Risks associated with antidepressants in patients with hypertension during pregnancy: a retrospective cohort study.

PURPOSE: In a cohort of pregnant women using antihypertensive drugs, we compared exposure to antidepressants versus no exposure and the possible association with birth weight, APGAR scores, NICU admission, and maternal admission to an obstetrical intensive care unit (OHC). It was hypothesized that pregnant women with hypertensive disorders using antidepressants are at greater risk of complications. METHODS: A retrospective cohort study in a general teaching hospital in Zwolle, in the Middle-Northern part of The Netherlands. Finally, 58 pregnancies in the exposed group and 273 pregnancies in the reference group met all inclusion and exclusion criteria. We compared the neonate's birthweight between the exposed to antidepressants group and the reference group as the primary outcome. Secondary outcomes were the APGAR score at 1 and 5 min and obstetric high care (OHC) admission of the mother and neonatal intensive care unit (NICU) admission of the child. RESULTS: We found no differences in birth weight in neonates of mothers with hypertensive disorders and whether or not to use antidepressants. Besides a possible higher risk of admission to an OHC in women with hypertension-complicated pregnancies using antidepressants, we found no other maternal or neonatal risks in this population. CONCLUSION: We found no additional maternal or neonatal risks of using antidepressants prescribed to women with hypertension disorders during pregnancy.

Glucose measurements with accu check inform II versus hexokinase plasma method during surgery under general anesthesia, an observational cohort study.

PURPOSE: Limited research exists on translation of in-vitro glucose measurement interfering compounds to the in-vivo situation. We investigated whether Point-of-Care glucose measurements by Accu Chek Inform II (ACI II) were accurate to monitor glucose concentrations during surgery with general anesthesia by comparing with the reference laboratory hexokinase plasma glucose test. METHOD: Patients undergoing surgery with general anesthesia were included. Anesthesia was maintained with either Sevoflurane or Total intravenous anesthesia (TIVA). Prior to and after induction, blood glucose was measured with ACI II and the hexokinase test. Bland-Altman analysis was performed to assess method agreement. Subgroup analyses on glucose measurement differences per type of maintenance anesthesia were performed. RESULTS: Thirty-nine patients were included, and 78 measurements were performed. All paired measurements had clinically acceptable agreement with a percentage error of 10.0% (95% CI 8.0 to 11.9). The mean difference (95% limits of agreement) between ACI II and hexokinase for all measurements was 0.0 mmol/L (-0.7 to 0.7 mmol/L). Before induction (n = 39), mean difference was -0.1 mmol/L (-0.6 to 0.4 mmol/L), and after induction (n = 39), mean difference was 0.1 mmol/L (-0.8 to 0.9 mmol/L). Further investigation showed the difference varied per test for patients receiving Sevoflurane compared to patients receiving TIVA (-0.2 ± 0.4 mmol/L vs. 0.4 ± 0.3 mmol/L, p < 0.001). Before and after induction, the difference between ACI II and hexokinase measurements increased for patients receiving Sevoflurane compared to patients receiving TIVA (0.4 ± 0.4 mmol/L vs. -0.4 ± 0.3 mmol/L, p < 0.001). CONCLUSION: The agreement between glucose measurements using ACI II and the reference laboratory hexokinase test was clinically acceptable with a percentage error of 10.0% (95% CI 8.0 to 11.9). The use of TIVA may negatively affect the measurement performance of the ACI II.

Maternal and neonatal outcomes after benzodiazepine and benzodiazepine agonist exposure during pregnancy in women with mental disorders.

AIMS: To compare the gestational age of neonates in utero exposed to benzodiazepines (BDZs) with nonexposed controls. Secondary objectives were birth weight, presence of congenital malformations, APGAR score and the need for >3 months (prolonged) maternal psychiatric care. METHODS: A retrospective cohort study of women and neonates from 2013 to 2021 with univariate and multivariable analysis to study the associations between BDZ exposure and gestational age compared to nonexposed women with mental health problems. RESULTS: We found that BDZ exposure was not associated with a lower gestational age. We found that women in the exposed group had an increased risk of psychiatric care (adjusted odds ratio 2.58 [95% confidence interval 1.71-3.91], P < .001). CONCLUSION: We found that in utero BDZ exposure was not associated with a significantly lower gestational age of the neonates and was associated with prolonged psychiatric care of their mothers.

Nicardipine for treating severe antepartum hypertension during pregnancy: Nine years of experience in more than 800 women.

INTRODUCTION: Women with severe hypertension during pregnancy require prompt stabilization with a combination of magnesium sulfate and rapidly acting intravenously administered antihypertensives. It remains unknown which antihypertensive is best suited for pregnancy. The present study evaluated the intravenous use of the calcium antagonist, nicardipine. MATERIAL AND METHODS: This multicenter, retrospective case series included all pregnant women beyond 20 weeks of gestation with severe antepartum hypertension that were treated with intravenous nicardipine. PRIMARY OUTCOME MEASURES: successful treatment, time to successful treatment, and maternal safety. Severe hypertension was defined as systolic blood pressure (SBP) of 160 mm Hg or more and/or diastolic blood pressure (DBP) of 110 mm Hg or more. RESULTS: This study included 830 women. After 1 h of treatment, two-thirds of the women had SBP below 160 mm Hg and DBP below 100 mm Hg. In three out of four women, the mean arterial pressure was below 120 mm Hg. Within 2 h of treatment, 77.4% of women achieved successful treatment. In all cases, nicardipine was eventually effective. Within the first 2 h, 42.7% of women experienced temporary low DBP (ie below 70 mm Hg) without clinical consequences for the mother or fetus. In all cases, the low DBP resolved after discontinuing or reducing the dosage of nicardipine. One case of fetal distress was attributable to maternal hypotension, and a cesarean section was performed at more than 2 h after initiating therapy. During treatment, headache, nausea, and vomiting decreased significantly. CONCLUSIONS: To date, this was the largest case-series study on the use of nicardipine for treating severe antepartum hypertension in pregnancy. We found that nicardipine could effectively and safely treat this condition. Based on its high success rate and acceptable safety profile, nicardipine should be considered a first-line treatment in women with severe hypertension in pregnancy.

Frozen section diagnosis of borderline ovarian tumors with suspicious features of invasive cancer is a devil's dilemma for the surgeon: A systematic review and meta-analysis.

INTRODUCTION: Frozen section diagnoses of borderline ovarian tumors are not always straightforward and a borderline frozen section diagnosis with suspicious features of invasive carcinoma (reported as "at least borderline" or synonymous descriptions) presents us with the dilemma of whether or not to perform a full surgical staging procedure. By performing a systematic review and meta-analysis, the prevalence of straightforward borderline and "at least borderline" frozen section diagnoses, as well as proportion of patients with a final diagnosis of invasive carcinoma in these cases, were assessed and compared, as quantification of this dilemma may help us with the issue of this clinical decision. MATERIAL AND METHODS: PubMed, EMBASE and Cochrane library databases were searched and studies discussing "at least borderline" frozen section diagnoses were included in the review. Numbers of specific frozen section diagnoses and subsequent final histological diagnoses were extracted and pooled analysis was performed to compare the proportion of patients diagnosed with invasive carcinoma following borderline and "at least borderline" frozen section diagnoses, presented as risk ratio and risk difference with 95% confidence intervals (95% CI). RESULTS: Of 4940 screened records, eight studies were considered eligible for quantitative analysis. A total of 921 women was identified and 230 (25.0%) of these women were diagnosed with "at least borderline" ovarian tumor at the time of frozen section. Final histological diagnoses were reported in five studies, including 61 women with an "at least borderline" diagnosis and 290 women with a straightforward borderline frozen section diagnosis. Twenty-five of 61 women (41.0%) of the "at least borderline" group had invasive cancer at final diagnosis, compared with 28 of 290 women (9.7%) of the straightforward borderline frozen section group (risk difference -0.34, 95% CI -0.53 to -0.15; relative risk 0.25, 95% CI 0.13-0.50). CONCLUSIONS: Women diagnosed with "at least borderline" frozen section diagnoses were found to have a higher chance of carcinoma upon final diagnosis when compared with women with a straightforward borderline frozen section diagnosis (41.0% vs 9.7%). Especially in the serous subtype, and after preoperative consent, full staging during initial surgery might be considered in these cases to prevent a second surgical procedure.

Use of multiparametric MRI to characterize uterine fibroid tissue types.

BACKGROUND: Although the biological characteristics of uterine fibroids (UF) have implications for therapy choice and effectiveness, there is limited MRI data about these characteristics. Currently, the Funaki classification and Scaled Signal Intensity (SSI) are used to predict treatment outcome but both screening-tools appear to be suboptimal. Therefore, multiparametric and quantitative MRI was studied to evaluate various biological characteristics of UF. METHODS: 87 patients with UF underwent an MRI-examination. Differences between UF tissues and myometrium were investigated using T2-mapping, Apparent Diffusion Coefficient (ADC) maps with different b-value combinations, contrast-enhanced T1-weighted and T2-weighted imaging. Additionally, the Funaki classification and SSI were calculated. RESULTS: Significant differences between myometrium and UF tissue in T2-mapping (p = 0.001), long-TE ADC low b-values (p = 0.002), ADC all b-values (p < 0.001) and high b-values (p < 0.001) were found. Significant differences between Funaki type 3 versus type 1 and 2 were observed in SSI (p < 0.001) and T2-values (p < 0.001). Significant correlations were found between SSI and T2-mapping (p < 0.001; ρs = 0.82), ADC all b-values (p = 0.004; ρs = 0.31), ADC high b-values (p < 0.001; ρs = 0.44) and long-TE ADC low b-values (p = 0.004; ρs = 0.31). CONCLUSIONS: Quantitative MR-data allowed us to distinguish UF tissue from myometrium and to discriminate different UF tissue types and may, therefore, be a useful tool to predict treatment outcome/determine optimal treatment modality.

CT radiation dose reduction in patients with total hip arthroplasties using model-based iterative reconstruction and orthopaedic metal artefact reduction.

OBJECTIVE: To evaluate the impact of radiation dose reduction on image quality in patients with metal-on-metal total hip arthroplasties (THAs) using model-based iterative reconstruction (MBIR) combined with orthopaedic metal artefact reduction (O-MAR). MATERIALS AND METHODS: Patients with metal-on-metal THAs received a pelvic CT with a full (FD) and a reduced radiation dose (RD) with -20%, -40%, -57%, or -80% CT radiation dose respectively, when assigned to group 1, 2, 3, or 4 respectively. FD acquisitions were reconstructed with iterative reconstruction, iDose4. RD acquisitions were additionally reconstructed with iterative model-based reconstruction (IMR) levels 1-3 with different levels of noise suppression. CT numbers, noise and contrast-to-noise ratios were measured in muscle, fat and bladder. Subjective image quality was evaluated on seven aspects including artefacts, osseous structures, prosthetic components and soft tissues. RESULTS: Seventy-six patients were randomly assigned to one of the four groups. While reducing radiation dose by 20%, 40%, 57%, or 80% in combination with IMR, CT numbers remained constant. Compared with iDose4, the noise decreased (p < 0.001) and contrast-to-noise ratios increased (p < 0.001) with IMR. O-MAR improved CT number accuracy in the bladder and reduced noise in the bladder, muscle and fat (p < 0.01). Subjective image quality was rated lower on RD IMR images than FD iDose4 images on all seven aspects (p < 0.05) and was not related to the applied radiation dose reduction. CONCLUSION: In RD IMR with O-MAR images, CT numbers remained constant, noise decreased and contrast-to-noise ratios between muscle and fat increased compared with FD iDose4 with O-MAR images in patients with metal-on-metal THAs. Subjective image quality reduced, regardless of the degree of radiation dose reduction.

Computed Tomography Imaging of a Hip Prosthesis Using Iterative Model-Based Reconstruction and Orthopaedic Metal Artefact Reduction: A Quantitative Analysis.

OBJECTIVES: To quantify the combined use of iterative model-based reconstruction (IMR) and orthopaedic metal artefact reduction (O-MAR) in reducing metal artefacts and improving image quality in a total hip arthroplasty phantom. METHODS: Scans acquired at several dose levels and kVps were reconstructed with filtered back-projection (FBP), iterative reconstruction (iDose) and IMR, with and without O-MAR. Computed tomography (CT) numbers, noise levels, signal-to-noise-ratios and contrast-to-noise-ratios were analysed. RESULTS: Iterative model-based reconstruction results in overall improved image quality compared to iDose and FBP (P < 0.001). Orthopaedic metal artefact reduction is most effective in reducing severe metal artefacts improving CT number accuracy by 50%, 60%, and 63% (P < 0.05) and reducing noise by 1%, 62%, and 85% (P < 0.001) whereas improving signal-to-noise-ratios by 27%, 47%, and 46% (P < 0.001) and contrast-to-noise-ratios by 16%, 25%, and 19% (P < 0.001) with FBP, iDose, and IMR, respectively. CONCLUSIONS: The combined use of IMR and O-MAR strongly improves overall image quality and strongly reduces metal artefacts in the CT imaging of a total hip arthroplasty phantom.

Use of internal references for assessing CT density measurements of the pelvis as replacement for use of an external phantom.

PURPOSE: The purpose of this research is to study the use of an internal reference standard for fat- and muscle as a replacement for an external reference standard with a phantom. By using a phantomless internal reference standard, Hounsfield unit (HU) measurements of various tissues can potentially be assessed in patients with a CT scan of the pelvis without an added phantom at time of CT acquisition. This paves the way for development of a tool for quantification of the change in tissue density in one patient over time and between patients. This could make every CT scan made without contrast available for research purposes. MATERIALS AND METHODS: Fifty patients with unilateral metal-on-metal total hip replacements, scanned together with a calibration reference phantom used in bone mineral density measurements, were included in this study. On computed tomography scans of the pelvis without the use of intravenous iodine contrast, reference values for fat and muscle were measured in the phantom as well as within the patient's body. The conformity between the references was examined with the intra-class correlation coefficient. RESULTS: The mean HU (± SD) of reference values for fat for the internal- and phantom references were -91.5 (±7.0) and -90.9 (±7.8), respectively. For muscle, the mean HU (± SD) for the internal- and phantom references were 59.2 (±6.2) and 60.0 (±7.2), respectively. The intra-class correlation coefficients for fat and muscle were 0.90 and 0.84 respectively and show excellent agreement between the phantom and internal references. CONCLUSION: Internal references can be used with similar accuracy as references from an external phantom. There is no need to use an external phantom to asses CT density measurements of body tissue.

Development and first validation of a simplified CT-based classification system of soft tissue changes in large-head metal-on-metal total hip replacement: intra- and interrater reliability and association with revision rates in a uniform cohort of 664 arthroplasties.

OBJECTIVE: After implantation of a metal-on-metal total hip arthroplasty (MoM THA), a large incidence of pseudotumor formation has been described recently. Several centers have invited patients for follow-up in order to screen for pseudotumor formation. The spectrum of abnormalities found by CT in MoM THA patients can be unfamiliar to radiologists and orthopedic surgeons. Previously, a CT five-point grading scale has been published. In this paper, a simplification into a three-point classification system gives insight in the morphological distinction of abnormalities of the postoperative hip capsule in MoM implants in relation to the decision for revision. The reliability of this simplified classification regarding intra- and interrater reliability and its association with revision rate is investigated and discussed. MATERIALS AND METHODS: All patients who underwent MoM THA in our hospital were invited for screening. Various clinical measures and CT scan were obtained in a cross-sectional fashion. A decision on revision surgery was made shortly after screening. CT scans were read in 582 patients, of which 82 patients were treated bilaterally. CT scans were independently single read by two board-certified radiologists and classified into categories I-V. In a second meeting, consensus was obtained. Categories were subsequently rubricated in class A (categories I and II), B (category III), and C (categories IV and V). Intra- and inter-radiologist agreement on MoM pathology was assessed by means of the weighted Cohen's kappa. Categorical data were presented as n (%), and tested by means of Fisher's exact test. Continuous data were presented as median (min-max) and tested by means of Mann-Whitney U test (two group comparison) or Kruskal-Wallis test (three group comparison). Logistic regression analysis was performed in order to study independence of CT class for association with revision surgery. Univariate statistically significant variables were entered in a multiple model. All statistical analysis was performed two-tailed using alpha 5% as the significance level. RESULTS: In total, 664 scores from 664 MoM hips obtained by two observers were available for analyses. Interobserver reliability for the non-simplified version (I-V) was κw = 0.71 (95% CI: 0.62-0.79), which indicates good agreement between the two musculoskeletal radiologists. Intra- and interobserver reliability for the simplified version (A-C) were respectively κw 0.78 (95% CI: 0.68-0.87), and κw = 0.71 (95% CI: 0.65-0.76). This indicates good agreement within and between the two observers. The simplified A-C version is significantly associated with revision exclusively due to MoM pathology, in both patients with unilateral MoM THA (p < 0.001) and patients with bilateral MoM THA (p < 0.044). The simplified A-C version is associated with several clinical measures. In patients with unilateral MoM THA, with or without contralateral THA, in situ time (p < 0.008), cobalt and chromium (p < 0.001) were statistically significant. In patients with bilateral MoM, cobalt (p < 0.001) and chromium (p < 0.027) were statistically significant. Revision is significantly associated with cup size (p < 0.001), anteversion of the cup (p < 0.004), serum ion levels of cobalt and chromium (p < 0.001) and the adapted classification system (p < 0.001). In univariate logistic regression analysis on revision, cup, anteversion of the cup, cobalt-chromium ion serum levels, and the simplified (A-C) CT category system were statistically significant. The simplified (A-C) CT category system was an independent associate of revision, in several multiple logistic regression models. CONCLUSIONS: The presented simplified CT grading system (A-C) in its first clinical validation on 48- and 64-multislice systems is reliable, showing good intra- and interrater reliability and is independently associated with revision surgery.

Mid-term results of cemented hip arthroplasties through the direct anterior approach in the lateral decubitus position: a retrospective cohort study.

BACKGROUND: Reports show a high complication rate when starting with the Direct Anterior Approach (DAA) in a supine position for hip arthroplasty. The DAA with the patient in lateral decubitus position may avoid this problem because it supposedly provides better visibility, especially on the femoral side. However, this approach did show a rather high complication rate during the adoption of the approach at 1 year follow up in our previous report. We were interested what the overall 7 year survival estimate would be and whether improvement could be seen with growing experience. METHODS: A cohort of patients undergoing total hip arthroplasty right from the start of applying the DAA in lateral decubitus position was analysed. RESULTS: In total 175 hip prostheses (162 patients) were evaluated. The 7-year survival estimate was 95.1%, 95 CI: 91.8-98.4%. In 6 of 8 revisions there was aseptic loosening of the stem. By dividing the cohort into 3 consecutive groups in time we did not see a significantly improving revision rate. CONCLUSIONS: In our experience, the adoption of the direct anterior approach in lateral decubitus position caused a relatively low 7-year survival estimate without an apparent decrease with growing experience, however given the low number of cases further research is needed to investigate the long-term risk of adopting a new approach.

Comparison of osteolysis around 3 different cement restrictors in total hip arthroplasty.

BACKGROUND AND AIM: Several studies reported osteolysis around polyethylene glycol/polybutylene terephthalate (PEG/PBT) based femoral cement restrictors. Our goal was to evaluate and compare osteolysis around 3 different plug designs: the slow biodegradable PEG/PBT cement restrictor; the fast biodegradable gelatin cement restrictor; and the non-biodegradable polyethylene plug. PATIENTS AND METHODS: In a retrospective multicentre cohort study chart data were extracted of patients who received a total hip arthroplasty between 2008 and 2012. A total of 961 hips were included. Cortical ratio between inner and outer cortices at the centre of the plug was measured on routine postoperative follow-up moments. Median follow up of all 3 hospitals was 3.5 years (1.4-7.3). The primary outcome was evidence of osteolysis (i.e. the difference in cortical ratio [CR]) on anteroposterior (AP) radiographs at final follow-up. RESULTS: Progressive osteolysis was found around the PEG/PBT cement restrictor represented by a significantly increasing cortical ratio (ΔCR 0.067 (95% CI, 0.063-0.071). Distance from tip prosthesis to plug and size of the plug were found to be independent factors in predicting increased cortical ratio. CONCLUSIONS: Our multicentre cohort shows increase of cortical ratio around the PEG/PBT cement restrictor which progresses over time. Physicians should be aware of this fact and are advised to intensify follow-up of patients who received this cement restrictor.

Determinants of excessive weight gain after the initiation of insulin therapy in type 2 diabetes mellitus: Retrospective inception cohort study (ZODIAC 60).

AIMS: To explore determinants of excessive weight gain after initiation of insulin therapy in type 2 diabetes mellitus (T2DM), in particular variables identified in the pre-insulin phase. METHODS: We performed a retrospective observational intervention cohort study, by means of a new user design/ inception cohort concerning n = 5086 patients. We studied determinants of excessive weight gain (5 kg or more) in the first year after initiation of insulin therapy, using both visualization and logistic regression analysis with subsequent receiver operation characteristic (ROC) analyses. Potential determinants pre-, at- and post-insulin initiation were included. RESULTS: One out of 10 patients (10.0%) gained 5 kg weight or more. The earliest determinants of excessive weight gain were weight change (inversely) and HbA1c change in the two years prior to insulin therapy (p < 0.001). Patients that lost weight parallel with HbA1c rise in the two-years pre-insulin, showed the most pronounced weight gain. Of these patients, roughly one out of five (20.3%) gained 5 kg weight or more. CONCLUSIONS: Clinicians and patients should be alert for excessive weight gain after initiation of insulin, in the case of weight loss prior to insulin therapy initiation, particularly with increasing and prolonged high HbA1c at (and after) insulin initiation.

Sonographic follow-up of diaphragm function in COVID-19: an exploratory study.

Introduction: Survivors of COVID-19 frequently endure chronic disabilities. We hypothesise that diaphragm function has a long recovery time after COVID-19 hospitalisation and may play a role in post-COVID-19 syndrome. The aim of this study was to assess diaphragm function during COVID-19 hospitalisation and during recovery. Methods: We conducted a prospective single-centre cohort study in 49 enrolled patients, of which 28 completed 1-year follow-up. Participants were evaluated for diaphragm function. Diaphragm function was assessed using ultrasound measuring of diaphragm thickening fraction (TF) within 24 h after admission, after 7 days of admission or at discharge, whichever came first, and 3 and 12 months after hospital admission. Results: Estimated mean TF increased from 0.56 (95% CI 0.46-0.66) on admission to 0.78 (95% CI 0.65-0.89) at discharge or 7 days after admission, to 1.05 (95% CI 0.83-1.26) 3 months after admission and to 1.54 (95% CI 1.31-1.76) 12 months after admission. The improvements from admission to discharge, 3 months and 12 months were all significant (linear mixed modelling; p=0.020, p<0.001 and p<0.001, respectively), and the improvement from discharge to 3-month follow-up was borderline significant (p<0.1). Conclusion: Diaphragm function was impaired during hospitalisation for COVID-19. During recovery in hospital and up to 1-year follow-up, diaphragm TF improved, suggesting a long recovery time of the diaphragm. Diaphragm ultrasound may be a valuable modality in the screening and follow-up of (post-)COVID-19 patients for diaphragm dysfunction.

The demographics, clinical characteristics and quality of life of patients with chronic cough from the Isala Cough Clinic in the Netherlands.

Introduction: Chronic cough affects ∼10% of the population and adversely impacts quality of life. This retrospective observational cohort study aimed to identify the demographics, clinical characteristics and quality of life of the chronic cough population in a Dutch chronic cough clinic, at baseline and following treatment at 6 months. Patients were categorised based on the underlying phenotype and response to treatment. Methods: Retrospective data on 2397 patients who were diagnosed according to standard guidelines of the American College of Chest Physicians were analysed. Quality of life was captured via the Leicester Cough Questionnaire, the Cough Numeric Rating Scale and the Hospital Anxiety and Depression Scale. Results: Mean patient age was 59 years; 62.5% of the patients were female; and 69.1% had at least one underlying phenotype associated with chronic cough. Of the latter, 52.1% had bronchial hyperresponsiveness/airflow limitation, 33.3% had airway reflux and 20.1% had upper airway cough syndrome. 46% of patients with a phenotype, and 51% without, experienced no improvement in their quality of life or still had significant cough remaining after 6 months. Of patients with available quality-of-life data, 37.5% were categorised as having refractory chronic cough, and 9.5% were categorised as unexplained chronic cough. Discussion: This study highlights the poor quality-of-life outcomes in patients with chronic cough, despite interventions to treat underlying conditions, and indicates a need to manage chronic cough irrespective of phenotype.

Personalizing the Use of a Intermittently Scanned Continuous Glucose Monitoring (isCGM) Device in Individuals With Type 1 Diabetes: A Cost-Effectiveness Perspective in the Netherlands (FLARE-NL 9).

AIMS: Intermittently scanned continuous glucose monitoring (isCGM) is a method to monitor glucose concentrations without using a finger prick. Among persons with type 1 diabetes (T1D), isCGM results in improved glycemic control, less disease burden and improved health-related quality of life (HRQoL). However, it is not clear for which subgroups of patients isCGM is cost-effective. We aimed to provide a real-world cost-effectiveness perspective. METHODS: We used clinical data from a 1-year nationwide Dutch prospective observational study (N = 381) and linked these to insurance records. Health-related quality of life was assessed with the EQ-5D-3L questionnaire. Individuals were categorized into 4 subgroups: (1) frequent hypoglycemic events (58%), (2) HbA1c > 70 mmol/mol (8.5%) (19%), (3) occupation that requires avoiding finger pricks and/or hypoglycemia (5%), and (4) multiple indications (18%). Comparing costs and outcomes 12 months before and after isCGM initiation, incremental cost-effectiveness ratios (ICERs) were calculated for the total cohort and each subgroup from a societal perspective (including healthcare and productivity loss costs) at the willingness to pay of €50,000 per quality-adjusted life year (QALY) gained. RESULTS: From a societal perspective, isCGM was dominant in all subgroups (ie higher HRQoL gain with lower costs) except for subgroup 1. From a healthcare payer perspective, the probabilities of isCGM being cost-effective were 16%, 9%, 30%, 98%, and 65% for the total cohort and subgroup 1, 2, 3, and 4, respectively. Most sensitivity analyses confirmed these findings. CONCLUSIONS: Comparing subgroups of isCGM users allows to prioritize them based on cost-effectiveness. The most cost-effective subgroup was occupation-related indications, followed by multiple indications, high HbA1c and the frequent hypoglycemic events subgroups. However, controlled studies with larger sample size are needed to draw definitive conclusions.

Course of body weight before and after the initiation of insulin therapy in type 2 diabetes mellitus: Retrospective inception cohort study (ZODIAC 58).

Aims: The aim of this study was to explore the effect of insulin treatment initiation on weight by taking weight change prior to initiation into account. Materials and methods: We performed an observational retrospective inception cohort study, concerning Dutch primary care. We identified all patients that initiated insulin treatment (n = 7967) and individually matched patients with a reference patient (n = 5213 pairs). We obtained estimated mean weight changes in the five years prior to five years post insulin therapy. We applied linear regression analysis on weight change in the first year after insulin therapy (T0 to T+1), with matched group as primary determinant adjusted for pre-insulin weight change and additional covariates. Results: Estimated mean weight increased in the five consecutive years prior to insulin therapy (-0.23 kg in year T-5 to T-4, 0.01 kg in year T-4 to T-3, 0.07 kg in year T-3 to T-2, 0.24 kg in year T-2 to T-1, and 0.46 kg in year T-1 to T0) and continued to increase in the first year after, that is T0 to T+1, at a slightly lower rate (0.31 ± 3.9 kg). Pre-insulin weight change had the highest explained variance and was inversely and independently associated with weight change (p < .001). Starting insulin was associated with weight increase, independent of pre-insulin weight change (ß-adjusted 1.228, p < .001). Stratification revealed that despite having a more or less similar baseline BMI, patients with substantial weight increase showed higher estimated mean BMI's followed by weight loss pre-insulin. In matched references, estimated mean weight changes were negative in all years concerning the study period, indicating consistent weight loss. Conclusions: Initiation of insulin therapy was independently associated with weight increase; however, overall effect on weight was small and subject to substantial variation. Pre-insulin weight change is identified as a relatively strong inverse determinant of weight change after insulin initiation.

Two-year use of flash glucose monitoring is associated with sustained improvement of glycemic control and quality of life (FLARE-NL-6).

INTRODUCTION: The FreeStyle Libre (FSL) is a flash glucose monitoring (FGM) system. The Flash Monitor Register in the Netherlands (FLARE-NL-4) study previously demonstrated the positive effects of FSL-FGM use during 1 year on glycemic control, quality of life and disease burden among persons with diabetes mellitus (DM). The present follow-up study assesses the effects of FSL-FGM after 2 years. RESEARCH DESIGN AND METHODS: Patients included in the FLARE-NL-4 study who continued FSL-FGM during the 1-year study period were invited to participate (n=687). Data were collected using questionnaires (the 12-Item Short Form Health Survey version 2 (SF-12v2) and the EuroQol 5-Dimension 3-Level (EQ-5D-3L) for quality of life), including self-reported hemoglobin A1c (HbA1c). RESULTS: A total of 342 patients agreed to participate: mean age 48.0 (±15.6) years, 52% men and 79.5% with type 1 DM. HbA1c decreased from 60.7 (95% CI 59.1 to 62.3) mmol/mol before use of FSL-FGM to 57.3 (95% CI 55.8 to 58.8) mmol/mol after 1 year and 57.8 (95% CI 56.0 to 59.5) mmol/mol after 2 years. At the end of the 2-year follow-up period, 260 (76%) persons were still using the FSL-FGM and 82 (24%) had stopped. The main reason for stopping FSL-FGM was financial constraints (55%). Concerning the whole 2-year period, there was a significant decrease in HbA1c among persons who continued use of FSL-FGM (-3.5 mmol/mol, 95% CI -6.4 to -0.7), while HbA1c was unaltered compared with baseline among persons who stopped FSL-FGM (-2.4 mmol/mol, 95% CI -7.5 to 2.7): difference between groups 2.2 (95% CI -1.3 to 5.8) mmol/mol. After 2 years, persons who continued use of FSL-FGM had higher SF-12 mental component score and higher EQ-5D Dutch tariff score and felt less often anxious or depressed compared with persons who discontinued FSL-FGM. CONCLUSIONS: Although the considerable number of non-responders limits generalizability, this study suggests that persons who continue to use FSL-FGM for 2 years may experience sustained improvement in glycemic control and quality of life.

Flash Glucose Monitoring in the Netherlands: Increased monitoring frequency is associated with improvement of glycemic parameters.

AIMS: To evaluate the association between Flash Glucose Monitoring (FLASH) frequency and glycemic parameters during real-life circumstances in the Netherlands. METHODS: Obtained glucose readings were de-identified and uploaded to a dedicated database when FLASH reading devices were connected to internet. Data between September 2014 and March 2020, comprising 16,331 analyzable readers (163,762 sensors) were analyzed. Scan rate per reader was determined and each reader was sorted into 20 equally sized rank ordered groups (n = 817 each). RESULTS: Users performed a median of 11.5 [IQR 7.7-16.7] scans per day. Those in the lowest and highest ventiles scanned on average 3.7 and 40.0 times per day and had an eHbA1c of 8.6% (71 mmol/mol) and 6.9% (52 mmol/mol), respectively. Increasing scan rates were associated with more time in target range (3.9-10 mmol/L), less time in hyperglycemia (>10 mmol/L), and a lower standard deviation of glucose. An eHbA1c of 7.0% (53 mmol/mol) translated in approximately 65% time in target range, 30% time in hyperglycemia and 5% time in hypoglycemia (<3.9 mmol/L). CONCLUSIONS: These outcomes among Dutch FLASH users suggest that with higher scan rate glycemic control improves.

Health claims databases used for kidney research around the world.

Health claims databases offer opportunities for studies on large populations of patients with kidney disease and health outcomes in a non-experimental setting. Among others, their unique features enable studies on healthcare costs or on longitudinal, epidemiological data with nationwide coverage. However, health claims databases also have several limitations. Because clinical data and information on renal function are often lacking, the identification of patients with kidney disease depends on the actual presence of diagnosis codes only. Investigating the validity of these data is therefore crucial to assess whether outcomes derived from health claims data are truly meaningful. Also, one should take into account the coverage and content of a health claims database, especially when making international comparisons. In this article, an overview is provided of international health claims databases and their main publications in the area of nephrology. The structure and contents of the Dutch health claims database will be described, as well as an initiative to use the outcomes for research and the development of the Dutch Kidney Atlas. Finally, we will discuss to what extent one might be able to identify patients with kidney disease using health claims databases, as well as their strengths and limitations.