The impact of cancer on diabetes outcomes.

BACKGROUND: Survival from many cancer types is steadily increasing, and as a result, a growing number of cancer patients will live with other chronic diseases, of which diabetes is one of the most prevalent. This study aims to describe the impact of cancer on health outcomes in patients with type 2 diabetes and to compare the effectiveness of a multifactorial intervention in diabetes patients with and without cancer. METHODS: The randomized controlled trial Diabetes Care in General Practice (DCGP) included 1381 patients newly diagnosed with type 2 diabetes. Patients were randomized to either six years of structured personal diabetes care or routine care. In a post hoc analysis, we followed patients for 19 years in Danish national registries for the occurrence of diabetes-related outcomes. We used Cox regression models to estimate hazard ratios for outcomes. RESULTS: At diagnosis 48 patients had cancer, and 243 patients were diagnosed with cancer during follow up. Patients with diabetes and cancer had excess all-cause mortality (HR 3.33; 95%CI 2.72-4.06), as well as an increased incidence of myocardial infarction (HR 1.76; 95%CI 1.29-2.39) and any diabetes-related outcome (HR 1.36; 95%CI 1.07-1.71). The intervention reduced the risk of both these endpoints in patients without cancer. Furthermore, there was no statistically significant difference in the effectiveness of the intervention among patients with and without cancer. CONCLUSIONS: Diabetes patients with cancer had an increased risk of myocardial infarction and any diabetes-related outcome. The observed positive effect of structured personal diabetes care on clinical outcomes did not differ between patients with and without cancer. Attention to and prevention of diabetes complications in patients with both type 2 diabetes and cancer is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01074762 (February 24, 2010).

The effect of structured personal care on RNA oxidation: A 19-year follow-up of the randomized trial Diabetes Care in General Practice (DCGP).

AIMS: The urinary marker of RNA oxidation, 8­oxo­7,8­dihydroguanosine (8-oxoGuo), but not the corresponding marker of DNA oxidation, 8­oxo­7,8­dihydro­2'­deoxyguanosine (8-oxodG), is a prognostic biomarker in patients with type 2 diabetes (T2D). The aim of the present study was to investigate the effect of structured personal care (individualized multifactorial treatment) versus standard care on RNA oxidation level in patients with T2D and to assess if the effect of structured personal care on all-cause and diabetes-related mortality was modified by RNA oxidation level. METHODS: Urine samples were analyzed for 8-oxoGuo/8-oxodG from 1381 newly diagnosed T2D patients from the cluster randomized trial Diabetes Care in General Practice cohort, and 970 patients were reexamined after six years of intervention. RESULTS: The yearly variation in RNA oxidation levels were not significantly different between the structured personal care group and standard care group. The effect of treatment on all-cause and diabetes-related mortality was not modified by the level of RNA oxidation. No changes in DNA oxidation were seen. CONCLUSIONS: Structured personal care does not influence RNA oxidation level nor is it better for patients with high RNA oxidation level. Thus, structured personal care may not impact the disease-related aspects identified by RNA oxidation level in T2D patients.

Brain Natriuretic Peptide in Plasma as Predictor of All-Cause Mortality in a Large Danish Primary Health Care Population Suspected of Heart Failure.

BACKGROUND: Measurement of B-type natriuretic peptide (BNP) in plasma may have its greatest potential in primary care, as general practitioners need to rapidly identify patients who warrant further medical review. The aim of the present study was to examine the prognostic information of BNP measurement on all-cause mortality in a large Danish primary care cohort. METHODS: This study covered a cohort of Danish primary care patients (n = 61665) with a median follow-up period of 4.36 years (interquartile range, 2.29-6.62 years). BNP was measured in plasma using the ADVIA Centaur/CentaurXP platform. The association of BNP with mortality was assessed with a hazard ratio for all-cause mortality from a multivariable Cox proportional hazards model. RESULTS: Kaplan-Meier curves showed decreasing survival probability with increasing BNP (P < 0.001). Each doubling of BNP increased mortality by 32.3% (95% CI, 30.8-33.8) when adjusted for sex and age, and by 25.3% (95% CI, 23.8-26.8) when further adjusted for Charlson comorbidity index, hemoglobin, estimated glomerular filtration rate, glycohemoglobin, and thyroid-stimulating hormone. Also, in a subcohort (n = 10824) without biochemical signs of severe kidney failure, anemia, polycythemia, hypothyroidism or hyperthyroidism, or dysregulated diabetes, each doubling of BNP increased mortality by 28.6% (95% CI, 22.8-34.7). CONCLUSIONS: Our results show that even in a primary care population, BNP measurements contain prognostic information regarding all-cause mortality.

The effect of structured personal care on diabetes symptoms and self-rated health over 14 years after diabetes diagnosis.

AIMS: To explore the effect of structured personal care on diabetes symptoms and self-rated health over 14 years after diabetes diagnosis while patients are gradually diagnosed with other chronic conditions (multimorbidity). METHODS: Post hoc analysis of the Danish randomized controlled trial Diabetes Care in General Practice including 1381 patients newly diagnosed with type 2 diabetes. The effect of structured personal care compared with routine care on diabetes symptoms and self-rated health was analysed 6 and 14 years after diagnosis with a generalized multilevel Rasch model. RESULTS: Structured personal care reduced the overall likelihood of reporting diabetes symptoms at the end of the intervention (OR 0.79; 95% CI: 0.64-0.97), but this effect was not explained by glycaemic control or multimorbidity. There was no effect of the intervention on diabetes symptoms after 14 years or on self-rated health after 6 years or 14 years. CONCLUSIONS: Structured personal care had a beneficial effect on diabetes symptoms 6 years after diagnosis, but not on self-rated health at either follow up point. To optimally manage patients over time it is important to supplement clinical information by information provided by the patients.

Socio-demographic determinants and effect of structured personal diabetes care: a 19-year follow-up of the randomized controlled study diabetes Care in General Practice (DCGP).

BACKGROUND: We investigated how four aspects of socio-demography influence the effectiveness of an intervention with structured personal diabetes care on long-term outcomes. METHODS: The Diabetes Care in General Practice (DCGP) study is a cluster-randomized trial involving a population-based sample of 1381 patients with newly diagnosed type 2-diabetes mellitus. We investigated how education, employment, cohabitation status and residence influenced the effectiveness of 6 years of intervention with structured personal diabetes care, resembling present day recommendations. Outcomes were incidence of any diabetes-related endpoint and death during 19 years after diagnosis, and cardiovascular risk factors, behaviour, attitudes and process-of-care variables 6 years after diagnosis. RESULTS: Structured personal care reduced the risk of any diabetes-related endpoint and the effect of the intervention was modified by geographical area (interaction p = 0.034) with HR of 0.71 (95%CI: 0.60-0.85) and of 1.07 (95%CI: 0.77-1.48), for patients in urban and rural areas, respectively. Otherwise, there was no effect modification of education, employment and civil status on the intervention for the final endpoints. There were no noticeable socio-demographic differences in the effect of the intervention on cardiovascular risk factors, behaviour, attitudes, and process-of-care. CONCLUSION: Structured personal care reduced the aggregate outcome of any diabetes-related endpoint and independent of socio-demographic factors similar effect on cardiovascular risk factors, behaviour, attitudes and process of care, but the intervention did not change the existing inequity in mortality and morbidity. Residence modified the uptake of the intervention with patients living in urban areas having more to gain of the intervention than rural patients, further investigations is warranted. TRIAL REGISTRATION: ClinicalTrials.gov registration no. NCT01074762 (February 24, 2010).

Urinary albumin and 8-oxo-7,8-dihydroguanosine as markers of mortality and cardiovascular disease during 19 years after diagnosis of type 2 diabetes - A comparative study of two markers to identify high risk patients.

Urinary albumin is an important biomarker used to identify high risk patients with diabetes, but there is a need for new biomarkers that alone or in combination with urinary albumin could give an even better prediction of clinical patient outcomes. One promising biomarker is 8-oxo-7,8-dihydroguanosine (8-oxoGuo) that represents intracellular oxidative stress. We investigated the ability of microalbuminuria (MA) and urinary 8-oxoGuo, alone and in combination, to predict mortality and cardiovascular disease (CVD) in patients with type 2 diabetes. We used data from 1381 newly diagnosed diabetes patients, and urinary albumin and 8-oxoGuo were assessed in morning urine collected at the time of diabetes diagnosis and at a follow-up visit 6 years later. Associations between the urinary markers and mortality and CVD were assessed in Cox proportional hazards regression models. Test performance was assessed using sensitivity, specificity, positive predictive value and negative predictive value for 10-year mortality and 10-year incidence of CVD. Both 8-oxoGuo and urinary albumin were statistically significantly associated with all-cause mortality at diagnosis as well as at 6-year follow-up. At diagnosis only urinary albumin was associated with CVD. In contrast, only 8-oxoGuo was associated with CVD at 6-year follow-up. When investigating test performance, we found that by combining information from MA and 8-oxoGuo the ability to correctly identify patients at risk could be improved. The findings suggest that measurement of urinary 8-oxoGuo provides additional information about risk to that obtained from urinary albumin, and that the combined use of 8-oxoGuo and urinary albumin could be useful for a better identification of patients at risk of CVD and death.

Intentional Weight Loss and Longevity in Overweight Patients with Type 2 Diabetes: A Population-Based Cohort Study.

OBJECTIVE: This study examined the influence of weight loss on long-term morbidity and mortality in overweight (BMI≥25 kg/m2) patients with type 2 diabetes, and tested the hypothesis that therapeutic intentional weight loss supervised by a medical doctor prolongs life and reduces the risk for cardiovascular disease in these patients. METHODS: This is a 19 year cohort study of patients in the intervention arm of the randomized clinical trial Diabetes Care in General Practice. Weight and prospective intentions for weight loss were monitored every third month for six years in 761 consecutive patients (≥40 years) newly diagnosed with diabetes in general practices throughout Denmark in 1989-92. Multivariable Cox regression was used to estimate the association between weight change during the monitoring period (year 0 to 6) and the outcomes during the succeeding 13 years (year 6 to 19) in 444 patients who were overweight at diagnosis and alive at the end of the monitoring period (year 6). The analysis was adjusted for age, sex, education, BMI at diagnosis, change in smoking, change in physical activity, change in medication, and the Charlson comorbidity 6-year score. Outcomes were from national registers. RESULTS: Overall, weight loss regardless of intention was an independent risk factor for increased all-cause mortality (P<0.01). The adjusted hazard ratio for all-cause mortality, cardiovascular mortality, and cardiovascular morbidity attributable to an intentional weight loss of 1 kg/year was 1.20 (95%CI 0.97-1.50, P = 0.10), 1.26 (0.93-1.72, P = 0.14), and 1.06 (0.79-1.42, P = 0.71), respectively. Limiting the analysis to include only those patients who survived the first 2 years after the monitoring period did not substantially change these estimates. A non-linear spline estimate indicated a V-like association between weight change and all-cause mortality, suggesting the best prognosis for those who maintained their weight. CONCLUSIONS: In this population-based cohort of overweight patients with type 2 diabetes, successful therapeutic intentional weight loss, supervised by a doctor over six years, was not associated with reduced all-cause mortality or cardiovascular morbidity/mortality during the succeeding 13 years.

The impact of gender on the long-term morbidity and mortality of patients with type 2 diabetes receiving structured personal care: a 13 year follow-up study.

AIMS/HYPOTHESIS: The aim of this study was to assess gender differences in mortality and morbidity during 13 follow-up years after 6 years of structured personal care in patients with type 2 diabetes mellitus. METHODS: In the Diabetes Care in General Practice (DCGP) multicentre, cluster-randomised, controlled trial (ClinicalTrials.gov registration no. NCT01074762), 1,381 patients newly diagnosed with type 2 diabetes were randomised to receive 6 years of either structured personal care or routine care. The intervention included regular follow-up, individualised goal setting and continuing medical education of general practitioners participating in the intervention. Patients were re-examined at the end of intervention. This observational analysis followed 970 patients for 13 years thereafter using national registries. Outcomes were all-cause mortality, incidence of diabetes-related death, any diabetes-related endpoint, myocardial infarction, stroke, peripheral vascular disease and microvascular disease. RESULTS: In women, but not men, a lower HR for structured personal care vs routine care emerged for any diabetes-related endpoint (0.65, p = 0.004, adjusted; 73.4 vs 107.7 events per 1,000 patient-years), diabetes-related death (0.70, p = 0.031; 34.6 vs 45.7), all-cause mortality (0.74, p = 0.028; 55.5 vs 68.5) and stroke (0.59, p = 0.038; 15.6 vs 28.9). This effect was different between men and women for diabetes-related death (interaction p = 0.015) and all-cause mortality (interaction p = 0.005). CONCLUSIONS/INTERPRETATION: Compared with routine care, structured personal diabetes care reduced all-cause mortality and diabetes-related death in women but not in men. This gender difference was also observed for any diabetes-related outcome and stroke but was not statistically significant after extensive multivariate adjustment. These observational results from a post hoc analysis of a randomised controlled trial cannot be explained by intermediate outcomes like HbA1c alone, but involves complex social and cultural issues of gender. There is a need to rethink treatment schemes for both men and women to gain benefit from intensified treatment efforts.

The excess mortality of patients with diabetes and concurrent psychiatric illness is markedly reduced by structured personal diabetes care: A 19-year follow up of the randomized controlled study Diabetes Care in General Practice (DCGP).

OBJECTIVE: To assess the effectiveness of an intervention in Type 2 diabetic patients with concurrent psychiatric illness (PI) and compare this with the effectiveness in patients without PI. METHOD: In the Diabetes Care in General Practice trial, 1381 patients newly diagnosed with Type 2 diabetes were randomized to 6 years of structured personal diabetes care or routine diabetes care (ClinicalTrials.gov NCT01074762). In this observational post-hoc analysis, the effectiveness of the intervention for diabetes in 179 patients with concurrent PI was analyzed. RESULTS: During the 19-year follow-up period, patients with PI in the structured personal care group experienced a lower risk for all-cause mortality [105.3 vs. 140.4 events per 1000 patient-years; hazard ratio (HR): 0.63, P=0.023, multivariably adjusted], diabetes-related death (66.0 vs. 95.1; HR: 0.57, P=0.015), any diabetes-related endpoint (169.5 vs. 417.5; HR: 0.47, P=0.0009) and myocardial infarction (54.1 vs. 104.4; HR: 0.48, P=0.013), compared to patients with PI in the routine care group. This translates into a number needed to treat over 10 years of three or lower for these outcomes. CONCLUSION: These findings suggest that in primary care, structured diabetes care allowing for individualization was highly effective among diabetic patients with co-occurring PI.

Back on track-Smoking cessation and weight changes over 9 years in a community-based cohort study.

OBJECTIVE: To examine the impact of smoking cessation on body weight compared with normal long-term weight development. METHODS: Of 1970 adults (20-69 years) in a rural town in Denmark invited to take part in the study in 1998-2000, 1374 (70%) participated. After 9 years, 1121 participated in the follow-up study. Weight changes were compared using multivariable regression models. RESULTS: The mean baseline weight of never-smokers was 76.4 kg (SD 16.0). The adjusted weight of smokers and ex-smokers differed by -4.2 kg (95% CI: -5.9, -2.6), and -0.7 kg (95% CI: -2.5, 1.1), respectively. The adjusted weight gain rate (kg/year) of never-smokers, smokers, and ex-smokers was 0.213, 0.127, and 0.105, respectively. The absolute post cessation weight gain (PCWG) was 5.0 kg (SD 7.0), and the adjusted PCWG was 2.8 kg (95% CI: 1.7, 3.9) compared with never-smokers, and 3.5 kg (95% CI: 2.3, 4.8) compared with smokers. The follow-up weight did not differ between quitters and never-smokers (0.1 kg; 95% CI: -2.4, 2.6). CONCLUSION: Smokers weigh less than never-smokers. By quitting, they gain weight and end up weighing the same as comparable never-smokers. Weight gain rates differ by smoking status. Consequently, PCWG depends on the length of follow-up. Our graphical model indicates that smoking cessation results in a return to normal weight development.

Weight changes following the diagnosis of type 2 diabetes: the impact of recent and past weight history before diagnosis. results from the Danish Diabetes Care in General Practice (DCGP) study.

AIMS: The association between recent and more distant weight changes before and after the diagnosis of type 2 diabetes has been little researched. The aim of this study is to determine the influence of patients' weight history before diabetes diagnosis on the observed 6-year weight changes after diagnosis. METHODS: A clinical cohort study combined with self-reported past weight history. In total 885 patients aged ≥40 years and newly diagnosed with clinical type 2 diabetes were included. Body weight was measured immediately after diabetes diagnosis and again at the 6-year follow up examination (median, 5.7 years). At diagnosis patients reported their weight 1 year and 10 years previously, and also at the age of 20. Multivariate linear regression analyses controlled for 20 baseline patient characteristics. RESULTS: The median (interquartile range) age at diagnosis was 63.2 (53.9; 71.4) years. Median body weight was 80.0 (72.0; 90.0) kg 10 years before diagnosis, 85.0 (75.0; 95.0) kg 1 year before diagnosis, 82.4 (72.0; 94.0) kg at diagnosis, and 80.0 (70.0; 91.1) kg at 6-year follow up. Each kg of weight gain during the year preceding the diagnosis was associated with a weight change (95% CI) of -0.20 (-0.28; -0.13) kg during the follow up period. In all models age and body mass index at diagnosis predicted future weight changes, while the weight at age 20 (-0.01 (-0.06; 0.03) kg/kg), and the weight change from 10 years to 1 year before diagnosis (-0.01 (-0.06; 0.04) kg/kg), did not predict weight change after diagnosis. CONCLUSIONS: During the first on average 5.7 years after diagnosis of type 2 diabetes, patients generally follow a course of declining average weight, and these weight developments are related primarily to recent weight changes, body mass index, and age, but not to the more distant weight history.

The impact of patients' involvement in cooking on their mortality and morbidity: a 19-year follow-up of patients diagnosed with type 2 diabetes mellitus.

OBJECTIVE: This study explored the impact of involvement in cooking on long-term morbidity and mortality among patients newly diagnosed with type 2 diabetes mellitus (T2DM). DESIGN AND SUBJECTS: Data are from the population-based study Diabetes Care in General Practice. In baseline questionnaires, 1348 patients newly diagnosed with T2DM gave information on how frequently they consumed a warm main meal and how often they cooked it themselves. The selected patients were followed up for 19 years in the Danish National Patient Registry and the Danish Register of Causes of Death. MAIN OUTCOME MEASURES: This study analysed the association between involvement in cooking and each of seven pre-specified outcomes was analysed in Cox regression models with stepwise adjustment for possible confounders and mediators. RESULTS: 92% of the patients with T2DM consumed a warm main meal ≥ five times per week. Among these, women who cooked for themselves less than once a week had a higher risk of diabetes-related deaths (HR 1.86 [95% CI 1.03-3.35], p = 0.039) and stroke (HR 2.47 [95% CI 1.08-5.65], p = 0.033), after adjustment for confounders. For men, infrequent cooking was not related to increased risk for the outcomes investigated. CONCLUSIONS: In patients newly diagnosed with T2DM and with a regular intake of warm main meals, infrequent involvement in cooking was associated with an increased risk of diabetes-related death and stroke for women, but not for men. General practitioners should pay special attention to managing diabetes treatment in female patients newly diagnosed with T2DM who report infrequent involvement in cooking.

Missing portion sizes in FFQ--alternatives to use of standard portions.

OBJECTIVE: Standard portions or substitution of missing portion sizes with medians may generate bias when quantifying the dietary intake from FFQ. The present study compared four different methods to include portion sizes in FFQ. DESIGN: We evaluated three stochastic methods for imputation of portion sizes based on information about anthropometry, sex, physical activity and age. Energy intakes computed with standard portion sizes, defined as sex-specific medians (median), or with portion sizes estimated with multinomial logistic regression (MLR), 'comparable categories' (Coca) or k-nearest neighbours (KNN) were compared with a reference based on self-reported portion sizes (quantified by a photographic food atlas embedded in the FFQ). SETTING: The Danish Health Examination Survey 2007-2008. SUBJECTS: The study included 3728 adults with complete portion size data. RESULTS: Compared with the reference, the root-mean-square errors of the mean daily total energy intake (in kJ) computed with portion sizes estimated by the four methods were (men; women): median (1118; 1061), MLR (1060; 1051), Coca (1230; 1146), KNN (1281; 1181). The equivalent biases (mean error) were (in kJ): median (579; 469), MLR (248; 178), Coca (234; 188), KNN (-340; 218). CONCLUSIONS: The methods MLR and Coca provided the best agreement with the reference. The stochastic methods allowed for estimation of meaningful portion sizes by conditioning on information about physiology and they were suitable for multiple imputation. We propose to use MLR or Coca to substitute missing portion size values or when portion sizes needs to be included in FFQ without portion size data.

Urinary markers of nucleic acid oxidation and cancer in type 2 diabetes.

AIMS/HYPOTHESIS: We investigated whether urinary markers of nucleic acid oxidation are associated with an increased risk of cancer in type 2 diabetes patients. METHODS: Urine samples from 1381 newly diagnosed diabetes patients were assayed for the oxidatively modified guanine nucleosides 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). Cox proportional hazards regression was used to examine the relationship between the urinary markers and cancer incidence. RESULTS: The crude analyses showed an association between overall cancer and urinary excretion of the RNA oxidation marker 8-oxoGuo (unadjusted hazard ratio for cancer per natural log increase in 8-oxoGuo 1.35 [95% CI, 1.01-1.81]), however, in the adjusted analyses, no significant associations between 8-oxodG or 8-oxoGuo and overall cancer were found. For site-specific cancers 8-oxodG was associated with breast cancer in the crude analyses (unadjusted hazard ratio for breast cancer per natural log increase in 8-oxodG was 2.37 [95% CI, 1.07-5.26]), although the association was attenuated in the adjusted analyses (sex- and age-adjusted hazard ratio 2.15 [95% CI, 0.92-5.02] and multivariate adjusted hazard ratio1.98 [95% CI, 0.95-4.10]). CONCLUSIONS: Urinary excretion of the nucleic acid oxidation markers 8-oxodG and 8-oxoGuo at the time of diagnosis was not associated with cancer overall in type 2 diabetes patients. For site-specific cancers, risk elevations were seen for breast cancer (8-oxodG). These findings should be examined in future and larger studies.

Eosinophilia in routine blood samples as a biomarker for solid tumor development - A study based on the Copenhagen Primary Care Differential Count (CopDiff) Database.

BACKGROUND: Eosinophilia may represent an early paraclinical sign of malignant disease and a host anti-tumor effect. The association between eosinophilia and the development of solid tumors has never before been examined in an epidemiological setting. The aim of the present study was to investigate eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. MATERIAL AND METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing the eosinophil count during 2000-2007. From these, one DIFF was randomly chosen and categorized according to no (< 0.5 × 10(9)/l), mild (≥ 0.5-1.0 × 10(9)/l) or severe (≥ 1.0 × 10(9)/l) eosinophilia. From the Danish Civil Registration System and the Danish Cancer Registry we ascertained all-cause death and solid tumors within the first three years following the DIFF. Using multivariable logistic regression, odds ratios (OR) were calculated and adjusted for previous eosinophilia, sex, age, year, month, C-reactive protein, previous cancer and Charlson's Comorbidity Index. RESULTS: The risk of bladder cancer was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers. CONCLUSION: We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize that additional preclinical studies are needed in order to shed further light on the role of eosinophils in carcinogenesis, where it is still unknown whether the cells contribute to tumor immune surveillance or neoplastic evolution.

Risk of lymphoma and solid cancer among patients with rheumatoid arthritis in a primary care setting.

BACKGROUND: Several studies have demonstrated an association between rheumatoid arthritis (RA) and lymphoproliferative malignancies, but pathogenic mechanisms remain unclear. We investigated 1) the risk of lymphoproliferative malignancies and solid tumors in adults with RA identified in primary care and 2) the possible mediating role of blood eosinophilia in the clonal evolution of cancer in these patients. METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count (DIFF) encompassing the eosinophil count between 2000-2007. From these, one DIFF was randomly chosen (the index DIFF). By linking to the Danish National Patient Register, we categorized the selected individuals according to known longstanding (≥3 years) or recent onset (<3 years) RA prior to the index DIFF. In addition, the cohort was stratified according to management in primary or secondary care. From the Danish Cancer Registry we ascertained malignancies within four years following the index DIFF. Using multivariable logistic regression, odds ratios (OR) were calculated and adjusted for sex, age, year, month, eosinophilia, comorbid conditions and C-reactive protein (CRP). RESULTS: 921 patients had recent onset RA and 2,578 had longer disease duration. Seventy three percent of RA patients were managed in primary care. After adjustment for sex, age, year, and month, neither recent onset nor long-standing RA was associated with incident lymphoproliferative malignancies or solid cancers. These risk estimates did not change when eosinophilia, CRP, and comorbidities were included in the models. CONCLUSIONS: In this large cohort of patients with RA of short or long duration recruited from a primary care resource, RA was not associated with an increased risk of lymphoproliferative or solid cancers during 4 years of follow-up, when the models were adjusted for confounders. Blood eosinophilia could not be identified as a mediator of cancer development in the present setting.

The Copenhagen Primary Care Differential Count (CopDiff) database.

BACKGROUND: The differential blood cell count provides valuable information about a person's state of health. Together with a variety of biochemical variables, these analyses describe important physiological and pathophysiological relations. There is a need for research databases to explore associations between these parameters, concurrent comorbidities, and future disease outcomes. METHODS AND RESULTS: The Copenhagen General Practitioners' Laboratory is the only laboratory serving general practitioners in the Copenhagen area, covering approximately 1.2 million inhabitants. The Copenhagen General Practitioners' Laboratory has registered all analytical results since July 1, 2000. The Copenhagen Primary Care Differential Count database contains all differential blood cell count results (n=1,308,022) from July 1, 2000 to January 25, 2010 requested by general practitioners, along with results from analysis of various other blood components. This data set is merged with detailed data at a person level from The Danish Cancer Registry, The Danish National Patient Register, The Danish Civil Registration System, and The Danish Register of Causes of Death. CONCLUSION: This paper reviews methodological issues behind the construction of the Copenhagen Primary Care Differential Count database as well as the distribution of characteristics of the population it covers and the variables that are recorded. Finally, it gives examples of its use as an inspiration to peers for collaboration.

The effectiveness of structured personal care of type 2 diabetes on recurrent outcomes: a 19 year follow-up of the study Diabetes Care in General Practice (DCGP).

AIMS/HYPOTHESIS: The estimation of effect size in clinical trials commonly disregards recurrent outcomes. We investigated the effectiveness of a complex intervention on recurrent outcomes in patients with type 2 diabetes. METHODS: In the Diabetes Care in General Practice (DCGP) randomised controlled trial, 1,381 patients newly diagnosed with type 2 diabetes were randomised to 6 years of structured personal care or routine care (ClinicalTrials.gov NCT01074762). The trial had 19 years of registry-based follow-up and was analysed with Cox regression models. Repeated occurrences in the same patient of outcomes (any diabetes-related endpoint, myocardial infarction [MI], stroke, peripheral vascular disease and microvascular disease) were accounted for with the Wei, Lin and Weissfeld method. RESULTS: As previously shown, the intervention reduced the rates of first occurrence of both MI and any diabetes-related endpoint. However, for all outcomes, the HR for a second event showed a statistically non-significant tendency to be increased. We estimated a combined HR for all marginal failure times, regardless of whether they were first, second or later events. This showed that the intervention had no effect on the rate of any of the outcomes, including MI (HR 0.89, 95% CI 0.76, 1.05) and any diabetes-related endpoint (HR 0.98, 95% CI 0.87, 1.09). CONCLUSIONS/INTERPRETATION: In the DCGP study, a smaller proportion of patients who received structured care experienced a first occurrence of MI or any diabetes-related endpoint compared with patients who received routine care. However, the patients who received structured care tended to experience more recurrent outcomes, so the total outcome rate was not affected by the intervention.