Methodology of the brodalumab assessment of hazards: a multicentre observational safety (BRAHMS) study.

INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.

Socioeconomic Status And Acute Stroke Care: Has The Inequality Gap Been Closed?

PURPOSE: Socioeconomic inequality in stroke care occurs even in countries with free access to health care. We aimed to investigate the association between socioeconomic status and guideline-recommended acute care in Denmark during the last decade. DESIGN: We conducted a nationwide, population-based study. We used household income, employment status, and education as markers of socioeconomic status and adjusted the results for relevant clinical covariates. We used weighted linear regression models to analyse empirical log odds of performance measure fulfillment at patient level. SETTING: Public hospitals in Denmark. PARTICIPANTS: A total of 110,848 consecutive stroke patients discharged between 2004 and 2014. INTERVENTIONS: Acute stroke care according to clinical guidelines. MAIN OUTCOME MEASURES: Guideline-recommended care was defined in two ways based on clinical performance measures: the percentage of fulfilled measures used throughout the study period (m=8) (model 1) and the percentage of fulfilled measures used at the time of discharge (m=8 to 16) (model 2). RESULTS: Compared with high family income, low income was negatively associated with the guideline-recommended care; odds ratios (95% CI) were 0.89 (0.85-0.93) in model 1 and 0.81 (0.77-0.85) in model 2. Low family income was negatively associated with fulfillment of 14 of the 16 performance measures. In general, the percentage of performance measures fulfilled increased over time from 70% (95% CI 63-76) to 85% (95% CI 83-87). CONCLUSION: Socioeconomic inequality in guideline-recommended stroke care remains despite overall improvements in a setting with free access to care and systematic monitoring of health care quality.

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).

Maternal pre-pregnancy BMI and intelligence quotient (IQ) in 5-year-old children: a cohort based study.

BACKGROUND: An association between maternal pre-pregnancy BMI and childhood intelligence quotient (IQ) has repeatedly been found but it is unknown if this association is causal or due to confounding caused by genetic or social factors. METHODS: We used a cohort of 1,783 mothers and their 5-year-old children sampled from the Danish National Birth Cohort. The children participated between 2003 and 2008 in a neuropsychological assessment of cognitive ability including IQ tests taken by both the mother and the child. Linear regression analyses were used to estimate the associations between parental BMI and child IQ adjusted for a comprehensive set of potential confounders. Child IQ was assessed with the Wechsler Primary and Preschool Scales of Intelligence--Revised (WPPSI-R). RESULTS: The crude association between maternal BMI and child IQ showed that BMI was adversely associated with child IQ with a reduction in IQ of -0.40 point for each one unit increase in BMI. This association was attenuated after adjustment for social factors and maternal IQ to a value of -0.27 (-0.50 to -0.03). After mutual adjustment for the father's BMI and all other factors except maternal IQ, the association between paternal BMI and child IQ yielded a regression coefficient of -0.26 (-0.59 to 0.07), which was comparable to that seen for maternal BMI (-0.20 (-0.44 to 0.04)). CONCLUSION: Although maternal pre-pregnancy BMI was inversely associated with the IQ of her child, the similar association with paternal BMI suggests that it is not a specific pregnancy related adiposity effect.

The impact of ageing and changing utilization patterns on future cardiovascular drug expenditure: a pharmacoepidemiological projection approach.

PURPOSE: To develop a method for projecting the impact of ageing and changing drug utilization patterns on future drug expenditure. METHODS: Applying nationwide registries, prescriptions of three categories of cardiovascular drugs were followed for all Danish residents from 1 January 1996 until 2006. The official Danish population forecast 2006-2015 was applied for projecting the population composition. A previously developed pharmacoepidemiological semi-Markov model was extended to apply for projection of future drug utilization. We either assumed that past trends in model parameters (incidence, discontinuation and drug user mortality) would continue during 2006-2015, or that all model parameters would remain unchanged at their values in 2005. Yearly drug expenditure per user of a particular drug was assumed to remain unchanged. Scenarios of future treatment prevalence with different drug categories were modelled by extrapolating future age- and gender-specific parameter values (treatment incidence, discontinuation and drug user mortality) from historic point estimates and their historic trend. RESULTS: Provided a continuance of past trends, increasing utilization of ACE inhibitors, angiotensin II antagonists and statins translates into a rise in annual expenditure of 176%, mainly explained by increases in treatment incidence. Due to pharmacoepidemiological disequilibrium, unchanged model parameters would imply an increase of 64%, ageing alone 14%. CONCLUSION: Increasing cardiovascular drug utilization may pose a substantial burden on future health care resources. However, prescribing behaviour is likely to depend on changing clinical guidelines. Despite the limited impact as cost driver, population ageing remains a challenge for future health care services.

Can differences in medical drug compliance between European countries be explained by social factors: analyses based on data from the European Social Survey, round 2.

BACKGROUND: Non-compliance with medication is a major health problem. Cultural differences may explain different compliance patterns. The size of the compliance burden and the impact of socio-demographic and socio-economic status within and across countries in Europe have, however, never been analysed in one survey. The aim of this study was to analyse 1) medical drug compliance in different European countries with respect to socio-demographic and socio-economic factors, and to examine 2) whether cross-national differences could be explained by these factors. METHODS: A multi-country interview survey European Social Survey, Round 2 was conducted in 2004/05 comprising questions about compliance with last prescribed drug. Non-compliance was classified as primary and secondary, depending whether the drug was purchased or not. Statistical weighting allowed for adjustment for national differences in sample mechanisms. A multiple imputation strategy was used to compensate for missing values. The analytical approach included multivariate and multilevel analyses. RESULTS: The survey comprised 45,678 participants. Response rate was 62.5% (range 43.6-79.1%). Reported compliance was generally high (82%) but the pattern of non-compliance showed large variation between countries. Some 3.2% did not purchase the most recently prescribed medicine, and 13.6% did not take the medicine as prescribed. Multiple regression analyses showed that each variable had very different and in some cases opposite impact on compliance within countries. The multilevel analysis showed that the variation between countries did not change significantly when adjusted for increasing numbers of covariates. CONCLUSION: Reported compliance was generally high but showed wide variation between countries. Cross-national differences could, however, not be explained by the socio-demographic and socio-economic variables measured.

Impact of post-abortion family planning services on contraceptive use and abortion rate among young women in China: a cluster randomised trial.

OBJECTIVES: To compare two post-abortion family planning (FP) service packages on contraceptive use and repeat abortion rate among young women in three cities in China. METHODS: In this cluster-randomized trial, one FP service package included provision of limited information and referral to existing FP services, and the other, more comprehensive, package consisted--in addition to the above simple package--of individual counselling, free provision of contraceptive materials, and involvement of the male partner. Eight matched pairs of hospitals were certified by centralized randomization. Women undergoing abortion were followed up for six months, and data were collected in two rounds, before and after the intervention. RESULTS: We followed a total of 2336 women younger than 25 years (555 before and 555 after the simple intervention package; 634 before and 592 after the comprehensive intervention package). Both packages increased use of any contraceptive method, but the comprehensive approach also increased use of more effective methods. Odds ratios for consistent and correct use of condoms were 2.32 (95% confidence interval 1.55-3.46) and 2.78 (1.81-4.26), respectively, compared with the simple package. The rates of unwanted pregnancies and repeat abortions were somewhat reduced for both packages, with no significant statistical difference between them. CONCLUSION: Couples who received the comprehensive post-abortion FP service appear to use more effective contraceptive methods and show better compliance.

[Adverse incidents in a cervical cancer screening programme]. / Utilsigtede haendelser i et vaginalcytologisk screeningsprogram.

INTRODUCTION: In about 10% of routine vaginal smears, pathologists recommend a repeat smear. The purpose of this paper is to describe the extent to which this recommendation is followed, reasons why this is not always the case, and possible ways of improvement. MATERIALS AND METHODS: Data on follow-up rates were extracted from the cervical cancer screening database in Aarhus County. Through facilitator visits information was obtained about the routine procedures for informing women about the test results, reasons for lack of follow-up and suggestions for improvement of the follow-up rate. RESULTS: One third of the recommended follow-up smears were not taken. Patients from single-handed practices were less likely to have a follow-up smear than those registered with group practices. The follow-up rate was independent of the organisation of the procedures for informing the women about the test results. Reasons at practice level for lack of follow-up included failure to convey the test results, unclear information to the women and lack of procedures to identify those who did not have the recommended test taken. To improve the follow-up rate, the general practitioners who were interviewed suggested a number of procedures to identify the women who did not receive the recommended follow-up smear. CONCLUSION: The follow-up rate is not acceptable, and a systematic follow-up procedure is necessary to ensure that the recommended follow-up tests are carried out. This is most efficiently done at a central level.

[Physical training as treatment of reduced functional ability in frail 75+ year-olds living at home. A randomized intervention study in general practice with technological assessment elements]. / Fysisk traening som behandling af nedsat funktionsevne hos svage, hjemmeboende 75+ -årige. Et randomiseret interventionsstudie i almen praksis omfattende elementer til en teknologivurdering.

INTRODUCTION: The aim of this study was to establish the value of physical training as a treatment of reduced physical ability in frail, elderly patients living at home. MATERIAL AND METHODS: 46 community-dwelling frail elderly patients (> 74 years) participated in a randomised, controlled intervention study. The intervention group was transported to training, whilst the control group was not activated. All had their physical functional ability determined using SF-36, Berg's Balance Scale, 10 m walking test and muscle strength test. RESULTS: The intervention group had a significant improvement in functional ability measured by means of Berg's Balance Scale, walking test, muscle strength test and SF-36 (p < 0.01) compared with the control group. The average cost per patient was estimated at 121 DKK per training session, equivalent to 1452 DKK for a 12-week training period. DISCUSSION: The establishing of a "multi-component-training" as a treatment offer, to which general practitioners could refer their patients, would involve some costs, but savings due to reduced nursing care can be expected.