Background: In settings with large case detection gaps, active case-finding (ACF) may play a critical role in the uberculosis (TB) response. However, ACF is resource intensive, and its effectiveness depends on whether people detected with TB through ACF might otherwise spontaneously resolve or be diagnosed through routine care. We analysed the potential effectiveness of ACF for TB relative to the counterfactual scenario of routine care alone.
Methods: We constructed a Markov simulation model of TB natural history, diagnosis, symptoms, ACF and treatment, using a hypothetical reference setting using data from South East Asian countries. We calibrated the model to empirical data using Bayesian methods, and simulated potential 5-year outcomes with an 'aspirational' ACF intervention (reflecting maximum possible effectiveness) compared with the standard-of-care outcomes.
Results: Under the standard of care, 51% (95% credible interval, CrI: 31%, 75%) of people with prevalent TB at baseline were estimated to be diagnosed and linked to care over 5 years. With aspirational ACF, this increased to 88% (95% CrI: 84%, 94%). Most of this difference represented people who were diagnosed and treated through ACF but experienced spontaneous resolution under standard-of-care. Aspirational ACF was projected to reduce the average duration of TB disease by 12 months (95% CrI: 6%, 18%) and TB-associated disability-adjusted life-years by 71% (95% CrI: 67%, 76%).
Conclusion: These data illustrate the importance of considering outcomes in a counterfactual standard of care scenario, as well as trade-offs between overdiagnosis and averted morbidity through earlier diagnosis-not just for TB, but for any disease in which population-based screening is recommended.
Background: Most previous studies of rheumatoid arthritis (RA) and cancer risk have lacked information on potential confounding factors. We investigated RA-associated cancer risks in a large cohort of women in the UK, taking account of shared risk factors.
Methods: In 1996-2001, women aged 50-64, who were invited for routine breast screening at 66 National Health Service (NHS) screening centres in England and Scotland, were also invited to take part in the Million Women Study. Participants provided information on sociodemographic, lifestyle and health-related factors, including RA, and were followed up for cancers and deaths. Cox regression yielded RA-associated hazard ratios (HRs) of 20 cancers, adjusted for 10 characteristics including smoking status and adiposity.
Results: Around 1.3 million women (half of those invited) were recruited into the study. In minimally adjusted analyses, RA was associated with the risk of 13 of the 20 cancers. After additional adjustment for lifestyle factors, many of these associations were attenuated but there remained robust evidence of RA-associated increases in the risk of lung (HR 1.21, 95% confidence interval 1.15-1.26), lymphoid (1.25, 1.18-1.33), myeloid (1.12, 1.01-1.25), cervical (1.39, 1.11-1.75) and oropharyngeal (1.40, 1.21-1.61) cancers, and decreases in the risk of endometrial (0.84, 0.77-0.91) and colorectal (0.82, 0.77-0.87) cancers.
Conclusions: After taking account of shared risk factors, RA is positively associated with lung and certain blood and infection-related cancers, and inversely associated with colorectal cancer. These findings are consistent with existing hypotheses around immune response, susceptibility to infections, and chronic inflammation. The inverse association observed for endometrial cancer merits further investigation.
Background: Rising midlife mortality in the USA has raised concerns, particularly the increase in 'deaths of despair' (due to drugs, alcohol and suicide). Life expectancy is also stalling in other countries such as the UK, but how trends in midlife mortality are evolving outside the USA is less understood. We provide a synthesis of cause-specific mortality trends in midlife (25-64 years of age) for the USA and the UK as well as other high-income and Central and Eastern European (CEE) countries.
Methods: We document trends in midlife mortality in the USA, UK and a group of 13 high-income countries in Western Europe, Australia, Canada and Japan, as well as seven CEE countries from 1990 to 2019. We use annual mortality data from the World Health Organization Mortality Database to analyse sex- and age-specific (25-44, 45-54 and 55-64 years) age-standardized death rates across 15 major cause-of-death categories.
Results: US midlife mortality rates have worsened since 1990 for several causes of death including drug-related, alcohol-related, suicide, metabolic diseases, nervous system diseases, respiratory diseases and infectious/parasitic diseases. Deaths due to homicide, transport accidents and cardiovascular diseases have declined since 1990 but saw recent increases or stalling of improvements. Midlife mortality also increased in the UK for people aged 45-54 year and in Canada, Poland and Sweden among for those aged 25-44 years.
Conclusions: The USA is increasingly falling behind not only high-income, but also CEE countries, some of which were heavily impacted by the post-socialist mortality crisis of the 1990s. Although levels of midlife mortality in the UK are substantially lower than those in the USA overall, there are signs that UK midlife mortality is worsening relative to that in Western Europe.
Background: Attempts at assessing heterogeneity in countries' mortality profiles often rely on measures of cause of death (CoD) diversity. Unfortunately, such indicators fail to take into consideration the degree of (dis)similarity among pairs of causes (e.g. 'transport injuries' and 'unintentional injuries' are implicitly assumed to be as dissimilar as 'transport injuries' and 'Alzheimer's disease')-an unrealistic and unduly restrictive assumption.
Development: We extend diversity indicators proposing a broader class of heterogeneity measures that are sensitive to the similarity between the causes of death one works with. The so-called 'CoD inequality' measures are defined as the average expected 'dissimilarity between any two causes of death'. A strength of the approach is that such measures are decomposable, so that users can assess the contribution of each cause to overall CoD heterogeneity levels-a useful property for the evaluation of public health policies.
Application: We have applied the method to 15 low-mortality countries between 1990 and 2019, using data from the Global Burden of Disease project. CoD inequality and CoD diversity generally increase over time across countries and sex, but with some exceptions. In several cases (notably, Finland), both indicators run in opposite directions.
Conclusions: CoD inequality and diversity indicators capture complementary information about the heterogeneity of mortality profiles, so they should be analysed alongside other population health metrics, such as life expectancy and lifespan inequality.