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Introduction: As continuous intraperitoneal insulin infusion (CIPII) results in a more physiologic action of insulin than subcutaneous (SC) insulin administration, we hypothesized that CIPII would result in less glycemic variability (GV) than SC insulin therapy among type 1 diabetes mellitus (T1DM) patients. Materials and Methods: Data from 5-day blind continuous glucose monitoring (CGM) measurements performed during a 26-week, prospective, observational case-control study were analyzed. The coefficient of variation (CV) was the primary measure of GV. In addition, the SD of the mean glucose level, mean of daily differences, and mean amplitude of glycemic excursions were calculated. Results: In total, 176 patients (36% male; mean age, 49 [SD 13] years; median diabetes duration, 24 [interquartile range, 17, 35] years; glycated hemoglobin level, 63 [10] mmol/mmol), of which 37 used CIPII and 139 SC insulin therapy, were analyzed. CGM data were available for 169 patients at baseline (CIPII, n=35; SC, n=134) and for 164 patients at 26 weeks (CIPII, n=35; SC, n=129). After adjustment for baseline differences, the CV was 4.9% (95% confidence interval, 1.0, 8.8) lower with CIPII- compared with SC-treated patients, irrespective of the use of multiple daily injections or continuous SC insulin infusion. There were no differences in other indices of GV between groups. Conclusions: Despite higher blood glucose, the CV was slightly lower with CIPII compared with SC insulin therapy in T1DM patients, and other measures of GV were identical. Future studies are needed to confirm these findings and investigate whether this results in prevention of hypoglycemia and even perhaps (less) microvascular complications. [ABSTRACT FROM AUTHOR]

Objective: Communication between professionals is essential because it contributes to an optimal continuum of care. Whether patients experience adequate continuum of care is uncertain. To address this, a questionnaire was developed to elucidate this care process from a patients’ perspective. In this study, the instrument's ability to measure differences in “Consumer Quality Index Continuum of Care” scores between hospitals was investigated. Methods: The questionnaire was mailed to a random sample of 2159 patients and comprised of 22 items divided over four domains, GP approach, GP referral, specialist and collaboration. Multilevel analysis was conducted to identify case-mix and determine this questionnaire's ability to measure differences in domain scores between hospitals. Results: Based on a 65% response rate, 1404 questionnaires were available for analysis. Case-mix of patient characteristics across hospitals could not be demonstrated. Some differences in scores between hospitals were observed. At most two in eight hospitals showed different domain scores. Conclusion: The ability of this questionnaire to measure differences in continuum of care scores between hospitals is limited. The outcome of this survey suggests that hospitals provide a similar level of continuum of care from a patient's perspective. Practical implications: This questionnaire is especially useful for measuring differences between patients. [Copyright &y& Elsevier]

Objective: Development and validation of a questionnaire that measures patients’ experiences of collaboration between general practitioners (GPs) and specialists. Methods: A questionnaire was developed using the method of the consumer quality index and validated in a cross-sectional study among a random sample of patients referred to medical specialists in the Netherlands. Validation included factor analysis, ascertain internal consistency, and the discriminative ability. Results: The response rate was 65% (1404 patients). Exploratory factor analysis indicated that four domains could be distinguished (i.e. GP Approach; GP Referral; Specialist; Collaboration). Cronbach''s alpha coefficients ranged from 0.51 to 0.93 indicating sufficient internal consistency to make comparison of groups of respondents possible. The Pearson correlation coefficients between the domains were <0.4, except between the domains GP Approach and GP Referral. All domains clearly produced discriminating scores for groups with different characteristics. Conclusions: The Consumer Quality Index (CQ-index) Continuum of Care can be a useful instrument to assess aspects of the collaboration between GPs and specialists from patients’ perspective. Practice implications: It can be used to give feedback to both medical professionals and policy makers. Such feedback creates an opportunity for implementing specific improvements and evaluating quality improvement projects. [Copyright &y& Elsevier]

Abstract: Objective: To construct an empirical classification of patients with shoulder complaints, and then to investigate the relationship between the empirical classification and the setting in which the patients were recruited, their demographic and clinical characteristics, and the original diagnostic categories. Study Design and Setting: A latent class analysis was performed on the combined data of two previous studies. Results: Four clusters of patients emerged, one with patients who have a small chance of any restriction of the motion of the shoulder and a moderate chance of restriction of the motions of the neck, a second with patients who have a high chance of restriction of the motions of the shoulder and a moderate chance of restriction of motions of the neck, a third with patients who have a low to moderate chance of restriction of all motions, and a fourth with patients who have a high chance of restriction of all of the motions. Patients recruited from a clinic for rheumatology and rehabilitation and from the orthopedic clinic were more present in the second cluster. Patients in the third cluster were on average younger than those in the other clusters. There appeared to be little agreement between the clusters found and the classification of patients according to the original diagnostic categories. Conclusion: Patients experiencing shoulder pain can be classified in a simple way into four categories, reflecting the distinction between problems of the shoulder and those of the neck. A simple classification rule is proposed with which almost all patients can be classified into the four clusters. [Copyright &y& Elsevier]

Objective: To construct a classification of patients with shoulder complaints based on their physical examination. To investigate (1) the interobserver reliability, (2) to what extent the setting in which the patients were recruited, and demographic and clinical characteristics are related to the classification.Study design and setting: Data from 132 patients with shoulder complaints recruited in various health care settings in The Netherlands were examined. Two observers independently performed a physical examination of the cervical spine and shoulder joint. A nonmetric multidimensional scaling procedure was performed for each observer separately. The interobserver reliability of both observers was computed. Differences between setting, demographic and clinical characteristics, and the resulting dimensions were investigated.Results: For both observers two dimensions (severity of complaints of the shoulder joint, and severity of problems of the cervical spine) were sufficient to classify all patients. Agreement between the two observers was good (r = 0.84) to moderate (r = 0.69). Patients with neck pain in history taking showed higher scores on both dimensions.Conclusion: Despite moderate interobserver agreement for each variable from physical examination found in previous studies, observers agree on the scores of the patients on the relevant dimensions. Given the limited number of effective treatments available to the general practitioner, a more sophisticated classification system seems unnecessary. [Copyright &y& Elsevier]

Aim: This study assessed the impact of illness perceptions, emotional responses to the disease and its management, and patient characteristics on the adherence to optimal insulin pump management in adolescents with type 1 diabetes mellitus.Methods: From May to December 2013 and May 2015 to September 2016, we investigated 90 adolescents (50% boys), 12-18 years with type 1 diabetes. We analysed the association of optimal adherence to insulin pump therapy to age, gender, diabetes duration, results of questionnaires relating to fear and problems of self-testing, illness perceptions, emotional distress and family conflicts. Optimal adherence was defined as bolusing insulin on average ≥2.5/3 main meals/d.Results: Adolescents with suboptimal adherence were on average 1.8 years older (95% Confidence Interval 1.09-2.50 years, P < .001) than those with optimal adherence. After adjustment for age, no other patient or parent factors were related to optimal adherence.Conclusion: Adherence to insulin pump self-management in adolescents with type 1 diabetes declined with increasing age, illustrating the challenges of transition of self-management from parents to the adolescent patient themselves. [ABSTRACT FROM AUTHOR]

Poor self-management contributes to insufficient glycemic control in adolescents with type 1 diabetes (T1DM). We assessed the effects on glycemic control of adherence to self-measurement of blood glucose (SMBG) and insulin boluses in 90 adolescents with T1DM on insulin pump therapy over a 2-month period. We compared the number of insulin boluses and SMBGs around main meals to the "gold standard" of optimal diabetes management (SMBGs and a bolus before each main meal and SMBG before bedtime). The mean (95% CI) HbA1c levels were 2.9(1.7 to 4.0) mmol/mol lower for every additional insulin bolus and 3.1(1.6 to 4.5) mmol/mol lower for every additional SMBG. Patients performing SMBG and bolusing around each main meal had considerably lower HbA1c levels than those unable to do (95% CI for difference 4.3 to 10.4 mmol/mol and 11.5 to 20.1 mmol/mol respectively). For each additional mealtime bolus/day, the odds ratio of achieving target HbA1c levels of <58 mmol/mol was 6.73 (95% CI 2.94-15.38), after adjustment for gender, age, diabetes duration, and affective responses to SMBG in a multiple logistic regression model.Conclusion: Glycemic control in adolescents with T1DM on insulin pump therapy is strongly dependent on adherence to insulin boluses around mealtimes. What is Known: • In mixed groups of children and adolescents, insulin bolus frequency and self-monitoring of blood glucose (SMBG) frequency were determinants of HbA1c levels. • Adherence to insulin boluses and SMBG is particularly challenging in adolescents. What is New: • In adolescents on insulin pump therapy, each additional insulin bolus, particularly around mealtime, was significantly associated with approximately 3 mmol/mol lower HbA1c levels. • This beneficial effect of mealtime bolusing was strongest for the evening meal. [ABSTRACT FROM AUTHOR]

Background C-reactive protein (CRP), procalcitonin (PCT) and pro-adrenomedullin (MR-proADM) are inflammation markers associated with long-term mortality risk. We compared the associations and predictive capacities of CRP, PCT and MR-proADM with cardiovascular and all-cause mortality in patients with type 2 diabetes. Methods This study included primary care treated patients with type 2 diabetes participating in the ZODIAC cohort study. A total of 1005 out of 1688 patients (60%) had complete baseline variables. Baseline CRP, PCT and MR-proADM were assessed in relation to cardiovascular and all-cause mortality with Cox proportional hazard analyses. Hazard Ratios (HR) were adjusted for age, gender, BMI, smoking, systolic blood pressure, cholesterol-HDL ratio, duration of diabetes, HbA 1c , history of cardiovascular diseases, albumin-creatinine ratio and creatinine. Risk prediction capabilities were assessed with Harrell's C statistics and proportion of explained variance ( R 2 ). Results After a median follow-up of 11 years, 472 (47%) of 1005 patients had died. The likelihood ratio test showed that CRP and MR-proADM significantly improved prediction in cardiovascular mortality [HRs 1.20 (95%CI 1.09–1.33) and 1.56 (95%CI 1.06–2.30)] and in all-cause mortality [HRs 1.10 (95%CI: 1.03–1.18) and 1.31 (95%CI 1.02–1.69)]. Harrell's C values and R 2 measures showed slightly improved discrimination for cardiovascular mortality in patients without macrovascular disease (C: 0.80 to 0.81; R 2 : 0.50 to 0.52) and MR-proADM (C: 0.80 to 0.82; R 2 : 0.50 to 0.52). Conclusions CRP and MR-proADM, but not PCT, were independently associated with cardiovascular and all-cause mortality. In patients without macrovascular diseases, CRP and MR-proADM slightly improved discrimination, in absolute sense, of patients at risk for cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to investigate whether trends in quality of diabetes care differ between sexes in the Netherlands from 1998 till 2013. Research Design and Methods: In this prospective observational cohort study quality of care was measured using process and outcome measures in patients with type 2 diabetes in primary care. Trend and absolute differences between sexes were investigated for patients <75 years. Subgroup analyses were performed in patients ≥75 years. 10-year mortality risk was assessed with the Globorisk risk equation in patients without cardiovascular diseases <75 years. Results: The number of patients increased from 2,644 in 1998 to 62,230 in 2013. In 1998, 51% of the men and 60% of the women <75 years had an HbA1c >53 mmol/mol; this decreased to approximately 29% in both sexes in 2013. Patients having a systolic blood pressure >140 mmHg decreased from 70% to 42%, and from 80% to 40% in men and women <75 years, respectively. In patients ≥75 years it decreased from 72% to 50% in men and 85% to 56% in women. Obesity increased in both sexes, whereas smoking in men and women declined in patients <75 years (men: 34% to 22%; women: 22% to 18%). The number of patients with a mortality risk >20% over 10 years decreased from 15% to 3% in men and from 18% to 3% in women. Conclusions: Quality of diabetes care has improved considerably in the period 1998–2013 in both sexes. Possibly relevant trend differences between sexes were observed for HbA1c, systolic blood pressure, BMI and smoking. The predicted mortality risk decreased over time in both sexes. Except for BMI in both age groups and systolic blood pressure in patients ≥75 years, no evident poorer risk factor control in women compared to men was found at the end of the study period. [ABSTRACT FROM AUTHOR]

Background and aims Hyponatremia has been associated with an increased mortality risk in the general population. Diabetes is a condition predisposing for elevated levels of arginine vasopressin (AVP) and heart failure, both common causes of hyponatremia. These factors, however, are also associated with an increased mortality risk. We aimed to investigate whether serum sodium is associated with cardiovascular and all-cause mortality in type 2 diabetes and whether these associations could be explained by copeptin, a surrogate for AVP, or NT-proBNP, a marker for heart failure. Methods Patients with type 2 diabetes participating in the observational ZODIAC study were included. Cox regression analyses were used to investigate the association of serum sodium with mortality. Results We included 1068 patients (age 67 ± 12 years, 45% male, serum sodium 142 ± 3 mmol/L). After 15 years of follow-up, 519 patients (49%) died, with 225 cardiovascular deaths (21%). In univariable analyses, serum sodium, copeptin, and NT-proBNP were all significantly associated with cardiovascular and all-cause mortality. These associations remained significant after combination of these markers in a multivariable model. Serum sodium and NT-proBNP remained significantly associated with mortality after further adjustment for potential confounders, whereas copeptin lost significance after adjustment for SCr and ACR. Conclusion Low serum sodium was associated with an increased risk of cardiovascular and all-cause mortality in type 2 diabetes. Moreover, these associations were not explained by copeptin and NT-proBNP. Whether low serum sodium itself leads to poor outcome or is a marker for (unidentified) co-morbidity severity or use of specific medications remains to be elucidated. [ABSTRACT FROM AUTHOR]

Aim This study described the incidence and prevalence of type 1 diabetes in children in the Netherlands in 2010-2011 and to compare these results with earlier studies. Methods This was a retrospective nationwide cohort study of Dutch children aged 14 years or younger. Patients were identified using health insurance reimbursement registries for hospital care and invoices for insulin. In the Netherlands, all children with diabetes are treated by hospital-based paediatricians and health care for all Dutch citizens is covered by law. Results The incidence of type 1 diabetes almost doubled between 1978-1980 and 2010-2011, from 11.1 to 21.4 per 100 000. In the youngest age group, who were under 5 years, the incidence rate doubled between 1996 and 1999 and remained stable after that. There were no relevant incidence differences between the sexes. The overall prevalence of type 1 diabetes in the Netherlands during 2009-2011 was 143.6 (95% confidence interval 141.1-146.2) per 100 000 children and was similar for boys and girls. Conclusion The incidence of type 1 diabetes in children in the Netherlands almost doubled between 1978-1980 and 2010-2011, but the incidence in children under 5 years appeared to stabilise between 1996 and 1999. There were no statistical differences between the sexes. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that the carpal tunnel syndrome seems to occur more frequently in patients with diabetes mellitus and might be associated with the duration of diabetes mellitus, microvascular complications and degree of glycaemic control. Primary aim was to determine if type 2 diabetes can be identified as a risk factor for carpal tunnel syndrome after adjusting for possible confounders. Furthermore, the influence of duration of diabetes mellitus, microvascular complications and glycaemic controlon the development of carpal tunnel syndrome was investigated. Methods: Retrospective, case–control study using data from electronic patient charts from the Isala (Zwolle, the Netherlands). All patients diagnosed with carpal tunnel syndrome in the period from January 2011 to July 2012 were included and compared with a control group of herniated nucleus pulposus patients. Results: A total of 997 patients with carpal tunnel syndrome and 594 controls were included. Prevalence of type 2 diabetes was 11.5% in the carpal tunnel syndrome group versus 7.2% in the control group (Odds Ratio 1.67 (95% confidence interval 1.16-2.41)). In multivariate analyses adjusting for gender, age and body mass index, type 2 diabetes was not associated with carpal tunnel syndrome (OR 0.99 (95% CI 0.66-1.47)). No differences in duration of diabetes mellitus, microvascular complications or glycaemic control between groups were detected. Conclusion: Although type 2 diabetes was more frequently diagnosed among patients with carpal tunnel syndrome, it could not be identified as an independent risk factor. [ABSTRACT FROM AUTHOR]

Background Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a treatment option for patients with type 1 diabetes mellitus (T1DM). Aim of the present study was to describe the long-term course of glycaemic control, complications, health related quality of life (HRQOL) and treatment satisfaction among T1DM patients treated with CIPII. Methods Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) therapy in 2006 were followed until 2012. Laboratory, continuous glucose monitoring, HRQOL and treatment satisfaction measurements were performed at the start of the study,the end of the SC-, the end of the CIPII treatment phase in 2006 and during CIPII therapy in 2012. Linear mixed models were used to calculate estimated values and to test differences between the moments in time. Results In 2012, more time was spent in hyperglycaemia than after the CIPII treatment phase in 2006: 37% (95% CI 29, 44) vs. 55% (95% CI 48, 63), mean difference 19.8% (95% CI 3.0, 36.6). HbA1c was 65 mmol/mol (95% CI 60, 71) at the end of the SC treatment phase in 2006, 58 mmol/mol (95% CI 53, 64) at the end of the CIPII treatment phase and 65 mmol/mol (95% CI 60, 71) in 2012, respectively (p > 0.05). In 2012, the median number of grade 2 hypoglycaemic events per week (1 (95% CI 0, 2)) was still significantly lower than during prior SC therapy (3 (95% CI 2, 4)): mean change -1.8 (95% CI -3.4, -0.4). Treatment satisfaction with CIPII was better than with SC insulin therapy and HRQOL remained stable. Pump or catheter dysfunction of the necessitated re-operation in 7 patients. No mortality was reported. Conclusions After 6 years of CIPII treatment, glycaemic regulation is stable and the number of hypoglycaemic events decreased compared to SC insulin therapy. Treatment satisfaction with CIPII is superior to SC insulin therapy, HRQOL is stable and complications are scarce. CIPII is a safe and effective treatment option for selected patients with T1DM, also on longer term. [ABSTRACT FROM AUTHOR]

Background: Formation of advanced glycation endproducts (AGEs), endothelial dysfunction, and low-grade inflammation are intermediate pathways of hyperglycemia-induced vascular complications. We investigated the effect of benfotiamine on markers of these pathways in patients with type 2 diabetes and nephropathy. Methods: Patients with type 2 diabetes and urinary albumin excretion in the high-normal and microalbuminuric range (15- 300 mg/24h) were randomized to receive benfotiamine (n = 39) or placebo (n = 43). Plasma and urinary AGEs (Nϵ- (carboxymethyl) lysine [CML], Nϵ-(Carboxyethyl) lysine [CEL], and 5-hydro-5-methylimidazolone [MG-H1]) and plasma markers of endothelial dysfunction (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1], soluble E-selectin) and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP], serum amyloid-A [SAA], myeloperoxidase [MPO]) were measured at baseline and after 6 and 12 weeks. Results: Compared to placebo, benfotiamine did not result in significant reductions in plasma or urinary AGEs or plasma markers of endothelial dysfunction and low-grade inflammation. Conclusions: Benfotiamine for 12 weeks did not significantly affect intermediate pathways of hyperglycemia-induced vascular complications. [ABSTRACT FROM AUTHOR]

Background: An observational study to examine whether thrombolytic therapy in stroke patients realizes better quality of life outcomes compared to patients without thrombolytic therapy one year after stroke. We also examined whether daily functioning, mental functioning and activities improved after thrombolytic treatment. Methods: A total of 88 stroke patients were interviewed at home one year post-stroke. Health-related quality of life (HRQOL) was assessed using the RAND-36, disability with the Barthel Index, depression and anxiety with the Hospital Anxiety and Depression Scale, and a questionnaire about patient way of life was completed. People aged under 60, moving to a nursing home or with a haemorrhage were excluded. Results: The thrombolysis group (TG) had more severe stroke (higher NIHSS) scores and were younger than the group without thrombolytic therapy (WTG). The primary outcome was HRQOL, which was high and nearly identical in both groups, however the TG had significantly better HRQOL for the 'mental health' and 'vitality' scales. Patients who stopped or reduced their hobbies because of stroke had a significantly worse HRQOL. One year after stroke, more patients in the TG were totally or severely ADL dependent (12% TG and 0% WTG, p = 0.022). The level of dependence decreased in the TG (p = 0.042) and worsened in the WTG (p<0.001) after one year. Being more dependent is related to diminishing daily occupations in both groups. In the TG the level of dependence had less impact on visiting family and friends and going on holiday. The prevalence of anxiety disorder and depression was low compared to other studies and there is no significant difference between the two groups. Conclusion: No major differences in the primary outcome (HRQOL) could be found between the two groups. In addition, no essential difference could be found in mental functioning and participation. We expected that patients undergoing thrombolytic therapy would have worse quality of life because of the greater initial severity of their stroke. Therefore, thrombolytic therapy seems to be of great importance in achieving better quality of life in ischemic stroke patients who respond to this therapy. [ABSTRACT FROM AUTHOR]

Background: Annually, 41,000 people in the Netherlands have strokes. This has multiple physical and psychosocial consequences. Most patients return home after discharge from hospital. Quality aftercare by general practitioners is important to support patients at home. The purpose of this study is to examine the wellbeing of patients who returned home immediately after discharge from hospital, one year post stroke, in comparison with the general Dutch population of the same age and to determine factors that could influence wellbeing. Methods: All the stroke patients from the Department of Neurology, Martini Hospital Groningen in the period November 2006 to October 2007 were included. People aged under 65 years or with haemorrhaging were excluded. All the patients (N = 57) were interviewed at home using the following questionnaires: Barthel Index, SF-36, HADS, CSI and a questionnaire about their way of life. Results: 31% of the patients in this study experienced a decrease in functional status after one year. Nevertheless, there was no significant difference between the median Barthel Index value at discharge from hospital and one year post stroke. ADL independence correlated with a better quality of life. The health-related quality of life was high. Stroke patients have almost the same quality of life as the 'average' Dutch elderly population. Where patients can no longer fully participate in society, their perceived quality of life is also lower. In this study there is an indication of a high prevalence of depression and anxiety disorders in stroke patients. This negatively affects the quality of life a year after stroke. Although caregiver strain was low for the partners of stroke patients, a reduced quality of life is correlated to greater burden. Conclusions: This study provides valuable insight into the wellbeing of patients living at home one year post stroke. Physical functioning and quality of life are comparable to the general population of the same age, but improvements in mental functioning can be envisaged. In addition, more attention should be paid to maintaining the patients' activities. The wellbeing of these stroke patients could be increased further if greater attention is paid to these aspects of life. This seems to be applicable to general practice. [ABSTRACT FROM AUTHOR]

Background: Patients suffering from psychotic disorders have an increased risk of comorbid somatic diseases such as cardiovascular disorders and diabetes mellitus. Doctor-related factors, such as unfamiliarity with these patients, as well as patient-related factors, such as cognitive disturbance and negative symptoms, contribute to suboptimal health care for these patients. General practitioners (GPs) could play a key role in diagnosing and treating this somatic comorbidity as in the Netherlands, almost all residents are registered at a general practice. This study aims to find out whether there are any differences between the levels of health care provided by GPs to patients with psychotic disorders, compared to other types of patients. Methods: A cohort of patients with an ICPC code of psychosis and two matched control groups, one consisting of patients with other mental problems and the other one of patients without any mental problems, were followed over a period of 5 years. Results: Patients with psychotic disorders (N = 734) contacted the GP practice more often than patients in the control groups. These patients, both adults (p = 0.051) and the elderly (p < 0.005), received more home visits from their GPs. In the adult group (16 to 65 years old inclusive), the number of consultations was significantly higher among both psychosis patients and the group of patients with other mental problems (p < 0.0005). The number of telephone consultations was significantly higher in both age categories, adult group (p < 0.0005), and > 65 years old (p = 0.007). With regard to chronic illnesses, elderly psychosis patients had fewer contacts related to cardiovascular diseases or chronic lung diseases. Conclusion: Patients with psychotic disorders contact the GP practice more frequently than other types of patients. Adult psychosis patients with diabetes mellitus, cardiovascular diseases or chronic lung diseases receive the same amount of health care for these diseases as other primary care patients. The finding that older patients with psychotic disorders are diagnosed with cardiovascular diseases and obstructive lung diseases less frequently than other types of elderly patients requires further study. [ABSTRACT FROM AUTHOR]

Background: Carpal tunnel syndrome is caused by entrapment of the median nerve and results in pain, tingling and numbness in the wrist and hand. It is a common condition in general practice. Effectiveness of treatment by intracarpal corticosteroid injection has never been investigated in general practice. The objective of this study was to determine if corticosteroid injections for carpal tunnel syndrome provided by general practitioners are effective. Methods: In this study 69 participants with a clinical diagnosis of carpal tunnel syndrome were recruited from 20 general practices. Short-term outcomes were assessed in a randomised, placebo-controlled trial. Long-term results were assessed in a prospective cohort-study of steroid responders. Participants were randomised to intracarpal injections of 1 ml triamcinolonacetonide 10 mg/ml (TCA) or 1 ml NaCl (placebo). Non-responders to NaCl were treated with additional TCA injections. Main outcomes were immediate treatment success, mean score of the Symptom Severity Scale (SSS) and Functional Status Scale (FSS) of the Boston carpal tunnel questionnaire, subjective improvement and proportion of participants with recurrences during followup. Duration of follow-up was twelve months. Results: The TCA-group (36 participants) had better outcomes than the NaCl-group (33 participants) during shortterm assessment for outcome measures treatment response, mean improvement of SSS-score (the mean difference in change score was 0.637 {95% CI: 0.320, 0.960; p < 0.001}) and FSS-score (the mean difference in change score was 0.588 {95% CI: 0.232, 0.944; p = 0.002}) and perceived improvement (p = 0.01). The number to treat to achieve satisfactory partial treatment response or complete resolution of symptoms and signs was 3 (95% CI:1.83, 9.72). 49% of TCA-responders (17/35) had recurrences during follow-up. In the group of TCA-responders without recurrences (51%, 18/35) outcomes for SSS-score and FSS-score deteriorated during the follow-up period of 12 months (resp. p = 0.008 and p = 0.012). Conclusions: Corticosteroid injections for CTS provided by general practitioners are effective regarding short-term outcomes when compared to placebo injections. The short-term beneficial treatment effects of steroid injections deteriorated during the follow-up period of twelve months and half of the cohort of steroid-responders had recurrences. Trial registration: Current Controlled Trials ISRCTN53171398. [ABSTRACT FROM AUTHOR]

Background: Dysfunction of the cervicothoracic spine and the adjacent ribs (also called the shoulder girdle) is considered to predict occurrence and poor outcome of shoulder symptoms. It can be treated with manipulative therapy, but scientific evidence for the effectiveness of such therapy is lacking. Objective: To study the effectiveness of manipulative therapy for the shoulder girdle in addition to usual medical care for relief of shoulder pain and dysfunction. Design: Randomized, controlled trial. Setting: General practices in Groningen, the Netherlands. Patients: 150 patients with shoulder symptoms and dysfunction of the shoulder girdle. Interventions: All patients received usual medical care from their general practitioners. Only the intervention group received additional manipulative therapy, up to 6 treatment sessions in a 12-week period. Measurements: Patient-perceived recovery, severity of the main complaint shoulder pain, shoulder disability, and general health. Data were collected during and at the end of the treatment period (at 6 and 12 weeks) and during the follow-up period (at 26 and 52 weeks). Results: During treatment (6 weeks), no significant differences were found between study groups. After completion of treatment (12 weeks), 43% of the intervention group and 21% of the control group reported full recovery. After 52 weeks, approximately the same difference in recovery rate (17 percentage points) was seen between groups. During the intervention and follow-up periods, a consistent between-group difference in severity of the main complaint shoulder pain and disability, and general health favored additional manipulative therapy. Limitations: The sample size was small, and assessment of end points was subjective. Conclusion: Manipulative therapy for the shoulder girdle in addition to usual medical care accelerates recovery of shoulder symptoms. [ABSTRACT FROM AUTHOR]

The Abstract section and the in the Results sections of the original version of this article, unfortunately, contained errors. The correct data are now shown in this article. [ABSTRACT FROM AUTHOR]

Objective: The optimal frequency of self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes (T2DM) with stable glycemic control is unknown. This study investigated effects of 3 frequencies of SMBG on glycemic control and quality of life after 9 months in patients using one long-acting insulin injection a day. In an openlabel, multi-center, primary-care, parallel (1:1:1) randomized trial in the Netherlands including patients with T2DM, HbA1c ≤ 58 mmol/mol (≤ 7.5%), stable glycemic control, treated with one insulin injection daily, three frequencies of 4-point glucose measurements (before meals and bedtime) were weekly (n = 22), every 2 weeks (n = 16) and monthly (n = 20) were compared. Results: A total of 58 patients with T2DM were included by 38 general practitioners, which was lower then anticipated. There were no significant between group differences in HbA1c (mmol/mol); group C compared to A and B; - 2.7 (95% CI - 6.4, 1.0) and - 1.0 (95% CI - 4.9, 3.0) and quality of life. Baring in mind the lower than anticipated inclusion rate, there were no significant differences in HbA1c and quality of life between three different frequencies of SMBG in patients with stable glycemic control using one long-acting insulin injection. [ABSTRACT FROM AUTHOR]

Background: Patients with type 2 diabetes (T2D) are at increased risk for developing cancer. As approximately 8% of the world's population is living with T2D, even a slight increase in cancer risk could result in an enormous impact on the number of persons developing cancer. In addition, several glucose lowering drug classes for treating patients with T2D have been associated with a difference in risk of cancer overall, and especially for obesity related cancers. In what way and to what degree cancer risk is modified by the use of different sulfonylureas (SU) is unclear. The primary aim of this study will be to evaluate within-class SU differences in obesity related cancer risk. Secondary aims will be to investigate within-class SU differences in risk for all cancers combined and site-specific cancers separately (i.e. breast, colorectal, prostate, bladder and lung cancer) and to account for duration-response relationships between individual SU use and cancer risk.Methods: Patients will be selected from a Dutch primary care cohort of patients with T2D linked with the Dutch Cancer Registration (ZODIAC-NCR). Within this cohort study annually collected clinical data (e.g. blood pressure, weight, HbA1c) and nationwide data on cancer incidence are available. Time-dependent cox proportional hazard analyses will be performed to evaluate SU cancer risk, adjusted for potential confounders.Discussion: This study will be the first prospective cohort study investigating within-class SU differences in cancer risk and could contribute to improved decision making regarding the individual drugs within the class of SUs, and possibly improve quality of life and result in an increased cost-effectiveness of healthcare in patients with T2D.Trial Registration: Nederlands Trialregister ( NTR6166 ), 6 Jan 2017. [ABSTRACT FROM AUTHOR]

Aim To investigate changes in body weight trajectories after the addition of individual sulphonylureas ( SUs) to metformin in patients with type 2 diabetes. Materials and methods We conducted a retrospective observational cohort study, in a primary care setting in the Netherlands. Patients aged ≥18 years with type 2 diabetes who were included in the ZODIAC cohort between 1998 and 2012 and who received metformin monotherapy at inclusion (n = 29 195), and had used metformin as monotherapy for at least 1 year before receiving dual therapy through the addition of an SU for at least 1 year were eligible for inclusion. The primary outcome was within-drug yearly change in body weight after receiving add-on therapy with individual SUs during 5 years of follow-up. The secondary outcome was within-drug yearly change in glycated haemoglobin ( HbA1c). Annual changes in weight and HbA1c were estimated with linear mixed models, adjusted for age, gender and diabetes duration. Results A total of 2958 patients were included. No significant weight changes were observed within and between any of the individual SUs after treatment intensification (p = 0.24). In addition, no significant difference in weight between the add-on therapy combinations was observed (p = 0.26). The average HbA1c the year before intensification was 7.2% (55 mmol/mol) and dropped below 7.0% (53 mmol/mol) the year after. Conclusions In patients with type 2 diabetes treated in primary care, strict glycaemic control can be maintained with SUs used as add-on therapy to metformin, without the offset of relevant weight changes. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that many within-class differences exist between sulfonylureas (SUs), however, whether differences exist regarding the time it takes between initiating an SU and the need to intensify treatment with insulin is unclear. The aim of this study was investigate the relationships between the three frequently used sulphonylureas, prescribed as dual therapy next to metformin, and the time needed to treatment intensification with either insulin or oral triple therapy in patients with type 2 diabetes mellitus. Methods: Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) is a prospective observational cohort study set in primary care in the Netherlands. Annually collected data on diabetes medication and clinical variables within ZODIAC are used to evaluate the primary outcome, time to insulin and secondary outcome, time to either insulin or triple oral therapy. For statistical analysis a time-dependent cox proportional hazard model was used. Results: 3507 patients were included in the analysis, with a mean age of 61 (SD 11.4) and a median HbA1c of 6.8% [IQR 6.4–7.4] (50.8 mmol/mol [IQR 46.4–57.4]).The hazard ratio (HR) for the primary endpoint was 1.10 (95% CI 0.78–1.54) for metformin/glimepiride and 0.93 (95% CI 0.67–1.30) for metformin/tolbutamide with metformin/gliclazide as reference group. The HR for the secondary outcome was 1.04 (95% CI 0.78–1.40) and 0.85 (95% CI 0.64–1.13), respectively. Conclusion: In this large Dutch primary care cohort, new users of neither gliclazide, glimepiride nor tolbutamide as dual therapy with metformin, resulted in differences in the time needed for further treatment intensification. [ABSTRACT FROM AUTHOR]

Background. Online platforms offer opportunities for support in changing lifestyle and taking responsibility for one’s health, but engaging patients with type 2 diabetes is challenging. Previous studies have shown that patients interested in platforms were more often male, younger, and higher educated. This study aims to investigate differences in clinical and psychological characteristics between users and nonusers of a newly developed platform. Methods. A prospective study started in the Drenthe region of Netherlands. Participants in the study concerning quality of care and quality of life were additionally invited to use the platform. Results. 633 patients were registered after they opted for platform use. Of these patients, 361 (57.0%) never logged on, 184 (29.1%) were labeled “curious” users, and 88 (13.9%) were identified as “active” users. Users had lower HbA1c levels and more often hypertension compared to nonusers, and reported higher quality of life, better well-being, lower diabetes-related distress, and better medication adherence. Discussion. Platform use was associated with more favorable clinical and psychological characteristics relative to nonuse. Those with greater severity of disease, lower mood, and progression of disease used the platform the least. Other approaches need to be developed to reach these patients. Furthermore, improving the platform could also help to reach them. This trial is registered with Clinicaltrials.gov NCT01570140. [ABSTRACT FROM AUTHOR]

Background. Online platforms offer opportunities for support in changing lifestyle and taking responsibility for one’s health, but engaging patients with type 2 diabetes is challenging. Previous studies have shown that patients interested in platforms were more often male, younger, and higher educated. This study aims to investigate differences in clinical and psychological characteristics between users and nonusers of a newly developed platform. Methods. A prospective study started in the Drenthe region of Netherlands. Participants in the study concerning quality of care and quality of life were additionally invited to use the platform. Results. 633 patients were registered after they opted for platform use. Of these patients, 361 (57.0%) never logged on, 184 (29.1%) were labeled “curious” users, and 88 (13.9%) were identified as “active” users. Users had lower HbA1c levels and more often hypertension compared to nonusers, and reported higher quality of life, better well-being, lower diabetes-related distress, and better medication adherence. Discussion. Platform use was associated with more favorable clinical and psychological characteristics relative to nonuse. Those with greater severity of disease, lower mood, and progression of disease used the platform the least. Other approaches need to be developed to reach these patients. Furthermore, improving the platform could also help to reach them. This trial is registered with Clinicaltrials.gov NCT01570140. [ABSTRACT FROM AUTHOR]

Background: The howRu and howRwe are new short questionnaires which are meant to measure health-related quality of life and patient experience. However, validation at the individual patient level has not yet taken place. We aimed to investigate the validity of both questionnaires at the individual patient level.Methods: In this prospective validation study, patients were asked to complete both questionnaires and comment on their answers in a semi-structured in-depth interview. Based on the transcribed interviews, a panel of 45 general practitioners and 45 patients filled out the questionnaires as they thought the patients had completed them. The questionnaires were considered valid instruments when a reliable and acceptable level of agreement was reached between the patient's score and the score of a review panel, defined as a concordance correlation coefficient (CCC) of ≥0.70. Bland-Altman plots were also made.Results: Ninety patients were included. The CCC of the howRu total score of the review panel and patients was 0.80 (95 % CI 0.73 to 0.86). Bland-Altman plots showed a mean difference of -0.96 and the limits of agreement ranged from -2.87 to 0.95. The CCC of the howRwe total score was 0.57 (95 % CI 0.42 to 0.69). The mean difference on the Bland-Altman plots was -0.54 and the limits of agreement ranged from -3.59 to 2.52.Conclusions: The howRu seems to be a valid questionnaire for measuring health-related quality of life at the individual patient level. We do not advice to use the tested version of the howRwe questionnaire for assessing patient experience at the individual patient level.Trial Registration: The study was registered at clinicaltrials.gov NCT01830803 . Registration date: 5 April 2013. [ABSTRACT FROM AUTHOR]

Introduction Combined data suggest a bimodal association of alanine aminotransferase ( ALT) with mortality in the general population. Little is known about the association of ALT with mortality in patients with type 2 diabetes. We therefore investigated the association of ALT with all-cause, cardiovascular and noncardiovascular mortality in patients with type 2 diabetes. Design A prospective study was performed in patients with type 2 diabetes, treated in primary care, participating in the Zwolle Outpatient Diabetes project Integrating Available Care ( ZODIAC) study. Cox regression analyses were performed to determine the associations of log2-transformed baseline ALT with all-cause, cardiovascular and noncardiovascular mortality. Results In 1187 patients with type 2 diabetes (67 ± 12 years, 45% female), ALT levels were 11 (8-16) U/L. During median follow-up for 11·1 (6·1-14·0) years, 553 (47%) patients died, with 238 (20%) attributable to cardiovascular causes. Overall, ALT was inversely associated with all-cause mortality (hazard ratio [ HR] 0·81; 95% confidence interval [ CI] 0·72-0·92), independently of potential confounders. This was less attributable to cardiovascular mortality ( HR 0·87; 95% CI 0·72-1·05), than to noncardiovascular mortality ( HR 0·77; 95% CI 0·65-0·90). Despite the overall inverse association of ALT with mortality, it appeared that a bimodal association with all-cause mortality was present with increasing risk for levels of ALT above normal ( P = 0·003). Discussion In patients with type 2 diabetes, low levels of ALT are associated with an increased risk of all-cause mortality, in particular noncardiovascular mortality, compared to normal levels of ALT, while risk again starts to increase when levels are above normal. [ABSTRACT FROM AUTHOR]

Background: Two previous studies concluded that proenkephalin A (PENK-A) had predictive capabilities for stroke severity, recurrent myocardial infarction, heart failure and mortality in patients with stroke and myocardial infarction. Objectives: This study aimed to investigate the value of PENK-A as a biomarker for predicting mortality in patients with type 2 diabetes mellitus. Methods: Patients with type 2 diabetes mellitus were included from the prospective observational ZODIAC (Zwolle Outpatient Diabetes project Integrating Available Care) study. The present analysis incorporated two ZODIAC cohorts (1998 and 2001). Since blood was drawn for 1204 out of 1688 patients (71%), and information on relevant confounders was missing in 47 patients, the final sample comprised 1157 patients. Cox proportional hazard models were used for evaluating the relationship between PENK-A and (cardiovascular) mortality. Risk prediction capabilities were assessed with Harrell’s C statistics and the integrated discrimination improvement (IDI). Results: After a follow-up period of 14 years, 525 (45%) out of 1157 patients had died, of which 224 (43%) were attributable to cardiovascular factors. Higher Log PENK-A levels were not independently associated with increased (cardiovascular) mortality. Patients with PENK-A values in the highest tertile had a 49% (95%CI 1%-121%) higher risk of cardiovascular mortality compared to patients in the reference category (lowest tertile). C-values were not different after removing PENK-A from the Cox models and there were no significant differences in IDI values. Conclusions: The associations between PENK-A and mortality were strongly attenuated after accounting for all traditional risk factors. Furthermore, PENK-A did not seem to have additional value beyond conventional risk factors when predicting all-cause and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Background: In a sham-controlled double-blind trial, we aim to establish the efficacy and safety of the local application of laser therapy in patients with diabetes, onychomycosis and risk factors for diabetes-related foot complications. Onychomycosis leads to thickened and distorted nails, which in turn lead to increased local pressure. The combination of onychomycosis and neuropathy or peripheral arterial disease (PAD) increases the risk of developing diabetes-related foot complications. Usual care for high-risk patients with diabetes and onychomycosis is completely symptomatic with frequent shaving and clipping of the nails. No effective curative local therapies exist, and systemic agents are often withheld due to concerns for side effects and interactions. Methods/Design: The primary aim is to evaluate the efficacy of four sessions of Nd:YAG 1064 nM laser application on the one-year clinical and microbiological cure rate in a randomized, double-blind, sham-controlled design with blinded outcome assessment. Mandatory inclusion criteria are diagnosis of diabetes, risk factors for developing foot ulcers defined as a modified Simm's classification score 1 or 2 and either neuropathy or PAD. A total of 64 patients are randomized to intervention or sham treatment performed by a podiatrist. Discussion: This study will be the first double-blind study that investigates the effects of local laser therapy on onychomycosis, specifically performed in patients with diabetes with additional risk factors for foot complications. [ABSTRACT FROM AUTHOR]

Background: The hormone somatostatin inhibits growth hormone release from the pituitary gland and is theoretically linked to diabetes and diabetes related complications. This study aimed to investigate the relationship between levels of the stable somatostatin precursor, N-terminal prosomatostatin (NT-proSST), with mortality in type 2 diabetes (T2DM) patients. Methods: In 1,326 T2DM outpatients, participating in this ZODIAC prospective cohort study, Cox proportional hazards models were used to investigate the independent relationship between plasma NT-proSST concentrations with all-cause and cardiovascular mortality. Results: Median concentration of NT-proSST was 592 [IQR 450-783] pmol/L. During follow-up for 6 [3-10] years, 413 (31%) patients died, of which 176 deaths (43%) were attributable to cardiovascular causes. The age and sex adjusted hazard ratios (HRs) for all-cause and cardiovascular mortality were 1.48 (95%CI 1.14 - 1.93) and 2.21 (95%CI 1.49 - 3.28). However, after further adjustment for cardiovascular risk factors there was no independent association of log NT-proSST with mortality, which was almost entirely attributable to adjustment for serum creatinine. There were no significant differences in Harrell's C statistics to predict mortality for the models with and without NT-proSST: both 0.79 (95%CI 0.77 - 0.82) and 0.81 (95%CI 0.77 - 0.84). Conclusions: NT-proSST is unsuitable as a biomarker for cardiovascular and all-cause mortality in stable outpatients with T2DM. [ABSTRACT FROM AUTHOR]

Background: In a sham-controlled double-blind trial, we aim to establish the efficacy and safety of the local application of laser therapy in patients with diabetes, onychomycosis and risk factors for diabetes-related foot complications. Onychomycosis leads to thickened and distorted nails, which in turn lead to increased local pressure. The combination of onychomycosis and neuropathy or peripheral arterial disease (PAD) increases the risk of developing diabetes-related foot complications. Usual care for high-risk patients with diabetes and onychomycosis is completely symptomatic with frequent shaving and clipping of the nails. No effective curative local therapies exist, and systemic agents are often withheld due to concerns for side effects and interactions. Methods/Design: The primary aim is to evaluate the efficacy of four sessions of Nd:YAG 1064 nM laser application on the one-year clinical and microbiological cure rate in a randomized, double-blind, sham-controlled design with blinded outcome assessment. Mandatory inclusion criteria are diagnosis of diabetes, risk factors for developing foot ulcers defined as a modified Simm’s classification score 1 or 2 and either neuropathy or PAD. A total of 64 patients are randomized to intervention or sham treatment performed by a podiatrist. Discussion: This study will be the first double-blind study that investigates the effects of local laser therapy on onychomycosis, specifically performed in patients with diabetes with additional risk factors for foot complications. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to calculate the incidence and prevalence of radiating low back pain, to explore the long-term clinical course of radiating low back pain including the influence of radiculopathy (in a subsample of the study population) and non-radiating low back pain thereon, and to describe general practitioners' (GPs') treatment strategies for radiating low back pain. Design. A historic prospective cohort study. Setting. Dutch general practice. Subjects. Patients over 18 years of age with a first episode of radiating low back pain, registered by the ICPC code L86. Main outcome measures. Incidence and prevalence, clinical course of illness, initial diagnoses established by the GPs, and treatment strategies. Results. Mean incidence was 9.4 and mean prevalence was 17.2 per 1000 person years. In total, 390 patients had 1193 contacts with their GPs; 50% had only one contact with their GP. Consultation rates were higher in patients with a history of non-radiating low back pain and in patients with a diagnosis of radiculopathy in the first five years. In this study's subsample of 103 patients, L86 episodes represented radiculopathy in 50% of cases. Medication was prescribed to 64% of patients, mostly NSAIDs. Some 53% of patients were referred, mainly to physiotherapists and neurologists; 9% of patients underwent surgery. Conclusion. Watchful waiting seems to be sufficient general practice care in most cases of radiating low back pain. Further research should be focused on clarifying the relationship between radicular radiating low back pain, non-radicular radiating low back pain, and non-radiating low back pain. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes are at high risk of death prior to reaching end-stage renal disease, but most models predicting the risk of kidney disease do not take this competing risk into account. We aimed to compare the performance of Cox regression and competing risk models for prediction of early- and late-stage renal complications in type 2 diabetes. Methods: Patients with type 2 diabetes participating in the observational ZODIAC study were included. Prediction models for (micro)albuminuria and 50% increase in serum creatinine (SCr) were developed using Cox regression and competing risk analyses. Model performance was assessed by discrimination and calibration. Results: During a total follow-up period of 10 years, 183 out of 640 patients (28.6%) with normoalbuminuria developed (micro)albuminuria, and 22 patients (3.4%) died without developing (micro)albuminuria (i.e. experienced the competing event). Seventy-nine out of 1,143 patients (6.9%) reached the renal end point of 50% increase in SCr, while 219 (19.2%) died without developing the renal end point. Performance of the Cox and competing risk models predicting (micro)albuminuria was similar and differences in predicted risks were small. However, the Cox model increasingly overestimated the risk of increase in SCr in presence of a substantial number of competing events, while the performance of the competing risk model was quite good. Conclusions: In this study, we demonstrated that, in case of substantial numbers of competing events, it is important to account for the competing risk of death in renal risk prediction in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that the carpal tunnel syndrome seems to occur more frequently in patients with diabetes mellitus and might be associated with the duration of diabetes mellitus, microvascular complications and degree of glycaemic control. Primary aim was to determine if type 2 diabetes can be identified as a risk factor for carpal tunnel syndrome after adjusting for possible confounders. Furthermore, the influence of duration of diabetes mellitus, microvascular complications and glycaemic control on the development of carpal tunnel syndrome was investigated.Methods: Retrospective, case-control study using data from electronic patient charts from the Isala (Zwolle, the Netherlands). All patients diagnosed with carpal tunnel syndrome in the period from January 2011 to July 2012 were included and compared with a control group of herniated nucleus pulposus patients.Results: A total of 997 patients with carpal tunnel syndrome and 594 controls were included. Prevalence of type 2 diabetes was 11.5% in the carpal tunnel syndrome group versus 7.2% in the control group (Odds Ratio 1.67 (95% confidence interval 1.16-2.41)). In multivariate analyses adjusting for gender, age and body mass index, type 2 diabetes was not associated with carpal tunnel syndrome (OR 0.99 (95% CI 0.66-1.47)). No differences in duration of diabetes mellitus, microvascular complications or glycaemic control between groups were detected.Conclusion: Although type 2 diabetes was more frequently diagnosed among patients with carpal tunnel syndrome, it could not be identified as an independent risk factor. [ABSTRACT FROM AUTHOR]

Background Due to ongoing rise in need for care for people with chronic diseases and lagging increase in number of care providers, alternative forms of care provision and self-management support are needed. Empowering patients through an online care platform could help to improve patients' self-management and reduce the burden on the healthcare system. Methods Access to laboratory results and educational modules on diabetes will be offered through a platform for subjects with type 2 diabetes mellitus treated in primary care. Differences in socio-demographic and clinical characteristics between subjects expressing interest vs. disinterest to use the platform will be explored. Platform usage will be tracked and compared. Patient satisfaction and quality of life will be measured by validated questionnaires and economic analyses will be performed. Discussion This study is designed to assess the feasibility of use of an online platform in routine primary healthcare for subjects with type 2 diabetes mellitus in the Netherlands, and to study effects of use of the platform on treatment satisfaction, quality of life and clinical parameters. Although providing access to a online platform is not a novel intervention, usage and effects have not yet been studied in this patient population. Trial registration Trial registration: NCT01570140. [ABSTRACT FROM AUTHOR]

OBJECTIVE The midregional fragment of proadrenomedullin (MR-proADM) is a marker of endothelial dysfunction and has been associated with a variety of diseases. Our aim was to investigate whether MR-proADM is associated with new-onset albuminuria and cardiovascular (CV) and all-cause mortality in patients with type 2 diabetes treated in primary care. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes participating in the observational Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses were used to assess the relation of baseline MR-proADM with new-onset albuminuria and CV and all-cause mortality. Risk prediction capabilities of MR-proADM for new-onset albuminuria and CV and all-cause mortality were assessed with Harrell's C and the integrated discrimination improvement. RESULTS In 1,243 patients (mean age 67 [±12] years), the median follow-up was 5.6 years (interquartile range 3.1-10.1); 388 (31%) patients died, with 168 (12%) CV deaths. Log2 MR-proADM was associated with CV (hazard ratio 1.96 [95% CI 1.27-3.01]) and all-cause mortality (1.78 [1.34-2.36]) after adjusting for age, sex, BMI, smoking, systolic blood pressure, cholesterol-to-HDL ratio, duration of diabetes, HbA1c, ACE inhibitor/angiotensin receptor blocker, history of CV diseases, log serum creatinine, and log albumin-to-creatinine ratio. MR-proADM slightly improved mortality risk prediction. The age- and sex-adjusted, but not multivariate-adjusted, MR-proADM levels were associated with new-onset albuminuria. CONCLUSIONS MR-proADM was associated with CV and all-cause mortality in patients with type 2 diabetes after a median follow-up of 5.6 years. There was no independent relationship with new-onset albuminuria. In the availability of an extensive set of risk factors, there was little added effect of MR-proADM in risk prediction of CV and all-cause mortality. [ABSTRACT FROM AUTHOR]

The midregional fragment of proadrenomedullin (MR-proADM) is a marker of endothelial dysfunction and has been associated with a variety of diseases. Our aim was to investigate whether MR-proADM is associated with new-onset albuminuria and cardiovascular (CV) and all-cause mortality in patients with type 2 diabetes treated in primary care. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes participating in the observational Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses were used to assess the relation of baseline MR-proADM with new-onset albuminuria and CV and all-cause mortality. Risk prediction capabilities of MR-proADM for new-onset albuminuria and CV and all-cause mortality were assessed with Harrell's C and the integrated discrimination improvement. RESULTS In 1,243 patients (mean age 67 [±12] years), the median follow-up was 5.6 years (interquartile range 3.1-10.1); 388 (31%) patients died, with 168 (12%) CV deaths. Log2 MR-proADM was associated with CV (hazard ratio 1.96 [95% CI 1.27-3.01]) and all-cause mortality (1.78 [1.34-2.36]) after adjusting for age, sex, BMI, smoking, systolic blood pressure, cholesterol-to-HDL ratio, duration of diabetes, HbA1c, ACE inhibitor/angiotensin receptor blocker, history of CV diseases, log serum creatinine, and log albumin-to-creatinine ratio. MR-proADM slightly improved mortality risk prediction. The age- and sex-adjusted, but not multivariate-adjusted, MR-proADM levels were associated with new-onset albuminuria. CONCLUSIONS MR-proADM was associated with CV and all-cause mortality in patients with type 2 diabetes after a median follow-up of 5.6 years. There was no independent relationship with new-onset albuminuria. In the availability of an extensive set of risk factors, there was little added effect of MR-proADM in risk prediction of CV and all-cause mortality. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress plays an underlying pathophysiologic role in the development of diabetes complications. The aim of this study was to investigate peroxiredoxin 4 (Prx4), a proposed novel biomarker of oxidative stress, and its association with and capability as a biomarker in predicting (cardiovascular) mortality in type 2 diabetes mellitus. Methods: Prx4 was assessed in baseline serum samples of 1161 type 2 diabetes patients. Cox proportional hazard models were used to evaluate the relationschip between Prx4 and (cardiovascular) mortality. Risk prediction capabilities of Prx4 for (cardiovascular) mortality were assessed with Harrell’s C statistic, the integrated discrimination improvement and net reclassification improvement. Results: Mean age was 67 and the median diabetes duration was 4.0 years. After a median follow-up period of 5.8 years, 327 patients died; 137 cardiovascular deaths. Prx4 was associated with (cardiovascular) mortality. The Cox proportional hazard models added the variables: Prx4 (model 1); age and gender (model 2), and BMI, creatinine, smoking, diabetes duration, systolic blood pressure, cholesterol-HDL ratio, history of macrovascular complications, and albuminuria (model 3). Hazard ratios (HR) (95% CI) for cardiovascular mortality were 1.93 (1.57 – 2.38), 1.75 (1.39 – 2.20), and 1.63 (1.28 – 2.09) for models 1, 2 and 3, respectively. HR for all-cause mortality were 1.73 (1.50 – 1.99), 1.50 (1.29 – 1.75), and 1.44 (1.23 – 1.67) for models 1, 2 and 3, respectively. Addition of Prx4 to the traditional risk factors slightly improved risk prediction of (cardiovascular) mortality. Conclusions: Prx4 is independently associated with (cardiovascular) mortality in type 2 diabetes patients. After addition of Prx4 to the traditional risk factors, there was a slightly improvement in risk prediction of (cardiovascular) mortality in this patient group. [ABSTRACT FROM AUTHOR]

Objective and Design: Gliclazide has been associated with a low risk of hypoglycemic episodes and beneficial long-term cardiovascular safety in observational cohorts. The aim of this study was to assess in a systematic review and meta-analysis of randomized controlled trials the safety and efficacy of gliclazide compared to other oral glucose-lowering agents (PROSPERO2013:CRD42013004156) Data Sources: Medline, EMBASE, Clinicaltrials.gov, Trialregister.nl, Clinicaltrialsregister.eu and the Cochrane database. Selection: Included were randomized studies of at least 12 weeks duration with the following outcomes: HbA1c change, incidence of severe hypoglycemia, weight change, cardiovascular events and/or mortality when comparing gliclazide with other oral blood glucose lowering drugs. Bias was assessed with the Cochrane risk of bias tool. The inverse variance random effects model was used. Results: Nineteen trials were included; 3,083 patients treated with gliclazide and 3,155 patients treated with other oral blood glucose lowering drugs. There was a considerable amount of heterogeneity between and bias in studies. Compared to other glucose lowering agents except metformin, gliclazide was slightly more effective (−0.13% (95%CI: −0.25, −0.02, I2 55%)). One out of 2,387 gliclazide users experienced a severe hypoglycemic event, whilst also using insulin. There were 25 confirmed non-severe hypoglycemic events (2.2%) in 1,152 gliclazide users and 22 events (1.8%) in 1,163 patients in the comparator group (risk ratio 1.09 (95% CI: 0.20, 5.78, I2 77%)). Few studies reported differences in weight and none were designed to evaluate cardiovascular outcomes. Conclusions: The methodological quality of randomized trials comparing gliclazide to other oral glucose lowering agents was poor and effect estimates on weight were limited by publication bias. The number of severe hypoglycemic episodes was extremely low, and gliclazide appears at least equally effective compared to other glucose lowering agents. None of the trials were designed for evaluating cardiovascular outcomes, which warrants attention in future randomized trials. [ABSTRACT FROM AUTHOR]

Objective: Copeptin, a surrogate marker for arginine vasopressin, has been associated with cardiovascular (CV) events and mortality in patients with type 2 diabetes complicated by end-stage renal disease or acute myocardial infarction. For stable outpatients, these associations are unknown. Our aim was to investigate whether copeptin is associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care.Research Design and Methods: Patients with type 2 diabetes participating in the observational Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses with age as time scale were used to assess the relationship of baseline copeptin with CV and all-cause mortality.Results: We included 1,195 patients (age 67±12 years, 44% male). Median baseline copeptin concentration was 5.4 (interquartile range [IQR] 3.1-9.6) pmol/L. After a median follow-up of 5.9 (IQR 3.2-10.1) years, 345 patients died (29%), with 148 CV deaths (12%). Log2 copeptin was associated with CV (hazard ratio 1.17 [95% CI 0.99-1.39]; P=0.068) and all-cause mortality (1.22 [1.09-1.36]; P=0.001) after adjustment for age, sex, BMI, smoking, systolic blood pressure, total cholesterol to HDL ratio, duration of diabetes, HbA1c, treatment with ACE inhibitors and angiotensin receptor blockers, history of CV diseases, log serum creatinine, and log albumin to creatinine ratio; however, copeptin did not substantially improve risk prediction for CV (integrated discrimination improvement 0.14% [IQR -0.27 to 0.55%]) and all-cause mortality (0.77% [0.17-1.37%]) beyond currently used clinical markers.Conclusions: We found copeptin to be associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care. Intervention studies should show whether the high CV risk in type 2 diabetes can be reduced by suppression of vasopressin, for example by reducing salt intake. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Copeptin, a surrogate marker for arginine vasopressin, has been associated with cardiovascular (CV) events and mortality in patients with type 2 diabetes complicated by end-stage renal disease or acute myocardial infarction. For stable outpatients, these associations are unknown. Our aim was to investigate whether copeptin is associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care. RESEARCH DESIGN AND METHODS--Patients with type 2 diabetes participating in the observational ZwolleOutpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses with age as time scale were used to assess the relationship of baseline copeptin with CV and all-cause mortality. RESULTS--We included 1,195 patients (age 67 ± 12 years, 44% male). Median baseline copeptin concentration was 5.4 (interquartile range [IQR] 3.1-9.6) pmol/L. After a median follow-up of 5.9 (IQR 3.2-10.1) years, 345 patients died (29%), with 148 CV deaths (12%). Log2 copeptin was associated with CV (hazard ratio 1.17 [95%CI 0.99-1.39]; P = 0.068) and all-cause mortality (1.22 [1.09-1.36]; P = 0.001) after adjustment for age, sex, BMI, smoking, systolic blood pressure, total cholesterol to HDL ratio, duration of diabetes, HbA1c, treatment with ACE inhibitors and angiotensin receptor blockers, history of CV diseases, log serum creatinine, and log albumin to creatinine ratio; however, copeptin did not substantially improve risk prediction for CV (integrated discrimination improvement 0.14% [IQR 20.27 to 0.55%]) and all-cause mortality (0.77% [0.17-1.37%]) beyond currently used clinical markers. CONCLUSIONS--We found copeptin to be associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care. Intervention studies should show whether the high CV risk in type 2 diabetes can be reduced by suppression of vasopressin, for example by reducing salt intake. [ABSTRACT FROM AUTHOR]

Objective: Evidence that midregional fragment of pro-A-type natriuretic peptide (MR-proANP) is a marker of mortality in patients with type 2 diabetes is limited. Therefore, we aimed to investigate the capabilities of MR-proANP in predicting mortality. We also investigated whether MR-proANP influences the relationship between blood pressure and mortality in old age.Research Design and Methods: In 1998, 1,143 primary care patients with type 2 diabetes participated in the ZODIAC study. Because blood was drawn for 867 patients (76%) and confounders were missing for 19 patients, the final study sample comprised 848 patients. After a follow-up time of 10 years, we used Cox proportional hazard models to evaluate the relationship between MR-proANP and (cardiovascular) mortality. Harrell C statistic was used to compare models with and without MR-proANP. The regression analyses were repeated without MR-proANP for patients aged older than 75 years.Results: Median MR-proANP in the total study sample was 75 pmol/L (interquartile range, 48-124 pmol/L). During follow-up, 354 (42%) out of 848 patients had died, of whom 152 (43%) deaths were attributable to cardiovascular factors. MR-proANP was independently associated with all-cause and cardiovascular mortality, irrespective of age. During old age, there was a significant inverse relationship between blood pressure and mortality. This relationship did not change after adjustment for MR-proANP.Conclusions: MR-proANP is independently associated with mortality in patients with type 2 diabetes. MR-proANP did not influence the inverse relationship between blood pressure and mortality in elderly patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Evidence that midregional fragment of pro-A-type natriuretic peptide (MR-proANP) is a marker of mortality in patients with type 2 diabetes is limited. Therefore, we aimed to investigate the capabilities of MR-proANP in predicting mortality. We also investigated whether MR-proANP influences the relationship between blood pressure and mortality in old age. RESEARCHDESIGNANDMETHODS--In 1998, 1,143 primary care patients with type 2 diabetes participated in the ZODIAC study. Because blood was drawn for 867 patients (76%) and confounders were missing for 19 patients, the final study sample comprised 848 patients. After a follow-up time of 10 years, we used Cox proportional hazard models to evaluate the relationship between MR-proANP and (cardiovascular) mortality. Harrell C statistic was used to compare models with and without MR-proANP. The regression analyses were repeated without MR-proANP for patients aged older than 75 years. RESULTS--Median MR-proANP in the total study sample was 75 pmol/L (interquartile range, 48-124 pmol/L). During follow-up, 354 (42%) out of 848 patients had died, of whom152 (43%) deaths were attributable to cardiovascular factors. MR-proANP was independently associated with all-cause and cardiovascular mortality, irrespective of age. During old age, there was a significant inverse relationship between blood pressure and mortality. This relationship did not change after adjustment for MR-proANP. CONCLUSIONS--MR-proANP is independently associated with mortality in patients with type 2 diabetes. MR-proANP did not influence the inverse relationship between blood pressure and mortality in elderly patients. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is a leading cause of death. It is important to identify patient and treatment factors that are related to successful cardiovascular risk reduction in general practice. This study investigates which patient and treatment factors are related to changes in cardiovascular risk estimation, expressed as the Systematic Coronary Risk Evaluation (SCORE) 10 year risk of cardiovascular mortality. Methods: 179 general practice patients with mild-moderately elevated cardiovascular risk followed a one-year programme which included structured lifestyle and medication treatment by practice nurses, with or without additional self-monitoring. From the patient and treatment data collected as part of the "Self-monitoring and Prevention of RIsk factors by Nurse practitioners in the region of Groningen" randomized controlled trial (SPRING-RCT), the contribution of patient and treatment factors to the change in SCORE was analysed with univariate and multivariate analyses. Results: In multivariate analyses with multiple patient and treatment factors, only SCORE at baseline, and addition of or dose change in lipid lowering or antihypertensive medications over the course of the study were significantly related to change in SCORE. Conclusions: Our analyses support the targeting of treatment at individuals with a high SCORE at presentation. Lipid lowering medication was added or changed in only 12% of participants, but nevertheless was significantly related to ΔSCORE in this study population. Due to the effect of medication in this practice-based project, the possible additional effect of the home monitoring devices, especially for individuals with no indication for medication, may have been overshadowed. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the association between plasma COOH-terminal proendothelin-1 (CT-proET-1) and fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in patients with type 2 diabetes.Research Design and Methods: A total of 1,225 patients with type 2 diabetes participated in this prospective observational study of two combined cohorts. Three clinical end points were studied: fatal cardiovascular events, all-cause mortality, and new-onset albuminuria. After a median follow-up of 3 or 10 years, Cox proportional hazard modeling was used to investigate the association between CT-proET-1 and the end points. Harrell C statistic, the Groennesby and Borgan test, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI) were used to evaluate whether CT-proET-1 is of additional value compared with classic cardiovascular and renal risk factors.Results: During follow-up, 364 (30%) patients died, 150 (42%) of whom died of cardiovascular disease; 182 (26.7%) of 688 patients with normoalbuminuria at baseline developed albuminuria. CT-proET-1 was associated with fatal cardiovascular events, all-cause mortality, and new-onset albuminuria with hazard ratios of 1.59 (95% CI 1.15-2.20), 1.41 (95% CI 1.14-1.74), and 1.48 (95% CI 1.10-2.01), respectively. Addition of CT-proET-1 to a model containing traditional risk factors leads only to improved prediction of fatal cardiovascular events. The IDI appeared significant for fatal cardiovascular events (0.82 [0.1-1.54]) and all-cause mortality (0.4 [0.05-0.92]), but not for new-onset albuminuria.Conclusions: CT-proET-1 has additional value for the prediction of fatal cardiovascular events and new-onset albuminuria in patients with type 2 diabetes, compared with conventional risk factors, but not for all-cause mortality. [ABSTRACT FROM AUTHOR]

OBJECTIVE--The aim of this study was to investigate the association between plasma COOH-terminal proendothelin-1 (CT-proET-1) and fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS--A total of 1,225 patients with type 2 diabetes participated in this prospective observational study of two combined cohorts. Three clinical end points were studied: fatal cardiovascular events, all-cause mortality, and new-onset albuminuria. After a median follow-up of 3 or 10 years, Cox proportional hazard modeling was used to investigate the association between CT-proET-1 and the end points. Harrell C statistic, the Groennesby and Borgan test, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI) were used to evaluate whether CT-proET-1 is of additional value compared with classic cardiovascular and renal risk factors. RESULTS--During follow-up, 364 (30%) patients died, 150 (42%) of whom died of cardiovascular disease; 182 (26.7%) of 688 patients with normoalbuminuria at baseline developed albuminuria. CT-proET-1 was associated with fatal cardiovascular events, all-cause mortality, and new-onset albuminuria with hazard ratios of 1.59 (95% CI 1.15-2.20), 1.41 (95% CI 1.14-1.74), and 1.48 (95% CI 1.10-2.01), respectively. Addition of CT-proET-1 to a model containing traditional risk factors leads only to improved prediction of fatal cardiovascular events. The IDI appeared significant for fatal cardiovascular events (0.82 [0.1-1.54]) and all-cause mortality (0.4 [0.05-0.92]), but not for new-onset albuminuria. CONCLUSIONS--CT-proET-1 has additional value for the prediction of fatal cardiovascular events and new-onset albuminuria in patients with type 2 diabetes, compared with conventional risk factors, but not for all-cause mortality. [ABSTRACT FROM AUTHOR]