbidity in individuals with MMI, it is likely that these findings represent a significant under reporting and likely under recognition of physical health comorbidity in this population. This is likely due to a combination of patient, health professional and healthcare system factors and requires further investigation. Moreover, evidence of inequality in access to healthcare in terms of: physical health promotion (namely smoking cessation advice), recording of physical health indices (BMI and BP), prescribing of medications for the treatment of physical illness and prescribing of NRT has been found at a national level. While significant premature mortality in individuals with MMI within a Scottish setting has been confirmed, more work is required to further detail and investigate the impact of socioeconomic deprivation on cause and rate of death in this population. It is clear that further education and training is required for all healthcare staff to improve the recognition, diagnosis and treatment of physical health problems in this population with the aim of addressing the significant premature mortality that is seen. Conclusions: Future work lies in the challenge of designing strategies to reduce health inequalities and narrow the gap in premature mortality reported in individuals with MMI. Models of care that allow a much more integrated approach to diagnosing, monitoring and treating both the physical and mental health of individuals with MMI, particularly in areas of social and economic deprivation may be helpful. Strategies to engage this “hard to reach” population also need to be developed. While greater integration of psychiatric services with primary care and with specialist medical services is clearly vital the evidence on how best to achieve this is limited. While the National Health Service (NHS) is currently undergoing major reform, attention needs to be paid to designing better ways to improve the current disconnect between primary and secondary care. This should then help to improve physical, psychological and social outcomes for individuals with MMI.

Chromatographic analysis and survey studies to evaluate the emerging drugs of synthetic cannabinoids in Scotland and Saudi Arabia

Synthetic cannabinoid receptor agonists or more commonly known as synthetic cannabinoids (SCs) were originally created to obtain the medicinal value of THC but they are an emerging social problem. SCs are mostly produced coated on herbal materials or in powder form and marketed under a variety of brand names, e.g. “Spice”, “K2”. Despite many SCs becoming controlled under drug legislation, many of them remain legal in some countries around the world. In Scotland, SCs are controlled under the Misuse of Drugs Act 1971 and Psychoactive Substances Act 2016 that only cover a few early SCs. In Saudi Arabia, even fewer are controlled. The picture of the SCs-problem in Scotland is vague due to insufficient prevalence data, particularly that using biological samples. Whilst there is evidence of increasing use of SCs throughout the world, in Saudi Arabia, there is currently no data regarding the use of products containing SCs among Saudi people. Several studies indicate that SCs may cause serious toxicity and impairment to health therefore it is important to understand the scale of use within society. A simple and sensitive method was developed for the simultaneous analysis of 10 parent SCs (JWH-018, JWH-073, JWH-250, JWH-200, AM-1248, UR-144, A-796260, AB-FUBINACA, 5F-AKB-48 and 5F-PB-22) in whole blood and 8 corresponding metabolites (JWH-018 4-OH pentyl, JWH-073 3-OH butyl, JWH-250 4-OH pentyl, AM-2201 4-OH pentyl, JWH-122 5-OH pentyl, JWH-210 5-OH pentyl, 5F-AKB-48 (N-4 OH pentyl), 5F-PB-22 3-carboxyindole)in urine using LLE and LC-MS/MS. The method was validated according to the standard practices for method validation in forensic toxicology (SWGTOX, May 2013). All analytes gave acceptable precision, linearity and recovery for analysing blood and urine samples. The method was applied to 1,496 biological samples, a mixture of whole blood and urine. Blood and/or urine samples were analysed from 114 patients presenting at Accident and Emergency in Glasgow Royal Infirmary, in spring 2014 and JuneDecember 2015. 5F-AKB-48, 5F-PB-22 and MDMB-CHMICA were detected in 9, 7 and 9 cases respectively. 904 urine samples from individuals admitted to/liberated from Scottish prisons over November 2013 were tested for the presence of SCs. 5F-AKB-48 (N-4 OH pentyl) was detected in 10 cases and 5F-PB-22 3-carboxyindole in 3 cases. Blood and urine samples from two post-mortem cases in Scotland with suspected ingestion of SCs were analysed. Both cases were confirmed positive for 5F-AKB-48. A total of 463 urine samples were collected from personnel who presented to the Security Forces Hospital in Ryiadh for workplace drug testing as a requirement for their job during July 2014. The results of the analysis found 2 samples to be positive for 5F-PB-22 3carboxyindole. A further study in Saudi Arabia using a questionnaire was carried out among 3 subpopulations: medical professionals, members of the public in and around smoking cafes and known drug users. With regards to general awareness of Spice products, 16%, 11% and 22% of those participants of medical professionals, members of the public in and around smoking cafes and known drug users, respectively, were aware of the existence of SCs or Spice products. The respondents had an overall average of 4.5% who had a friend who used these Spice products. It is clear from the results obtained in both blood and urine testing and surveys that SCs are being used in both Scotland and Saudi Arabia. The extent of their use is not clear and the data presented here is an initial look into their prevalence. Blood and urine findings suggest changing trends in SC use, moving away from JWH and AM SCs to the newer 5F-AKB-48, 5-F-PB-22 and MDMBCHMICA compounds worldwide. In both countries 5F-PB-22 was detected. These findings clarify how the SCs phenomenon is a worldwide problem and how the information of every country regarding what SCs are seized can help and is not specific for that country. The analytes included in the method were selected due to their apparent availability in both countries, however it is possible that some newer analytes have been used and these would not have been detected. For this reason it is important that methods for testing SCs are updated regularly and evolve with the ever-changing availability of these drugs worldwide. In addition, there is little published literature regarding the concentrations of these drugs found in blood and urine samples and this work goes some way towards understanding these.