Peroperative administration of tranexamic acid in Roux-en-Y and one-anastomosis gastric bypass to reduce haemorrhage in patients with morbid obesity: protocol for randomised controlled trial (PATRY trial).

INTRODUCTION: By implementation of Enhanced Recovery After Bariatric Surgery protocols and day-care surgery, early discharge poses a challenge if excessive bleeding occurs after bariatric surgery. Tranexamic acid (TXA) has demonstrated efficacy in other surgical fields and in bariatric pilot studies. This trial aims to assess the efficacy of peroperative administration of TXA in reducing haemorrhage in patients undergoing gastric bypass surgery. METHOD AND ANALYSIS: This is a multicentre, phase III, double-blind randomised controlled trial in six high-volume bariatric centres in the Netherlands. A total of 1524 eligible patients, aged 18 years or older, undergoing primary gastric bypass surgery (either Roux-en-Y gastric bypass or one-anastomosis gastric bypass) will be randomised between TXA and placebo (1:1, variable block, stratified for centre, day-care/overnight stay and type of surgery) after obtaining informed consent (2.5% less haemorrhage, power 80%, 2-sided-α 0.05 and 10% dropout). Exclusion criteria are pregnancy, amedical history of acute bleeding (without cause), venous thrombotic events (VTEs), epilepsy, anticoagulant use and iatrogenic bleeding during surgery (aside from staple line). The primary outcome is postoperative haemorrhage requiring intervention within 30 days postoperatively. Secondary outcome measures are staple line reinforcement, blood loss, duration of surgery, postoperative haemoglobin, vital parameters, minor and major complications, side effects of TXA (nausea, hypotension and VTE), length of hospital stay and directly made costs. ETHICS AND DISSEMINATION: Written informed consent will be obtained from all participants. The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 7 February 2023 (registration number: R22.102). Results will be disseminated through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT05464394.

Is the QCI framework suited for monitoring outcomes and costs in a teaching hospital using value-based healthcare principles? A retrospective cohort study.

OBJECTIVES: The objective is to develop a pragmatic framework, based on value-based healthcare principles, to monitor health outcomes per unit costs on an institutional level. Subsequently, we investigated the association between health outcomes and healthcare utilisation costs. DESIGN: This is a retrospective cohort study. SETTING: A teaching hospital in Rotterdam, The Netherlands. PARTICIPANTS: The study was performed in two use cases. The bariatric population contained 856 patients of which 639 were diagnosed with morbid obesity body mass index (BMI) <45 and 217 were diagnosed with morbid obesity BMI ≥45. The breast cancer population contained 663 patients of which 455 received a lumpectomy and 208 a mastectomy. PRIMARY AND SECONDARY OUTCOME MEASURES: The quality cost indicator (QCI) was the primary measures and was defined asQCI = (resulting outcome * 100)/average total costs (per thousand Euros)where average total costs entail all healthcare utilisation costs with regard to the treatment of the primary diagnosis and follow-up care. Resulting outcome is the number of patients achieving textbook outcome (passing all health outcome indicators) divided by the total number of patients included in the care path. RESULTS: The breast cancer and bariatric population had the highest resulting outcome values in 2020 Q4, 0.93 and 0.73, respectively. The average total costs of the bariatric population remained stable (avg, €8833.55, min €8494.32, max €9164.26). The breast cancer population showed higher variance in costs (avg, €12 735.31 min €12 188.83, max €13 695.58). QCI values of both populations showed similar variance (0.3 and 0.8). Failing health outcome indicators was significantly related to higher hospital-based costs of care in both populations (p <0.01). CONCLUSIONS: The QCI framework is effective for monitoring changes in average total costs and relevant health outcomes on an institutional level. Health outcomes are associated with hospital-based costs of care.

Variation Between Hospitals in Outcomes and Costs of IBD Care: Results From the IBD Value Study.

BACKGROUND: Data on variation in outcomes and costs of the treatment of inflammatory bowel disease (IBD) can be used to identify areas for cost and quality improvement. It can also help healthcare providers learn from each other and strive for equity in care. We aimed to assess the variation in outcomes and costs of IBD care between hospitals. METHODS: We conducted a 12-month cohort study in 8 hospitals in the Netherlands. Patients with IBD who were treated with biologics and new small molecules were included. The percentage of variation in outcomes (following the International Consortium for Health Outcomes Measurement standard set) and costs attributable to the treating hospital were analyzed with intraclass correlation coefficients (ICCs) from case mix-adjusted (generalized) linear mixed models. RESULTS: We included 1010 patients (median age 45 years, 55% female). Clinicians reported high remission rates (83%), while patient-reported rates were lower (40%). During the 12-month follow-up, 5.2% of patients used prednisolone for more than 3 months. Hospital costs (outpatient, inpatient, and medication costs) were substantial (median: €8323 per 6 months), mainly attributed to advanced therapies (€6611). Most of the variation in outcomes and costs among patients could not be attributed to the treating hospitals, with ICCs typically between 0% and 2%. Instead, patient-level characteristics, often with ICCs above 50%, accounted for these variations. CONCLUSIONS: Variation in outcomes and costs cannot be used to differentiate between hospitals for quality of care. Future quality improvement initiatives should look at differences in structure and process measures of care and implement patient-level interventions to improve quality of IBD care. TRIAL REGISTRATION NUMBER: NL8276.

Variation in outcomes and costs cannot be used to differentiate between hospitals for quality of inflammatory bowel disease care. Future quality improvement initiatives should look at differences in structure and process measures and implement patient-level interventions to improve quality of inflammatory bowel disease care.

Long-term effect of sleeve gastrectomy vs Roux-en-Y gastric bypass in people living with severe obesity: a phase III multicentre randomised controlled trial (SleeveBypass).

Background: Sleeve gastrectomy is the most performed metabolic surgical procedure worldwide. However, conflicting results offer no clear evidence about its long-term clinical comparability to Roux-en-Y gastric bypass. This study aims to determine their equivalent long-term weight loss effects. Methods: This randomised open-label controlled trial was conducted from 2012 until 2017 in two Dutch bariatric hospitals with a 5-year follow-up (last follow-up July 29th, 2022). Out of 4045 patients, 628 were eligible for metabolic surgery and were randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass (intention-to-treat). The primary endpoint was weight loss, expressed by percentage excess body mass index (BMI) loss. The predefined clinically relevant equivalence margin was -13% to 13%. Secondary endpoints included percentage total kilograms weight loss, obesity-related comorbidities, quality of life, morbidity, and mortality. This trial is registered with Dutch Trial Register NTR4741: https://onderzoekmetmensen.nl/nl/trial/25900. Findings: 628 patients were randomised between sleeve gastrectomy (n = 312) and Roux-en-Y gastric bypass (n = 316) (mean age 43 [standard deviation (SD), 11] years; mean BMI 43.5 [SD, 4.7]; 81.8% women). Excess BMI loss at 5 years was 58.8% [95% CI, 55%-63%] after sleeve gastrectomy and 67.1% [95% CI, 63%-71%] after Roux-en-Y gastric bypass (difference 8.3% [95% CI, -12.5% to -4.0%]). This was within the predefined margin (P < 0.001). Total weight loss at 5 years was 22.5% [95% CI, 20.7%-24.3%] after sleeve gastrectomy and 26.0% [95% CI, 24.3%-27.8%] after Roux-en-Y gastric bypass (difference 3.5% [95% CI, -5.2% to -1.7%]). In both groups, obesity-related comorbidities significantly improved after 5 years. Dyslipidaemia improved more frequently after Roux-en-Y gastric bypass (83%, 54/65) compared to sleeve gastrectomy (62%, 44/71) (P = 0.006). De novo gastro-oesophageal reflux disease occurred more frequently after sleeve gastrectomy (16%, 46/288) vs Roux-en-Y gastric bypass (4%, 10/280) (P < 0.001). Minor complications were more frequent after Roux-en-Y gastric bypass (5%, 15/316) compared to sleeve gastrectomy (2%, 5/312). No statistically significant differences in major complications and health-related quality of life were encountered. Interpretation: In people living with obesity grades 2 and 3, sleeve gastrectomy and Roux-en-Y gastric bypass had clinically comparable excess BMI loss according to the predefined definition for equivalence. However, Roux-en-Y gastric bypass showed significantly higher total weight loss and significant advantages in secondary outcomes, including dyslipidaemia and GERD, yet at a higher rate of minor complications. Major complications, other comorbidities, and overall HRQoL did not significantly differ between the groups. Funding: Not applicable.

The Effect of Intraoperative Margin Assessment During Breast Conserving Surgery for Breast Cancer in a Dutch Cohort.

INTRODUCTION: Intraoperative specimen radiography is a routinely used procedure to ensure adequate resection of non-palpable breast tumors. Intraoperative digital specimen mammography (IDSM) is an alternative to conventional specimen radiography (CSR) which provides immediate specimen evaluation and can potentially decrease operation time. IDSM may also result in lower positive margin and re-excision rates. IDSM was implemented in our hospital in 2018. The objective of this study was to evaluate the effect of using IDSM versus CSR on operation time, margin status and re-excision rates in breast conserving surgery. METHODS: The present study is a single-center retrospective cohort study with 2 patient cohorts: one which underwent CSR (n = 532) and one which underwent IDSM (n = 475). The primary outcome was the operation time. Secondary outcomes were the margin status of the primary surgery, the cavity shaving rate, and the re-excision rate. Differences between cohorts were compared using univariate statistics and multiple regression analyses to adjust for variables that were significantly different between the groups. RESULTS: IDSM use was associated with an 8-minute reduction in surgery time (B = -8.034, 95% CI [-11.6, -4.5]; P < .001). Treatment variables independently associated with the operation time included use of IDSM, type of surgery, and performance of cavity shaving. Cavity shaves were more often performed when IDSM was used (24% for IDSM vs. 14% for CSR, P < .001), while the proportion of negative margin rates (93% for IDSM vs. 96% for CSR, P = .070) was comparable. CONCLUSION: IDSM was associated with a modest reduction in operation time. Surgeons performed more cavity shaves since the introduction of IDSM, but this increase was not reflected by difference in negative margin rates.

Implementing integrated care guidelines in asthma and COPD: It ain't easy!

Objective: To evaluate the implementation of a guideline-based, integrated, standardised, personal approach in patients with Chronic Obstructive Pulmonary Disease (COPD) or Asthma in a real-life situation. Methods: Patients at the outpatient clinic of the department of pulmonary disease were included in a controlled cohort study, comparing the use of diagnostic items and 'Personalised care plans' (PCPs) in patients with obstructive lung disease before (2013) and after (2015) implementation of a personalised diagnostic pathway. Results were compared with reference data (2016) from two control hospitals that used the same guidelines but did not implement this pathway. Results: 100 patients were selected for all three cohorts. After implementing the diagnostic pathway in 2015, 35 % of patients visited attended all pre-planned appointments, whereas 65 % of patients did not: they were diagnosed using usual care. Factors contributing to patients not attending the diagnostic care pathway were: the logistical complexity and intensity of the 2-day pathway, patients willingness to participate in a personalised pathway, and low social economic status or low literacy. After the implementation of the pathway, a significant improvement was seen in the number of PCPs (P < 0.001) and the number of diagnostic items registered recorded in the patients' electronic medical records (P < 0.001). Conclusion: Implementing a standardised diagnostic pathway in a real-life population significantly improved the number of personalised care plans, demonstrating that the implementation of holistic care planning is feasible in this population. Nevertheless, the pathway needs further improvements to maximize the number of patients benefitting from it, including logistical streamlining, removing unnecessary diagnostic tools, and increasing the focus on low literacy. Additionally, we found that implementing existing guidelines in a real life context is complex. Therefore, it is required to prioritize the translation of current guidelines into every-day practice, before expanding existing guidelines and protocols.

Effect of bariatric surgery on lung function and asthma control after 8 years of follow-up.

Background: Bariatric surgery has a proven beneficial effect on asthma symptoms and lung function in patients with class III obesity and asthma. The effects of bariatric surgery on asthma control and small airway function persist for at least 12 months after bariatric surgery. However, long-term follow-up data are lacking. Objectives: To evaluate the very-long term effects of bariatric surgery on asthma symptoms and lung function. Methods: In a prospective, longitudinal follow-up study, we planned an 8-year follow-up visit for patients previously included in the OBAS 1.0 trial, which evaluated the effects of bariatric surgery on asthma control and lung function in patients with asthma and class III obesity in The Netherlands. Results: Fifteen of 78 patients from the OBAS trial completed the 8-year follow-up visit. Nine patients underwent bariatric surgery, and six patients did not. After 8 years of follow-up, asthma control (Asthma Control Questionnaire [ACQ] score at 12 months of 0,4 versus an ACQ score of 0.7 at 8 years of follow-up; p = 0.075) and small airway function (R5-R20 (frequency-dependent resistance at 5Hz-20Hz); score at 12 months of 0,25 versus an ACQ score of 0.07 at 8 years of follow-up; p = 0.345) remained clinically stable compared with 12 months of follow-up. Patients who underwent bariatric surgery had a statistically significant weight regain between 12 months of follow-up and 8 years of follow-up (median [interquartile range] body mass index 30.2 kg/m² [23.9-43.4 kg/m²] versus 32.3 kg/m² [24.0-36.4 kg/m²]; p = 0.025). However, the impact of weight regain on asthma control, and asthma quality of life was clinically insignificant (ACQ, ß (regression coefficient) = 0.04; 95% Confidence Interval [0.02; 0.06]; p < 0.001; and AQLQ; ß = -0.04 CI [-0.07; -0.009]; p = 0.013). Conclusion: These results emphasize the importance of bariatric surgery in treating obesity-related asthma.

Implementation of vacuum-assisted excision as a management option for benign and high-risk breast lesions.

OBJECTIVE: Previous studies have shown that vacuum-assisted excision (VAE) is a safe and effective alternative for surgical excision (SE) of benign breast lesions. However, the use of VAE in high-risk lesions is controversial and guidelines are ambiguous. This study describes the impact of the implementation of VAE in terms of management and outcomes compared to a cohort before implementation. METHODS: A single centre retrospective study with two cohorts: 'before' and 'after' implementation of VAE was performed. All patients with a benign or high-risk lesion treated by VAE or SE between 2016 and 2019 were included. Excision, complication, and upgrade rates were compared between both cohorts. Cox regression was used for the evaluation of recurrences and re-excisions. RESULTS: The overall excision rate of all benign and high-risk lesions was comparable in both cohorts (17% vs 16%, p = 0.700). After implementation, benign lesions were significantly more often managed by VAE (101/151, 67%, p < 0.001). Re-excision, recurrence, and complication rates were low and comparable between cohorts (4.3% vs 3.9%, p > 0.999; 3.0 vs 2.0%, p = 0.683; 3.4 vs 6.6%, p = 0.289, respectively). CONCLUSION: SE could safely be replaced by VAE in 58% of patients treated for a benign or high-risk lesion. With this shift in management, the use of operating rooms and general anaesthesia can safely be omitted in this patient group. Further research on high-risk lesions is warranted since our data are exploratory. ADVANCES IN KNOWLEDGE: This study provides supportive data for the use of VAE as a management option for both benign (up to 5 cm) and high-risk lesions. Outcomes on re-excision, recurrence should be confirmed in prospective studies especially in high-risk lesions.

Prevalence of and Reasons for Discontinuation of Continuous Subcutaneous Insulin Infusion in People with Type 1 Diabetes: A Systematic Review.

The introduction of continuous subcutaneous insulin infusion in clinical care has led to more optimal glycemic and quality-of-life outcomes, compared with multiple daily injections (MDI). Despite this, some insulin pump users revert back to MDI. The aim of this review was to include the most recent rates of insulin pump discontinuation among people with type 1 diabetes and to identify reasons for and factors associated with discontinuation. A systematic literature search was conducted using the Embase.com, MEDLINE (via OVID), PsycINFO, and CINAHL databases. Titles and abstracts of eligible publications were screened, and baseline characteristics of the included studies were extracted, as were variables in the context of insulin pump use. Data were synthesized into themes: indications for insulin pump initiation, persons with type 1 diabetes (PWD)-reported reasons for, and factors associated with insulin pump discontinuation. A total of 826 eligible publications were identified and 67 were included. Discontinuation percentages ranged from 0% to 30% (median 7%). The most frequently mentioned reasons for discontinuation were wear-related issues (e.g., device attached to the body, interference with daily activities, discomfort, affected body image). Related factors included hemoglobin A1c (HbA1c) (17%), issues with following treatment recommendations (14%), age (11%), gender (9%), side effects (7%), and comorbidity- and complication-related factors (6%). Despite many developments in insulin pump technology, discontinuation rates and PWD-reported reasons for and factors associated with insulin pump discontinuation in more recent studies were comparable to earlier reviews/meta-analyses. Continuation of insulin pump treatment depends on a knowledgeable and willing health care provider (HCP) team and a close match with PWDs' wishes and needs.

Organ-specific learning curves of sonographers performing first-trimester anatomical screening and impact of score-based evaluation on ultrasound image quality.

INTRODUCTION: First-trimester anatomical screening (FTAS) by ultrasound has been introduced in many countries as screening for aneuploidies, but also as early screening for fetal structural abnormalities. While a lot of emphasis has been put on the detection rates of FTAS, little is known about the performance of quality control programs and the sonographers' learning curve for FTAS. The aims of the study were to evaluate the performance of a score-based quality control system for the FTAS and to assess the learning curves of sonographers by evaluating the images of the anatomical planes that were part of the FTAS protocol. METHODS: Between 2012-2015, pregnant women opting for the combined test in the North-Netherlands were also invited to participate in a prospective cohort study extending the ultrasound investigation to include a first-trimester ultrasound performed according to a protocol. All anatomical planes included in the protocol were documented by pictures stored for each examination in logbooks. The logbooks of six sonographers were independently assessed by two fetal medicine experts. For each sonographer, logbooks of examination 25-50-75 and 100 plus four additional randomly selected logbooks were scored for correct visualization of 12 organ-system planes. A plane specific score of at least 70% was considered sufficient. The intra-class correlation coefficient (ICC), was used to measure inter-assessor agreement for the cut-off scores. Organ-specific learning curves were defined by single-cumulative sum (CUSUM) analysis. RESULTS: Sixty-four logbooks were assessed. Mean duration of the scan was 22 ± 6 minutes and mean gestational age was 12+6 weeks. In total 57% of the logbooks graded as sufficient. Most sufficient scores were obtained for the fetal skull (88%) and brain (70%), while the lowest scores were for the face (29%) and spine (38%). Five sonographers showed a learning curve for the skull and the stomach, four for the brain and limbs, three for the bladder and kidneys, two for the diaphragm and abdominal wall and one for the heart and spine and none for the face and neck. CONCLUSION: Learning curves for FTAS differ per organ system and per sonographer. Although score-based evaluation can validly assess image quality, more dynamic approaches may better reflect clinical performance.

Primary care professionals' views on population-based expanded carrier screening: an online focus group study.

BACKGROUND: Population-based expanded carrier screening (ECS) involves screening for multiple recessive diseases offered to all couples considering a pregnancy or during pregnancy. Previous research indicates that in some countries primary care professionals are perceived as suitable providers for ECS. However, little is known about their perspectives. We therefore aimed to explore primary care professionals' views on population-based ECS. METHODS: Four online focus groups with 14 general practitioners (GPs) and 16 community midwives were conducted in the Netherlands. RESULTS: Our findings highlight various perspectives on the desirability of population-based ECS. Participants agreed that ECS could enhance reproductive autonomy and thereby prevent suffering of the child and/or parents. However, they also raised several ethical, societal, and psychological concerns, including a tendency towards a perfect society, stigmatization, unequal access to screening and negative psychosocial consequences. Participants believed that provision of population-based ECS would be feasible if prerequisites regarding training and reimbursement for providers would be fulfilled. most GPs considered themselves less suitable or capable of providing ECS, in contrast to midwives who did consider themselves suitable. Nevertheless, participants believed that, if implemented, ECS should be offered in primary care or by public health services rather than as hospital-based specialized care, because they believed a primary care ECS offer increases access in terms of time and location. CONCLUSIONS: While participants believed that an ECS offer would be feasible, they questioned its desirability and priority. Studies on the desirability and feasibility of population-based ECS offered in primary care or public health settings are needed.

Type 1 diabetes management: Room for improvement.

AIMS/HYPOTHESIS: Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D). Ongoing improvement of management strategies requires the evaluation of target achievement and identification of risk factors in individuals who do (or do not) achieve these targets. METHODS: Cross-sectional data were collected from adults with T1D visiting six diabetes centers in the Netherlands in 2018. Targets were defined as glycated hemoglobin (HbA1c) <53 mmol/mol, low-density lipoprotein-cholesterol (LDL-c) <2.6 mmoL/L (no cardiovascular disease [CVD] present) or <1.8 mmoL/L (CVD present), or blood pressure (BP) <140/90 mm Hg. Target achievement was compared for individuals with and without CVD. RESULTS: Data from 1737 individuals were included. Mean HbA1c was 63 mmol/mol (7.9%), LDL-c was 2.67 mmoL/L, and BP 131/76 mm Hg. In individuals with CVD, 24%, 33%, and 46% achieved HbA1c, LDL-c, and BP targets respectively. In individuals without CVD these percentages were 29%, 54%, and 77%, respectively. Individuals with CVD did not have any significant risk factors for HbA1c, LDL-c, and BP target achievement. In comparison, individuals without CVD were more likely to achieve glycemic targets if they were men and insulin pump users. Smoking, microvascular complications, and the prescription of lipid-lowering and antihypertensive medication were negatively associated with glycemic target achievement. No characteristics were associated with LDL-c target achievement. Microvascular complications and antihypertensive medication prescription were negatively associated with BP target attainment. CONCLUSION: Opportunities for improvement of diabetes management exist for the achievement of glycemic, lipid, and BP targets but may differ between individuals with and without CVD.

Fasting and meal-stimulated serum C-peptide in long-standing type 1 diabetes mellitus.

AIMS: This study aims to evaluate the stability of C-peptide over time and to compare fasting C-peptide and C-peptide response after mixed-meal tolerance test (MMTT) at T90 or T120 with C-peptide area under the curve (AUC) in long-standing type 1 diabetes. METHODS: We included 607 type 1 diabetes individuals with diabetes duration >5 years. C-peptide concentrations (ultrasensitive assay) were collected in the fasting state, and in a subpopulation after MMTT (T0, just prior to, T30-T60-T90-T120, 30-120 min after ingestion of mixed-meal) (n = 168). Fasting C-peptide concentrations (in n = 535) at Year 0 and Year 1 were compared. The clinical determinants associated with residual C-peptide secretion and the correspondence of C-peptide at MMTT T90 / T120 and total AUC were assessed. RESULTS: A total of 153 participants (25%) had detectable fasting serum C-peptide (i.e ≥ 3.8 pmol/L). Fasting C-peptide was significantly lower at Year 1 (p < 0.001, effect size = -0.16). Participants with higher fasting C-peptide had a higher age at diagnosis and shorter disease duration and were less frequently insulin pump users. Overall, 109 of 168 (65%) participants had both non-detectable fasting and post-meal serum C-peptide concentrations. The T90 and T120 C-peptide values at MMTT were concordant with total AUC. In 17 (10%) individuals, C-peptide was only detectable at MMTT and not in the fasting state. CONCLUSIONS: Stimulated C-peptide was detectable in an additional 10% of individuals compared with fasting in individuals with >5 years of diabetes duration. T90 and T120 MMTT measurements showed good concordance with the MMTT total AUC. Overall, there was a decrease of C-peptide at 1-year follow-up.

Normalization of Cardiac Function After Bariatric Surgery Is Related to Autonomic Function and Vitamin D.

PURPOSE: Subclinical cardiac dysfunction is common in patients with obesity. Bariatric surgery is associated with normalization of subclinical cardiac function in 50% of the patients with obesity. The aim of this study was to identify predictors for a lack of improvement of subclinical cardiac dysfunction 1-year post-bariatric surgery. METHODS: Patients who were referred for bariatric surgery were enrolled in a longitudinal study. Inclusion criteria were age 35-65 years and BMI ≥ 35 kg/m2. Patients with a suspicion of or known cardiovascular disease were excluded. Conventional and advanced echocardiography, Holter monitoring, and blood tests were performed pre- and 1-year post-bariatric surgery. Subclinical cardiac dysfunction was defined as either a reduced left ventricular ejection fraction, decreased global longitudinal strain (GLS), diastolic dysfunction, arrhythmia, or an increased BNP or hs Troponin I. RESULTS: A total of 99 patients were included of whom 59 patients had cardiac dysfunction at baseline. Seventy-two patients completed the 1-year follow-up after bariatric surgery. There was a significant reduction in weight and cardiovascular risk factors. Parameters of cardiac function, such as GLS, improved. However, in 20 patients cardiac dysfunction persisted. Multivariate analysis identified a decreased heart rate variability (which is a measure of autonomic function), and a decreased vitamin D pre-surgery as predictors for subclinical cardiac dysfunction after bariatric surgery. CONCLUSION: Although there was an overall improvement of cardiac function 1-year post-bariatric surgery, autonomic dysfunction and a decreased vitamin D pre-bariatric surgery were predictors for a lack of improvement of subclinical cardiac dysfunction.

Societal implications of expanded universal carrier screening: a scoping review.

Carrier screening aims to identify couples at risk of conceiving children with a recessive condition. Until recently, carrier screening was primarily offered ancestry-based. Technological advances now facilitate expanded universal carrier screening (EUCS). This scoping review aimed to map EUCS's potential societal implications based on both theoretical studies and empirical evidence. To this aim, we performed a CoCites search to find relevant articles, including articles describing carrier screening for at-risk populations, based on five selected query articles. Forty articles were included. Three main potential societal implications were identified: (1) unwanted medicalization, (2) stigmatization and discrimination of carriers and people affected with the conditions screened and (3) challenges in achieving equitable access. Within these themes, potential positive implications are reduction of ethnic stigmatization in ancestry-based offers and increased equity. Potential negative implications are reinforcement of disability-based stigmatization, less possibility for developing expertise in healthcare and societal pressure to partake in screening. Empirical evidence on all these implications is however scarce. In conclusion, both positive and negative potential societal implications of implementing EUCS, primarily theoretical, were identified, even in at-risk groups where evidence is mostly lacking. Empirical research in EUCS pilots is needed to identify which societal implications are likely to occur and therefore should be overcome when implementing EUCS.

Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.

INTRODUCTION: The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients. METHODS AND ANALYSIS: Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed. ETHICS AND DISSEMINATION: Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences. TRIAL REGISTRATION NUMBER: NCT05240742.

Cardiovascular risk management in people with type 1 diabetes: performance using three guidelines.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality in individuals with type 1 diabetes mellitus (T1DM). Cardiovascular risk management is therefore essential in the management of individuals with T1DM. This study describes the performance of lipid and blood pressure management in individuals with T1DM using three guidelines. RESEARCH DESIGN AND METHODS: Individuals ≥18 years with T1DM, treated with insulin for ≥1 year, visiting Diabeter or the University Medical Center Groningen between January 1, 2018 and December 31, 2018, were included. Lipid and blood pressure management were examined using the Dutch, American Diabetes Association (ADA) and National Institute for Health and Care Excellence (NICE) guidelines. Concordance of recommended and prescribed lipid-lowering (LLM) or antihypertensive medication (AHM) was assessed per guideline and 10-year age groups. Achievement of treatment targets was assessed for those prescribed medication. RESULTS: A total of 1855 individuals with T1DM were included. LLM and AHM was prescribed in 19% and 17%, respectively. In individuals recommended LLM, this was prescribed in 22%-46% according to Dutch, ADA or NICE guideline recommendations. For individuals recommended AHM, this was prescribed in 52%-75%. Recommended and actual prescription of LLM and AHM increased over age for all three guidelines. However, discordance between treatment recommendation and medication prescribed was higher in younger, compared with older, age groups. Low-density lipoprotein-cholesterol targets were achieved by 50% (without CVD) and 31% (with CVD) of those prescribed LLM. The blood pressure target was achieved by 46% of those prescribed AHM. CONCLUSION: This study suggests that there is undertreatment of lipid and blood pressure according to guideline recommendations, particularly in younger age groups. Treatment targets are not met by most individuals prescribed medication, while guidelines recommendations differ considerably. We recommend to investigate the factors influencing undertreatment of lipid and blood pressure management in individuals with T1DM.

Effects of dapagliflozin on postprandial lipid metabolism in type 2 diabetes mellitus.

Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) modulate lipid metabolism and improve cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The exact cardioprotective mechanism of SGLT2i is unclear. We evaluated the effects of SGLT2i on postprandial lipids, lipoprotein concentrations, glucose and fatty acids. Design: A placebo-controlled randomized, proof-of-concept study. Methods: Fourteen male patients with T2DM on intensive insulin regimen were randomly and double-blind allocated to 12 weeks dapagliflozin (10 mg) or placebo. Postprandial effects were assessed with an 8-h standardized oral fat loading test. Results: Mean glycated A1c did not change by dapagliflozin, but the mean daily insulin dose was significantly reduced. Although dapagliflozin did not affect fasting or postprandial levels of glucose and insulin, it increased the postprandial levels of glucagon. While fasting levels of free fatty acids and beta-hydroxybutyrate (bHBA) were unchanged, dapagliflozin significantly increased the postprandial bHBA response. This was seen in the context of increased postprandial glucagon levels by dapagliflozin, without influencing postprandial insulin or glucose levels. Dapagliflozin did not affect fasting or postprandial plasma cholesterol and triglycerides nor postprandial inflammatory markers. Fasting apolipoprotein B48 was decreased without affecting the postprandial response. Markers of inflammation and vascular function did not change. Conclusion: Treatment with dapagliflozin of patients with T2DM led to a reduction of fasting chylomicron remnants and increased postprandial ketone bodies compared to placebo suggesting enhanced hepatic fatty acid oxidation. The latter may have been caused by decreasing the insulin-glucagon ratio. The beneficial clinical effects seen in the trials using dapagliflozin most likely are not due to effects on postprandial inflammation nor postprandial lipemia.

Effects of Peri-Conception and Pregnancy Glycemic Variability on Pregnancy and Perinatal Complications in Type 1 Diabetes: A Pilot Study.

BACKGROUND: Not much is known about the effects of glycemic variability (GV) during the pre- and periconception period on pregnancy/perinatal complications. GV could potentially contribute to identification of high-risk pregnancies in women with type 1 diabetes. METHODS: An explorative retrospective cohort study was conducted between January 2014 and May 2019. Glucose data were retrieved from electronic patient charts. Pre-/periconceptional GV and GV during all three trimesters was expressed as mean glucose, standard deviation (SD), Coefficient of Variation (CV), High Blood Glucose Index (HBGI), Low Blood Glucose Index (LBGI) and Average Daily Risk Range (ADRR). Maternal and neonatal complications were summarized using a composite total complication score. Binary logistic regression analyses were conducted to assess associations between the GV measures and a total complication score>3, a maternal complication score>1 and a neonatal complication score>1. RESULTS: Of 63 eligible women, 29 women (38 pregnancies) were included. Women in the group with a total complication score>3 had a significantly higher ADRR at conception (OR 1.1, CI 1.0-1.2, p=0.048). No statistically significant correlations between complication score and any other GV metric besides the ADRR were found. Although not significant, in the group with a complication score>3, odds ratios>1 were found for SD in trimester 1 (OR 1.6, CI 0.6-4.5, p=0.357) and trimester 2 (OR 1.8, CI 0.5-6.2, p=0.376). CONCLUSIONS: Presence of a positive association between GV and pregnancy and perinatal complications depends on which pregnancy period is assessed and the GV metrics that are used.

How low is really low? Comparison of two C-peptide assays to establish residual C-peptide production in type 1 diabetes.

INTRODUCTION: C-peptide is an important marker to assess residual insulin production in individuals with type 1 diabetes (T1D). The accuracy and detection limits of C-peptide assays are important to detect C-peptide microsecretion and to reliably observe changes over time in these people. We compared and verified two commercially available assays able to measure C-peptide in the picomolar range. METHODS: The ultrasensitive Mercodia enzyme-linked immunosorbent C-peptide assay (ELISA) was compared with the Beckman immunoradiometric assay (IRMA) for C-peptide, assessing reproducibility (coefficient of variation [CV]), limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ). RESULTS: For both assays within-run and between-run variation were high at the low (around the detection limit) C-peptide concentration range, with CVs of around 40%. LoB values for the ultrasensitive ELISA and the IRMA were 1.3 and 0.16 pmol/L respectively. LoD values were 2.4 and 0.54 pmol/L respectively. LoQ values were 9.7 and 3.8 pmol/L respectively. Only the IRMA met the specifications claimed by the manufacturer. CONCLUSIONS: The IRMA provided the lowest threshold for quantification of serum C-peptide. LoQ of commercially available assays should be established in-house before applying them in research studies and clinical trials in which low C-peptide levels have clinical or scientific relevance.