Family screening in patients with isolated bicuspid aortic valve : Restriction to those with aortic dilatation is not justified.

AIM: To determine the prevalence of undiagnosed bicuspid aortic valve (BAV) and isolated aortic dilatation in first-degree relatives (FDRs) of patients with isolated BAV and to explore the recurrence risk of BAV in different subgroups of probands with BAV. Recent American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines recommend family screening in patients with associated aortopathy only. METHODS: During follow-up visits, patients with isolated BAV received a printed invitation for their FDRs advising cardiac screening. RESULTS: From 2012-2019, 257 FDRs of 118 adult BAV patients were screened, among whom 63 (53%) index patients had undergone aortic valve surgery (AVS), including concomitant aortic replacement in 25 (21%). Of the non-operated index patients, 31 (26%) had aortic dilatation (> 40 mm). Mean age of the FDRs was 48 years (range 4-83) and 42% were male. The FDR group comprised 20 parents, 103 siblings and 134 offspring. Among these FDRs, 12 (4.7%) had a previously undiagnosed BAV and 23 (8.9%) had an isolated aortic dilatation. FDRs of the probands with previous AVS (n = 147) had a risk ratio for BAV of 2.25 (95% confidence interval (CI) 0.62-8.10). FDRs of the probands with BAV and repaired or unrepaired aortic dilatation (n = 127) had a risk ratio for BAV of 0.51 (95% CI 0.16-1.66). CONCLUSION: Screening FDRs of patients with isolated BAV resulted in a reasonable yield of 14% new cases of BAV or isolated aortic dilatation. A trend towards an increased risk of BAV in FDRs was observed in the probands with previous AVS, whereas this risk seemed to be diminished in the probands with associated aortic dilatation. This latter finding does not support the restrictive ACC/AHA recommendation.

Heart rate increase and inappropriate sinus tachycardia after cryoballoon pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Cryoballoon pulmonary vein isolation (PVI) is a common therapy for atrial fibrillation (AF). While moderately increased sinus rhythm heart rate (HR) after PVI has been observed, inappropriate sinus tachycardia (IST) is a rare phenomenon. We aimed to investigate the prevalence and natural history of an abnormal sinus HR response after cryoballoon PVI. METHODS: We included 169/646 (26.2%) patients with AF undergoing PVI with available Holter recordings before and 3, 6 and 12 months after the procedure. Patients with AF on Holter monitoring were excluded. Mean HR increase ≥ 20 bpm or an IST-like pattern (mean HR > 90 bpm or > 80 bpm when beta-blocking agents were used) following PVI was categorised as abnormal sinus HR response. RESULTS: Following PVI, mean HR ± standard deviation increased in the entire group from 63.5 ± 8.4 to 69.1 ± 9.9 bpm at 3 months (p < 0.001), and to 71.9 ± 9.4 bpm at 6 months (p < 0.001). At 12 months, mean HR was 71.2 ± 10.1 bpm (p < 0.001). Only 7/169 patients (4.1%) met criteria for abnormal sinus HR response: mean HR was 61.9 ± 10.6 bpm (pre-ablation), 84.6 ± 9.8 bpm (3 months), 80.1 ± 6.5 bpm (6 months) and 76.3 ± 10.1 bpm (12 months). Even at 12 months, mean HR was significantly different from that pre-ablation in this group (p = 0.033). However, in patients meeting IST-like pattern criteria, mean HR at 12 months was no longer significantly different from that pre-ablation. CONCLUSION: Few patients had an abnormal sinus HR response after PVI. Peak HR was observed 3 months after PVI, but HR was still significantly increased 12 months post-ablation compared with pre-ablation. An IST-like pattern was rarely observed. In these patients, HR decreased to pre-ablation values within a year.

International consensus: ovarian tissue cryopreservation in young Turner syndrome patients: outcomes of an ethical Delphi study including 55 experts from 16 different countries.

STUDY QUESTION: What is the standpoint of an international expert panel on ovarian tissue cryopreservation (OTC) in young females with Turner syndrome (TS)? SUMMARY ANSWER: The expert panel states that OTC should be offered to young females with TS, but under strict conditions only. WHAT IS KNOWN ALREADY: OTC is already an option for preserving the fertility of young females at risk of iatrogenic primary ovarian insufficiency (POI). Offering OTC to females with a genetic cause of POI could be the next step. One of the most common genetic disorders related to POI is TS. Due to an early depletion of the ovarian reserve, most females with TS are confronted with infertility before reaching adulthood. However, before offering OTC as an experimental fertility preservation option to young females with TS, medical and ethical concerns need to be addressed. STUDY DESIGN, SIZE, DURATION: A three-round ethical Delphi study was conducted to systematically discuss whether the expected benefits exceed the expected negative consequences of OTC in young females with TS. The aim was to reach group consensus and form an international standpoint based on selected key statements. The study took place between February and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Anonymous panel selection was based on expertise in TS, fertility preservation or medical ethics. A mixed panel of 12 gynaecologists, 13 (paediatric) endocrinologists, 10 medical ethicists and 20 patient representatives from 16 different countries gave consent to participate in this international Delphi study. In the first two rounds, experts were asked to rate and rank 38 statements regarding OTC in females with TS. Participants were offered the possibility to adjust their opinions after repetitive feedback. The selection of key statements was based on strict inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 46 participants completed the first Delphi round (response rate 84%). Based on strict selection criteria, six key statements were selected, and 13 statements were discarded. The remaining 19 statements and two additional statements submitted by the expert panel were re-evaluated in the second round by 41 participants (response rate 75%). The analysis of the second survey resulted in the inclusion of two additional key statements. After the approval of these eight key statements, the majority of the expert panel (96%) believed that OTC should be offered to young females with TS, but in a safe and controlled research setting first, with proper counselling and informed consent procedures, before offering this procedure in routine care. The remaining participants (4%) did not object but did not respond despite several reminders. LIMITATIONS, REASONS FOR CAUTION: The anonymous nature of this study may have led to lack of accountability. The selection of experts was based on their willingness to participate. The fact that not all panellists took part in all rounds may have resulted in selection bias. WIDER IMPLICATIONS OF THE FINDINGS: This international standpoint is the first step in the global acceptance of OTC in females with TS. Future collaborative research with a focus on efficacy and safety and long-term follow-up is urgently needed. Furthermore, we recommend an international register for fertility preservation procedures in females with TS. STUDY FUNDING/COMPETING INTEREST(S): Unconditional funding (A16-1395) was received from Merck B.V., The Netherlands. The authors declare that they have no conflict of interest.

New developments in adult congenital heart disease.

Congenital heart disease (CHD) affects 0.8% of live births and over the past decades technical improvements and large-scale repair has led to increased survival into adulthood of over 95% of the new-born. A new group of patients, those who survived their congenital heart defect, has emerged but late complications including heart failure, pulmonary hypertension (PH), arrhythmias, aneurysms and endocarditis appeared numerous, with a huge impact on mortality and morbidity. However, innovations over the past years have changed the landscape of adult CHD dramatically. In the diagnostic process important improvements have been made in the use of MRI, biomarkers, e­health concepts and 3D visualisation of anatomy. Care is now concentrated in specialised centres, with a continuous emphasis on education and the introduction of weekly multidisciplinary consultations on diagnosis and intervention. Surgery and percutaneous intervention have been refined and new concepts applied, further reducing the burden of the congenital malformations. Research has matured from case series to global networks. Currently, adults with CHD are still facing high risks of early mortality and morbidity. By global collaboration and continuous education and development and innovation of our diagnostic and therapeutic arsenal, we will improve the perspectives of these young patients.

Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation: a multidisciplinary expert advisory board.

The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5 mg, 5 mg, 15 mg and 20 mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise.

Impact of resection margin status on recurrence and survival in pancreatic cancer surgery.

BACKGROUND: The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is poor and selection of patients for surgery is challenging. This study examined the impact of a positive resection margin (R1) on locoregional recurrence (LRR) and overall survival (OS); and also aimed to identified tumour characteristics and/or technical factors associated with a positive resection margin in patients with PDAC. METHODS: Patients scheduled for pancreatic resection for PDAC between 2006 and 2016 were identified from an institutional database. The effect of resection margin status, patient characteristics and tumour characteristics on LRR, distant metastasis and OS was assessed. RESULTS: A total of 322 patients underwent pancreatectomy for PDAC. A positive resection (R1) margin was found in 129 patients (40·1 per cent); this was associated with decreased OS compared with that in patients with an R0 margin (median 15 (95 per cent c.i. 13 to 17) versus 22 months; P < 0·001). R1 status was associated with reduced time to LRR (median 16 versus 36 (not estimated, n.e.) months; P = 0·002). Disease recurrence patterns were similar in the R1 and R0 groups. Risk factors for early recurrence were tumour stage, positive lymph nodes (N1) and perineural invasion. Among 100 patients with N0 disease, R1 status was associated with shorter OS compared with R0 resection (median 17 (10 to 24) versus 45 (n.e.) months; P = 0·002), whereas R status was not related to OS in 222 patients with N1 disease (median 14 (12 to 16) versus 17 (15 to 19) months after R1 and R0 resection respectively; P = 0·068). CONCLUSION: Although pancreatic resection with a positive margin was associated with poor survival and early recurrence, particularly in patients with N1 disease, disease recurrence patterns were similar between R1 and R0 groups.

Maternal right ventricular function, uteroplacental circulation in first trimester and pregnancy outcome in women with congenital heart disease.

OBJECTIVE: Pregnant women with congenital heart disease (CHD) have an increased risk of abnormal uteroplacental flow, measured from the second trimester onwards, which is associated with pregnancy complications affecting the mother and the fetus. Maternal right ventricular (RV) dysfunction has been suggested as a predisposing factor for impaired uteroplacental flow in these women. The aim of this study was to investigate the association of first-trimester uteroplacental flow measurements with prepregnancy maternal cardiac function and pregnancy complications in women with CHD, with particular focus on the potential role of RV (dys)function. METHODS: This study included 138 pregnant women with CHD from the prospective ZAHARA III study (Zwangerschap bij Aangeboren HARtAfwijkingen; Pregnancy and CHD). Prepregnancy clinical and echocardiographic data were collected. Clinical evaluation, echocardiography (focused on RV function, as assessed by tricuspid annular plane systolic excursion (TAPSE)) and uterine artery (UtA) pulsatility index (PI) measurements were performed at 12, 20 and 32 weeks of gestation. Univariable and multivariable regression analyses were performed to assess the association between prepregnancy variables and UtA-PI during pregnancy. The association between UtA-PI at 12 weeks and cardiovascular, obstetric and neonatal complications was also assessed. RESULTS: On multivariable regression analysis, prepregnancy TAPSE was associated negatively with UtA-PI at 12 weeks of gestation (ß = -0.026; P = 0.036). Women with lower prepregnancy TAPSE (≤ 20 mm vs > 20 mm) had higher UtA-PI at 12 weeks (1.5 ± 0.5 vs 1.2 ± 0.6; P = 0.047). Increased UtA-PI at 12 weeks was associated with obstetric complications (P = 0.003), particularly hypertensive disorders (pregnancy-induced hypertension and pre-eclampsia, P = 0.019 and P = 0.026, respectively). CONCLUSIONS: In women with CHD, RV dysfunction before pregnancy seems to impact placentation, resulting in increased resistance in UtA flow, which is detectable as early as in the first trimester. This, in turn, is associated with pregnancy complications. Early monitoring of uteroplacental flow might be of value in women with CHD with pre-existing subclinical RV dysfunction to identify pregnancies that would benefit from close obstetric surveillance. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Quantitative margin assessment of radiofrequency ablation of a solitary colorectal hepatic metastasis using MIRADA RTx on CT scans: a feasibility study.

BACKGROUND: Compared to surgery, radiofrequency ablation(RFA) for colorectal liver metastasis(CRLM) is associated with higher local recurrence(LR) rates. A wide margin (at least 5 mm) is generally recommended to prevent LR, but the optimal method to assess ablation margins is yet to be established. The aim of our study was to evaluate the feasibility and reproducibility of CT-CT co-registration, using MIRADA software, in order to assess ablation margins of patients with CRLM. METHODS: In this retrospective study, pre- and post-ablation contrast-enhanced CT scans of 29 patients, treated with percutaneous RFA for a solitary CRLM, were co-registered. Co-registration was performed by two independent radiologist, based on venous structures in proximity to the tumor. Feasibility of CT-CT co-registration and inter-observer agreement for reproducibility and ablation margins was determined. Furthermore, the minimal ablation margin was compared with the occurrence of LR during follow-up. RESULTS: Co-registration was considered feasible in 18 patients (61% male, 63.1(±10.9) year), with a perfect inter-observer agreement for completeness of ablation: κ = 1.0(p < 0.001). And substantial inter-observer agreement for measurement of the minimal margin (≤ 0 mm, 1-5 mm, ≥ 5 mm): κ = 0.723(p-value < 0.001). LR occurred in eight of nine(88.9%) incompletely ablated CRLM and in one of the nine completely ablated CRLM(11.1%). CONCLUSION: Co-registration using MIRADA is reproducible and potentially a valuable tool in defining technical success. Feasibility of co-registration of pre- and post-ablation CT scans is suboptimal if scans are not acquired concordantly. Co-registration may potentially aid in the prediction of LR after percutaneous ablation.

Adults with congenital heart disease: ready for mobile health?

PURPOSE: Mobile health (mHealth) could improve the outcome of grown-up patients with congenital heart disease (GUCH) and reduce their emergency care utilisation. Inappropriate use of mHealth, however, can lead to data overload for professionals and unnecessary data collection for patients, increasing the burden for both. We aimed to determine the clinical characteristics of patients with high emergency care utilisation and to test whether these patients were willing to start using mHealth. METHODS: Clinical characteristics and emergency care utilisation of consecutive GUCH patients who visited one of the two participating cardiologists at the outpatient clinic of the Academic Medical Centre in Amsterdam were studied retrospectively. All patients were approached to fill in an mHealth questionnaire. A frequency of three or more emergency visits in 5 years was defined as high emergency care utilisation. RESULTS: In total, 202 consecutive GUCH patients who visited one of the two participating cardiologists were studied. Median age was 41 years, 47% were male, and 51% were symptomatic. In the previous 5 years, 134 emergency visits were identified. Of all patients, 8% had high emergency care utilisation. High emergency care utilisation was associated with patients being symptomatic, using antiarrhythmic drugs or diuretics. In total, 75% of all patients with high emergency care utilisation were willing to start using mHealth. CONCLUSION: GUCH patients who are symptomatic, those on antiarrhythmic drug therapy and those on diuretics are suitable candidates for enrolment in future mHealth initiatives because of both high care utilisation and high motivation to start using mHealth.

Differences at surgery between patients with bicuspid and tricuspid aortic valves.

AIM: To determine differences in surgical procedures and clinical characteristics at the time of surgery between native bicuspid aortic valves (BAV) and tricuspid aortic valves (TAV) in patients being followed up after aortic valve surgery (AVS). METHODS: In this retrospective cohort study in a non-academic hospital, we identified patients who had a surgeon's report of the number of native valve cusps and were still being followed up. We selected patients with BAV and TAV, and used multivariable regression analyses to identify associations between BAV-TAV and pre-specified clinical characteristics. RESULTS: Of 439 patients, 140 had BAV (32%) and 299 TAV (68%). BAV patients were younger at the time of surgery (mean age 58.6 ± 13 years) than TAV patients (69.1 ± 12 years, p < 0.001) and were more often male (64% vs 53%; p = 0.029). Cardiovascular risk factors were less prevalent in BAV than in TAV patients at the time of surgery (hypertension (31% vs 55%), hypercholesterolaemia (29% vs 58%) and diabetes (7% vs 16%); all p < 0.005). Concomitant coronary artery bypass grafting (CABG) was performed less often in BAV than in TAV patients (14% vs 39%, p < 0.001), even when adjusted for confounders (adjusted odds ratio (adj.OR) 0.45; 95% CI: 0.25-0.83). In contrast, surgery of the proximal aorta was performed more often (31% vs 11%, respectively, p < 0.001; adj.OR 2.3; 95% CI: 1.3-4.0). CONCLUSIONS: Whereas mechanical stress is the supposed major driver of valvulopathy towards AVS in BAV, prevalent cardiovascular risk factors are a suspected driver towards the requirement for AVS and concomitant CABG in TAV, an observation based on surgical determination of the number of valve cusps.

First real-world experience with mobile health telemonitoring in adult patients with congenital heart disease.

BACKGROUND: Arrhythmias and heart failure are common and invalidating sequelae in adult patients with congenital heart disease (CHD). Mobile health (m-Health) enables daily monitoring and a timely response that might prevent deterioration. We present an observational prospective registry to evaluate feasibility of an m­Health telemonitoring program for managing arrhythmia, heart failure and blood pressure in symptomatic adults with CHD. METHODS: Symptomatic adult patients with CHD are enrolled in an m­Health telemonitoring program, which evaluates single-lead ECG, blood pressure and weight measurements. In case of symptoms extra measurements could be performed. Data are collected by mobile apps, matched with individualised thresholds. Patients are contacted if thresholds were exceeded or if arrhythmias were found, for treatment adjustments or reassurance. Data on emergency care utilisation, hospitalisation and patient-reported outcome measures are used to assess quality of life and self-management. RESULTS: 129 symptomatic CHD patients were invited to participate, 55 participated. Reasons for refusing consent included too time consuming to participate in research (30) and to monitor vital signs (14). At baseline 22 patients were in New York Heart Association class ≥ II heart failure, 43 patients had palpitations or documented arrhythmias, and 8 had hypertension. Mean follow-up was 3.0 months, one patient dropped out, and adherence was 97%. CONCLUSION: The first results indicate that this program is feasible with high adherence.

PREVENTION-ACHD: PRospEctiVE study on implaNTable cardioverter-defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease; Rationale and Design.

BACKGROUND: Many adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). An implantable cardioverter-defibrillator (ICD) may prevent SCD, but the evidence for primary prevention indications is still unsatisfactory. STUDY DESIGN: PREVENTION-ACHD is a prospective study with which we aim to prospectively validate a new risk score model for primary prevention of SCD in ACHD patients, as well as the currently existing guideline recommendations. Patients are screened using a novel risk score to predict SCD as well as current ICD indications according to an international Consensus Statement. Patients are followed up for two years. The primary endpoint is the occurrence of SCD and sustained ventricular arrhythmias. The Study was registered at ClinicalTrials.gov (NCT03957824). CONCLUSION: PREVENTION-ACHD is the first prospective study on SCD in ACHD patients. In the light of a growing and aging population of patients with more severe congenital heart defects, more robust clinical evidence on primary prevention of SCD is urgently needed.

Differences in Treatment and Outcome of Pancreatic Adenocarcinoma Stage I and II in the EURECCA Pancreas Consortium.

BACKGROUND: The EUropean REgistration of Cancer CAre (EURECCA) consortium aims to investigate differences in treatment and to improve cancer care through Europe. The purpose of this study was to compare neo- and adjuvant chemotherapy (ACT) and outcome after tumor resection for pancreatic adenocarcinoma stage I and II in the EURECCA Pancreas consortium. METHODS: The eight, collaborating national, regional, and single-center partners shared their anonymized dataset. Patients diagnosed in 2012-2013 who underwent tumor resection for pancreatic adenocarcinoma stage I and II were investigated with respect to treatment and survival and compared using uni- and multivariable logistic and Cox regression analyses. All comparisons were performed separately per registry type: national, regional, and single-center registries. RESULTS: In total, 2052 patients were included. Stage II was present in the majority of patients. The use of neo-ACT was limited in most registries (range 2.8-15.5%) and was only different between Belgium and The Netherlands after adjustment for potential confounders. The use of ACT was different between the registries (range 40.5-70.0%), even after adjustment for potential confounders. Ninety-day mortality was also different between the registries (range 0.9-13.6%). In multivariable analyses for overall survival, differences were observed between the national and regional registries. Furthermore, patients in ascending age groups and patients with stage II showed a significant worse overall survival. CONCLUSIONS: This study provides a clear insight in clinical practice in the EURECCA Pancreas consortium. The differences observed in (neo-)ACT and outcome give us the chance to further investigate the best practices and improve outcome of pancreatic adenocarcinoma.

Gadoxetic acid-enhanced magnetic resonance imaging significantly influences the clinical course in patients with colorectal liver metastases.

BACKGROUND: Gadoxetic acid (Primovist™)-enhanced magnetic resonance imaging (P-MRI) scans have higher accuracy and increased detection of small colorectal liver metastases (CRLM) compared to CT scans or conventional MRI scans. But, P-MRI scans are still inconsistently acquired in the diagnostic work up of patients with CRLM. The aim of this study was to determine the influence of P-MRI scans on treatment plan proposition and subsequently the clinical course of the patient. METHODS: Eighty-three consecutive patients with potentially resectable CRLM based on a conventional CT scan underwent P-MRI scanning prior to treatment. Treatment plans proposed by the multidisciplinary team were compared before and after P-MRI scanning and related to the final treatment and diagnosis, the accuracy for the CT scan and P-MRI scan was calculated. RESULTS: P-MRI scans led to a change of treatment in 15 patients (18%) and alteration of extensiveness of local therapy in another 17 patients (20%). All changes were justified leading to an accuracy of 93% for treatment proposition based on P-MRI scan, compared to an accuracy of 75% for the CT scan. CONCLUSIONS: P-MRI scans provide additional information that can aid in proposing the most suitable treatment for patients with CRLM and might prevent short-term reintervention.

Uteroplacental Doppler flow and pregnancy outcome in women with tetralogy of Fallot.

OBJECTIVE: Pregnancy in women with surgically corrected tetralogy of Fallot (ToF) is associated with cardiac, obstetric and neonatal complications. We compared uteroplacental Doppler flow (UDF) measurements and pregnancy outcome in women with ToF and in healthy women and aimed to assess whether a relationship exists between cardiac function and UDF in women with ToF. METHODS: We evaluated prospectively pregnant women with ToF and healthy pregnant women from the ZAHARA studies. Clinical evaluation, standardized echocardiography and UDF measurements were performed at 20 and 32 weeks' gestation. RESULTS: We included 62 women with ToF and 69 healthy controls. Cardiac complications, mostly arrhythmia, occurred in 8.1% of women with ToF. There was a higher incidence of small-for-gestational age (21.0% vs 4.4%, P = 0.004) and low birth weight (16.1% vs 2.9%, P = 0.009) in the group of women with ToF than in healthy controls. In women with ToF, early diastolic notching of uterine artery waveform at 20 and 32 weeks occurred more frequently (9.8% vs 1.5%, P = 0.034 and 7.0% vs 0%, P = 0.025, respectively) and the umbilical artery pulsatility index at 32 weeks was higher (1.02 ± 0.20 vs 0.94 ± 0.17, P = 0.015) than in healthy controls. Right ventricular function parameters prepregnancy and at 20 weeks' gestation were significantly associated with abnormal UDF. UDF parameters were associated with adverse neonatal outcome. CONCLUSION: The majority of women with surgically corrected ToF tolerate pregnancy well. However, UDF indices are more frequently abnormal in these women, suggesting impaired placentation. The association of impaired right ventricular function parameters with abnormal UDF suggests that cardiac dysfunction contributes to defective placentation or placental perfusion mismatch and may explain the increased incidence of obstetric and neonatal complications. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Antibiotic use during pregnancy and asthma in preschool children: the influence of confounding.

BACKGROUND: A recent study suggested that early-life intestinal microbiota may play an important role in the development of childhood asthma, indicating that antibiotics taken during early life or in late pregnancy may be associated with childhood asthma. OBJECTIVE: This study aims to assess the association between prenatal antibiotic use and asthma in preschool children using data from the prescription database IADB.nl. To assess the influence of potential confounding, we conducted both a case-sibling and a case-control study and compared the results. METHODS: We conducted a case-sibling study in which 1228 children with asthma were compared to 1228 siblings without asthma, using data from the prescription database IADB.nl. In addition, a case-control study was conducted. Asthma in preschool children was defined as ≥ 3 prescriptions for anti-asthma medication within a year before the fifth birthday. Conditional logistic regression was used to estimate crude and adjusted odds ratios (aORs). RESULTS: In both the case-sibling and case-control analysis, the use of antibiotics in the third trimester of pregnancy was associated with an increased risk of asthma in preschool children (aOR 1.37; 95% CI 1.02-1.83 and aOR 1.40; 95% CI 1.15-1.47). Time-trend analyses showed that results were not influenced by a time trend in antibiotic exposure. A significant association between exposure to antibiotics in any trimester of pregnancy and the development of asthma in preschool children was observed in the case-control analysis only (aOR 1.46; 95% CI 1.34-1.59). CONCLUSION: Antibiotic use in the third trimester of pregnancy was associated with a small increased risk of asthma in preschool children. This association was robust to time-invariant confounding or exposure time trends, further supporting the important role for early-life intestinal microbiota in the development of childhood asthma.

Identification of Dutch children diagnosed with atopic diseases using prescription data: a validation study.

PURPOSE: The aim of this study is to validate medication proxies for the identification of children diagnosed with atopic disorders that can be applied in various types of epidemiological research. METHODS: Records of 7439 children, aged between 0 and 10 years, in the period 2001 until 2010, were retrieved from the Registration Network Groningen database, a general practitioners database in the north-eastern part of the Netherlands. The sensitivity and positive predictive value (PPV) of 22 medication proxies for the identification of children diagnosed with atopic disorders (asthma, atopic dermatitis, and allergic rhinitis) were computed using the registered diagnoses as gold standards. In addition, different capture periods (1 year, half year, and length of study period) for the detection of prescriptions were tested for all the medication proxies. RESULTS: The highest PPV (0.84, 95 % CI 0.81-0.87) in combination with a sufficient sensitivity value (0.54, 95 % CI 0.50-0.57) for the identification of children diagnosed with asthma was yielded for the medication proxy, ≥2 prescriptions for anti-asthma medication within 1 year, including 1 inhaled steroid. PPV and sensitivity were even higher in the age group 6-10 years. The proxies designed for the identification of children diagnosed with atopic dermatitis and allergic rhinitis yielded only high PPVs (≥0.75) in combination with low sensitivity values (≤0.22). Altering the capture period for the detection of prescriptions to half a year or the length of the study period only affected sensitivity values. CONCLUSION: Children diagnosed with asthma can be identified reliably with a range of medication proxies. The use of prescription data for the identification of children diagnosed with atopic dermatitis and allergic rhinitis is questionable.

Relationship between atrial septal defects and asthma-like dyspnoea: the impact of transcatheter closure.

BACKGROUND: Patients with atrial septal defects (ASD) are often misdiagnosed as asthma patients and accordingly receive erroneous bronchodilator treatment. In order to characterise their symptoms of dyspnoea to explain this clinical observation, we investigated the prevalence of asthma-like symptoms in patients with secundum ASD who then underwent successful percutaneous closure. METHODS: A total of 80 ASD patients (74 % female, mean age 46.7 ± 16.8 years, median follow-up 3.0 [2.0-5.0] years) retrospectively completed dyspnoea questionnaires determining the presence and extent of cough, wheezing, chest tightness, effort dyspnoea and bronchodilator use on a 7-point scale (0 = none, 6 = maximum) before and after ASD closure. The Mini Asthma Quality of Life (Mini-AQLQ) and Asthma Control Questionnaire with bronchodilator use (ACQ6) were administered. RESULTS: A total of 48 (60 %) patients reported cough, 27 (34 %) wheezing, 26 (33 %) chest tightness and 62 (78 %) effort dyspnoea. Symptom resolution or reduction was found in 64 (80 %) patients after ASD closure. Asthma symptom scores decreased significantly on the Mini-AQLQ and ACQ6 (both p < 0.001). The number of patients using bronchodilators decreased from 16 (20 %) to 8 (10 %) patients after ASD closure (p = 0.039) with less frequent use of bronchodilators (p = 0.015). CONCLUSIONS: A high prevalence of asthma-like symptoms and bronchodilator use is present in ASD patients, which exceeds the low prevalence of bronchial asthma in this study population. Future prospective research is required to confirm this phenomenon. The presence of an ASD should be considered in the differential diagnosis of patients with asthma-like symptoms, after which significant symptom relief can be achieved by ASD closure.

Transition from paediatric to adult care of adolescent patients with congenital heart disease: a pathway to optimal care.

INTRODUCTION: Adolescents with congenital heart disease transition from a paediatric to an adult setting. This is associated with loss-to-follow-up and suboptimal care. Increasing numbers of patients justify a special program. In this study we evaluated the cooperative program between paediatric and adult cardiology departments in a tertiary referral centre. METHODS: In this retrospective study, patients with congenital heart disease with at least one appointment scheduled at the transition program between January 2010 and January 2015 were included. They were seen by a paediatric cardiologist at the age of 15 years in the paediatric department and from age 18 to 25 in the adult department. Demographic and medical data were collected from the electronic patient files. RESULTS: A total of 193 patients (105 males, 88 females) were identified. Sex distribution was almost equal. Most patients were 18-21 years of age. The largest group, 128 patients (67 %), lived within 50 kilometres of our hospital. Paediatric cardiologists referred 157 (81 %) of patients. General practitioners and cardiologists from outside our centre were important referrers for patients lost to follow-up, together accounting for 9 %. A total of 34 (18 %) patients missed an appointment without notification. Repeat offenders, 16 of 34 patients, formed a significant minority within this group. A total of 114 (59 %) patients were attending school, 46 (24 %) were employed, and 33 (17 %) patients were inactive. Activities are in line with capabilities. A nurse practitioner was involved with the 7 % with complex and psychosocial problems. Moderately severe congenital heart defects formed the largest patient category of 102 (53 %) patients. In 3 % of patients the diagnosis had to be revised or was significantly incomplete. In 30 (16 %) patients, cardiac diagnosis was part of a syndrome. Of the 193 patients, 117 (92 %) were in NYHA class I, with 12 (6 %) and 4 (2 %) patients falling into classes II and III, respectively. CONCLUSIONS: A viable transition program can be built by collaboration between paediatric and adult cardiology departments with the same treating physician taking care of patients between 15 and 25 years of age. General practitioners are important in returning lost-to-follow-up patients to specialised care. Nurse practitioners are essential in the care for patients with complex congenital heart disease.