BACKGROUND:Electronic dance music festivals (EDMF) can cause a significant disruption in the standard operational capacity of emergency medical services (EMS) and hospitals. We determined whether or not the presence of in-event health services (IEHS) can reduce the impact of Europe's largest EDMF on the host community EMS and local emergency departments (EDs).METHODS:We conducted a pre-post analysis of the impact of Europe's largest EDMF in July 2019, in Boom, Belgium, on the host community EMS and local EDs. Statistical analysis included descriptive statistics, independent t-tests, and χ2 analysis.RESULTS:Of 400,000 attendees, 12,451 presented to IEHS. Most patients only required in-event first aid, but 120 patients had a potentially life-threatening condition. One hundred fifty-two patients needed to be transported by IEHS to nearby hospitals, resulting in a transport-to-hospital rate of 0.38/1000 attendees. Eighteen patients remained admitted to the hospital for >24 h; one died after arrival in the ED. IEHS limited the overall impact of the MGE on regular EMS and nearby hospitals. No predictive model proved optimal when proposing the optimal number and level of IEHS members.CONCLUSIONS:This study shows that IEHS at this event limited ambulance usage and mitigated the event's impact on regular emergency medical and health services.

Importance The drug HD201 is a biosimilar candidate for breast cancer treatment as the reference trastuzumab. Objective To compare the efficacy of HD201 with referent trastuzumab. Design, Setting, and Participants This randomized clinical trial (TROIKA) included 502 women with ERBB2-positive early breast cancer treated with either HD201 or referent trastuzumab. It was conducted across 70 centers in 12 countries, including Western and Eastern Europe and Asian countries. Randomization was stratified by tumor hormone receptor status, clinical stage, and geographic region of recruitment. This analysis was conducted on February 12, 2021, after the completion of the adjuvant phase at a median of 31 months (IQR, 28-33 months) of follow-up. Interventions Patients with ERBB2-positive early breast cancer were randomly assigned to receive HD201 or referent trastuzumab in the neoadjuvant setting for 8 cycles, concurrently with 4 cycles of docetaxel, which was followed by 4 cycles of epirubicin and cyclophosphamide. Patients then underwent surgery, which was followed by treatment with 10 cycles of adjuvant HD201 or referent trastuzumab. Main Outcome and Measures The primary end point was the total pathological complete response (tpCR) assessed after neoadjuvant treatment. Equivalence was concluded if the 95% CI of the absolute difference in tpCR between arms in the per-protocol set was within the margin of more or less than 15%. Other objectives included the breast pathological complete response, overall response, event-free and overall survival, safety, pharmacokinetics, and immunogenicity. Results A total of 502 female patients (mean [range] age, 53 [26-82] years) were randomized to receive either HD201 or referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. The baseline characteristics were well balanced between the 2 arms; 195 tumors (38.8%) were hormone receptor-negative , and 213 patients (42.4%) had clinical stage III disease. The tpCR rates were 45% and 48.7% for HD201 and referent trastuzumab, respectively. The difference between the 2 groups was not significant at −3.8% (95% CI, −12.8% to 5.4%) and fell within the predefined equivalence margins. The ratio of the tpCR rates between the 2 arms was 0.92 (95% CI, 0.76 to 1.12). A total of 433 patients (86.1%) presented with 2232 treatment-emergent adverse events of special interest for trastuzumab during the entire treatment period, with 220 (88.0%) and 213 (84.5%) patients in the HD201 and referent trastuzumab groups, respectively. Conclusions and Relevance The results of this randomized clinical trial found that HD201 demonstrated equivalence to referent trastuzumab in terms of efficacy for the end point of tpCR, with a similar safety profile. Trial Registration ClinicalTrials.gov Identifier:NCT03013504

IMPORTANCE The drug HD201 is a biosimilar candidate for breast cancer treatment as the reference trastuzumab. OBJECTIVE To compare the efficacy of HD201with referent trastuzumab. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial (TROIKA) included 502 women with ERBB2-positive early breast cancer treated with either HD201 or referent trastuzumab. It was conducted across 70 centers in 12 countries, including Western and Eastern Europe and Asian countries. Randomization was stratified by tumor hormone receptor status, clinical stage, and geographic region of recruitment. This analysis was conducted on February 12, 2021, after the completion of the adjuvant phase at a median of 31 months (IQR, 28-33 months) of follow-up. INTERVENTIONS Patients with ERBB2-positive early breast cancer were randomly assigned to receive HD201or referent trastuzumab in the neoadjuvant setting for 8 cycles, concurrently with 4 cycles of docetaxel, which was followed by 4 cycles of epirubicin and cydophosphamide. Patients then underwent surgery, which was followed by treatment with 10 cycles of adjuvant HD201or referent trastuzumab. MAIN OUTCOME AND MEASURES The primary end point was the total pathological complete response (tpCR) assessed after neoadjuvant treatment. Equivalence was concluded if the 95% CI of the absolute difference in tpCR between arms in the per-protocol set was within the margin of more or less than 15%. Other objectives included the breast pathological complete response, overall response, event-free and overall survival, safety, pharmacokinetics, and immunogenicity. RESULTS A total of 502 female patients (mean [range] age, 53 [26-82] years) were randomized to receive either HD201 or referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. The baseline characteristics were well balanced between the 2 arms; 195 tumors (38.8%) were hormone receptor-negative , and 213 patients (42.4%) had clinical stage III disease. The tpCR rates were 45% and 48.7% for HD201 and referent trastuzumab, respectively. The difference between the 2 groups was not significant at -3.8% (95% CI, -12.8% to 5.4%) and fell within the predefined equivalence margins. The ratio of the tpCR rates between the 2 arms was 0.92 (95% CI, 0.76 to 1.12). A total of 433 patients (86.1%) presented with 2232 treatment-emergent adverse events of special interest for trastuzumab during the entire treatment period, with 220 (88.0%) and 213 (84.5%) patients in the HD201 and referent trastuzumab groups, respectively. CONCLUSIONS AND RELEVANCE The results of this randomized clinical trial found that HD201 demonstrated equivalence to referent trastuzumab in terms of efficacy for the end point of tpCR, with a similar safety profile.

This study aimed to describe the demographic and clinical characteristics of individuals involved in electric scooter (E-scooter) accidents and the factors associated with these incidents. We conducted a prospective observational study of individuals involved in E-scooter accidents admitted to the emergency department of Saint-Pierre Hospital. The highest abbreviated injury score above or equal to two classified the injury as significant. Injuries during working hours were compared to those during off-working hours. During the study period from June 1, 2019, to June 30, 2020, 170 individuals were admitted to the emergency department following an E-scooter accident. In 73.5

Objective: To compare actual patient presentation rates from Belgium's largest public open-air cultural festival with predictions provided by existing models and the Belgian Plan Risk Manifestations model. Methods: Retrospectively, actual patient presentation rates gathered from the Ghent Festivities (Belgium) during 2013-2019 were compared to predicted patient presentation rates by the Arbon, Hartman, and PRIMA models. Results: During 7 editions, 8673000 people visited the Ghent Festivities; 9146 sought medical assistance resulting in a mean patient presentation rate (PPR) of 1.05. The PRIMA model overestimated the number of patient encounters for each occasion. The other models had a high rate of underprediction. When comparing deviations in predictions between the PRIMA model to the other models, there is a significant difference in the mean deviation (Arbon: T = 0.000, P < 0.0001, r = -0.8701; Hartman: T = 0.000, P < 0.0001, r = -0.869). Conclusion: Despite the differences between the predictions of all 3 models, our results suggest that the PRIMA model is a valid tool to predict patient presentations to IEHS during public cultural MG. However, to substantiate the PRIMA model even further, more research is needed to further validate the model for a broad range of MG.

Introduction: The liver plays a central role in thyroid hormone metabolism, transport, and clearance. A normal function of both the thyroid gland and the liver is therefore necessary to maintain normal thyroid hormone levels and action. Data regarding thyroid function in patients with liver cirrhosis are scarce and variable. The most consistent finding is a decreased free triiodothyronine (fT3) level, which correlates with the severity of liver disease and has been proposed as a prognostic factor for liver-related complications. Aim of the study: To evaluate thyroid hormone values in patients with stable liver cirrhosis and to compare them with healthy controls without liver disease. We also assessed the prevalence of thyroid autoimmunity and whether liver function tests correlated with thyroid function. Material and methods: We performed a prospective case–control study in an endocrinological setting. Twenty-nine patients with stable cirrhosis (20 males and 9 females, mean age 60.97 ± 7.17 years) were included in the case group and 50 healthy subjects (22 males and 28 females, mean age 61.70 ± 13.00 years) in the control group. We excluded patients with confounding factors known to influence thyroid function. Levels of serum thyroid-stimulating hormone (TSH), fT3, free thyroxine (fT4) and anti-TPO-antibodies (TPO-Ab) were measured. These thyroid hormone values were compared in both groups. Biochemical indices of liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [AP], gamma-glutamyl transpeptidase [GGT], INR, total bilirubin, and albumin levels) were correlated with thyroid function tests. Results: fT3 en fT4 levels were significantly lower in patients with cirrhosis than in healthy subjects (p = 0.001 and 0.002, respectively). TSH levels were not statistically significantly different in the two groups. The level of TPO-Ab was not increased in patients with cirrhosis compared to healthy controls. fT3 correlated negatively with the Child–Pugh score. Discussion: These results indicate that, compared to healthy controls, patients with cirrhosis have decreased fT3 and fT4 levels and comparable TSH levels and may be consistent with findings of limited acquired central hypothyroidism as observed in the non-thyroidal illness syndrome (NTIS). fT3 levels correlated negatively with Child–Pugh score, a measure of severity of liver dysfunction. We did not find an increased prevalence of thyroid autoimmunity in these patients.

Background: Recombinant human C1 inhibitor (rhC1INH) for on-demand treatment of hereditary angioedema is purified from milk of transgenic rabbits. It contains low amounts (<0.002%) of host-related impurities, which could trigger hypersensitivity reactions in patients with rabbit allergy (RA) and/or cow's milk allergy (CMA). Objective: This study is an assessment of allergenicity and safety of rhC1INH in patients with RA and/or CMA. Methods: Patients with CMA and/or RA underwent skin prick test (SPT), intracutaneous test (ICT), and, when results for both were negative, subcutaneous (SC) challenge with up to 2100U (14 mL) rhC1INH. The negative predictive value of the skin test protocol was calculated, defined as the ratio of patients without systemic symptoms of hypersensitivity following SC challenge, over the number of patients having tested negative for both the SPT and the ICT. Adverse events after exposure to rhC1INH were recorded. Results: Twenty-six patients with RA and/or CMA were enrolled. Twenty-four had negative SPT and ICT results for rhC1INH, whereas 2 had negative SPT result but positive ICT result to rhC1INH (only the highest concentration). Twenty-two patients with negative SPT and ICT results underwent SC challenge. None developed allergic symptoms. Local treatment-emergent adverse events occurred in 7 patients (32%) after SC challenge. In 5 these were considered drug related. All were mild. Conclusions: None of the patients with negative SPT and ICT results for rhC1INH had allergic symptoms during rhC1INH challenge. The negative predictive value of the combination of SPT and ICT for the outcome of the SC challenge was 100% (95% CI, 84.6%-100%). SC administration of rhC1INH was well tolerated.

BACKGROUND AND AIMS:The aim of this study was to assess prevalence and associated bother of male lower urinary tract symptoms (LUTS), especially of urgency and other storage symptoms, since these are generally assumed to be underdiagnosed/undertreated in men.METHODS:Data on bladder condition of men ≥ 40 years were prospectively collected by 124 general practitioners (GPs) during a regular visit for any reason, using the validated ICIQ-MLUTS questionnaire. For 13 symptoms, prevalence (scale 0-4) and bother (scale 0-10) were scored. General bladder-related quality of life (scale 0-3) was also assessed.RESULTS:Data from 5890 men (mean age: 61.2 years) were analysed. A total of 7.7% had urgency most or all of the time (score ≥ 3) and 6.2% had bothersome urgency (score ≥ 3 + bother score ≥ 5). Nocturia (69.2%) and urgency (58.3%) were the most prevalent and bothersome symptoms. Both prevalence and bother of all LUTS increased with age. Additionally, 28.9% of men reported to be a little bothered by their bladder condition in everyday life, while 11.9% were bothered a lot/very much (2.5% in age group 40-49 years increasing to 29.2% in those > 80 years).CONCLUSIONS:In the general population of men ≥ 40 years who visited a GP for any reason, 41% indicated to be at least a little bothered by their bladder condition. The prevalence of LUTS, especially nocturia and urgency, is high and a significant number of men indicated to be seriously bothered. Increasing awareness of male LUTS, and storage symptoms in particular, is warranted to discuss management options that could increase quality of life.

OBJECTIVE:Immune intervention trials in recent-onset type 1 diabetes would benefit from biomarkers associated with good therapeutic response. In the previously reported randomized placebo-controlled anti-CD3 study (otelixizumab; GlaxoSmithKline), we tested the hypothesis that specific diabetes autoantibodies might serve this purpose.RESEARCH DESIGN AND METHODS:In the included patients (n = 40 otelixizumab, n = 40 placebo), β-cell function was assessed as area under the curve (AUC) C-peptide release during a hyperglycemic glucose clamp at baseline (median duration of insulin treatment: 6 days) and every 6 months until 18 months after randomization. (Auto)antibodies against insulin (I[A]A), GAD (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A) were determined on stored sera by liquid-phase radiobinding assay.RESULTS:At baseline, only better preserved AUC C-peptide release and higher levels of IAA were associated with better preservation of β-cell function and lower insulin needs under anti-CD3 treatment. In multivariate analysis, IAA (P = 0.022) or the interaction of IAA and C-peptide (P = 0.013) independently predicted outcome together with treatment. During follow-up, good responders to anti-CD3 treatment (i.e., IAA(+) participants with relatively preserved β-cell function [≥ 25% of healthy control subjects]) experienced a less pronounced insulin-induced rise in I(A)A and lower insulin needs. GADA, IA-2A, and ZnT8A levels were not influenced by anti-CD3 treatment, and their changes showed no relation to functional outcome.CONCLUSIONS:There is important specificity of IAA among other diabetes autoantibodies to predict good therapeutic response of recent-onset type 1 diabetic patients to anti-CD3 treatment. If confirmed, future immune intervention trials in type 1 diabetes should consider both relatively preserved functional β-cell mass and presence of IAA as inclusion criteria.

AIM:This Belgian epidemiological study aimed to assess the prevalence of overactive bladder (OAB) and stress urinary incontinence (SUI) and associated bother in a female primary care population.METHODS:Data on OAB and SUI were prospectively collected among women ≥ 40 years by general practitioners (GP) during a regular visit for any reason. The validated Bladder Control Self-Assessment Questionnaire (B-SAQ) was used and complemented with a question on SUI and bladder bother. The presence of mild bladder control symptoms (BCS) was defined as an overall B-SAQ symptom score (OSS) ≥ 4 and an overall bother score (OBS) ≥ 1. Descriptive statistics were performed.RESULTS:Data from 7139 women were analysed. About 33.9% had mild BCS. Most women reported overall mild OAB symptoms (46.9%) and 34.9% had moderate-to-(very) severe symptoms. The prevalence of moderate-severe urgency, frequency or nocturia was higher than that of moderate-severe incontinence. Urgency and nocturia were considered the most bothersome symptoms. Moderate-severe SUI affected 17.7% of women. About 16.4% of women reported to be moderately-severely bothered by their bladder in everyday life. The risk of severe symptoms and bother increased with age. About 10% of women had clinically significant BCS (OSS ≥ 7 and OBS ≥ 4).CONCLUSIONS:In Belgian women ≥ 40 years visiting a GP for any reason, one in three had mild BCS and might benefit from further evaluation. Up to 10% of these women had clinically significant BCS for which medical therapy might be necessary. This warrants awareness for early diagnosis and intervention.

OBJECTIVE Previous work has shown a correlation between β-cell number in cultured islet cell grafts and their ability to induce C-peptide secretion after intraportal implantation in C-peptide–negative type1 diabetic patients. In this cross-sectional study, we examined the minimal functional β-cell mass (FBM) in the implant that induces metabolic improvement. RESEARCH DESIGN AND METHODS Glucose clamps assessed FBM in 42 recipients with established implants. C-peptide release during each phase was expressed as percentage of healthy control values. Its relative magnitude during a second hyperglycemic phase was most discriminative and therefore selected as a parameter to be correlated with metabolic effects. RESULTS Recipients with functioning β-cell implants exhibited average FBM corresponding to 18% of that in normal control subjects (interquartile range 10–33%). Its relative magnitude negatively correlated with HbA1c levels (r = −0.47), daily insulin dose (r = −0.75), and coefficient of variation of fasting glycemia (CVfg) (r = −0.78, retained in multivariate analysis). A correlation between FBM and CVfg <25% appeared from the receiver operating characteristic curve (0.97 [95% CI 0.93–1.00]). All patients with FBM >37% exhibited CVfg <25% and a >50% reduction of their pretransplant CVfg; this occurred in none with FBM <5%. Implants with FBM >18% reduced CVfg from a median pretransplant value of 46 to <25%. CONCLUSIONS Glucose clamping assesses the degree of restoration in FBM achieved by islet cell implants. Values >37% of normal control subjects appear needed to reduce glycemic variability in type 1 diabetic recipients. Further studies should examine whether the test can help guide decisions on additional islet cell transplants and on adjusting or stopping immunotherapy.

Background Recombinant C1 inhibitor (rhC1INH) is a novel therapeutic option for the treatment of acute angioedema attacks in patients with hereditary angioedema (HAE). The amino acid sequence of rhC1INH is identical to that of endogenous C1INH. However, any recombinant protein may elicit antibodies against the protein and/or host related impurities (HRI). Clinical consequences of these antibodies can theoretically range from no clinical symptoms to allergic reactions and reduced C1INH activity due to neutralizing antibodies.

The aim of the study was to examine the 48 month outcome of treating recent-onset type 1 diabetic patients for 6 days with humanised CD3-antibody, ChAglyCD3.

Previous studies in healthy volunteers reported a possible impact of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) on stress hormones, like cortisol. In this sham-controlled, "single blind'', crossover study, we examined whether HF-rTMS had an effect on the hypothalamic-pituitary-adrenal (HPA) axis, by analysing salivary cortisol levels. Two studies were conducted. First, HF-rTMS on the left dorsolateral prefrontal cortex (DLPFC) was performed in 28 young healthy female volunteers. Second, in a comparable, but different group of 26 healthy females, HF-rTMS was performed on the right DLPFC. Salivary cortisol levels were assessed before, immediately after and 30 min after real and sham HF-rTMS. We found no support for the hypothesis that one single session of HF-rTMS on the left or the right DLPFC has an immediate or delayed impact on the HPA-axis, as measured by salivary cortisol. Although we controlled for several methodological problems in HF-rTMS research, the hypothesis that one single session of HF-rTMS on the left or on the right DLPFC can influence the HPA-axis in healthy volunteers was not supported.

Background-Repolarization abnormalities in the inferior-lateral leads in Brugada syndrome (BS) have not been systematically investigated.Methods and Results-280 patients (age, 41 +/- 18 years; 168 males) with BS were screened for inferior-lateral repolarization abnormalities. The repolarization abnormalities were classified either as early repolarization pattern or coved >= 2-mm Brugada pattern and as spontaneous or class I antiarrhythmic drug (AAD) induced. Thirty-two patients (11%) had inferior-lateral spontaneous early repolarization pattern. These patients were less likely to be asymptomatic at first presentation (13 of 32 versus 156 of 248 patients, P=0.02), and spontaneous type I ECG was more frequent among them (38% versus 21%, P=0.05). The spontaneous early repolarization pattern occurred more frequently among patients with BS than in 283 family members not having BS (11% versus 6%, P=0.03). Class I AAD administration provoked interior-lateral coved Brugada pattern in 13 patients with BS. These patients had longer baseline PR intervals (206 +/- 48 versus 172 +/- 31 ms, P<0.001) and class I AAD-induced QRS interval prolongation (108 to 178 versus 102 ms to 131 ms, P<0.001). In 3 patients, the class I AAD-provoked coved Brugada pattern was only present in the inferior leads.Conclusions-Inferior-lateral early repolarization pattern occurs spontaneously relatively frequently in BS. These patients have a more severe phenotype. Class I AAD administration provokes inferior-lateral coved Brugada pattern in 4.6% of patients. We report for the first time 3 patients in whom the class I AAD-provoked coved Brugada pattern was only observed in the inferior leads. (Circ Arrhythmia Electrophysiol. 2009;2:154-161.)

OBJECTIVE The metabolic outcome of islet cell transplants in type 1 diabetic patients is variable. This retrospective analysis examines whether differences in recipient characteristics at the time of transplantation are correlated with inadequate graft function. RESEARCH DESIGN AND METHODS Thirty nonuremic C-peptide–negative type 1 diabetic patients had received an intraportal islet cell graft of comparable size under an ATG-tacrolimus–mycophenolate mofetil regimen. Baseline patient characteristics were compared with outcome parameters during the first 6 posttransplant months (i.e., plasma C-peptide, glycemic variability, and gain of insulin independence). Correlations in univariate analysis were further examined in a multivariate model. RESULTS Patients that did not become insulin independent exhibited significantly higher counts of B-cells as well as a T-cell autoreactivity against insulinoma-associated protein 2 (IA2) and/or GAD. In one of them, a liver biopsy during posttransplant year 2 showed B-cell accumulations near insulin-positive β-cell aggregates. Higher baseline total lymphocytes and T-cell autoreactivity were also correlated with lower plasma C-peptide levels and higher glycemic variability. CONCLUSIONS Higher total and B-cell counts and presence of T-cell autoreactivity at baseline are independently associated with lower graft function in type 1 diabetic patients receiving intraportal islet cells under ATG-tacrolimus–mycophenolate mofetil therapy. Prospective studies are needed to assess whether control of these characteristics can help increase the function of islet cell grafts during the first year posttransplantation.

AIMS:Currently used diagnostic manoeuvres at the electrophysiology study do not always allow for consistent identification of atrial tachycardia (AT), either because of inapplicability of the technique or because of low predictive value and specificity. The aim of this study was to determine whether overdrive atrial pacing during paroxysmal supraventricular tachycardia (SVT) with the same cycle length from both the high right atrium and the coronary sinus can accurately identify or exclude AT by examining the difference between the V-A intervals of the first returning beat of tachycardia between the two pacing sites. METHODS AND RESULTS:Fifty-two patients were included; 24 patients with atrioventricular nodal re-entry tachycardia (AVNRT), 13 patients with atrioventricular re-entry tachycardia (AVRT), and 15 patients with AT. Comparing the 37 non-AT patients with the 15 AT patients, there was a highly significant difference between the mean V-A interval difference, (delta V-A) 2.1 +/- 1.8 ms (range 0-9 ms) vs. 79.1 +/- 42 (range 22-267 ms) (P < 0.001), respectively. None of the patients in the non-AT group had a delta V-A > 10 ms. In contrast, all 15 patients with AT had a delta V-A interval >10 ms. Thus, the diagnostic accuracy of the delta V-A interval cut-off of >10 ms was 100%, with a 95% confidence interval of 93.1-100% for AT. In 11 (73%) of the 15 AT patients, the standard ventricular overdrive pacing manoeuvre was not possible. In 14 of the 15 patients (93%) in the AT group, standard atrial overdrive pacing showed variable V-A intervals, correctly diagnosing AT. In all 52 patients, this measurement was repeated during pacing from the other location. In five patients from the AT group, the result of the second attempt was different from the result of the first attempt. CONCLUSION:We found that atrial differential pacing during paroxysmal SVT without termination of tachycardia and the finding of variable returning V-A interval was highly sensitive and specific for the diagnosis of AT. The manoeuvre can be easily performed in all patients with SVT and is highly reproducible. It is a useful adjunct to the currently available ventricular and atrial pacing manoeuvres.