Factors associated with attendance at clinical follow-up of a cohort with screen-detected type 2 diabetes: ADDITION-Denmark.

AIMS: To determine the association between concurrent overall burden of disease, cardiovascular disease, cancer, self-rated health, HbA1c levels, and attendance at clinical follow-up of the Danish arm of the ADDITION-study. METHODS: Logistic regression models were used to study factors proposed being associated with attendance in clinical follow-up. We used data from clinical examinations, questionnaires and national registers at a time-point near the follow-up examination. RESULTS: A total of 1119 participants were eligible for the follow-up conducted a median of 12.8 years (IQR 11.6; 13.4) after type 2 diabetes diagnosis by screening. Concurrent high burden of disease was associated with lower attendance (OR 0.6 (95% CI: 0.4; 0.9) for high-versus no burden of disease). Concurrent cardiovascular disease and cancer showed no statistically significant association with attendance (OR 1.0 (95% CI: 0.7; 1.4)) and (OR 0.8 (95% CI: 0.6; 1.1) for (disease versus no disease). Similarly, self-rated health (OR 0.7 (95% CI: 0.5; 1.0) poor-versus good self-rated health) and HbA1c levels (OR 1.0 (95% CI: 0.9; 1.2 unit=10mmol/mol)) were not statistically significant associated with attendance. CONCLUSIONS: This study showed a lower attendance in clinical follow-up after nearly 13years among individuals with concurrent high burden of disease. No associations were found between concurrent CVD, cancer, self-rated health and Hba1c levels and attendance.

Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-up of the ADDITION-Europe cluster-randomised trial.

BACKGROUND: The multicentre, international ADDITION-Europe study investigated the effect of promoting intensive treatment of multiple risk factors among people with screen-detected type 2 diabetes over 5 years. Here we report the results of a post-hoc 10-year follow-up analysis of ADDITION-Europe to establish whether differences in treatment and cardiovascular risk factors have been maintained and to assess effects on cardiovascular outcomes. METHODS: As previously described, general practices from four centres (Denmark, Cambridge [UK], Leicester [UK], and the Netherlands) were randomly assigned by computer-generated list to provide screening followed by routine care of diabetes, or screening followed by intensive multifactorial treatment. Population-based stepwise screening programmes among people aged 40-69 years (50-69 years in the Netherlands), between April, 2001, and December, 2006, identified patients with type 2 diabetes. Allocation was concealed from patients. Following the 5-year follow-up, no attempts were made to maintain differences in treatment between study groups. In this report, we did a post-hoc analysis of cardiovascular and renal outcomes over 10 years following randomisation, including a 5 years post-intervention follow-up. As in the original trial, the primary endpoint was a composite of first cardiovascular event, including cardiovascular mortality, cardiovascular morbidity (non-fatal myocardial infarction and non-fatal stroke), revascularisation, and non-traumatic amputation, up to Dec 31, 2014. Analyses were based on the intention-to-treat principle. ADDITION-Europe is registered with ClinicalTrials.gov, NCT00237549. FINDINGS: 343 general practices were randomly assigned to routine diabetes care (n=176) or intensive multifactorial treatment (n=167). 317 of these general practices (157 in the routine care group, 161 in the intensive treatment group) included eligible patients between April, 2001, and December, 2006. Of the 3233 individuals with screen-detected diabetes, 3057 agreed to participate (1379 in the routine care group, 1678 in the intensive treatment group), but at the 10-year follow-up 14 were lost to follow-up and 12 withdrew, leaving 3031 to enter 10-year follow-up analysis. Mean duration of follow-up was 9·61 years (SD 2·99). Sustained reductions over 10 years following diagnosis were apparent for bodyweight, HbA1c, blood pressure, and cholesterol in both study groups, but between-group differences identified at 1 and 5 years were attenuated at the 10-year follow-up. By 10 years, 443 participants had a first cardiovascular event and 465 died. There was no significant difference between groups in the incidence of the primary composite outcome (16·1 per 1000 person-years in the routine care group vs 14·3 per 1000 person-years in the intensive treatment group; hazard ratio [HR] 0·87, 95% CI 0·73-1·04; p=0·14) or all-cause mortality (15·6 vs 14·3 per 1000 person-years; HR 0·90, 0·76-1·07). INTERPRETATION: Sustained reductions in glycaemia and related cardiovascular risk factors over 10 years among people with screen-detected diabetes managed in primary care are achievable. The differences in prescribed treatment and cardiovascular risk factors in the 5 years following diagnosis were not maintained at 10 years, and the difference in cardiovascular events and mortality remained non-significant. FUNDING: National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Novo Nordisk, Novo Nordisk Foundation, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Wellcome Trust, UK Medical Research Council, UK National Institute for Health Research, UK National Health Service, Merck, Julius Center for Health Sciences and Primary Care, UK Department of Health, and Nuts-OHRA.

Validity of Danish register diagnoses of myocardial infarction and stroke against experts in people with screen-detected diabetes.

BACKGROUND: Administrative patient registers are often used to estimate morbidity in epidemiological studies. The validity of register data is thus important. This study aims to assess the positive predictive value of myocardial infarction and stroke registered in the Danish National Patient Register, and to examine the association between cardiovascular risk factors and cardiovascular disease based on register data or validated diagnoses in a well-defined diabetes population. METHODS: We included 1533 individuals found with screen-detected type 2 diabetes in the ADDITION-Denmark study in 2001-2006. All individuals were followed for cardiovascular outcomes until the end of 2014. Hospital discharge codes for myocardial infarction and stroke were identified in the Danish National Patient Register. Hospital medical records and other clinically relevant information were collected and an independent adjudication committee evaluated all possible events. The positive predictive value for myocardial infarction and stroke were calculated as the proportion of cases recorded in the Danish National Patient Register confirmed by the adjudication committee. RESULTS: The positive predictive value was 75% (95% CI: 64;84) for MI and 70% (95% CI: 54;80) for stroke. The association between cardiovascular risk factors and incident cardiovascular disease did not depend on using register-based or verified diagnoses. However, a tendency was seen towards stronger associations when using verified diagnoses. CONCLUSIONS: Our results show that studies using only register-based diagnoses are likely to misclassify cardiovascular outcomes. Moreover, the results suggest that the magnitude of associations between cardiovascular risk factors and cardiovascular outcomes may be underestimated when using register-based diagnoses.

Initiation and cessation of mental healthcare after mental health screening in primary care: a prospective cohort study.

BACKGROUND: Mental health (MH) problems have considerable personal and societal implications. Systematic MH screening may raise general practitioners' (GP) awareness of the current need of treatment in their listed patients. The focus of MH screening has so far been on increasing diagnostic rates and treatment of mental disorders, whereas cessation of MH treatment after normal test results has rarely been studied. This study aims to examine the mental healthcare trajectories after MH screening combined with feedback on both positive and negative screening results to the GP. METHODS: This prospective cohort study is based on data from 11,714 randomly selected individuals aged 30-49 years, who were invited to a preventive health check in Denmark during 2012-2015. A total of 5970 (51%) were included. MH status was assessed using the SF-12 Health Survey Mental Component Summary score, and scores were categorised into poor, moderate, and good MH. 'Mental healthcare' within 1 year of follow-up covered the following MH support: psychometric testing by GP, talk therapy by GP, contact to psychologist, contact to psychiatrist, and psychotropic medication. RESULTS: MH was found to be poor in 9%, moderate in 25%, and good in 66% of participants. After 1 year, mental healthcare was initiated in 29% of the participants with poor MH who did not receive mental healthcare at baseline, and mental healthcare was ceased in 44% of the participants with good MH who received mental healthcare at baseline. Odds ratio (OR) for initiation of mental healthcare was associated with worse MH screening status: poor MH: OR 7.1 (5.4-9.4), moderate MH: OR 2.4 (1.9-3.1), compared to those with good MH. OR for cessation of mental healthcare was associated with better MH screening status: good MH: OR 1.6 (1.1-2.6), moderate MH: OR 1.6 (1.0-2.4), compared to those with poor MH. Initiation and cessation of mental healthcare appeared to be time-related to the MH screening. CONCLUSIONS: MH screening combined with feedback on both positive and negative screening results to the GP may contribute to relevant initiation and cessation of mental healthcare. TRIAL REGISTRATION: Registration of the Check Your Health-trial: ClinicalTrials.gov ( NCT02028195 ), 7 March 2014.

Risk Factors for Incident Diabetic Polyneuropathy in a Cohort With Screen-Detected Type 2 Diabetes Followed for 13 Years: ADDITION-Denmark.

OBJECTIVE: To study incident diabetic polyneuropathy (DPN) prospectively during the first 13 years after a screening-based diagnosis of type 2 diabetes and determine the associated risk factors for the development of DPN. RESEARCH DESIGN AND METHODS: We assessed DPN longitudinally in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION) using the Michigan Neuropathy Screening Instrument questionnaire (MNSIQ), defining DPN with scores ≥4. Risk factors present at the diabetes diagnosis associated with the risk of incident DPN were estimated using Cox proportional hazard models adjusted for trial randomization group, sex, and age. RESULTS: Of the total cohort of 1,533 people, 1,445 completed the MNSIQ at baseline and 189 (13.1%) had DPN at baseline. The remaining 1,256 without DPN entered this study (median age 60.8 years [interquartile range 55.6; 65.6], 59% of whom were men). The cumulative incidence of DPN was 10% during 13 years of diabetes. Age (hazard ratio [HR] 1.03 [95% CI 1.00; 1.07]) (unit = 1 year), weight (HR 1.09 [95% CI 1.03; 1.16]) (unit = 5 kg), waist circumference (HR 1.14 [95% CI 1.05; 1.24]) (unit = 5 cm), BMI (HR 1.14 [95% CI 1.06; 1.23]) (unit = 2 kg/m2), log2 methylglyoxal (HR 1.45 [95% CI 1.12; 1.89]) (unit = doubling), HDL cholesterol (HR 0.82 [95% CI 0.69; 0.99]) (unit = 0.25 mmol/L), and LDL cholesterol (HR 0.92 [95% CI 0.86; 0.98]) (unit = 0.25 mmol/L) at baseline were significantly associated with the risk of incident DPN. CONCLUSIONS: This study provides further epidemiological evidence for obesity as a risk factor for DPN. Moreover, low HDL cholesterol levels and higher levels of methylglyoxal, a marker of dicarbonyl stress, are identified as risk factors for the development of DPN.

Does Training and Support of General Practitioners in Intensive Treatment of People with Screen-Detected Diabetes Improve Medication, Morbidity and Mortality in People with Clinically-Diagnosed Diabetes? Investigation of a Spill-Over Effect in a Cluster RCT.

INTRODUCTION: Very few studies have examined the potential spill-over effect of a trial intervention in general practice. We investigated whether training and support of general practitioners in the intensive treatment of people with screen-detected diabetes improved rates of redeemed medication, morbidity and mortality in people with clinically-diagnosed diabetes. METHODS: This is a secondary, post-hoc, register-based analysis linked to a cluster randomised trial. In the ADDITION-Denmark trial, 175 general practices were cluster randomised (i) to routine care, or (ii) to receive training and support in intensive multifactorial treatment of individuals with screen-detected diabetes (2001 to 2009). Using national registers we identified all individuals who were diagnosed with clinically incident diabetes in the same practices over the same time period. (Patients participating in the ADDITION trial were excluded). We compared rates of redeemed medication, a cardiovascular composite endpoint, and all-cause mortality between the routine care and intensive treatment groups. RESULTS: In total, 4,107 individuals were diagnosed with clinically incident diabetes in ADDITION-Denmark practices between 2001 and 2009 (2,051 in the routine care group and 2,056 in the intensive treatment group). There were large and significant increases in the proportion of patients redeeming cardio-protective medication in both treatment groups during follow-up. After a median of seven years of follow-up, there was no difference in the incidence of a composite cardiovascular endpoint (HR 1.15, 95% CI 0.95 to 1.38) or all-cause mortality between the two groups (HR 1.08, 95% CI 0.94 to 1.23). DISCUSSION: There was no evidence of a spill-over effect from an intervention promoting intensive treatment of people with screen-detected diabetes to those with clinically-diagnosed diabetes. Overall, the proportion of patients redeeming cardio-protective medication during follow-up was similar in both groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT00237549.

Psychological distress, cardiovascular complications and mortality among people with screen-detected type 2 diabetes: follow-up of the ADDITION-Denmark trial.

AIMS/HYPOTHESIS: The aim of this study was to examine the association between psychological distress and the risk of cardiovascular disease (CVD) events and all-cause mortality in patients with screen-detected type 2 diabetes mellitus. In addition, we explored whether or not metabolic control and medication adherence could explain part of this association. METHODS: A follow-up study was performed including 1,533 patients aged 40-69 years with screen-detected type 2 diabetes mellitus identified in general practice during 2001-2006 in the Denmark arm of the ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care) study. Mental health was measured at baseline with the Mental Health Inventory 5 (MHI-5). Psychological distress was defined as an MHI-5 score of ≤ 68 (18.2% of the population). CVD risk factors were measured at baseline and repeated at the follow-up examination. Information on death, hospital discharge diagnosis, and antihypertensive and lipid-lowering drug treatment was obtained from national registers. Cox proportional regression was used to estimate HRs for the association between psychological distress, CVD events and all-cause mortality. Age- and sex-adjusted risk difference analyses were performed to estimate differences in meeting treatment targets. RESULTS: Patients with psychological distress had a 1.8-fold higher mortality rate (HR 1.76, 95% CI 1.23, 2.53) and a 1.7-fold higher risk of having a CVD event (HR: 1.69, 95% CI 1.05, 2.70) compared with those with an MHI-5 score of >68. Overall, psychological distress was not associated with the ability to meet treatment targets for HbA1c levels, cholesterol levels or BP, or to redeem antihypertensive or lipid-lowering drug treatment. CONCLUSIONS/INTERPRETATION: In people detected and treated early in the diabetes disease trajectory, those with psychological distress at the time of diagnosis had a higher risk of CVD events and death than those without psychological distress.

Comparison of different stepwise screening strategies for type 2 diabetes: Finding from Danish general practice, Addition-DK.

AIM: To examine attendance, number of people with T2DM and costs of three different stepwise screening strategies for T2DM in general practice (GP). METHODS: Diabetes risk questionnaires were mailed to individuals aged 40-69 years from 45 general practices in 2001-2002 and individuals at high risk for T2DM, were asked to contact their GP to arrange a screening test. In 2005-2006, 26 general practices were randomised into two different opportunistic screening programmes (OP-direct and OP-subsequent) and risk questionnaires were distributed to individuals aged 40-69 years during GP consultations. In the OP-direct approach, high-risk individuals were offered to start the screening during the actual consultation while high-risk individuals in the OP-subsequent approach, were invited to a screening test at a later date. We report attendance, number of people with T2DM and costs of each screening approach. RESULTS: The mail-distributed approach identified 0.8% of the target population with T2DM, the OP-direct approach and the OP-subsequent approach, 0.9% and 0.5% respectively. Cost per person with T2DM was in the mail-distributed approach: € 1058, OP-direct approach: € 707 and the OP-subsequent approach: € 727. CONCLUSION: This study indicates that opportunistic screening identifies the same level of unknown diabetes as a mail-distributed approach but with lower costs.