Recent publications
Background
Individuals with a germline CDKN2A pathogenic variant (PV) have an increased lifetime risk of melanoma and pancreatic cancer. It is unknown whether the CDKN2A PV impacts quality of life (QoL). Therefore we aimed to assess QoL and psychological distress in families affected by the PV.
Methods
This cross‐sectional study included confirmed carriers and those with a 50% likelihood of carrying the PV (at‐risk carriers) under cancer surveillance who were invited to complete a one‐time questionnaire. Both confirmed and at‐risk carriers are offered skin surveillance, whereas only confirmed carriers aged 40 years or older can participate in pancreatic surveillance.
Results
In total, 59/247 (24%) individuals under skin surveillance only (skin surveillance group) and 188/290 (65%) individuals under both skin and pancreatic cancer surveillance (pancreatic surveillance group) responded. In both surveillance groups, health‐related QoL and general distress levels were within the general population norms. However, more than 40% of all study participants reported melanoma‐related distress. Pancreatic cancer‐related distress was experienced by 45% of the pancreatic surveillance group. Determinants of cancer‐related distress were a first‐degree relative with melanoma or pancreatic cancer, increased cancer risk perception, and poor general health perception. Over 80% of the participants felt that the benefits of cancer surveillance outweigh the disadvantages.
Conclusion
In conclusion, confirmed and at‐risk carriers of the CDKN2A PV under cancer surveillance experienced similar levels of QoL and general distress compared to the general population. However, cancer‐related worry was substantial in this population. These findings can help identify individuals who may benefit from psychological support.
Objective
To compare the 12‐year effectiveness of pelvic floor muscle training versus midurethral sling surgery for moderate to severe female stress urinary incontinence.
Design
Observational follow‐up study of a randomised controlled trial.
Setting
Conducted at the Division of Gynaecology, University Medical Centre Utrecht, The Netherlands.
Population
Women from the PORTRET study experiencing moderate to severe stress urinary incontinence.
Methods
A validated questionnaire was sent to participants.
Main Outcome Measures
The primary outcome was subjective improvement in urinary incontinence symptoms. Secondary outcomes included subjective cure, severity of incontinence, impact of incontinence as urogenital symptom and cross‐over and re‐operation rates.
Results
In this long‐term study, 184 of 386 (47.7%) women responded to the questionnaire. Cross‐over (86.9%) from the initial physiotherapy group to surgery was very high. No statistically significant differences were found in the intention to treat analysis. However, the post hoc analysis showed that women who underwent physiotherapy only reported a statistically significant lower improvement compared to those who underwent initial surgery (50.6% absolute difference; 95% CI 28.2–73.1) or surgery after physiotherapy (49.7% absolute difference; 95% CI 25.8–73.7). Subjective cure, decrease in perceived severity and impact of urinary incontinence also statistically significantly favoured women who underwent (initial) surgery Re‐operation was reported by 4.6% of women.
Conclusion
This 12‐year follow‐up study showed a very high cross‐over rate to surgical treatment, considering a substantial proportion of non‐responders. Midurethral sling surgery, either initial or after physiotherapy, statistically significantly improved subjective outcomes for moderate to severe stress urinary incontinence as compared to pelvic floor muscle physiotherapy only in the long‐term.
The purpose of this study is to evaluate the efficacy of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) in adolescents with irritable bowel syndrome (IBS) and functional abdominal pain-not otherwise specified (FAP-NOS) in a non-guided setting, resembling clinical practice. This prospective multicenter cohort study conducted in 13 centers included patients aged 12–18 years diagnosed with IBS or FAP-NOS. Patients received educational material on FODMAPs, including extensive lists of high and low FODMAP foods and additional online information. They were instructed to replace high FODMAP foods with low FODMAP alternatives for the duration of 4 weeks. No dietician was consulted. The primary end point was the proportion of patients with treatment success (≥ 30% reduction of abdominal pain intensity) at 4 weeks. The key secondary outcome was adequate relief of IBS/FAP-NOS symptoms. Of the 325 included patients, 81 patients (24.9%) achieved treatment success (≥ 30% reduction of abdominal pain intensity) after 4 weeks, with higher rates in patients with IBS (29.3%) than FAP-NOS (16.8%, OR 2.16 (1.04–4.48)). Adequate relief was reported in 51 patients (15.7%). There was a significant decrease in abdominal pain intensity (2.2 (1.1) vs. 2.5 (1.0), P < 0.001), daily bloating (2.4 (2.1) vs. 2.8 (2.3), P < 0.001), and flatulence (2.4 (2.1) vs. 2.8 (2.3), P = 0.001). Adverse events were mild and infrequent.
Conclusion: The low FODMAP diet in a non-guided setting, mimicking clinical practice, yielded treatment success in almost 30% adolescents with IBS and 17% in FAP-NOS, suggesting it may not be the first treatment option for these patients.
Trial registration: EUCTR2015-003293–32-NL. What is Known:
• Irritable bowel syndrome (IBS) and functional abdominal pain-not otherwise specified (FAP-NOS) are common disorders in children which negatively impact quality of life.
• While a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) has demonstrated effectiveness in adult IBS, its efficacy in pediatric IBS and FAP-NOS remains uncertain.
• Clinical application of the low FODMAP diet often occurs without dietician consultation, contrary to controlled trial settings.
What is New:
• The low FODMAP diet, without dietician guidance, resulted in treatment success in almost 30% of adolescents with IBS and only 17% with FAP-NOS.
• With only 15.7% of participants achieving adequate relief of IBS/FAP-NOS symptoms, the non-guided low FODMAP diet may not be the first treatment option for pediatric IBS and FAP-NOS.
Importance
Perineal wound complications are common following abdominoperineal resection for rectal cancer and might have substantial and long-lasting implications for patients’ recovery.
Objective
To evaluate the superiority of gluteal turnover flap closure compared to primary closure in patients with rectal cancer undergoing abdominoperineal resection.
Design, Setting, and Participants
The BIOPEX-2 study was an investigator-initiated, parallel-group, multicenter randomized clinical trial conducted at 19 centers in the Netherlands and the UK between June 2019 and November 2023, including 12 months of follow-up. Data analysis was performed from October 2023 to December 2023. Independent perineal wound assessors were masked to the type of closure. Eligibility criteria were resection of rectal cancer by abdominoperineal resection, aged 18 years or older, and ability to complete follow-up. In modified intention-to-treat analyses, patients were assigned to either primary closure or gluteal turnover flap closure.
Intervention
Gluteal turnover flap closure started with a half-moon–shaped perineal skin island that was incised and deepithelialized. Subsequently, the subcutaneous fat was dissected toward the gluteal fascia, after which the dermis was sutured to the contralateral levator remnant, followed by midline closure.
Main Outcomes and Measures
The primary outcome was uncomplicated wound healing at 30 days postoperatively, defined as a Southampton wound score less than 2. Secondary outcomes included presacral abscess formation and wound-related readmissions.
Results
A total of 175 patients were randomized, but 7 did not undergo abdominoperineal resection and 3 withdrew consent. In the modified intention-to-treat analyzes, 86 patients were assigned to primary closure and 79 patients to gluteal turnover flap closure. Of these 165 patients, mean (SD) patient age was 67 (10) years, and 57 patients (34.5%) were female. Uncomplicated perineal wound healing was present in 49 of 82 patients (60%) after primary closure, which did not significantly differ from flap closure (42 of 76 patients [55%]). Presacral abscess developed significantly more often after primary closure than flap closure (19 of 86 patients [22%] vs 7 of 78 patients [9%]; P = .02), and more percutaneous presacral abscess drainage was performed in the control group (primary closure) (7 patients [8%] vs 1 patient [1%]; P = .04). Perineal wound–related readmission occurred in 18 patients (21%) after primary closure and in 10 patients (13%) after gluteal flap closure ( P = .17).
Conclusion and Relevance
In this parallel-group, multicenter randomized clinical trial, gluteal turnover flap closure did not show superiority over primary closure in 30-day perineal wound healing after abdominoperineal resection for rectal cancer. However, flap closure significantly reduced presacral abscess formation.
Trial Registration
ClinicalTrials.gov Identifier: NCT04004650
Background
Internal herniation (IH) is a potentially life-threatening complication after gastric bypass. Accurate diagnosis of IH remains challenging. This study aims to validate the Eindhoven2020 (EHV20) scoring system for ruling out IH and seeks to improve its diagnostic accuracy through additional radiologic parameters.
Methods
Patients participating in a prospective study on abdominal pain after gastric bypass surgery were selected if a CT scan was performed. CT scans were scored following the EHV20 scoring system containing ten signs of IH to confirm the individual and collective accuracy of these signs. Also, we evaluated the diagnostic value of additional radiologic parameters: delayed passage of contrast, dilated intestinal loops, and free fluid.
Results
A total of 375 patients with abdominal pain were included. IH was confirmed during laparoscopy in 27 patients. On CT, the highest sensitivity was achieved by the swirl sign (66.7%) and the highest specificity by a small bowel behind the superior mesenteric artery (99.7%). The area under the receiver operating characteristic curve (AUC) based on the EHV20 scoring system for ruling out IH was 0.845 (95% CI 0.730–0.959). The AUC could be improved to 0.905 (95% CI 0.825–0.985) (p = 0.088) through the incorporation of several additional signs. Overall, this new scoring system included swirl sign, small bowel obstruction, enlarged nodes, venous congestion, mesenteric edema, dilated alimentary or biliary loop, free fluid, and backward flow in the biliary loop with possible backflow in the residual stomach.
Conclusions
Incorporation of additional CT signs into an existing scoring system can help clinicians to safely rule out IH in patients with abdominal pain after bariatric surgery.
Purpose
Thoracolumbar kyphosis (TLK) is frequently reported in children with achondroplasia. The combination of TLK and the narrow spinal canal in achondroplasia increases the risk of developing symptomatic spinal stenosis. However, there is no consensus on the optimal management of TLK.
Methods
This retrospective cohort study evaluated children under four years old with achondroplasia, monitoring TLK every six months. Pathologic TLK was defined as a Cobb angle of 20 degrees or more between T10 and L2. Management involved either a wait-and-see policy, which prohibited unsupported sitting, or bracing. Surgery was reserved for severe progressive TLK or spinal stenosis cases. TLK was evaluated over time. A receiver operating characteristic curve determined the baseline threshold where wait-and-see management failed to resolve TLK below 20 degrees. Multiple linear regression compared bracing versus wait-and-see management for cases exceeding 40 degrees.
Results
Sixty-two patients were included, with a median age of 10 months and a median follow-up of 31 months. TLK prevalence decreased from 85% at baseline to 42% at final follow-up. The mean Cobb angle decreased from 31 ± 11 degrees to 22 ± 16 degrees (p < 0.001). The threshold for ineffective wait-and-see management was identified as 33 degrees. Bracing resulted in significantly more TLK reduction than wait-and-see management for cases exceeding 40 degrees (15 degree difference, 95% CI 2–28, p = 0.023). Three patients required surgery.
Conclusion
TLK is highly prevalent in achondroplasia, necessitating careful monitoring. A wait-and-see policy with restrictions on unsupported sitting is recommended initially, but early bracing should be considered for more severe cases.
Background
Early surgery in traumatic spinal fracture treatment may facilitate prompt mobilization, encountering affiliated complications. However, the safety and the benefits of early surgery are being questioned in spinal trauma patients. Therefore, the objective of this retrospective study is to investigate the effect of surgical timing on perioperative complications in these patients.
Methods
Spinal trauma patients who underwent surgery between 2010 and 2020 in two Dutch Level-I trauma centers were included retrospectively and divided into an early (< 24 h), late (between 24 and 72 h) and delayed (> 72 h) surgical cohort. The primary outcome was the occurrence of peri-operative complications. Besides surgical timing, trauma and patient-specific factors were also analyzed as potential risk factors for the occurrence of complications.
Results
A total of 394 patients were included, of whom 149 received early, 159 late and 86 delayed surgical treatment. The occurrence of perioperative complications was significantly associated with age, body mass index, comorbidities, ASA grade 3 and 4, spinal cord injury (SCI), AO Spine type C injury, additional chest injury, and surgical delay. A multivariable analysis showed that age, ASA category, AO Spine classification and SCI were significantly associated with perioperative complications. Moreover, a subsequent analysis in non-SCI patients demonstrated an association between perioperative complications and delayed surgery.
Conclusions
In this study, delayed surgical treatment is potentially associated with more perioperative complications compared to early surgery in non-SCI patients. Other possible risk factors for the occurrence of perioperative complications may be older age, ASA 3 and 4, AO spine C injury and SCI.
Purpose
This study aimed to identify trajectories of BMI, obesity-specific health-related quality of life (HR-QoL), and depression trajectories from pre-surgery to 24 months post-bariatric metabolic surgery (BMS), and explore their associations, addressing subgroup differences often hidden in group-level analyses.
Method
Patients with severe obesity (n = 529) reported their HR-QoL and depression before undergoing BMS, and at 12 and 24 months post-operation. Latent Class Growth Analysis was used to identify trajectories of BMI, HR-QoL and depression.
Results
BMI and HR-QoL improved significantly for all patients from pre-surgery to 24 months post-operation, though some patients deteriorated in their outcomes after 12 months. Three distinct trajectories of BMI were identified: Low (35.4%), Medium (45.5%), and High (19.2%), and of HR-QoL: High (38.4%), Medium (43.4%), and Poor (18.1%). Three trajectories of depression were extracted: Low/none (32.4%), Medium–low (45.3%), and Worsening (22.3%). The association between the trajectories of BMI and depression was significant, but not between the BMI and HR-QoL trajectories. Specifically, the Low BMI trajectory patients were more likely to follow the Worsening depression trajectory and reported poorer preoperative psychological health than the other two BMI trajectories.
Conclusion
Patients following the most favourable weight loss trajectory may not manifest psychologically favourable outcomes (i.e., Worsening depression), and preoperative characteristics do not consistently describe post-surgical BMI trajectories. Clinicians should tend to patients’ mental wellbeing besides weight loss post-BMS. The study findings emphasize the significance of incorporating psychological health as an essential component of surgical outcomes.
To compare the diagnostic accuracy of ULDCT to CXR for detecting non-traumatic pulmonary diseases at the emergency department (ED) and to study diagnostic confidence levels.
Secondary analysis of the prospective OPTIMACT trial (2418 ED participants randomly allocated to ULDCT or CXR). Diagnoses at imaging at the ED were compared to the reference diagnosis on day 28. Ratios of positive diagnoses, true positives (TP), false positives (FP), false negatives (FN), and positive predictive values (PPV) were assessed with 95% confidence intervals (CI). The diagnostic confidence levels of the radiologists were studied.
One thousand one hundred sixty-one ULDCT participants (mean age, 59 years ± 18 [standard deviation], 587 female) and 1151 CXR participants (mean age, 59 years ± 18 [standard deviation], 561 female) were evaluated. With ULDCT, pneumonia was 1.55 times (95% CI: 1.33–1.80) more often diagnosed at imaging at the ED, with significantly more TP (ratio 1.50; 95% CI: 1.26–1.76) and fewer FN (0.61; 95% CI: 0.37–0.99) but more FP (1.75; 95% CI: 1.19–2.58); a similar pattern was observed for other lower respiratory tract infections (LRTI). Pulmonary congestion was less often observed with ULDCT (0.45; 95% CI: 0.34–0.61), with fewer TP (0.50; 95% CI: 0.34–0.73), and FP (0.40; 95% CI: 0.24–0.65). PPVs were not significantly different. With ULDCT, radiologists were more often certain in diagnosing pneumonia (ULDCT 121/324, 37% vs CXR 48/208, 23%), LRTI (84/192, 44% vs 18/63, 29%), and no established disease (350/382, 92% vs 447/544, 82%).
Compared to CXR, ULDCT led to more TP but also more FP in detecting pneumonia and LRTI, while fewer TP and FP were found for pulmonary congestion. PPVs were comparable.
Question Is ultra-low dose CT (ULDCT) more accurate than chest X-ray (CXR) for identifying non-traumatic pulmonary diseases in patients presenting at the ED?
Findings ULDCT detects more pulmonary infections in patients presenting at the ED with non-traumatic pulmonary complaints, while CXR detects more pulmonary congestion.
Clinical relevance ULDCT is superior to CXR in detecting pneumonia and other LRTI in ED patients, while CXR is superior in detecting pulmonary congestion. ULDCT can be an alternative for CXR in a selected group of patients.
This study compared the dynamics of SARS-CoV-2 viral shedding in saliva between wild-type virus-infected and Omicron-infected household cohorts. Pre-existing immunity in participants likely shortens the viral RNA shedding duration and lowers viral load peaks. Frequent saliva sampling can be a convenient tool to study viral load dynamics.
Background
Addressing the growing challenge of nurse retention requires coordinated actions at national and global levels to improve recruitment, retention policies, and investments in the nursing work environment. The nursing work environment, defined as the "organizational characteristics of a work setting that facilitate or constrain professional nursing practice", is critical in influencing whether nurses decide to leave their jobs. This study investigates the impact of differentiated nursing practices – which involved tailoring roles and responsibilities based on nurses’ training, skills, and experience in Dutch hospitals – and investigated their impact on the nursing work environment and turnover intention (i.e., nurses’ intentions to leave their organization). We also explored whether the work environment mediates this relationship.
Methods
A multicenter longitudinal cohort study was conducted across 19 Dutch hospitals between 2019 and 2023. Nursing professionals participated via digital surveys administered before (T0) and after (T1) differentiated nursing practices were introduced. The nursing work environment was assessed using the Practice Environment Scale of the Nursing Work Index. A multilevel analysis with a random intercept and fixed slope was used to evaluate the impact of differentiated nursing practices on the work environment and on nurses' turnover intentions.
Results
We received 5411 responses to our questionnaire – 4259 at T0 and 1152 at T1. Results showed that, while the overall work environment improved, particularly in the dimensions of staffing and resource adequacy, collegial nurse–physician relationships, and participation in hospital affairs, there were no significant improvements in nursing foundation for quality of care or nurse managers' ability, leadership, and support of nurses. Additionally, differentiated nursing practices did not significantly impact turnover intention, nor did the work environment mediate this relationship.
Conclusions
This study is the first to explore the unique effects of practice differentiation on turnover intention mediated by the work environment. The findings suggest that, while differentiated practices can enhance certain aspects of the work environment, a more systemic and integrated approach is required for sustained improvements. Future research should include longer term studies to fully understand the complex relationship and accompanying mechanisms between differentiated nursing practices, the nursing work environment, and turnover intention.
Trial registration
Clinical trial number not applicable.
Background and purpose
Early migration of the uncemented cruciate-sacrificing rotating platform ATTUNE and Low Contact Stress (LCS) tibial components was classified as at-risk for aseptic loosening rates exceeding 6.5% at 15 years based on recent fixation-specific migration thresholds. In this secondary report of a randomized controlled trial (RCT) we aimed to evaluate whether the 5-year migration, inducible displacement, and the clinical outcome of the ATTUNE components were comparable to those of the LCS.
Methods
Patients from the initial 2-year radiostereometric analysis (RSA) RCT were recruited for a 5-year follow-up. At 5 years, participants underwent 2 supine and 1 loaded RSA examination, clinical assessments, and questionnaires. Migration was analyzed using maximum total point motion (MTPM), translations, and rotations, focusing on 5-year migration, continuous migration (> 0.10 mm/year), and inducible displacement. Revisions, along with clinical and functional outcomes, were also evaluated.
Results
At 5 years, 24 ATTUNE and 24 LCS implants were analyzed. The mean MTPM was similar for tibial components (ATTUNE 1.13mm [confidence interval (CI) 0.94–1.33]; LCS 1.24 mm [CI 1.05–1.46]) but significantly lower for the ATTUNE femoral component (1.14 mm [CI 0.92–1.39]) than LCS 1.87 mm [CI 1.57–2.21]). 2-to-5-year migration rates were comparable, but 11 ATTUNE and 7 LCS exceeded 0.10 mm MTPM/year, indicating a higher risk of loosening. Inducible displacement was similar, although 1 patient with a tibial ATTUNE showed excessive displacement (3.34 mm MTPM) with focal osteolysis but no symptoms. 1 revision 10 days post-surgery was performed for an ATTUNE insert spinout, resolved with an isolated insert exchange. Clinical and functional outcomes were comparable.
Conclusion
At the 5-year follow-up, ATTUNE tibial components showed similar migration, while the femoral component migrated significantly less than the LCS, which mainly occurred during the first 2 years. 2-to-5-year migration rates, inducible displacement, and clinical and functional outcomes were comparable. These findings suggest a comparable long-term risk of aseptic loosening between the uncemented ATTUNE and LCS knee systems.
Aims
Duodenal Mucosal Resurfacing (DMR) is an endoscopic ablation technique aimed at improving glycemia in patients with type 2 diabetes mellitus (T2DM). Although the exact underlying mechanism is still unclear, it is postulated that the DMR-induced improvements are the result of changes in the duodenal mucosa. For this reason, we assessed macroscopic and microscopic changes in the duodenal mucosa induced by DMR + GLP-1RA.
Methods
We included 16 patients with T2DM using basal insulin that received a combination treatment of a single DMR and GLP-1RA. Endoscopic evaluation was performed before the DMR procedure and 3 month after, and duodenal biopsies were obtained. Histological evaluation was performed and L and K cell density was calculated. In addition, gene-expression analysis and Western blotting was performed.
Results
Endoscopic evaluation at 3 month showed duodenal mucosa with a normal appearance. In line, microscopic histological evaluation showed no signs of villous atrophy or inflammation and unchanged L and K cell density. Unbiased transcriptome profiling and western blotting revealed that PDZK1 expression was higher in responders at baseline and after DMR. GATA6 expression was significantly increased in responders after DMR compared to non-responders.
Conclusion
The absence of macroscopic and microscopic changes after 3 month suggest that improvements in glycemic parameters after DMR do not result from significant histological changes in duodenal mucosa. It is more likely that these improvements result from more subtle changes in enteroendocrine signaling. PDZK1 and GATA6 expression might play a role in DMR; this needs to be confirmed in pre-clinical studies.
Background and purpose: This study updates 2 parallel systematic reviews and meta-analyses from 2012, which established the 1-year radiostereometric (RSA) migration thresholds for tibial components of total knee replacements (TKR) based on the risk of late revision for aseptic loosening from survival studies. The primary aim of this study was to determine the (mis)categorization rate of the 2012 thresholds using the updated review as a validation dataset. Secondary aims were evaluation of 6-month migration, mean continuous (1- to 2-year) migration, and fixation-specific thresholds for tibial component migration.Methods: One review comprised early migration data, measured by maximum total point motion (MTPM), from RSA studies, while the other focused on revision rates for aseptic loosening of tibial components from survival studies. Studies were matched based on prosthesis, fixation (i.e., cemented and uncemented, and uncemented with screw fixation), and insert (PFI). For the primary aim, newly included study group combinations were compared with the 2012 RSA thresholds to determine the (mis)categorization rate. For the secondary aims, new thresholds were determined based on revision rates for any reason in national registries (5-year < 3%, 10-year < 5%, 15-year < 6.5%).Results: After matching studies on PFI, a total of 157 survival and 82 RSA studies were included, comprising 504 study group combinations, 51 different PFIs, and 186,974 TKRs. We found that the 2012 thresholds were valid, with a misclassification rate of 0.5% at 5 and 0.3% at 10 years. Mean continuous migration could not be used to identify safe or unsafe implants. For cemented TKR, the 6-month mean MTPM was acceptable below 0.30 mm and unacceptable above 1.10 mm. For uncemented TKR, it was acceptable below 1.10 mm and unacceptable above 1.55 mm.Conclusion: The updated data reaffirm the 2012 RSA thresholds, confirming their validity in estimating revision risks for tibial component aseptic loosening. The newly proposed fixation-specific 6-month migration thresholds were found to be reliable for early identification of unsafe TKR designs, while 1- to 2-year mean continuous migration data were found not to be reliable for this purpose. These findings support and refine the migration thresholds to improve the evidence-based introduction of new TKR systems.
Importance
Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown.
Objective
To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants.
Design, Setting, and Participants
Randomized, open-label noninferiority trial conducted at 25 Dutch centers from June 2016 to November 2022 with follow-up completed in May 2023. The study enrolled 820 individuals with gestational diabetes and singleton pregnancies between 16 and 34 weeks of gestation who had insufficient glycemic control after 2 weeks of dietary changes (defined as fasting glucose >95 mg/dL [>5.3 mmol/L], 1-hour postprandial glucose >140 mg/dL [>7.8 mmol/L], or 2-hour postprandial glucose >120 mg/dL [>6.7 mmol/L], measured by capillary glucose self-testing).
Interventions
Participants were randomly assigned to receive metformin (initiated at a dose of 500 mg once daily and increased every 3 days to 1000 mg twice daily or highest level tolerated; n = 409) or insulin (prescribed according to local practice; n = 411). Glyburide was added to metformin, and then insulin substituted for glyburide, if needed, to achieve glucose targets.
Main Outcomes and Measures
The primary outcome was the between-group difference in the percentage of infants born large for gestational age (birth weight >90th percentile based on gestational age and sex). Secondary outcomes included maternal hypoglycemia, cesarean delivery, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm delivery, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admission.
Results
Among 820 participants, the mean age was 33.2 (SD, 4.7) years). In participants randomized to oral agents, 79% (n = 320) maintained glycemic control without insulin. With oral agents, 23.9% of infants (n = 97) were large for gestational age vs 19.9% (n = 79) with insulin (absolute risk difference, 4.0%; 95% CI, −1.7% to 9.8%; P = .09 for noninferiority), with the confidence interval of the risk difference exceeding the absolute noninferiority margin of 8%. Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%). All other secondary outcomes did not differ between groups.
Conclusions and Relevance
Treatment of gestational diabetes with metformin and additional glyburide, if needed, did not meet criteria for noninferiority compared with insulin with respect to the proportion of infants born large for gestational age.
Trial Registration
Netherlands Trial Registry Identifier: NTR6134
Importance
In the Netherlands, a growing group of young people request medical assistance in dying based on psychiatric suffering (MAID-PS). Little is known about this group, their characteristics, and outcomes.
Objective
To assess the proportion of requests for and deaths by MAID-PS among young patients, outcomes of their application and assessment procedures, and characteristics of those patients who died by either MAID or suicide.
Design, Setting, and Participants
This retrospective cohort study included Dutch individuals younger than 24 years requesting MAID-PS between January 1, 2012, and June 30, 2021, whose patient file had been closed by December 1, 2022, at the Expertisecentrum Euthanasie, a specialized health care facility providing MAID consultation and care.
Main Outcomes and Measures
Outcomes of the MAID-PS assessment procedure (discontinued, rejected, or MAID-PS) and clinical characteristics of patients who died by MAID or suicide.
Results
The study included 397 processed applications submitted by 353 individuals (73.4% female; mean [SD] age, 20.84 [1.90] years). Between 2012 and the first half of 2021, the number of MAID-PS applications by young patients increased from 10 to 39. The most likely outcome was application retracted by the patient (188 [47.3%]) followed by application rejected (178 [44.8%]). For 12 applications (3.0%), patients died by MAID. Seventeen applications (4.3%) were stopped because the patient died by suicide during the application process and 2 (0.5%) because the patient died after they voluntarily stopped eating and drinking. All patients who died by suicide or MAID (n = 29) had multiple psychiatric diagnoses (most frequently major depression, autism spectrum disorder, personality disorders, eating disorder, and/or trauma-related disorder) and extensive treatment histories. Twenty-eight of these patients (96.5%) had a history of suicidality that included multiple suicide attempts prior to the MAID application. Among 17 patients who died by suicide, 13 of 14 (92.9%) had a history of crisis-related hospital admission, and 9 of 12 patients who died by MAID (75.0%) had a history of self-harm.
Conclusions and Relevance
This cohort study found that the number of young psychiatric patients in the Netherlands who requested MAID-PS increased between 2012 and 2021 and that applications were retracted or rejected for most. Those who died by MAID or suicide were mostly female and had long treatment histories and prominent suicidality. These findings suggest that there is an urgent need for more knowledge about persistent death wishes and effective suicide prevention strategies for this high-risk group.
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