The increasing significance of disease severity in a burden of disease framework.

Recent estimates have reiterated that non-fatal causes of disease, such as low back pain, headaches and depressive disorders, are amongst the leading causes of disability-adjusted life years (DALYs). For these causes, the contribution of years lived with disability (YLD) - put simply, ill-health - is what drives DALYs, not mortality. Being able to monitor trends in YLD closely is particularly relevant for countries that sit high on the socio-demographic spectrum of development, as it contributes more than half of all DALYs. There is a paucity of data on how the population-level occurrence of disease is distributed according to severity, and as such, the majority of global and national efforts in monitoring YLD lack the ability to differentiate changes in severity across time and location. This raises uncertainties in interpreting these findings without triangulation with other relevant data sources. Our commentary aims to bring this issue to the forefront for users of burden of disease estimates, as its impact is often easily overlooked as part of the fundamental process of generating DALY estimates. Moreover, the wider health harms of the COVID-19 pandemic have underlined the likelihood of latent and delayed demand in accessing vital health and care services that will ultimately lead to exacerbated disease severity and health outcomes. This places increased importance on attempts to be able to differentiate by both the occurrence and severity of disease.

Widening of inequalities in COVID-19 years of life lost from 2020 to 2021: a Scottish Burden of Disease Study.

BACKGROUND: Previous studies have highlighted the large extent of inequality in adverse COVID-19 health outcomes. Our aim was to monitor changes in overall, and inequalities in, COVID-19 years of life lost to premature mortality (YLL) in Scotland from 2020 and 2021. METHODS: Cause-specific COVID-19 mortality counts were derived at age group and area deprivation level using Scottish death registrations for 2020 and 2021. YLL was estimated by multiplying mortality counts by age-conditional life expectancy from the Global Burden of Disease 2019 reference life table. Various measures of absolute and relative inequality were estimated for triangulation purposes. RESULTS: There were marked inequalities in COVID-19 YLL by area deprivation in 2020, which were further exacerbated in 2021; confirmed across all measures of absolute and relative inequality. Half (51%) of COVID-19 YLL was attributable to inequalities in area deprivation in 2021, an increase from 41% in 2020. CONCLUSION: Despite a highly impactful vaccination programme in preventing mortality, COVID-19 continues to represent a substantial area of fatal population health loss for which inequalities have widened. Tackling systemic inequalities with effective interventions is required to mitigate further unjust health loss in the Scottish population from COVID-19 and other causes of ill-health and mortality.

Measuring disability-adjusted life years (DALYs) due to COVID-19 in Scotland, 2020.

BACKGROUND: Disability-adjusted life years (DALYs) combine the impact of morbidity and mortality and can enable comprehensive, and comparable, assessments of direct and indirect health harms due to COVID-19. Our aim was to estimate DALYs directly due to COVID-19 in Scotland, during 2020; and contextualise its population impact relative to other causes of disease and injury. METHODS: National deaths and daily case data were used. Deaths were based on underlying and contributory causes recorded on death certificates. We calculated DALYs based on the COVID-19 consensus model and methods outlined by the European Burden of Disease Network. DALYs were presented as a range, using a sensitivity analysis based on Years of Life Lost estimates using: cause-specific; and COVID-19 related deaths. All COVID-19 estimates were for 2020. RESULTS: In 2020, estimates of COVID-19 DALYs in Scotland ranged from 96,500 to 108,200. Direct COVID-19 DALYs were substantial enough to be framed as the second leading cause of disease and injury, with only ischaemic heart disease having a larger impact on population health. Mortality contributed 98% of total DALYs. CONCLUSIONS: The direct population health impact of COVID-19 has been very substantial. Despite unprecedented mitigation efforts, COVID-19 developed from a single identified case in early 2020 to a condition with an impact in Scotland second only to ischaemic heart disease. Periodic estimation of DALYs during 2021, and beyond, will provide indications of the impact of DALYs averted due to the national rollout of the vaccination programme and other continued mitigation efforts, although new variants may pose significant challenges.

Inequalities in population health loss by multiple deprivation: COVID-19 and pre-pandemic all-cause disability-adjusted life years (DALYs) in Scotland.

BACKGROUND: COVID-19 has caused almost unprecedented change across health, education, the economy and social interaction. It is widely understood that the existing mechanisms which shape health inequalities have resulted in COVID-19 outcomes following this same, familiar, pattern. Our aim was to estimate inequalities in the population health impact of COVID-19 in Scotland, measured by disability-adjusted life years (DALYs) in 2020. Our secondary aim was to scale overall, and inequalities in, COVID-19 DALYs against the level of pre-pandemic inequalities in all-cause DALYs, derived from the Scottish Burden of Disease (SBoD) study. METHODS: National deaths and daily case data were input into the European Burden of Disease Network consensus model to estimate DALYs. Total Years of Life Lost (YLL) were estimated for each area-based deprivation quintile of the Scottish population. Years Lived with Disability were proportionately distributed to deprivation quintiles, based on YLL estimates. Inequalities were measured by: the range, Relative Index of Inequality (RII), Slope Index of Inequality (SII), and attributable DALYs were estimated by using the least deprived quintile as a reference. RESULTS: Marked inequalities were observed across several measures. The SII range was 2048 to 2289 COVID-19 DALYs per 100,000 population. The rate in the most deprived areas was around 58% higher than the mean population rate (RII = 1.16), with 40% of COVID-19 DALYs attributed to differences in area-based deprivation. Overall DALYs due to COVID-19 ranged from 7 to 20% of the annual pre-pandemic impact of inequalities in health loss combined across all causes. CONCLUSION: The substantial population health impact of COVID-19 in Scotland was not shared equally across areas experiencing different levels of deprivation. The extent of inequality due to COVID-19 was similar to averting all annual DALYs due to diabetes. In the wider context of population health loss, overall ill-health and mortality due to COVID-19 was, at most, a fifth of the annual population health loss due to inequalities in multiple deprivation. Implementing effective policy interventions to reduce health inequalities must be at the forefront of plans to recover and improve population health.

Population vulnerability to COVID-19 in Europe: a burden of disease analysis.

BACKGROUND: Evidence has emerged showing that elderly people and those with pre-existing chronic health conditions may be at higher risk of developing severe health consequences from COVID-19. In Europe, this is of particular relevance with ageing populations living with non-communicable diseases, multi-morbidity and frailty. Published estimates of Years Lived with Disability (YLD) from the Global Burden of Disease (GBD) study help to characterise the extent of these effects. Our aim was to identify the countries across Europe that have populations at highest risk from COVID-19 by using estimates of population age structure and YLD for health conditions linked to severe illness from COVID-19. METHODS: Population and YLD estimates from GBD 2017 were extracted for 45 countries in Europe. YLD was restricted to a list of specific health conditions associated with being at risk of developing severe consequences from COVID-19 based on guidance from the United Kingdom Government. This guidance also identified individuals aged 70 years and above as being at higher risk of developing severe health consequences. Study outcomes were defined as: (i) proportion of population aged 70 years and above; and (ii) rate of YLD for COVID-19 vulnerable health conditions across all ages. Bivariate groupings were established for each outcome and combined to establish overall population-level vulnerability. RESULTS: Countries with the highest proportions of elderly residents were Italy, Greece, Germany, Portugal and Finland. When assessments of population-level YLD rates for COVID-19 vulnerable health conditions were made, the highest rates were observed for Bulgaria, Czechia, Croatia, Hungary and Bosnia and Herzegovina. A bivariate analysis indicated that the countries at high-risk across both measures of vulnerability were: Bulgaria; Portugal; Latvia; Lithuania; Greece; Germany; Estonia; and Sweden. CONCLUSION: Routine estimates of population structures and non-fatal burden of disease measures can be usefully combined to create composite indicators of vulnerability for rapid assessments, in this case to severe health consequences from COVID-19. Countries with available results for sub-national regions within their country, or national burden of disease studies that also use sub-national levels for burden quantifications, should consider using non-fatal burden of disease estimates to estimate geographical vulnerability to COVID-19.

Correction to: Population vulnerability to COVID-19 in Europe: a burden of disease analysis.

[This corrects the article DOI: 10.1186/s13690-020-00433-y.].

Correction to: Prioritising the development of severity distributions in burden of disease studies for countries in the European region.

[This corrects the article DOI: 10.1186/s13690-019-0385-6.].

Prioritising the development of severity distributions in burden of disease studies for countries in the European region.

Severity distributions are a means of summarising the range of health loss suffered to disease which enables estimates of disease occurrence to be paired with disability weights to estimate Years Lost to Disability (YLD) in burden of disease studies. There is a lack of current data exploring severity distributions, which has led to the Global Burden of Disease (GBD) study relying on using the same severity distributions across countries and regions across the world. This is also largely true for some national studies, although there are exceptions. Recent evidence has raised concerns that severity distributions are unlikely to be generalisable as major differences arise when using country-specific data to develop severity distributions. These issues raise uncertainties over interpreting YLD estimates, particularly if they are being used to develop and influence policies and to determine priorities across diseases and populations. It is clear that GBD researchers and those carrying out national studies need to work towards ensuring that estimates are based upon country-specific data, and, if possible, that the impact of assumptions are fully tested and understood. There is a lack of strategy about if, where, and how, this could be achieved, particularly around how efforts should be prioritised. This commentary advocates and presents a possible strategic approach to better understanding how efforts may be best placed.

How do world and European standard populations impact burden of disease studies? A case study of disability-adjusted life years (DALYs) in Scotland.

BACKGROUND: Disability-Adjusted Life Years (DALYs) are an established method for quantifying population health needs and guiding prioritisation decisions. Global Burden of Disease (GBD) estimates aim to ensure comparability between countries and over time by using age-standardised rates (ASR) to account for differences in the age structure of different populations. Different standard populations are used for this purpose but it is not widely appreciated that the choice of standard may affect not only the resulting rates but also the rankings of causes of DALYs. We aimed to evaluate the impact of the choice of standard, using the example of Scotland. METHODS: DALY estimates were derived from the 2016 Scottish Burden of Disease (SBoD) study for an abridged list of 68 causes of disease/injury, representing a three-year annual average across 2014-16. Crude DALY rates were calculated using Scottish national population estimates. DALY ASRs standardised using the GBD World Standard Population (GBD WSP) were compared to those using the 2013 European Standard Population (ESP2013). Differences in ASR and in rank order within the cause list were summarised for all-cause and for each individual cause. RESULTS: The ranking of causes by DALYs were similar using crude rates or ASR (ESP2013). All-cause DALY rates using ASR (GBD WSP) were around 26% lower. Overall 58 out of 68 causes had a lower ASR using GBD WSP compared with ESP2013, with the largest falls occurring for leading causes of mortality observed in older ages. Gains in ASR were much smaller in absolute scale and largely affected causes that operated early in life. These differences were associated with a substantial change to the ranking of causes when GBD WSP was used compared with ESP2013. CONCLUSION: Disease rankings based on DALY ASRs are strongly influenced by the choice of standard population. While GBD WSP offers international comparability, within-country analyses based on DALY ASRs should reflect local age structures. For European countries, including Scotland, ESP2013 may better guide local priority setting by avoiding large disparities occurring between crude and age-standardised results sets, which could potentially confuse non-technical audiences.

The impact of worldwide, national and sub-national severity distributions in Burden of Disease studies: A case study of cancers in Scotland.

BACKGROUND: Increasingly Burden of Disease (BOD) measures are being used to influence policy decisions because they summarise the complete effects of morbidity and mortality in an equitable manner. An important element of producing non-fatal BOD estimates are severity distributions. The Global Burden of Disease (GBD) study use the same severity distributions across countries due to a lack of available country-specific data. In the Scottish BOD (SBOD) study we developed national severity distributions for cancer types. The main aim of this study was to consider the extent to which the use of worldwide severity distributions in BOD studies are influencing cross-country comparisons, by comparing weighted-average disability weights (DW) based on GBD severity distributions with nationally derived severity distributions in Scotland for cancer types. METHODS: We obtained individual records from the Scottish Cancer Registry for 21 cancer types and linked these to registered deaths. We estimated prevalent cancer cases for 2016 and assigned each case to sequelae using GBD 2016 study definitions. We compared the impact of using severity distributions based on GBD 2016, a Scotland-wide distribution, and distributions specific to deprivation strata in Scotland, on the weighted-average DW for each cancer type. RESULTS: The relative difference in point estimates of weighted-average DW based on GBD 2016 worldwide severity distributions compared with Scottish national severity distributions resulted in overestimates in the majority of cancers (17 out of 21 cancer types). The largest overestimates were for gallbladder and biliary tract cancer (70.8%), oesophageal cancer (31.6%) and pancreatic cancer (31.2%). Furthermore, the use of weighted-average DW based on Scottish national severity distributions rather than sub-national Scottish severity distributions stratified by deprivation quintile overestimated weighted-average DW in the least deprived areas (16 out of 18 cancer types), and underestimated in the most deprived areas (16 out of 18 cancer types). CONCLUSION: Our findings illustrate a bias in point estimates of weighted-average DW created using worldwide severity distributions. This bias would have led to the misrepresentation of non-fatal estimates of the burden of individual cancers, and underestimated the scale of socioeconomic inequality in this non-fatal burden. This highlights the importance of not interpreting non-fatal estimates of burden of disease too precisely, especially for sub-national estimates and those comparing populations when relying on data inputs from other countries. It is essential to ensure that any estimates are based upon country-specific data as far as possible.

Breastfeeding is associated with reduced childhood hospitalization: evidence from a Scottish Birth Cohort (1997-2009).

OBJECTIVE: To evaluate the risk of childhood hospitalization associated with infant feeding patterns at 6-8 weeks of age in Scotland. STUDY DESIGN: A retrospective population level study based on the linkage of birth, death, maternity, infant health, child health surveillance, and admission records for children born as single births in Scotland between 1997 and 2009 (n = 502 948) followed up to March 2012. Descriptive analyses, Kaplan Meier tests, and Cox regression were used to quantify the association between the mode of infant feeding and risk of childhood hospitalization for respiratory, gastrointestinal, and urinary tract infections, and other common childhood ailments during the study period. RESULTS: Within the first 6 months of life, there was a greater hazard ratio (HR) of hospitalization for common childhood illnesses among formula-fed infants (HR 1.40; 95% CI 1.35-1.45) and mixed-fed infants (HR 1.18; 95% CI 1.11-1.25) compared with infants exclusively breastfed after adjustment for parental, maternal, and infant health characteristics. Within the first year of life and beyond, a greater relative risk of hospitalization was observed among formula-fed infants for a range of individual illnesses reported in childhood including gastrointestinal, respiratory, and urinary tract infections, otitis media, fever, asthma, diabetes, and dental caries. CONCLUSIONS: Using linked administrative data, we found greater risks of hospitalization in early childhood for a range of common childhood illnesses among Scottish infants who were not exclusively breastfed at 6-8 weeks of age.

Risk of skin cancer after neonatal phototherapy: retrospective cohort study.

OBJECTIVE: To assess the risk of skin cancer in persons treated with neonatal phototherapy (NNPT) for jaundice. DESIGN: Retrospective cohort study. SETTING: Grampian Region, Scotland, UK. DATA SOURCE: Aberdeen Maternity and Neonatal Databank. NNPT exposure was abstracted from paper records spanning 1976-1990. Follow-up to 31 December 2006 by linkage to cancer registration and mortality records. MAIN OUTCOME MEASURES: Incidence ratios, standardised for age, sex, calendar period and socio-economic position. RESULTS: After excluding neonatal deaths (n=435), the cohort comprised 77,518 persons. 5868 Received NNPT, providing 138,000 person-years at risk (median follow-up, 24 years). Two cases of melanoma occurred in persons exposed to NNPT versus 16 cases in unexposed persons, yielding a standardised incidence ratio of 1.40 (95% CI, 0.17 to 5.04; p=0.834). No cases of squamous cell or basal cell carcinoma of skin were observed in exposed persons. CONCLUSIONS: Although there is no statistically significant evidence of an excess risk of skin cancer following NNPT, limited statistical power and follow-up duration mean it is not possible categorically to rule out an effect. However, taken in conjunction with the results of the only other study to investigate risk of melanoma following NNPT, evidence available so far does not suggest a major cause for concern.

Ascertainment of breast cancer by the Scottish Cancer Registry: an assessment based on comparison with five independent breast cancer trials databases.

Completeness of ascertainment of breast cancer cases by the Scottish Cancer Registry (SCR) was assessed by independent comparison with five clinical trials databases, comprising 2621 patients and spanning the total period of diagnosis 1978-2000. Overall, ascertainment was estimated to exceed 98%, although 0.3% of matched cases were misclassified as carcinoma in situ by the SCR. These results support the validity of national estimates of incidence of, and survival from, breast cancer in Scotland.

Risk of breast cancer after miscarriage or induced abortion: a Scottish record linkage case-control study.

STUDY OBJECTIVE: To assess the risk of breast cancer in patients with a previous history of miscarriage or induced abortion. DESIGN: Case-control study relating "exposure" to outcome by linkage of national hospital discharge and maternity records, the national cancer registry, and death records. SETTING: Scotland. PARTICIPANTS: Miscarriage analysis-2828 women with breast cancer and 9781 matched controls; induced abortion analysis-2833 women with breast cancer and 9888 matched controls. MAIN RESULTS: After stratification for age at diagnosis, parity, and age at first birth, the odds ratio (95% confidence intervals) of breast cancer was 1.02 (0.88 to 1.18) in women with a previous miscarriage, and 0.80 (0.72 to 0.89) in women with a previous induced abortion. Further adjustments for age at bilateral oophorectomy, socioeconomic status (based on small area of residence), and health board area of residence had only minor effects on these odds ratios. CONCLUSION: These data do not support the hypothesis that miscarriage or induced abortion represent substantive risk factors for the future development of breast cancer.

Changing trends in incidence and mortality of thyroid cancer in Scotland.

OBJECTIVE: The incidence of thyroid cancer is increasing in several countries. The aim was to investigate trends in the incidence and mortality of thyroid cancer in Scotland, where thyroid cancer is relatively uncommon, between 1960 and 2002. DESIGN: Descriptive epidemiological study. METHODS: Thyroid cancer registrations between 1960 and 2000 were obtained from the Scottish Cancer Registry. Mortality data (1960-2002) and population estimates were supplied by the Registrar General for Scotland. Incidence and mortality data are expressed as age-specific rates and European age-standardized rates (EASRs). RESULTS: Thyroid cancer was three times more common in females than in males and was more common in older than younger age groups. Between 1960 and 2000, the annual EASR of thyroid cancer increased from 1.76 to 3.54 per 100,000 for females (P < 0.001) and from 0.83 to 1.25 per 100,000 in males (P < 0.001). The overall thyroid cancer increase between 1975 and 2000 was primarily caused by an increase in papillary thyroid cancer, particularly over the most recent decade. The incidence of follicular thyroid cancer also increased while the incidence of anaplastic and medullary thyroid cancer did not change significantly. Mortality from thyroid cancer fell progressively between 1960 and 2002. EASR for females decreased from 1.05 to 0.28 (P < 0.001) and in males from 0.73 to 0.34 (P < 0.001). For both sexes, in general, survival at 1-, 5- and 10-year follow-up intervals from diagnosis improved steadily over the study period. In both females and males, survival from thyroid cancer was better if the diagnosis was made under the age of 50 years. CONCLUSIONS: Thyroid cancer incidence has increased in Scotland over the past 40 years. This is accompanied by a change in the distribution of histological type with a particular increase in papillary carcinoma. The reasons for this may relate partly to changes in clinical practice and histological criteria. Falling mortality in the face of increasing incidence reflects improvements in survival, which should improve further with the introduction and implementation of standardized treatment protocols.