Using large-scale syndromic datasets to support epidemiology and surveillance

Using large-scale syndromic datasets to support epidemiology and surveillance Healthcare and the healthcare industry have traditionally produced huge amounts of data and information; patient care necessitates accurate record keeping, records of attendances and often details of the reason for contact with healthcare and outcomes.7 During the past decade, there has been a dramatic shift to digitize healthcare related information, with a view to both increasing efficiencies in these areas, and to generate new insights.8 These rich, but often unstructured data sources can present both opportunities and challenges to data scientists and epidemiologists. Syndromic surveillance (SS) is the real-time (or near real-time) collection, analysis, interpretation, and dissemination of health-related data to enable the early identification of the impact (or absence of impact) of potential human or veterinary public-health threats which require effective public-health action.9 In England, Public Health England (PHE) coordinates a suite of national real-time syndromic surveillance systems. Underpinning their operation is the collation, analysis and interpretation of large-scale datasets (“big data”). This PhD by Published Works describes work which has evaluated, developed or utilised a number of these large healthcare datasets for both surveillance and epidemiology of public health events. The thesis is divided into four themes covering critical aspects of SS. Firstly, developing SS systems using novel data sources; something which is currently under-reported in the literature. Secondly, using syndromic data systems for non-infectious disease epidemiology; understanding how these systems can inform public health insight and action outside of their original remit. Thirdly, determining the utility in identifying outbreaks which was one of the original envisioned purposes of SS, using gastrointestinal illness (GI) as a case-study. The final theme is understanding how SS is used in the context of mass gatherings; again, a key original aspect of syndromic surveillance. The thesis collates a portfolio of indexed works, all of which use (combined with other data sources) large, health-related data collated and operated by the PHE Real-Time Syndromic Surveillance Team (ReSST) and employ a range of different methodologies to translate data into public health action. These include describing the development of a novel system, observational studies and time series analysis. Key findings from the papers include; learning how to develop these systems, demonstration of their utility in non-infectious disease epidemiology, leading to new insights into the socio-demographic distribution and causes of presentations to healthcare with Allergic Rhinitis, understanding the challenges and limitations of syndromic surveillance in identifying outbreaks of GI disease and how they can be used during mass gatherings. Using diverse methodologies and data as a collective, the papers have led to significant public health impacts; both in terms of how these systems are used in England currently and how they have influenced global development of this small but growing specialit

Extending the diabetic retinopathy screening interval beyond 1 year : systematic review

To determine whether the recommended screening interval for diabetic retinopathy (DR) in the UK can safely be extended beyond 1 year. Systematic review of clinical and cost-effectiveness studies. Nine databases were searched with no date restrictions. Randomised controlled trials (RCTs), cohort studies, prognostic or economic modelling studies which described the incidence and progression of DR in populations with type 1 diabetes mellitus or type 2 diabetes mellitus of either sex and of any age reporting incidence and progression of DR in relation to screening interval (vs annual screening interval) and/or prognostic factors were included. Narrative synthesis was undertaken. 14 013 papers were identified, of which 11 observational studies, 5 risk stratification modelling studies and 9 economic studies were included. Data were available for 262 541 patients of whom at least 228 649 (87%) had type 2 diabetes. There were no RCTs. Studies concluded that there is little difference between clinical outcomes from screening 1 yearly or 2 yearly in low-risk patients. However there was high loss to follow-up (13–31%), heterogeneity in definitions of low risk and variation in screening and grading protocols for prior retinopathy results. Observational and economic modelling studies in low-risk patients show little difference in clinical outcomes between 1-year and 2-year screening intervals. The lack of experimental research designs and heterogeneity in definition of low risk considerably limits the reliability and validity of this conclusion. Cost-effectiveness findings were mixed. There is insufficient evidence to recommend a move to extend the screening interval beyond 1 year

Potential excess spend in primary care due to NHS drug tariff variability in vitamin D preparations

Objectives Vitamin D is commonly prescribed in primary care for the prevention and treatment of deficiency and for maintenance after treatment (although supplementation for maintenance and prevention can be bought over-the-counter). There is wide variation in the costs to the NHS in England of oral preparations of vitamin D, even for a single-specific dose and route.1 It is possible that the availability of multiple options for the same intended medicine, the costs of which are unlikely to be known by the prescriber, could result in an inadvertent excess spend. We aimed to estimate the annual cost-saving if only the cheapest vitamin D preparations were prescribed. Design Primary care prescribing data for 2018 were downloaded from NHS Digital (https://digital.nhs.uk).2 Monthly datasets include the number of items, quantity and cost of each drug prescribed and dispensed. Private prescriptions are not recorded. All prescription items relating to the vitamin D preparations colecalciferol and ergocalciferol, regardless of dose, route or manufacturer, were extracted. Data for each specific preparation were aggregated across all practices and all months to give the annual number of items and their cost across England. All liquid and injectable preparations were assumed to be appropriately prescribed and therefore excluded from the analysis. Combined preparations – such as calcium/vitamin D, calcium/alendronate and multivitamins – were also excluded. For each defined dose range of vitamin D, the lowest cost preparation was identified, and the potential cost-savings if only these preparations were prescribed was calculated. Setting Primary care in England. Participants All patients registered with a general practitioner in England in 2018. Main Outcome Measure The difference between actual and potential spend on vitamin D prescriptions, if only the lowest priced preparation were available. Results In 2018, over 4 million vitamin D items were prescribed in primary care, at a cost of over £21 million. If only the cheapest options were prescribed for non-liquid preparations across all dose ranges, and assuming all prescriptions were appropriate, it would have resulted in an approximate £15 million (>70%) cost-saving to the NHS. Maintenance doses of vitamin D (designated as 800 to 2000 international units per day as per NICE guidelines3) accounted for more than half of the spend (∼£12 million). It was noted that all the cheapest options available are suitable for vegetarians. Conclusion The prescribing of more expensive vitamin D preparations in primary care may have significant financial consequences, although our results relate to a single year of prescribing within NHS primary care. Since choice of preparation may intentionally be based on factors other than cost (e.g. dietary requirements, bioavailability, what was initially prescribed by a hospital), work is needed nationally to rationalise available prescribing options. If national guidance were produced, the difficulties of implementation within individual Clinical Commissioning Groups might limit economic benefit. National efficient procurement strategies are an alternative approach, but require careful consideration of legislative frameworks (such as the Public Contract Regulations 20154) with safeguards to prevent horizontal cooperation between suppliers

Socioeconomic status and HRT prescribing : a study of practice-level data in England

Background Concerns have been raised that women from deprived backgrounds are less likely to be receiving hormone replacement therapy (HRT) treatment and its benefits, although evidence in support of this is lacking. Aim To investigate general practice HRT prescription trends and their association with markers of socioeconomic deprivation. Design Cross-sectional study of primary care prescribing data in England in 2018. Method Practice-level prescribing rate was defined as the number of items of HRT prescribed per 1000 registered female patients over the age of 40 years. The association between Index of Multiple Deprivation (IMD) score and HRT prescribing rate was tested using multivariate Poisson regression, adjusting for practice proportions of obesity, smoking, hypertension, diabetes, coronary heart disease and cerebrovascular disease and practice list size. Results The overall prescribing rate of HRT was 29% lower in practices from the most deprived quintile compared with the most affluent (incidence rate ratio [IRR] 0.71, 95% CI 0.68-0.73). After adjusting for all cardiovascular disease outcomes and risk factors, the prescribing rate in the most deprived quintile was still 18% lower than in the least deprived quintile (adjusted IRR 0.82, 95% CI 0.77-0.86). In more deprived practices, there was a significantly higher tendency to prescribe oral HRT than transdermal preparations (p < 0.001). Conclusion This study has highlighted inequalities associated with HRT prescription. This may reflect a large unmet need in terms of menopause care in areas of deprivation. Further research is needed to identify the factors from patient and GP perspectives that may explain this

Socioeconomic status and benzodiazepine and Z-drug prescribing : a cross-sectional study of practice-level data in England

Background Benzodiazepines and Z-drugs (such as zopiclone) are widely prescribed in primary care. Given their association with addiction and dependence, understanding where and for whom these medications are being prescribed is a necessary step in addressing potentially harmful prescribing. Objective To determine whether there is an association between primary care practice benzodiazepine and Z-drug prescribing and practice population socioeconomic status in England. Methods This was a cross-sectional study. An aggregated data set was created to include primary care prescribing data for 2017, practice age and sex profiles and practice Index of Multiple Deprivation (IMD) scores—a marker of socioeconomic status. Drug doses were converted to their milligram-equivalent of diazepam to allow comparison. Multiple linear regression was used to examine the association between IMD and prescribing (for all benzodiazepines and Z-drugs in total, and individually), adjusting for practice sex (% male) and older age (>65 years) distribution (%). Results Benzodiazepine and Z-drug prescribing overall was positively associated with practice-level IMD score, with more prescribing in practices with more underserved patients, after adjusting for age and sex (P < 0.001), although the strength of the association varied by individual drug. Overall, however, IMD score, age and sex only explained a small proportion of the overall variation in prescribing across GP practices. Conclusion Our findings may, in part, be a reflection of an underlying association between the indications for benzodiazepine and Z-drug prescribing and socioeconomic status. Further work is required to more accurately define the major contributors of prescribing variation

Associations between socioeconomic deprivation and pharmaceutical prescribing in primary care in England

Background Socioeconomic deprivation is associated with health inequality. Previous studies have described associations between primary care prescribing rates and deprivation for individual drugs or drug classes. We explore the correlation between socioeconomic deprivation and the rate of prescribing of individual pharmaceutical drugs, and drug classes, in primary care in England, to identify prescribing inequalities that would require further investigation. Methods In this cross-sectional study, national primary care prescribing data, by GP practice, were retrieved for the calendar year 2019 in England. Socioeconomic deprivation was quantified using the Index of Multiple Deprivation (IMD) score. Correlations were calculated using Spearman’s rank correlation coefficient (), adjusting for practice list size and demographics, with a Bonferroni-corrected p value threshold of 5x10-5. Results We included 1.05 billion prescription items dispensed from 6896 England practices. 142/206 (69%) drug classes and 505/774 (65%) drugs were significantly correlated with IMD score (p0.4). Only one was moderately negatively correlated with IMD score (< -0.4), suggesting higher prescribing rates in more affluent areas. The drug classes most strongly associated with IMD score included opioid and non-opioid analgesics, antipsychotics and reflux medications. Drug classes most strongly associated with affluence included adrenaline, combined oral contraceptives and hormone replacement therapy. Conclusion We identify novel associations of prescribing with deprivation. Further work is required to identify the underlying reasons for these associations so that appropriate interventions can be formulated to address drivers of inequality

Pertussis immunisation strategies to optimise infant pertussis control : a narrative systematic review

Objective Countries routinely offering acellular pertussis vaccine, where long-term protection is not sustained, have the challenge of selecting an optimal schedule to minimise disease among young infants. We conducted a narrative systematic review and synthesis of information to evaluate different pertussis immunisation strategies at controlling pertussis disease, hospitalisation, deaths, and vaccine effectiveness among young infants. Methods We conducted a review of the literature on studies about the primary, booster, and/or maternal vaccination series and synthesised findings narratively. Countries offering the first three doses of vaccine within six-months of life and a booster on or before the second year or life were defined as accelerated primary and booster schedules, respectively. Countries offering primary and booster doses later were defined as extended primary and booster schedules. All search results were screened, and articles reviewed and reconciled, by two authors. The Risk of Bias in Non-randomised Studies of Intervention tool was used to evaluate the risk of bias. Findings A total of 98 studies were included in the analyses and the following recurring themes were described: timing of vaccination, vaccine coverage, waning immunity/vaccine effectiveness, direct and indirect effectiveness, switching from an accelerated to extended schedule, impact of changes in testing. The risk of bias was generally low to moderate for most studies. Conclusion Comparing schedules is challenging and there was insufficient evidence to that one schedule was superior to another. Countries must select a schedule that maintains high vaccine coverage and reduced the risk of delaying the delivery vaccines to protect infants

The Epidemiology of Chickenpox in England, 2016-2022: An Observational Study Using General Practitioner Consultations.

Chickenpox is a common childhood disease caused by varicella-zoster virus (VZV). VZV vaccination is not part of the UK childhood immunisation programme, but its potential inclusion is regularly assessed. It is therefore important to understand the ongoing burden of VZV in the community to inform vaccine policy decisions. General practitioner (GP) chickenpox consultations were studied from 1 September 2016 to 9 December 2022. Over the study period, the mean weekly chickenpox consultation rate per 100,000 population in England was 3.4, with a regular peak occurring between weeks 13 and 15. Overall, rates decreased over time, from a mean weekly rate of 5.5 in 2017 to 4.2 in 2019. The highest mean weekly rates were among children aged 1-4 years. There was no typical epidemic peak during the COVID-19 pandemic, but in 2022, rates were proportionally higher among children aged < 1 year old compared to pre-pandemic years. Chickenpox GP consultation rates decreased in England, continuing a longer-term decline in the community. The COVID-19 pandemic impacted rates, likely caused by the introduction of non-pharmaceutical interventions to prevent SARS-CoV-2 transmission. The lasting impact of the interruption of typical disease transmission remains to be seen, but it is important to monitor the chickenpox burden to inform decisions on vaccine programmes