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.

Effectiveness of a patient decision aid for patients with superficial basal cell carcinoma: A pre- and post-implementation study.

OBJECTIVE: This study evaluates whether using a patient decision aid (PDA) for patients with superficial basal-cell carcinoma (sBCC) results in a decreased decisional conflict level and increased knowledge. METHODS: In a prospective multicentre study, patient groups were included before and after implementation of a PDA. Decisional conflict levels were compared directly after making the treatment decision, measured once as the mean score on the decisional conflict scale (DCS). Higher scores correspond with higher conflict levels (0-100). Secondary outcomes were knowledge on treatment options, recognizing a BCC, and risk factors for developing a BCC measured on an adapted version of a validated knowledge questionnaire for melanoma patients, and patient satisfaction with the PDA. RESULTS: Data was available for 103 patients in the control-group and 109 in the PDA-group. The mean DCS score in the control-group was 22.78 (SD 14.76) compared to 22.34 (SD 14.54) in the PDA-group; the decrease was non-significant (p = 0.828). The average percentage correct answers on the knowledge questionnaire increased from 76.5% in the control-group to 80.5% in the PDA-group (p = 0.044). According to the majority of patients in the PDA-group (73.7%) the PDA had added value. CONCLUSION: Using the PDA had no significant effect on decisional conflict levels, but increased overall knowledge on relevant issues concerning sBCC. PRACTICE IMPLICATIONS: The PDA can be used as an informational tool by patients with sBCC.

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.

Risk of Invasive Cutaneous Squamous Cell Carcinoma After Different Treatments for Actinic Keratosis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Treatment of actinic keratosis (AK) aims to prevent cutaneous squamous cell carcinoma (cSCC). However, whether AK can progress into invasive cSCC is a matter of debate, and little is known about the effect of treatment on preventing cSCC. Objectives: To evaluate the risk of invasive cSCC and factors that may contribute to increased risk in patients with multiple AKs. Design, Setting, and Participants: In this secondary analysis of a multicenter randomized clinical trial, 624 patients with a minimum of 5 AKs within an area of 25 to 100 cm2 on the head were recruited from the Department of Dermatology of 4 hospitals in the Netherlands. Long-term follow-up was performed from July 1, 2019, to December 31, 2020. Interventions: Patients were randomized to treatment with 5% fluorouracil, 5% imiquimod cream, methylaminolevulinate photodynamic therapy, or 0.015% ingenol mebutate gel. Main Outcomes and Measures: The primary outcome was the proportion of patients with invasive cSCC in the target area during follow-up. Secondary outcomes were the associations between risk of invasive cSCC and a priori defined potential prognostic factors, including type of treatment, severity of AK (Olsen grade), history of nonmelanoma skin cancer, and additional treatment. Results: Of the 624 patients (558 [89.4%] male; median age, 73 years [range, 48-94 years]) in the study, 26 were diagnosed with a histologically proven invasive cSCC in the target area during follow-up. The total 4-year risk of developing cSCC in a previously treated area of AK was 3.7% (95% CI, 2.4%-5.7%), varying from 2.2% (95% CI, 0.7%-6.6%) in patients treated with fluorouracil to 5.8% (95% CI, 2.9%-11.3%) in patients treated with imiquimod. In patients with severe AK (Olsen grade III), the risk was 20.9% (95% CI, 10.8%-38.1%), and the risk was especially high (33.5%; 95% CI, 18.2%-56.3%) in patients with severe AK who needed additional treatment. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, risk of invasive cSCC was highest in patients with Olsen grade III AK and was substantially increased in patients who received additional treatment. These patients should be closely followed up after treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02281682.

A trial-based economic evaluation of peppermint oil for the treatment of irritable bowel syndrome.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a prevalent, chronic gastrointestinal disorder that imposes a substantial socioeconomic burden. Peppermint oil is a frequently used treatment for IBS, but evidence about cost-effectiveness is lacking. OBJECTIVE: We aimed to assess cost-effectiveness of small-intestinal release peppermint oil versus placebo in IBS patients. METHODS: In a multicenter randomized placebo-controlled trial, cost-effectiveness was evaluated from a societal perspective. The incremental cost-effectiveness ratios (ICERs) were expressed as (1) incremental costs per Quality Adjusted Life Years (QALY), and (2) incremental costs per successfully treated patient, that is per abdominal pain responder (according to FDA definitions), both after an eight-week treatment period with placebo versus peppermint oil. Cost-utility and uncertainty were estimated using non-parametric bootstrapping. Sensitivity analyses were performed. RESULTS: The analysis comprised 126 patients (N = 64 placebo, N = 62 small-intestinal release peppermint oil). Peppermint oil was a dominant treatment compared to placebo in 46% of bootstrap replications. Peppermint oil was also more effective but at higher cost in 31% of replications. The net-benefit acceptability curve showed that peppermint oil has a 56% probability of being cost-effective at a conservative willingness-to-pay threshold of €10.000/QALY. Peppermint oil was also a dominant treatment per additional successfully treated patient according to FDA definitions, that is in 51% of replications. In this case, the acceptability curve showed an 89% probability of being cost-effective. CONCLUSIONS: In patients with IBS, small-intestinal release peppermint oil appears to be a cost-effective treatment although there is uncertainty surrounding the ICER. When using abdominal pain responder as outcome measure for the ICER, peppermint oil has a high probability of being cost-effective. The use of peppermint oil, which is a low-cost treatment, can be justified by the modest QALY gains and slightly higher proportion of abdominal pain responders. More research and long-term data are necessary to confirm the cost-effectiveness of peppermint oil. 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.

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.

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.).

Five-Year Results of a Randomized Controlled Trial Comparing Effectiveness of Photodynamic Therapy, Topical Imiquimod, and Topical 5-Fluorouracil in Patients with Superficial Basal Cell Carcinoma.

For the treatment of superficial basal cell carcinoma, a prospective, noninferiority, randomized controlled multicenter trial with 601 patients showed that 5% imiquimod cream was superior and 5-fluorouracil cream not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) at 1 and 3 years after treatment. No definite conclusion could be drawn regarding the superiority of imiquimod over 5-fluorouracil. We now present the 5-year follow-up results according to the intention-to-treat analysis. Five years after treatment, the probability of tumor-free survival was 62.7% for methyl aminolevulinate photodynamic therapy (95% confidence interval [CI] = 55.3-69.2), 80.5% for imiquimod (95% CI = 74.0-85.6), and 70.0% for 5-fluorouracil (95% CI = 62.9-76.0). The hazard ratio for treatment failure of imiquimod and 5-fluorouracil were 0.48 (95% CI = 0.32-0.71, P < 0.001) and 0.74 (95% CI = 0.53-1.05, P = 0.09), respectively, when compared with methyl aminolevulinate photodynamic therapy. Compared with 5-fluorouracil, imiquimod showed a hazard ratio of 0.65 (95% CI 0.43-0.98, P = 0.04). In conclusion, 5 years after treatment, the results of this trial show that 5% imiquimod cream is superior to both methyl aminolevulinate photodynamic therapy and 5-fluorouracil cream in terms of efficacy for superficial basal cell carcinoma. We therefore consider 5% imiquimod cream as the first choice for noninvasive treatment in most primary superficial basal cell carcinomas.

Treatment of Cervical Intraepithelial Neoplasia: Patients Preferences for Surgery or Immunotherapy with Imiquimod.

Imiquimod has been studied as a noninvasive pharmacological treatment alternative to large loop excision of the transformation zone (LLETZ) for high-grade cervical intraepithelial neoplasia (CIN), to prevent long-term obstetric complications from surgical treatment. This study aims to investigate womens' preferences for treatment of high-grade CIN with imiquimod or LLETZ. A labeled discrete choice experiment was conducted among 100 women with abnormal cervical cytology in 5 hospitals in the Netherlands between March 2014 and December 2015. Participants were asked to choose between imiquimod treatment or standard surgical treatment in 9 separate scenarios, based on the following treatment characteristics: treatment success rate, rate of side effects, risk of premature birth in subsequent pregnancies, and risk of subfertility after treatment. The levels of these characteristics differed for the imiquimod alternatives. Women assigned a positive utility to LLETZ compared with imiquimod. When making a choice for imiquimod, women preferred a higher treatment success rate and a lower risk of premature birth, infertility and side effects. The choice for imiquimod treatment was also influenced by the intention of a future pregnancy. Subgroup analyses revealed that a lower efficacy regarding imiquimod might be more acceptable for women who desired a future pregnancy compared with women who did not desire a future pregnancy. Women with a future pregnancy wish may prefer treatment of high-grade CIN with imiquimod cream over LLETZ, if the risk of subfertility and premature birth is low.

Three-Year Follow-Up Results of Photodynamic Therapy vs. Imiquimod vs. Fluorouracil for Treatment of Superficial Basal Cell Carcinoma: A Single-Blind, Noninferiority, Randomized Controlled Trial.

A randomized controlled trial including 601 patients previously showed that the effectiveness of imiquimod and fluorouracil cream were not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) in patients with superficial basal cell carcinoma after 1 year of follow-up. We now present the 3-year follow-up results. The probability of tumor-free survival at 3 years post-treatment was 58.0% for MAL-PDT (95% confidence interval [CI] = 47.8-66.9), 79.7% for imiquimod (95% CI = 71.6-85.7), and 68.2% for fluorouracil (95% CI = 58.1-76.3). The hazard ratio for treatment failure comparing imiquimod with MAL-PDT was 0.50 (95% CI = 0.33-0.76, P = 0.001). Comparison of fluorouracil with MAL-PDT and fluorouracil with imiquimod showed hazard ratios of 0.73 (95% CI = 0.51-1.05, P = 0.092) and 0.68 (95% CI = 0.44-1.06, P = 0.091), respectively. Subgroup analysis showed a higher probability of treatment success for imiquimod versus MAL-PDT in all subgroups with the exception of elderly patients with superficial basal cell carcinoma on the lower extremities. In this subgroup, the risk difference in tumor-free survival was 57.6% in favor of MAL-PDT. In conclusion, according to results at 3 years post-treatment, imiquimod is superior and fluorouracil not inferior to MAL-PDT in treatment of superficial basal cell carcinoma.

Survival or Mortality: Does Risk Attribute Framing Influence Decision-Making Behavior in a Discrete Choice Experiment?

OBJECTIVE: To test how attribute framing in a discrete choice experiment (DCE) affects respondents' decision-making behavior and their preferences. METHODS: Two versions of a DCE questionnaire containing nine choice tasks were distributed among a representative sample of the Dutch population aged 55 to 65 years. The DCE consisted of four attributes related to the decision regarding participation in genetic screening for colorectal cancer (CRC). The risk attribute included was framed positively as the probability of surviving CRC and negatively as the probability of dying from CRC. Panel mixed-logit models were used to estimate the relative importance of the attributes. The data of the positively and negatively framed DCE were compared on the basis of direct attribute ranking, dominant decision-making behavior, preferences, and importance scores. RESULTS: The majority (56%) of the respondents ranked survival as the most important attribute in the positively framed DCE, whereas only a minority (8%) of the respondents ranked mortality as the most important attribute in the negatively framed DCE. Respondents made dominant choices based on survival significantly more often than based on mortality. The framing of the risk attribute significantly influenced all attribute-level estimates and resulted in different preference structures among respondents in the positively and negatively framed data set. CONCLUSIONS: Risk framing affects how respondents value the presented risk. Positive risk framing led to increased dominant decision-making behavior, whereas negative risk framing led to risk-seeking behavior. Attribute framing should have a prominent part in the expert and focus group interviews, and different types of framing should be used in the pilot version of DCEs as well as in actual DCEs to estimate the magnitude of the effect of choosing different types of framing.

Functional outcome and cost-effectiveness of pulsed electromagnetic fields in the treatment of acute scaphoid fractures: a cost-utility analysis.

BACKGROUND: Physical forces have been widely used to stimulate bone growth in fracture repair. Addition of bone growth stimulation to the conservative treatment regime is more costly than standard health care. However, it might lead to cost-savings due to a reduction of the total amount of working days lost. This economic evaluation was performed to assess the cost-effectiveness of Pulsed Electromagnetic Fields (PEMF) compared to standard health care in the treatment of acute scaphoid fractures. METHODS: An economic evaluation was carried out from a societal perspective, alongside a double-blind, randomized, placebo-controlled, multicenter trial involving five centres in The Netherlands. One hundred and two patients with a clinically and radiographically proven fracture of the scaphoid were included in the study and randomly allocated to either active bone growth stimulation or standard health care, using a placebo. All costs (medical costs and costs due to productivity loss) were measured during one year follow up. Functional outcome and general health related quality of life were assessed by the EuroQol-5D and PRWHE (patient rated wrist and hand evaluation) questionnaires. Utility scores were derived from the EuroQol-5D. RESULTS: The average total number of working days lost was lower in the active PEMF group (9.82 days) compared to the placebo group (12.91 days) (p = 0.651). Total medical costs of the intervention group (€1594) were significantly higher compared to the standard health care (€875). The total amount of mean QALY's (quality-adjusted life year) for the active PEMF group was 0.84 and 0.85 for the control group. The cost-effectiveness plane shows that the majority of all cost-effectiveness ratios fall into the quadrant where PEMF is not only less effective in terms of QALY's but also more costly. CONCLUSION: This study demonstrates that the desired effects in terms of cost-effectiveness are not met. When comparing the effects of PEMF to standard health care in terms of QALY's, PEMF cannot be considered a cost-effective treatment for acute fractures of the scaphoid bone. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2064.

Cost-effectiveness of ablation surgery in patients with atrial fibrillation undergoing cardiac surgery.

This study was performed to assess the cost-effectiveness of concomitant ablation surgery (AS) compared to regular cardiac surgery in atrial fibrillation (AF) patients over a one-year follow-up. Cost analysis was performed from a societal perspective alongside a prospective, randomised, double-blinded, multicentre trial. One hundred and fifty patients with documented AF were randomly assigned to undergo cardiac surgery with or without AS. One hundred and thirty-two patients were included in the cost-effectiveness study. All costs (medical and non-medical) were measured during follow-up. Costs data were combined with quality adjusted life years (QALYs) to obtain the incremental costs per QALY. Total costs of the AS group were significantly higher compared to the regular cardiac surgery group [cost difference bootstrap: €4,724; 95% uncertainty interval (UI), €2,770-€6,678]. The bootstrapped difference in QALYs was not statistically significant (0.06; 95% UI: -0.024 to 0.14). The incremental cost-effectiveness ratio is €73,359 per QALY. The acceptability curve showed that, even in the case of a maximum threshold value of €80,000 per QALY gained, the probability of AS being more cost-effective than regular cardiac surgery did not reach beyond 50%. Concluding that concomitant AS in AF is not cost-effective after a one-year follow-up compared to regular cardiac surgery.

Assessing the public's preference for surgical treatment of primary basal cell carcinoma: a discrete-choice experiment in the south of the Netherlands.

BACKGROUND: Basal cell carcinoma (BCC) is a slowly growing nonmelanoma type of skin cancer that often is located on the face. Different therapies are available to treat BCC, of which surgical excision (SE) and Mohs micrographic surgery (MMS) are the most frequently used surgical procedures. OBJECTIVES: To examine which attributes of a surgical treatment the general public values as important and to determine the incremental willingness to pay for MMS versus SE. METHODS: A discrete-choice experiment (DCE) was conducted among members of the general public to examine which attributes of a surgical treatment for primary BCC are valued as important. In addition, based on the attributes included in the experiment, the willingness to pay for MMS versus SE was determined. RESULTS: Respondents (N=312) preferred a treatment with a lower recurrence rate, shorter surgery time, shorter travelling time, shorter waiting time, no risk for re-excision, and lower cost. The incremental willingness to pay for MMS was 847 euro ($1,203). CONCLUSIONS: Results from this DCE indicate that, when outcome and process attributes are considered from a societal perspective, MMS is preferred over SE for primary BCC. The authors have indicated no significant interest with commercial supporters.

Does the inclusion of a cost attribute result in different preferences for the surgical treatment of primary basal cell carcinoma?: a comparison of two discrete-choice experiments.

BACKGROUND: Nowadays, an increasing number of discrete-choice experiments (DCEs) incorporate cost as an attribute. However, the inclusion of a cost attribute, particularly within collectively funded healthcare systems, can be challenging because health services or goods are generally not traded in a market situation and individuals are not used to paying for a service or a good at the point of consumption. OBJECTIVE: To examine whether the inclusion of a cost attribute in a DCE results in different preferences regarding a surgical treatment for primary basal cell carcinoma (BCC) compared with a DCE without a cost attribute. METHODS: A randomized study was performed in which the impact of a cost attribute on the general public's preferences for a surgical treatment (Mohs micrographic surgery [MMS] or standard excision [SE]) to remove BCC was examined. This was done by comparing the outcomes of two DCEs, one with a cost attribute (DCE_cost) and one without (DCE_nocost). Six attributes (recurrence, re-excision, travel time, surgical time, waiting time for surgical results, costs) and their levels were selected, based on results of a clinical trial, a cost-effectiveness study, a review and a focus group of patients who had recently received treatment for BCC. Outcomes of both DCEs were compared in terms of theoretical validity, relative importance of the attributes and the rank order of preferences. RESULTS: A total of 615 respondents (n = 303 for DCE_nocost; n = 312 for DCE_cost) were interviewed by telephone. This gave an overall response rate of 38%. Respondents in DCE_nocost preferred a surgical treatment with a lower probability of recurrence, lower surgery time, lower waiting time and no risk for a re-excision. Respondents in DCE_cost showed the same preferences, but also preferred a treatment with less travel time and lower costs. Overall, respondents in both DCEs showed the same preference for a surgical treatment: MMS was preferred over SE. CONCLUSION: Results suggest that, in this population, the inclusion of a cost attribute in a DCE leads to the same preference regarding a surgical treatment to remove BCC as a DCE without a cost attribute. However, further research in different settings is needed to confirm these findings.