BackgroundPeople with epilepsy often experience daytime vigilance problems and fatigue. This may be related to disturbed sleep due to nocturnal seizures.AimTo compare subjective and objective... Show moreBackgroundPeople with epilepsy often experience daytime vigilance problems and fatigue. This may be related to disturbed sleep due to nocturnal seizures.AimTo compare subjective and objective markers of vigilance and circadian function in adults with epilepsy with nocturnal seizures to those with daytime seizures and healthy controls and to identify determinants of impaired daytime vigilance in epilepsy in an explorative study.MethodsWe included 30 adults with epilepsy (15 with daytime seizures and 15 with nocturnal seizures), and 15 healthy controls. All participants filled out the Epworth sleepiness scale (ESS), fatigue severity scale (FSS), Pittsburgh sleep quality index (PSQI) and the Munich chronotype questionnaire (MCTQ). Each participant performed two trials of the sustained attention to response task (SART) as a measure of vigilance, and had a post-illumination pupil response (PIPR) assessment as a marker for the circadian function.ResultsBoth epilepsy groups reported more fatigue on the FSS than healthy controls (p < .001) and had higher SART error scores (p = .026). The poorer FSS and SART scores were most prominent among those with nocturnal seizures. The ESS, PSQI, MCTQ and the primary PIPR outcome did not differ between groups. Having nocturnal seizures (p = .010) and using more antiseizure medications (p = .004) were related to increased SART error scores.ConclusionsNocturnal epilepsy is associated with poorer vigilance, indicating lower quality of wake time. We could not relate this to circadian dysfunction. Further studies should focus on vigilance problems in people with nocturnal epilepsy and explore interventions to improve the quality of wake time. Show less
MET exon 14 ( MET ex14) skipping mutations occur in 3% to 4% of non-small cell lung cancer (NSCLC) cases. Currently, four oral MET tyrosine kinase inhibitors (TKIs) are in use for the treatment of... Show moreMET exon 14 ( MET ex14) skipping mutations occur in 3% to 4% of non-small cell lung cancer (NSCLC) cases. Currently, four oral MET tyrosine kinase inhibitors (TKIs) are in use for the treatment of patients with MET ex14 skipping NSCLC (tepotinib, capmatinib, savolitinib, and crizotinib). To support optimal management of MET ex14 skipping NSCLC in this typically older patient population, the safety profiles of these treatment options are reviewed here. Published safety data from prospective clinical trials with MET TKIs in patients with MET ex14 skipping NSCLC were reviewed. Treatmentrelated adverse events (TRAEs) occurring in > 10% of patients were reported where feasible. Guidance on clinical monitoring and management of key MET TKI TRAEs and dr ug-dr ug interactions is provided. Across the clinical trials, safety data for MET TKIs were reported for 442 patients with MET ex14 skipping. Peripheral edema was the most reported TRAE (50%-63% of patients; grade > 3: 1%-11%), followed by nausea (26%-46% of patients; grade > 3: 0%1%). TRAEs led to dose reductions in 33% to 38% of patients and to discontinuation in 7% to 14% of patients, across the MET TKIs. Considerations on interpreting available safety data are provided, along with insights into monitoring and managing specific MET TKI TRAEs of interest and dr ug-dr ug interactions. Overall, MET TKIs are tolerable treatment options for patients with MET ex14 skipping NSCLC, an older population for whom chemo- or immuno-therapy may not be an effective nor tolerable option. More data regarding the effectiveness of safety interventions and management strategies are needed. Show less
Hany, M.; Torensma, B.; Abouelnasr, A.A.; Zidan, A.; Ibrahim, M.; Agayby, A.S.S.; ... ; Abu-Sheasha, G.A. 2022
Purpose The primary objective of the current study is to determine whether bariatric surgery reversed the negative impact of obesity on the serological response after the COVID-19 vaccination. This... Show morePurpose The primary objective of the current study is to determine whether bariatric surgery reversed the negative impact of obesity on the serological response after the COVID-19 vaccination. This objective is achieved in two steps: (a) quantifying the negative impact of obesity on the serological response after COVID-19 vaccination if it is present, and (b) testing whether bariatric surgery reversed this impact. The secondary objective was to monitor the occurrence of adverse events. Methods This is a prospective cohort study between May 2021 and August 2021 on the strength of serological response after COVID-19 vaccination. Patients were classified into three groups. Group A (controls with normal or overweight), Group B (bariatric patients pre-operative), and Group C (bariatric patients post-operative). Quantitative antibodies against SARS-CoV-2 RBD with a strong neutralizing capacity were quantified from sera after at least 2 weeks post-vaccination. Results Of the 276 participants, Group A had n = 73, Group B had n = 126, and Group C had n = 77 patients. Overall, a strongly positive vaccine serological response was observed among 86% in group A, 63% in Group B, and 88% in Group C. Group C showed 5.33 times [95% CI 2.15 to 13.18] higher immune response than group B. Mild to moderate adverse events occurred in 30.1% [95% CI 24.7 to 35.9] of the study samples. Adverse events with the whole virus, mRNA, and vector vaccines occurred in 25%, 28%, and 37%, respectively. Conclusion Vaccinating and bariatric surgery are safe and effective treatments in the serological response in patients who suffer from obesity. Show less
The COVID-19 pandemic has galvanized the global response towards the development of new vaccines based on novel technologies at an unprecedented pace. Since the widespread implementation of... Show moreThe COVID-19 pandemic has galvanized the global response towards the development of new vaccines based on novel technologies at an unprecedented pace. Since the widespread implementation of vaccination campaigns, case reports on vaccines' systemic side effects, including ocular manifestations, have emerged. Since administered vaccines are generally not able to cause the disease in the recipient, or induce an immune response against the pathogen, we hypothesize that the development of ocular phenomena post-COVID-19 vaccination may occur via an immune response elicited by the vaccine. Of many, the most common ocular adverse events include facial nerve palsy, central venous sinus thrombosis and acute anterior uveitis. These COVID-19 vaccine-induced ocular (CVIO) adverse events could resemble the ocular findings in some of the COVID-19 patients. This review will provide a comprehensive overview of published ocular side effects potentially associated with COVID-19 vaccination and serve as a springboard for further research into CVIO adverse events. Show less
Background European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially... Show moreBackground European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)-piperaquine (APQ) Eurartesim(R) during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap. Methods Participants were recruited through Health Care Provider's safety registry in 15 centres across 6 European countries in the period 2013-2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett's (QTcB) or Fridericia's (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females. Results Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m(2) (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p < 0.05) more AEs. Among AEs, 21 were due to cardiotoxicity (7.1%), mostly QT prolongation, while 6 were due to neurotoxicity (2.0%), mostly dizziness. Using QTcF correction, QT prolongation was observed in 17/143 participants (11.9%), only 2 of them reporting QTcF > 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%). Conclusions APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries. Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942 Show less
This thesis assesses multiple monitoring modalities that can be used in the peri-operative period to reduce respiratory adverse events associated with the use of anesthetic drugs, particularly... Show moreThis thesis assesses multiple monitoring modalities that can be used in the peri-operative period to reduce respiratory adverse events associated with the use of anesthetic drugs, particularly opioids and neuromuscular blocking drugs. Monitors of analgesia, neuromuscular block and ventilation are studied in both healthy volunteers and surgical patient populations to assess proof of concept, efficacy, feasibility of clinical use and effect on clinical outcomes. Show less
Felix, S.E.A.; Jonge, N. de; Caliskan, K.; Birim, O.; Damman, K.; Kuijpers, M.; ... ; Ramjankhan, F.Z. 2020
In patients with end-stage heart failure, advanced therapies such as heart transplantation and long-term mechanical circulatory support (MCS) with a left ventricular assist device (LVAD) have to be... Show moreIn patients with end-stage heart failure, advanced therapies such as heart transplantation and long-term mechanical circulatory support (MCS) with a left ventricular assist device (LVAD) have to be considered. LVADs can be implanted as a bridge to transplantation or as an alternative to heart transplantation: destination therapy. In the Netherlands, long-term LVAD therapy is gaining importance as a result of increased prevalence of heart failure together with a low number of heart transplantations due to shortage of donor hearts. As a result, the difference between bridge to transplantation and destination therapy is becoming more artificial since, at present, most patients initially implanted as bridge to transplantation end up receiving extended LVAD therapy. Following LVAD implantation, survival after 1, 2 and 3 years is 83%, 76% and 70%, respectively. Quality of life improves substantially despite important adverse events such as device-related infection, stroke, major bleeding and right heart failure. Early referral of potential candidates for long-term MCS is of utmost importance and positively influences outcome. In this review, an overview of the indications, contraindications, patient selection, clinical outcome and optimal time of referral for long-term MCS is given. Show less
Is de geboden cardiologische zorg `sufficiently safe' ? Dit proefschrift richtte zich op de vraag hoe je kwaliteit van zorg kan meten om te kijken of de geboden zorg voor de behandeling van acuut... Show moreIs de geboden cardiologische zorg `sufficiently safe' ? Dit proefschrift richtte zich op de vraag hoe je kwaliteit van zorg kan meten om te kijken of de geboden zorg voor de behandeling van acuut coronair syndroom sufficiently safe is en deed dit middels twee methoden: lokaal dossieronderzoek ten aanzien van patiëntveiligheid (Deel 1) en nationaal declaratie data-registratie voor kwaliteit-van-zorg onderzoek (Deel 2). Waar declaratiedata in detail moet inleveren, levert dossieronderzoek in op de efficiëntie. De twee verschillende methodes vullen elkaar aan en dienen een verschillend doel: veiligheid en kwaliteit van zorg. De geboden zorg lijkt veilig, maar toch ervaart 13% zorggerelateerde schade bij de behandeling van een acuut coronair syndroom. Welk onderzoek is hiervoor nodig? Dossieronderzoek is zeer arbeidsintensief, zelfs een onderzoek binnen het heldere MISSION!-protocol leidt nog tot heterogene antwoorden op causale relaties van zorggerelateerde schade. Real-time monitoring van afwijkende processen met reeds geregistreerde data biedt meer inzicht in zorggerelateerde schade. De geboden zorg lijkt volgens de richtlijnen te gaan, maar toch krijgt slechts 49% zijn preventieve medicatie. Ook hier is ruimte voor verbetering. Toekomstige analyses met declaratiedata, gecombineerd met klinische data en andere databronnen, kan meer inzicht geven om zo de kwaliteit van zorg continu te blijven verbeteren. Show less
Quality and safety improvement is a relatively novel discipline in healthcare practice and research that solidified in the early 21st century. Since then, various systems have been installed to... Show moreQuality and safety improvement is a relatively novel discipline in healthcare practice and research that solidified in the early 21st century. Since then, various systems have been installed to collect information on various types of adverse outcomes, such as adverse events, incidents and patient complaints. Data from these systems can be used to evaluate care delivered to individual cases as well as to study aggregated data for patterns, trends and other insights. More research is warranted to assess whether these systems actually meet the objective of continuous, systemwide learning and improvement. It was expected that existing practices could benefit from individual optimization as well as better integration, because most of this intelligence is currently stored and used in isolation. The research in this PhD thesis focused on how we can learn most effectively from various types of adverse outcomes in healthcare, in order to continuously improve the care delivered to patients. Specific research questions included how we can learn from: i) case discussions at morbidity and mortality conferences ; ii) integrating available information sources (e.g., incidents, patient experiences); iii) the context of everyday practice that produces both adverse and desired outcomes. Show less
Blok, E.J.; Kroep, J.R.; Kranenbarg, E.M.K.; Duijm-De Carpentier, M.; Putter, H.; Liefers, G.J.; ... ; TEAM Study Group 2018
In this thesis long-term effects and quality of life after treatment for rectal cancer are evaluated. Long-term data were assessed from the TME trial. In this trial 1530 Dutch patients with... Show moreIn this thesis long-term effects and quality of life after treatment for rectal cancer are evaluated. Long-term data were assessed from the TME trial. In this trial 1530 Dutch patients with rectal cancer were included between 1996 and 1999. These patients were randomly assigned to total mesorectal excision (TME) or to short-course preoperative radiotherapy (5x5 Gy) followed by TME surgery. Show less
