The effect of basal-bolus therapy varies with baseline 1,5-anhydroglucitol level in people with Type 2 diabetes: a post hoc analysis.

AIMS: To investigate the impact of baseline 1,5-anhydroglucitol on the treatment effect of basal-bolus therapy in people with Type 2 diabetes. METHODS: Post hoc analysis of onset 3, an 18-week, randomized, phase 3 trial evaluating the efficacy and safety of fast-acting insulin aspart in basal-bolus therapy (n = 116) vs. basal insulin-only therapy (n = 120) in people with Type 2 diabetes. The estimated treatment difference in change from baseline in HbA1c was investigated for different cut-off values of baseline 1,5-anhydroglucitol (2, 3, 4, 5 and 6 µg/ml). RESULTS: The estimated treatment difference in change from baseline in HbA1c between basal-bolus therapy and basal insulin-only therapy was statistically significantly greater in participants with baseline 1,5-anhydroglucitol ≤3 µg/ml (n = 34) vs. >3 µg/ml (n = 198) [estimated treatment difference (95% CI): -1.53% (-2.12; -0.94) vs. -0.82% (-1.07; -0.57); P-value for interaction = 0.03]. The estimated treatment difference became more pronounced when comparing participants with 1,5-anhydroglucitol ≤2 µg/ml (n = 15) vs. >2 µg/ml (n = 217) [estimated treatment difference (95% CI): -2.26% (-3.15; -1.36) vs. -0.85% (-1.08; -0.62); P-value for interaction = 0.003]. For cut-off values ≥4 µg/ml, estimated treatment differences were numerically greater below the cut-off compared with above, although the interaction terms were not statistically significant. CONCLUSION: This analysis indicates that people with Type 2 diabetes with low 1,5-anhydroglucitol have an added treatment benefit with basal-bolus therapy compared with people with higher 1,5-anhydroglucitol. Further research is needed to clarify any clinical utility of these findings. Clinical Trials Registry No: NCT01850615.

Dabigatran adherence in atrial fibrillation patients during the first year after diagnosis: a nationwide cohort study.

BACKGROUND: There is a perception among physicians that lack of routine monitoring with non-vitamin K antagonist oral anticoagulants (NOACs) may lead to poor adherence to medication. We studied adherence during the first year of usage in a cohort of patients with newly diagnosed non-valvular atrial fibrillation (AF) started on the NOAC, dabigatran etexilate. METHODS AND RESULTS: Nationwide Danish patient and prescription purchase registries were used to identify newly diagnosed AF patients taking dabigatran, comorbidities, and refill patterns under a twice-daily, one pill regimen. Adherence was characterized among remaining users (N = 2960) after 1 year using the proportion of days covered (PDC), gap rates and restart rates. The overall 1-year PDC was 83.9%, with 76.8% of patients having a 1-year PDC in excess of 80%. Patients with a CHA2 DS2 -VASc score ≥ 2 were more adherent to medication regimes than patients with a CHA2 DS2 -VASc score of 1 (PDC ratio, 1.12; 95% confidence interval [CI], 1.08-1.17) and generally patients with higher morbidity showed more adherence. Patients with prior bleeding were not less adherent to medication regimes than patients with no prior bleeding (PDC ratio, 1.02; 95% CI, 0.98-1.06). The overall gap rate was 1.4 gaps per year. There were no clear tendencies in gap rates among subgroups, although patients with higher morbidity tended to have slightly more, but shorter, gap periods. CONCLUSIONS: More than 75% of patients were showed > 80% adherence to medication regimes during the first year. Patients with higher morbidity, including patients with a higher risk of stroke or bleeding, exhibited better adherence. This improvement may be attributable to more regular contact with the healthcare system.

Baseline patterns of adipose tissue fatty acids and long-term risk of breast cancer: a case-cohort study in the Danish cohort Diet, Cancer and Health.

BACKGROUND/OBJECTIVES: The evidence regarding fatty acids and breast cancer risk is inconclusive. Adipose tissue fatty acids can be used as biomarkers of fatty acid intake and of endogenous fatty acid exposure. Fatty acids in adipose tissue are correlated owing to common dietary sources and shared metabolic pathways, which group fatty acids into naturally occurring patterns. We aimed to prospectively investigate associations between adipose tissue fatty acid patterns and long-term risk of total breast cancer and breast cancer subtypes characterised by oestrogen and progesterone receptor status (ER and PR). SUBJECTS/METHODS: This case-cohort study was based on data from the Danish cohort Diet, Cancer and Health. At baseline, a fat biopsy and information on lifestyle and reproductive factors were collected. From the 31 original fatty acids measured, patterns of fatty acids were identified using the treelet transform. During a median follow-up of 5.3 years, 474 breast cancer cases were identified. Hazard ratios and 95% confidence intervals of risk of total breast cancer and of subtypes according to quintiles of factor score were determined by weighted Cox proportional hazards regression. RESULTS: After adjustment for potential confounders, factor scores for the seven patterns identified by the treelet transform were not associated with risk of total breast cancer, nor with risk of ER+, ER-, PR+ or PR- tumours. CONCLUSIONS: No clear associations between the patterns of fatty acids at baseline and long-term risk of total breast cancer or ER+, ER-, PR+ or PR- tumours were observed.

Blood reinfusion combined with femoral nerve block in total knee replacement for patients with increased risk of bleeding.

PURPOSE: To compare patients with increased risk of bleeding who received combined blood reinfusion and femoral nerve block in total knee replacement (TKR) to regular patients treated routinely with respect to pain relief, blood loss, and knee function. METHODS: In a consecutive series of 67 patients who underwent unilateral TKR, 12 patients with increased risk of bleeding owing to cardiac disease or previous thromboembolic events received continuous femoral nerve block and blood reinfusion, without tranexamic acid (TA) injection. The remaining 55 patients were controls who received standard postoperative treatment (TA injection, local injection of analgesics, and suction drainage without reinfusion). The volume of blood loss (drained or reinfused), pain score (using a visual analogue scale) and knee function (using the Knee Society Score [KSS]) in the 2 groups were compared. RESULTS: In the study group, patients were 5 years older and tended to have a lower preoperative KSS function score (35 vs. 45, p=0.08) and a higher function-related pain score (6.5 vs. 6, p=0.10). The mean volume of drained blood wasted in the study group did not differ significantly from the mean total volume of drained blood in the control group (235 vs. 300 ml, p=0.14). Similarly, the mean decrease in postoperative haemoglobin concentration did not differ significantly between the respective groups (2.1 vs. 2.1 mmol/l, p=0.97). A significantly greater proportion of patients received allogenic blood transfusion in the study group than in controls (3/12 vs. 2/55, p<0.01). The study group exhibited significantly higher pain scores during training (1.7 vs. 1.4, p=0.03) and lower escape oxycodone consumption (5 vs. 15 mg/kg, p=0.06) on postoperative day 1 (but not other days). The duration of hospitalisation was also longer (5.5 vs. 4 days, p=0.04). CONCLUSION: In TKR patients with increased risk of bleeding, blood reinfusion combined with femoral nerve block is safe and comparable to standard methods of pain control (local injection of analgesics).

Parity and risk of diabetes in a Danish nationwide birth cohort.

AIMS: The purpose was to elucidate the association between parity and the incidence of diabetes using national register data. METHODS: The study population consisted of all Danish women with a singleton delivery in 1982/1983 (n = 100,669), who subsequently had 74,966 deliveries. The included women were followed up via registries until the end of 2006 for subsequent deliveries, diagnosis of diabetes and death/emigration. RESULTS: A total of 2021 cases (2.0%) were diagnosed with diabetes in connection with hospitalization or outpatient treatment during follow-up. Analyses were adjusted for fetal weight and duration of gestation, both at index pregnancy. Cox regression analysis with parity as a time-varying exposure, stratified in two age groups, showed an association between parity and risk of a diagnosis of diabetes. In women <33 years of age, parity 2, 3 and 4 + were associated with an increased risk of being diagnosed with diabetes compared with parity 1 [relative risks: 1.6 (95% confidence interval 1.1-2.3), 2.8 (1.8-4.3) and 2.5 (1.3-4.8), respectively]. Among women >33 years of age, parity 2 was associated with a significantly lower risk of diabetes diagnosis compared with parity 1, whereas parity 4 + was associated with a significantly higher risk of diabetes diagnosis compared with parity 1. CONCLUSIONS: The study shows that the risk of diabetes diagnosis increases with parity in young Danish women. This may support a causal association between diabetes and parity.

NT-pro-BNP is an independent predictor of mortality in patients with end-stage renal disease.

AIM: Patients with end-stage renal disease (ESRD) have an increased mortality from cardiovascular disease (CVD). N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is an independent predictor of mortality in patients with ischemic heart disease and congestive heart failure. Previous data have shown markedly elevated levels of NT-pro-BNP in patients with ESRD, while the prognostic value of elevated levels of NT-pro-BNP in patients with ESRD is largely unknown. The aim of the present study was to examine if the level of NT-pro-BNP predicts mortality in patients with ERSD and CVD. METHODS: We prospectively followed 206 patients with ESRD and documented CVD. Levels of NT-pro-BNP were measured at baseline, and patients were followed for 2 years or until they reached the predefined endpoint of all-cause mortality. RESULTS: During follow-up, the total mortality was 44% (90/206). Patients who died were followed for a median of 314 days (interquartile range 179 - 530). Using Cox regression analysis, age, female sex, systolic blood pressure, dialysis efficiency and plasma levels of NT-pro-BNP were independent prognostic risk factors of mortality. In receiver operating characteristic curve analysis a cut off value for NT-pro-BNP was determined. Patients with values of NT-pro-BNP above 12.200 pg/ml had a 3 times higher risk of death than patients below the cut-off value (HR 3.05 95% CI 1.96 - 4.77, p < 0.0001). CONCLUSION: In spite of generally elevated levels of NT-pro-BNP, NT-pro-BNP is still an independent predictor of mortality and might add prognostic information in patients with ESRD and documented CVD.

Examining secular trends and seasonality in count data using dynamic generalized linear modelling: a new methodological approach illustrated with hospital discharge data on myocardial infarction.

Time series of incidence counts often show secular trends and seasonal patterns. We present a model for incidence counts capable of handling a possible gradual change in growth rates and seasonal patterns, serial correlation, and overdispersion. The model resembles an ordinary time series regression model for Poisson counts. It differs in allowing the regression coefficients to vary gradually over time in a random fashion. During the 1983-1999 period, 17,989 incidents of acute myocardial infarction were recorded in the Hospital Discharge Registry for the county of North Jutland, Denmark. Records were updated daily. A dynamic model with a seasonal pattern and an approximately linear trend was fitted to the data, and diagnostic plots indicated a good model fit. The analysis conducted with the dynamic model revealed peaks coinciding with above-average influenza A activity. On average the dynamic model estimated a higher peak-to-trough ratio than traditional models, and showed gradual changes in seasonal patterns. Analyses conducted with this model provide insights not available from more traditional approaches.

Risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in patients with unexplained chest/epigastric pain and normal upper endoscopy: a 10-year Danish cohort study.

BACKGROUND: No studies have examined the risk of upper gastrointestinal diseases among patients with unexplained chest/epigastric pain (UCEP) and a normal upper endoscopy. AIM: To examine the relative risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in UCEP patients. METHODS: This Danish 10-year cohort study focused on UCEP patients (n = 386), diagnosed in 1992-93. Ten age- and gender-matched controls were selected per patient from Denmark's Civil Registration System (n = 3860). Kaplan-Meier analysis and Cox's regression analysis was used to calculate the risk of hospitalization for peptic ulcer, oesophagitis, pancreatitis or gallstone. RESULTS: Compared with controls, the adjusted relative risks among UCEP patients <1 and > or = 1 year after upper endoscopy were for peptic ulcer 2.0 [95% confidence interval (CI) 0.2-18.4] and 1.7 (95% CI 0.9-3.4), for oesophagitis 8.2 (95% CI 1.2-59.2) and 1.9 (95% CI 0.7-5.0), for pancreatitis 9.2 (95% CI 2.0-41.8) and 3.9 (95% CI 1.4-10.5), and for gallstone 14.1 (95% CI 5.4-37.2) and 3.3 (95% CI 1.9-5.8). CONCLUSIONS: UCEP is positively associated with all study outcomes especially in the first year after upper endoscopy, indicating that peptic ulcer, oesophagitis, pancreatitis or gallstone could be underlying early UCEP symptoms. However, the long-term association remained strong for pancreatitis and gallstone, suggesting a genuine excess risk.

The North Jutland County Diabetic Retinopathy Study (NCDRS) 2. Non-ophthalmic parameters and clinically significant macular oedema.

BACKGROUND: The influence of non-ophthalmic parameters on the prevalence of clinically significant macular oedema has not been unambiguously established. The present study was initiated with the aim of clarification. METHODS: This cross-sectional study comprised 656 type 1 and 328 type 2 diabetic subjects undergoing retinopathy screening in the county of North Jutland. The association between the presence of clinically significant macular oedema and blood pressure, HbA1c, BMI, age, onset of diabetes, duration of diabetes, blood-pressure-reducing medication, lipid-lowering medication, neuropathy and urinary albumin excretion was explored using multiple logistic regression analysis. RESULTS: We found no significant association between the presence of clinically significant macular oedema and any of the examined parameters in type 1 diabetic subjects. In type 2 diabetic subjects, the duration of diabetes, HbA1c, neuropathy and increased urinary albumin excretion was significantly associated with the presence of clinically significant macular oedema. CONCLUSIONS: The risk factors for clinically significant macular oedema differ in type 1 and type 2 diabetic subjects and can account only in part for this manifestation.

Monitoring the introduction of a surgical intervention with long-term consequences.

Surgical innovations are often introduced for their expected long-term benefits, but the decision to abandon the existing treatment must be based on the available short-term data and rational judgment. We present a framework for monitoring the introduction of a surgical intervention with long-term consequences and failure-time endpoints. The framework is based on Bayesian methods, and formally combines study data, clinical opinion, and external evidence to construct a posterior survival function from which intuitive summary statistics can be extracted to aid decision making. It incorporates learning effects and is adaptable to a wide variety of settings. The methods are illustrated on survival data from a cohort of 325 consecutive neonates treated for simple transposition of the great arteries with either the Senning or the Switch operation during the period 1978-1998.

The North Jutland County Diabetic Retinopathy Study: population characteristics.

BACKGROUND: Several population-based studies have reported blood glucose levels and blood pressure to be risk factors for the development of diabetic retinopathy. These studies were initiated more than two decades ago and may therefore reflect the treatment and population composition of a previous era, suggesting new studies of the present population with diabetes. AIM AND METHODS: This cross-section study included 656 people with type 1 diabetes and 328 with type 2 diabetes. Crude prevalence rates of proliferative diabetic retinopathy, clinically significant macular oedema and several specific retinal lesions were assessed, together with their association to a simplified and internationally approved retinal grading. RESULTS: The point prevalence of proliferative retinopathy was found to be 0.8% and 0.3% for type 1 and type 2 diabetes. Equivalent prevalence rates of clinically significant macular oedema were 7.9% and 12.8%, respectively. The most frequently occurring retinal manifestations increased in number until retinopathy level 3, and then decreased. CONCLUSION: The point prevalence of proliferative retinopathy is lower than that found in previous studies, whereas it is increased for clinically significant macular oedema. These data suggest different risk factors for these clinical entities.