Yearly hypertension screening in women with a history of pre-eclampsia: a cost-effectiveness analysis.

BACKGROUND: Women with a history of preeclampsia are at increased risk for future hypertension and cardiovascular disease (CVD); until now it is not clear whether preventive measures are needed. METHODS: A decision-analytic Markov model was constructed to evaluate healthcare costs and effects of screening and treatment (100 % compliance) for hypertension post preeclampsia based on the available literature. Cardiovascular events and CVD mortality were defined as health states. Outcomes were measured in absolute costs, events, life-years and quality-adjusted life-years (QALYs). Sensitivity and threshold analyses were performed to address uncertainty. RESULTS: Over a 20-year time horizon, events occurred in 7.2 % of the population after screening, and in 8.5 % of the population without screening. QALYs increased from 16.37 (no screening strategy) to 16.40 (screening strategy), an increment of 0.03 (95 % CI 0.01;0.05) QALYs. Total expected costs were € 8016 in the screening strategy, and € 9087 in the none screening strategy (expected saving of € 1071 (95 % CI - 3146;-87) per person). CONCLUSION: Annual hypertension screening and treatment in women with a history of preeclampsia may save costs, for at least a similar quality of life and survival due to prevented CVD compared with standard care.

The current and future role of general practitioners in skin cancer care: an assessment of 268 general practitioners.

BACKGROUND: Given the increase in skin cancer (SC) it seems inevitable that general practitioners (GPs) will play a larger role in SC care in the near future. OBJECTIVES: To obtain insights into the opinion of GPs with respect to their role in SC care, and their SC knowledge and skills. METHODS: A self-administered questionnaire was sent to GPs in the region of Nijmegen, the Netherlands. RESULTS: In total 268 GPs (49%) responded. An overwhelming majority were willing to extend their role in SC care. Furthermore, we noted the following results: (i) > 50% of GPs requested additional SC knowledge; (ii) GPs often treat actinic keratosis (AK) themselves, primarily with cryotherapy; (iii) > 50% would treat (low-risk) basal cell carcinoma (BCC) after additional training; (iv) only a few GPs are familiar with BCC guidelines; (v) the majority of patients with high-risk SC are referred to dermatologists; (vi) only a few GPs perform total body inspection and palpation of lymph nodes; and (vii) a large number of GPs inform their patients on risk factors in SC development. CONCLUSIONS: Most GPs are willing to extend their role in SC care; however, more training is requested and the usage of guidelines should be encouraged. Those willing to extend their role should focus on improving their clinical diagnosis of skin tumours, treatment of low-risk skin (pre)malignancies, including field-directed treatment of AK and noninvasive treatment of BCC, and on prevention.

On the normativity of evidence - Lessons from philosophy of science and the "VALIDATE" project.

"Evidence" is a key term in medicine and health services research, including Health Technology Assessment (HTA). Randomized clinical trials (RCTs) have undoubtedly dominated the scene of generating evidence for a long period of time, becoming the hallmark of evidence-based medicine (EBM). However, due to a number of misunderstandings, the lay audience and some researchers have sometimes placed too much trust in RCTs compared to other methods of investigation. One of the principal misunderstandings is to consider RCTs findings as isolated and self-apparent pieces of information. In other words, what has been essentially lacking was the awareness of the value-context of the evidence and, in particular, the value- and theory-ladenness (normativity) of scientific knowledge. This paper aims to emphasize the normativity that exists in the production of scientific knowledge, and in particular in the conduct of RCTs as well as in the performance of HTA. The work is based on some lessons learned from Philosophy of Science and the European project "VALIDATE" (VALues In Doing Assessments of healthcare TEchnologies"). VALIDATE was a three-year EU Erasmus+ strategic partnerships project (2018-2021), in which training in the field of HTA was further optimized by using insights from political science and ethics (in accordance with the recent definition of HTA). Our analysis may reveal useful insights for addressing some challenges that HTA is going to face in the future.

Acute intoxication patients presenting to an emergency department in The Netherlands: admit or not? Prospective testing of two algorithms.

STUDY OBJECTIVE: After acute intoxication, most patients presenting to the emergency department (ED)--76% of them in The Netherlands--are admitted to hospital. Many will not need medical treatment on the ward. The authors tested two algorithms in the ED, based on vital parameters, ECG findings, and ingested substances, to identify patients who will receive treatment in hospital. METHODS: This prospective inception study enrolled patients aged 14 years and older presenting with acute intoxication between January 2006 and April 2008 to a Dutch university hospital. An algorithm was developed based on a previous retrospective study and the medical literature. In a second algorithm the clinical course during the stay in the ED was also taken into account. RESULTS: Of 313 patients presenting with acute intoxication to the ED, 134 (42.8%) were admitted to a ward for somatic care, but only 74 (23.6%) were treated on the ward. Algorithm 1 had 91.9% sensitivity (95% CI 82.6% to 96.7%) and 53.6% specificity (95% CI 47.0% to 60.0%). Algorithm 2 had 90.5% sensitivity (95% CI 80.9% to 95.8%) and 65.3% specificity (95% CI 58.8% to 71.2%). In line with hospital policy, several patients received N-acetylcysteine treatment for subtoxic paracetamol ingestion because they presented outside of office hours, when no measurements of blood paracetamol concentration are performed by the laboratory. When these patients are considered as untreated, both algorithms had 98.5% sensitivity (95% CI 90.6% to 99.9%). CONCLUSION: The algorithms had good sensitivity and better specificity than current clinical practice in most hospitals. It is too early to advocate their implementation, but results indicate that it is possible to use clinical parameters objectively to reduce unnecessary admissions to the ward.

Speech pathology interventions in patients with neuromuscular diseases: a systematic review.

PURPOSE: A systematic review was conducted to summarize and evaluate the literature on the effectiveness of speech pathology interventions in adults with neuromuscular diseases. METHOD: Databases searched included the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, EMBASE, PsycINFO and PubMed. A total of 1,772 articles were independently screened on title and abstract by 2 reviewers. RESULTS: No randomized controlled trials or clinical controlled trials were found. Four other designs were included. Only one study on oculopharyngeal muscle dystrophy (OPMD) appeared to have sufficient methodological quality. There is evidence indicating that correction of head position in patients with OPMD improves swallowing efficiency (level III evidence). CONCLUSION: Despite 1,772 studies, there is only evidence of level III regarding the effectiveness of speech pathology interventions in patients with OPMD. Recommendations for future research are given.

Evaluation of prednisolone treatment in the acute phase of neuralgic amyotrophy: an observational study.

BACKGROUND: Effective treatment for neuralgic amyotrophy (NA), a disabling brachial plexus syndrome of supposed immunomediated origin, is currently lacking. Given the circumstantial evidence of a beneficial effect of prednisolone on pain and paresis, this report evaluates the effects of prednisolone treatment administered in the acute phase in a retrospective case series of 50 NA patients. METHODS: Baseline variables (eg, age, sex, type of NA and number of attacks), treatment variables (eg, time until treatment, regimen and use of analgesics) and outcome measures (eg, duration and severity of pain, time course and severity of paresis and functional outcome) were statistically analysed and compared with a historical control group of 203 untreated NA patients. RESULTS: The baseline characteristics of the two patient groups were comparable. The median time until initial pain relief was lower in the study group (12.5 days vs 20.5 days), and a significantly higher percentage already recovered strength in the first month of treatment (18% vs 6.3%; p = 0.011). Twelve per cent had fully recovered within 1 year, while this was 1% for the controls (p<0.001), with the proportion reporting a "good" 12-month outcome also being higher (44% vs 10.7%; p<0.001). Side effects were reported by 20%, but none led to a discontinuation of treatment. CONCLUSION: Oral prednisolone seems effective in the acute phase of neuralgic amyotrophy with the current results supporting previous case reports. A regimen of oral prednisolone is therefore recommended in the acute phase of the syndrome pending a prospective, randomised trial verifying the results obtained.

Optimizing referral of patients with neuromuscular disorders to allied health care.

BACKGROUND AND PURPOSE: To report the predictive validity of the perceived limitations in activities and need questionnaire (PLAN-Q), a screening instrument to support neurologists to select patients with neuromuscular disorders (NMD) for referral for a one-off consultation by occupational therapist (OT), physical therapist (PT) and speech therapist (ST). METHODS: In a cross-sectional validation study, 102 patients with various NMD participated. Patients received a one-off consultation by an expert OT, PT and ST and filled out the PLAN-Q. Therapists rated the appropriateness of the one-off consultations based on need, available treatment and patient's motivation. Receiver Operation Characteristic analysis and multivariate logistic regression analysis were used to obtain a PLAN-Q based prediction model for the appropriateness of the one-off consultations. RESULTS: Probability for a one-off OT consultation increased from 64% to 78% (95% CI: 69-85%). Prior test probability for a one-off ST consultation increased from 44% to 61% (95% CI: 48-73%). Prior test probability for one-off PT consultation could not be increased. CONCLUSION: Screening patients with NMD using the PLAN-Q may assist neurologists in selecting the appropriate patients for a one-off consultation by OT and ST. Unlike our expectations the screening did not guide referral for a one-off consultation by PT.

Motivation of university and non-university stakeholders to change medical education in Vietnam.

BACKGROUND: Both university and non-university stakeholders should be involved in the process of curriculum development in medical schools, because all are concerned with the competencies of the graduates. That may be difficult unless appropriate strategies are used to motivate each stakeholder. From 1999 to 2006, eight medical schools in Vietnam worked together to change the curriculum and teaching for general medical students to make it more community oriented. This paper describes the factors that motivated the different stakeholders to participate in curriculum change and teaching in Vietnamese medical schools and the activities to address those factors and have sustainable contributions from all relevant stakeholders. METHODS: Case study analysis of contributions to the change process, using reports, interviews, focus group discussions and surveys and based on Herzberg's Motivation Theory to analyze involvement of different stakeholders. RESULTS: Different stakeholders were motivated by selected activities, such as providing opportunities for non-university stakeholders to share their opinions, organizing interactions among university stakeholders, stimulating both bottom-up and top-down inputs, focusing on learning from each other, and emphasizing self-motivation factors. CONCLUSION: The Herzberg Motivation theory helped to identify suitable approaches to ensure that teaching topics, materials and assessment methods more closely reflected the health care needs of the community. Other medical schools undertaking a reform process may learn from this experience.

Management of patients with asymptomatic colorectal cancer and synchronous irresectable metastases.

BACKGROUND: In patients with asymptomatic colorectal cancer with irresectable metastatic disease, the optimal treatment strategy remains controversial. Resection of the primary tumor followed by chemotherapy when possible versus systemic chemotherapy followed by resection of the primary tumor when necessary are compared in this systematic review. PATIENTS AND METHODS: Seven studies reported series of patients with asymptomatic stage IV colorectal cancer and compared first-line chemotherapy with surgery for the primary tumor (n = 850 patients). Primary outcome measure was the complication rate related to the primary tumor in situ in patients receiving first-line systemic chemotherapy. RESULTS: When leaving the primary tumor in situ, the mean complications were intestinal obstruction in 13.9% [95% confidence interval (CI) 9.6% to 18.8%] and hemorrhage in only 3.0% (95% CI 0.95% to 6.0%) of the patients. After resection, the overall postoperative morbidity ranged from 18.8% to 47.0%. CONCLUSIONS: For patients with stage IV colorectal cancer, resection of the asymptomatic primary tumor provides only minimal palliative benefit, can give rise to major morbidity and mortality and therefore potentially delays beneficial systemic chemotherapy. When presenting with asymptomatic disease, initial chemotherapy should be started and resection of the primary tumor should be reserved for the small portion of patients who develop major complications from the primary tumor.

Prevalence and mutation spectrum of skeletal muscle channelopathies in the Netherlands.

Few reliable data exist on the prevalence of skeletal muscle channelopathies. We determined the minimum point prevalence of genetically-defined skeletal muscle channelopathies in the Netherlands and report their mutation spectrum. Minimum point prevalence rates were calculated as number of genetically-confirmed skeletal muscle channelopathy patients (CLCN1, SCN4A, CACNA1S and KCNJ2 gene mutations) in the Netherlands (1990-2015) divided by the total number of at-risk individuals. Rates were expressed as cases/100.000 and 95% confidence intervals were calculated based on Poisson distribution. Results of standardized genetic diagnostic procedures were used to analyze mutation spectra. We identified 405 patients from 234 unrelated pedigrees, resulting in a minimum point prevalence of 2.38/100.000 (95% CI 2.16-2.63) for skeletal muscle channelopathies in the Netherlands. Minimum point prevalence rates for the disease groups, non-dystrophic myotonia and periodic paralysis, were 1.70/100.000 and 0.69/100.000 respectively. Sixty-one different CLCN1 mutations (including 12 novel mutations) were detected in myotonia congenita. Twenty-eight different SCN4A missense mutations (including three novel mutations) were identified in paramyotonia congenita/sodium channel myotonia, hypokalemic periodic paralysis and hyperkalemic periodic paralysis. Four different CACNA1S missense mutations were detected in hypokalemic periodic paralysis and five KCNJ2 missense mutations in Andersen-Tawil syndrome. The minimum point prevalence rates for genetically-defined skeletal muscle channelopathies confirm their rare disease status in the Netherlands. Rates are almost twice as high as in the UK and more in line with pre-genetic prevalence estimates in parts of Scandinavia. Future diagnostic and therapeutic studies may benefit from knowledge of the mutation spectrum of skeletal muscle channelopathies.

Timing of surgery for primary exotropia in children.

OBJECTIVE: To compare the postoperative alignment and sensory functions in patients with primary exotropia who had been operated at an early age (< 7 years) with those in patients who had been operated at an older age (> 7 years). METHODS: In a consecutive retrospective cohort study, 112 patients who had had a surgical intervention for primary exotropia between 1997 and 2003 were evaluated for postoperative results. After applying criteria for eligibility, the group of patients was divided into two groups: those who had had surgery before the age of seven years (n = 24) and those who had had surgery after the age of seven years (n = 36). Age at surgery, preoperative alignment and sensory functions were correlated with the postoperative status. The follow-up was at least one year (1.0 year to 7 years; median: 2.3 and 3.5 years, respectively). RESULTS: Patients who had had surgery before the age of seven had significantly better alignment and sensory functions. The univariate logistic regression model confirmed a statistically significant association between motor outcome (exodeviation less than 10 diopters) and age at the time of surgery (before or after the age of seven; p = 0.002). In the multivariate model, the association between age at time of surgery and motor outcome was even stronger. The number of re-operations in the group operated before the age of 7 years was significantly less than in the group operated after the age of seven (2 versus 12, p = 0.023). CONCLUSION: The postoperative alignment and sensory functions for patients with primary exotropia who had had a surgical intervention before the age of seven years were, in this study, better than those in patients who had had surgery after the age of seven years.

[Donor nephrectomy: less fatigue and better quality of life following laparoscopic kidney removal compared with an open procedure by mini-incision: blind randomised study]. / Donornefrectomie: minder vermoeidheid en meer kwaliteit van leven na een laparoscopische uitname dan na een open ingreep met een mini-incisie: geblindeerd, gerandomiseerd onderzoek.

OBJECTIVE: Determining possible differences in living donor nephrectomy procedures: laparoscopy against mini-incision concerning discomfort to the donor and the maintenance of good graft function. DESIGN: Blind randomized study. METHOD: In two university medical centres, one hundred living kidney donors were randomly assigned to either total laparoscopic donor nephrectomy or mini-incision muscle-splitting open donor nephrectomy. Primary outcome was physical fatigue measured with the 'Multidimensional Fatigue Inventory' (MFI-20) during one-year follow-up. Secondary outcomes were physical function measured with the 'Short form-36' questionnaire, postoperative hospital stay, amount of pain, operating times and graft and patient survival. RESULTS: Donors who underwent laparoscopy experienced less fatigue (difference: -1.3; 95% CI: -2.4 - (-0.1)) and physical function was better (difference: 6.2; 95% CI: 2.0-10.3) during one-year follow-up. Those donors who underwent laparoscopy required less morphine (16 mg versus 25 mg; p = 0.005) and the duration of hospital stay was shorter (3 versus 4 days; p = 0.003). The laparoscopic procedure resulted in a longer operation time (221 versus 164 min; p < 0.001) a longer first warm ischaemia time (6 versus 3 min; p < 0.001) and less blood loss (100 versus 240 ml; p < 0.001). Recipient renal function and one-year graft survival rates did not differ. The number of preoperative and postoperative complications did not differ significantly between both surgery techniques. Conversions did not occur. CONCLUSION: Donor nephrectomy through laparoscopy led to less fatigue and a better quality of life compared with the open procedure. The safety factors for donors and recipients were comparable for both techniques. Laparoscopic donor nephrectomy is therefore the better surgical choice for kidney donor programmes with living donors.

The yield of diagnostic work-up of patients presenting with myalgia, exercise intolerance, or fatigue: A prospective observational study.

Myalgia, fatigue, and exercise intolerance are cause for referral to a neurologist. However, the diagnostic value of history, neurological examination, and ancillary investigations in patients with these symptoms is unknown. This study provides a sound footing for deciding which ancillary investigations should be conducted. A prospective observational study of the diagnostic approach in 187 patients with myalgia, exercise intolerance, or fatigue as their predominant symptom was performed. The primary outcomes were independent contribution of referral letter, history, examination, and ancillary investigations to a myopathy diagnosis. The secondary outcome was diagnostic value of combined ancillary investigations. 27% of patients had a myopathy. Positive family history (OR 3.2), progressive symptoms (OR 2.2), atrophy (OR 9.7), weakness (OR 10.9), and hyporeflexia (OR 4.4) were associated with a myopathy. Positive predictive values for myopathy were calculated for CK (0.32), EMG (0.66), ultrasound (0.47), and muscle biopsy (0.78). All contributed significantly in predicting myopathy. Multivariate analysis yielded a diagnostic algorithm facilitating a more efficient work-up in future patients. CK levels, EMG, ultrasound, and muscle biopsy independently contribute to predicting a myopathy. The diagnostic algorithm shows which combination of ancillary investigations should be employed in different subgroups and when to omit invasive techniques. This algorithm may drastically improve diagnostic efficiency.

Timing of surgery for primary exotropia in children.

OBJECTIVE: To compare postoperative alignment and sensory functions in children with primary exotropia who were operated at an early age (< 7 years) with patients who were operated at an older age (> 7 years). METHODS: In a consecutive retrospective cohort study, 112 patients who had a surgical intervention for primary exotropia between 1997 and 2003 were evaluated for postoperative results. After applying criteria for eligibility, the group of patients was divided into two groups: those who had surgical intervention before the age of seven years (n = 24) and those who had surgery after the age of seven years (n = 36). Age at surgery, preoperative alignment and sensory functions were correlated with the postoperative status. The follow-up was at least one year (1.0 year to 7 years; median: 2.3 and 3.5 years, respectively). RESULTS: Children who had surgery before the age of seven had significantly better alignment and sensory functions. The univariate logistic regression model confirmed a statistically significant association between motor outcome (exodeviation less than 10 prism-diopters) and age at the time of surgery (before or after the age of seven; p = 0.002). In the multivariate model, the association between age at time of surgery and motor outcome was even stronger. The number of reoperations in the group operated before the age of 7 years was significantly less than in the group operated after the age of seven (2 versus 12, p = 0.023). CONCLUSION: The postoperative alignment and sensory functions in patients with primary exotropia who had surgical intervention before the age of seven years were, in this study, better than in patients who had surgery after the age of seven years.

Why is it so difficult to integrate ethics in Health Technology Assessment (HTA)? The epistemological viewpoint.

Ethics has been identified as a key element in Health Technology Assessment (HTA) since its conception. However, ethical issues are still not frequently addressed explicitly in HTA. Several valuable reasons have been identified. The basis of the article is the claim that ethics is often not part of HTA for "epistemological reasons". Hence, the main aim of the contribution is to explore in more details and emphasize them by using the fact/value dichotomy. Our conclusion is that current HTA configuration is predominantly based on the comparison among objective and empirically testable "facts", whilst ethics is not empirically testable. In this sense, there is a sort of "epistemological gap", which can explain why it is so difficult to integrate ethics in HTA. We suggest that the epistemological differences among the various domains of HTA are addressed more explicitly.

Parental quality of life in complex paediatric neurologic disorders of unknown aetiology.

Complex paediatric neurology (CPN) patients generally present with non-specific symptoms, such as developmental delay, impaired movement and epilepsy. The diagnostic trajectory in these disorders is usually complicated and long-lasting, and may be burdensome to the patients and their parents. Additionally, as caring for a chronically ill child can be stressful and demanding, parents of these patients may experience impaired health-related quality of life (HRQoL). This study aims to assess parental HRQoL and factors related to it in CPN. Physical and mental HRQoL of 120 parents was measured and compared to the general population using the SF-12 questionnaire. Parents also completed this questionnaire for the measurement of patient HRQoL. Additional questionnaires were used to measure parental uncertainty (Visual Analogue Scale) and worry phenomena (Penn State Worry Questionnaire), and to obtain socio-demographic data. A linear mixed model with random effect was used to investigate which of these variables were associated with parental HRQoL. As compared to the general population, HRQoL of these parents appeared diminished. Fathers showed both lowered physical (51.76, p < 0.05) and mental (49.41, p < 0.01) HRQoL, whereas mothers only showed diminished mental (46.46, p < 0.01) HRQoL. Patient HRQoL and parental worry phenomena were significantly correlated with overall and mental parental HRQoL. The reduction in parental mental HRQoL is alarming, also because children strongly rely on their parents and parental mental health is known to influence children's health. Awareness of these problems among clinicians, and supportive care if needed are important to prevent exacerbation of the problems.

Impact of the introduction of a guideline on the targeted detection of hereditary haemochromatosis.

BACKGROUND: In 1998 a clinical guideline for the targeted, accurate and early detection and treatment of HFE-related hereditary haemochromatosis (HH), which comprises a test for the causative HFE-gene mutations, was introduced in our outpatient department. METHODS: The impact of this guideline was evaluated retrospectively. Data were acquired from medical records of patients with discharge diagnosis codes suggestive of HH (n=878 patients), obtained from a period before (n=422) and after guideline introduction (n=456). RESULTS: Combined measurements of serum transferrin saturation and serum ferritin rose from 12.2% (n=53) to 29.5% (n=138, p<0.001), leaving 70% of the patients eligible for HH not tested for iron parameters. The HFE-gene mutation detection test was correctly used in II (40.7%) of 27 tested patients and improperly interpreted in six (22.2%) of these 27 patients. Five new HH patients were diagnosed before and 13 after introduction. Seven of these 13 patients appeared to be incorrectly diagnosed, due to misinterpretation of laboratory results. Diagnostic costs of case detection for each accurately diagnosed patient were euro 2380 before and euro 2600 after introduction of the guideline. CONCLUSION: Evaluation of the introduction of a practical guideline for targeted HH detection reveals a low compliance with the guideline, resulting in both a small percentage of patients tested for HH and overdiagnosis of HH. Therefore, the introduction of the guideline should be combined with a more appropriate implementation strategy which includes education on its most critical points, i.e. the indication and interpretation of the iron parameters and the HFE genotype.

Ventilation tubes in infants increase the risk of otorrhoea and antibiotic usage.

1) PROBLEM/OBJECTIVE: The effect of ventilation tubes on acute otitis related symptoms (otorrhoea, earache, and fever) and on antibiotic usage was investigated in children with persistent otitis media with effusion, as part of a multicenter, randomised, controlled clinical trial. 2) METHODOLOGY: One hundred-eighty-seven children were randomly placed into either a watchful waiting group (WW group) (n = 94) or a group treated with ventilation tubes (VT group) (n = 93). Both groups were followed for 12 months. Data were collected from parental reports and from medical files kept by the attending ENT-surgeons. 3) RESULTS: There were significant differences in the reported frequency of otorrhoea (but not of earache or fever) between both groups during follow-up, i.e. children in the VT group had more episodes of otorrhoea than the children in the WW group (p < 0.003). As a consequence, children in the VT group had been prescribed antibiotics more often. 4) CONCLUSIONS: Young children treated with ventilation tubes due to persistent otitis media with effusion have a higher risk of developing otorrhoea because of the tubes, and they have a higher risk of needing treatment with antibiotics.

The diagnostic pathway in complex paediatric neurology: a cost analysis.

BACKGROUND: The diagnostic trajectory of complex paediatric neurology may be long, burdensome, and expensive while its diagnostic yield is frequently modest. Improvement in this trajectory is desirable and might be achieved by innovations such as whole exome sequencing. In order to explore the consequences of implementing them, it is important to map the current pathway. To that end, this study assessed the healthcare resource use and associated costs in this diagnostic trajectory in the Netherlands. METHODS: Fifty patients presenting with complex paediatric neurological disorders of a suspected genetic origin were included between September 2011 and March 2012. Data on their healthcare resource utilization were collected from the hospital medical charts. Unit prices were obtained from the Dutch Healthcare Authority, the Dutch Healthcare Insurance Board, and the financial administration of the hospital. Bootstrap simulations were performed to determine mean quantities and costs. RESULTS: The mean duration of the diagnostic trajectory was 40 months. A diagnosis was established in 6% of the patients. On average, patients made 16 physician visits, underwent four imaging and two neurophysiologic tests, and had eight genetic and 16 other tests. Mean bootstrapped costs per patient amounted to €12,475, of which 43% was for genetic tests (€5,321) and 25% for hospital visits (€3,112). CONCLUSION: Currently, the diagnostic trajectories of paediatric patients who have complex neurological disease with a strong suspected genetic component are lengthy, resource-intensive, and low-yield. The data from this study provide a backdrop against which the introduction of novel techniques such as whole exome sequencing should be evaluated.

Generalizability of trial results based on randomized versus nonrandomized allocation of OME infants to ventilation tubes or watchful waiting.

The objective was to study the generalizability of trial results by comparing randomized patients to eligible but nonrandomized patients who received the same management. Implementation of trial results is only justifiable when the results can be generalized to the total domain population. The design was a multicentre randomized controlled trial on the effect of early screening and treatment with ventilation tubes on infants with otitis media with effusion. Randomized (n = 187) and nonrandomized eligible patients (n = 133) were followed up. The study population comprised children who were detected by auditory screening at the age of 9-12 months and who were subsequently diagnosed with persistent bilateral otitis media with effusion for 4-6 months. A significant difference was found in the distribution of some prognostic factors: more randomized children had older siblings, did not attend day care and had mothers with a lower educational level than the nonrandomized children. These factors, however, did not modify the outcome. No differences were found in mean hearing levels between the randomized and nonrandomized children: in both the randomized and nonrandomized children ventilation tubes improved the hearing level, especially after 6 months. However, in the long term (12 months), the hearing levels were equal again. The results of the randomized and nonrandomized patients were comparable. The results of this trial appear to be generalizable to the total domain population. The procedure of following up both randomized and nonrandomized patients is recommended when there is concern about selective participation and reduced generalizability.