Wetenschappelijk onderzoek gespiegeld: van Evidence-Based Medicine naar evaluatie van zorg

Oratie uitgesproken door Prof.dr. P.P.G. van Benthem bij de aanvaarding van het ambt van hoogleraar in de Keel-, Neus- en Oorheelkunde aan de Universiteit Leiden op vrijdag 8 april 2016Oratie uitgesproken door Prof.dr. P.P.G. van Benthem bij de aanvaarding van het ambt van hoogleraar in de Keel-, Neus- en Oorheelkunde aan de Universiteit Leiden op vrijdag 8 april 201

Response rate of patient reported outcomes: the delivery method matters

Background Patient Reported Outcomes (PROs) are subjective outcomes of disease and/or treatment in clinical research. For effective evaluations of PROs, high response rates are crucial. This study assessed the impact of the delivery method on the patients' response rate. Methods A cohort of patients with a unilateral vestibular schwannoma (a condition with substantial impact on quality of life, requiring prolonged follow-up) was assigned to three delivery methods: email, regular mail, and hybrid. Patients were matched for age and time since the last visit to the outpatient clinic. The primary outcome was the response rate, determinants other than delivery mode were age, education and time since the last consultation. In addition, the effect of a second reminder by telephone was evaluated. Results In total 602 patients participated in this study. The response rates for delivery by email, hybrid, and mail were 45, 58 and 60%, respectively. The response rates increased after a reminder by telephone to 62, 67 and 64%, respectively. A lower response rate was associated with lower level of education and longer time interval since last outpatient clinic visit. Conclusion The response rate for PRO varies by delivery method. PRO surveys by regular mail yield the highest response rate, followed by hybrid and email delivery methods. Hybrid delivery combines good response rates with the ease of digitally returned questionnaires.Analysis and support of clinical decision makin

Two symptoms strongly suggest benign paroxysmal positional vertigo in a dizzy patient

Introduction: This prospective cohort study determined which questions in patient history are most likely to identify symptoms that are independently associated with a diagnosis of benign paroxysmal positional dizziness (BPPV) in patients presenting with dizziness, and to evaluate whether the patient's age and type of BPPV are of influence.Methods: We included adult patients with dizziness referred to our dizziness center, Apeldoorn, the Netherlands, from December 2018 to November 2019. All patients completed a questionnaire, underwent vestibular testing and received a diagnosis. Symptoms strongly suggesting BPPV were tested with multivariable analysis to determine their independent associations with BPPV. Subgroup analysis was performed for patient age, and the type of BPPV.Results: We included a total of 885 patients, 113 of whom (13%) were diagnosed with BPPV. The duration of dizziness spells <1 min (Q2) and dizziness provoked by rolling over in bed (Q4) were independently associated with the diagnosis BPPV. Q2 showed a sensitivity of 43%, and a specificity of 75%; Q4 scored 81% and 68%, respectively. Overall, the way patients perceived their dizziness (vertigo, light-headedness or instability) was not independently associated with the diagnosis BPPV. In younger patients, light-headedness and instability decreased the likelihood of BPPV compared to vertigo.Conclusion: The most reliable predictors for BPPV in patient history are a short duration of the dizziness spell and provocation of dizziness by rolling over in bed. Unlike younger patients, elderly patients with BPPV do not only perceive the dizziness as vertigo, but also as a feeling of instability.Disorders of the head and nec

Treatment results of geotropic and apogeotropic horizontal canal benign paroxysmal positional vertigo in a tertiary dizziness clinic

Purpose: To determine the effectiveness of our treatment protocol for geotropic and apogeotropic horizontal canal benign paroxysmal positional vertigo (h-BPPV).Methods: We retrospectively evaluated patients with newly diagnosed geotropic and apogeotropic h-BPPV who visited our clinic between July 2017 and December 2019. Patients were treated according to our treatment protocol, which was implemented in 2017. Patients with geotropic h-BPPV were preferably treated with the Gufoni maneuver. In patients with apogeotropic h-BPPV we executed the modified Gufoni maneuver to achieve conversion to the geotropic type. We looked at the number of successful treatments and the number of recurrences within 1 year.Results: We included 102 patients with h-BPPV, 62 (61%) of whom were treated for geotropic h-BPPV. The ratio of apogeotropic to geotropic h-BPPV was 0.65. After the first visit, we observed resolution of horizontal canal BPPV in 71 and 63% of the geotropic and the apogeotropic group, respectively. After the second visit, this percentage increased to 92% for geotropic h-BPPV and 78% for apogeotropic h-BPPV. After 1 year of follow-up we determined a recurrence rate of 32 and 24% for the geotropic and apogeotropic group, respectively.Conclusion: With our treatment protocol we managed to achieve high rates of symptom resolution in the geotropic and apogeotropic type of h-BPPV with acceptable recurrence rates. We observed a relatively high ratio of apogeotropic h-BPPV to geotropic h-BPPV.Disorders of the head and nec

Building an artificial stem cell niche: prerequisites for future 3D-formation of inner ear structures-toward 3D inner ear biotechnology

In recent years, there has been an increased interest in stem cells for the purpose of regenerative medicine to deliver a wide range of therapies to treat many diseases. However, two-dimensional cultures of stem cells are of limited use when studying the mechanism of pathogenesis of diseases and the feasibility of a treatment. Therefore, research is focusing on the strengths of stem cells in the three-dimensional (3D) structures mimicking organs, that is, organoids, or organ-on-chip, for modeling human biology and disease. As 3D technology advances, it is necessary to know which signals stem cells need to multiply and differentiate into complex structures. This holds especially true for the complex 3D structure of the inner ear. Recent work suggests that although other factors play a role, the extracellular matrix (ECM), including its topography, is crucial to mimic a stem cell niche in vitro and to drive stem cells toward the formation of the tissue of interest. Technological developments have led to the investigation of biomaterials that closely resemble the native ECM. In the fast forward moving research of organoids and organs-on-chip, the inner ear has hardly received attention. This review aims to provide an overview, by describing the general context in which cells, matrix and morphogens cooperate in order to build a tissue, to facilitate research in 3D inner ear technology

Saccades matter: reduced need for caloric testing of cochlear implant candidates by joint analysis of v-HIT gain and corrective saccades

Objectives: Video head impulse test (v-HIT) is a quick, non-invasive and relatively cheap test to evaluate vestibular function compared to the caloric test. The latter is, however, needed to decide on the optimal side to perform cochlear implantation to avoid the risk on inducing a bilateral vestibular areflexia. This study evaluates the effectiveness of using the v-HIT to select cochlear implant (CI) candidates who require subsequent caloric testing before implantation, in that way reducing costs and patient burden at the same time. Study Design: Retrospective study using clinical data from 83 adult CI-candidates, between 2015 and 2020 at the Leiden University Medical Center. Materials and Methods: We used the v-HIT mean gain, MinGain_LR, the gain asymmetry (GA) and a newly defined parameter, MGS (Minimal Gain & Saccades) as different models to detect the group of patients that would need the caloric test to decide on the ear of implantation. The continuous model MGS was defined as the MinGain_LR, except for the cases with normal gain (both sides >= 0.8) where no corrective saccades were present. In the latter case MGS was defined to be 1.0 (the ideal gain value). Results: The receiver operating characteristics curve showed a very good diagnostic accuracy with and area under the curve (AUC) of 0.81 for the model MGS. The v-HIT mean gain, the minimal gain and GA had a lower diagnostic capacity with an AUC of 0.70, 0.72, and 0.73, respectively. Using MGS, caloric testing could be avoided in 38 cases (a reduction of 46%), with a test sensitivity of 0.9 (i.e., missing 3 of 28 cases). Conclusions: The newly developed model MGS balances the sensitivity and specificity of the v-HIT better than the more commonly evaluated parameters such as mean gain, MinGain_LR and GA. Therefore, taking the presence of corrective saccades into account in the evaluation of the v-HIT gain can considerably reduce the proportion of CI-candidates requiring additional caloric testing.Disorders of the head and nec

The impact of new evidence on regional variation in paediatric tonsillectomy and adenoidectomy: a historical review

BackgroundTonsillectomy and adenoidectomy have been among the most commonly performed procedures in children for approximately 100 years. These procedures were the first for which unwarranted regional variation was discovered, in 1938. Indications for these procedures have become stricter over time, which might have reduced regional practice variation.MethodsThis paper presents a historical review on practice variation in paediatric tonsillectomy and adenoidectomy rates. Data on publication year, region, level of variation, methodology and outcomes were collected.ResultsTwenty-one articles on practice variation in paediatric tonsil surgery were included, with data from 12 different countries. Significant variation was found throughout the years, although a greater than 10-fold variation was observed only in the earliest publications.ConclusionNo evidence has yet been found that better indications for tonsillectomy and adenoidectomy have reduced practice variation. International efforts are needed to reconsider why we are still unable to tackle this variation.Otorhinolaryngolog

Cost-benefit Analysis of Cochlear Implants: A Societal Perspective

Objectives: While the costs and outcomes of cochlear implantation (CI) have been widely assessed, most of these analyses were solely performed from the perspective of healthcare costs. This study assesses the costs and benefits of CI in the Netherlands from a broader societal perspective, including health outcomes, healthcare cost, educational cost, and productivity losses and gains. Design: The cost and benefits of CI were analyzed in this cost-benefit analysis, in which a monetary value is put on both the resources needed and the outcomes of CI. The costs and benefits were analyzed by prototypical instances of three groups, representing the majority of cochlear implant patients: prelingually deaf children implanted at the age of 1, adults with progressive profound hearing loss implanted at the age of 40 and seniors implanted at the age of 70 with progressive profound hearing loss. Costs and benefits were estimated over the expected lifetimes of the members of each group, using a Markov state transition model. Model parameters and assumptions were based on published literature. Probabilistic and one-way sensitivity analyses were performed. Results: In all three patient groups, the total benefits of CI exceeded the total cost, leading to a net benefit of CI. Prelingually deaf children with a bilateral CI had a lifetime positive outcome net benefit of euro433,000. Adults and seniors with progressive profound hearing loss and a unilateral CI had a total net benefit of euro275,000 and euro76,000, respectively. These results ensue from health outcomes expressed in monetary terms, reduced educational cost, and increased productivity. Conclusions: Based on estimates from modeling, the increased healthcare costs due to CI were more than compensated by the value of the health benefits and by savings in educational and productivity costs. In particular, for children and working adults, the societal benefit was positive even without taking health benefits into account. Therefore, CI generates an advantage for both patients and society.Disorders of the head and nec

Regional and hospital variation in commonly performed paediatric otolaryngology procedures in the Netherlands: a population-based study of healthcare utilisation between 2016 and 2019

Objective In the past few decades, there has been an increase in high-quality studies providing evidence on the effectiveness of commonly performed procedures in paediatric otolaryngology. We believe that now is the time to re-evaluate the care process. We aimed to analyse (1) the regional variation in incidence and referrals of adenoidectomies, tonsillectomies and ventilation tube insertions in children in the Netherlands between 2016 and 2019, (2) whether regional surgical rates, referral rates and in-hospital surgical rates were associated with one another, and (3) the hospital variation in healthcare costs, which indicates the utilisation of resources. Design Repeated cross-sectional analysis. Setting Four neighbouring Dutch provinces comprising 2.8 million inhabitants and 14 hospitals. Participants Children aged 0-15 years. Outcome measures We analysed variation in regional surgical rates and referral rates per 1000 inhabitants and in-hospital surgical rates per 1000 clinic visitors, adjusted for age and socioeconomic status. Furthermore, the relationships between referral rates, regional surgical rates and in-hospital surgical rates were estimated. Lastly, variation in resource utilisation between hospitals was estimated. Results Adenoidectomy rates differed sixfold between regions. Twofold differences were observed for adenotonsillectomy rates, ventilation tube insertion rates and referral rates. Referral rates were negatively associated with in-hospital surgical rates for adenotonsillectomies, but not for adenoidectomies and ventilation tube insertions. In-hospital surgical rates were positively associated with regional rates for adenoidectomies and adenotonsillectomies. Significant variation between hospitals was observed in costs for all resources. Conclusions We observed low variation in tonsillectomies and ventilation tube insertion and high variation in adenoidectomies. Indications for a tonsillectomy and ventilation tube insertion are well defined in Dutch guidelines, whereas this is not the case for an adenoidectomy. Lack of agreement on indications can be expected and high-quality effectiveness research is required to improve evidence-based guidelines on this topic.Analysis and support of clinical decision makin

Long-term quality of life of vestibular schwannoma patients: a longitudinal Analysia

Objective: Vestibular schwannoma management aims to maintain optimal quality of life (QoL) while preventing severe sequelae of the tumor or its treatment. This study assessed long-term QoL of patients with vestibular schwannoma in relation to treatment modality and decisional regret. Study Design:  A longitudinal study, in which clinical and QoL data were used that were cross-sectionally acquired in 2014 and again in 2020 from the same patient group. Setting: A tertiary expert center for vestibular schwannoma care in the Netherlands. Methods: QoL was measured by the Penn Acoustic Quality of Life (PANQOL) scale. Changes in time were assed using a linear mixed model. In addition, the Decision Regret Scale was analyzed. Results: Of 867 patients, 536 responded (62%), with a median follow-up of 11 years. All PANQOL subdomain scores remained stable over time and did not exceed minimal clinically important difference (MCID) levels. Time since treatment did not affect QoL. Patients had comparable average QoL scores and proportions of patients with changing QoL scores (ie, exceeding the MCID) over time, irrespective of the received initial treatment. Female patients and those who required salvage therapy (either by radiotherapy or surgery) reported a lower QoL. The latter patient group reported the highest decisional regret. Conclusion: On average, the long-term QoL of patients with vestibular schwannoma is comparable for patients under active surveillance and those who have received active treatment, and it remains stable over time. This suggests that, on average, preservation of QoL of patients with vestibular schwannoma is feasible when adequately managed.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie