Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study).

BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherlands Trial Register, NTR6268.

Funnel plots a graphical instrument for the evaluation of population performance and quality of trauma care: a blueprint of implementation.

BACKGROUND: Using patient outcomes to monitor medical centre performance has become an essential part of modern health care. However, classic league tables generally inflict stigmatization on centres rated as "poor performers", which has a negative effect on public trust and professional morale. In the present study, we aim to illustrate that funnel plots, including trends over time, can be used as a method to control the quality of data and to monitor and assure the quality of trauma care. Moreover, we aimed to present a set of regulations on how to interpret and act on underperformance or overperformance trends presented in funnel plots. METHODS: A retrospective observational cohort study was performed using the Dutch National Trauma Registry (DNTR). Two separate datasets were created to assess the effects of healthy and multiple imputations to cope with missing values. Funnel plots displaying the performance of all trauma-receiving hospitals in 2020 were generated, and in-hospital mortality was used as the main indicator of centre performance. Indirect standardization was used to correct for differences in the types of cases. Comet plots were generated displaying the performance trends of two level-I trauma centres since 2017 and 2018. RESULTS: Funnel plots based on data using healthy imputation for missing values can highlight centres lacking good data quality. A comet plot illustrates the performance trend over multiple years, which is more indicative of a centre's performance compared to a single measurement. Trends analysis offers the opportunity to closely monitor an individual centres' performance and direct evaluation of initiated improvement strategies. CONCLUSION: This study describes the use of funnel and comet plots as a method to monitor and assure high-quality data and to evaluate trauma centre performance over multiple years. Moreover, this is the first study to provide a regulatory blueprint on how to interpret and act on the under- or overperformance of trauma centres. Further evaluations are needed to assess its functionality. LEVEL OF EVIDENCE: Retrospective study, level III.

Trends in data quality and quality indicators 5 years after implementation of the Dutch Hip Fracture Audit.

PURPOSE: The Dutch Hip Fracture Audit (DHFA), a nationwide hip fracture registry in the Netherlands, registers hip fracture patients and aims to improve quality of care since 2016. This study shows trends in the data quality during the first 5 years of data acquisition within the DHFA, as well as trends over time for designated quality indicators (QI). METHODS: All patients registered in the DHFA between 1-1-2016 and 31-12-2020 were included. Data quality-registry case coverage and data completeness-and baseline characteristics are reported. Five QI are analysed: Time to surgery < 48 h, assessment for osteoporosis, orthogeriatric co-management, registration of functional outcomes at three months, 30-day mortality. The independent association between QI results and report year was tested using mixed-effects logistic models and in the case of 30-day mortality adjusted for casemix. RESULTS: In 2020, the case capture of the DHFA comprised 85% of the Dutch hip fracture patients, 66/68 hospitals participated. The average of missing clinical values was 7.5% in 2016 and 3.2% in 2020. The 3 months follow-up completeness was 36.2% (2016) and 46.8% (2020). The QI 'time to surgery' was consistently high, assessment for osteoporosis remained low, orthogeriatric co-management scores increased without significance, registration of functional outcomes improved significantly and 30-day mortality rates remained unchanged. CONCLUSION: The DHFA has successfully been implemented in the past five years. Trends show improvement on data quality. Analysis of several QI indicate points of attention. Future perspectives include lowering the burden of registration, whilst improving (registration of) hip fracture patients outcomes.

Dysphagia, Fear of Choking and Preventive Measures in Patients with Huntington's Disease: The Perspectives of Patients and Caregivers in Long-Term Care.

OBJECTIVES: To explore the prevalence of dysphagia and fear of choking in patients with Huntington's disease (HD) as well as preventive measures, both those applied and those not included in managing dysphagia. Also, to investigate related problems encountered by their formal and informal caregivers. DESIGN: A multi-center observational cross-sectional study. SETTING AND PARTICIPANTS: 158 HD patients, recruited from six Dutch nursing homes specialized in HD, and their formal and informal caregivers. MEASUREMENTS: Patients were assessed by means of questionnaires enquiring about dysphagia, fear of choking and measures to manage dysphagia. Also, questionnaires were administered about awareness of dysphagia symptoms, cognition and anxiety. Because we expected individuals with greater care dependency to have a higher severity of dysphagia, we distinguished between a care-independent and a care-dependent group of HD patients. RESULTS: In the total group, 90.5% of HD patients had one or more dysphagia symptoms. The prevalence of FoC in HD patients and the formal and informal caregivers' fears about choking in HD patients was 45.7%, 19.0% and 59.5%, respectively, for care-independent patients and 58.7%, 50.1% and 77.5% for care-dependent patients. The score on the Huntington's Disease Dysphagia Scale was a predictor for fear of FoC in care-independent patients. Speech-language therapy, supervision during eating and drinking and adaptation of food and drink consistency were the most frequently applied measures to manage dysphagia, a combination was used in most HD patients. CONCLUSIONS: In HD patients, the prevalence of dysphagia is high and fear of choking is common among both patients and caregivers. A more severe degree of dysphagia is a predictor of FoC in care-independent HD patients. A combination of measures was used to manage dysphagia in most HD patients.

Depressive symptoms during the different phases of a migraine attack: A prospective diary study.

BACKGROUND: The relationship between migraine and depression has been thoroughly investigated, indicating a bidirectional comorbidity. The exact temporal relationship between acute depressive symptoms (mood changes) and the various phases of the migraine attack has not yet been examined. METHODS: We performed a prospective diary study in n = 487 participants with migraine. Participants filled out a daily diary on migraine and acute depressive symptoms during a 1-month period. We randomly selected one migraine attack per participant, consisting of six days around an attack, including the interictal, premonitory, ictal, and postdromal phases. Acute depressive symptoms covered five major items from the DSM-5 classification. Primary analysis was performed using a mixed model with post-hoc testing. We also tested whether lifetime depression influenced the presence of acute depressive symptoms. RESULTS: During a migraine headache day, patients scored higher on acute depressive symptoms than on all other days of the migraine attack (p < 0.001). There were no early warning signs for an upcoming headache attack through acute depressive symptomatology. Migraine patients with lifetime depression scored overall higher during the migraine attack than those without lifetime depression (p < 0.001). LIMITATIONS: Migraine attacks were based on self-reported migraine and one migraine attack per patient was randomly selected. CONCLUSION: We now clearly demonstrate that during the migraine headache phase, but not in the prodromal phase, patients report increased depressive symptomatology. No evidence was found for mood changes as an early warning sign for an upcoming migraine attack.

Effects of hospital preference for endovascular repair on postoperative mortality after elective abdominal aortic aneurysm repair: analysis of the Dutch Surgical Aneurysm Audit.

BACKGROUND: Increased use of endovascular aneurysm repair (EVAR) and reduced open surgical repair (OSR), has decreased postoperative mortality after elective repair of abdominal aortic aneurysms (AAAs). The choice between EVAR or OSR depends on aneurysm anatomy, and the experience and preference of the vascular surgeon, and therefore differs between hospitals. The aim of this study was to investigate the current mortality risk difference (RD) between EVAR and OSR, and the effect of hospital preference for EVAR on overall mortality. METHODS: Primary elective infrarenal or juxtarenal aneurysm repairs registered in the Dutch Surgical Aneurysm Audit (2013-2017) were analysed. First, mortality in hospitals with a higher preference for EVAR (high-EVAR group) was compared with that in hospitals with a lower EVAR preference (low-EVAR group), divided by the median percentage of EVAR. Second, the mortality RD between EVAR and OSR was determined by unadjusted and adjusted linear regression and propensity-score (PS) analysis and then by instrumental-variable (IV) analysis, adjusting for unobserved confounders; percentage EVAR by hospital was used as the IV. RESULTS: A total of 11 997 patients were included. The median hospital rate of EVAR was 76.6 per cent. The overall mortality RD between high- and low-EVAR hospitals was 0.1 (95 per cent -0.5 to 0.4) per cent. The OSR mortality rate was significantly higher among high-EVAR hospitals than low-EVAR hospitals: 7.3 versus 4.0 per cent (RD 3.3 (1.4 to 5.3) per cent). The EVAR mortality rate was also higher in high-EVAR hospitals: 0.9 versus 0.7 per cent (RD 0.2 (-0.0 to 0.6) per cent). The RD following unadjusted, adjusted, and PS analysis was 4.2 (3.7 to 4.8), 4.4 (3.8 to 5.0), and 4.7 (4.1 to 5.3) per cent in favour of EVAR over OSR. However, the RD after IV analysis was not significant: 1.3 (-0.9 to 3.6) per cent. CONCLUSION: Even though EVAR has a lower mortality rate than OSR, the overall effect is offset by the high mortality rate after OSR in hospitals with a strong focus on EVAR.

Striped occipital cortex and intragyral hemorrhage: Novel magnetic resonance imaging markers for cerebral amyloid angiopathy.

BACKGROUND AND AIM: To investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary cerebral amyloid angiopathy (CAA), also occur in sporadic CAA (sCAA) or non-sCAA intracerebral hemorrhage (ICH). METHODS: We performed 7-tesla-magnetic resonance imaging in patients with probable sCAA and patients with non-sCAA-ICH. Striped occipital cortex (linear hypointense stripes perpendicular to the cortex) and intragyral hemorrhage (hemorrhage restricted to the juxtacortical white matter of one gyrus) were scored on T2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features. RESULTS: We included 33 patients with sCAA (median age 70 years) and 29 patients with non-sCAA-ICH (median age 58 years). Striped occipital cortex was detected in one (3%) patient with severe sCAA. Five intragyral hemorrhages were found in four (12%) sCAA patients. The markers were absent in the non-sCAA-ICH group. Patients with intragyral hemorrhages had more lobar ICHs (median count 6.5 vs. 1.0), lobar microbleeds (median count >50 vs. 15), and lower median cognitive scores (Mini Mental State Exam: 20 vs. 28, Montreal Cognitive Assessment: 18 vs. 24) compared with patients with sCAA without intragyral hemorrhage. In 12 (36%) patients, sCAA diagnosis was changed to mixed-type small vessel disease due to deep bleeds previously unobserved on lower field-magnetic resonance imaging. CONCLUSION: Whereas a striped occipital cortex is rare in sCAA, 12% of patients with sCAA have intragyral hemorrhages. Intragyral hemorrhages seem to be related to advanced disease and their absence in patients with non-sCAA-ICH could suggest specificity for CAA.

Cold extremities in migraine: a marker for vascular dysfunction in women.

BACKGROUND AND PURPOSE: Migraine is recognized as a vascular risk factor, especially in women. Presumably, migraine, stroke and cardiovascular events share pathophysiological mechanisms. Self-reported cold extremities were investigated as a marker for vascular dysfunction in migraine. Secondly, it was hypothesized that suffering from cold extremities affects sleep quality, possibly exacerbating migraine attack frequency. METHODS: In this case-control study, a random sample of 1084 migraine patients and 348 controls (aged 22-65 years) from the LUMINA migraine cohort were asked to complete questionnaires concerning cold extremities, sleep quality and migraine. RESULTS: A total of 594 migraine patients and 199 controls completed the questionnaires. In women, thermal discomfort and cold extremities (TDCE) were more often reported by migraineurs versus controls (odds ratio 2.3, 95% confidence interval 1.4-3.7; P < 0.001), but not significantly so in men (odds ratio 2.5, 95% confidence interval 0.9-6.9; P = 0.09). There was no difference in TDCE comparing migraine with or without aura. Female migraineurs who reported TDCE had higher attack frequencies compared to female migraineurs without TDCE (4 vs. 3 attacks per month; P = 0.003). The association between TDCE and attack frequency was mediated by the presence of difficulty initiating sleep (P = 0.02). CONCLUSION: Women with migraine more often reported cold extremities compared with controls, possibly indicating a sex-specific vascular vulnerability. Female migraineurs with cold extremities had higher attack frequencies, partly resulting from sleep disturbances. Future studies need to demonstrate whether cold extremities in female migraineurs are a predictor for cardiovascular and cerebrovascular events.

Fetuses with Isolated Congenital Heart Defects Show Normal Cerebral and Extracerebral Fluid Volume Growth: A 3D Sonographic Study in the Second and Third Trimester.

OBJECTIVE: The aim of our study is to explore whether the cerebral growth is delayed in fetuses with congenital heart defects (CHD) in the second and early third trimester. METHODS: A prospective cohort study was conducted in 77 CHD cases, with 75 healthy controls. 3D cerebral volume acquisition was performed sequentially. The volumes of the fetal hemicerebrum and extracerebral fluid were compared by linear regression analysis, and the Sylvian fissure was measured. RESULTS: Between 19 and 32 weeks of gestation, 158 measurements in cases and 183 measurements in controls were performed (mean 2.2/subject). The volume growth of the hemicerebrum (R2 = 0.95 vs. 0.95; p = 0.9) and the extracerebral fluid (R2 = 0.84 vs. 0.82, p = 0.9) were similar. Fetuses with abnormal oxygen delivery to the brain have a slightly smaller brain at 20 weeks of gestation (p = 0.02), but this difference disappeared with advancing gestation. CHD cases demonstrated a slightly shallower Sylvian fissure (mean ratio 0.146 vs. 0.153; p = 0.004). CONCLUSIONS: Our study shows no differences in cerebral growth, studied in an unselected cohort, with successive cases of isolated CHD. Even in the severest CHD cases, cerebral size is similar in the early third trimester. The cause and meaning of a shallower Sylvian fissure is unclear; possibly, it is a marker for delayed cerebral maturation or it might be an expression of decreasing amount of extracerebral fluid.

Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small vessel disease caused by C-terminal truncating TREX1 mutations. The disease is typically characterized by vascular retinopathy and focal and global brain dysfunction. Systemic manifestations have also been reported but not yet systematically investigated. METHODS: In a cross-sectional study, we compared the clinical characteristics of 33 TREX1 mutation carriers (MC+) from three Dutch RVCL-S families with those of 37 family members without TREX1 mutation (MC-). All participants were investigated using personal interviews, questionnaires, physical, neurological and neuropsychological examinations, blood and urine tests, and brain MRI. RESULTS: In MC+, vascular retinopathy and Raynaud's phenomenon were the earliest symptoms presenting from age 20 onwards. Kidney disease became manifest from around age 35, followed by liver disease, anaemia, markers of inflammation and, in some MC+, migraine and subclinical hypothyroidism, all from age 40. Cerebral deficits usually started mildly around age 50, associated with white matter and intracerebral mass lesions, and becoming severe around age 60-65. CONCLUSIONS: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare, but likely underdiagnosed, systemic small vessel disease typically starting with vascular retinopathy, followed by multiple internal organ disease, progressive brain dysfunction, and ultimately premature death.

Sensitivity of MG-ADL for generalized weakness in myasthenia gravis.

BACKGROUND AND PURPOSE: Myasthenia gravis activities of daily living (MG-ADL) is a commonly used questionnaire in MG trials. To investigate whether MG-ADL is equally sensitive to oculobulbar and generalized weakness, its correlation with the oculobulbar and generalized domain of the quantitative myasthenia gravis (QMG) score was analyzed (QMGob and QMGgen, respectively). To test whether the sensitivity of MG-ADL for generalized weakness could be improved, the additional value of ACTIVLIM on top of MG-ADL in the prediction QMGgen in was investigated. METHODS: MG-ADL, QMG and ACTIVLIM, an ADL questionnaire focusing on generalized weakness, were analyzed in a prospective cohort of 112 MG patients. A generalized linear model was used to calculate the correlation of MG-ADL with QMGob and QMGgen and to assess the additional value of ACTIVLIM on top of MG-ADL for its correlation with QMGgen. RESULTS: MG-ADL had a higher correlation with QMGob than with QMGgen (B = 0.68, P < 0.001, and B = 0.38, P < 0.001, respectively). A similar trend was found for changes in the scores (B = 0.68, P = 0.132, and B = 0.39, P = 0.492, respectively). ACTIVLIM had a significant additional value on top of MG-ADL in the prediction of QMGgen, both cross-sectionally (B = -0.61, P < 0.001) and for changes within individual patients (B = -0.93, P = 0.041). CONCLUSION: MG-ADL has a lower sensitivity for generalized weakness than for oculobulbar weakness. Adding questions on generalized weakness would improve the sensitivity of the MG-ADL for generalized weakness.

Outcome of Carpal Tunnel Release and the Relation With Depression.

PURPOSE: To examine the relation between depressive symptoms and outcome of carpal tunnel release (CTR). METHODS: Prospective study in a general hospital with data collection at baseline and 3 and 12 months after CTR. We quantified depressive symptoms using the Center for Epidemiologic Studies Depression (CES-D) scale and performed multivariable analyses on 2 outcome measures: (1) carpal tunnel syndrome (CTS) symptoms (Boston Carpal Tunnel Questionnaire [BCTQ]) and (2) palmar pain, focusing on preoperative CES-D and BCTQ score, sex, age, alcohol use, diabetes, and severity of nerve conduction abnormalities. RESULTS: We included 227 patients. Before surgery, patients with depression had a higher BCTQ score than patients without depression. After 1 year, depressed patients had a higher BCTQ score and more palmar pain. The CES-D decreased by a median of 2 points from baseline to 1 year. This correlated with the decrease in BCTQ score. Multivariable analyses showed that preoperative depression had a small but statistically significant influence on palmar pain, but not on postoperative BCTQ score. CONCLUSIONS: Depression is not an independent predictor of residual CTS symptoms 1 year after CTR. Depressive symptoms in patients with CTS decrease after CTR, along with a decrease in CTS symptoms. The nature of this relationship is unknown. Patients with CTS and depression may expect a somewhat higher degree of palmar pain after CTR, the clinical relevance of which is small. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Adjusted Hospital Outcomes of Abdominal Aortic Aneurysm Surgery Reported in the Dutch Surgical Aneurysm Audit.

OBJECTIVE/BACKGROUND: The Dutch Surgical Aneurysm Audit (DSAA) is mandatory for all patients with primary abdominal aortic aneurysms (AAAs) in the Netherlands. The aims are to present the observed outcomes of AAA surgery against the predicted outcomes by means of V-POSSUM (Vascular-Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity). Adjusted mortality was calculated by the original and re-estimated V(physiology)-POSSUM for hospital comparisons. METHODS: All patients operated on from January 2013 to December 2014 were included for analysis. Calibration and discrimination of V-POSSUM and V(p)-POSSUM was analysed. Mortality was benchmarked by means of the original V(p)-POSSUM formula and risk-adjusted by the re-estimated V(p)-POSSUM on the DSAA. RESULTS: In total, 5898 patients were included for analysis: 4579 with elective AAA (EAAA) and 1319 with acute abdominal aortic aneurysm (AAAA), acute symptomatic (SAAA; n = 371) or ruptured (RAAA; n = 948). The percentage of endovascular aneurysm repair (EVAR) varied between hospitals but showed no relation to hospital volume (EAAA: p = .12; AAAA: p = .07). EAAA, SAAA, and RAAA mortality was, respectively, 1.9%, 7.5%, and 28.7%. Elective mortality was 0.9% after EVAR and 5.0% after open surgical repair versus 15.6% and 27.4%, respectively, after AAAA. V-POSSUM overestimated mortality in most EAAA risk groups (p < .01). The discriminative ability of V-POSSUM in EAAA was moderate (C-statistic: .719) and poor for V(p)-POSSUM (C-statistic: .665). V-POSSUM in AAAA repair overestimated in high risk groups, and underestimated in low risk groups (p < .01). The discriminative ability in AAAA of V-POSSUM was moderate (.713) and of V(p)-POSSUM poor (.688). Risk adjustment by the re-estimated V(p)-POSSUM did not have any effect on hospital variation in EAAA but did in AAAA. CONCLUSION: Mortality in the DSAA was in line with the literature but is not discriminative for hospital comparisons in EAAA. Adjusting for V(p)-POSSUM, revealed no association between hospital volume and treatment or outcome. Risk adjustment for case mix by V(p)-POSSUM in patients with AAAA has been shown to be important.

Pretransplantation Donor-Recipient Pair Seroreactivity Against BK Polyomavirus Predicts Viremia and Nephropathy After Kidney Transplantation.

Kidney transplant donors are not currently implicated in predicting BK polyomavirus (BKPyV) infection in kidney transplant recipients. It has been postulated, however, that BKPyV infection originates from the kidney allograft. Because BKPyV seroreactivity correlates with BKPyV replication and thus might mirror the infectious load, we investigated whether BKPyV seroreactivity of the donor predicts viremia and BKPyV-associated nephropathy (BKPyVAN) in the recipient. In a retrospective cohort of 407 living kidney donor-recipient pairs, pretransplantation donor and recipient sera were tested for BKPyV IgG levels and correlated with the occurrence of recipient BKPyV viremia and BKPyVAN within 1 year after transplantation. Donor BKPyV IgG level was strongly associated with BKPyV viremia and BKPyVAN (p < 0.001), whereas recipient BKPyV seroreactivity showed a nonsignificant inverse trend. Pairing of high-BKPyV-seroreactive donors with low-seroreactive recipients resulted in a 10-fold increased risk of BKPyV viremia (hazard ratio 10.1, 95% CI 3.5-29.0, p < 0.001). In multivariate analysis, donor BKPyV seroreactivity was the strongest pretransplantation factor associated with viremia (p < 0.001) and BKPyVAN (p = 0.007). The proportional relationship between donor BKPyV seroreactivity and recipient infection suggests that donor BKPyV seroreactivity reflects the infectious load of the kidney allograft and calls for the use of pretransplantation BKPyV serological testing of (potential) donors and recipients.

Progression of motor subtypes in Huntington's disease: a 6-year follow-up study.

The objective of this study is to investigate the progression of predominantly choreatic and hypokinetic-rigid signs in Huntington's disease (HD) and their relationship with cognitive and general functioning over time. The motor signs in HD can be divided into predominantly choreatic and hypokinetic-rigid subtypes. It has been reported in cross-sectional studies that predominantly choreatic HD patients perform better on functional and cognitive assessments compared to predominantly hypokinetic-rigid HD patients. The course of these motor subtypes and their clinical profiles has not been investigated longitudinally. A total of 4135 subjects who participated in the European HD Network REGISTRY study were included and classified at baseline as either predominantly choreatic (n = 891), hypokinetic-rigid (n = 916), or mixed-motor (n = 2328), based on a previously used method. The maximum follow-up period was 6 years. The mixed-motor group was not included in the analyses. Linear mixed models were constructed to investigate changes in motor subtypes over time and their relationship with cognitive and functional decline. Over the 6-year follow-up period, the predominantly choreatic group showed a significant decrease in chorea, while hypokinetic-rigid symptoms slightly increased in the hypokinetic-rigid group. On the Total Functional Capacity, Stroop test, and Verbal fluency task the rate of change over time was significantly faster in the predominantly choreatic group, while on all other clinical assessments the decline was comparable for both groups. Our results suggest that choreatic symptoms decrease over time, whereas hypokinetic-rigid symptoms slightly increase in a large cohort of HD patients. Moreover, different motor subtypes can be related to different clinical profiles.

Head growth in fetuses with isolated congenital heart defects: lack of influence of aortic arch flow and ascending aorta oxygen saturation.

OBJECTIVES: Congenital heart defects (CHDs) are reported to be associated with a smaller fetal head circumference (HC) and neurodevelopmental delay. Recent studies suggest that altered intrauterine brain hemodynamics may explain these findings. Our objectives were to evaluate the pattern of head growth in a large cohort of fetuses with various types of CHD, analyze these patterns according to the type of CHD and estimate the effect of cerebral hemodynamics with advancing gestation in the second and third trimesters. METHODS: Singleton fetuses with an isolated CHD were selected from three fetal medicine units (n = 436). Cases with placental insufficiency or genetic syndromes were excluded. CHD types were clustered according to the flow and oxygen saturation in the aorta. Z-scores of biometric data were constructed using growth charts of a normal population. HC at different gestational ages was evaluated and univariate and multivariate mixed regression analyses were performed to examine the patterns of prenatal HC growth. RESULTS: Fetuses with severe and less severe types of CHD demonstrated statistically significant HC growth restriction with increasing gestational age (slope of -0.017/day); however, there was no statistically significant effect of fetal hemodynamics on HC growth. Fetuses with CHD but normal brain oxygenation and normal aortic flow showed a significant decrease in HC growth (slope of -0.024/day). Only fetuses with isolated tetralogy of Fallot demonstrated a smaller HC z-score at 20 weeks of gestation (-0.67 (95% CI, -1.16 to -0.18)). CONCLUSIONS: Despite the decline in head growth in fetuses with a prenatally detected isolated CHD, HC values were within the normal range, raising the question of its clinical significance. Furthermore, in contrast to other studies, this large cohort did not establish a significant correlation between aortic flow or oxygen saturation and HC growth. Factors other than altered fetal cerebral hemodynamics may contribute to HC growth restriction with increasing gestational age, such as (epi)genetic or placental factors. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Detoxification in medication-overuse headache, a retrospective controlled follow-up study: Does care by a headache nurse lead to cure?

AIM: J.A.P. and M.A.L. contributed equally to this manuscript.The aim of this article is to determine whether support by a headache nurse in the treatment of medication-overuse headache (MOH) increases successful withdrawal, and to study determinants of response to withdrawal therapy. METHODS: A retrospective, controlled follow-up study was performed with 416 MOH patients. All patients were treated with outpatient withdrawal therapy, with two treatment arms: with or without the support of a specialised headache nurse. The outcome measures were: i) successful withdrawal, defined as discontinuation of all headache medication according to the study protocol; and ii) the responder rate, defined as the percentage of patients with ≥ 50% reduction in headache days after successful withdrawal and iii) relative reduction in headache days after successful withdrawal. RESULTS: Successful withdrawal percentages were significantly higher in the group supported by the headache nurse than in the group without support (73.1% vs. 60.7%; p = 0.008), which was confirmed in multivariate analysis (OR 1.73, 95% CI 1.11-2.71, p = 0.016). Support by a headache nurse was not associated with response. The underlying primary headache diagnosis, determined after withdrawal, was significantly correlated with response. CONCLUSION: The support by a headache nurse results in an increased adherence to detoxification.

Symptom dimensions of affective disorders in migraine patients.

OBJECTIVE: A strong association has been established between migraine and depression. However, this is the first study to differentiate in a large sample of migraine patients for symptom dimensions of the affective disorder spectrum. METHODS: Migraine patients (n=3174) from the LUMINA (Leiden University Medical Centre Migraine Neuro-analysis Program) study and patients with current psychopathology (n=1129), past psychopathology (n=477), and healthy controls (n=561) from the NESDA (Netherlands Study of Depression and Anxiety) study, were compared for three symptom dimensions of depression and anxiety. The dimensions -lack of positive affect (depression specific); negative affect (nonspecific); and somatic arousal (anxiety specific)- were assessed by a shortened adaptation of the Mood and Anxiety Symptom Questionnaire (MASQ-D30). Within the migraine group, the association with migraine specific determinants was established. Multivariate regression analyses were conducted. RESULTS: Migraine patients differed significantly (p<0.001) from healthy controls for all three dimensions: Cohen's d effect sizes were 0.37 for lack of positive affect, 0.68 for negative affect, and 0.75 for somatic arousal. For the lack of positive affect and negative affect dimensions, migraine patients were predominantly similar to the past psychopathology group. For the somatic arousal dimension, migraine patients scores were more comparable with the current psychopathology group. Migraine specific determinants for high scores on all dimensions were high frequency of attacks and cutaneous allodynia during attacks. CONCLUSION: This study shows that affective symptoms in migraine patients are especially associated with the somatic arousal component.

Correlation between veno-venous anastomoses, TTTS and perinatal mortality in monochorionic twin pregnancies.

INTRODUCTION: The clinical significance of veno-venous (VV) anastomoses in monochorionic (MC) placentas remains inconclusive and controversial. The purpose of this study was to investigate the correlation between the presence of VV anastomoses and clinical outcome in a large cohort of MC twin pregnancies. METHODS: All MC placentas injected with colored dye from 2002 to 2014 were included in the study. We excluded MC pregnancies managed with fetoscopic laser surgery. RESULTS AND DISCUSSION: A total of 384 MC placentas were analyzed. VV anastomoses were detected in 27% (104/384) of MC placentas. The prevalence of twin-twin transfusion syndrome (TTTS) in MC placentas with VV anastomoses was significantly higher compared to MC placentas without VV anastomoses, 20% (21/104) versus 10% (29/280), respectively (P = .01). The overall perinatal mortality in MC twins with and without VV anastomoses was 16% versus 10%, respectively (P = .02). Risk factor analysis showed the presence of VV anastomoses was associated with perinatal mortality (P = .02; odds ratio (OR): 1.76; 95% confidence interval (CI): 1.11-2.79), but was not an independent risk factor for perinatal mortality (P = .26, OR: .66; 95% CI: .33-1.35) in MC twin pregnancies. However, VV anastomoses was associated with and was an independent risk factor for TTTS (P = .00, OR: 3.59; 95% CI: 1.72-7.47). VV anastomoses-related perinatal mortality may be due to the high rate of TTTS in MC twins with VV anastomoses. CONCLUSION: The presence of VV anastomoses is correlated with TTTS and perinatal mortality, but is not an independent risk factor for perinatal mortality in MC twin pregnancies.