Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxygenation in a patient who does not have spontaneous circulation. The evidence with regard to the effect of extracorporeal CPR on survival with a favorable neurologic outcome in refractory out-of-hospital cardiac arrest is inconclusive. METHODS: In this multicenter, randomized, controlled trial conducted in the Netherlands, we assigned patients with an out-of-hospital cardiac arrest to receive extracorporeal CPR or conventional CPR (standard advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, had an initial ventricular arrhythmia, and did not have a return of spontaneous circulation within 15 minutes after CPR had been initiated. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 (range, 1 to 5, with higher scores indicating more severe disability) at 30 days. Analyses were performed on an intention-to-treat basis. RESULTS: Of the 160 patients who underwent randomization, 70 were assigned to receive extracorporeal CPR and 64 to receive conventional CPR; 26 patients who did not meet the inclusion criteria at hospital admission were excluded. At 30 days, 14 patients (20%) in the extracorporeal-CPR group were alive with a favorable neurologic outcome, as compared with 10 patients (16%) in the conventional-CPR group (odds ratio, 1.4; 95% confidence interval, 0.5 to 3.5; P = 0.52). The number of serious adverse events per patient was similar in the two groups. CONCLUSIONS: In patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR and conventional CPR had similar effects on survival with a favorable neurologic outcome. (Funded by the Netherlands Organization for Health Research and Development and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.gov number, NCT03101787.).

Surgical excision versus topical 5% 5-fluorouracil and photodynamic therapy in treatment of Bowen's disease: A multicenter randomized controlled trial.

BACKGROUND: Randomized controlled trials comparing the effectiveness of 5-fluorouracil cream, methylaminolevulinate photodynamic therapy (MAL-PDT) and surgical excision in patients with Bowen's disease are lacking. METHODS: In this multicenter noninferiority trial, patients with a histologically proven Bowen's disease of 4-40 mm were randomly assigned to excision with 5 mm margin, 5% 5-fluorouracil cream twice daily for 4 weeks, or 2 sessions of MAL-PDT with 1 week interval. The primary outcome was the proportion of patients with sustained clearance at 12 months after treatment. A noninferiority margin of 22% was used. RESULTS: Between May 2019 and January 2021, 250 patients were randomized. The proportion of patients with sustained clearance was 97.4% (75/77) after excision, 85.7% (66/77) after 5-fluorouracil, and 82.1% (64/78) after MAL-PDT. Absolute differences were -11.7% (95% CI -18.9 to -4.5; P = .0049) for 5-fluorouracil versus excision and -15.4% (95% CI -23.1 to -7.6; P = .00078) for MAL-PDT versus excision. Both noninvasive treatments significantly more often led to good or excellent cosmetic outcome. CONCLUSIONS: Based on our predefined noninferiority margin of 22%, 5-fluorourcail is noninferior to excision and associated with better cosmetic outcome. For MAL-PDT noninferiority to excision cannot be concluded. Therefore, 5-fluorouracil should be preferred over excision and MAL-PDT in treatment of Bowen's disease.

Development, validation and feasibility of a Patient Satisfaction Questionnaire for evaluating the quality performance of a diagnostic small fibre neuropathy service: A qualitative study.

INTRODUCTION AND AIM: Small fibre neuropathy (SFN) is a peripheral neuropathy, leading to neuropathic pain and autonomic dysfunction. An evidence-based standardized patient diagnostic SFN service has been implemented in the Netherlands for improving patient-centred SFN care. However, the quality of care of this diagnostic SFN service has never been assessed from a patient perspective. The aim of this study was to develop and validate an SFN-Patient Satisfaction Questionnaire (SFN-PSQ) to measure the quality performance of a standardized diagnostic SFN service. METHODS: A descriptive qualitative study to create the SFN-PSQ was performed using the (COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist. For item generation and content development, domains and/or items from validated PSQs were selected. The content development and content validity were performed using a Delphi method with SFN expert caregivers with different backgrounds. By using the three-step-test method in individual cognitive interviews, the content validity by patients was finalized. RESULTS: In one online Delphi panel round, the content of the first concept of the SFN-PSQ was validated, which resulted in the second concept of the SFN-PSQ. From July 2019 till March 2020, nine patients consented to participate in the individual cognitive interviews. The most significant changes of the new questionnaire were adding domains and items concerning the waiting list, the diagnostic services and consultation by the hospital psychiatrist. Also, a differentiation was made for both an inpatient and outpatient diagnostic SFN service. Furthermore, the clarity and intelligibility of the domains/items were improved, resulting in an increased comprehension of the SFN-PSQ. Ultimately, the new developed SFN-PSQ consisted of 10 domains and 51 items, suitable for measuring patient satisfaction of the neurological analysis in patients with SFN. CONCLUSION: Through item generation, expert opinions and interviews with patients, the SFN-PSQ was developed and validated, and feasibility was confirmed. The structure of the questionnaire, based on the logistic and diagnostic SFN pathway, could be used as a model in other hospitals to improve the quality, continuity and access of SFN care and other chronic diseases taking into account potential cross-cultural differences. PATIENT OR PUBLIC CONTRIBUTION: Caregivers were involved in the item generation and content development of the questionnaire. Patients were directly involved in testing the content validity and feasibility of the SFN-PSQ. CLINICAL TRIAL REGISTRATION: Not applicable.

Patient's preference for sacrospinous hysteropexy or modified Manchester operation: A discrete choice experiment.

OBJECTIVE: To investigate women's preference for modified Manchester (MM) or sacrospinous hysteropexy (SH) as surgery for uterine prolapse. DESIGN: Labelled discrete choice experiment (DCE). SETTING: Eight Dutch hospitals. POPULATION: Women with uterine prolapse, eligible for primary surgery and preference for uterus preservation. METHODS: DCEs are attribute-based surveys. The two treatment options were labelled as MM and SH. Attributes in this survey were treatment success ( levels SH: 84%, 89%, 94%; levels MM: 89%, 93%, 96%), dyspareunia (levels: 0%, 5%, 10%), cervical stenosis (levels: 1%, 6%, 11%) and severe buttock pain (levels: 0%, 1%). A different combination of attribute levels was used in each choice set. Women completed nine choice sets, making a choice based on attribute levels. Data were analysed in multinomial logit models. MAIN OUTCOME MEASURES: Women's preference for MM or SH. RESULTS: 137 DCEs were completed (1233 choice sets). SH was chosen in 49% of the choice sets, MM in 51%. Of all women, 39 (28%) always chose the same surgery. After exclusion of this group, 882 choice sets were analysed, in which women preferred MM, likely associated with a labelling effect, i.e. description of the procedure, rather than the tested attributes. In that group, MM was chosen in 53% of the choice sets and SH in 47%. When choosing MM, next to the label, dyspareunia was relevant for decision-making. For SH, all attributes were relevant for decision-making. CONCLUSIONS: The preference of women for MM or SH seems almost equally divided. The variety in preference supports the importance of individualised healthcare.

Gynecologists' perspectives on surgical treatment for apical prolapse: a qualitative study.

INTRODUCTION AND HYPOTHESIS: Vaginal sacrospinous fixation (VSF) without mesh and sacrocolpopexy (SCP) with mesh are the most frequently performed surgical procedures for apical prolapse in the Netherlands. There is no long-term evidence suggesting the optimal technique, however. The aim was to identify which factors play a role in the choice between these surgical treatment options. METHODS: A qualitative study using semi-structured interviews amongst Dutch gynecologists was carried out. An inductive content analysis was performed with Atlas.ti. RESULTS: Ten interviews were analyzed. All gynecologists performed vaginal surgeries for apical prolapse, six gynecologists perform SCP themselves. Six gynecologists would perform VSF for a primary vaginal vault prolapse (VVP); three gynecologists preferred a SCP. All participants prefer a SCP for recurrent VVP. All participants have stated that multiple comorbidities could be a reason for choosing VSF, as this procedure is considered less invasive. Most participants choose a VSF in the case of older age (6 out of 10) or higher body mass index (7 out of 10). All treat primary uterine prolapse with vaginal, uterine-preserving surgery. CONCLUSIONS: Recurrent apical prolapse is the most important factor in advising patients which treatment they should undergo for VVP or uterine descent. Also, the patient's health status and the patient's own preference are important factors. Gynecologists who do not perform the SCP in their own clinic are more likely to perform a VSF and find more reasons not to advise a SCP. All participants prefer a vaginal surgery for a primary uterine prolapse.

Optical coherence tomography versus punch biopsy for diagnosis of basal cell carcinoma: a multicentre, randomised, non-inferiority trial.

BACKGROUND: Punch biopsy is the gold standard for diagnosis and subtyping of basal cell carcinoma. The aim of this study was to assess whether use of optical coherence tomography (OCT), a non-invasive imaging tool, might avoid the need for biopsy. METHODS: In a multicentre, randomised, non-inferiority trial, patients (aged ≥18 years) with an indication for biopsy of a suspected basal cell carcinoma outside the H-zone (high-risk zone) of the face were randomly assigned (1:1) to receive either OCT or punch biopsy (regular care) via a web-based randomisation system. Patients were enrolled from three participating centres in the Netherlands: Maastricht University Medical Centre+, Catharina Hospital Eindhoven, and Zuyderland Medical Centre Heerlen. Stratification factors for randomisation were participating centre and the grade of clinical basal cell carcinoma suspicion (high vs low). The primary endpoint was the proportion of patients free from a recurrent or residual lesion (malignant or premalignant) 12 months after treatment. Modified intention-to-treat and per-protocol analyses were conducted, with a predefined non-inferiority margin of -10%. This trial is registered with ClinicalTrials.gov number, NCT03848078, and is complete. FINDINGS: Between Feb 25, 2019, and Sept 2, 2020, 598 patients were enrolled and randomly assigned to either the regular care group (n=299) or the OCT group (n=299). Data on the primary endpoint were available in 553 patients (n=268 in the regular care group, n=285 in the OCT group). After median follow-up of 12·7 months (IQR 11·2-14·1) in the OCT group and 12·6 months (10·8-14·3) in the regular care group, 253 (94%) of 268 patients in the OCT group and 266 (93%) of 285 patients in the regular care group were free from recurrent or residual lesions (malignant or pre-malignant) 12 months after treatment. According to our modified intention-to-treat analysis, the absolute difference (OCT vs regular care) was 1·07% (95% CI -2·93 to 5·06; one-sided p=0·30), with the lower limit of the 95% CI not exceeding the predefined non-inferiority margin of -10%. Per-protocol analyses led to proportions free from a residual or recurrent lesion (premalignant or malignant) of 95% (250 of 263) in the OCT group and 94% (262 of 278) in the regular care group, and an absolute difference of 0·81% (95% CI -2·98 to 4·60; one-sided p=0·34). INTERPRETATION: OCT-guided diagnosis and treatment of basal cell carcinoma is non-inferior to regular care punch biopsy. Implementation of OCT for diagnosis of basal cell carcinoma could reduce the number of consultations and invasive procedures. FUNDING: The Netherlands Organization for Health Research and Development and Maurits en Anna de Kock Stichting.

Randomized Trial of Four Treatment Approaches for Actinic Keratosis.

BACKGROUND: Actinic keratosis is the most frequent premalignant skin disease in the white population. In current guidelines, no clear recommendations are made about which treatment is preferred. METHODS: We investigated the effectiveness of four frequently used field-directed treatments (for multiple lesions in a continuous area). Patients with a clinical diagnosis of five or more actinic keratosis lesions on the head, involving one continuous area of 25 to 100 cm2, were enrolled at four Dutch hospitals. Patients were randomly assigned to treatment with 5% fluorouracil cream, 5% imiquimod cream, methyl aminolevulinate photodynamic therapy (MAL-PDT), or 0.015% ingenol mebutate gel. The primary outcome was the proportion of patients with a reduction of 75% or more in the number of actinic keratosis lesions from baseline to 12 months after the end of treatment. Both a modified intention-to-treat analysis and a per-protocol analysis were performed. RESULTS: A total of 624 patients were included from November 2014 through March 2017. At 12 months after the end of treatment, the cumulative probability of remaining free from treatment failure was significantly higher among patients who received fluorouracil (74.7%; 95% confidence interval [CI], 66.8 to 81.0) than among those who received imiquimod (53.9%; 95% CI, 45.4 to 61.6), MAL-PDT (37.7%; 95% CI, 30.0 to 45.3), or ingenol mebutate (28.9%; 95% CI, 21.8 to 36.3). As compared with fluorouracil, the hazard ratio for treatment failure was 2.03 (95% CI, 1.36 to 3.04) with imiquimod, 2.73 (95% CI, 1.87 to 3.99) with MAL-PDT, and 3.33 (95% CI, 2.29 to 4.85) with ingenol mebutate (P≤0.001 for all comparisons). No unexpected toxic effects were documented. CONCLUSIONS: At 12 months after the end of treatment in patients with multiple actinic keratosis lesions on the head, 5% fluorouracil cream was the most effective of four field-directed treatments. (Funded by the Netherlands Organization for Health Research and Development; ClinicalTrials.gov number, NCT02281682.).

Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation.

BACKGROUND: Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously. METHODS: In a multicenter, randomized, open-label, noninferiority trial, we randomly assigned patients with hemodynamically stable, recent-onset (<36 hours), symptomatic atrial fibrillation in the emergency department to be treated with a wait-and-see approach (delayed-cardioversion group) or early cardioversion. The wait-and-see approach involved initial treatment with rate-control medication only and delayed cardioversion if the atrial fibrillation did not resolve within 48 hours. The primary end point was the presence of sinus rhythm at 4 weeks. Noninferiority would be shown if the lower limit of the 95% confidence interval for the between-group difference in the primary end point in percentage points was more than -10. RESULTS: The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P = 0.005 for noninferiority). In the delayed-cardioversion group, conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients (69%) and after delayed cardioversion in 61 patients (28%). In the early-cardioversion group, conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients (16%) and after cardioversion in 171 patients (78%). Among the patients who completed remote monitoring during 4 weeks of follow-up, a recurrence of atrial fibrillation occurred in 49 of 164 patients (30%) in the delayed-cardioversion group and in 50 of 171 (29%) in the early-cardioversion group. Within 4 weeks after randomization, cardiovascular complications occurred in 10 patients and 8 patients, respectively. CONCLUSIONS: In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. (Funded by the Netherlands Organization for Health Research and Development and others; RACE 7 ACWAS ClinicalTrials.gov number, NCT02248753.).

Discrete Choice Experiment Reveals Strong Preference for Dietary Treatment Among Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder of the gut-brain interaction that significantly affects quality of life. Several treatments, with comparable clinical efficacy, are available. Patient preferences can therefore be an important determinant of an effective management strategy. Treatment preferences of patients regarding decision making remain unclear. We aimed to examine these preferences and estimate trade-offs between different attributes. METHODS: A total of 427 patients from the Maastricht IBS cohort were invited to participate. A labeled discrete choice experiment survey, containing 9 scenarios with each 3 alternatives (medication, diet, psychotherapy), was developed in order to estimate preferences. The treatment scenarios were based on 6 attributes: effectiveness, time to response, time until recurrence, side effects, time required, and frequency of appointments. The preference weights and relative importance were analyzed using a mixed logit model. RESULTS: A total of 185 (43.3%) of 427 potential respondents completed the questionnaire (mean age 49.51 years, 69.2% female). The most preferred treatment was dietary intervention (48.1%), followed by pharmacotherapy (29.2%) and psychotherapy (22.7%). IBS patients preferred a higher effectiveness, shorter time interval to response, longer time interval until recurrence, no severe side effects, and frequent appointments when attending psychotherapy. Younger patients (≤50 years of age) preferred dietary interventions and a long period until recurrence, whereas older patients (>50 years of age) were more inclined to choose pharmacotherapy and the period until recurrence was not important. CONCLUSIONS: Dietary interventions were the most preferred IBS therapy. Identifying patients' treatment preferences during shared decision making will provide more optimal management strategies and could be the best approach to diminish disease burden.

The ICEpop Capability Measure for Adults Instrument for Capabilities: Development of a Tariff for the Dutch General Population.

OBJECTIVES: The ICEpop Capability Measure for Adults (ICECAP-A) assesses 5 capabilities (stability, attachment, autonomy, achievement, and enjoyment) that are important to one's quality of life and might be an important addition to generic health questionnaires currently used in economic evaluations. This study aimed to develop a Dutch tariff of the Dutch translation of the ICECAP-A. METHODS: The methods used are similar to those used in the development of the UK tariff. A profile case best-worst scaling task was presented to 1002 participants from the general Dutch population. A scale-adjusted latent class analysis was performed to test for preferences of ICECAP-A capabilities and scale heterogeneity. RESULTS: A 3-preference class 2-scale class model with worst choice as scale predictor was considered optimal and was used to calculate the resulting tariff. Results indicated that the capabilities stability, attachment, and enjoyment were considered more important aspects of quality of life than autonomy and achievement. Additionally, improving capabilities from low to moderate levels had a larger effect on quality of life than improving capabilities that were already at a higher level. CONCLUSIONS: The ICECAP-A tariffs found in this study could be used in economic evaluations of healthcare interventions in The Netherlands.

Treatment preferences for medication or surgery in patients with deep endometriosis and bowel involvement - a discrete choice experiment.

OBJECTIVE: To study the preferences of women with deep endometriosis (DE) with bowel involvement when they have to choose between conservative (medication) or surgical treatment. DESIGN: Labelled discrete choice experiment (DCE). SETTING: Dutch academic and non-academic hospitals and online recruitment. POPULATION OR SAMPLE: A total of 169 women diagnosed with DE of the bowel. METHODS: Baseline characteristics and the fear of surgery were collected. Women were asked to rank attributes and choose between hypothetical conservative or surgical treatment in different choice sets (scenarios). Each choice set offered different levels of all treatment attributes. Data were analysed by using multinomial logistic regression. MAIN OUTCOME MEASURES: The following attributes - effect on/risk of pain, fatigue, pregnancy, endometriosis lesions, mood swings, osteoporosis, temporary stoma and permanent intestinal symptoms - were used in this DCE. RESULTS: In the ranking, osteoporosis was ranked with low importance, whereas in the DCE, a lower chance of osteoporosis was one of the most important drivers when choosing a conservative treatment. Women with previous surgery showed less fear of surgery compared with women without surgery. Low anterior resection syndrome was almost equally important for patients as the chance of pain reduction. Pain reduction had higher importance than improving fertility chances, even in women with desire for a future child. CONCLUSIONS: The risk of developing low anterior resection syndrome as a result of treatment is almost equally important as the reduction of pain symptoms. Women with previous surgery experience less fear of surgery compared with women without a surgical history. TWEETABLE ABSTRACT: First discrete choice experiment in patients with deep endometriosis.

The estimation of a preference-based single index for the IBS-QoL by mapping to the EQ-5D-5L in patients with irritable bowel syndrome.

PURPOSE: The Irritable Bowel Syndrome Quality of Life (IBS-QoL) questionnaire is a commonly used and validated IBS-specific QoL instrument. However, this questionnaire is in contrast to the EQ-5D-5L, not preference-based and as such does not allow calculation of QALYs. The objective of this study was to describe the convergent- and known-group validity of both questionnaires and to develop a mapping algorithm from EQ-5D-5L which enable IBS-QoL scores to be transformed into utility scores for use in economic evaluations. METHODS: We used data from two multicenter randomized clinical trials, which represented the estimation and external validation dataset. The convergent validity was investigated by examining correlations between the EQ-5D-5L and IBS-QoL and the known-group validity by calculating effect sizes. Ordinary least squares (OLS), censored least absolute deviations (CLAD), and mixture models were used in this mapping approach. RESULTS: 283 IBS patients were included (n = 189 vs. n = 84). Mean IBS-QoL score was 71.13 (SD 15.66) and mean EQ-5D-5L utility score was 0.73 (SD 0.19). The overall sensitivity of the IBS-QoL and EQ-5D-5L to discriminate between patient and disease characteristics was similar. CLAD model 4, containing the total IBS-QoL score and squared IBS-SSS (IBS severity scoring system), was chosen as the most appropriate model to transform IBS-QoL scores into EQ-5D-5L utility scores. CONCLUSION: This study reports the development of an algorithm where the condition-specific questionnaire IBS-QoL can be used to calculate utility values for use in economic evaluations. Including a clinical measure, IBS-SSS, in the model improved the performance of the algorithm.

The ICECAP-A instrument for capabilities: assessment of construct validity and test-retest reliability in a general Dutch population.

PURPOSE: The ICEpop CAPability measure for Adults (ICECAP-A) assesses five capabilities that are important to one's well-being. The instrument might be an important addition to generic health questionnaires when evaluating quality of life extending beyond health. This study aimed to conduct a psychometric assessment of the Dutch translation of the ICECAP-A. METHODS: Construct validity of the instrument was assessed in two ways. First, by measuring correlations with the EQ-5D-5L questionnaire and a measure of self-efficacy and, second, by investigating the ability to distinguish between groups known to differ on the construct the ICECAP-A means to capture. Additionally, test-retest reliability was evaluated. RESULTS: In total, 1002 participants representative of the general Dutch population completed an online survey. For test-retest reliability, 252 participants completed the same questionnaire 2 weeks later. The ICECAP-A indicated moderate to strong correlations with the EQ-5D-5L and a strong correlation with self-efficacy. Furthermore, it was capable of differentiating known groups. Moreover, results indicated adequate test-retest reliability with an intraclass correlation coefficient of 0.79. CONCLUSION: In summary, results suggest adequate test-retest reliability and construct validity and indicate that the ICECAP-A might be of added value, especially when considering areas outside of the traditional health intervention model.

Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal-release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. METHODS: We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal-release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. RESULTS: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal-release peppermint oil group had a response (46.8%, P = .170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P = .385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4%). We did not find differences among the groups in overall relief (9.7%, P = .317 and 1.6%, P = .351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P = .016), discomfort (P = .020), and IBS severity (P = .020). Adverse events, although mild, were more common in both peppermint oil groups (P < .005). CONCLUSIONS: In a randomized trial of patients with IBS, we found that neither small-intestinal-release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal-release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS. Clinicaltrials.gov, Number: NCT02716285.

Gynecologists' perspectives on two types of uterus-preserving surgical repair of uterine descent; sacrospinous hysteropexy versus modified Manchester.

INTRODUCTION AND HYPOTHESIS: The modified Manchester (MM) and sacrospinous hysteropexy (SSH) are the most common uterus-preserving surgical procedures for uterine descent. Little is known about gynecologists' preferences regarding the two interventions. The study's aim was to identify which factors influence Dutch (uro)gynecologists when choosing one of these techniques. METHODS: This qualitative study consists of ten semi-structured interviews with Dutch (uro)gynecologists using predetermined, open explorative questions, based on a structured topic list. An inductive content analysis was performed using Atlas.ti. RESULTS: For SSH, the majority (6/10 gynecologists) reported the more dorsal change of direction of the vaginal axis as a disadvantage and expected more cystocele recurrences (7/10). The most reported disadvantage of MM was the risk of cervical stenosis (7/10). Four gynecologists found MM not to be appropriate for patients with higher stage uterine prolapse. The quality of the uterosacral ligaments was related to the chance of recurrence according to five gynecologists. Patient counseling was biased toward one of the uterus-preserving operations (7/10). Four gynecologists stated they make the final decision while two let patient-preference lead the final decision. CONCLUSIONS: Preference for one of the uterus-preserving interventions is mainly based on the gynecologist's own experience and background. The lack of information regarding these two uterus-preserving procedures hampers evidence-based decision making, which explains the practice pattern variation. In conclusion, further research is needed to improve evidence-based counseling and shared decision making regarding the choice of procedure.

Discrete choice experiment on educating value-based healthcare.

INTRODUCTION: Identifying costs and values in healthcare interventions as well as the ability to measure and consider costs relative to value for patients are pivotal in clinical decision-making and medical education. This study explores residents' preferences in educating value-based healthcare (VBHC) during postgraduate medical education. Exploring residents' preferences in VBHC education, in order to understand what shapes their choices, might contribute to improved medical residency education and healthcare as a whole. METHODS: A discrete choice experiment (DCE) examined which conditions for educating VBHC are preferred by residents. DCE gives more insight into the trade-off's residents make when choosing alternatives, and which conditions for educating VBHC have the most influence on residents' preference. RESULTS: This DCE shows that residents prefer knowledge on both medical practice as well as the process of care-to be educated by an expert on VBHC together with a clinician. They prefer limited protected time to conduct VBHC initiatives (thus while at work) and desire the inclusion of VBHC in formal educational plans. CONCLUSION: When optimising graduate and postgraduate medical education curricula, these preferences should be considered to create necessary conditions for the facilitation and participation of residents in VBHC education and the set-up of VBHC initiatives.

Age dependency of EQ-5D-Youth health states valuations on a visual analogue scale.

BACKGROUND: Examine whether the use of different ages has an impact on the valuation of EQ-5D-Y health states for a hypothetical child or adolescent. METHODS: A survey was administered during regular classes among a convenience sample of university students in the Netherlands. Respondents first valued 6 EQ-5D-Y health states (2 mild, 2 moderate, 2 severe) describing a hypothetical child/adolescent of a certain age on a visual analogue scale (VAS). After 1 h respondents valued the same six health states again but this time the age of the child was different. Age differed between 4, 10 and 16 year old. RESULTS: Number of respondents was 311. No significant differences in valuation of the six health states were found between the age of 10 and 16. One moderate health state was valued significantly better for a 4-year old compared to a 10 and a 16 year old. The same applied for one severe health state that was valued higher for a 4-year old compared to a 16-year old. CONCLUSION: Our study shows that, except for one moderate and one severe health state, other EQ-5D-Y health states were not valued significantly different when description of age differed. It is possible that problems in specific health domains are considered more severe for older children/adolescents compared to younger children who might still be dependent on their caregivers. Future research should examine whether our findings are also present in a broader set of EQ-5D-Y health states, with a choice-based method like TTO or DCE, and a more heterogeneous sample.

A discrete choice experiment to identify the most efficient quality indicators for the supervision of psychiatric hospitals.

BACKGROUND: In the Netherlands, health care is regulated by the Health and Youth Care Inspectorate. Forty-six indicators are used to prioritize supervision of psychiatric hospitals. The objective of this study is to define a smaller set of weighted indicators which reflects a consensus among inspectors about which aspects are most important for risk assessment. METHODS: The set of 46 indicators, complemented with missing information, was reduced to six indicators by means of interviews, group discussions and ranking among the inspectors. These indicators were used as attributes in a discrete choice experiment (DCE) to define their weights. RESULTS: Twenty-six inspectors defined the top four indicators suitable for the risk assessment of psychiatric hospitals. These are: the policy on prevention of compulsory treatment; the policy on dysfunctional professionals; the quality of internal research after a serious incident; and the implementation of multidisciplinary guidelines on suicidal behaviour. These indicators share the same importance with regard to risk assessment. The screening of somatic symptoms and the policy on integrated care are important indicators too, but less relevant. CONCLUSION: Through a DCE, we reduced the amount of information for risk assessment of psychiatric hospitals to six weighted indicators. Inspectors can use these indicators to prioritize their inspections.

Early initiation of extracorporeal life support in refractory out-of-hospital cardiac arrest: Design and rationale of the INCEPTION trial.

Return of spontaneous circulation occurs in less than 10% of patients with cardiac arrest undergoing cardiopulmonary resuscitation (CPR) for more than 15 minutes. Studies suggest that extracorporeal life support during cardiopulmonary resuscitation (ECPR) improves survival rate in these patients. These studies, however, are hampered by their non-randomized, observational design and are mostly single-center. A multicenter, randomized controlled trial is urgently warranted to evaluate the effectiveness of ECPR. HYPOTHESIS: We hypothesize that early initiation of ECPR in refractory out-of-hospital cardiac arrest (OHCA) improves the survival rate with favorable neurological status. STUDY DESIGN: The INCEPTION trial is an investigator-initiated, prospective, multicenter trial that will randomly allocate 110 patients to either continued CPR or ECPR in a 1:1 ratio. Patients eligible for inclusion are adults (≤ 70 years) with witnessed OHCA presenting with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT), who received bystander basic life support and who fail to achieve sustained return of spontaneous circulation within 15 minutes of cardiopulmonary resuscitation by emergency medical services. The primary endpoint of the study is 30-day survival rate with favorable neurological status, defined as 1 or 2 on the Cerebral Performance Category score. The secondary endpoints include 3, 6 and 12-month survival rate with favorable neurological status and the cost-effectiveness of ECPR compared to CCPR. SUMMARY: The INCEPTION trial aims to determine the clinical benefit for the use of ECPR in patients with refractory OHCA presenting with VF/VT. Additionally, the feasibility and cost-effectiveness of ECPR will be evaluated.

Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial.

BACKGROUND: Intravenous saline is recommended in clinical practice guidelines as the cornerstone for preventing contrast-induced nephropathy in patients with compromised renal function. However, clinical-effectiveness and cost-effectiveness of this prophylactic hydration treatment in protecting renal function has not been adequately studied in the population targeted by the guidelines, against a group receiving no prophylaxis. This was the aim of the AMACING trial. METHODS: AMACING is a prospective, randomised, phase 3, parallel-group, open-label, non-inferiority trial of patients at risk of contrast-induced nephropathy according to current guidelines. High-risk patients (with an estimated glomerular filtration rate [eGFR] of 30-59 mL per min/1·73 m2) aged 18 years and older, undergoing an elective procedure requiring iodinated contrast material administration at Maastricht University Medical Centre, the Netherlands, were randomly assigned (1:1) to receive intravenous 0·9% NaCl or no prophylaxis. We excluded patients with eGFR lower than 30 mL per min/1·73 m2, previous dialysis, or no referral for intravenous hydration. Randomisation was stratified by predefined risk factors. The primary outcome was incidence of contrast-induced nephropathy, defined as an increase in serum creatinine from baseline of more than 25% or 44 µmol/L within 2-6 days of contrast exposure, and cost-effectiveness of no prophylaxis compared with intravenous hydration in the prevention of contrast-induced nephropathy. We measured serum creatinine immediately before, 2-6 days, and 26-35 days after contrast-material exposure. Laboratory personnel were masked to treatment allocation. Adverse events and use of resources were systematically recorded. The non-inferiority margin was set at 2·1%. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT02106234. FINDINGS: Between June 17, 2014, and July 17, 2016, 660 consecutive patients were randomly assigned to receive no prophylaxis (n=332) or intravenous hydration (n=328). 2-6 day serum creatinine was available for 307 (92%) of 332 patients in the no prophylaxis group and 296 (90%) of 328 patients in the intravenous hydration group. Contrast-induced nephropathy was recorded in eight (2·6%) of 307 non-hydrated patients and in eight (2·7%) of 296 hydrated patients. The absolute difference (no hydration vs hydration) was -0·10% (one-sided 95% CI -2·25 to 2·06; one-tailed p=0·4710). No hydration was cost-saving relative to hydration. No haemodialysis or related deaths occurred within 35 days. 18 (5·5%) of 328 patients had complications associated with intravenous hydration. INTERPRETATION: We found no prophylaxis to be non-inferior and cost-saving in preventing contrast-induced nephropathy compared with intravenous hydration according to current clinical practice guidelines. FUNDING: Stichting de Weijerhorst.