Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have... Show moreIntroduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM.Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals.Trial registration number NTR6134; Pre-results. Show less
Veenbrink, A.; Kroon, F.; Mutsert, R. de; Visser, W.; Cessie, S. le; Rosendaal, F.; Kloppenburg, M. 2017
Objective To assess causes, trends and substandard care factors in maternal mortality in the Netherlands. Design Confidential enquiry into the causes of maternal mortality. Setting Nationwide in... Show moreObjective To assess causes, trends and substandard care factors in maternal mortality in the Netherlands. Design Confidential enquiry into the causes of maternal mortality. Setting Nationwide in the Netherlands. Population 2,557,208 live births. Methods Data analysis of all maternal deaths in the period 1993-2005. Main outcome measures Maternal mortality. Results The overall maternal mortality ratio was 12.1 per 100 000 live births, which was a statistically significant rise compared with the maternal mortality ratio of 9.7 in the period 1983-1992 (OR 1.2, 95% CI 1.0-1.5). The most frequent direct causes were (pre-) eclampsia, thromboembolism, sudden death in pregnancy, sepsis, obstetric haemorrhage and amniotic fluid embolism. The number of indirect deaths also increased, mainly caused by an increase in cardiovascular disorders (OR 2.5, 95% CI 1.4-4.6). Women younger than 20 years and older than 45 years, those with high parity or from nonwestern immigrant populations were at higher risk. Most substandard care was found in women with pre-eclampsia (91%) and in immigrant populations (62%). Conclusions Maternal mortality in the Netherlands has increased since 1983-1992. Pre-eclampsia remains the number one cause. Groups at higher risk for complications during pregnancy should be better identified early in pregnancy or before conception, in order to receive preconception advice and more frequent antenatal visits. There is an urgent need for the better education of women and professionals concerning the danger signs, and for the training of professionals in order to improve maternal health care. Show less
Objective To assess the impact of different subsets of symptomatic hand osteoarthritis (OA) on pain and disability. Methods From 308 patients with hand OA a group with carpometacarpal joint (CMCJ)... Show moreObjective To assess the impact of different subsets of symptomatic hand osteoarthritis (OA) on pain and disability. Methods From 308 patients with hand OA a group with carpometacarpal joint (CMCJ) symptoms only (group I, n = 20) was identified as well as groups with symptoms at the interphalangeal joints (IPJs) only (group II, n = 138), and symptoms at both sites (group III, n = 150). Hand pain and function, assessed with the AUSCAN, were compared between groups using linear mixed models. Radiological OA was assessed using the Kellgren-Lawrence grading scale. Results Mean (SD) AUSCAN scores for groups I, II and III were 23.1 (11.7), 18.3 (11.9) and 26.4 (12.5), respectively. After adjustment for age, gender, body mass index, family effects and number of symptomatic hand joints, significant differences in AUSCAN scores of 7.4 (95% CI 1.8 to 13.0) between groups I and II, and 5.7 (95% CI 2.7 to 8.6) between groups II and III were found. AUSCAN scores were 5.8 (95% CI 3.1 to 8.6) higher for patients with versus patients without CMCJ symptoms. Kellgren-Lawrence scores did not differ between groups. Conclusion In symptomatic hand OA, CMCJ OA contributes more to pain and disability than IPJ OA. Hence, treatment of CMCJ OA should be emphasised, even if it coincides with IPJ OA. Show less
OBJECTIVE: /st> To assess the impact of different subsets of symptomatic hand osteoarthritis (OA) on pain and disability. METHODS: /st> From 308 patients with hand OA a group with... Show moreOBJECTIVE: /st> To assess the impact of different subsets of symptomatic hand osteoarthritis (OA) on pain and disability. METHODS: /st> From 308 patients with hand OA a group with carpometacarpal joint (CMCJ) symptoms only (group I, n=20) was identified as well as groups with symptoms at the interphalangeal joints (IPJs) only (group II, n=138), and symptoms at both sites (group III, n=150). Hand pain and function, assessed with the AUSCAN, were compared between groups using linear mixed models. Radiological OA was assessed using the Kellgren-Lawrence grading scale. RESULTS: /st> Mean (SD) AUSCAN scores for groups I, II and III were 23.1 (11.7), 18.3 (11.9) and 26.4 (12.5), respectively. After adjustment for age, gender, body mass index, family effects and number of symptomatic hand joints, significant differences in AUSCAN scores of 7.4 (95% CI 1.8 to 13.0) between groups I and II, and 5.7 (95% CI 2.7 to 8.6) between groups II and III were found. AUSCAN scores were 5.8 (95% CI 3.1 to 8.6) higher for patients with versus patients without CMCJ symptoms. Kellgren-Lawrence scores did not differ between groups. CONCLUSION: /st> In symptomatic hand OA, CMCJ OA contributes more to pain and disability than IPJ OA. Hence, treatment of CMCJ OA should be emphasised, even if it coincides with IPJ OA. Show less
OBJECTIVE: To assess the impact of different subsets of symptomatic hand osteoarthritis (OA) on pain and disability. METHODS: From 308 hand OA patients a group with CMCJ symptoms only (group I, n... Show moreOBJECTIVE: To assess the impact of different subsets of symptomatic hand osteoarthritis (OA) on pain and disability. METHODS: From 308 hand OA patients a group with CMCJ symptoms only (group I, n=20) was identified as well as groups with symptoms at the interphalangeal joints (IPJs) only (group II, n=138), and symptoms at both sites (group III, n=150). Hand pain and function, assessed with the AUSCAN, were compared between groups using linear mixed models. Radiological OA was assessed using the Kellgren-Lawrence grading scale. RESULTS: Mean (SD) AUSCAN scores for group I, II and III were 23.1 (11.7), 18.3 (11.9) and 26.4 (12.5), respectively. After adjustment for age, gender, BMI, family effects and number of symptomatic hand joints, significant differences in AUSCAN scores of 7.4 (95% CI 1.8-13.0) between group I and II, and 5.7 (95% CI 2.7-8.6) between group II and III were found. AUSCAN scores were 5.8 (95% CI 3.1-8.6) higher for patients with versus patients without CMCJ symptoms. Kellgren-Lawrence scores did not differ between groups. CONCLUSION: In symptomatic hand OA, CMCJ OA contributes more to pain and disability than IPJ OA. Hence, treatment of CMCJ OA should be emphasized, even if it coincides with IPJ OA. Show less
