Effectiveness of the population-based Check your health preventive programme conducted in primary care with 4 years follow-up [the CORE trial]: study protocol for a randomised controlled trial

BACKGROUND: The periodic health check-up has been a fundamental part of routine medical practice for decades, despite a lack of consensus regarding its value in health promotion and disease prevention. A large-scale Danish population-based preventive programme ‘Check your health’ was developed based on available evidence of screening and successive accepted treatment, prevention for diseases and health promotion, and is closely aligned with the current health care system. The objective of the ‘Check your health’ [CORE] trial is to investigate effectiveness on health outcomes of a preventive health check offered at a population-level to all individuals aged 30–49 years, and to establish the cost-effectiveness. METHODS/DESIGN: The trial will be conducted as a pragmatic household-cluster randomised controlled trial involving 10,505 individuals. All individuals within a well-defined geographical area in the Central Denmark Region, Denmark (DK) were randomised to be offered a preventive health check (Intervention group, n = 5250) or to maintain routine access to healthcare until a delayed intervention (Comparison group, n = 5255). The programme consists of a health examination which yields an individual risk profile, and according to this participants are assigned to one of the following interventions: (a) referral to a health promoting consultation in general practice, (b) behavioural programmes at the local Health Centre, or (c) no need for follow-up. The primary outcomes at 4 years follow-up are: ten-year-risk of fatal cardiovascular event (Heart-SCORE model), physical activity level (self-report and cardiorespiratory fitness), quality of life (SF12), sick leave and labour market attachment. Cost-effectiveness will be evaluated according to life years gained, direct costs and total health costs. Intention to treat analysis will be performed. DISCUSSION: Results from the largest Danish health check programme conducted within the current healthcare system, spanning the sectors which share responsibility for the individual, will provide a scientific basis to be used in the development of systems to optimise population health in the 21st century. TRIAL REGISTRATION: The trial has registered at ClinicalTrials.gov with an ID: NCT02028195 (7. March 2014)

Quantifying the impact of unmeasured confounding in observational studies with the E value

The E value method deals with unmeasured confounding, a key source of bias in observational studies. The E value method is described and its use is shown in a worked example of a meta-analysis examining the association between the use of antidepressants in pregnancy and the risk of miscarriage

Trends in cause-specific mortality among people with type 2 and type 1 diabetes from 2002 to 2019:A Danish population-based study

BackgroundDespite advances in primary and secondary prevention of cardiovascular disease,excess mortality persists within the diabetes population. This study explores thecomponents of this excess mortality and their interaction with sex.MethodsUsing Danish registries (2002-2019), we identified residents aged 18-99 years, theirdiabetes status, and recorded causes of death. Applying Lexis-based methods, wecomputed age-standardized mortality rates (asMRs), mortality relative risks (asMRRs),and log-linear trends for cause-specific mortality.FindingsFrom 2002-2019, 958,278 individuals died in Denmark (T2D: 148,620; T1D: 7,830)during 84.4M person-years. During the study period, overall asMRs declined, driven byreducing cardiovascular mortality, notably in men with T2D. Conversely, cancermortality remained high, making cancer the leading cause of death in individuals withT2D. Individuals with T2D faced an elevated mortality risk from nearly all cancer types,ranging from 9% to 257% compared to their non-diabetic counterparts. Notably,obesity-related cancers exhibited the highest relative risks: liver cancer (Men: asMRR3·58(3·28;3·91); Women: asMRR 2·49(2·14;2·89)), pancreatic cancer (Men: asMRR3·50(3·25;3·77); Women: asMRR 3·57(3·31;3·85)), and kidney cancer (Men: asMRR2·10(1·84;2·40); Women: asMRR 2·31(1·92;2·79)). In men with type 2 diabetes, excessmortality remained stable, except for dementia. In women, diabetes-related excessmortality increased by 6-17% per decade across all causes of death, exceptcardiovascular disease.InterpretationIn the last decade, cancer has emerged as the leading cause of death amongindividuals with T2D in Denmark, emphasizing the need for diabetes managementstrategies incorporating cancer prevention. A sex-specific approach is crucial toaddress persistently higher relative mortality in women with diabetes.FundingSupported by Steno Diabetes Center Aarhus, which is partially funded by anunrestricted donation from the Novo Nordisk Foundation, and by The Danish DiabetesAcademy.<br/

A new approach of nonparametric estimation of incidence and lifetime risk based on birth rates and incident events

<p>Abstract</p> <p>Background</p> <p>Incidence and lifetime risk of diabetes are important public health measures. Traditionally, nonparametric estimates are obtained from survey data by means of a Nelson-Aalen estimator which requires data information on both incident events and risk sets from the entire cohort. Such data information is rarely available in real studies.</p> <p>Methods</p> <p>We compare two different approaches for obtaining nonparametric estimates of age-specific incidence and lifetime risk with emphasis on required assumptions. The first and novel approach only considers incident cases occurring within a fixed time window–we have termed this <it>cohort-of-cases </it>data–which is linked explicitly to the birth process in the past. The second approach is the usual Nelson-Aalen estimate which requires knowledge on observed time at risk for the entire cohort and their incident events. Both approaches are used on data on anti-diabetic medications obtained from Odense Pharmacoepidemiological Database, which covers a population of approximately 470,000 over the period 1993–2003. For both methods we investigate if and how incidence rates can be projected.</p> <p>Results</p> <p>Both the new and standard method yield similar sigmoidal shaped estimates of the cumulative distribution function of age-specific incidence. The Nelson-Aalen estimator gives somewhat higher estimates of lifetime risk (15.65% (15.14%; 16.16%) for females, and 17.91% (17.38%; 18.44%) for males) than the estimate based on cohort-of-cases data (13.77% (13.74%; 13.81%) for females, 15.61% (15.58%; 15.65%) for males). Accordingly the projected incidence rates are higher based on the Nelson-Aalen estimate–also too high when compared to observed rates. In contrast, the cohort-of-cases approach gives projections that fit observed rates better.</p> <p>Conclusion</p> <p>The developed methodology for analysis of cohort-of-cases data has potential to become a cost-effective alternative to a traditional survey based study of incidence. To allow more general use of the methodology, more research is needed on how to relax stationarity assumptions.</p

Medication effectiveness may not be the major reason for accepting cardiovascular preventive medication: A population-based survey

Background: Shared decision-making and patients’ choice of interventions are areas of increasing importance, not least seen in the light of the fact that chronic conditions are increasing, interventions considered important for public health, and still non-acceptance of especially risk-reducing treatments of cardiovascular diseases (CVD) is prevalent. A better understanding of patients’ medication-taking behavior is needed and may be reached by studying the reasons why people accept or decline medication recommendations. The aim of this paper was to identify factors that may influence people’s decisions and reasoning for accepting or declining a cardiovascular preventive medication offer. Methods: From a random sample of 4,000 people aged 40–59 years in a Danish population, 1,169 participants were asked to imagine being at increased risk of cardiovascular disease and being offered a preventive medication. After receiving ‘complete’ information about effectiveness of the medication they were asked whether they would accept medication. Finally, they were asked about reasons for the decision. Results: A total of 725 (67%) of 1,082 participants accepted the medication offer. Even quite large effects of medication (up to 8 percentage points absolute risk reduction) had a smaller impact on acceptance to medication than personal experience with cardiovascular disease. Furthermore, increasing age of the participant and living with a partner were significantly associated with acceptance. Some 45% of the respondents accepting justified their choice as being for health reasons, and they were more likely to be women, live alone, have higher income and higher education levels. Among those who did not accept the medication offer, 56% indicated that they would rather prefer to change lifestyle. Conclusions: Medication effectiveness seems to have a moderate influence on people’s decisions to accept preventive medication, while factors such as personal experience with cardiovascular disease may have an equally strong or stronger influence, indicating that practitioners could do well to carefully identify the reasons for their patients’ treatment decisions

Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756